Association between maternal diabetes and neurodevelopmental outcomes in children: a systematic review and meta-analysis of 202 observational studies comprising 56·1 million pregnancies

Abstract

Background

Maternal diabetes might alter fetal brain development. However, well-designed systematic analyses are needed to comprehensively assess and quantify the association between maternal diabetes and neurodevelopmental outcomes in children. We aimed to synthesise and evaluate the available evidence on the effects of maternal diabetes on neurodevelopmental outcomes in children.

Methods

For this systematic review and meta-analysis we searched PubMed, Web of Science, Embase, and EBSCO databases from inception to Dec 1, 2024, for studies exploring neurodevelopmental outcomes of children born to mothers with diabetes. The primary outcome was neurodevelopmental disorders, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and International Classification of Diseases 11th Revision. Data were extracted from published reports. Data were pooled with random-effects models and presented as risk ratios or standard mean differences with 95% CIs. This study was prospectively registered on PROSPERO (CRD42023395464).

Findings

202 studies, involving 56 082 462 mother–child pairs, were included in the meta-analysis. Of these, 110 (54%) examined gestational diabetes, while 80 (40%) investigated pre-gestational diabetes. Among the total studies reviewed, 169 (84%) exclusively focused on children and adolescents aged up to 18 years. In studies adjusting for at least one key confounder, maternal diabetes was associated with increased risks of all types of neurodevelopmental disorders as well as lower intelligence and psychomotor scores. In studies adjusting for multiple confounders (n=98, 49%), children exposed to maternal diabetes had an increased risk of any neurodevelopmental disorder (risk ratio 1·28; 95% CI 1·24–1·31), autism spectrum disorder (1·25; 1·20–1·31), attention-deficit hyperactivity disorder (1·30; 1·24–1·37), intellectual disability (1·32; 1·18–1·47), specific developmental disorders (1·27; 1·17–1·37), communication disorder (1·20; 1·11–1·28), motor disorder (1·17; 1·10–1·26), and learning disorder (1·16; 1·06–1·26), compared with unexposed children. Maternal pre-gestational diabetes was more strongly associated with the risk of most neurodevelopmental disorders in children than gestational diabetes (risk ratio 1·39; [95% CI 1·34–1·44] vs 1·18 [1·14–1·23]; subgroup difference p<0·0001).

Interpretation

Maternal diabetes is associated with an increased risk of neurodevelopmental disorders and impaired neurodevelopmental performance in children. Further high-quality research is needed to establish causality and clarify the associations between specific types of diabetes and the full spectrum of neurodevelopmental disorders.

Funding

The National Natural Science Foundation of China, and the Science and Technology Innovation Program of Hunan Province.

Translation

For the Mandarin translation of the abstract see Supplementary Materials section.