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EUROCAT Statistical Monitoring Report 2010 1

EUROCAT Statistical

Monitoring Report – 2010

(Uploaded to EUROCAT website February 2013)

EUROCAT Central Registry

University of Ulster Newtownabbey, Co Antrim Northern Ireland, BT37 0QB

Tel: +44 28 9036 6639 Fax: +44 28 9036 8341

Email: [email protected] Web: www.eurocat-network.eu

EUROCAT Joint Action 2011-2013 is funded by the Public Health Programme 2008-2013 of the

European Commission

WHO Collaborating Centre for the Surveillance of Congenital Anomalies

http://www.eurocat-network.eu/


Table of Contents

Acknowledgements

4

1 EUROCAT 2010 Statistical Monitoring of Congenital Anomalies: Key Findings 6

2 Introduction

2.1 Overview of Annual Statistical Monitoring 8

3 Population and Monitoring Process

3.1 Registries included in the 2010 trend analysis 9

3.2 Registries included in the 2010 cluster analysis 9

3.3 What was monitored? 10

3.4 Investigation process 11

3.5 Statistical software updates from previous reports 13

4 Trends

4.1 Overview 15

4.2 Increasing trends 15

4.2.1 New increasing trends 15

4.2.2 Continuing increasing trends 21

4.3 Decreasing trends 24

5 Clusters

5.1 Overview 33

5.2 Reports of preliminary investigations by registries (selected clusters) 33

5.3 Taskforce for the evaluation of clusters 39

5.3.1 Improving the quality of preliminary cluster investigations 39

5.4 Dissemination of the Statistical Monitoring Report 40

5.4.1 Survey on the use of the Statistical Monitoring Report: key findings 41

6 Conclusion 42

List of Tables

Table 1 Central Registry Statistical Monitoring Results: reported 10 year trends by individual registry

32

Table 2 Outcomes of local registry preliminary investigations of new clusters detected in 2010 monitoring

35


List of Figures

Figure 1 Prioritisation criteria for the investigation of ten year trends 12

Figure 2 Prevalence of cardiac anomalies showing a significant increase in

the pan-Europe analysis

16

Figure 3 Prevalence of Tetralogy of Fallot over time by classification using

the multiple malformation algorithm (including and excluding 22q

deletion)

17

Figure 4 Prevalence of digestive system anomalies showing a significant

increase in the pan-Europe analysis

18

Figure 5 Increasing pan-Europe trend in Renal dysplasia by registry 19

Figure 6 Average annual change in prevalence in Craniosynostosis by

registry

20

Figure 7 Increasing pan-Europe trend in Complete absence of the limb 21

Figure 8 Increasing pan-Europe trend in Cystic adenomatous malformation

of the lung by UK registry and the rest of Europe

22

Figure 9 Increasing pan-Europe trend in Gastroschisis in registries with

low, medium and high prevalence

23

Figure 10 Prevalence of chromosomal anomalies showing a significant

increase in the pan-Europe analysis

24

Figure 11 Prevalence of Neural tube defects showing a significant decrease

in the pan-Europe analysis

25

Figure 12 Average annual change in prevalence in Spina bifida by registry 25

Figure 13 Decreasing pan-Europe trend in CHD, ASD, VSD and severe

CHD

26

Figure 14 Decreasing pan-Europe trend in Atresia of the bile ducts 28

Figure 15 Estimated average percentage change in prevalence and 95%

confidence intervals (Pan-Europe analysis)

30

List of Boxes

Box 1 Registry inclusion criteria for trend analysis 9

Box 2 Registry inclusion criteria for cluster analysis 10


Appendices

Appendix A Congenital anomaly subgroup inclusion list

Appendix B Summary of statistical methods

Appendix C Summary of local registry preliminary investigation protocols for identified ten year trends and clusters

Appendix D Summary of significant ten year increasing and decreasing trends detected in the pan-Europe analysis

Appendix E Forest plots showing ten year increasing and decreasing trends detected in the pan-Europe analysis by anomaly subgroups

Appendix F Forest plots showing ten year increasing and decreasing trends detected in the pan-Europe analysis by registry

Appendix G1 Outcomes of local registry preliminary investigations into increasing ten year trends

Appendix G2 Outcomes of local registry preliminary investigations into decreasing ten year trends

Appendix H Central Registry Statistical Monitoring Results: table of detected clusters by registry and by anomaly 2009-2010

Appendix I Clusters identified in the cluster analysis

Appendix J Trends by anomaly and registry– website details

Appendix K Survey on the use of the Annual Statistical Monitoring Report

Appendix L Pan-Europe and individual registry 10 year average rates for congenital anomalies

Acknowledgements

This report was compiled by Nichola McCullough, Maria Loane, Ruth Greenlees and Helen

Dolk. Statistical methods were designed by Alan Kelly, Conor Teljeur and Joan Morris.

Statistical software was created by BioMedical Computing Ltd (James Densem). Reports of

registry investigations were provided by: Antwerp (Vera Nelen), Hainaut (Christine Verellen

Dumoulin), Zagreb (Ingeborg Barisic), Odense (Ester Garne), Paris (Babak Khoshnood),

Mainz (Awi Weisel), Saxony-Anhalt (Anke Rißmann), Hungary (Judit Beres ) South East

Ireland (Carmel Mullaney), Emilia Romagna (Elisa Calzolari), Tuscany (Fabrizio Bianchi),

Malta (Miriam Gatt), Northern Netherlands (Marian Bakker), South Portugal (Carlos Dias),

Basque Country (Larraitz Arriola), Vaud (Marie-Claude Addor), East Midlands and South

Yorkshire (Elizabeth Draper), Thames Valley (Patricia Boyd), Wales (David Tucker) Wessex

(Diana Wellesley) and South West England (Rosie Thompson).


EUROCAT 2010 Statistical Monitoring of Congenital Anomalies: Key Findings

Congenital anomalies are a leading cause of fetal death, infant mortality and morbidity in

childhood. EUROCAT is a European network of population-based registries with the general

objective of supporting the reduction of the public health burden of congenital anomalies by

conducting coordinated epidemiological surveillance.

EUROCAT annually performs statistical monitoring for both trends and clusters in time in

order to detect signals of new or increasing teratogenic exposures and monitor progress in

the prevention of congenital anomalies. Total prevalence rates of 81 subgroups of

congenital anomalies, including all cases of livebirths, stillbirths and late fetal deaths from 20

weeks gestational age, and terminations of pregnancy for fetal anomaly are monitored and

reported. This report concerns the ten year period 2001-2010, including data from 24

EUROCAT registries. In the period 2001-2010, 82% of cases notified to the registries were

liveborn, 2% were stillborn and 16% were terminations of pregnancy for fetal anomaly.

Our key findings concentrate on the pan-European analysis, which gives a snapshot of the

situation in Europe. Within the main report, information on trends in the rates of congenital

anomalies in individual registries is also presented.

Key findings

In this year’s pan-Europe analysis a decreasing trend was identified for Neural tube

defects (NTDs) which declined on average by 1.7% per year to 9.42 per 10,000

births in 2009-2010. In particular, rates for Spina bifida declined on average by 2.1%

per year to 4.67 in 2009-2010. The decreasing pan-Europe trend for NTDs suggests

that public health measures, such as folic acid supplementation are becoming

effective. However the decline has been shallow, and mainly occurred in the first half

of the decade.

Congenital heart defects (CHD) account for a third of all congenital anomaly cases. A

decreasing trend was detected for the subgroup CHD overall which decreased on

average by 0.6% per year to 62.37 per 10,000 births in 2009-2010. Ventricular

septal defect (VSD) and Atrial septal defect (ASD), the most common and less

severe types of CHD, both decreased; Potential explanations for the decline in CHD

include folic acid supplementation and better management of maternal illness or


decline in maternal smoking. However, increasing trends were detected in some of

the more severe types of CHD with Tetralogy of Fallot, a type of cyanotic congenital

heart defect increasing on average by 2.3% per year to 3.26 per 10,000 births 2009-

2010, and Single ventricle increasing on average by 5.9% per year to 0.74 per

10,000 births in 2009-2010.

Increasing trends were found for several subgroups of digestive anomalies:

Oesophageal atresia with or without trachea-oesophageal fistula, Duodenal

atresia and stenosis, Atresia and Stenosis of other parts of the small intestine.

The rare digestive system anomaly Atresia of the bile ducts (biliary atresia)

declined markedly by an average of 9% per year to 0.17 per 10,000 births in 2009-

2010. Maternal infective causes have been suggested as aetiological factors for

biliary atresia.

For the fourth consecutive year of pan-Europe monitoring an increasing trend was

observed for the abdominal wall defect Gastroschisis, a rare type of defect that

requires corrective surgery at birth. An average increase of 1.6 % per year was

detected, with average rates rising to 2.87 per 10,000 births in 2009-2010. The

largest increase in rates occurred in the early part of the decade. Gastroschisis is

associated with risk factors such as low socioeconomic status (SES), young maternal

age, low maternal body mass index (BMI) and maternal smoking. Four out of five

registries with the highest prevalence rates for this anomaly were located in the UK.

More directed action, particularly in the UK, is needed to address this public health

concern.

There was an increasing trend for the very rare anomaly Complete absence of a

limb, with rates increasing on average by 7.8% per year to 0.22 per 10,000 births in

2009-2010. However this occurred in the context of a decreasing trend for Upper

limb reduction. The data are being validated to make sure that this is not a

classification problem.

As in the previous report the three main chromosomal trisomy syndromes increased

in prevalence. Down syndrome/trisomy 21 increased on average by 1.1% per

year to 22.38, Patau syndrome/trisomy 13 by 2.4% per year to 2.09 and Edward

syndrome/trisomy 18 by 2.3% per year to 5.56 per 10,000 births in 2009-2010.


Following adjustment for maternal age these trends were no longer present,

indicating that increases in trisomy syndromes in general are associated with rises in

the proportion of women delaying child birth until later in life.

Clusters

Whilst the cluster analysis did not identify any clusters thought to be of immediate concern, a

number (n=8) could not be explained by information held within the registries. The registries

reported that these clusters, identified in the period 2009-2010, would remain under

surveillance.

Conclusion

The statistical monitoring of trends and clusters is fundamental to the primary prevention of

congenital anomalies, providing timely information on the stability and change in rates.

Primary prevention of congenital anomalies continues to be a key objective of the

EUROCAT network, and is reflected in the current ethos of the Joint Action between the

European Union and Member States.


2. Introduction

2.1 Overview of Annual Statistical Monitoring

Each year, EUROCAT performs statistical monitoring for both trends and clusters in time.

Statistical monitoring relates to two of EUROCAT’s objectives:

to provide essential epidemiologic information on congenital anomalies in Europe

to co-ordinate the detection of and response to clusters and early warning of

teratogenic exposures

A full protocol is published annually online, providing details of the rationale and

methodology of the statistical monitoring, including changes to methodology and software.

The protocol is available at EUROCAT Statistical Monitoring Protocol http://www.eurocat-

network.eu/content/EUROCAT-Statistical-Monitoring-Protocol-2010.pdf ).

We report here the results up to birth year 2010. Cases of congenital anomaly among

livebirths, fetal deaths and terminations of pregnancy for fetal anomaly are included. We

report both the statistical results, and where available the outcome of preliminary

investigations conducted by registries.

Registries can also use the statistical monitoring software to conduct their own monitoring on

more recent data, and reports of any such analyses that may have been conducted up to

June 2012 are also included in this Report. In addition, any trends or clusters detected

outside of formal statistical monitoring (e.g. reported to the registry by local clinicians) are

reported.

The distribution of epidemiological information on the prevalence of congenital anomalies

and the investigation of clusters and trends detected through the Annual Statistical

Monitoring has been identified as key strategies within Work Package 2: Dissemination of

the Joint Action. A review of the dissemination strategies for previous Statistical Monitoring

Reports by individual registries is included in this year’s Report (see section 5.4).

http://www.eurocat-network.eu/content/EUROCAT-Statistical-Monitoring-Protocol-2010.pdf



3. Population and Monitoring Process

3.1 Registries included in the 2010 trend analysis

At the time of statistical monitoring in Spring 2012, there were 33 full member registries in

EUROCAT. Twenty-five full member registries met the inclusion criteria for the individual 10-

year trend analysis (see Box 1), with twenty-four of these registries meeting the criteria for

the pan-Europe analysis.

Ukraine, South West England, Cork and Kerry, French West Indies and Valencia Region

were excluded from the trend analysis as they did not meet the inclusion criteria for the time

period coverage. Barcelona, Norway and Strasbourg were excluded due to being more than

one year late with their data. Ile de la Reunion was not included in the pan-Europe analysis

as they did not have data for the year 2001.

3.2 Registries included in the 2010 cluster analysis

EUROCAT defines clusters as 'An aggregation of cases of congenital anomaly in time

and/or space which appears to be unusual'1. Registries classified as “early response” i.e.

registries that meet the EUROCAT data transmission deadline of February 15th, with data for

the most recent 5 years (2006-2010) were included in cluster monitoring (see Box 2). Five

years is considered an optimal period for cluster monitoring as the inclusion of more than

five years data may detect trends rather than clusters, while less than five years may fail to

detect if the most recent years are unusual compared to preceding years (see EUROCAT

1 EUROCAT Working Group on the Management of Clusters and Environmental Exposure Incidents, 2003

Box 1 Registry inclusion/ exclusion criteria for trend analysis

Registries >1 year late with data transmission excluded from

analysis

Pan-Europe: Registries with 9 or 10 years of continuous data

starting from 2001 included (i.e. 2001-2010 or 2001-2009)

Individual registry analysis: Registries with 8 or 10 years of

continuous data included (i.e. 2001-2010 or 2002-2009)


Statistical Monitoring Protocol 2010 http://www.eurocat-network.eu/content/EUROCAT-

Statistical-Monitoring-Protocol-2010.pdf).

A total of 20 full member registries transmitted year 2010 data to EUROCAT Central

Registry by Feb 15th 2012. Three registries were excluded from the cluster monitoring for the

following reasons: Zagreb – population fluctuation; Saxony-Anhalt – did not have full date of

birth information and French West Indies – less than 5 years continuous data.

Where registries do not meet the data transmission deadline, monitoring can be run locally

to detect clusters and trends using software available in the EDMP (EUROCAT Data

Management Program). Pan-Europe monitoring can only be conducted centrally as it uses

data from all the registries combined.

3.3 What was monitored?

Data from EUROCAT registries were transmitted to Central Registry in February 2012.

Cases included livebirths, stillbirths from 20 weeks gestational age and terminations of

pregnancy for fetal anomaly. In the period 2001-2010, 82% of cases were liveborn, 2% were

stillborn and 16% were terminations of pregnancy for fetal anomaly.

Box 2 Registry inclusion criteria for cluster analysis

Registries must have transmitted year 2006-2010

data

Registries must have transmitted full date of birth

information

Registries must have individual case data (i.e. full

member registries only)

Registries must have a stable birth population

(annual birth population changes must be less than

+/- 10%)




Statistical monitoring is conducted to detect changes in time within individual registries, and

also to detect trends across all registries (pan-Europe trends). Seventy-eight EUROCAT

congenital anomaly subgroups plus the three trisomy subgroups adjusted for maternal age

and fetal survival to 20 weeks were included in both the pan-Europe and individual registry

trend analyses compared to 96 subgroups monitored in previous years (see Appendix A for

the anomaly subgroup inclusion list). This year, main organ subgroups with the exception of

congenital heart defects (CHD) were excluded from monitoring of trends. Changes to the

EUROCAT list of subgroups implemented in January 2012 means there are now fewer

subgroups of congenital anomalies compared to previous years which also explains the

decrease in the number of congenital anomaly subgroups included in statistical monitoring

(see http://www.eurocat-network.eu/content/EUROCAT-Guide-1.3-Chapter-3.3-Jan2012.pdf).

Trend tests were performed for the most recent five and ten years of data (or eight years if

ten years were unavailable).

Cluster analysis, which detects clusters or deficits occurring in the last 2 years (2009-2010)

that are less than 18 months in length, was run on 73 EUROCAT subgroups of congenital

anomalies (see Appendix A for the anomaly subgroup inclusion list and Appendix B for

summary of statistical methods).

The following analyses were carried out:

Analysis of individual registry trends for 25 registries covering 5.60 million births

(2001-2010)

Analysis of pan-European trends for 24 registries covering 5.65 million births (2001-

2010)

Cluster analysis to detect unusual aggregations of cases in 17 registries covering

0.95 million births (2009-2010)

3.4 Investigation process

The results of the statistical monitoring were reviewed by to the Project Management

Committee (PMC) in late March 2012. Registries were asked to investigate all clusters

detected in the monitoring. Due to the large number of significant trends detected, the PMC

identified and prioritised a number of significant trends for preliminary investigation using a

predefined prioritisation protocol (see Figure 1).

http://www.eurocat-network.eu/content/EUROCAT-Guide-1.3-Chapter-3.3-Jan2012.pdf


The PMC agreed that all NEW increasing trends and the NEW decreasing trend for upper

limb reduction anomalies detected in the pan-Europe analysis were to be investigated by

local registries with a significant trend for that anomaly at local level. Trends not prioritised

for investigation are not discussed in this report but will be subject to further monitoring.

Figure 1: Prioritisation criteria for the investigation of ten year trends2

The results of the trends and cluster analysis were communicated to the registries. Each

registry was asked to conduct preliminary investigations of the following outcomes using

standardised guidelines (EUROCAT Statistical Monitoring Protocol)

All significant increasing trends found in their registry if the trends were also found in

the pan-Europe analysis

Decreasing trends in upper limb reduction anomalies if this trend was also found in

their registry

Registries were also given the option to investigate and report on increasing and

decreasing trends unique to their registry if they thought these were of interest to

other parties.

Registries reported their findings to Central Registry using standard reporting templates (see

EUROCAT Statistical Monitoring Protocol 2010). They were asked to provide specific details

2 Loane M, Dolk H, Kelly A, Teljeur, C, Greenlees, R, Densem, J and a EUROCAT Working Group, (2011). Paper 4:

EUROCAT Statistical Monitoring: Identification and investigation of ten year trends of congenital anomalies in Europe. Birth Defects Research (Part A), 91. pp. S31-S43.


that included the methods used, results of the investigation and the public health authorities

to be notified if necessary (see Appendix C for a summary).

Preliminary reports were received from 19 registries investigating significant trends detected

in the monitoring (see Table 1). Preliminary reports of cluster investigations were received

from all registries found to have newly detected clusters in this year’s monitoring (see Table

2 and Appendix G). Eleven registries stated that they would notify the results and the

findings of their preliminary investigations to public health authorities.

The preliminary reports of the trend and cluster investigations were reviewed and discussed

by the PMC in late May 2012, and congenital anomalies thought to be of interest were

selected for oral presentation at the Registry Leaders Meeting (RLM) in June 2012.

Registries were given feedback from the PMC discussion of their investigation reports. At the

RLM, Central Registry also presented analyses of the pan-European data for these

anomalies in order to put the local registry investigations into context. Full details of the

registry preliminary investigations for all identified trends and clusters are located in a

separate Annex on the membership-only section of the EUROCAT website.

3.5 Statistical software updates from previous report

There have been a number of changes made to the software for this year’s statistical

monitoring. We have adjusted Down syndrome for maternal age and fetal survival to 20

weeks gestational age since publication of the EUROCAT Statistical Monitoring Report

2008. This year we also performed this adjustment for the Edward and Patau syndromes.

Both adjusted and unadjusted results are presented.

We reviewed the reporting of significant non-linear change in monitoring of trends. In

individual registry trend analysis, if there is a monotonic increasing or decreasing trend over

time, the trend is reported as opposed to the significant variation from linearity. The pan-

Europe analysis does not test for non-linearity. For monitoring of 10-year trends, data is now

presented by individual year unless there are too few cases to meet the criterion for testing

by single year, in which case it is grouped by 2-year intervals. Pan-Europe analysis now also

adjusts for the effect of registry size.

The graphical output of the analysis has been updated to include forest plots showing the

average percentage change in prevalence and the 95% confidence intervals per year for

individual registries. In addition the EUROCAT average prevalence per year (or per 2-year


interval) is plotted on each graph so that a registry can see if it is above or below the

average prevalence.

All of the above changes should be taken into consideration when comparing the results of

this year’s statistical monitoring with monitoring conducted in previous years.


4. Trends

4.1 Overview

Once again there was a decline in the prevalence of all non-chromosomal anomalies at pan-

European level. The analysis identified increasing trends for 14 subgroups of anomalies,

decreasing trends for 21 subgroups (see Figure 15 and Appendix D). Nineteen trends

reported in the 2009 report were also detected in the 2010 statistical monitoring, five of

which were increasing trends and fourteen were decreasing trends (see Appendix D for

details). For ten year trends in individual registries a total of 1219 chi squared tests were

performed with 31% being statistically significant compared with the 5% expected by

chance. The analysis identified a total of 89 increasing trends, 125 decreasing trends and

164 non-linear changes (see Table 1). This section provides details of the results,

investigations and interpretation of trends in specific anomaly subgroups that were prioritised

for further investigation by the PMC (see section 3.4).

4.2 Increasing trends

New increasing trends were identified in the 2010 Annual Statistical Monitoring for the

following anomaly subgroups: Single ventricle; Tetralogy of Fallot; Oesophageal atresia;

Duodenal atresia; Atresia and stenosis of other parts of the small intestine; Renal dysplasia;

Complete absence of the limb; Craniosynostosis and Chromosomal anomalies. Five trends

present in the 2009 report were once again found for the following anomaly subgroups:

Cystic adenomatous malformation of the lung; Gastroschisis; Down syndrome/trisomy 21;

Patau syndrome/trisomy 13 and Edward syndrome/trisomy 18.

4.2.1 New increasing trends

Despite the overall decreasing pan-Europe trend found for CHD significant increasing pan-

Europe trends were found for two cardiac anomalies (see Figures 2 and 15).

Tetralogy of Fallot, is a well-defined cyanotic congenital heart defect. Some infants have

severe symptoms from birth while others may be asymptomatic for several months.

Corrective surgery is possible for most cases and is necessary for long-term survival.

Newborns with severe cyanosis will need a shunt surgery in infancy. Corrective surgery is

usually performed between 3 and 9 months of age. Following surgery most children will go

on to have a normal life, though some may require additional surgery or may develop new

cardiac problems. Pan-Europe analysis showed that the prevalence of Tetralogy of Fallot

had increased on average by 2.3% per year from 2.79 per 10,000 births in 2001-2002 to


3.26 in 2009-2010 (see Figures 2 and 15).

Figure 2. Prevalence of cardiac anomalies showing a significant increase in the pan-Europe

analysis

The increase in Tetralogy of Fallot was explored by Central Registry, using the multiple

malformation algorithm3. The increase in prevalence of Tetralogy of Fallot was greatest

amongst cases with isolated cardiac malformations, with rates rising from around 2 per

10,000 births in the early years of the decade to more than 2.5 per 10,000 births by 2008

(see Figure 3). In contrast the prevalence rates for cases with potential multiple

malformations and syndromes were relatively stable. Fourteen registries recorded increases

of various magnitudes in rates of Tetralogy of Fallot (see Appendices E, F and G), but Wales

was the only registry to record a statistically significant increase. The prevalence rate in

Wales also had the greatest magnitude of change. Following a preliminary investigation the

registry have informed us that they plan to investigate the trend further.

3 Garne E, Dolk H, Loane M, Wellesley D, Barisic I, Calzolari E and Densem J (2011). Paper 5: Surveillance of multiple

congenital anomalies: implementation of a computer algorithm in European registers for classification of cases. Birth Defects

Research (Part A). 91: S44-S50.


Figure 3. Prevalence of Tetralogy of Fallot over time by classification using the multiple malformation algorithm (including and excluding 22q deletion)

The cardiac anomaly Single ventricle, is a very severe univentricular cardiac defect. If the

anomaly is diagnosed prenatally, parents may decide for termination of pregnancy. Infants

will be symptomatic from birth. Corrective surgery is not possible, but staged surgery for a

Fontan circulation is usually possible. Pan-Europe analysis showed that the prevalence of

this particular anomaly has risen on average by an estimated 5.9% per year from 0.53 per

10,000 births in 2001-2002 to 0.74 in 2009-2010. The increasing trends found for these two

severe cardiac anomalies are in contrast to the new decreasing trend detected for CHD

overall (see section 4.3). A recent EUROCAT paper4, using a longer time period (1990-

2007) reported a decrease in CHD overall. Subgroups of CHD were categorised into three

levels of severity, and it was found that the time trend for the most severe group, which

included single ventricle, remained relatively stable. Severity group II which included

Tetralogy of Fallot, showed evidence of a decline in prevalence from 2000 onward. More

epidemiological studies are needed to identify public health strategies that are effective in

producing a decline across all types of CHD.

Three new increasing pan-Europe trends were identified in the group of digestive anomalies

(see Figures 4 and 15). In Oesophageal atresia with or without trachea-oesophageal

fistula the upper part of the esophagus ends in a blind-ended pouch without connection to

4 Khoshnood, B. et al. Recent decreases in the Prevalence of Congenital Heart Defects in Europe. The Journal of Pediatrics

(in press)


the stomach. This makes enteral feeding impossible and gives respiratory problems. Surgery

is necessary to correct this anomaly. The survival rate is high (>90%), though there is the

potential for gastric and respiratory associated morbidity throughout the lifespan. Anomalies

common associated with this condition include the VACTERL syndrome; the CHARGE

association and also chromosomal anomalies. Using the EUROCAT multiple malformation

algorithm, 48% of the non-chromosomal cases notified during this time period had potential

multiple malformations. The prevalence rate increased on average by an estimated 1.8%

each year from 2.19 per 10,000 births in 2001-2002 to 2.69 in 2009-2010. There has been

some suggestion of geographical variation in rates of this anomaly. Across the individual

registries overall rates ranged from 0.63 to 3.97 per 10,000 births. There were increasing

trends detected in eight registries, but Wielkopolska and Hungary were the only registries to

record statistically significant increases (see Appendix E and F). Following preliminary

investigations Hungary were able to confirm that this increase was not a consequence of

exposure to risk factors but was due to data quality improvement (see Appendix G).

Figure 4. Prevalence of the digestive system anomalies showing a significant increase in the pan-Europe analysis

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Osophagealatresia

Duodenalatresia

Atresia andstenosis

Increasing pan-European trends were also found for two of the less numerically large

subgroups of digestive anomalies. Duodenal atresia and stenosis increased each year

on average by 4.4% from 0.73 per 10,000 births in 2001-2002 to 1.03 in 2009-2010. Due to

small numbers it was not possible to test for individual trends in all registries, though

increasing trends were identified in two registries, Wielkopolska and Wales. Following


preliminary investigation Wales reported that the increase in prevalence was due to changes

in case ascertainment. Atresia and Stenosis of other parts of the small intestine

increased from 0.55 per 10,000 births in 2001-2002 to 0.96 in 2009-2010 with an estimated

annual average change of 4.4%. Whilst some individual registries showed evidence of

increasing trends for this anomaly these were not statistically significant and were not

investigated further.

Renal dysplasia is a urinary anomaly in which abnormal tissue develops in either one or

both of the kidneys causing them to stop working. The impact of this condition is more

severe when both kidneys are affected, with many cases unable to survive after birth. If only

one kidney is affected most individuals will survive to adulthood but may require regular

monitoring in case of kidney failure. The prevalence rate for this condition increased on

average by 3% per year rising 3.14 per 10,000 births in 2001-2002 to 4.55 in 2009-2010,

with statistically significant increasing trends also observed in six registries (see Figures 5

and 15). Preliminary investigations by the five of the registries indicated that the increasing

trends were likely due to changes in either case ascertainment or in local registry methods

and improvements in antenatal diagnostic techniques leading to more cases being detected

(see Appendix G).

Figure 5. Average annual change in prevalence in renal dysplasia by registry

WielkopolskaBasque CountryTuscanyN NetherlandsSaxony AnhaltEmilia RomagnaEast Midlands and South YorkshireThames ValleyDublinSummary estimateVaudParisHainautZagrebMaltaHungarySE IrelandNorthern EnglandOdenseWalesWessexMainzAntwerpStyriaS Portugal

Renal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasia

30% 20% 10% 10% 20% 30%Nochange

<-- Decrease Increase -->Average annual change in prevalence

Non-linear change

Rate of change

Too few cases


Craniosynostosis is a skeletal anomaly in which premature closure of the cranial sutures

results in an abnormal development of the shape of the head. This is a rare defect that

occurs in isolation or with other syndromes, and has the potential to cause developmental

problems due to the restricted physical growth of the brain. Surgery is the recommended

treatment within the first year of life. The prevalence of this condition increased on average

by 3.6% per year rising from 1.37 per 10,000 births in 2001-2002 to 2.07 in 2009-2010.

Individual increasing trends were also detected in nine registries, four of which were

statistically significant with rates that were higher than the EUROCAT average, (two were

approximately 3 times higher (Basque country: 5.07 per 10,000 births and Vaud: 6.62 per

10,000 births). Preliminary investigations by three of the registries indicated that the

increasing trends could be explained by factors that included changes in case ascertainment

procedures and/or diagnostic definitions. Vaud indicated that they would undertake further

surveillance before conducting a more detailed investigation. A definitive risk factor has yet

to be identified for nonsyndromic Craniosynostosis. Possible causes include increasing

maternal and paternal age, maternal smoking, ethnicity, multiple births and exposure to

valproate.

Figure 6. Average annual change in prevalence in Craniosynostosis by registry

Thames ValleyEmilia RomagnaVaudBasque CountryHainautN NetherlandsSummary estimateTuscanyParisWalesDublinHungaryOdenseZagrebMaltaS PortugalMainzWessexSE IrelandAntwerpWielkopolskaEast Midlands and South YorkshireSaxony AnhaltStyriaNorthern England

CraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosis

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


There were significant increasing trends for two of the limb subgroups in the pan-Europe

analysis (see Figures 7 and 15). Complete absence of the limb is a rare defect, with

known causes of this anomaly including exposure to the teratogenic drug thalidomide.

Complete absence of a limb can have a significant effect on both the infant and the family

and will require significant input from multi-disciplinary healthcare teams throughout life.

Treatment usually includes the fitting of prosthesis to provide function and appearance. The

prevalence of this condition increased on average by 7.8% per year rising from 0.11 per

10,000 births in 2001-2002 to 0.22 in 2009-2010. The low numbers of this anomaly meant

that it was not possible to test for trends in individual registries. This increasing trend also

occurred in the context of a decreasing trend for upper limb reduction. The data are being

validated to ensure that this is not a classification problem.

Figure 7. Increasing pan-Europe trend in Complete absence of the limb

0

0.05

0.1

0.15

0.2

0.25

0.3

Pre

va

len

ce

pe

r 1

0,0

00

Complete absence oflimb

Prevalence rates for the major subgroup Chromosomal anomalies increased on average

by 0.3% per year rising from 34.97 per 10,000 births in 2001-2002 to 38.67 in 2009-2010

(see Figure 10 and 15), with individual increasing trends found in the Odense and Tuscany

registries. Preliminary investigations by the registries showed that the increasing trends were

due to changes in case ascertainment (Tuscany) and diagnostic methods (Odense).

Tuscany also had increasing trends in Down syndrome and Edward syndrome, both of which

were explained as being due to changes in case ascertainment.


4.2.2 Continuing increasing trends

Five of the increasing trends detected in this year’s monitoring were investigated and

reported on in last years (2009) report. This section will outline similarities and differences in

the trends between each of the time periods.

Cystic adenomatous malformation of the lung (CCAM), a rare condition in which a

benign mass of abnormal lung tissue is present in a section of the lung, increased on

average by 7.8% per year with the prevalence rising from 0.51 per 10,000 births in 2001-

2002 to 1.11 in 2009-2010 (see Figure 15). In the 2009 monitoring statistically significant

increasing trends were observed in two individual registries, Wales and Wessex. In this

year’s analysis a statistically significant increasing trend was again detected in Wales, with a

new trend identified in the East Midlands and South Yorkshire registry, indicating that CCAM

may be a UK concern (see appendix E). The geographical variation of trends for this

anomaly was explored at this year’s RLM, comparing the individual UK registries with the

remaining registries (see Figure 8).

Figure 8. Increasing pan-Europe trend in Cystic adenomatous malformation of the lung by UK registry and the rest of Europe

All UK registries had rates that were higher than the rest of Europe, though Northern

England did show evidence of a decline in the latter half of the decade. Most cases of CCAM

are prenatally detected, and the increasing rates in the UK could reflect uniform changes in

the health service. However as the trends vary between the UK registries this may not fully

explain the increasing trend. Currently, the causes of this anomaly are not well understood.

Surgery is the recommended treatment for this condition. In some instances the tissue mass

detected prenatally may either reduce or disappear before birth.

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

2001-02 2003-04 2005-06 2007-08 2009-10

Prev

alen

ce p

er 1

0,00

0 bi

rths

Wales

East Mids & S York

Wessex

N England

Thames Valley

Rest of Europe


The prevalence rate of Gastroschisis increased again in this year’s statistical monitoring

(on average by 1.6% per year) rising from 2.19 per 10,000 births in 2001-2002 to 2.87 in

2009-2010 (see Figure 15). This condition is characterised by a hole in the abdomen

through which some of the intestine protrudes and requires corrective surgery in the

neonatal period. It is associated with factors such as young maternal age, maternal smoking,

low maternal BMI and socioeconomic status. Individual increasing trends detected in

Northern England and Ile de la Reunion in last year’s monitoring were once again detected

this year, with an additional new trend found in the Hungary registry. Additional exploratory

analysis by Central Registry showed that, of those registries with the highest prevalence

rates (>4 per 10,000 births), four out of five were in the UK (see Figure 9). More directed

action, particularly in the UK, is needed to address this public health concern.

Figure 9. Increasing pan-Europe trend in Gastroschisis in registries with low, medium and high prevalence

Once again all three chromosomal trisomies significantly increased in prevalence. Similar to

the 2009 Report individual trends in Down syndrome/trisomy 21 were again found in the

Paris and Tuscany registries. In 2009 increasing trends were not detected in individual

registries for Patau syndrome/trisomy 13, mostly due to the low numbers of cases in

individual registries limiting the opportunity to test for trends. In this year’s analysis

significant increasing trends were observed in two individual registries, Hungary and

Wielkopolska. There were increasing trends in Edward syndrome/trisomy 18 detected in

Tuscany and also Northern Netherlands (which also had an increasing trend in the 2009


report). Following adjustment for maternal age across all the trisomy groups these trends

were no longer found at pan-Europe or individual registry level. A recent EUROCAT paper

which examined temporal and geographic trends in the trisomies over a twenty year period

also reported an increase in total and total corrected prevalence of all three trisomies, which

was mostly explained by increasing maternal age5. This indicates that increases in trisomy

syndromes in general are associated with rises in the proportion of women delaying child

birth until later in life.

Figure 10 Prevalence of chromosomal anomalies showing a significant increase in the pan-Europe analysis

0

5

10

15

20

25

30

35

40

45

Pre

vala

nc

e p

er

10,0

00

Chromosomal anomalies

Down syndrome (unadj)

Edward syndrome(unadj)

Patau syndrome (unadj)

4.3 Decreasing trends

Decreasing trends identified in the 2009 pan-Europe statistical monitoring for the following

14 anomaly subgroups were also identified in 2010: All non-chromosomal anomalies; NTDs;

Spina bifida; Anophthalmos /Microphthalmos; VSD; ASD; Atresia of bile ducts; Congenital

hydronephrosis; Limb reduction; Hip dislocation; Syndactyly; Congenital skin disorders;

Genetic syndromes and microdeletions and Turner syndrome. New decreasing trends were

also detected for the following 7 subgroups: Anencephalus; Microcephaly; CHD;

Omphalocele; Upper limb reduction; Klinefelter syndrome; Down syndrome/trisomy 21

5 Loane et al (2012) Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: impact of

maternal age and prenatal screening European Journal of Human Genetics, 21: 27–33


(adjusted) (see Figure 15). This section summarises the results, investigation and

interpretation of specific anomaly subgroups that are considered to be either numerically

large (in comparison to other subgroups), may have clinical relevance to public health

authorities, or have shown evidence of strong trends.

The prevalence of NTDs, which includes anencephaly, spina bifida and encephalocele,

decreased for the fourth consecutive year of statistical monitoring. The prevalence rates

decreased by 1.7% per year from 10.25 per 10,000 births in 2001-2002 to 9.42 in 2009-2010

(see Figures 11 and 15), significant decreases observed in six individual registries (see

Appendix E and F).

Figure 11 Prevalence of the Neural tube defects showing a significant decrease in the pan-Europe analysis

0

2

4

6

8

10

12

Pre

vale

nce p

er

10,0

00

NTD

Spina bifida

Anencephalus andsimilar

In particular, rates for Spina bifida decreased on average by 2.1 % per year from 5.32 per

10,000 births in 2001-2002 to 4.67 in 2009-2010 (see Figures 12 and 15). In the 2009 report

statistically significant decreasing trends in spina bifida were also identified in four individual

registries, Odense, Dublin, Emilia Romagna and Wales. In this year’s analysis statistically

significant decreasing trends were observed in 3 different registries, Hainaut, South Portugal

and Wielkopolska. Hainaut have reported that their trend may have been a consequence of

changes in case ascertainment and South Portugal reported that they were investigating the

decreasing trend further.


Figure 12. Average annual change in prevalence in Spina bifida by registry

Anencephalus is characterised by the total or partial absence of brain tissue and the cranial

vault. The anomaly is incompatible with survival. A new decreasing trend was identified for

this anomaly which declined on average each year by 1.9% from 3.82 per 10,000 births in

2001-2002 to 3.6 in 2009-2010 (see Figures 12 and 15). Statistically significant individual

trends were found in the Wielkopolska and Wales registries. Overall the decreasing pan-

Europe trend for NTDs does indicate that public health measures aimed at reducing their

occurrence e.g. folic acid supplementation may be becoming effective. However of note are

the small annual percentage changes, ranging from 1.7 to 2.1%, suggesting that renewed or

more focused campaigns may be required to accelerate the reduction in NTDs across

Europe.

Congenital heart defects (CHD) are the most common subgroup of congenital anomaly,

with known risk factors including maternal chronic health conditions and maternal health

risk behaviours. This year a new decreasing trend was detected for the subgroup CHD

overall, which decreased on average by 0.6% per year from 74.17 per 10,000 births in

2001-2002 to 62.37 in 2009-2010 (see Figures 13 & 15).

Malta Basque Country N Netherlands Tuscany Hungary Vaud Thames Valley Odense East Midlands and South Yorkshire Zagreb Saxony Anhalt Paris Summary estimate Northern England Wessex Wales Dublin Antwerp Wielkopolska Emilia Romagna Styria Mainz Hainaut SE Ireland S Portugal

Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida Spina bifida

30% 20% 10% 10% 20% 30% No

change <-- Decrease Increase -->

Average annual change in prevalence

Non-linear change Rate of change Too few cases


Figure 13. Decreasing pan-Europe trend in CHD, ASD, VSD and severe CHD

0

10

20

30

40

50

60

70

80P

revale

nce p

er

10,0

00

CHD

VSD

ASD

Severe CHD

In particular decreasing trends were found for the two most common, and less severe, types

of cardiac defects, Ventricular septal defects (VSD) and Atrial septal defect (ASD), both

of which were also detected in the previous year’s monitoring. VSD decreased on average

by 0.4% per year from 30.44 per 10,000 births in 2001-2002 to 26.95 in 2009-2010, and

ASD decreased on average by 1.7% per year from 26.81 per 10,000 births in 2001-2002 to

16.39 in 2009-2010. A recent EUROCAT paper has examined trends in the prevalence of

CHD in Europe over the period 1990-2007. A decline in prevalence for all CHD types

combined was observed from 2004 onwards, prior to which there had been an increasing

trend. Our analysis, which includes post 2007 data, shows this decline to be continuing.

However, the decline in CHD was not consistent across all registries, with over half having

significant non-linear change (NLC) for both CHD overall and ASD. Fewer NLC were

detected for VSD (see Appendices E & F). The prevalence of VSD in a population is very

dependent on the access to echocardiography in infancy. For ASD there is no internationally

agreed definition in infancy. Possible reasons for the decrease in CHD may be an increased

uptake of folic acid supplementation by women of child bearing age. The limited studies that

have investigated this potential association have also reported decreases in relation to ASD

and VSD. It is also possible that other maternal risk factors known to be associated with

CHD may have received increased focus from public health authorities’ e.g. maternal

smoking. More population based research is required in order to better inform public health

interventions.


Once again there was a significant decline in Atresia of the bile ducts (biliary atresia) in

the pan-Europe analysis. This condition is characterised by the congenital absence of the

lumen of the extrahepatic bile ducts, which results in biliary obstruction and jaundice and

requires early surgery. Following treatment survival rates are high (90%) though a few

individuals may require a transplant. This defect is very rare – 0.26 per 10,000 births on

average over the monitoring period. This particular anomaly showed evidence of a strong

decrease with an annual average rate of change of 9%, with rates reducing from 0.39 per

10,000 births in 2001-2002 to 0.17 in 2009-2010 (see Figures 12 & 15). Investigation of the

trend by Central Registry showed that 68% of cases had no other recorded congenital

anomaly, and 38% were diagnosed after the first week of life. The decline in cases seemed

to be a general phenomenon across many registries, although the very low numbers

affected make this difficult to analyse. Maternal infective causes have been suggested as

aetiology for biliary atresia. Changes in types of infections in Europe or new vaccination

strategies may theoretically explain part of the decline.

Figure 14. Decreasing pan-Europe trend in Atresia of the bile ducts

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

0.4

0.45

Pre

vale

nce p

er

10,0

00

Atresia of Bile Ducts

Pan-Europe analysis for limb anomalies showed that once again there was a decrease in

prevalence for the subgroup Limb reduction anomalies. A new decreasing trend for the

subgroup Upper limb reduction was also detected (see Figure 15). The prevalence of limb

anomalies reduced on average by 2.1% per year from 5.48 per 10,000 births in 2001-2002

to 4.56 in 2009-2010, with statistically significant decreasing trends detected in three

individual registries Dublin, Styria and East Midland and South Yorkshire (see Appendix E).


The prevalence rate of upper limb reduction defects declined on average by 2.3% per year

from 3.83 per 10,000 births in 2001-2002 to 3.16 in 2009-2010, with statistically significant

individual decreasing trends observed in the Styria, Mainz and East Midland and South

Yorkshire registries. East Midland and South Yorkshire reported that the decreasing trend

observed in their registry was likely due to changes in case ascertainment, with delays in

and reduced reporting of cases.

Anophthalmos/microphthalmos is a rare condition in which the normal development of the

eye is disrupted. The pan-Europe analysis showed that the prevalence of this anomaly

decreased on average by 4% per year from 1.01 per 10,000 births in 2000-2001 to 0.70 in

2009-2010 (see Figure 15). A decreasing trend was also detected in the 2009 report. The

small numbers of cases in over half of the registries limited the testing of this trend in

individual registries, though a statistically significant decreasing trend was detected in East

Midlands and South Yorkshire registry, who reported that they did not consider this to be a

real trend (see Appendix G).

The chromosomal subgroups Turner syndrome and Klinefelter syndrome also decreased

in prevalence. Turner syndrome, which was also reported as declining in the previous year’s

monitoring decreased from 2.65 per 10,000 births in 2001-2002 to 2.43 in 2009-2010 (on

average each year by 1.9%), with individual decreasing trends observed in Basque country

and Vaud registries. The decreasing trend for Klinefelter syndrome, which was newly

detected this year, reduced in prevalence from 0.92 per 10,000 births in 2001-2002 to 0.68

in 2009-2010 (on average each year by 3.6%), and a statistically significant individual

decreasing trend was only observed in one registry, Tuscany. Changes in prenatal screening

methods towards more selective karyotyping analysis and/or towards a lower proportion of

women having invasive tests are possible explanations for these decreasing trends.


Figure 15: Estimated average percentage change in prevalence and 95% confidence intervals (Pan-Europe analysis)

All non-chromosomal anomalies Neural tube defects Anencephalus and similar Encephalocele Spina bifida Hydrocephaly Microcephaly Arhinencephaly/holoprosencephaly Anophthalmos/microphthalmos Anophthalmos Congenital cataract Congenital glaucoma Anotia Congenital heart disease Severe CHD Common arterial truncus Transposition of great vessels Single ventricle Ventricular septal defect Atrial septal defect Atrioventricular septal defect Tetralogy of Fallot Tricuspid atresia and stenosis Ebstein's anomaly Pulmonary valve stenosis Pulmonary valve atresia Aortic valve atresia/stenosis Hypoplastic left heart Hypoplastic right heart Coarctation of aorta Total anomalous pulmonary venous return Patent ductus arteriosus Choanal atresia Cystic adenomatous malformation of lung Cleft lip with or without palate Cleft palate Oesophageal atresia with or without trachea-oesophageal fistula Duodenal atresia or stenosis Atresia or stenosis of other parts of small intestine Ano-rectal atresia and stenosis Hirschsprung's disease

Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe

30% 20% 10% 10% 20% 30% No



Rate of change Too few cases


Atresia of bile ducts Annular pancreas Diaphragmatic hernia Gastroschisis Omphalocele Bilateral renal agenesis including Potter syndrome Renal dysplasia Congenital hydronephrosis Bladder exstrophy and/or epispadias Posterior urethral valve and/or prune belly Hypospadias Indeterminate sex Limb reduction Upper limb reduction Lower limb reduction Complete absence of a limb Club foot - talipes equinovarus Hip dislocation and/or dysplasia Polydactyly Syndactyly Skeletal dysplasias Craniosynostosis Congenital constriction bands/amniotic bands Situs inversus Conjoined twins Congenital skin disorders Teratogenic syndromes with malformations Fetal alcohol syndrome Valproate syndrome Maternal infections resulting in malformations Genetic syndromes + microdeletions Chromosomal Down syndrome Patau syndrome Edwards syndrome Turner syndrome Klinefelter syndrome Down syndrome adjusted Patau syndrome adjusted Edwards syndrome adjusted

Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe Pan-Europe

30% 20% 10%

10% 20% 30% No change

<-- Decrease Increase --> Average annual change in prevalence

Rate of change Too few cases


Table 1 Central Registry Statistical Monitoring Results: Reported 10 year trends by individual registry

Registry

Sty

ria

(A

T)

An

twe

rp (

BE

)

Hain

au

t (B

E)

Za

gre

b (

HR

)

Od

en

se

(D

K)

Isle

de

Re

un

ion

(F

R)

Pa

ris

(F

R)

Ma

inz (

DE

)

Sa

xo

ny

An

ha

lt (

DE

)

Hu

ng

ary

(H

U)

Du

bli

n (

IE)

SE

Ire

lan

d (

IE)

Em

ilia

Ro

ma

gn

a (

IT)

Tu

sc

an

y (

IT)

Ma

lta

(M

T)

N N

eth

erl

an

ds

(N

L)

Wie

lko

po

lska

(P

L)

S P

ort

ug

al

(PT

)

Bas

qu

e C

ou

ntr

y (

ES

)

Va

ud

(C

H)

E M

id &

S Y

ork

(G

B)

N E

ng

lan

d (

GB

)

Th

am

es

Va

lle

y (

GB

)

Wa

les

(G

B)

We

ss

ex

(G

B)

Years tested

20

02

-20

09

20

01

-20

10

20

01

-20

10

20

01

-20

10

20

01

-20

10

20

02

-20

09

20

01

-20

10

20

01

-20

10

20

01

-20

10

20

02

-20

09

20

01

-20

10

20

02

-20

09

20

01

-20

10

20

01

-20

10

20

02

-20

09

20

01

-20

10

20

02

-20

09

20

02

-20

09

20

01

-20

10

20

01

-20

10

20

01

-20

10

20

01

-20

10

20

01

-20

10

20

01

-20

10

20

01

-20

10

Total / in registries

89

1 1 3 2 1 4 5 0 5 16 0 1 3 4 2 8 3 0 9 4 4 4 3 3 3

Total \ in registries

125

9 3 4 1 1 1 1 3 6 1 11 3 9 4 3 3 12 6 3 5 17 7 1 10 1

Total ~ in registries

134 7 5 5 4 3 3 9 1 12 25 8 0 13 8 0 3 6 11 7 1 8 5 9 10 1

Total any in registries

378 17 9 12 7 5 8 15 4 23 42 19 4 25 16 5 14 21 17 19 10 29 16 13 23 5

Key: / = significant upward trend \ = significant downward trend ~ = non-linear change over time


5. Clusters

5.1 Overview

For cluster analysis a total of 882 tests were performed with 3.1% being statistically

significant, which is the proportion we would expect by chance (see Appendix H). Twenty

seven clusters were identified, three of which had been reported in the previous year’s

Statistical Monitoring Report (http://www.eurocat-network.eu/content/Stat-Mon-Report-

2009.pdf) (also see Appendix I). Preliminary investigations by registries into the clusters

detected in the analysis indicated that 12 of the 24 newly detected clusters were not ‘true’

clusters as defined by the EUROCAT definition, and could be explained by data quality

errors, late case ascertainment and changes in diagnostic methods (see Table 2).

For the remaining 8 clusters the respective registries confirmed an excess of cases that

could not be explained by data contained within the registry. Clusters were confirmed for the

following anomalies: Anencephalus (SW England); Cleft lip with /without palate (East Mids

and S Yorkshire); Omphalocele (N Netherlands); Renal dysplasia (Thames Valley);

Congenital hydronephrosis (Antwerp); Bladder exstrophy/epispadia (N Netherlands); Club

foot (Antwerp) and Syndactyly (Emilia Romagna). The registries reported that no further

investigations were planned at local level beyond continued surveillance. The PMC met in

May 2012 to discuss these 8 clusters, with a consensus that the Bladder

exstrophy/epispadia and Anencephalus clusters were of the most interest. It was agreed that

the relevant registries should report these at the RLM.

5.2 Reports of preliminary investigations of specific clusters by registries

Bladder exstrophy and/or epispadia is a rare urinary anomaly, with an overall prevalence

rate of 0.63 per 10,000 births established in this year’s statistical monitoring. Cases with this

anomaly have a spectrum of defects affecting the bladder, the lower abdominal wall, the

ureteral tract and genitalia. This cluster in Northern Netherlands started at the end of May

2008, and ended approximately one week after the beginning of December 2008. In 202

days 7 cases were found when only an average of 1.17 cases would normally occur

(p<0.001). The preliminary investigation by the registry confirmed the diagnosis, verifying

this through examination of medical files. The registry reported that there were no duplicate

cases, and that the mothers lived in different places in the registration area. There was some

evidence of a family history for 2 of the cases. The registry reviewed the following

aetiological factors: maternal age; use of artificial reproductive technology; use of folic acid;

http://www.eurocat-network.eu/content/Stat-Mon-Report-2009.pdf

http://www.eurocat-network.eu/content/Stat-Mon-Report-2009.pdf


lifestyle risk factors (which were available in Northern Netherlands) and maternal occupation.

Of the 7 cases in the cluster 3 had bladder exstrophy and 4 had epispadias.

Within the bladder exstrophy cases 1 was isolated, 1 had bladder exstrophy as part of OEIS

complex and 1 had associated anomalies (congenital hip dysplasia). Within the Epispadias

cases 2 were isolated, 2 had associated anomalies (1 case with bilateral multicystic renal

dysplasia, 1 case with mild dysplastic hip (this is a minor anomaly in EUROCAT)). The

registry concluded that because of the heterogeneous nature of the malformations combined

with the low numbers per year that the cluster most likely occurred by chance. The registry

also drew attention to the fact that a cluster of Omphalocele, an abdominal wall defect, was

also detected in their registry. This cluster of 8 cases started one week into July 2008 and

ended in the middle of August 2008, and the registry suggested a possible joint analysis of

both clusters given the omphalocele, exstrophy, imperforate anus, and spinal defects (OEIS)

complex. The registry decided that before proceeding further they would observe the

prevalence of both malformations for the next year.

The second cluster considered to be of interest to the PMC was for the anomaly

Anencephalus. This cluster was detected in the South West England registry, and started

towards the end of December 2008, and ended approximately three weeks after the

beginning of January 2009. Over a period of 29 days 9 cases were found when only an

average of 1.32 cases would normally occur (p=0.024). The preliminary investigation by the

registry confirmed the diagnosis of the cases as accurate. They reported that there was no

evidence of geographical clustering, that no particular hospital was “repeatedly involved”,

and that they did not consider the cluster to be part of a longer time trend. Of the 9 cases 7

were isolated anencephaly, (one of which was associated with maternal diabetes) and 2 had

exomphalos (of which, 1 was limb-body-wall complex). The registry reviewed the aetiological

factors maternal diabetes (see above) and periconceptional folic acid. They reported that 3

mothers had taken folic acid but not known when; 2 were recorded as not taking folic acid;

and it was not known for 5 if they took folic acid. The registry concluded that cluster could

not be explained by the preliminary investigations, though they did point out that the annual

prevalence rate of this anomaly had not “obviously increased” locally. The registry reported

that it has sought further opinion from clinicians within their Health trust, and stated that “no

further investigations are planned locally”.


Table 2: Outcomes of local registry preliminary investigations of new clusters detected in 2010 monitoring (n=24)

Anomaly Registry EUROCAT Classification of Explanation No of

cases in cluster

Length of

cluster (days)

P

Neural tube defects Mainz

Data Quality Issues found to explain cluster: changes in ascertainment methods; duplicate cases or miscoding. Of the five cases found in 1 month 1 was a duplicate

5 34

0.025

Anencephalus & Similar

SW England

Excess of cases confirmed, but no further investigation proposed other than further surveillance. Further opinion sought locally, but no further investigations are planned locally.

9 29

0.024

Transposition of GV Hainaut

Excess of cases confirmed, but no further investigation proposed other than further surveillance. Thought to be part of increasing trend observed during 2001-2010

5 36

0.039

Ventricular septal defect

Thames valley

Data Quality Issues found to explain cluster: changes in ascertainment methods; duplicate cases or miscoding. Access to outpatient records since 2009 has led to increased

numbers of isolated VSD diagnosed after the neonatal period

116 541

<0.001

Atrial septal defect Thames valley

Data Quality Issues found to explain cluster: changes in ascertainment methods; duplicate cases or miscoding. Access to outpatient records since 2009 has led to increased

numbers of ASD diagnosed after the neonatal period.

68 347

<0.001

Atrial septal defect Emilia

Romagna

Cluster associated with diagnostic criteria: aetiologic heterogeneity, changes in inclusion criteria or diagnosis, familial or twin occurrence. Cases were identified by

specific surgery notifications after the first week of life and had not been notified to the registry previously

85 525

<0.001

Pulmonary valve atresia

Emilia Romagna



9 157

0.008



cases in cluster

Length of

cluster (days)

P

Aortic valve atresia/stenosis #

Emilia Romagna



5 100 0.04

Hypoplastic right heart SW England

Data Quality Issues found to explain cluster: changes in ascertainment methods; duplicate cases or miscoding. 1 of 6 cases in cluster was found to be miscoded

6 304 0.043

Cleft lip with or without palate#

Hainaut

Excess of cases confirmed. No further action other than continued surveillance. Registry to investigate aetiologic factors.

9 34 0.017

Cleft lip with or without palate

E Mids & S Yorkshire

Excess of cases confirmed. No further action other than continued surveillance. Registry

do not considered this cluster worthy of investigation as it is geographically widespread. Some data verification on-going

5 2 0.019

Cleft palate Hainaut

Excess of cases confirmed with no explanation in registry data; no further action other than continued surveillance.

7 64 0.019

Cleft palate Emilia

Romagna



5 4 0.007

Hirschsprung’s disease

Emilia Romagna



13 332 <0.001



cases in cluster

Length of

cluster (days)

P

Omphalocele N Netherlands

Excess of cases confirmed with no explanation in registry data. No further action other than continued surveillance.

8 404 0.041

Renal dysplasia Thames Valley

Excess of cases confirmed with no explanation in registry data. No further action other than continued surveillance

7 22 0.019

Congenital hydronephrosis

Antwerp


15 105 0.027


N England No report of preliminary investigations sent to Central Registry 75 544 0.044

Bladder exstrophy and/or epispadia

N Netherland

Excess of cases confirmed with no explanation in registry data. No further action other than continued surveillance. The registry will look at the heterogeneous nature of the

malformations and the low numbers per year, and will follow up the prevalence of these malformations in the next year.

7 202 <0.001

Club foot Antwerp


11 39 0.018

Club foot Emilia

Romagna



7 5 0.009



cases in cluster

Length of

cluster (days)

P

Polydactyly Paris

Data Quality Issues found to explain cluster: changes in ascertainment methods; duplicate cases or miscoding. Under registration of cases in the immediate preceding years

19 164 0.006

Syndactyly Emilia

Romagna

Data Quality Issues found to explain cluster: changes in ascertainment methods; duplicate cases or miscoding. Of the 6 cases in the cluster 2 duplicate cases were found.

Registry will continue surveillance.

6 10 0.007

Down syndrome Mainz

Excess of cases confirmed with no explanation in registry data; no further action other than continued surveillance.

9 45 0.026

Note : # Cluster detected using Date of Birth


5.3 Taskforce for the Evaluation of Clusters

The Taskforce for Evaluation of Clusters (TEC) is a permanent committee, reporting to the

EUROCAT Project Management Committee (PMC) and has the following remit:

To comment on the output of cluster investigations conducted by EUROCAT,

including its presentation and possible uses, at the request of the PMC.

To serve as a consulting unit in cases of clusters, commissioned by EUROCAT or

individual member registries.

At the 2012 Registry Leaders Meeting in Budapest the TEC held an open consultation

session. The aim of this was to inform the registries of the role of the TEC, to provide them

with the opportunity to receive advice on any clusters detected in their registry and to

discuss in general how the preliminary investigation of clusters by the registries could be

improved. It was highlighted by members of the TEC that as a dedicated committee they

would have more time to investigate the cluster compared to registries, and that there was

expertise available to provide advice on the medical genetic components of clusters. A key

concern raised by the registry leaders was the difficulty in obtaining and interpreting the

aetiological data needed to inform the preliminary investigation of clusters. In particular the

paucity of population-based exposure data for comparison was highlighted. It was suggested

that available data on exposures between registries could be compared to determine if there

is something different about the detected cluster. Registries were reminded that the purpose

of the preliminary investigation of clusters was not to prove cause, but to generate

hypotheses that can be tested through further research. Also identified was the variability in

the quality of reports sent to Central Registry, using the cluster template. This is outlined in

the next section. The high number of ‘explained excesses of cases’ were discussed, and the

importance of continuing with high quality surveillance in order to prevent another

thalidomide type event was emphasised. Registries were reminded that EUROCAT’s

statistical monitoring is the only surveillance of congenital anomalies that takes place in

Europe at present. The TEC continues to be available for consultation on clusters identified

by registries.

5.3.1 Improving the quality of preliminary cluster investigations

When a cluster is detected registries are sent a number of documents associated with the

analysis. Among this is a standardised form referred to as the cluster template. Both the

PMC and TEC highlighted the need for the full completion and expedient return of the


investigation template. Should clusters be identified as a cause for concern, it is important

that these are investigated further in a timely manner with the appropriate authorities

notified. Also the comprehensive completion of the cluster template at the preliminary

investigations stage facilitates the TEC in providing advice. At the 2012 RLM Central

Registry delivered a presentation on the completion of the cluster template, highlighting

sections of the template that were considered cause for concern due to limited completion by

the registries. One specific area was the section on aetiological factors, which is of particular

importance in helping to justify the conclusion of the preliminary investigations. Key issues

identified included the provision of limited information, and also the lack of clarity in

identifying which factors had/had not been investigated and the associated reasons for not

investigating certain factors. There are a number of reasons why this section of the report

may be poorly completed. For example one general issue for many of the registries is that

their database may have incomplete data. It was recognised that registries should use their

judgement to determine which factors should be investigated at the preliminary stage.

Registries were reminded that advice could also be obtained from the TEC regarding which

factors to focus investigations on. A discussion between the TEC panel and registry leaders

led to suggestions of a more detailed template being developed, listing the aetiological

factors that should be investigated, where possible, with a response format that allows the

registries to clearly indicate if they did or did not investigate these factors. The feasibility of

developing a new template for the next Annual Statistical Monitoring is under review.

5.4 Dissemination of the findings of the Statistical Monitoring Report

The distribution of epidemiological information on the prevalence of congenital anomalies,

and the investigation of clusters and trends detected through statistical monitoring have

been identified as key strategies within Work Package 2: Dissemination of the Joint Action.

Also recognised is the need to ensure that this information is made widely available to all

stakeholders with an interest in congenital anomalies. The Annual Statistical Monitoring

Report is considered to be an important tool in delivering timely information on the stability

and change in the prevalence of congenital anomalies across Europe. This section reports

on the findings of a survey administered to the registries to determine the use of the Report

in their region. A press release of the 2009 Report was issued by Central Registry and can

be viewed at the following location: http://news.ulster.ac.uk/releases/2012/6415.html. In

future a system of coordinated press releases across registries is planned.

http://news.ulster.ac.uk/releases/2012/6415.html


5.4.1 Survey on the use of the Statistical Monitoring Report

From 2007 the EUROCAT Annual Statistical Monitoring Report has been published online

on the EUROCAT web site, making them accessible for any individual or group. Registries

are encouraged to disseminate the findings in their own region. In 2011 Central Registry

administered a brief questionnaire asking registries to provide details of who they had

disseminated the findings of the Report to, how they had done this and if the findings are/or

had ever been used to influence or change public health agendas within their region or

country. Out of the 30 registries asked to take part in the survey 19 (63%) completed and

returned the questionnaire to central registry. The key findings of the survey were:

•Thirteen registries (68%) reported that they had submitted the findings of the Report to the

relevant person within the public health system in their region:

o Three registries (15%) stated that submission of this report to public health authorities was a compulsory requirement

o The remaining 10 registries indicated that it was voluntary

•Eight registries (42%) reported that they disseminated the findings of the report to others in

the health care system, including obstetricians, geneticists, paediatricians, midwives,

neonatologists and gynaecologists. Other recipients identified included a registry steering

group, parents groups, associations and initiative groups of scientists.

•The most common format of dissemination was through written report, either in full or

summarised to include the important findings only.

•The findings of the Report were not widely disseminated on local registry websites or on

‘other’ websites. Four registries made the report available on the local registry website, with

a further two publishing the report on websites outside their organisations.

•Seminars and scientific meetings, a more common method of dissemination, were mostly at

local/regional level. Only one registry reported disseminating the findings through co-

ordinated press releases with their local Birth Defects Prevention Program.

•Three registries stated that the Report had been used to influence changes in public health

agendas within their region. This included being used in regional health planning

preparation, influencing dietary changes in folic acid intake and in instigating the creation of

a regional Centre for Prenatal Diagnostics.

A full copy of the report can be viewed in Appendix K


6. Conclusion

The EUROCAT network, now in its 33rd year, continues to make available much needed

epidemiologic data for a comprehensive range of congenital anomalies within Europe. Of

particular concern is the identification of increasing trends in gastroschisis, which has now

been detected in the pan-Europe analysis for the fourth consecutive year. For trisomy 13,

18 and 21 the application of analytic methods allowing for the adjustment for maternal age

across all the three trisomy anomalies has clarified that the lifestyle choice of delaying

childbirth until later in life has led to an increase in the prevalence of these chromosomal

anomalies. It should be noted that this year there was a significant rise in the number of

increasing trends identified compared to previous years. Co-ordinated surveillance of these

trends both at pan-Europe and individual registry level should continue to ascertain if these

are early signals of emerging public health concerns. Also detected were decreasing trends

for a significant number of anomaly subgroups. In particular rates of NTDs including spina

bifida have been decreasing over the last decade although this has been a shallow decline

and has recently levelled off. Primary prevention of congenital anomalies continues to be a

key objective of the EUROCAT network, and is reflected in the current ethos of the Joint

Action. By systematically coordinating both the surveillance and investigations of risk factors

for congenital anomalies at European level this will provide information for the development

and evaluation of primary prevention strategies.


Appendix A: Congenital anomaly subgroup inclusion list The EUROCAT congenital anomaly subgroups are defined in EUROCAT Guide 1.3, Chapter 3.3 (http://www.eurocat-network.eu/content/EUROCAT-Guide-1.3.pdf). The following list shows which subgroups are to be analysed in the following ways:

1. Prevalence by outcome of pregnancy, by registry and year (or combined registries/years). All cases and all cases excluding chromosomal cases.

2. Analysis of trends, all outcomes of pregnancy combined. Chromosomal cases excluded from all subgroups except chromosomal subgroups.

3. Detection of clusters, all outcomes of pregnancy combined. Chromosomal cases excluded from all subgroups except chromosomal subgroups.

.

EUROCAT Subgroups

Prevalence by pregnancy outcome,

registry, year

Include in monitoring of

trends

Include in monitoring of

clusters

All anomalies NO Nervous system NO NO Neural Tube Defects Anencephalus and similar Encephalocele Spina Bifida Hydrocephalus Microcephaly Arhinencephaly / holoprosencephaly

Eye NO NO Anophthalmos / microphthalmos Anophthalmos Congenital cataract Congenital glaucoma Ear, face and neck NO NO Anotia Congenital heart defects (CHD) NO Severe CHD Common arterial truncus Transposition of great vessels Single ventricle VSD ASD AVSD Tetralogy of Fallot Tricuspid atresia and stenosis Ebstein's anomaly Pulmonary valve stenosis

http://www.eurocat-network.eu/content/EUROCAT-Guide-1.3.pdf


Aortic valve atresia/stenosis Hypoplastic left heart Hypoplastic right heart Coarctation of aorta Total anomalous pulm venous return

PDA as only CHD in term infants (GA +37 weeks)

Respiratory NO NO Choanal atresia Cystic adenomatous malf of lung Oro-facial clefts NO NO Cleft lip with or without cleft palate Cleft palate Digestive system NO NO Oesophageal atresia with or without tracheo-oesophageal fistula

Duodenal atresia or stenosis Atresia or stenosis of other parts of small intestine

Ano-rectal atresia and stenosis Hirschsprung's disease Atresia of bile ducts Annular pancreas Diaphragmatic hernia Abdominal wall defects NO NO Gastroschisis Omphalocele Urinary NO NO Bilateral renal agenesis including Potter syndrome

Renal Dysplasia Congenital hydronephrosis Bladder exstrophy and/or epispadia Posterior urethral valve and/or prune belly

Genital NO NO

Hypospadias

Indeterminate sex

Limb NO NO

Limb reduction

Upper limb reduction

Lower limb reduction Complete absence of a limb


Club foot - talipes equinovarus

Hip dislocation and/or dysplasia

Polydactyly

Syndactyly

Other anomalies/ syndromes

Skeletal dysplasias

Craniosynostosis

Congenital constriction bands/amniotic band

Situs inversus

Conjoined twins

Congenital skin disorders

Teratogenic syndromes with malformations

NO

Fetal alcohol syndrome

Valproate syndrome

Maternal infections resulting in malformations

Genetic syndromes + microdeletions NO

Sequences NO NO

Chromosomal NO

Down syndrome

Patau syndrome/trisomy 13

Edward syndrome/trisomy 18

Turner syndrome

Klinefelter syndrome Down syndrome Adjusted NO NO

Patau syndrome Adjusted NO NO

Edward syndrome Adjusted NO NO


Appendix B: Summary of statistical methods Trends

The pan-Europe monitoring can only be conducted centrally as it uses data from all the

registries combined. The methodology used for pan-Europe monitoring is the same as for

the ten year trend monitoring (Box 1) with the exception that it is run using the last 10 years

of data (2001-2010) or using 9 years of data within the 10 year period (2001-2010) and

adjusts for the effect of registry.

1. A chi square test for trend and for non-linear change based on number of cases and

number of births per year is performed.

2. Ten year trend tests are run using at least eight years of data within the 10 year

period (2001-2010). Data before the year 2001 cannot be included.

3. Trend analysis is presented by individual year unless there are too few cases, when

data is then grouped by two year intervals.

4. Trend analysis is always based on year of birth/delivery.

5. A trend test is performed if the average expected number of cases per 2 year interval

is 5 or more, OR if the observed number of cases per 2 year interval is 2 or more

6. Significant increasing or decreasing monotonic (going in one direction) trends are

reported.

Where p<0.05 for trend component and p>0.01 for non-linear component, the

results are identified as ‘increasing or decreasing trend‘

Where p<0.05 for trend component and p<0.01 for non-linear component and the

prevalence trend is monotonic, the results are identified as ‘increasing or

decreasing trend '

Where p<0.05 for trend component and p<0.01 for non-linear component and the

prevalence trend is not monotonic, the results are identified as 'non-linear

change'

Where p>0.05 for trend component and p<0.05 for non-linear component, the

results are identified as 'non-linear change'.

Where p>0.05 for trend component and p>0.05 for non-linear component, the

results are interpreted as showing no significant change over time.


7. Trend analysis is conducted on all 78 EUROCAT congenital anomaly subgroups and

the following computer generated subgroups adjusted for maternal age and in utero

survival: Down syndrome, Patau syndrome and Edward syndrome.

8. Registries must have used ICD10 coding for the whole 10 year period tested to be

included in surveillance of the following 7 subgroups:

Severe CHD

Aortic valve atresia/stenosis

Hypoplastic right heart

Cystic adenomatous malformation of lung

Skeletal dysplasia


Valproate syndrome

Clusters

1. A ‘scan’ moving window method is used to detect clusters, (See EUROCAT

Statistical Monitoring Protocol http://www.eurocat-network.eu/content/EUROCAT-

Statistical-Monitoring-Protocol-2010.pdf), scanning all recorded cases in the period

2006-2010.

2. Clusters or deficits occurring in the last 2 years (2009-2010) that are less than 18

months in length are reported.

3. A minimum of 7 cases over the surveillance period (2006-2010) is needed to run the

scan analysis.

4. The default scan analysis uses estimated date of conception, if date of conception

cannot be estimated for more than 10% of cases, then cluster analysis uses date of

birth.

5. When date of conception is used as a basis for cluster detection, the period of

surveillance ENDS with dates of conception on 31 March in the last year under

surveillance (2010). If date of birth/delivery is used to detect clusters, the last full

year (1 January – 31 December) is included in the surveillance.

6. The output of cluster analyses lists all significant clusters which may be over-lapping.

All the output data should be examined to determine the full time period over which


the excess number of cases is observed. This may be outside the start and end date

of the most significant cluster.

Cluster analysis is run on 73 EUROCAT subgroups of congenital anomalies

(Appendix A). Seventeen major heterogeneous subgroups (e.g. Nervous system,

Eye, Congenital heart disease etc.) are excluded from analysis.

7. Cluster test results are presented alongside 5-year trend (chi square) results, to help

assess whether the cluster could be described as a short term trend.


Appendix C: Summary of local registry preliminary investigation protocols for

identified ten year trends and clusters

Investigation protocols and templates provided to make the reporting process consistent

between registries are described in full in the EUROCAT Statistical Monitoring Protocol

(http://www.eurocat-network.eu/content/EUROCAT-Statistical-Monitoring-Protocol-2010.pdf).

Using the templates registries were asked to include the following in their investigation

report:

Ten year trends:

1. Are there changes in diagnosis, in reporting, in coding, or in population definition that explain the trend?

2. Are there any known reasons why this might be a “real” trend in frequency of the anomaly?

3. Will the investigation continue (if so, how? if not, why not?)?

4. Which public health authority will the result be reported to?

Investigations into significant decreasing trends are classified as follows:

A: Changes in case ascertainment (data quality)

B: Changes in local or central registry methods e.g. definitions and inclusion criteria

C: Changes in diagnostic methods

D: Trend confirmed, due to known demographic changes

E: Trend confirmed, investigation on-going

F: Trend confirmed, further surveillance proposed before more detailed investigation

G: Not real trend when additional years added, or heterogeneous subgroup

H: No report or clear interpretation of preliminary investigations sent

Some trends can be explained by a combination of the classification categories e.g. A/B.

The first classification category is considered the principal one, so trends classified as A/B

are counted in the A category.



Clusters:

1. The methods and results of investigations as to whether changes in diagnostic

methods, training, personnel or reporting practice contributed to the cluster.

2. The methods and results of any investigation into aetiological factors, including which

aetiological factors were investigated and which source of information was used (registry database, further access to medical records or parents etc.).

3. Any local concerns about exposures and how they came to your attention.

4. Whether anyone in your region (e.g. local community or health professional) had

previously been aware of the cluster.

5. The basis for your decisions to conduct the investigation in the way you did, and whether you will continue to investigate (if so, how? if not, why not?).

6. Which public health authorities have been or will be notified about the cluster?

7. Registries are asked to conclude from their preliminary investigations if this is a ‘true

cluster of concern or not’

Cluster investigations can be classified as follows:

Apparent cluster with cause for concern, further investigation on-going

Cluster associated with aetiologic heterogeneity, changes in inclusion criteria,

diagnosis, familial or twin recurrence

Excess of cases confirmed, but no further investigation proposed other than further

surveillance

Increase in cases, due to increasing use of invasive prenatal diagnostic procedures

or improvements in prenatal ultrasound detection rates

Data quality issues found to explain cluster

No report of preliminary investigations sent to Central Registry


Appendix D: Summary of significant ten year increasing and decreasing trends detected in the pan-Europe analysis*

Anomaly Subgroup Direction Signalled in 2009

% Change

Lower CI Upper CI

All non-chromosomal anomalies Decreasing Yes -1.0 -1.2 -0.8

Neural tube defects Decreasing Yes -1.7 -2.7 -0.8

Anencephalus and similar Decreasing No -1.9 -3.5 -0.3

Spina bifida Decreasing Yes -2.1 -3.4 -0.7

Microcephaly Decreasing No -2.0 -3.9 -0.1

Anophthalmos/microphthalmos Decreasing Yes -4.0 -7.1 -0.8

Congenital heart defects Decreasing No -0.6 -0.9 -0.2

Single ventricle Increasing No +5.9 +1.9 +10.0

Ventricular septal defect ‡ Decreasing Yes -0.4 -0.9 +0.1

Atrial septal defect Decreasing Yes -1.7 -2.3 -1.1

Tetralogy of Fallot Increasing No +2.3 +0.5 +4.1

Cystic adenomatous malformation of lung Increasing Yes +7.8 +4.1 +11.6

Oesophageal atresia with or without trachea-oesophageal fistula

Increasing No +1.8 -0.2 +3.9

Duodenal atresia or stenosis Increasing No +4.4 +1.1 +7.9

Atresia or stenosis of other parts of small intestine

Increasing No +4.4 +0.9 +8.1

Atresia of bile ducts Decreasing Yes -9.0 -14.1 -3.4

Gastroschisis ‡ Increasing Yes +1.6 -0.2 +3.5

Omphalocele Decreasing No -2.2 -4.2 -0.2

Renal dysplasia Increasing No -3.0 +1.5 +4.6

Congenital hydronephrosis Decreasing Yes -2.0 -2.9 -1.1

Limb reduction Decreasing Yes -2.1 -3.4 -0.8

Upper limb reduction Decreasing No -2.3 -3.8 -0.7

Complete absence of a limb Increasing No +7.8 +0.3 +15.8

Hip dislocation and/or dysplasia Decreasing Yes -3.6 -4.8 -2.5

Syndactyly Decreasing Yes -3.7 -5.0 -2.5

Craniosynostosis Increasing No +3.6 1.3 5.9

Congenital skin disorders Decreasing Yes -17.6 -19.4 -15.8

Genetic syndromes + microdeletions Decreasing Yes -3.6 -4.9 -2.3

Chromosomal Increasing No +0.3 -0.2 +0.7

Down syndrome (unadjusted) Increasing Yes +1.1 +0.4 +1.7

Patau syndrome (unadjusted) Increasing Yes +2.4 +0.1 +4.6

Edwards syndrome (unadjusted) Increasing Yes +2.3 +0.9 3.7

Turner syndrome Decreasing Yes -1.9 -3.8 +0.0

Klinefelter syndrome Decreasing No -3.6 -6.5 -0.5

Down syndrome adjusted Decreasing No -0.9 -1.6 -0.2

Note: *Significant non-linear change not included in this table; ‡ Borderline


Appendix E: Forest plots showing ten year increasing and decreasing trends detected

in the pan-Europe analysis by anomaly subgroup

WessexOdenseParisTuscanyDublinEmilia RomagnaZagrebS PortugalAntwerpBasque CountryWalesWielkopolskaThames ValleyEast Midlands and South YorkshireHungaryN NetherlandsSummary estimateSaxony AnhaltNorthern EnglandVaudHainautMainzMaltaStyriaSE Ireland

All non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomaliesAll non-chromosomal anomalies

20% 10% 10% 20%Nochange


Non-linear change

Rate of change

Too few cases

N NetherlandsMaltaTuscanyZagrebAntwerpBasque CountryOdenseSaxony AnhaltHungaryVaudEast Midlands and South YorkshireParisNorthern EnglandThames ValleySummary estimateWalesHainautWessexEmilia RomagnaMainzDublinWielkopolskaStyriaSE IrelandS Portugal

Neural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defectsNeural tube defects

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


N NetherlandsAntwerpHainautVaudEast Midlands and South YorkshireStyriaNorthern EnglandTuscanyHungaryZagrebMaltaMainzThames ValleyParisSummary estimateBasque CountryEmilia RomagnaWessexOdenseSaxony AnhaltWalesSE IrelandDublinWielkopolskaS Portugal

Anencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similarAnencephalus and similar

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

ParisNorthern EnglandWalesSummary estimateHungaryHainautOdenseTuscanyDublinN NetherlandsZagrebMaltaS PortugalAntwerpBasque CountryMainzStyriaSE IrelandEmilia RomagnaWielkopolskaEast Midlands and South YorkshireSaxony AnhaltVaudThames ValleyWessex

EncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephaloceleEncephalocele

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


MaltaBasque CountryN NetherlandsTuscanyHungaryVaudThames ValleyOdenseEast Midlands and South YorkshireZagrebSaxony AnhaltParisSummary estimateNorthern EnglandWessexWalesDublinAntwerpWielkopolskaEmilia RomagnaStyriaMainzHainautSE IrelandS Portugal

Spina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifidaSpina bifida

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

HainautBasque CountryN NetherlandsParisVaudThames ValleyTuscanyEast Midlands and South YorkshireHungaryZagrebMaltaS PortugalSE IrelandWessexSummary estimateWalesNorthern EnglandAntwerpWielkopolskaOdenseEmilia RomagnaStyriaMainzDublinSaxony Anhalt

HydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephalyHydrocephaly

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


Basque CountryHungaryWielkopolskaAntwerpParisN NetherlandsWessexHainautSaxony AnhaltOdenseZagrebMaltaS PortugalMainzThames ValleySE IrelandVaudEmilia RomagnaSummary estimateTuscanyWalesNorthern EnglandDublinStyriaEast Midlands and South Yorkshire

MicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephalyMicrocephaly

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

Basque CountryWessexHungaryHainautOdenseTuscanyDublinN NetherlandsVaudZagrebMaltaS PortugalAntwerpSaxony AnhaltMainzStyriaWielkopolskaThames ValleySE IrelandParisSummary estimateEast Midlands and South YorkshireEmilia RomagnaNorthern EnglandWales

Arhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephalyArhinencephaly/holoprosencephaly

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


HungaryWessexEmilia RomagnaHainautOdenseVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaThames ValleySE IrelandN NetherlandsSummary estimateDublinWalesWielkopolskaTuscanyParisNorthern EnglandEast Midlands and South Yorkshire

Anophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmosAnophthalmos/microphthalmos

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

HainautOdenseParisTuscanyDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaWalesWielkopolskaThames ValleyWessexEast Midlands and South YorkshireNorthern EnglandHungarySE IrelandSummary estimate

AnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmosAnophthalmos

10% 5% 5% 10%Nochange


Non-linear change

Rate of change

Too few cases


Emilia RomagnaHungaryBasque CountrySummary estimateN NetherlandsTuscanyHainautOdenseParisVaudZagrebMaltaS PortugalAntwerpSaxony AnhaltMainzStyriaWielkopolskaThames ValleyWessexSE IrelandDublinWalesNorthern EnglandEast Midlands and South Yorkshire

Congenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataractCongenital cataract

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

HungarySummary estimateWalesHainautOdenseParisTuscanyDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaWielkopolskaThames ValleyWessexEast Midlands and South YorkshireNorthern EnglandSE Ireland

Congenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucomaCongenital glaucoma

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


ParisHainautOdenseTuscanyDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaWalesWielkopolskaThames ValleyWessexEast Midlands and South YorkshireNorthern EnglandSE IrelandSummary estimateHungary

AnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotiaAnotia

20% 10% 10% 20%Nochange


Non-linear change

Rate of change

Too few cases

WessexParisTuscanyDublinEmilia RomagnaZagrebS PortugalAntwerpSaxony AnhaltWalesWielkopolskaThames ValleyNorthern EnglandHungarySummary estimateBasque CountryN NetherlandsOdenseVaudHainautMainzEast Midlands and South YorkshireMaltaSE IrelandStyria

Congenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart diseaseCongenital heart disease

20% 10% 10% 20%Nochange


Non-linear change

Rate of change

Too few cases


MaltaThames ValleyTuscanyWessexEmilia RomagnaWalesBasque CountryParisN NetherlandsNorthern EnglandSummary estimateEast Midlands and South YorkshireS PortugalSaxony AnhaltHungaryStyriaOdenseHainautAntwerpZagrebSE IrelandVaudDublinMainzWielkopolska

Severe CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHDSevere CHD

20% 10% 10% 20%Nochange


Non-linear change

Rate of change

Too few cases

WessexHungaryWielkopolskaEast Midlands and South YorkshireSummary estimateWalesHainautOdenseParisTuscanyN NetherlandsVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaThames ValleySE IrelandEmilia RomagnaNorthern EnglandDublin

Common arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncusCommon arterial truncus

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


HainautEast Midlands and South YorkshireTuscanyThames ValleyParisEmilia RomagnaN NetherlandsDublinSummary estimateNorthern EnglandBasque CountryHungaryOdenseVaudZagrebMaltaS PortugalMainzSE IrelandWalesWessexAntwerpWielkopolskaSaxony AnhaltStyria

Transposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vesselsTransposition of great vessels

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

HungaryWielkopolskaParisSummary estimateEast Midlands and South YorkshireWalesHainautOdenseDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalBasque CountrySaxony AnhaltMainzStyriaThames ValleyWessexNorthern EnglandSE IrelandTuscanyAntwerp

Single ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricleSingle ventricle

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


MainzOdenseHainautParisTuscanyDublinEmilia RomagnaZagrebAntwerpSaxony AnhaltStyriaWalesWielkopolskaThames ValleyEast Midlands and South YorkshireHungaryWessexSummary estimateBasque CountrySE IrelandS PortugalN NetherlandsNorthern EnglandMaltaVaud

Atrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defectAtrial septal defect

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


N NetherlandsHungaryBasque CountrySaxony AnhaltWessexThames ValleyAntwerpWalesStyriaEast Midlands and South YorkshireSummary estimateEmilia RomagnaOdenseZagrebMaltaS PortugalMainzSE IrelandParisTuscanyNorthern EnglandVaudDublinHainautWielkopolska

Atrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defectAtrioventricular septal defect

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

WalesVaudS PortugalStyriaParisThames ValleyHainautWessexEmilia RomagnaSaxony AnhaltNorthern EnglandSummary estimateDublinTuscanyEast Midlands and South YorkshireBasque CountryZagrebMaltaMainzSE IrelandHungaryAntwerpN NetherlandsOdenseWielkopolska

Tetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of FallotTetralogy of Fallot

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


WessexHungaryEast Midlands and South YorkshireSummary estimateHainautOdenseParisTuscanyDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaWielkopolskaThames ValleyNorthern EnglandSE IrelandWales

Tricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosisTricuspid atresia and stenosis

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

WalesWessexHainautOdenseTuscanyDublinEmilia RomagnaVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaWielkopolskaThames ValleyHungarySE IrelandN NetherlandsSummary estimateEast Midlands and South YorkshireNorthern EnglandParis

Ebstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomalyEbstein's anomaly

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


Thames ValleyS PortugalSaxony AnhaltEmilia RomagnaParisVaudWessexAntwerpDublinStyriaWalesNorthern EnglandHungaryZagrebMainzSE IrelandTuscanySummary estimateN NetherlandsEast Midlands and South YorkshireHainautMaltaBasque CountryOdenseWielkopolska

Pulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosisPulmonary valve stenosis

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

Emilia RomagnaN NetherlandsEast Midlands and South YorkshireParisNorthern EnglandSummary estimateWalesTuscanyHainautOdenseDublinVaudZagrebMaltaS PortugalAntwerpSaxony AnhaltMainzStyriaWielkopolskaThames ValleyWessexHungarySE IrelandBasque Country

Pulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresiaPulmonary valve atresia

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


East Midlands and South YorkshireThames ValleyWessexWalesSaxony AnhaltHungaryHainautOdenseParisEmilia RomagnaZagrebMaltaS PortugalAntwerpMainzSE IrelandBasque CountrySummary estimateTuscanyStyriaNorthern EnglandVaudN NetherlandsWielkopolskaDublin

Aortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosisAortic valve atresia/stenosis

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

HainautN NetherlandsStyriaNorthern EnglandWessexHungaryVaudTuscanyBasque CountryEast Midlands and South YorkshireOdenseZagrebMaltaS PortugalMainzSE IrelandDublinSummary estimateParisSaxony AnhaltAntwerpThames ValleyWalesEmilia RomagnaWielkopolska

Hypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heartHypoplastic left heart

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


WessexWalesWielkopolskaSummary estimateEast Midlands and South YorkshireHainautOdenseParisTuscanyDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaThames ValleyNorthern EnglandHungarySE Ireland

Hypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heartHypoplastic right heart

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

Saxony AnhaltEmilia RomagnaBasque CountrySE IrelandNorthern EnglandTuscanyParisAntwerpThames ValleyHungaryOdenseZagrebMaltaS PortugalStyriaSummary estimateN NetherlandsWalesEast Midlands and South YorkshireDublinWessexMainzHainautWielkopolskaVaud

Coarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aortaCoarctation of aorta

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


Northern EnglandHungarySummary estimateHainautOdenseTuscanyN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaWielkopolskaThames ValleyWessexSE IrelandDublinWalesParisEast Midlands and South Yorkshire

Total anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous returnTotal anomalous pulmonary venous return

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

StyriaNorthern EnglandDublinEmilia RomagnaBasque CountrySaxony AnhaltHungaryHainautOdenseParisN NetherlandsZagrebMaltaS PortugalMainzWielkopolskaThames ValleyWessexSE IrelandWalesSummary estimateAntwerpEast Midlands and South YorkshireTuscanyVaud

Patent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosusPatent ductus arteriosus

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


ParisHungaryWessexSummary estimateHainautOdenseN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalSaxony AnhaltMainzStyriaWielkopolskaThames ValleyEast Midlands and South YorkshireSE IrelandNorthern EnglandTuscanyBasque CountryAntwerpWalesDublin

Choanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresiaChoanal atresia

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

WalesEast Midlands and South YorkshireWessexSummary estimateParisHainautOdenseTuscanyDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaWielkopolskaHungarySE IrelandNorthern EnglandThames Valley

Cystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lungCystic adenomatous malformation of lung

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


SE IrelandZagrebHainautEmilia RomagnaMaltaStyriaWessexVaudWalesThames ValleyNorthern EnglandTuscanyParisHungaryAntwerpSummary estimateEast Midlands and South YorkshireDublinBasque CountryN NetherlandsWielkopolskaS PortugalSaxony AnhaltOdenseMainz

Cleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palateCleft lip with or without palate

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

ZagrebMaltaBasque CountryS PortugalVaudEmilia RomagnaOdenseMainzParisWessexN NetherlandsHungaryNorthern EnglandSummary estimateAntwerpStyriaThames ValleyWalesHainautSE IrelandWielkopolskaEast Midlands and South YorkshireTuscanyDublinSaxony Anhalt

Cleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palateCleft palate

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


WielkopolskaDublinHungaryThames ValleyNorthern EnglandEast Midlands and South YorkshireTuscanySummary estimateBasque CountryEmilia RomagnaZagrebMaltaMainzStyriaSE IrelandSaxony AnhaltWessexHainautS PortugalOdenseParisWalesVaudAntwerpN Netherlands

Oesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistulaOesophageal atresia with or without trachea-oesophageal fistula

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

WielkopolskaWalesEmilia RomagnaHungaryParisDublinSummary estimateWessexTuscanyEast Midlands and South YorkshireHainautOdenseN NetherlandsVaudZagrebMaltaS PortugalBasque CountrySaxony AnhaltMainzStyriaThames ValleySE IrelandAntwerpNorthern England

Duodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosisDuodenal atresia or stenosis

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


1

*Error in the Forest plot. Tuscany did not have an increasing trend in Atresia or stenosis of other small parts of the intestine.

VaudSaxony AnhaltOdenseWielkopolskaN NetherlandsHungaryDublinHainautStyriaAntwerpSummary estimateEast Midlands and South YorkshireThames ValleyZagrebMaltaMainzSE IrelandTuscanyNorthern EnglandWalesParisBasque CountryWessexEmilia RomagnaS Portugal

Ano-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosisAno-rectal atresia and stenosis

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

Tuscany* Hungary Basque Country Emilia Romagna N Netherlands Styria Summary estimate Northern England East Midlands and South Yorkshire Wales Hainaut Odense Vaud Zagreb Malta S Portugal Antwerp Mainz Wielkopolska Thames Valley Wessex SE Ireland

Ireland Saxony Anhalt Paris Dublin

Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine Atresia or stenosis of other parts of small intestine

30% 20% 10% 10% 20% 30% No change

<-- Decrease Increase --> Average annual change in prevalence



Thames ValleyParisAntwerpEast Midlands and South YorkshireBasque CountrySummary estimateEmilia RomagnaWielkopolskaHungaryHainautOdenseTuscanyVaudZagrebMaltaS PortugalSaxony AnhaltMainzStyriaSE IrelandWalesWessexN NetherlandsNorthern EnglandDublin

Hirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's diseaseHirschsprung's disease

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

Basque CountryHainautOdenseParisTuscanyDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalAntwerpSaxony AnhaltMainzStyriaWielkopolskaThames ValleyWessexEast Midlands and South YorkshireNorthern EnglandHungarySE IrelandSummary estimateWales

Atresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ductsAtresia of bile ducts

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


Summary estimateHainautOdenseParisTuscanyDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaWalesWielkopolskaThames ValleyWessexEast Midlands and South YorkshireNorthern EnglandHungarySE Ireland

Annular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreasAnnular pancreas

20% 10% 10% 20%Nochange


Non-linear change

Rate of change

Too few cases

HainautStyriaZagrebTuscanyBasque CountrySaxony AnhaltWielkopolskaSummary estimateHungaryOdenseMaltaS PortugalMainzSE IrelandVaudEast Midlands and South YorkshireWessexWalesEmilia RomagnaNorthern EnglandDublinN NetherlandsAntwerpThames ValleyParis

Diaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic herniaDiaphragmatic hernia

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


Basque CountryThames ValleyNorthern EnglandWessexAntwerpEast Midlands and South YorkshireSummary estimateStyriaSaxony AnhaltWalesHungaryOdenseTuscanyVaudZagrebMaltaSE IrelandWielkopolskaN NetherlandsMainzS PortugalHainautEmilia RomagnaDublinParis

GastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisisGastroschisis

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

N NetherlandsBasque CountryStyriaParisWessexVaudTuscanyEmilia RomagnaHungaryHainautZagrebMaltaS PortugalMainzSE IrelandEast Midlands and South YorkshireSummary estimateWalesDublinOdenseThames ValleyWielkopolskaNorthern EnglandSaxony AnhaltAntwerp

OmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphaloceleOmphalocele

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


HungaryWalesDublinWessexMainzNorthern EnglandEast Midlands and South YorkshireWielkopolskaN NetherlandsEmilia RomagnaHainautOdenseVaudZagrebMaltaS PortugalBasque CountryStyriaSE IrelandSummary estimateParisAntwerpSaxony AnhaltTuscanyThames Valley

Bilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndromeBilateral renal agenesis including Potter syndrome

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

WielkopolskaBasque CountryTuscanyN NetherlandsSaxony AnhaltEmilia RomagnaEast Midlands and South YorkshireThames ValleyDublinSummary estimateVaudParisHainautZagrebMaltaHungarySE IrelandNorthern EnglandOdenseWalesWessexMainzAntwerpStyriaS Portugal

Renal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasiaRenal dysplasia

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


Basque CountryMaltaN NetherlandsVaudWielkopolskaZagrebOdenseHungaryWessexHainautParisTuscanyDublinEmilia RomagnaS PortugalAntwerpMainzThames ValleyEast Midlands and South YorkshireNorthern EnglandSummary estimateStyriaWalesSE IrelandSaxony Anhalt

Congenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosisCongenital hydronephrosis

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

ParisAntwerpHungarySummary estimateWalesHainautOdenseTuscanyDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalBasque CountrySaxony AnhaltMainzStyriaWielkopolskaThames ValleyWessexNorthern EnglandSE IrelandEast Midlands and South Yorkshire

Bladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadiasBladder exstrophy and/or epispadias

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


East Midlands and South YorkshireVaudWessexThames ValleySummary estimateParisBasque CountryWalesHainautOdenseTuscanyDublinZagrebMaltaS PortugalSaxony AnhaltMainzStyriaWielkopolskaHungarySE IrelandEmilia RomagnaNorthern EnglandAntwerpN Netherlands

Posterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune bellyPosterior urethral valve and/or prune belly

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

Northern EnglandThames ValleySE IrelandEmilia RomagnaHainautAntwerpParisN NetherlandsZagrebS PortugalBasque CountryWessexHungarySummary estimateSaxony AnhaltTuscanyWalesMainzWielkopolskaOdenseVaudEast Midlands and South YorkshireDublinStyriaMalta

HypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadiasHypospadias

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


TuscanyWessexNorthern EnglandHainautOdenseDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaWalesWielkopolskaThames ValleySE IrelandSummary estimateParisEast Midlands and South YorkshireHungary

Indeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sexIndeterminate sex

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

Basque CountryZagrebThames ValleyOdenseHungaryWessexEmilia RomagnaMaltaSE IrelandWielkopolskaNorthern EnglandTuscanyN NetherlandsParisWalesSummary estimateSaxony AnhaltAntwerpEast Midlands and South YorkshireVaudHainautDublinMainzS PortugalStyria

Limb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reductionLimb reduction

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


OdenseThames ValleyBasque CountryN NetherlandsTuscanyWalesSaxony AnhaltWielkopolskaZagrebMaltaS PortugalSE IrelandNorthern EnglandWessexHungarySummary estimateParisEmilia RomagnaAntwerpEast Midlands and South YorkshireDublinVaudHainautMainzStyria

Upper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reductionUpper limb reduction

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

Basque CountryHungaryHainautWessexParisN NetherlandsEmilia RomagnaWielkopolskaZagrebMaltaS PortugalMainzThames ValleySE IrelandNorthern EnglandTuscanySummary estimateVaudEast Midlands and South YorkshireStyriaSaxony AnhaltWalesOdenseAntwerpDublin

Lower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reductionLower limb reduction

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


Summary estimateHainautOdenseParisTuscanyDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaWalesWielkopolskaThames ValleyWessexEast Midlands and South YorkshireNorthern EnglandHungarySE Ireland

Complete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limbComplete absence of a limb

20% 10% 10% 20%Nochange


Non-linear change

Rate of change

Too few cases

HainautParisWessexStyriaSummary estimateDublinEmilia RomagnaVaudS PortugalBasque CountryThames ValleyEast Midlands and South YorkshireHungaryNorthern EnglandN NetherlandsWielkopolskaSaxony AnhaltAntwerpWalesMainzOdenseZagrebTuscanySE IrelandMalta

Club foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarusClub foot - talipes equinovarus

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


Basque CountryThames ValleyEmilia RomagnaParisOdenseN NetherlandsTuscanyDublinS PortugalSaxony AnhaltStyriaWielkopolskaEast Midlands and South YorkshireHungaryMaltaWessexNorthern EnglandSE IrelandSummary estimateMainzWalesAntwerpVaudHainautZagreb

Hip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasiaHip dislocation and/or dysplasia

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

Thames ValleyVaudWessexAntwerpMainzWalesZagrebTuscanyMaltaEmilia RomagnaParisS PortugalBasque CountrySaxony AnhaltHungarySE IrelandSummary estimateN NetherlandsWielkopolskaStyriaHainautOdenseEast Midlands and South YorkshireDublinNorthern England

PolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactylyPolydactyly

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


VaudN NetherlandsHainautEmilia RomagnaHungaryOdenseZagrebMaltaMainzThames ValleySE IrelandBasque CountryDublinTuscanyWalesWessexSummary estimateWielkopolskaS PortugalEast Midlands and South YorkshireAntwerpNorthern EnglandSaxony AnhaltStyriaParis

SyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactylySyndactyly

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

Emilia RomagnaTuscanyBasque CountryWessexThames ValleyHainautHungaryN NetherlandsParisSummary estimateOdenseZagrebMaltaS PortugalSaxony AnhaltMainzStyriaWielkopolskaSE IrelandEast Midlands and South YorkshireNorthern EnglandAntwerpWalesVaudDublin

Skeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasiasSkeletal dysplasias

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


Thames ValleyEmilia RomagnaVaudBasque CountryHainautN NetherlandsSummary estimateTuscanyParisWalesDublinHungaryOdenseZagrebMaltaS PortugalMainzWessexSE IrelandAntwerpWielkopolskaEast Midlands and South YorkshireSaxony AnhaltStyriaNorthern England

CraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosisCraniosynostosis

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

Northern EnglandSummary estimateHainautOdenseParisTuscanyDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaWielkopolskaThames ValleyEast Midlands and South YorkshireHungarySE IrelandWessexWales

Congenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bandsCongenital constriction bands/amniotic bands

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


Summary estimateParisHungaryHainautOdenseTuscanyDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalBasque CountrySaxony AnhaltMainzStyriaWielkopolskaThames ValleyWessexSE IrelandEast Midlands and South YorkshireNorthern EnglandAntwerpWales

Situs inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversusSitus inversus

20% 10% 10% 20%Nochange


Non-linear change

Rate of change

Too few cases


Conjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twinsConjoined twins

10% 5% 5% 10%Nochange


Non-linear change

Rate of change

Too few cases


TuscanyS PortugalBasque CountrySaxony AnhaltStyriaWielkopolskaHungaryOdenseParisZagrebMaltaMainzThames ValleyWessexSE IrelandNorthern EnglandDublinHainautAntwerpN NetherlandsEmilia RomagnaSummary estimateEast Midlands and South YorkshireWalesVaud

Congenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disordersCongenital skin disorders

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

Basque CountrySaxony AnhaltWessexNorthern EnglandEmilia RomagnaSummary estimateThames ValleyOdenseTuscanyN NetherlandsVaudZagrebMaltaS PortugalMainzStyriaWielkopolskaHungarySE IrelandHainautWalesParisEast Midlands and South YorkshireDublinAntwerp

Teratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformationsTeratogenic syndromes with malformations

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


WalesHainautOdenseParisTuscanyDublinN NetherlandsEmilia RomagnaVaudZagrebMaltaS PortugalAntwerpBasque CountrySaxony AnhaltMainzStyriaWielkopolskaThames ValleyWessexEast Midlands and South YorkshireNorthern EnglandHungarySE IrelandSummary estimate

Fetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndromeFetal alcohol syndrome

20% 10% 10% 20%Nochange


Non-linear change

Rate of change

Too few cases


Valproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndromeValproate syndrome

20% 10% 10% 20%Nochange


Non-linear change

Rate of change

Too few cases


Summary estimateWalesHainautOdenseTuscanyN NetherlandsVaudZagrebMaltaS PortugalBasque CountrySaxony AnhaltMainzStyriaWielkopolskaThames ValleyWessexEast Midlands and South YorkshireNorthern EnglandHungarySE IrelandEmilia RomagnaParisAntwerpDublin

Maternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformationsMaternal infections resulting in malformations

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

Basque CountryParisMainzTuscanyWielkopolskaVaudOdenseHainautEmilia RomagnaThames ValleyNorthern EnglandHungaryZagrebMaltaS PortugalWessexAntwerpSE IrelandSummary estimateN NetherlandsDublinEast Midlands and South YorkshireSaxony AnhaltWalesStyria

Genetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletionsGenetic syndromes + microdeletions

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


OdenseTuscanyN NetherlandsSE IrelandStyriaMainzParisWessexZagrebAntwerpBasque CountryVaudHainautSummary estimateDublinWalesThames ValleyHungaryNorthern EnglandWielkopolskaMaltaSaxony AnhaltEmilia RomagnaEast Midlands and South YorkshireS Portugal

ChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomalChromosomal

20% 10% 10% 20%Nochange


Non-linear change

Rate of change

Too few cases

StyriaTuscanySE IrelandVaudBasque CountryParisWessexMainzAntwerpN NetherlandsSummary estimateDublinSaxony AnhaltNorthern EnglandHainautWalesOdenseHungaryEmilia RomagnaThames ValleyWielkopolskaZagrebEast Midlands and South YorkshireMaltaS Portugal

Down syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndromeDown syndrome

20% 10% 10% 20%Nochange


Non-linear change

Rate of change

Too few cases


WielkopolskaN NetherlandsHungaryTuscanyWessexNorthern EnglandEast Midlands and South YorkshireVaudAntwerpSummary estimateParisThames ValleyHainautOdenseZagrebMaltaS PortugalMainzSE IrelandSaxony AnhaltBasque CountryDublinWalesStyriaEmilia Romagna

Patau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndromePatau syndrome

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

TuscanyN NetherlandsVaudMainzBasque CountrySaxony AnhaltWessexOdenseParisHainautWalesSummary estimateNorthern EnglandDublinAntwerpHungaryZagrebS PortugalThames ValleyEast Midlands and South YorkshireStyriaMaltaEmilia RomagnaWielkopolskaSE Ireland

Edwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndromeEdwards syndrome

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


N NetherlandsEmilia RomagnaHainautWielkopolskaNorthern EnglandThames ValleyEast Midlands and South YorkshireParisHungaryOdenseZagrebMaltaS PortugalMainzSE IrelandAntwerpSummary estimateTuscanyWessexWalesStyriaDublinBasque CountrySaxony AnhaltVaud

Turner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndromeTurner syndrome

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases

HungaryEmilia RomagnaParisNorthern EnglandWalesHainautOdenseDublinN NetherlandsVaudZagrebMaltaS PortugalAntwerpMainzStyriaWielkopolskaThames ValleySE IrelandWessexSummary estimateBasque CountrySaxony AnhaltEast Midlands and South YorkshireTuscany

Klinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndromeKlinefelter syndrome

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


StyriaWessexTuscanyN NetherlandsSE IrelandAntwerpOdenseHungaryHainautBasque CountryParisVaudNorthern EnglandWalesMainzSummary estimateDublinSaxony AnhaltWielkopolskaThames ValleyEmilia RomagnaZagrebEast Midlands and South YorkshireMaltaS Portugal

Down syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjustedDown syndrome adjusted

20% 10% 10% 20%Nochange


Non-linear change

Rate of change

Too few cases

WielkopolskaN NetherlandsWessexNorthern EnglandTuscanyEast Midlands and South YorkshireAntwerpThames ValleyVaudSummary estimateParisHungaryHainautOdenseZagrebMaltaS PortugalMainzSE IrelandSaxony AnhaltBasque CountryDublinWalesStyriaEmilia Romagna

Patau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjustedPatau syndrome adjusted

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


N NetherlandsTuscanyOdenseVaudWessexSaxony AnhaltWalesMainzParisBasque CountrySummary estimateHungaryHainautZagrebS PortugalNorthern EnglandAntwerpDublinThames ValleyEast Midlands and South YorkshireStyriaMaltaWielkopolskaEmilia RomagnaSE Ireland

Edwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjustedEdwards syndrome adjusted

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


Appendix F: Forest plots showing ten year increasing and decreasing trends detected in the pan-Europe analysis by registry

All non-chromosomal anomalies

Neural tube defects

Anencephalus and similar

Encephalocele

Spina bifida

Hydrocephaly

Microcephaly

Arhinencephaly/holoprosencephaly

Anophthalmos/microphthalmos

Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia

Congenital heart disease

Severe CHD

Common arterial truncus

Transposition of great vessels

Single ventricle


Atrial septal defect

Atrioventricular septal defect

Tetralogy of Fallot

Tricuspid atresia and stenosis

Ebstein's anomaly

Pulmonary valve stenosis



Hypoplastic left heart


Coarctation of aorta

Total anomalous pulmonary venous return

Patent ductus arteriosus

Choanal atresia



Cleft palate


Duodenal atresia or stenosis


Ano-rectal atresia and stenosis

Hirschsprung's disease

StyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyria

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


Atresia of bile ducts

Annular pancreas

Diaphragmatic hernia

Gastroschisis

Omphalocele

Bilateral renal agenesis including Potter syndrome

Renal dysplasia


Bladder exstrophy and/or epispadias

Posterior urethral valve and/or prune belly

Hypospadias

Indeterminate sex

Limb reduction


Lower limb reduction

Complete absence of a limb



Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis

Congenital constriction bands/amniotic bands

Situs inversus

Conjoined twins




Valproate syndrome


Genetic syndromes + microdeletions

Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome

Klinefelter syndrome

Down syndrome adjusted

Patau syndrome adjusted

Edwards syndrome adjusted

StyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyriaStyria

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






AntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerp

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





AntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerpAntwerp

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






HainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainaut

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





HainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainautHainaut

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






ZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagreb

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





ZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagrebZagreb

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






OdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdense

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





OdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdenseOdense

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






ParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParis

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





ParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParisParis

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






MainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainz

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





MainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainzMainz

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






Saxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony Anhalt

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





Saxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony AnhaltSaxony Anhalt

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






HungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungaryHungary

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






DublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublin

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





DublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublinDublin

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






SE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE Ireland

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





SE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE IrelandSE Ireland

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






Emilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia Romagna

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





Emilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia RomagnaEmilia Romagna

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


*Syntax error. No increasing trend found in Atresia/ stenosis of other parts of small intestine

All non-chromosomal anomalies Neural tube defects Anencephalus and similar Encephalocele Spina bifida Hydrocephaly Microcephaly Arhinencephaly/holoprosencephaly Anophthalmos/microphthalmos Anophthalmos Congenital cataract Congenital glaucoma Anotia Congenital heart disease Severe CHD Common arterial truncus Transposition of great vessels Single ventricle Ventricular septal defect Atrial septal defect Atrioventricular septal defect Tetralogy of Fallot Tricuspid atresia and stenosis Ebstein's anomaly Pulmonary valve stenosis Pulmonary valve atresia Aortic valve atresia/stenosis Hypoplastic left heart Hypoplastic right heart Coarctation of aorta Total anomalous pulmonary venous return Patent ductus arteriosus Choanal atresia Cystic adenomatous malformation of lung Cleft lip with or without palate Cleft palate Oesophageal atresia with or without trachea-oesophageal fistula Duodenal atresia or stenosis Atresia or stenosis of other parts of small intestine* Ano-rectal atresia and stenosis Hirschsprung's disease

Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany Tuscany

30% 20% 10% 10% 20% 30% No






Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





TuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscanyTuscany

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






MaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMalta

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





MaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMaltaMalta

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






N NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN Netherlands

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





N NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN NetherlandsN Netherlands

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






WielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolska

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





WielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolskaWielkopolska

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






S PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS Portugal

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





S PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS PortugalS Portugal

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






Basque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque Country

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





Basque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque CountryBasque Country

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






VaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaud

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





VaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaudVaud

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






East Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South Yorkshire

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





East Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South YorkshireEast Midlands and South Yorkshire

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






Northern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern England

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





Northern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern EnglandNorthern England

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






Thames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames Valley

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





Thames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames ValleyThames Valley

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






WalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWales

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





WalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWalesWales

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Neural tube defects


Encephalocele

Spina bifida

Hydrocephaly

Microcephaly



Anophthalmos

Congenital cataract

Congenital glaucoma

Anotia


Severe CHD



Single ventricle




Tetralogy of Fallot


Ebstein's anomaly









Choanal atresia



Cleft palate






WessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessex

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases



Annular pancreas


Gastroschisis

Omphalocele


Renal dysplasia




Hypospadias

Indeterminate sex

Limb reduction






Polydactyly

Syndactyly

Skeletal dysplasias

Craniosynostosis


Situs inversus

Conjoined twins




Valproate syndrome



Chromosomal

Down syndrome

Patau syndrome

Edwards syndrome

Turner syndrome





WessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessexWessex

30% 20% 10% 10% 20% 30%Nochange


Non-linear change

Rate of change

Too few cases


Appendix G Outcomes of local registries preliminary investigations into Pan-Europe and individual registry ten year trends

Table G1: Increasing trends

Anomaly

Sty

ria (

AT

)

An

twerp

(B

E)

Hain

au

t (B

E)

Za

gre

b (

HR

)

Od

en

se (

DK

)

Isle

de

Reu

nio

n (

FR

)

Pari

s (

FR

)

Ma

inz (

DE

)

Saxo

ny

An

ha

lt (

DE

)

Du

blin

(IE

)

Hu

ng

ary

(H

U)

SE

Ire

lan

d (

IE)

Em

ilia

Ro

mag

na (

IT)

Tu

scan

y (

IT)

Ma

lta (

MT

)

N N

eth

erl

an

ds

(N

L)

Wie

lko

po

lska (

PL

)

Basq

ue

Co

un

try (

ES

)

Vau

d (

CH

)

E M

id &

S Y

ork

(G

B)

N E

ng

lan

d (

GB

)

Th

am

es V

alley (

GB

)

Wale

s (

GB

)

Wessex (

GB

)

All non chromosomal anomalies A


C,A

Hydrocephalus

G

Microcephaly

A,B

Arhinencephaly/ holoprosencephaly

A

Anophthalmos/ microphthalmos

A

Congenital cataract

A

Congenital heart defects

A

Severe CHD §

G


C

A

Single ventricle

A


A

NI


A


H

Tetralogy of Fallot

F


A

A


B


Anomaly

Sty

ria (

AT

)

An

twerp

(B

E)

Hain

au

t (B

E)

Za

gre

b (

HR

)

Od

en

se (

DK

)

Isle

de

Reu

nio

n (

FR

)

Pari

s (

FR

)

Ma

inz (

DE

)

Saxo

ny

An

ha

lt (

DE

)

Du

blin

(IE

)

Hu

ng

ary

(H

U)

SE

Ire

lan

d (

IE)

Em

ilia

Ro

mag

na (

IT)

Tu

scan

y (

IT)

Ma

lta (

MT

)

N N

eth

erl

an

ds

(N

L)

Wie

lko

po

lska (

PL

)

Basq

ue

Co

un

try (

ES

)

Vau

d (

CH

)

E M

id &

S Y

ork

(G

B)

N E

ng

lan

d (

GB

)

Th

am

es V

alley (

GB

)

Wale

s (

GB

)

Wessex (

GB

)


C?


A

PDA as only CHD in term infants (>=37 weeks)

H

H

Choanal atresia

A

Cystic adenomatous malf of lung §

B

F

Cleft palate

G

A

Oesophageal atresia with or without tracheo-oesophageal fistula

A

H


H

A


E

NI


A

Gastroschisis

A

H


A

Renal dysplasia

B

B

C H A,B?

C


C

A NI


F


G

Hypospadias

A A

H A

Limb reduction

A,B


Anomaly

Sty

ria (

AT

)

An

twerp

(B

E)

Hain

au

t (B

E)

Za

gre

b (

HR

)

Od

en

se (

DK

)

Isle

de

Reu

nio

n (

FR

)

Pari

s (

FR

)

Ma

inz (

DE

)

Saxo

ny

An

ha

lt (

DE

)

Du

blin

(IE

)

Hu

ng

ary

(H

U)

SE

Ire

lan

d (

IE)

Em

ilia

Ro

mag

na (

IT)

Tu

scan

y (

IT)

Ma

lta (

MT

)

N N

eth

erl

an

ds

(N

L)

Wie

lko

po

lska (

PL

)

Basq

ue

Co

un

try (

ES

)

Vau

d (

CH

)

E M

id &

S Y

ork

(G

B)

N E

ng

lan

d (

GB

)

Th

am

es V

alley (

GB

)

Wale

s (

GB

)

Wessex (

GB

)


A,B


F

A

A

Polydactyly

A

Syndactyly

A

Skeletal dysplasias §

A

Craniosynostosis

A,B

A F

A


H

Teratogenic syndromes with malformations §

E

A

G


F

Chromosomal

C

D

A

H

Down Syndrome H

D

A

Patau syndrome/trisomy 13

A

H

Patau syndrome/trisomy 13 Adjusted

H

Edward syndrome/trisomy 18

A

C

Edward syndrome/trisomy 18 Adjusted

A

C

Key: A: Changes in case ascertainment (data quality) ; B: Changes in local or central registry methods e.g. definitions and inclusion criteria; C: Changes in diagnostic methods; D: Trend confirmed,

due to known demographic changes E: Trend confirmed, investigation on-going F: Trend confirmed, further surveillance proposed before more detailed investigation G: Not real trend when additional

years added, or heterogeneous subgroup H : No report or clear interpretation of preliminary investigations sent


Table G2: Decreasing trends

Anomaly

Sty

ria (

AT

)

An

twerp

(B

E)

Hain

au

t (B

E)

Za

gre

b (

HR

)

Od

en

se (

DK

)

Isle

de

Reu

nio

n (

FR

)

Pari

s (

FR

)

Ma

inz (

DE

)

Saxo

ny

An

ha

lt (

DE

)

Hu

ng

ary

(H

U)

Du

blin

(IE

)

SE

Ire

lan

d (

IE)

Em

ilia

Ro

mag

na (

IT)

Tu

scan

y (

IT)

Ma

lta (

MT

)

N N

eth

erl

an

ds

(N

L)

Wie

lko

po

lska (

PL

)

S P

ort

ug

al

(PT

)

Basq

ue

Co

un

try (

ES

)

Vau

d (

CH

)

E M

id &

S Y

ork

(G

B)

N E

ng

lan

d (

GB

)

Th

am

es V

alley (

GB

)

Wale

s (

GB

)

Wessex (

GB

)

All Non-chromosomal Anomalies

C H F A A H NI H

Neural Tube Defects H NI H E E G

Anencephalus and similar H A

Spina Bifida A H E

Hydrocephalus H G NI A H

Microcephaly NI G

Anophthalmos/microphthalmos G

Congenital cataract G

Congenital heart defects A

Severe CHD § H

Ventricular septal defect NI A NI H A H

Atrial septal defect B,C A NI H

Atrioventricular septal defect H H

Pulmonary valve stenosis H B H A,B

Pulmonary valve atresia A,B

Aortic valve atresia/stenosis § H

Hypoplastic left heart F H E

Coarctation of aorta NI H NI


NI B


Anomaly

Sty

ria (

AT

)

An

twerp

(B

E)

Hain

au

t (B

E)

Za

gre

b (

HR

)

Od

en

se (

DK

)

Isle

de

Reu

nio

n (

FR

)

Pari

s (

FR

)

Ma

inz (

DE

)

Saxo

ny

An

ha

lt (

DE

)

Hu

ng

ary

(H

U)

Du

blin

(IE

)

SE

Ire

lan

d (

IE)

Em

ilia

Ro

mag

na (

IT)

Tu

scan

y (

IT)

Ma

lta (

MT

)

N N

eth

erl

an

ds

(N

L)

Wie

lko

po

lska (

PL

)

S P

ort

ug

al

(PT

)

Basq

ue

Co

un

try (

ES

)

Vau

d (

CH

)

E M

id &

S Y

ork

(G

B)

N E

ng

lan

d (

GB

)

Th

am

es V

alley (

GB

)

Wale

s (

GB

)

Wessex (

GB

)

Choanal atresia H

Cleft lip with or without palate H

Cleft palate G NI G


E


F

Omphalocele H


H

Renal dysplasia E

Congenital hydronephrosis B B


E

Hypospadias H NI A NI G A

Indeterminate sex NI

Limb reduction H NI G

Upper limb reduction H H A


A NI A A


A

Polydactyly G

Syndactyly B B A


Anomaly

Sty

ria (

AT

)

An

twerp

(B

E)

Hain

au

t (B

E)

Za

gre

b (

HR

)

Od

en

se (

DK

)

Isle

de

Reu

nio

n (

FR

)

Pari

s (

FR

)

Ma

inz (

DE

)

Saxo

ny

An

ha

lt (

DE

)

Hu

ng

ary

(H

U)

Du

blin

(IE

)

SE

Ire

lan

d (

IE)

Em

ilia

Ro

mag

na (

IT)

Tu

scan

y (

IT)

Ma

lta (

MT

)

N N

eth

erl

an

ds

(N

L)

Wie

lko

po

lska (

PL

)

S P

ort

ug

al

(PT

)

Basq

ue

Co

un

try (

ES

)

Vau

d (

CH

)

E M

id &

S Y

ork

(G

B)

N E

ng

lan

d (

GB

)

Th

am

es V

alley (

GB

)

Wale

s (

GB

)

Wessex (

GB

)

Skeletal dysplasias § Craniosynostosis H Congenital constriction bands/amniotic band

H H

Congenital skin disorders G B B Maternal infections resulting in malformations

NI


H F NI G G

Chromosomal A E G Down Syndrome E G Down Syndrome Adjusted A E G Patau syndrome/trisomy 13 Adjusted

A

Edward syndrome/trisomy 18 A Edward syndrome/trisomy 18 Adjusted

A

Turner syndrome A NI Klinefelter syndrome NI

Key: A: Changes in case ascertainment (data quality) ; B: Changes in local or central registry methods e.g. definitions and inclusion criteria; C: Changes in diagnostic methods; D: Trend confirmed,

due to known demographic changes E: Trend confirmed, investigation on-going F: Trend confirmed, further surveillance proposed before more detailed investigation G: Not real trend when

additional years added, or heterogeneous subgroup H : No report or clear interpretation of preliminary investigations sent NI: Not investigated


Appendix H Central Registry Statistical Monitoring Results: Table of detected clusters by registry and by anomaly 2009-2010

Anomaly

To

tal

clu

ste

rs:

Date

of

co

nc

ep

tio

n

To

tal

clu

ste

rs :

Date

of

bir

th

To

tal

clu

ste

rs:

All

reg

istr

ies

An

twe

rp (

BE

)

Hain

au

t (B

E)

Od

en

se

(D

K)

Pa

ris

(F

R)

Ma

inz (

DE

)

Du

bli

n (

IE)

Em

ilia

Ro

ma

gn

a (

IT)

Tu

sc

an

y (

IT)

N N

eth

erl

an

ds

(N

L)

Bas

qu

e C

ou

ntr

y (

ES

)

Va

ud

(C

H)

E M

id &

S Y

ork

(G

B)

N E

ng

lan

d (

GB

)

S W

es

t E

ng

lan

d (

GB

)

Th

am

es

Va

lle

y (

GB

)

Wa

les (

GB

)

We

sse

x (

GB

)

Neural Tube Defects 1 0 1

C

Anencephalus and similar 1 0 1

*

C

Encephalocele 0 0 0

*

*

*

Spina Bifida 0 0 0

Hydrocephalus 1 0 1

C

Microcephaly 0 0 0

*

X

Arhinencephaly/holoprosencephaly 0 0 0 * * *

* *

*

*

Anophthalmos/microphthalmos 0 0 0 * * *

*

*

Anophthalmos 0 0 0 * * * * * * * * * * * * * * * * *

Congenital cataract 0 0 0 * * *

*

*

*

*

Congenital glaucoma 0 0 0 * * * * * *

* *

* * *

*

*

Anotia 0 0 0 * * *

* * * * * * * * * * * * *

Severe CHD § 0 0 0

Common arterial truncus 0 0 0 * * * * *

* * * *

*

Transposition of great vessels 1 0 1

C

*

Single ventricle 0 0 0

* *

* *

* *

*

*

*

Ventricular septal defect 1 0 1

C

Atrial septal defect 2 0 2

C

C

Atrioventricular septal defect 0 0 0

*

*

Tetralogy of Fallot 0 0 0

Tricuspid atresia and stenosis 0 0 0 * * * * *

* * * * *

Ebstein's anomaly 0 0 0 * * *

*

* * * * *

*

*

Pulmonary valve stenosis 0 0 0

*


Anomaly

To

tal

clu

ste

rs:

Date

of

co

nc

ep

tio

n

To

tal

clu

ste

rs :

Date

of

bir

th

To

tal

clu

ste

rs:

All

reg

istr

ies

An

twe

rp (

BE

)

Hain

au

t (B

E)

Od

en

se

(D

K)

Pa

ris

(F

R)

Ma

inz (

DE

)

Du

bli

n (

IE)

Em

ilia

Ro

ma

gn

a (

IT)

Tu

sc

an

y (

IT)

N N

eth

erl

an

ds

(N

L)

Bas

qu

e C

ou

ntr

y (

ES

)

Va

ud

(C

H)

E M

id &

S Y

ork

(G

B)

N E

ng

lan

d (

GB

)

S W

es

t E

ng

lan

d (

GB

)

Th

am

es

Va

lle

y (

GB

)

Wa

les (

GB

)

We

sse

x (

GB

)

Pulmonary valve atresia 1 0 1 * * *

* * C

* *

*

Aortic valve atresia/stenosis § 0 1 1

* *

*

B *

Hypoplastic left heart 0 0 0

*

*

Hypoplastic right heart § 1 0 1 * * * * * * * * * * *

* C *

Coarctation of aorta 0 0 0

*

*

Total anomalous pulm venous return

0 0 0 * * *

*

* * * * *


0 0 0

* * * *

*

Choanal atresia 0 0 0

* *

*

*

*

Cystic adenomatous malf of lung § 0 0 0

* *

* *

* *

Cleft lip with or without palate 1 1 2

B

C

Cleft palate 2 0 2

C

C


0 0 0

*

Duodenal atresia or stenosis 0 0 0

* *

*

* * *


0 0 0 * * *

*

*

Ano-rectal atresia and stenosis 0 0 0

*

Hirschsprung's disease 1 0 1

* *

*

C *

Atresia of bile ducts 0 0 0 * * * * * * * * * * * * *

*

*

Annular pancreas 0 0 0 * * * * * * * * * * * * * * * * *


Anomaly

To

tal

clu

ste

rs:

Date

of

co

nc

ep

tio

n

To

tal

clu

ste

rs :

Date

of

bir

th

To

tal

clu

ste

rs:

All

reg

istr

ies

An

twe

rp (

BE

)

Hain

au

t (B

E)

Od

en

se

(D

K)

Pa

ris

(F

R)

Ma

inz (

DE

)

Du

bli

n (

IE)

Em

ilia

Ro

ma

gn

a (

IT)

Tu

sc

an

y (

IT)

N N

eth

erl

an

ds

(N

L)

Bas

qu

e C

ou

ntr

y (

ES

)

Va

ud

(C

H)

E M

id &

S Y

ork

(G

B)

N E

ng

lan

d (

GB

)

S W

es

t E

ng

lan

d (

GB

)

Th

am

es

Va

lle

y (

GB

)

Wa

les (

GB

)

We

sse

x (

GB

)

Diaphragmatic hernia 0 0 0

*

*

*

Gastroschisis 0 0 0

Omphalocele 1 0 1

*

C

*


0 0 0

*

* *

Renal dysplasia 1 0 1

C

Congenital hydronephrosis 2 0 2 C

C


1 0 1

* *

* *

* C * *


0 0 0

* *

* *

*

Hypospadias 0 0 0

Indeterminate sex 0 0 0 * * *

* *

* * *

*

Limb reduction 0 0 0

Upper limb reduction 0 0 0

*

Lower limb reduction 0 0 0

*

Complete absence of a limb 0 0 0 * * * * * * * * * * *

* * * * *

Club foot - talipes equinovarus 2 0 2 C

C

*

Hip dislocation and/or dysplasia 0 0 0

*

*

Polydactyly 1 0 1

C

Syndactyly 1 0 1

*

C

Skeletal dysplasias § 0 0 0

*

Craniosynostosis 0 0 0

*

*

*


0 0 0 * * *

* *

* * *

*


Anomaly

To

tal

clu

ste

rs:

Date

of

co

nc

ep

tio

n

To

tal

clu

ste

rs :

Date

of

bir

th

To

tal

clu

ste

rs:

All

reg

istr

ies

An

twe

rp (

BE

)

Hain

au

t (B

E)

Od

en

se

(D

K)

Pa

ris

(F

R)

Ma

inz (

DE

)

Du

bli

n (

IE)

Em

ilia

Ro

ma

gn

a (

IT)

Tu

sc

an

y (

IT)

N N

eth

erl

an

ds

(N

L)

Bas

qu

e C

ou

ntr

y (

ES

)

Va

ud

(C

H)

E M

id &

S Y

ork

(G

B)

N E

ng

lan

d (

GB

)

S W

es

t E

ng

lan

d (

GB

)

Th

am

es

Va

lle

y (

GB

)

Wa

les

(G

B)

We

ss

ex

(G

B)

Situs inversus 0 0 0 * * * * * * * *

Conjoined twins 0 0 0 * * * * * * * * * * * * * * *

Congenital skin disorders 0 0 0

*

*

*

*

*

Fetal alcohol syndrome 0 0 0 * * * * * * * * * * * * * * *

*

Valproate syndrome § 0 0 0 * * * * * * * * * * * * * * * * *


1 0 1

* *

*

* *

C *

Down Syndrome 2 0 2

C

C

Patau syndrome/trisomy 13 0 0 0

*

Edward syndrome/trisomy 18 0 0 0

Turner syndrome 0 0 0

*

Klinefelter syndrome 0 0 0 * * *

* *

*

*

*

Totals by Registry 25

2 2 0 1 2 0 6 2 2 0 1 1 1 2 3 0 0

Totals by Registry

2

0 1 0 0 0 0 1 0 0 0 0 0 0 0 0 0 0

Totals by registry: All 27 C = Clusters run by date of conception, -C = Case deficit run by date of conception B = Clusters run by date of birth, -B = Case deficit run by date of birth T = Total clusters X = Data excluded from analysis * = Too few cases to run analysis (registries must have at least 7 cases over the surveillance period


Appendix: I Clusters identified in the cluster analysis

Anomaly subgroup (Outcome of local registry preliminary investigations)

Country Registry No of cases in cluster

Cluster start date

Cluster end date

Expected cases

Probability Valid cases

% estimated GA (invalid DOB)

Cluster/ case deficit

Trend summary

Neural Tube Defects Germany Mainz 5 28/06/2008 31/07/2008 0.43 0.025 20 0 Cluster Non-Linear

change


UK SW

England 9 23/12/2008 20/01/2009 1.32 0.024 73 1.4

Cluster No sig. change

Hydrocephalus Italy Tuscany 6 29/11/2008 18/12/2008 0.47 0.012 38 0 Cluster No sig.

change


Belgium Hainaut 5 12/05/2008 16/06/2008 0.47 0.039 21 4.8 Cluster No sig.

change


UK Thames Valley

116 13/05/2008 04/11/2009 74.85 <0.001 215 2.3 Cluster Non-Linear

change

Atrial septal defect UK Thames Valley

68 10/02/2009 22/01/2010 34.58 <0.001 155 5.8 Cluster

Inc. trend

Atrial septal defect Italy Emilia

Romagna 85 29/08/2008 04/02/2010 53.38 <0.001 158 2.5

Cluster Inc. trend


Italy Emilia

Romagna 9 25/03/2009 28/08/2009 1.71 0.008 17 5.9

Cluster *

Aortic valve atresia/stenosis § (B)

Italy Emilia

Romagna 5 31/08/2009 08/12/2009 0.65 0.04 12 0

Cluster *

Hypoplastic right heart §

UK SW

England 6 11/11/2008 10/09/2009 1.56 0.043 8 0

Cluster *

Cleft lip with or without palate (B)

Belgium Hainaut 9 14/01/2010 16/02/2010 1.25 0.017 69 5 Cluster No sig.

change


UK E Mid & S

York 5 29/10/2009 30/10/2009 0.16 0.019 253 1.2


Cleft palate Belgium Hainaut 7 13/02/2009 17/04/2009 0.93 0.019 23 4.3 Cluster No sig.

change

Cleft palate Italy Emilia

Romagna 5 29/09/2009 02/10/2009 0.18 0.007 91 3.3



Anomaly subgroup (Outcome of local registry preliminary investigations)

Country Registry No of cases in cluster

Cluster start date

Cluster end date

Expected cases

Probability Valid cases

% estimated GA (invalid DOB)

Cluster/ case deficit

Trend summary


Italy Emilia

Romagna 13 16/04/2009 13/03/2010 3.41 <0.001 16 6.2 Cluster *

Omphalocele NL N

Netherlands 8 07/07/2008 14/08/2009 2.6 0.041 10 0 Cluster *

Renal dysplasia UK Thames Valley

7 16/09/2009 07/10/2009 0.72 0.019 53 3.8 Cluster No sig. change


Belgium Antwerp 15 26/10/2009 07/02/2010 4.09 0.027 61 6.6 Cluster Non-Linear

change


UK N

England 75 01/10/2008 28/03/2010 49.01 0.044 140 0.7 Cluster Inc. trend


NL N

Netherlands 7 20/05/2008 07/12/2008 1.17 <0.001 9 0 Cluster *


Belgium Antwerp 11 26/05/2008 03/07/2008 1.94 0.018 79 6.3 Cluster No sig. change


Italy Emilia

Romagna 7 08/03/2010 12/03/2010 0.46 0.009 180 1.7 Cluster Inc. trend

Polydactyly France Paris 19 11/08/2009 21/01/2010 5.68 0.006 54 0 Cluster Non-Linear

change

Syndactyly Italy Emilia

Romagna 6 27/02/2010 08/03/2010 0.35 0.007 61 1.6 Cluster

No sig. change


Switzerland Vaud 6 31/03/2008 28/07/2008 0.84 0.013 11 0 Cluster *

Down Syndrome Germany Mainz 9 05/10/2009 18/11/2009 1.45 0.026 51 0 Cluster No sig. change

Down Syndrome Italy Tuscany 6 31/12/2008 01/01/2009 0.18 <0.001 272 4 Cluster Inc. trend Key: GA: Gestational age; DOB: Date of Birth; * Too few cases to run the analysis; §; incomplete or misspecification of ICD 9 codes; # Cluster identified and reported on in 2008 Report

Key for Outcome of local registry preliminary investigations of detected clusters

A: Clusters associated with aetiologic heterogeneity, changes in inclusion criteria, diagnosis, familial or twin recurrence

B: Excess of cases confirmed with no explanation in registry data; no further action other than continued surveillance C: Increase in cases/ascertainment, due to increasing use of invasive prenatal diagnostic procedures or improvements in prenatal ultrasound rates D: Clusters due to data quality errors or late case ascertainment


Appendix J: Trends by anomaly and registry– website details Information on the number of cases in each anomaly subgroup, by registry and time period

are available on the EUROCAT website: http://www.eurocatnetwork.

eu/ACCESSPREVALENCEDATA/PrevalenceTables To access this information, click on the

link and you will be direct to our revised prevalence tables web page (see below)

You can also access the old style formatted tables


Appendix K: Survey on the use of the Statistical Monitoring Report

From 2007 the reports have been published online on the EUROCAT web site, making them

accessible for any individual or group. A review of the website using Google analytic

showed that between 1 May 2010 and 8 August 2011 the web page with the Annual

Statistical Monitoring Report 2007 had been viewed 537 times. Registries can also

disseminate the findings of the Statistical Monitoring in their own region. To determine how

individual registries disseminated the report Central Registry sent out a brief questionnaire

asking them to provide details of who they had disseminated the findings of the Report to,

how they had done this and if the findings are/or had ever been used to influence or change

any public health agendas within their region or country. Out of the 30 registries asked to

take part in the survey 19 registries (63%) completed and returned the questionnaire to

central registry.

13 registries (71%) reported that they had submitted the findings of the annual statistical

monitoring to the relevant person within the public health system in their region. For six

registries this was a National organisation (Wales, Dublin, Saxony-Anhalt, Paris, Ile de la

Reunion, Northern Netherlands). In those registries with public health systems that were

regional organisations, Ukraine stated that the Report was also forwarded to a National

Organisation (Ministry of Health Care: Medical Statistic Centre and Chief Medical

Geneticist). One other registry (Tuscany) stated that the report was forwarded to a national

organisation when an “excess is relevant”. When asked of the submission of this report was

a compulsory or voluntary requirement three registries (Paris, Saxony-Anhalt and Emilia

Romagna) stated that it was compulsory whilst the remaining 10 registries indicated that it

was voluntary.

The registries were also asked if they had disseminated the Report to other groups within

the health care system, other interested parties and the press/media. Eight registries (42%)

reported that they had disseminated the findings of the report to others in the health care

system. Recipients included obstetricians, geneticists, paediatricians, midwives and those

with interests in birth defects e.g. neonatologists and gynaecologists. One registry sent the

report to the steering group. Of those registries that reported that they did not disseminate

the report (58%), two reported that they provided a copy of the report on request, and a

further registry stated that they were looking to address this, but that dissemination of the

report had took place in the context of audit meetings. A number of the registries stated that

the findings of the Statistical Monitoring Report were included in their respective annual


reports which are circulated to a range of health care professionals. Only two of the

registries disseminated the report to other interested parties (Emilia Romagna and Ukraine).

This included parents groups, associations and initiative groups of scientists. A further

registry (Zagreb) indicated that they would distribute the report to interested parties on

request. Only the Ukraine registry reported that they had disseminated the findings of the

Report to their local press/media. The Medical director and Regional director of the OMNI-

Net Birth Defects Program coordinated the press releases.

The registries were asked to indicate how they disseminated the findings of the report. Five

registries (29.4%) indicated that they produced a full written report, one of which also

produced a summarised version which included the important findings only. A further eight

registries indicated that they did produce summarised written reports only, with Zagreb

stating that this was included as part of a report to their local Ministry of Science, Education

and Sport. The findings of the report were not widely disseminated on the local registry

websites or on ‘other’ websites. Four registries did make the findings of the report available

on the local registry website (Mainz, Saxony-Anhalt, Tuscany and Ukraine). The Ukraine

registry also published the findings on other websites (the www.ibis-birth defects.

Org/start/Ukrainian/uabsp2.htm). Ile de la Reunion also reported that they published their

findings on other websites but did not specify where. Seminars and scientific meetings were

a more common method, with 68.8% of registries indicating that they had disseminated the

findings this way. Meetings were mostly at local/regional level.

Finally, registries were asked if they knew if the findings of the Annual Statistical Monitoring

Report had been used to influence or change any public health agendas within their region.

Three of the 19 registries (Ile de la Reunion, Tuscany and Ukraine) indicated that it had

been. Ile de la Reunion reported that the Report had been used for the “training of

obstetricians on the techniques and methods in screening for trisomy 21, and that there was

a project in progress for adding folic acid in the diet of women of child bearing age.” The

Ukraine registry reported that the initiation of the regional policy in Folic Acid

Supplementation was influenced by the Annual Statistical Monitoring showing high rates of

neural tube defects. They also reported that the regional Centre for Prenatal Diagnostics

was created based on the results of the monitoring of chromosomal anomalies. Tuscany

reported that attention to the findings is devoted by the regional department, particularly in

the regional health planning preparation.


Appendix L Pan-Europe and individual registry 10 year average rates for congenital

anomalies

Tota

l

Sty

ria

Antw

erp

Hain

aut

Zagre

b

Odense

Paris

Main

z

Saxony A

nhalt

Hungary

Dublin

SE

Ire

land

E R

om

agna

Tuscany

Malta

N N

eth

erla

nds

Weilk

opols

ka

S P

ort

ugal

Basque C

ountr

y

Vaud

Em

sy

N E

ngla

nd

Tham

es V

alle

y

Wale

s

Wessex

All Anomalies 214.6 300.97 205.52 213.67 162.7 244.75 244.18 435.38 292.16 272.98 156.92 132.31 158.64 182.55 272.4 222.57 250.77 92.2 153.73 311.04 177.39 196.46 147.77 325.39 152.85

Nervous system 21.88 27.42 25.39 22.94 11.61 24.21 36.13 28.65 41.2 17.55 14.4 17.68 16.72 13.53 21.45 17.71 21.62 7.39 22.44 25.52 21.49 27.25 21.26 33.31 21.33

Neural Tube Defects 9.15 8.17 8.58 9.43 4.52 10.97 12.3 16.06 9.58 6.36 6.59 9 5.76 4.99 10.58 7.23 9.3 3.9 9.79 10.53 11.31 13.42 10.68 14.41 11.95

Anencephalus and similar 3.41 1.83 2.79 3.28 1.81 3.97 5.05 3.15 2.35 1.95 2.56 3.79 2.13 1.54 1.67 2.13 1.56 1.83 5.12 3.78 4.94 5.42 4.85 5.58 5.94

Encephalocele 1.07 1.61 0.83 1.28 1.06 1.51 1.72 3.46 1.38 0.66 0.81 0.16 0.72 0.65 1.67 0.64 1.04 0.24 0.65 2.43 1.19 1.54 1.13 2.04 1.18

Spina Bifida 4.66 4.73 4.96 4.88 1.66 5.49 5.54 9.44 5.85 3.76 3.21 5.05 2.91 2.8 7.24 4.47 6.71 1.83 4.02 4.32 5.18 6.46 4.7 7.08 4.83

Hydrocephalus 5.14 7.31 5.02 4.72 3.17 6.05 12.87 7.24 5.45 5.23 1.63 3.16 4.65 3.01 2.51 3.62 5.18 1.3 4.02 3.38 5.05 5.86 5.29 7.38 4.76

Microcephaly 2.3 5.7 3.05 2.4 0.9 1.32 2.24 - 15.78 1.64 2.81 3.16 1.22 0.75 3.9 1.97 1.19 0.65 2.76 2.03 1.1 1.79 0.88 4.95 0.89

Arhinencephaly/holoprosencephaly 0.840.65 0.67 1.28 1.21 0.38 0.97 0.63 1.32 0.72 0.45

0.95 1.13 0.68 0.56 0.74 0.34 0.3 1.15 0.41 0.96 1.19 1.18 0.81 0.93

Eye 3.83 5.59 6.46 2.64 1.51 7.38 3.55 4.72 4.42 3.45 4.43 3.32 2.71 3.79 1.67 8.45 1.92 1.6 4.17 3.11 1.94 2.54 1.62 13.3 1.61

Anophthalmos/micropthalmos 0.82 0.75 1.09 0.64 0.15 3.03 0.97 2.2 0.63 0.79 0.98 0.47 1.02 0.82 0.56 1.06 0.82 0.47 0.9 0.54 0.43 0.78 0.69 1.5 0.5

Anophthalmos 0.18 0.54 0.16 0.08 0.00 0.38 0.3 0.31 0.23 0.15 0.2 0.32 0.19 0.1 0.00 0.27 0.34 0.00 0.15 0.14 0.12 * 0.24 0.15 *

Congenital cataract 1.06 1.61 1.03 0.32 0.3 2.27 0.82 0.94 0.34 1.08 2.07 0.95 0.69 1.61 0.28 1.97 0.4 0.12 1.61 0.41 0.56 0.94 0.34 3.45 0.5

Congenital glaucoma 0.32 0.43 0.62 0.32 0.3 0.38 0.26 0.63 0.52 0.47 0.49 0.32 0.3 0.44 0.00 0.64 0.12 0.06 0.5 0.27 * * * 0.72 *

Ear, face and neck 2.84 6.88 4.55 3.04 1.51 1.32 2.51 1.89 7.35 4.51 1.22 0.32 1.8 2.53 8.63 5.05 2.9 2.72 2.16 4.46 1.62 0.6 0.34 4.29 0.75

Anotia 0.36 0.00 0.47 0.4 0.3 0.57 1.42 0.00 0.29 0.74 0.2 0.00 0.28 0.34 0.00 0.05 0.43 0.06 0.05 0.54 * 0.5 * 0.21 *

Congenital heart defects 72.02 122.58 50.31 64.51 56.85 85.68 66.27 117.74 110.13 107.97 42.59 38.05 49.9 67.53 111.41 60.24 118.8 27.91 42.66 121.37 41.02 86.6 37.42 102.13 35.04

Severe CHD § 17.11 23.03 15.3 15.97 10.71 19.67 19.71 24.72 17.91 14.67 19.73 14.84 15.64 13.48 23.95 20.53 11.71 6.86 18.17 20.52 16.64 24.17 15.04 23.95 19.86

Common arterial truncus 0.63 0.86 0.41 0.96 0.6 0.19 0.49 1.26 0.4 0.77 0.65 0.16 0.66 0.31 0.28 0.37 0.43 0.12 0.7 0.95 0.71 1.13 0.49 1.02 0.64

Transposition of great vessels 3.35 4.95 4.19 2.96 2.86 3.4 3.1 5.04 3.27 3.2 3.74 2.53 2.96 3.08 3.9 4.25 2.53 1.24 4.57 2.97 3.32 4.45 3.38 3.42 3.29

Single ventricle 0.62 0.97 1.09 0.72 0.45 0.38 1.01 0.00 0.4 0.77 0.49 1.11 0.58 0.62 1.67 0.69 0.61 0.18 0.6 0.95 0.47 0.38 * 0.87 0.29

Ventricular septal defect 29.51 32.58 19.6 27.66 21.56 50.88 36.28 76.18 40.69 37.88 14.28 17.68 24.47 41.32 44.56 27.91 39.34 17.03 15.76 66.83 14.13 42.17 13.57 44.57 10.59

Atrial septal defect 24.24 86.02 8.74 22.46 27.9 10.59 6.06 14.8 47.23 58.88 7.93 13.58 8.41 8.95 49.02 7.18 77.18 3.55 7.08 31.59 5.65 14.61 9.11 20.95 5.23

Atrioventricular septal defect 1.68 1.83 1.19 2.48 1.06 3.03 2.69 2.2 2.12 0.96 1.3 0.95 1.55 1.4 1.39 1.86 0.82 0.71 1.46 2.7 1.83 2.79 1.32 2.58 2.33

Tetralogy of Fallot 2.9 3.12 3.41 2.88 2.11 3.97 2.58 5.04 3.04 2.48 2.6 2.37 3.24 2.43 2.79 3.14 1.89 1.66 2.51 2.97 2.97 4.8 3.09 3.48 3.01

Tricuspid atresia and stenosis 0.6 0.54 0.57 0.64 0.3 0.76 0.49 2.52 0.52 0.4 0.94 0.79 0.5 0.48 1.11 0.9 0.34 0.12 0.35 1.22 0.7 0.75 0.54 0.69 0.97

Ebstein's anomaly 0.43 0.86 0.26 0.08 0.15 0.19 1.05 0.63 0.52 0.27 0.77 0.47 0.25 0.21 1.11 0.58 0.15 0.12 0.25 0.68 0.46 0.47 0.29 0.69 0.75

Pulmonary valve stenosis 3.95 9.78 3.1 4.32 1.06 6.81 3.1 3.46 5.28 1.76 1.18 1.74 2.24 2.02 13.09 7.87 3.11 1.66 4.92 9.05 2.37 10.66 1.37 10.59 3.33

Pulmonary valve atresia 0.8 0.65 0.52 0.48 0.75 0.76 2.06 0.63 0.75 0.16 0.73 0.47 0.77 0.75 1.67 1.38 0.4 0.47 1.2 0.95 1.13 1.07 0.44 1.44 0.47

Aortic valve atresia/stenosis § 1.2 2.53 0.72 0.89 0.6 1.89 0.64 2.79 1.72 0.83 1.14 0.79 0.59 0.45 1.67 1.85 1.19 0.18 1.61 3.38 0.55 2.67 1.22 2.76 1.47

Hypoplastic left heart 2.51 3.44 1.45 2.16 2.41 3.22 2.77 1.57 2.41 2.13 2.68 3 2.32 2.39 4.46 3.14 1.95 1.12 2.71 2.43 3 2.04 2.35 2.85 3.97

Hypoplastic right heart § 0.39 0.84 0.36 0.27 0.00 1.51 0.22 1.39 0.52 0.19 0.33 0.95 0.15 0.11 0.56 0.18 0.37 0.06 0.3 1.08 0.62 * 0.29 0.72 1

Coarctation of aorta 3.49 6.45 3.05 3.04 1.36 2.46 3.29 5.04 4.19 3.71 5.49 3.95 2.68 2.19 4.18 4.31 1.89 1.06 3.76 3.92 2.75 5.36 2.64 5.22 3.76

Total anomalous pulm venous return 0.580.86 0.57 0.72 0.00 0.19 0.79 0.31 0.75 0.51 0.85

0.95 0.3 0.21 0.56 0.74 0.00 0.00 0.5 0.54 0.58 1.25 0.64 1.05 0.61

PDA as only CHD in term infants

(>=37 weeks) 2.623.23 1.55 0.24 1.51 1.89 0.07 0.00 8.38 5.58 2.56

0.95 0.89 1.67 2.51 1.12 0.7 0.65 1.3 5.4 3.4 1.57 0.29 5.58 0.36

Respiratory 5.36 13.44 6.46 4.8 3.47 2.08 4.79 8.5 6.83 5.71 3.38 8.84 2.77 2.56 3.62 4.94 4.42 1.83 ( 5.52 8.78 3.68 4.23 4.75 14.56 6.19

Choanal atresia 0.78 1.83 1.14 1.36 0.45 0.76 1.05 1.57 1.21 0.96 0.85 0.47 0.42 0.65 0.84 0.85 0.52 0.06 1.15 1.08 0.3 0.88 0.83 1.05 0.57

Cystic adenomatous malf of lung § 0.770.6 0.78 0.09 0.15 0.19 1.83 0 0.17 0.02 0.2

0.16 0.62 0.23 0.00 0.48 0.00 0.12 0.55 1.76 1.26 1.13 2.16 1.86 2

Oro-facial clefts 13.73 15.59 16.75 15.19 14.17 19.67 12.9 20.46 19.57 11.5 14.28) 9 10.32 8.68 19.5 20.15 ( 15.61 6.98 8.58 15.8 12.93 15.46 14.01 17.8 17.61

Cleft lip with or without palate 8.19 9.57 11.63 10.63 8.29 12.29 7.26 11.65 12.22 7.41 6.63 4.58 6.06 5.16 7.8 12.39 9.54 4.02 4.52 7.16 8.33 9.31 7.89 9.81 9.84

Cleft palate 5.53 6.02 5.12 4.56 5.88 7.38 5.65 8.81 7.35 4.1 7.65 4.42 4.26 3.52 11.7 7.76 6.07 2.96 4.07 8.64 4.6 6.15 6.12 7.98 7.77

Digestive system 16.38 28.17 27.51 16.39 10.1 16.64 15.93 17.94 20.83 15.51 14.11 12.32 14.45 11.55 22.28 20.74 13.66 6.33 15.96 29.03 14.68 16.52 11.95 24.1 17.32

Oesophageal atresia with or without

tracheo-oesophageal fistula 2.19

1.94 2.33 3.2 1.36 3.97 2.84 3.78 2.24 1.99 1.99

0.63 2.88 2.22 1.39 2.34 1.77 1.36 2.31 2.84 1.84 2.7 2.06 2.13 2.4

Duodenal atresia or stenosis 0.85 0.54 0.83 0.72 0.15 0.57 0.79 1.57 0.57 0.66 0.94 0.47 1.11 0.48 0.28 0.27 0.76 0.24 0.6 0.68 1.1 1.38 0.88 1.08 1.79

Atresia or stenosis of other parts of

small intestine 0.761.51 0.62 0.16 1.06 1.13 1.08 1.57 0.98 0.27 0.89

0.32 0.91 0.92 1.39 0.85 0.24 0.71 1.51 1.22 0.55 0.94 0.88 1.41 0.68

Ano-rectal atresia and stenosis 2.88 7.2 3.46 3.52 1.51 4.73 3.03 4.72 4.59 2.4 2.93 3.32 2.16 2.19 4.18 3.62 2.77 1.06 3.01 3.38 2.7 3.26 1.96 3.66 2.47

Hirschsprung's disease 1.11 2.47 2.02 0.48 0.75 1.89 0.75 0.94 0.75 0.68 1.55 1.42 0.69 0.31 3.62 1.22 0.79 0.06 1.51 2.16 0.99 1.69 1.22 2.1 1.54

Atresia of bile ducts 0.26 0.54 0.21 0.72 0.3 0.38 0.11 0.63 0.34 0.22 0.16 0.47 0.19 0.31 0.56 0.85 0.03 0.00 0.55 0.00 0.09 0.38 * 0.6 *

Annular pancreas 0.12 0.43 0.31 0.32 0.15 0.19 0.04 0.00 0.11 0.08 0.00 0.00 0.08 0.21 0.00 0.64 0.15 0.12 0.15 0.27 * * * * *

Diaphragmatic hernia 2.48 3.55 2.02 2.4 2.11 1.89 2.32 1.89 2.24 1.96 3.01 2.53 2.49 1.95 3.62 2.13 2.26 0.77 2.21 2.84 3.04 3.26 2.4 3.42 2.93

Abdominal wall defects 5.19 6.56 2.95 3.92 4.07 6.24 5.72 10.07 6.77 3.04 4.68 2.68 3.21 2.53 3.62 2.61 3.51 1.6 3.61 4.73 8.03 9.31 6.51 9.51 7.73

Gastroschisis 2.65 3.44 1.14 2.16 2.26 1.89 1.61 6.93 3.96 0.9 2.48 1.11 1.05 0.75 0.84 1.12 1.65 1.3 1.1 1.89 5.06 5.74 2.94 6.12 4.47

Omphalocele 2.13 2.69 1.6 1.76 1.36 3.78 2.99 3.15 2.24 1.66 2.2 1.58 1.85 1.47 2.51 1.44 1.83 0.3 2.41 2.43 2.7 2.29 3.13 2.76 2.43

Urinary 33.39 76.77 30.3 36.85 19.75 30.64 55.01 134.11 48.38 42.33 15.17 13.26 22.89 25.53 18.38 23.93 32.14 18.27 35.18 59.4 26.07 30.22 21.7 45.56 23.26

Bilateral renal agenesis including

Potter syndrome 1.11.4 1.03 1.36 0.75 1.51 0.82 5.04 1.78 0.55 1.67

1.42 0.64 0.82 1.39 1.7 0.76 0.59 0.95 0.95 1.31 1.94 0.98 1.32 1.11

Renal dysplasia 3.83 10.65 3.46 5.28 1.21 7.19 8.3 7.24 5.57 0.2 2.89 1.58 2.3 3.66 2.23 3.51 1.62 1.95 4.17 7.83 4.57 5.2 3.67 7.29 5.8

Congenital hydronephrosis 10.2 48.92 8.84 18.23 11.01 12.67 19.07 37.78 3.62 4.75 2.32 4.42 8.97 8.34 5.01 3.93 6.04 11.71 4.82 19.44 12.6 9.34 7.64 24.07 6.23

Bladder exstrophy and/or epispadia 0.620.75 0.62 0.64 0.15 0.95 1.01 1.26 0.52 0.44 0.77

0.47 0.5 0.41 0.00 1.01 0.37 0.12 0.6 1.22 0.8 0.66 0.83 0.66 0.72

Posterior urethral valve and/or prune

belly 0.881.94 1.76 0.48 0.00 1.7 1.83 1.57 0.86 0.13 0.57

0.79 0.61 0.65 0.56 1.54 0.43 0.12 1.66 2.43 0.47 0.91 1.22 2.22 1.25

Genital 19.86 34.3 20.32 16.63 20.51 20.81 18.03 40.3 23.13 27.58 13.67 11.53 14.14 23.44 42.34 22.12 18.66 6.56 11.49 32.27 19.22 6.36 12.29 32.11 15.46

Hypospadias 16.62 24.09 16.55 11.43 19 19.29 15.26 36.52 19.23 24.28 12.04 8.84 12.15 20.44 38.72 19.57 14.45 4.67 7.68 24.71 16.38 3.51 10.14 27.55 12.78

Indeterminate sex 0.65 0.54 0.47 1.2 0.75 0.76 0.75 0.31 0.29 0.47 0.37 1.74 0.42 0.72 1.39 0.58 0.43 0.35 0.25 0.81 0.89 0.88 0.88 0.57 1.22

Limb 37.91 35.05 45.29 39.73 28.35 48.8 43.12 63.59 65.94 43.14 45.56 23.68 28.81 26.93 41.22 63.8 37.63 25.02 20.63 38.34 37.56 10.06 22.73 66.75 22.87

Limb reduction 5.09 5.05 4.5 6.79 3.77 8.89 6.47 10.39 6.54 3.71 3.34 1.89 4.84 4.96 5.01 6.49 5.76 1.89 4.62 7.43 5.92 5.39 3.67 7.89 4.62

Upper limb reduction 3.54 3.33 2.69 5.84 2.71 6.05 4.67 6.93 4.65 2.42 2.2 1.58 3.57 3.25 2.79 4.15 4.3 1.06 3.11 5.67 3.96 3.42 2.79 5.85 3.15

Lower limb reduction 1.88 1.94 ( 1.81 1.36 1.21 3.22 2.28 4.41 3.44 1.3 1.18 0.32 1.77 1.98 2.51 2.45 2.1 0.83 2.21 3.51 1.75 1.88 1.08 3.09 1.9

Complete absence of a limb 0.18 0.32 0.1 0.24 0.45 0.95 0.26 0.31 0.29 0.1 0.12 0.16 0.14 0.17 0.00 0.11 0.18 0.00 0.3 0.68 0.18 * * 0.21 *

Club foot - talipes equinovarus 10.26 6.99 10.7 9.35 6.33 14.56 10.62 17.63 17.5 12.11 13.46 10.89 9.19 5.16 9.75 8.99 8.9 6.03 4.07 9.18 11.17 * 9.7 18.28 13.96

Hip dislocation and/or dysplasia 6.57 4.84 7.29 5.28 6.48 15.32 13.35 18.57 6.14 7.6 15.7 2.21 1.41 1.71 2.23 32.11 1.19 7.63 3.86 4.05 1.22 * 2.25 18.73 0.21

Polydactyly 8.21 8.6 13.49 7.83 7.69 6.05 9.61 13.54 12.05 ( 7.81 8.42 3.16 8.77 7.11 16.43 7.39 12.41 5.32 5.02 9.72 10.15 2.1 5.29 11.31 2.4

Syndactyly 5.27 4.3 4.86 6.16 2.71 3.78 3.63 2.2 8.32 9.72 3.34 2.21 4.07 5.26 3.62 4.57 5.79 1.95 1.86 5.4 7.11 1.22 0.69 7.35 1.79

Skeletal dysplasias § 1.67 1.69 2.02 1.69 0.9 2.08 3.33 3.13 1.03 0.94 1.83 1.58 1.25 1.35 2.23 2.98 0.61 0.47 1.91 4.05 1.2 2.1 2.55 2.37 2.68

Craniosynostosis 1.78 5.16 3.72 2.72 1.36 4.16 0.93 1.57 1.89 0.55 1.87 2.05 2.57 0.72 0.28 1.49 1.37 0.47 5.07 6.62 0.43 0.78 2.74 5.49 0.36

Congenital constriction bands/amniotic

band 0.50.32 0.57 0.24 0.00 1.51 0.52 0.31 1.15 0.15 0.37

0 0.44 0.07 0.56 0.48 0.21 0.35 0.3 2.3 0.27 0.85 0.98 1.56 0.57

Situs inversus 0.57 0.75 0.78 0.56 0.3 1.13 1.57 0.31 0.4 0.5 0.53 0.32 0.5 0.51 0.00 0.8 0.24 0.06 0.75 0.54 0.53 0.41 0.34 0.87 0.47

Conjoined twins 0.19 0.22 0.05 0.00 0.3 0.38 0.22 0.63 0.52 0.13 0.00 0.00 0.00 0.07 0.00 0.00 0.15 0.00 0.25 0.27 0.31 0.31 0.29 0.3 0.32

Congenital skin disorders 2.27 9.78 4.29 3.76 1.96 1.89 0.75 1.26 4.99 4.13 1.02 3.47 0.89 2.22 5.01 1.86 1.07 1.48 1.96 4.05 1.04 1.03 0.29 3.69 0.18

Teratogenic syndromes with

malformations § 0.892.05 1.86 1.42 0.45 1.13 1.2 1.04 1.84 0.05 2.24

0.63 0.92 0.19 1.39 0.6 0.37 0.18 1.05 2.57 0.37 0.6 1.96 1.98 1.18

Fetal alcohol syndrome § 0.19 0.86 0.05 0.96 0.3 0.19 0.19 0.31 0.69 0.01 0.37 0.16 0.00 0.03 0.00 0.00 0.06 0.12 0.1 0.27 0.18 * * 0.69 0.18

Valproate syndrome § 0.05 0.12 0.00 0.18 0.00 0.38 0.04 0.00 0.11 0.00 0.16 0.00 0.03 0.00 0.00 0.24 0.00 0.06 0.05 0.14 * * * * *

Maternal infections resulting in

malformations 0.520.65 1.71 0.24 0.00 0.57 0.97 0.00 0.63 0.00 1.63

0.32 0.75 0.14 1.39 0.21 0.27 0.00 0.85 2.03 0.1 0.38 0.64 1.08 0.75

Genetic syndromes + microdeletions 4.788.49 6.31 6.08 1.51 8.89 ( 4.9 13.22 3.56 2.26 6.18

3.95 3.57 1.81 5.57 9.84 1.59 0.59 2.81 14.72 3.18 9 6.76 8.64 7.62

Sequences 2.26 2.8 3.1 1.84 0.6 4.92 3.67 5.98 5.05 1.01 3.82 2.84 1.38 0.85 3.62 3.35 1.37 1.24 2.86 6.08 1.6 2.76 2.2 3.51 1.97

Chromosomal 36 37.63 26.89 38.77 16.74 45.77 72.85 57.93 29.27 20.12 34.53 29.37 35.2 30.72 29.25 36.42 20.64 11 54.36 69.26 34.8 45.18 48.29 43.19 55.72

Down Syndrome 20.38 21.18 13.7 20.94 12.06 23.64 40.61 36.52 16.13 14.09 22.29 20.37 20.45 18.66 20.61 17.28 15.37 6.86 30.97 35.24 18.68 22.95 26.94 21.49 26.84

Patau syndrome/trisomy 13 1.82 2.8 1.34 1.44 0.15 3.03 3.89 2.52 0.98 0.84 1.95 1.26 1.41 1.61 0.84 1.81 0.85 0.35 2.31 3.51 2.23 2.51 3.13 2.13 2.79

Edwards syndrome/trisomy 18 4.69 3.66 4.19 4.4 1.66 5.3 13.35 8.5 3.85 2.08 4.15 3 4.32 3.59 4.18 6.38 1.65 0.77 6.52 6.89 5.06 5.77 7.64 5.67 6.05

Turner syndrome 2.32 2.9 1.81 2.4 0.75 3.4 5.35 1.89 2.01 0.93 1.38 0.95 1.66 1.98 0.00 2.71 0.79 0.83 4.07 5.54 2.46 3.39 2.79 3.15 4.29

Klinefelter syndrome 0.89 0.75 0.47 1.2 0.75 1.13 1.53 1.57 1.21 0.59 0.33 0.32 1.58 1.61 0.28 0.21 0.18 0.65 2.41 2.57 0.52 1.1 0.69 0.75 1.11

eurocat statistical monitoring report 2010...eurocat statistical monitoring report 2010 6 decline in...

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