Maternal vitamin D status modifies the association between GDM and offspring neurodevelopment: a prospective birth...

Intrauterine hyperglycemia is a risk factor for offspring neurodevelopmental delay. While vitamin D is neuroprotective, its role in improving outcomes for the offspring of women with gestational diabetes mellitus (GDM) is unclear.

In a prospective cohort of 7438 pregnant women, serum 25-hydroxyvitamin D [25(OH)D] was measured at 16-23 weeks. GDM was diagnosed at 24-28 weeks, with simultaneous assessment of insulin resistance (HOMA-IR). Umbilical cord blood C-peptide concentrations were measured at delivery. Offspring neurodevelopment was screened at 5-7, 11-13, and 24-36 months.

GDM was associated with a 26% higher risk of neurodevelopmental delay (HR = 1.26, 95% CI: 1.02, 1.56), along with higher HOMA-IR and cord blood C-peptide. Serum 25(OH)D was negatively associated with HOMA-IR and cord blood C-peptide (P for trend < 0.05). In vitamin D-deficient women (25(OH)D < 50 nmol/L), HOMA-IR correlated with cord C-peptide (r = 0.48, P < 0.001), and GDM increased risks of neurodevelopmental delay (HR = 1.34, 95%CI: 1.05, 1.70) and hyperinsulinemia (HR = 1.39, 95%CI: 1.13, 1.72). These associations were absent in vitamin D-sufficient women.

Adequate gestational vitamin D may attenuate the intergenerational transmission of glucose metabolism disorders, thereby reducing neurodevelopmental delay risk in GDM offspring. This protective effect requires validation in randomized trials.

This study demonstrates that adequate maternal vitamin D status may protect against gestational diabetes mellitus (GDM)-associated neurodevelopmental delays in offspring, identifying a potentially modifiable prenatal factor. It proposes a novel mechanistic pathway, suggesting vitamin D may attenuate the intergenerational transmission of maternal glucose dysregulation, thereby mitigating fetal hyperinsulinemia and subsequent neurodevelopmental risk. The findings support integrating vitamin D assessment and optimization into prenatal care for women with GDM, offering a nutritional strategy for promoting offspring neurodevelopment.