The Influence of Gestational Diabetes on Neurodevelopment of Children in the First Two Years of Life: A Prospective Study

Abstract

Objective: Analyze the relation of gestational diabetes and maternal blood glucose levels to early cognitive functions in the first two years of life.

Methods: In a prospective Singaporean birth cohort study, pregnant women were screened for gestational diabetes at 26-28 weeks gestation using a 75-g oral glucose tolerance test. Four hundred and seventy three children (n = 74 and n = 399 born to mothers with and without gestational diabetes respectively) underwent neurocognitive assessments at 6, 18, and/or 24 month, including electrophysiology during an attentional task and behavioral measures of attention, memory and cognition.

Results: Gestational diabetes is related to left hemisphere EPmax amplitude differences (oddball versus standard) at both six (P = 0.039) and eighteen months (P = 0.039), with mean amplitudes suggesting offspring of mothers with gestational diabetes exhibit greater neuronal activity to standard stimuli and less to oddball stimuli. Associations between 2-hour maternal glucose levels and the difference in EPmax amplitude were marginal at 6 months [adjusted β = -0.19 (95% CI: -0.42 to +0.04) μV, P = 0.100] and significant at 18 months [adjusted β = -0.27 (95% CI: -0.49 to -0.06) μV, P = 0.014], and the EPmax amplitude difference (oddball-standard) associated with the Bayley Scales of Infant and toddler Development-III cognitive score at 24 months [β = 0.598 (95% CI: 0.158 to 1.038), P = 0.008].

Conclusion: Gestational diabetes and maternal blood glucose levels are associated with offspring neuronal activity during an attentional task at both six and eighteen months. Such electrophysiological differences are likely functionally important, having been previously linked to attention problems later in life.

Fig 1

Composite (grand average) ERP recording of electrodes in the left hemisphere of 6-month-old controls (A) and offspring of mothers with GDM (oGDMs) (B), as well as 18-month-old controls (C) and oGDMs (D). The solid line represents the standard stimulus and the dotted line represents the oddball stimulus. The boxed region of the graph corresponds to the EPmax, where the degree of differential neuronal activity (oddball-standard) significantly varied according to GDM status.

Fig 2. Scatterplots of stimuli difference (oddball-standard) in EPmax amplitudes, over the left hemisphere.

Stimuli difference in EPmax amplitudes over the left hemisphere in A) 6 months and B) 18 months old infants against maternal 2-hour plasma glucose at 26–28 weeks gestation. Curves lines correspond to 95% confidence interval of the mean.