Maternal diabetes during pregnancy and offspring's risk of autism spectrum disorder: A systematic review and meta-analysis

Abstract

Introduction

Whether in utero exposure to pregestational (type 2 [T2D] and type 1 diabetes [T1D]) and gestational diabetes (GDM) are contributing factors in the rise of neurodevelopmental alterations such as autism is yet unclear. Therefore, we summarized the evidence from studies that assessed such association.

Methods

A systematic review with meta-analyses was performed following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines; eligible studies were identified in PubMed, Web of Science, and EBSCO up to April 3rd, 2023. We estimated pooled OR of autism from random effects meta-analyses for each type of maternal diabetes.

Results

26 publications were selected (18 cohorts and 8 case-controls); 17 had data for the meta-analysis. We observed an increased risk of autism in the offspring exposed in utero to T2D (pooled OR = 1.48; 95%CI: 1.31, 1.68; n = 3,141,255), T1D (pooled OR = 1.73; 95%CI: 1.05, 2.87; n = 2,791,607), and GDM (pooled OR = 1.31; 95% CI: 1.16, 1.47; n = 3,259,557) compared to those unexposed. No evidence of heterogeneity (I² = 0.0%) was observed for T2D, whereas for T1D the heterogeneity was substantial (I² = 64.7%) and for GDM was moderate (I² = 53.1%). The evidence was stronger for in utero exposure to GDM, followed by T2D and T1D.

Conclusions

Our results support the hypothesis that in utero exposure to maternal T2D or GDM moderately increased the offspring's risk of developing autism later in life. Prospectively conducted studies are still warranted to better estimate the size of the effect of maternal diabetes on autism risk.