Neurodevelopment of children with congenital heart defect born preterm or growth restricted at birth: A systematic review and meta-analysis

Children born with either congenital heart defect (CHD), preterm (PT) or small for gestational age (SGA) are independently at higher risk to develop neurodevelopmental disorders (ND). The interaction effect between CHD and one of these neonatal vulnerability factors (PT and/or SGA) is suggested but not clearly established. To assess the prevalence of ND in children with CHD and at least one of the neonatal vulnerability factors. Then to assess whether children born with CHD and at least one neonatal vulnerability factor are at higher risk of ND than children born with CHD but without any neonatal vulnerability factors. We searched Medline and Embase (from inception until March 2022) and included studies that reported neurodevelopmental outcomes in children born with CHD and neonatal vulnerability factors at any age. Data extraction was independently performed by two blinded reviewers with outcomes agreed upon a priori. The quality of selected reports was critically examined with the critical appraisal skills programme (CASP) cohort study checklist. We performed a meta-analysis of pooled proportions of global cognitive impairment using a random effects model with inverse variance weighting. We included 12 studies for qualitative synthesis and 6 studies for meta-analysis. Risk of bias was deemed low in 4/12 studies. Regarding children born PT with CHD 26% (95%CI: 20–32%) of them had cognitive impairment and 19% (95%CI: 7–35%) had cognitive disability. Lower scores have been reported for some specific domains (working memory and visual-motor integration) especially for studies with children born with complex CHD. Other domain-specific cognitive functions assessed in these studies (language, social skills, life skills, communication, motor skills, executive functions, academic skills, attention and impulsivity…) were not associated with lower scores for children born PT with CHD. Regarding children born SGA with CHD requiring surgery, a single study reported lower IQ score compared to non-SGA CHD children. There is a lack of robust evidence that prematurity or SGA significantly increases the risk of ND in children with CHD. However, these groups of children remain independently at high risk for developing ND and need to be closely monitored.