ESPE Yearbook of Paediatric Endocrinology

J Clin Endocrinol Metab. 2021 Jul 13;106(8):2279-2290. doi: 10.1210/clinem/dgab331. PMID: 33982055.

Brief Summary: This prospective birth cohort study assessed the impact of maternal glycaemia on infant neurodevelopment at 12 months of age. Maternal glucose levels during pregnancy were associated with infant neurodevelopmental outcomes.

High maternal blood glucose levels may have a negative effect on fetal neurodevelopment outcome, although the evidence is unclear. To study this in more detail, the authors undertook a prospective birth cohort study of women with GDM (mother child-pairs) and assessed neurodevelopment outcome of the infants at 12 months of age using a questionnaire.

The study showed that maternal GDM was associated with developmental delay in the offspring. Infants born to mothers with GDM were more likely to fail the communication domain than those of mothers without GDM. After adjusting for confounders (such as maternal age, maternal education, maternal life-style and husbands’ education) there remained a positive association of maternal GDM and problems in the communication domain. The higher the maternal blood glucose levels, the greater was the difference in the communication domain and personal social domain. For each standard deviation higher maternal glucose the risk of failing the communication domain increased from 32% to 70%.

The relationships between maternal glucose and risks of poorer neurodevelopment were continuous without evidence of any threshold effect. Cord blood C-peptide levels > 90^th centile were associated with higher risk of failing the communication domain. Potential mechanisms include an adverse effect of fetal C-peptide on neurodevelopment through the nitric oxide signaling pathway, hypoxia, oxidative stress, or differences in gut microbiota between GDM and non-GDM mothers (1, 2).

This is the first prospective birth cohort study to show a positive linear association of maternal glucose levels with poor developmental outcomes. These findings are important and suggest that earlier screening and management of the maternal glycaemia might prevent or delay developmental changes in infants.

References: 1. Cotter MA, Ekberg K, Wahren J, Cameron NE. Effects of proinsulin C-peptide in experimental diabetic neuropathy: vascular actions and modulation by nitric oxide synthase inhibition. Diabetes. 2003;52(7):1812–1817. 2. Crusell MKW, Hansen TH, Nielsen T, Allin KH, Rühlemann MC, Damm P, Vestergaard H, Rørbye C, Jørgensen NR, Christiansen OB, Heinsen FA, Franke A, Hansen T, Lauenborg J, Pedersen O. Gestational diabetes is associated with change in the gut microbiota composition in third trimester of pregnancy and postpartum. Microbiome. 2018 May 15;6(1):89. doi: 10.1186/s40168-018-0472-x. PMID: 29764499; PMCID: PMC5952429.