Maternal diabetes has been related to an increased risk of congenital heart
disease (CHD) in offspring. However, inconsistent results were retrieved for
studies evaluating the association between gestational diabetes mellitus (GDM)
and CHD in offspring. We therefore performed a systematic review and
meta-analysis for comprehensive investigation. Observational studies were
identified by searching PubMed, Embase, and Web of Science according to the aim
of the meta-analysis. A randomized-effects model was used to pool the data by
incorporating the influence of potential heterogeneity. Twenty-three
observational studies, involving 46953078 mother-child pairs, were available for
the meta-analysis. Among them, 2131800 mothers were diagnosed as GDM and 214379
newborns had CHD. Overall, maternal GDM was associated with a higher incidence
of CHD in offspring [odds ratio (OR): 1.32, 95% confidence interval
(CI): 1.21 to 1.45, p<0.001; I2=62%]. Sensitivity
analysis limited to studies with adjustment of maternal age and other potential
confounding factors showed similar results (OR: 1.40, 95% CI: 1.30 to
1.51, p<0.001; I2=47%). Subgroup analysis suggested that
the association between maternal GDM and CHD in offspring was not significantly
affected by methods for diagnosis of GDM, methods for confirmation of CHD, or
study quality scores (p for subgroup difference all>0.05). Subsequent
analysis according to types of CHD showed that maternal GDM was associated with
higher risks of atrial septal defect, ventricular septal defect, and Tetralogy
of Fallot. Maternal GDM may be associated with a higher risk of CHD in
offspring.