Objectives: Our objective was to investigate if increased nuchal translucency (NT) was associated with excess mortality in chromosomally normal children with congenital heart defects (CHD)

Methods: In a nationwide cohort using population-based registers, we identified 5,633 liveborn children in Denmark with a pre- or postnatal diagnosis of CHD from 2008-2018 (incidence of CHD, 0.7%).  Children with chromosomal abnormalities and non-singletons were excluded. The final cohort compromised 4,469 children.
Increased NT was defined as NT >95th centile. Children with NT >95th centile vs. NT <95th centile including subgroups of simple- and complex CHD were compared. Survival analysis with Cox-regression was used to compare mortality rates. Analyses were adjusted for mediation by extracardiac anomalies, preeclampsia, preterm birth and small for gestational age, and for confounding effects of cardiac intervention.

Results: Of the 4,469 children with CHD, 754 (17%) had complex CHD and 3,715 (83%) simple CHD. 
In the combined group of CHDs, NT>95th centile compromised a larger proportion of mortalities (3.7 vs. 1.5 %, p = 0.01), but was not associated with higher mortality rate (HR 1.8, 95%CI 0.9;3.8, p=0.1).
In simple CHD there was a significantly higher mortality rate with a HR of 3.9 (95%CI: 1.3;11.4, p=0.01) when having NT >95th centile, adjusted for extracardiac anomalies.
Complex CHD had no differences in mortality rate between NT >95th centile and NT <95th centile (HR 1.1, 95%CI: 0.4;3.1, p=0.84). 
Due to limited numbers the association to mortality for NT >99th centile (>3.5 mm) could not be assessed.
Adjustment for confounding variables (preterm birth, small for gestational age, preeclampsia and extracardiac anomalies) did not alter the associations, except for extracardiac anomalies in simple CHD.

Conclusion: Children with a simple CHD have a higher risk of mortality with a HR of 3.9 if having a NT >95th centile compared to NT <95th centile.