Maternal diabetes mellitus and its impact on the risk of delivering a child with congenital heart disease: a systematic review and meta-analysis

Aim Maternal pregestational diabetes mellitus (PGDM), type 1 or type 2, has been established as a potential risk factor for congenital heart disease (CHD). At the same time, the correlation between gestational diabetes mellitus (GDM) and increased risk of CHD has not been yet fully elucidated. The objective of this systematic review and meta-analysis (PROSPERO number: CRD42020182390) was to analyze the existing evidence on PGDM and to attempt to fill, to the best of our ability, the remaining knowledge gap in the association of GDM with CHD. Materials and methods Two authors have independently searched the Pubmed/Medline, Scopus, Cochrane, Web of Science, and Theses Global databases with keywords and Boolean operators. The search yielded 9333 relevant articles, which were later screened for eligibility. Original peer-reviewed (case-control or cohort) studies were included if they were published in English between 1997 and 2020. Thirteen studies on mothers with PGDM and seven studies on mothers with GDM were finally included in our meta-analysis to investigate the association of maternal diabetes with the risk of delivering a child with CHD. The selected studies were all assessed for their methodological quality using the Newcastle-Ottawa scale. Associations with p < .05 were considered statistically significant. Results Our meta-analysis (I-2 > 75%, total population: n = 12,461,586) of 79,476 women with PGDM and 160,893 with GDM produced an odds ratio of 3.48 (2.36-4.61) and 1.55 (1.48-1.61), respectively. Additionally, we did not find any noticeable difference in the risk for CHD among diabetic women living in the USA and Europe. Nevertheless, it still needs to be clarified, whether or not the gestational diabetic population includes undiagnosed women with preexisting diabetes, which might account for the increased risk of delivering a child with CHD in women classified as suffering from GDM. Conclusion While both GDM and PGDM seem to significantly increase the risk of CHD in comparison with the general population, PDGM appears to have a greater association with CHD, being correlated with a 3.5-fold increase in the risk of malformation. Preconceptional and gestational diabetes care are, therefore, essential to mitigate the adverse effect of hyperglycemia on fetal heart formation during pregnancy.