Nackuppklarning och

hjärtmissbildningar

Gudmundur Gunnarsson

KK SUS Lund

Wright et al Ultrasound Obstet Gynecol

2008;31 376-383

Cardiac defects

Diaphragmatic hernia

Exomphalos

Achondrogenesis type II

Achondroplasia

Asphyxiating thoracic

dystrophy

Beckwith-Wiedemann

syndrome

Blomstrand

Osteochondrodysplasia

Body Stalk anomaly

Campomelic dysplasia

EEC syndrome

Fetal akinesia deformation

sequence

Fryn syndrome

GM1-gangliosidosis

Hydrolethalus syndrome

Jarcho-Levin syndrome

Joubert syndrome

Meckel-Gruber syndrome

Nance-Sweeney

syndrome

Noonan syndrome

Osteogenesis imperfecta

type II

Perlman syndrome

Roberts syndrome

Short-rib polydactily

syndrome

Smith-Lemli-Optiz

syndrome

Spinal muscular atrophy

type 1

Thanatophoric dysplasia

Trigonocephaly 'C'

syndrome

VACTEREL association

Zellweger syndrome

Conditions associated with increased nuchal translucency

Ultrasound Obstet Gynecol 1998;11:391–400

Samband mellan ökad

nackuppklarning och

• Hjärtfel

• Hernia diaphragmatica

• Exomphalos

• Body stalk anomaly

• Fetal akinesia deformation sequence

• Ökat antal spontanaborter och

perinatala dödsfall

Sannolikt samband med

• Stort antal sällsynta

skelettdysplasier

• Stort antal genetiska syndrom

• Men få fall

Förekomst som i

populationen av • Anencephaly

• Spina bifida

• Holoprosencephaly

• Microcephaly

• Läpp-gom spalt

• Gastroschisis

• Njurmissbildningar

• Tarmhinder

Ultrasound Obstet Gynecol 1998;11:391–400

Outcome in 4116 pregnancies with increased fetal nuchal translucency in The Fetal Medicine Foundation Project

Nuchal Translucency (mm)

n Major cardiac

defects Prevalence (per 1000)

< 95th centile 27.332 22 0,8

> 95th centile3,4 1.507 8 5,3

3,5 - 4,4 208 6 28,9

4,5 - 5,4 66 6 90,9

> 5,5 41 8 195,1

Total 29.154 50 1,7

Br Med J 1999:318:81–5

Prevalence of major defects of heart and great arteries in

fetuses that were chromosomally normal

29 154 singleton pregnancies with chromosomally normal fetuses

at 10-14 weeks of gestation (retrospective study)

Nucal Translucency

Cardiac defect Total > 95th centile > 99 centile

Tetralogy of Fallot 9 (18%) 2 (22%) 2 (22%)

Hypoplastic Left Heart 3 (6%) 2 (67%) 1 (33%)

Transposition of the great arteries 8 (16%) 4 (50%) 3 (38%)

Coarctation of the aorta or aortic stenosis/atresia 10 (20%) 10 (100%) 8 (80%)

Ventricular and atrioventricular septal defects 8 (16%) 4 (50%) 1 (42%)

Other defects 12 (24%) 6 (50%) 5 (42%)

Total 50 (100%) 28 (56%) 20 (40%)

Br Med J 1999:318:81–5

Detection of specific cardiac defects using increased fetal

nuchal translucency thickness

Using 95th centile

Using 99th centile

Sensitivity

56,0% (95% CI: 42,0-70,0)

40,0% (95% CI: 26,0-54,0)

Specificity

93,8% (95% CI: 93,6-94,1)

99,0% (95% CI: 98,9-99,1)

Positive predictive value

1,5% (95% CI: 1,0-2,1)

6,3% (95% CI: 3,7-9,0)

Negative predictive value

99,9% (95% CI: 99,8-100,0)

99,9% (95% CI: 99,8-100,0)

Br Med J 1999:318:81–5

Sensitivity and specificity of screening for major defects of

the heart and great arteries using fetal nuchal translucency

Contribution of Ductus venosus Doppler in

First-Trimester Screening for major Cardiac

Defects

• Prospektiv studie på 45191 foster, kromosomfel (332) och

andra missbildngar (403) exkluderade

• 85 fall med större hjärtfel

• NT över 95:e percentilen hos 35% av foster med större

hjärtfel, över 99:e hos 21%

• Reverserad a-våg i ductus venosus hos 28% av foster med

större hjärtfel, 2,1% utan hjärtfel

• Results: Specialist fetal echocardiography for cases with

NT above the 99th centile and those with reversed a-wave,

irrespektive of NT, would detect 39% of major cardiac

defects at an overall false-positive rate of 2.7%

Fetal Diagn Ther 2011; 29:127-134

Abnormal first trimester ductus venosus

blood flow: a marker of cardiac defects in

fetuses with normal karyotype and nuchal

translucency

• Prospektive studie 6120 graviditeter

• Ductus venosus studerad hos alla

• AR-DV hos 206 (3,3%) varav 70% hade normal karyotyp

• Av 90 foster med AR-DV och normal NT hade 5

hjärtmissbildning

• Konklusion 1: AR-DV oberoende prediktor av

hjärtmissbildningar

• Konklusion 2: AR-DV ökade detektion av

hjärtmissbildningar med 11%

Ultrasound Obstet Gynecol 2010; 35: 267-272

Patofysiologi okänd

• Ändrad sammansättning av extracellular

matrix?

• Venös stas i huvud och hals?

• Försenad utveckling av lymfsystemet?

• ”Hjärtsvikt”?

• Försämrad lymfdränage?

• Infektion?

• Anemi/hypoproteinemi?

Djurmodel för trisomi 21;

Trisomi 16 mus

• Patologiska lymfkärl

• Hjärtmissbildningar

• Tymus hypoplasi

Nuchal translucency and

congenital heart defects: heart

failure or not?

• METHODS: Retrospective analysis of the types

of congenital heart defect observed in fetuses

with increased nuchal translucency and those

with normal nuchal scans

– CONCLUSIONS: No specific type of congenital

heart lesion is associated with increased

nuchal translucency. The contention that heart

failure explains the association between

congenital heart defects and increased nuchal

translucency is not supported by this study Ultrasound Obstet Gynecol. 2000 Jul;16(1):30-6

Abnormal cardiac function in

fetuses with increased nuchal

translucency.

• METHODS: Forty-two structurally and

chromosomally normal fetuses with increased

NT at 11-14 weeks of gestation underwent fetal

echocardiographic examination at 20-23 weeks

– CONCLUSION: Structurally and

chromosomally normal fetuses with increased

NT have low E/A and E/TVI ratios at 20-23

weeks of gestation. These findings might

indicate cardiac diastolic dysfunction

Ultrasound Obstet Gynecol. 2003 Jun;21(6):539-42

Screening for fetal aneuploidies and fetal

cardiac abnormalities by nuchal

translucency thickness measurement at 10-

14 weeks of gestation as part of routine

antenatal care in an unselected population

• DESIGN: A prospective study

– SAMPLE: 4523 consecutive viable fetuses at 10-14 weeks

• RESULTS: Only one out of nine major congenital heart defects in this population was found within the 110 euploid fetuses with increased nuchal translucency thickness (> 2.5 mm)

• CONCLUSION: Our results do not support [screening] effectiveness in the detection of cardiac abnormalities

Br J Obstet Gynaecol. 1999 Oct;106(10):1029-34

Screening performance of first-

trimester nuchal translucency for

major cardiac defects: A meta-

analysis

• Study design A meta-analysis, 58.492 cases

– CONCLUSION: Nuchal translucency screening

is a modestly efficient strategy for congenital

heart defect detection; the use of the 99th

percentile threshold may capture

approximately 30% of congenital heart defects

Am J Obstet Gynecol. 2003 Nov;189(5):1330-5

Does nuchal translucency have a

role in fetal cardiac screening?

• 8 Studier, 67000 graviditeter

• 2,5 mm cut-off

• Detection 38%

• 4,9% falskt positiva

Prenat Diagn. 2004 Dec 30;24(13):1130-5.

Nackuppklarningsstudien

M. Westin et al. Ultrasound Obstet Gynecol 2006; 27: 632-639

Conclusions

” …because only a small proportion of fetuses

with a cardiac defect manifest increased NT,

its measurement is not a suitable screening

test for CHD. A method with a much higher

detection rate and with a reasonably low false

FPR is needed”

M. Westin et al. Ultrasound Obstet Gynecol 2006; 27: 632-639

Prenatal detection of heart defects in a

non-selected population of 30 149

fetuses - detection rates and outcome

• 57% upptäckta (97större avvikelser)

• 38% avvikande kromosomer

• 27% levande vid 2 år

E. Tegnander et al. Ultrasound Obstet Gynecol 2006; 27: 252-265

E. Tegnander et al. Ultrasound Obstet Gynecol 2006; 27: 252-265

När skall fosterhjärtat

granskas?

”Take home message”

• Ökad nackuppklarning är inte

sjukdom

• 90% av foster med ökad

nackuppklarning men NT <4,5 är

friska (4,5-6,4; 80%, >6,4; 45%)

• Indikation för riktad

fosterhjärtundersökning