pre eklampsi
TRANSCRIPT
J. Perinat. Med. 39 (2011) 257–265 • Copyright � by Walter de Gruyter • Berlin • New York. DOI 10.1515/JPM.2011.010
2010/096
Article in press - uncorrected proof
Risk groups and maternal-neonatal complications of
preeclampsia – Current results from the national German
Perinatal Quality Registry
Sven Schneider1,2,a,*, Nele Freerksen3,a, HolgerMaul4,a, Silke Roehrig2, Burkhard Fischer5 andBirgit Hoeft1,a
1 Mannheim Institute of Public Health, Social andPreventive Medicine (MIPH) Mannheim Medical Faculty,Heidelberg University, Ludolf-Krehl-Str. 7-11, D-68167Mannheim, Germany
2 Competence Center for Social Medicine and OccupationalHealth Promotion, Heidelberg University, Ludolf-Krehl-Str. 7-11, D-68167 Mannheim, Germany
3 University Women’s Hospital of the RWTH Aachen,Aachen University, Pauwelsstr. 30, D-52074 Aachen,Germany
4 Women’s Hospital, Katholisches Marienkrankenhaus,Alfredstr. 9, D-22087 Hamburg, Germany
5 German Federal Agency for Quality Assurance gGmbH,Dusseldorf, Kanzlerstr. 4, D-40472 Dusseldorf, Germany
Abstract
Aims: We investigated risk factors and neonatal outcomesof preeclampsia.Methods: We analyzed data of the German Perinatal QualityRegistry 2006 that contains the complete national birthcohort of 668,085 newborn infants and 647,392 mothersfrom 917 German obstetric clinics.Results: The prevalence of preeclampsia in 2006 was at2.31%. Higher maternal age, gestational diabetes, no previ-ous as well as multiple births, pre-pregnancy obesity andabove-average weight gain during pregnancy were signifi-cantly associated with preeclampsia. A positive relationshipbetween social burden (e.g., low social status, psychosocialstress) and the risk of preeclampsia appeared. Smokingappeared to be negatively correlated. Neonatal complicationsassociated with preeclampsia in the study were small babies,acute respiratory distress syndrome, postpartum neonatalhypoglycemia and low Apgar scores. We did not observe anincreased rate of stillbirths with preeclampsia pregnancies.
Authors contributed to this paper equally.a
*Corresponding author:Sven Schneider, Prof., Dr., MAMannheim Institute for Public HealthSocial and Preventive Medicine (MIPH) Medical Faculty MannheimHeidelberg UniversityLudolf-Krehl-Str 7-11D-68167 MannheimGermanyTel.: q49-621-383-9917Fax: q49-621-383-9920E-mail: [email protected]
Conclusions: Further studies and interventions regardingprenatal care should not focus only on how better diagnosticand treatment procedures can be implemented but also onhow these diagnostic and treatment procedures can reachhigh-risk groups.
Keywords: Abnormalities; gestational diabetes; gestosis;hypertension; preeclampsia; pregnancy complications; pro-teinuria; risk factors.
Introduction
Preeclampsia is a leading cause of serious complications dur-ing pregnancy. Prevalence rates of preeclampsia in developedcountries range from 3% to 8% among all pregnancies w2, 4,13, 15, 24x with reoccurrence rates of 13–18% w9x. As pre-eclampsia accounts for about 42% of all maternal deaths w5,25x increasing research efforts to investigate this seriouscondition have been made within the last years.
Preeclampsia is characterized by systemic endothelial dys-function resulting in elevated blood pressure and proteinuria.Maternal complications include eclampsia (onset of sei-zures), renal failure, placental abruption, stroke, major com-plications like infections, and maternal mortality w2, 4, 13,15, 24x. Fetal problems include stillbirths, neonatal mortality,intrauterine growth restriction (IUGR) and complications dueto preterm delivery caused by exacerbated preeclampsia w14x.
Despite intensive research, the causes of preeclampsia stillremain uncertain. Recent studies have found that angiogenicfactors, insulin-resistance and changes in the renin-angioten-sin system might be partially responsible for the pathogenesisof the disease w13x. Because the etiology is still unclear, it isnot surprising that no effective screening methods for theprediction of preeclampsia have been developed. Althoughvarious clinical trials have evaluated different modes of ther-apy, currently no effective preventive or therapeutic measureshave been found aside from immediate delivery of the fetus.
The absence of successful therapeutic measures calls forfurther research. Sound knowledge of the relevant risk fac-tors is necessary to develop effective screening methods. Inthis context, research has focused on various topics, such asthe relationship between gestational diabetes, pre-existingobesity, increased maternal weight gain and preeclampsia inthe last few years w3, 4, 6, 11, 15, 16, 20, 21, 23, 24, 26x.The role of parity w15, 26x and of multiple pregnancies w4xhas also been examined by various authors. So far, the find-ings of the influence of maternal age during pregnancy w10,21, 26x and tobacco consumption w15, 21, 26x are contradic-tory. Additionally, there is a surprising lack of research on
258 Schneider et al., Risk groups and outcomes of preeclampsia
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the influence of social risk factors (e.g., low socio-economicstatus, psychosocial stress and drug abuse).
Our study aims to add further knowledge to currentresearch. Specifically, we intend:
1. to investigate the importance of the above-mentioned riskfactors (especially factors that have scarcely been inves-tigated and those with contradictory results) and,
2. to study the impact of preeclampsia on the fetal, neonataland maternal outcomes.
Methods
Our study was the first to use data from the German Perinatal Qual-ity Registry. This national registry contains complete birth cohortdata and information that can be used for identifying high-riskgroups and evaluating current screening options. It is a full inven-tory of all hospital births in Germany. The Registry is part of astandardized national medical and nursing quality assurance pro-gram for German hospitals. The program was set up in 2001 withthe involvement of the governing bodies of the Statutory HealthInsurance System, the Association of German Private Health Insur-ance companies, the German Hospital Association, the GermanMedical Board and Long-Term Nursing Care Insurance organiza-tions w8x. One of the core areas covered in this healthcare qualityassurance system is obstetrics and gynecology. The German FederalAgency for Quality Assurance (Bundesgeschaftsstelle Qualitatssi-cherung gGmbH BQS) collects detailed data and quality indicatorsfor all hospital deliveries in a given calendar year on behalf of theaforementioned organizations. These data are made available in theGerman Perinatal Quality Registry w8; see also Attachment at theend of this articlex.
This is possible, because in Germany, the prenatal care duringpregnancy offered by health insurance organizations is nationallystandardized. Over 95% of all pregnant women submit a maternitylog (‘‘Mutterpass’’) prior to giving birth. The majority (98.3%) ofall pregnant women attend at least five of the regular examinationsat their obstetricians’ practices w7x. These examinations are con-ducted using clear, nationally standardized guidelines, which alsoinclude guidelines for further courses of action should any symp-toms of preeclampsia appear. For example, blood pressure shouldbe measured and a test for proteinuria carried out during each ofthe regular examinations. In accordance with the quality guidelines,each case should be registered in the maternity log and recorded inthe Perinatal Quality Survey.
As reporting is mandatory for all deliveries, perinatal data areavailable for 99.3% of births in Germany w8x. The current GermanPerinatal Quality Registry 2006 contains pre- and perinatal data on668,085 newborn infants and 647,392 mothers from all 917 Germanobstetric clinics. Approval for the study was received from the Uni-versity of Heidelberg Ethics Committee (protocol number AZ S-165/2008).
The database on obstetrics and gynecology includes informationon maternal sociodemographic factors and anamnestic maternaldata. To assess the influence of potential risk factors we adopted aresearch design similar to a recent publication w26x and included allof their risk factors as well as additional variables of our interest(social status and stress indicators, alcohol and drug abuse, and mul-tifetal pregnancies). The selection of potential risk factors has alsobeen approved by the panel of experts of the German Federal Agencyfor Quality Assurance and the Federal Joint Committee. Social stat-us was evaluated using employment status prior to pregnancy. Nom-
inal categories were used to label non-working women: housewives,trainees, and students. Ordinal categories were used to rank theemployment status prior to pregnancy: unskilled worker, skilledworker, higher service/management. The social burden of pregnantwomen included self-reports of psychosocial stress from work orhome. Drug abuse and average daily cigarette consumption wasmeasured after pregnancy confirmation. Data regarding weight atfirst antenatal visit, weight gain during pregnancy, number of priorpregnancies (including stillbirths and terminations) and multiplebirths were also collected. The data was derived from maternity logbooks, which are given to all women in Germany as soon as theprimary-care gynecologist confirms pregnancy. Information is reg-ularly entered into the maternity log during subsequent prenatalexaminations throughout pregnancy in a standardized fashion.Obstetric and neonatological outcomes are added to the log duringthe first few postpartum days and prior to discharge from the clinic.If the primary-care gynecologist or physician in the obstetric clinicdiagnoses preeclampsia, this diagnosis is also registered in thematernity log. In addition, all pregnancies with a simultaneous diag-nosis of hypertension (repeatedly )140/90) and proteinuria are rou-tinely coded as cases of preeclampsia in the German PerinatalQuality Registry. According to standard coding procedures, all caseswith a diagnosis of HELLP syndrome were coded as a variant ofpreeclampsia. Diagnoses of gestational diabetes were recorded aswell (e.g., as a pregnancy risk or flagged as indicator for hospitaladmission). In accordance with standard procedures w15x, pre-exist-ing cases of diabetes mellitus were excluded. German law (Pers-StdGAV§29) defines a stillbirth as a newborn with no signs of life(no heartbeat, no breathing movements, no umbilical pulsations) anda birth weight of at least 500 g. Sex stratified small-for-gestationalage (SGA) was coded as birth weight under the 10th percentile forgestational age. Hypertension, proteinuria, fetal malformations, typeof delivery, birth weight of the child, diagnoses of macrosomia,hypoglycaemia, acute respiratory distress syndrome (ARDS), neo-natal convulsions, and other relevant neonatal outcomes weredefined according to the International Statistical Classification ofDiseases and Related Health Problems (ICD 10).
In the first step, x2-testing was employed to determine the rela-tionship between the categorical variables of interest by comparingobserved frequencies in the normal population to frequencies in thepreeclampsia categories.
In the second step, logistic regression models were used to esti-mate the odds ratios (OR) and corresponding 95% confidence inter-vals (95% CI) for the purposes of identifying the separatecontribution of several risk factors (preeclampsias1, no preeclamp-sias0). ORs were calculated for each potential determinant (unad-justed ORs; Model 1). All variables were then included in a singlemultivariate adjusted model (adjusted ORs; Model 2). All P-valuesreported are two-tailed with significance level of P-0.05. All sta-tistical analyses were done using SPSS version 16.0. (SPSS Inc.,Chicago, IL, USA).
Results
In Germany, the prevalence of preeclampsia was 2.31%(14,934/647,385) among all pregnant women in 2006. High-risk groups for the development of preeclampsia were older,nulliparous, non-smoking women as well as women with lowsocioeconomic status, psychosocial stress, a history of drugabuse and multiple gestations. Preeclampsia was also asso-ciated with gestational diabetes, pre-pregnancy obesity andan above-average weight gain during pregnancy (Table 1).
Schneider et al., Risk groups and outcomes of preeclampsia 259
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Tab
le1
Biv
aria
tean
alys
esan
dm
ultip
lelo
gist
icre
gres
sion
anal
yses
for
corr
elat
esof
pree
clam
psia
duri
ngpr
egna
ncy
inG
erm
any.
Var
iabl
en
(tot
al)
n(P
reec
lam
psia
)%
(Pre
ecla
mps
ia)
P-va
luea
Mod
el1
Mod
el2
Sign
ific
ance
for
OR
bw9
5%C
IxO
Rad
just
edc
w95%
CIx
Mod
el2
Age
d-
0.00
1-
20ye
ars
18,1
7533
61.
8R
efer
ence
Ref
eren
ce20
–25
year
s98
,264
2193
2.2
1.21
2w1
.079
,1.
361x
1.19
8w1
.063
,1.
350x
0.00
325
–30
year
s18
6,81
842
602.
31.
239
w1.1
08,
1.38
6x1.
289
w1.1
45,
1.45
0x-
0.00
130
–35
year
s19
3,45
342
692.
21.
198
w1.0
71,
1.34
0x1.
406
w1.2
48,
1.58
4x-
0.00
1)
35ye
ars
150,
676
3876
2.6
1.40
2w1
.253
,1.
569x
1.83
1w1
.623
,2.
065x
-0.
001
Nat
iona
lity
-0.
001
Ger
man
524,
289
12,9
682.
5R
efer
ence
Ref
eren
ceE
aste
rnE
urop
e34
,154
607
1.8
0.71
3w0
.657
,0.
775x
0.84
6w0
.778
,0.
920x
-0.
001
(for
mer
Eas
tern
bloc
)M
edite
rran
ean
neig
hbou
r20
,906
325
1.6
0.62
3w0
.557
,0.
696x
0.71
1w0
.635
,0.
795x
-0.
001
Oth
erna
tiona
litie
s68
,036
1034
1.5
0.60
8w0
.571
,0.
649x
0.72
0w0
.674
,0.
770x
-0.
001
Job
stat
us-
0.00
1U
nski
lled
wor
kere
21,0
7961
22.
91.
301
w1.1
85,
1.42
8x1.
230
w1.1
17,
1.35
5x-
0.00
1Sk
illed
wor
ker,
mid
dle
serv
icee
192,
366
5297
2.8
1.23
2w1
.166
,1.
301x
1.15
2w1
.089
,1.
218x
-0.
001
Hig
her
serv
ice/
man
agem
ente
77,0
3617
312.
2R
efer
ence
Ref
eren
ceTr
aine
e,st
uden
tf20
,671
401
1.9
0.86
1w0
.771
,0.
960x
0.95
3w0
.849
,1.
070x
0.41
5H
ousw
ifef
220,
653
4139
1.9
0.83
2w0
.786
,0.
880x
1.05
3w0
.991
,1.
120x
0.09
8So
cial
orps
ycho
logi
cal
impa
ctsg
0.00
3N
o62
5,26
614
,358
2.3
Ref
eren
ceR
efer
ence
Yes
22,1
1957
62.
61.
138
w1.0
46,
1.23
8x1.
227
w1.1
25,
1.33
7x-
0.00
1B
MIg
-0.
001
-20
84,4
0019
471.
10.
677
w0.6
30,
0.72
8x0.
704
w0.6
55,
0.75
6x-
0.00
120
–25
305,
438
4779
1.7
Ref
eren
ceR
efer
ence
25–3
012
8,64
436
322.
81.
828
w1.7
50,
1.90
9x1.
943
w1.8
59,
2.03
0x-
0.00
130
–35
46,7
7622
574.
83.
190
w3.0
31,
3.35
7x3.
675
w3.4
89,
3.87
1x-
0.00
1)
3524
,933
2094
8.4
5.76
8w5
.470
,6.
083x
7.07
9w6
.699
,7.
480x
-0.
001
Wei
ght
gain
duri
ngpr
egna
ncy
-0.
001
-20
kg50
1,67
397
701.
9R
efer
ence
Ref
eren
ce20
–25
kg61
,904
2259
3.6
1.90
7w1
.820
,1.
998x
1.92
6w1
.836
,2.
021x
-0.
001
25–3
0kg
15,1
4085
55.
63.
013
w2.8
05,
3.23
8x2.
848
w2.6
45,
3.06
6x-
0.00
1)
30kg
4936
424
8.6
4.73
1w4
.274
,5.
237x
4.08
2w3
.675
,4.
534x
-0.
001
Smok
ing
-0.
001
Non
-sm
oker
462,
196
10,8
552.
3R
efer
ence
Ref
eren
ce1–
5ci
gare
ttes/
day
20,4
8044
12.
11.
025
w0.9
34,
1.12
4x0.
866
w0.7
85,
0.95
7x0.
005
6–10
ciga
rette
s/da
y24
,808
373
1.5
0.98
5w0
.904
,1.
073x
0.63
2w0
.566
,0.
706x
-0.
001
)11
ciga
rette
s/da
y18
,857
308
1.6
0.86
9w0
.787
,0.
960x
0.72
4w0
.633
,0.
828x
-0.
001
Alc
ohol
and/
ordr
ugab
use
-0.
001
No
619,
991
14,4
902.
3R
efer
ence
Ref
eren
ceY
es27
,394
444
1.6
0.68
8w0
.626
,0.
757x
0.92
9w0
.782
,1.
048x
0.23
1
260 Schneider et al., Risk groups and outcomes of preeclampsia
Article in press - uncorrected proof
(Tab
le1
cont
inue
d)
Var
iabl
en
(tot
al)
n(P
reec
lam
psia
)%
(Pre
ecla
mps
ia)
P-va
luea
Mod
el1
Mod
el2
Sign
ific
ance
for
OR
bw9
5%C
IxO
Rad
just
edc
w95%
CIx
Mod
el2
Num
ber
ofpr
egna
ncie
s-
0.00
1Fi
rst
preg
nanc
y32
1,56
399
893.
1R
efer
ence
Ref
eren
ceFu
rthe
rpr
egna
ncy
325,
822
4945
1.5
0.48
1w0
.464
,0.
498x
0.43
4w0
.417
,0.
451x
-0.
001
Mul
tifoe
tal
preg
nanc
ies
-0.
001
No
636,
837
14,3
062.
2R
efer
ence
Ref
eren
ceY
es10
,548
628
6.0
2.75
5w2
.537
,2.
991x
2.28
4w2
.098
,2.
486x
-0.
001
Ges
tatio
nal
diab
etes
mel
litus
-0.
001
No
632,
395
14,3
222.
3R
efer
ence
Ref
eren
ceY
es14
,990
612
4.1
1.83
7w1
.691
,1.
995x
1.29
4w1
.188
,1.
409x
-0.
001
Num
ber
ofpr
egna
ntw
omen
(n)
647,
385
14,9
342.
3
Dep
ende
ntva
riab
le:
Pree
clam
psia
s1,
OR
sod
dsra
tio,
95%
CIs
95%
conf
iden
cein
terv
al.
a x2-t
est;
bU
nadj
uste
dO
R’s
;c A
djus
ted
for
all
vari
able
s;dA
geat
deliv
ery;
e Ord
inal
cate
gori
zatio
n;f N
omin
alca
tego
riza
tion;
gkg
/m2.
The risk of developing preeclampsia increased with age.Compared to a prevalence of 1.8% among women -20 yearsof age, the prevalence was 2.6% for women )35 years.After adjusting for confounders, ORs increase almost linearlyup to 1.831 for the oldest pregnant women. Immigrantsshowed a significantly decreased risk of preeclampsia com-pared to German women (Table 1). An association was alsofound with socioeconomic status: women with low-incomejobs were diagnosed with preeclampsia more frequently thanpregnant women with high-income jobs (i.e., executive posi-tions or positions requiring a university degree). Pregnantwomen reporting particularly high social stress also showeda higher risk of preeclampsia. Whereas alcohol or drug abusedid not alter the risk of preeclampsia, minor and major tobac-co consumption were associated with a lower risk. Comparedto singleton gestations, multiple gestations were related to anincreased risk of developing preeclampsia.
The data set also permitted investigations into the rela-tionship between weight, weight gain, gestational diabetesand preeclampsia. The relationship between preeclampsiaand pre-pregnancy body weight as well as weight gain seemsto be linear. In bivariate comparisons, women with an initialbody mass index (BMI) )35 and women with a weight gainof more than 30 kg showed significantly higher rates of pre-eclampsica (8.4% and 8.6%, respectively). Gestational dia-betes was also associated with a higher preeclampsia risk. Ifthese three factors are taken into account within an adjustedmodel, it becomes clear that 1) the ORs remain significantwhen all other factors remain constant, and 2) BMI plays akey role in the etiology of the disease (Table 1, Model 2).
Preeclampsia increases the risk of several complications.The risk of SGA was 15.1 in preeclampsia cases comparedto 4.1 in non-cases, per thousand deliveries (P-0.001). Ana-lyzed in more detail, preeclampsia led more often to lowbirth weights and less often to above-average birth weightsin both male and female neonates (P-0.001; Table 2).
Low Apgar scores were further important complicationsduring pregnancy and delivery. These complications alsooccured significantly more often among preeclampsia preg-nancies (P-0.001; Table 2). For preeclampsia pregnanciesthe rate of fetal malformation did not differ significantly.Furthermore, preeclampsia was associated with a lower rateof stillbirths (P-0.001; Table 2). Additional analysesshowed that the rates of ARDS (0.37% vs. 0.11%) and therisk of postpartum neonatal hypoglycaemia (0.66% vs.0.26%) were also significantly higher among the preeclamp-sia cases (P-0.001). The rate of primary cesarean sectionswas three times as high and the rate of secondary sectiontwice as high compared to those without preeclampsia(P-0.001).
Discussion
The results demonstrate that the overall prevalence of pre-eclampsia in Germany is low (2.31%) but that certain groupsare at higher risk. Risk factors for preeclampsia are highermaternal age, lower social status, psychosocial stress, no pri-
Schneider et al., Risk groups and outcomes of preeclampsia 261
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Table 2 Outcome in children in regard to the independent variable preeclampsia.
Outcome variable n n Model 1 Model 2(dependent variable) Crude odds ratio for Adjusted odds ratio for
preeclampsia w95% CIx preeclampsia w95% CIx
Birth weight -10% percentile: Yes NoPreeclampsia 2407 12,527 1.902 w1.820, 1.989x 2.077 w1.984, 2.174xNo preeclampsia 58,022 574,429 Reference Reference
Birth weight )90% percentile: Yes NoPreeclampsia 1531 13,403 0.925 w0.877, 0.976x 0.789 w0.747, 0.834xNo preeclampsia 69,465 562,986 Reference Reference
5-min Apgar score -7: Yes NoPreeclampsia 356 14,487 2.271 w2.039, 2.529x 2.083 w1.876, 2.325xNo preeclampsia 6746 623,353 Reference Reference
Fetal malformation: Yes NoPreeclampsia 136 14,798 0.921 w0.777, 1.093x 0.908 w0.764, 1.078xNo preeclampsia 6246 626,205 Reference Reference
Stillbirth: Yes NoPreeclampsia 30 14,904 0.645 w0.449, 0.925x 0.598 w0.416, 0.860xNo preeclampsia 6246 626,205 Reference Reference
or as well as multiple births, pre-pregnancy obesity, above-average weight gain during pregnancy and gestationaldiabetes. Smoking appears to be negatively correlated withpreeclampsia. Neonatal complications are SGA, ARDS, post-partum neonatal hypoglycemia as well as low Apgar scores.In contrast to other countries, our results for Germany didnot show an increased rate of stillbirths from preeclamp-sia pregnancies.
The four most important limitations of this nationwide,register-based study are undetected cases, missing data andvalues, validity of self reports, and lack of causality. It isexpected that a certain number of preeclampsia cases gounreported every year. With regard to the interpretation ofthe results, it is important to consider that pregnant womenwith preeclampsia receive treatment once they are diagnosed.Any assumptions regarding the negative effects of pre-eclampsia that are based on the reported effect size are there-fore possibly underestimating the true effects.
Due to limited data access, not all possible maternal andfetal outcomes could be included. Therefore, no analyseswere conducted, among others, on the influence of the dateof diagnosis or the number of prenatal consultations, or con-cerning major complications like renal failure, placentalabruption or maternal or neonatal mortality.
As data on all pregnancies is collected systematically inthe national registry, little relevant information was missingfor the included variables. While the so-called ‘‘mandatory’’fields were almost complete (-1% missing values), datafrom the ‘‘optional information’’ sections were more fre-quently missing. The rates of missing data were 5.5% forBMI, 16.2% for occupation and 19.6% for tobacco con-sumption. In order to deal with this missing information, weincluded the category ‘‘missing data’’ in our regression mod-el. This helped to avoid a reduction in the total number ofcases and to maintain the representativeness of the remainingassociations. A desire to give socially approved responsescan result in under-reporting of smoking prevalence and drugabuse during pregnancy. This potential social desirability
bias was discussed recently w17, 18x. Current literature putsthe extent of under-reported smoking among pregnant wom-en at 3–5% points.
Due to the observational design of our study, we cannotconclude that preeclampsia is causally related to the risk fac-tors and adverse outcomes. However, the discussed relation-ships are plausible. The Bradford-Hill Criterion of‘‘dose’’-response relationships (i.e., age, BMI and smoking)is also met.
The Perinatal Quality Survey provides well-characterizedand (nearly) complete cohort information. Preeclampsia cas-es are diagnosed within a standardized health care and qual-ity controlled system where more than 98% of women accessprenatal care, ensuring the consistency and validity of thediagnostic outcome information w7x. The broad coverage ofthe registry and the large number of pregnancies included,are important strengths of our study. Information is lackingonly for out-of hospital births (births in midwives’ clinics orhome births), which amount to approximately 10,000/year(i.e., -1.5%; w12x).
The German preeclampsia prevalence rate of 2.3% is low-er than the rates from other countries (3–8%) w2, 4, 13, 15,24x. As described in detail above, Germany is a countrywhere more than 98% of all pregnant women receive highlystandardized prenatal care. This may explain why the ratesof preeclampsia (and the rate of consecutive stillbirths) inGermany are much lower compared with other countries.The ‘‘Mutterpass’’ (maternity log) that is distributed to allpregnant women thus could serve as a model for othernational prevention programmes.
In Germany, prevalence rates for preeclampsia are low, yetthe risk is not distributed equally over all social classes. Therisk is higher among certain groups. With regard to some ofthe risk factors examined in this study, the results of ourstatistical analyses confirm the findings of other authors w3,4, 6, 11, 15, 16, 19–21, 23, 24, 26x. For example, we alsofound that primiparity as well as multiple births, pre-preg-nancy obesity, above-average weight gain during pregnancy
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and gestational diabetes resulted in a higher risk of pre-eclampsia. We were also able to replicate the findings show-ing that GDM and obesity were important independent riskfactors for preeclampsia. The ORs we found equal those ofother authors w6, 15x. Whereas fetal macrosomia itself, whendefined as a birth weight over the 90th percentile, is nega-tively correlated with preeclampsia in our study, babies ofmothers with gestational diabetes are obviously too large rel-ative to the placental potential (Table 1). One may alsohypothesize that gestational diabetics exhibit a vascular pro-file that may enhance the development of preeclampsia as avascular reactivity disorder, as postulated by many authors.
Another important finding for future preventive measuresis the relationship between social burden (e.g., low socialstatus, psychosocial stress, and drug abuse) and the risk ofpreeclampsia, an aspect that has rarely been investigated.These factors are associated with an unhealthy lifestyle, met-abolic syndrome and fewer prenatal care visits w1, 17, 18,22x. This aspect of health inequality will not be amelioratedin the future if socially disadvantaged women are not reachedeffectively. Our data support the need for developing suchstrategies in order to reduce the rates of preeclampsia.
At the same time that Sibai et al. w21x did not find a sig-nificant effect with age, Krapp w10x reported a higher riskfor younger pregnant women. Conversely, Wendland et al.w26x showed an increased risk with age. Our data support thesame linear relationship.
Smoking as a risk factor for preeclampsia has been studiedwith mixed findings. Apart from our analysis, Wendland etal. w26x and Sibai et al. w21x found no effect. In contrast,smoking as a negatively correlated factor has also been foundin the study of Ostlund et al. w15x. Smoking may both altervascular reactivity during gestation and hinder growth there-by reducing the fetal need for oxygen and nutrients anddecreasing the risk of preeclampsia. It is important to pointout that smoking is not a strategy for prevention due to themany other effects it has on maternal and neonatal health aswell as its association with other adverse maternal and fetalmorbidity w18x.
It is important to note the complex relationship betweensociostructural and behavior-related variables in this context(such as age, social status, nationality and smoking). Germannationality has so far been associated with a higher socialstatus and higher age at delivery. Besides, smoking duringpregnancy is less common among non-German, higher edu-cated as well as older women w17, 18x. These confoundingphenomena are addressed and partially controlled for in themultiple logistic regression analysis (Table 1). Further analy-ses of complex interaction effects were beyond the scope ofthe study and data availability. Future studies should there-fore account for such interaction effects and include addi-tional variables, such as the date of diagnosis and prenatalhealth care use.
Although our findings seem to be partially contradictoryin the first place (smoking, stillbirths) they fit together verywell supporting the theory that preeclampsia may be theresult of an impaired relationship between offer and demand.Preeclampsia therefore is associated with low birth weight
babies. Their strategy to survive seems to be the signal tothe mother to increase blood pressure at the point when pla-cental function is no longer sufficiently promoting fetalgrowth. Increase in blood pressure enhance placental perfu-sion and improve the supply of nutrients and oxygen to thefetus in the short-term; however, this pathway is detrimentalin the long run. When this path does not work sufficiently,stillbirths may occur. Therefore, stillbirths are generally relat-ed to the development of preeclampsia. However, we foundlower stillbirth rates with preeclampsia pregnancies. Thisassociation may be due to the fact that women with pre-eclampsia may be exposed to improved or optimised prenatalcare and may be monitored better during pregnancy afterdiagnosis. We believe that this observation proves that pre-eclampsia screening is beneficial. The reported OR shouldtherefore be interpreted carefully.
We conclude that higher maternal age, several social risks,obesity and gestational diabetes are strongly related to pre-eclampsia. Further studies and interventions regarding pre-natal care should therefore not only focus on how betterdiagnostic and treatment procedures can be implemented butalso on how these diagnostic and treatment procedures reachobese and/or older women of low socio-economic status.Perinatal and maternal morbidity may not decrease any fur-ther if we are not able to clearly target these high-risk groupsof women. Otherwise, prenatal care will only become moreexpensive and thus even more ineffective. Increasing mater-nal age as well as increasing rates of maternal obesity jus-tifies this change of focus.
We are the first scientific research team that was grantedaccess to this sensitive data. To our knowledge, our study ofthese specific topics is the most comprehensive to date.
Acknowledgements
This publication was based on a research visit of the first (Sv.S.)and last (B.H.) authors to the Bundesgeschaftsstelle Qualitatssiche-rung gGmbH (BQS, Dusseldorf, Germany). We would like to thankMrs. Sandu, BQS staff scientist, for assessing and preparing thedata, for valuable technical and method information and for dis-cussing and interpreting the results. Finally, we wish to thank Dr.Shelby Yamamoto, PhD, Tatiana Yarmoliuk, M.A. and ChristinaHuy, Dipl.-Inform. Med. (all MIPH) for their assistance in preparingthis manuscript.
References
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The authors stated that there are no conflicts of interest regardingthe publication of this article.
Received May 7, 2010. Revised October 7, 2004. Accepted October21, 2010. Previously published online March 10, 2011.
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Attachment: Risk groups and neonatal outcomes of
preeclampsia – Current result from the national German
Perinatal Quality Registry w8x
German Federal Agency for Quality Assurance. Qualitatsreport2006 wQuality Report 2006x (in German). Dusseldorf: Bundesges-chaftsstelle Qualitatssicherung; 2007.
Variables in data set ‘‘Obstetrics’’
1. Data set Mother
Basic Documentation Mother
1. ID number of mother2. Date of birth of pregnant women3. Date of admittance4.1 Admittance diagnosis5.1 Number of days of treatment before admission in
hospital5.2 Number of days of treatment after discharge from
hospital6. Postcode of city of residence7.1 Nationality: Germany (yes/no)7.2 Nationality: Other country
1. Central and Northern Europe, North America2. Mediterranean countries3. Eastern Europe4. Asia5. Other countries
8. Single mother (yes/no)9.1 Occupation before/during current pregnancy9.2 Kind of occupation
1. Housewife2. Student/Trainee3. Unskilled worker4. Skilled worker, middle service5. Higher service, higher executive, self-employed,
freelancer6. Other
10.1 Amount of preceded pregnancies
Current pregnancy
11. Number of cigarettes (per day) after confirmingpregnancy12. Appointment at doctor’s/maternity clinic during thepregnancy (yes/no)13. Pregnancy registered as a high-risk pregnancy in the maternity
log14.1 Pregnancy risks (yes/no)14.2 Pregnancy risk
1. Psycho-social stress2. Familiar stress3. Diabetes mellitus
4. Obesity5. Long-term medication6. Substance abuse7. Placenta praevia8. Placental insufficiency9. Anemia10. Hypertension (blood pressure 140/90)11. Proteinuria12. Edema13. Gestational diabetes14. HELLP syndrome15. Eclampsia16. Others
15. Total number of inpatient stays in clinic duringpregnancy (in days)
16.1 Week of pregnancy when the first stay in clinic registered17.1 Week of pregnancy when the first examination
conducted17.2 Total number of prenatal care/prenatal examinations18.1 Week of pregnancy when the first ultrasound
examination was conducted18.2 Total number of ultrasound examinations19. Body weight at the first examination20. Last body weight before delivery21. Body height22. Chorionic villus biopsy (yes/no)23. Aminocentesis (until 22 weeks)24. Contraction stress test25. Doppler ultrasonography (yes/no)26. Pessary placed (yes/no)27. Tocolysis28. Expected adjusted date of delivery29. Antenatal diagnosed/suspected malformations
Information about delivery
30. Kind of admittance31. Uterine orifice32. Lung maturity treatment33. Last lung maturity treatment on: (date)34. Admittance CTG35.1 Doppler ultrasonography conducted in obstetric unit36.1 Delivery risks (yes/no)36.2 Delivery risk:
1. Premature rupture of membranes2. Exceeding of delivery date3. Malformation4. Placental insufficiency5. Eclampsia6. Diabetes mellitus7. Uterine bleedings
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8. Diseases of mother9. Complications of umbilical cord10. Abnormal position of fetus11. HELLP syndrome12. Intrauterine death of fetus13. Shoulder dystocia14. Others
37.-41. See below42. Medicamentous cervix maturation (yes/no)43. Induced delivery (yes/no)43.1 Indication for 4344. Oxytocics45. Tocolysis46. Analgetics47. Acupuncture
Complications Mother
48.-73. See below74. Perineal laceration75. Other lacerations76. Bleeding )1000 mL77. Wound healing/need of treatment78. Hysterectomy/Laparotomy79. Eclampsia80. Sepsis81. Fever during puerperal )388C )2 days82. Anemia Hb -10 g/dL (- 6.2 mmol/L)83.1 General complications in need of treatment
1. Pneumonia2. Cardiovascular disease3. Deep vein thrombosis4. Lung embolism5. Infection of the urinary tract6. Others
84.-90. See below91.1 Discharge diagnosis92. Discharge reason mother93. Discharge date mother94. Death of mother (yes/no)
2. Data Set Newborn
1. ID number of newborn33.1 Rupture of membranes before onset of labor37.1 CTG-Control38.1 Blood gas analysis fetal blood39. Position40. Delivery position at the time of birth41.1 Duration of labor45.1 Anesthesia51.1 Indication for operative delivery
1. Premature rupture of membranes2. Exceeding of delivery date3. Malformation4. Placental insufficiency5. Eclampsia6. Diabetes mellitus
7. Pathologic CTG8. Protracted delivery or delivery stagnation9. Absolute or relative disproportion of fetal head and mother’s
pelvis10. Complications of umbilical cord11. Abnormal position of fetus12. HELLP syndrome13. Intrauterine death of fetus14. Shoulder dystocia15. Others
51.2 Duration of intervention during caesarean section53.1 Emergency caesarean section53.2 Indication for 53.1:
1. Premature rupture of membranes2. Exceeding of delivery date3. Malformation4. Placental insufficiency5. Eclampsia6. Diabetes mellitus7. Pathologic CTG or bad fetal heart tones8. Protracted delivery or delivery stagnation9. Absolute or relative disproportion of fetal head and mother’s
pelvis10. Complications of umbilical cord11. Abnormal position of fetus12. HELLP syndrome13. Intrauterine death of fetus14. Shoulder dystocia15. Others
Basic documentation Newborn
60.1 Date of birth60.2 Time of birth61.1 Birth diagnosis62. Sex of the child63. Apgar score (1 min., 5 min., 10 min. after birth)64. Weight65.1 Length65.2 Head circumference66.1 Blood gas analysis67. Pulse oximetry68. Intubation70. Malformation71. Prenatally diagnosed malformation72. Diagnosed morbidity of the newborn73. Stillbirth74.-83. See above84.1 Newborn moved into children’s hospital85.1 Discharge date from the maternity clinic86. Final discharge from/death in (maternity/children’shospital)87. Discharge diagnosis88. Discharge reason89. Death of the born-alive infant within first 7 days90.1 Cause of death – born-alive infant90.2 Date of death – born-alive infant90.3 Time of death – born-alive infant
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