Nackuppklarning och hjärtmissbildningar. Gudmundur Gunnarsson KK SUS Lund

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2 Nackuppklarning och hjärtmissbildningar Gudmundur Gunnarsson KK SUS Lund

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4 Wright et al Ultrasound Obstet Gynecol 2008;

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7 Conditions associated with increased nuchal translucency 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

8 Ultrasound Obstet Gynecol 1998;11:

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10 Samband mellan ökad nackuppklarning och Hjärtfel Hernia diaphragmatica Exomphalos Body stalk anomaly Fetal akinesia deformation sequence Ökat antal spontanaborter och perinatala dödsfall

11 Sannolikt samband med Stort antal sällsynta skelettdysplasier Stort antal genetiska syndrom Men få fall

12 Förekomst som i populationen av Anencephaly Spina bifida Holoprosencephaly Microcephaly Läpp-gom spalt Gastroschisis Njurmissbildningar Tarmhinder

13 Outcome in 4116 pregnancies with increased fetal nuchal translucency in The Fetal Medicine Foundation Project Ultrasound Obstet Gynecol 1998;11:

14 Prevalence of major defects of heart and great arteries in fetuses that were chromosomally normal Nuchal Translucency (mm) n Major cardiac defects Prevalence (per 1000) < 95th centile ,8 > 95th centile 3, ,3 3,5-4, ,9 4,5-5, ,9 > 5, ,1 Total , singleton pregnancies with chromosomally normal fetuses at weeks of gestation (retrospective study) Br Med J 1999:318:81 5

15 Detection of specific cardiac defects using increased fetal nuchal translucency thickness 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

16 Sensitivity and specificity of screening for major defects of the heart and great arteries using fetal nuchal translucency Using 95th centile Using 99th centile Sensitivity Specificity Positive predictive value Negative predictive value 56,0% (95% CI: 42,0-70,0) 93,8% (95% CI: 93,6-94,1) 1,5% (95% CI: 1,0-2,1) 99,9% (95% CI: 99,8-100,0) 40,0% (95% CI: 26,0-54,0) 99,0% (95% CI: 98,9-99,1) 6,3% (95% CI: 3,7-9,0) 99,9% (95% CI: 99,8-100,0) Br Med J 1999:318:81 5

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22 Contribution of Ductus venosus Doppler in First-Trimester Screening for major Cardiac Defects Prospektiv studie på 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:

23 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:

24 Patofysiologi okänd Ändrad sammansättning av extracellular matrix? Venös stas i huvud och hals? Försenad utveckling av lymfsystemet? Hjärtsvikt? Försämrad lymfdränage? Infektion? Anemi/hypoproteinemi?

25 Djurmodel för trisomi 21; Trisomi 16 mus Patologiska lymfkärl Hjärtmissbildningar Tymus hypoplasi

26 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 Jul;16(1):30-6

27 Abnormal cardiac function in fetuses with increased nuchal translucency. METHODS: Forty-two structurally and chromosomally normal fetuses with increased NT at weeks of gestation underwent fetal echocardiographic examination at weeks CONCLUSION: Structurally and chromosomally normal fetuses with increased NT have low E/A and E/TVI ratios at weeks of gestation. These findings might indicate cardiac diastolic dysfunction Ultrasound Obstet Gynecol Jun;21(6):539-42

28 Screening for fetal aneuploidies and fetal cardiac abnormalities by nuchal translucency thickness measurement at weeks of gestation as part of routine antenatal care in an unselected population DESIGN: A prospective study SAMPLE: 4523 consecutive viable fetuses at 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 Oct;106(10):

29 Screening performance of firsttrimester nuchal translucency for major cardiac defects: A metaanalysis Study design A meta-analysis, 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 Nov;189(5):1330-5

30 Does nuchal translucency have a role in fetal cardiac screening? 8 Studier, graviditeter 2,5 mm cut-off Detection 38% 4,9% falskt positiva Prenat Diagn Dec 30;24(13):

31 Nackuppklarningsstudien M. Westin et al. Ultrasound Obstet Gynecol 2006; 27:

32 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:

33 Prenatal detection of heart defects in a non-selected population of 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:

34 E. Tegnander et al. Ultrasound Obstet Gynecol 2006; 27:

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36 När skall fosterhjärtat granskas?

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38 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