Maternal Glycemia During Pregnancy and Early Offspring Development: A Prospective Birth Cohort Study

Context The association of maternal gestational diabetes mellitus (GDM) with neurodevelopmental outcomes remains controversial and evidence that maternal increasing levels of glucose during pregnancy associated with the risk for impaired neurodevelopment were limited. Objective To identify the continuous association of increasing maternal glucose levels with neurodevelopmental disorders in offspring and explore the potential contribution of cord metabolites to this association. Methods The prospective birth cohort study included 1036 mother-child pairs. Primary predictors were maternal exposure GDM and maternal glucose values at a 75-g oral-glucose-tolerance test at 24 to 28 weeks during pregnancy. Primary neurodevelopmental outcomes at 12 months in offspring were assessed by the Ages and Stages Questionnaires, Third Edition (ASQ-3). Results Maternal GDM was associated with failing the communication domain in offspring in the adjusted models [relative risk (RR) with 95% CI: 1.97 (1.11, 3.52)]. Increasing levels of fasting plasma glucose (FPG), 1-h plasma glucose (1-h PG) and 2-h plasma glucose (2-h PG) with 1 SD change were at higher risks in failing the personal social domain of ASQ-3 [RRs with 95% CI for FPG: 1.49 (1.09, 2.04); for 1-h PG: 1.70 (1.27, 2.29); for 2-h PG: 1.36 (1.01, 1.84)]. The linear association was also demonstrated. Compared with girls, boys exposed to higher maternal glucose levels were inclined to the failure of the personal social domain. Mediation analysis showed the contribution of maternal GDM to failure of communication domain mediated by C-peptide. Conclusions Maternal glucose levels below those diagnostic of diabetes are continuously associated with impaired neurodevelopment in offspring at 12 months.