Birthweight of children with isolated congenital heart disease—A sibling analysis study

OBJECTIVE: Congenital heart disease (CHD) is associated with decreased birthweight (BW) compared to population-based references. The aim of this study was to compare the BW of isolated CHD cases to their siblings, thus controlling for unknown and unmeasured confounders within the family. METHODS: All isolated CHD cases in the Leiden University Medical Center were included (2002-2019). Generalized estimated equation models were constructed to compare BW z scores of CHD neonates with their siblings. Cases were clustered to minor or severe CHD and stratified according to the aortic flow and oxygenation to the brain. RESULTS: The overall BW z score of siblings was 0.032 (n = 471). The BW z score was significantly lower in CHD cases (n = 291) compared to their siblings (-0.20, p = 0.005). The results were consistent in the subgroup analysis of severe and minor CHD (BW z score difference -0.20 and -0.10), but did not differ significantly (p = 0.63). Stratified analysis regarding flow and oxygenation showed no BW difference between the groups (p = 0.1). CONCLUSION: Isolated CHD cases display a significantly lower BW z score compared to their siblings. As the siblings of these CHD cases show a BW distribution similar to the general population, this suggests that shared environmental and maternal influences between siblings do not explain the difference in BW.