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)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(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. Key points What is already known about this topic?� Congenital heart disease (CHD) is associated with decreased birthweight (BW) compared to population-based reference charts.� As both CHD and fetal growth have a multifactorial etiology, the contribution of environmental and maternal factors on impaired BW in CHD is not elucidated. What does this review add?� Neonates with CHD have a lower BW z score compared to their siblings, while the siblings display a BW distribution similar to the general population.

Conclusions: A structured intervention during pregnancy based on MBSR seem to reduce the prevalence of preterm birth below 32 weeks; however, these results should be considered with caution since the trial was not designed for this specific outcome.