Nackuppklarning och hjärtmissbildningar Gudmundur Gunnarsson KK SUS Lund
Wright et al Ultrasound Obstet Gynecol 2008;31 376-383
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
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
Outcome in 4116 pregnancies with increased fetal nuchal translucency in The Fetal Medicine Foundation Project Ultrasound Obstet Gynecol 1998;11:391 400
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 27.332 22 0,8 > 95th centile 3,4 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 29 154 singleton pregnancies with chromosomally normal fetuses at 10-14 weeks of gestation (retrospective study) Br Med J 1999:318:81 5
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
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
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 firsttrimester nuchal translucency for major cardiac defects: A metaanalysis 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