Maternal vitamin D concentrations during the second trimester and neurodevelopmental outcomes in preschool-aged children in the APrON cohort

Introduction Pregnancy is a critical period for fetal brain development and is sensitive to maternal micronutrient status. Maternal vitamin D [25(OH)D] concentrations have been associated with child neurodevelopmental outcomes, while biological aging processes reflected by epigenetic age acceleration (EAA) may contribute to these associations. This study examined associations between maternal vitamin D concentrations and neurodevelopmental outcomes in preschool-aged children and explored whether infant EAA mediated these associations. Methods We included 252 mother-child pairs from the APrON cohort. Maternal second trimester plasma 25(OH)D 3 concentrations were quantified, and children's cognitive, language, motor, and behavioural outcomes were assessed at 3–5-years. In a subsample of 130 children, buccal epithelial cells collected at 3 months were profiled using the Infinium HumanMethylation EPIC v1.0 BeadChip. EAA was estimated using the Pediatric-Buccal-Epigenetic clock. Adjusted linear regressions examined associations between maternal 25(OH)D 3 and children's outcomes, including models using quartiles and a 30 ng/mL threshold. Mann–Whitney U -tests compared outcomes according to a 20 ng/mL sufficiency threshold. In the subsample, exploratory mediation analyses examined the potential mediating role of infant EAA. Results No associations were found between maternal vitamin D and children's cognitive, language, or behavioural outcomes. Maternal vitamin D concentrations were positively associated with children's motor outcomes ( B = 0.04; 95% CI = 0.004, 0.076, p = 0.03), although this small, nominal association did not survive correction for multiple comparisons ( q = 0.18). This positive association was attenuated when vitamin D was modeled using quartiles or when “sufficiency” was defined as 30 ng/mL. No differences were found in neurodevelopmental outcomes based on vitamin D sufficiency defined as 20 ng/mL. No evidence of mediation via EAA was detected, although small indirect effects could have gone undetected due to the small sample size for this sub-analysis. Conclusions This study provides preliminary evidence that maternal vitamin D concentrations during pregnancy are associated with improved motor performance in children. A biomarker of biological aging, EAA, did not appear to play a role in this association. Examination of different forms of maternal vitamin D and statistical models that consider continuous measures and thresholds of “sufficiency” are needed to clarify associations between maternal vitamin D concentrations and children's neurodevelopment.