Relationship between Gestational 25-hydroxyvitamin D Status and Neurocognitive Development at Age 4

Abstract

Background: The gestational environment can influence brain development and have lasting impacts on future neurocognitive function. Vitamin D is critical to embryonic neuronal differentiation, and animal studies show that vitamin D deficiency can impair brain development. However, observational human studies have found inconsistent associations between gestational vitamin D and children’s neurocognitive outcomes. We assessed whether gestational 25-hydroxyvitamin D [25(OH)D] status was associated with children’s cognitive development at 4 years of age.Methods: This study used prospective data from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study, a large pregnancy cohort in Memphis, Tennessee (65% black, 32% white). We examined the relationship between second trimester maternal 25(OH)D plasma concentrations and age 4 child IQ through linear regression in 965 dyads. The primary outcome was Stanford-Binet full-scale IQ; additional modeling examined verbal and non-verbal IQ. Models were adjusted for children’s sex and age, as well as mothers’ age, race, parity, marital status, health insurance, pre-pregnancy BMI, IQ, education, diet quality, and alcohol and tobacco use. Interaction models explored effect modification by maternal race.Results: The mean gestational 25(OH)D was 21.8 ng/mL (SD: 8.4). In 44.7% of mothers, 25(OH)D was below 20 ng/mL. Gestational 25(OH)D differed by race with a mean of 19.8 ng/mL (SD: 7.2) in blacks compared to 25.9 ng/mL (SD: 9.3) in whites (p < 0.0001). In adjusted models full-scale IQ averaged 1.7 points (95% CI: 0.3, 3.1) higher per 10 ng/mL increase in 25(OH)D. Verbal and non-verbal IQ were also positively associated with 25(OH)D [0.9 (95% CI: 0.1, 1.7) and 0.7 (95% CI: 0, 1.5) points per 10 ng/mL 25(OH)D, respectively]. There was little evidence that associations varied by race.Conclusions: Gestational 25(OH)D was positively associated with age 4 IQ, suggesting that vitamin D status in pregnancy is an important determinant of children’s neurocognitive development.