• prenatal screening;
  • congenital heart defects;
  • alpha-fetoprotein (AFP);
  • human-chorionic-gonadotropin (hCG);
  • unconjugated estriol (uE3);
  • nuchal fold;
  • nuchal translucency (NT);
  • Down syndrome;
  • trisomy 18;
  • second trimester


Congenital heart defects (CHDs) are the most common of all birth defects. For many newborns with a CHD, prenatal versus postnatal detection is associated with substantially decreased morbidity and mortality risks. Although technological advances in fetal echocardiography have led to an increased capacity to detect CHDs prenatally, pregnancies without an identified risk factor are not routinely screened. With the aim of identifying pregnancies at increased risk for CHDs, this study examined the relationship between CHDs and typically collected second trimester biomarker data collected on a large population-based sample of singleton pregnancies with one or more second trimester screen positive result for Down syndrome, trisomy 18 (T-18), Smith–Lemli–Opitz syndrome (SLOS), or a neural tube defect (NTD). Where possible, logistic models for cases and controls were built and potential referral models were tested among study subsamples with information on the presence or absence of CHDs reported pre- and perinatally. When considered in combination, screen positive for T-18, screen positive for SLOS, nuchal fold measurement ≥ 5 mm, and/or having an adjusted hCG multiple of the median ≥ the 95th centile detected 42.7% of all pregnancies with a CHD in the combined subsample (where co-occurrence with chromosomal defects was not considered) and detected 29.7% of all pregnancies with a CHD in the no-chromosomal defect subsample. A nuchal fold measurement ≥ 5 mm detected 18.2% of those with a CHD in the Down syndrome subsample and an adjusted hCG multiple of the median (MoM) ≤ 5th centile detected 92.9% of those with a CHD in the T-18 subsample. © 2008 Wiley-Liss, Inc.