Abstract
BACKGROUND: Maternal vitamin D deficiency has been linked to fetal growth restriction, but the underlying mechanisms are unclear. OBJECTIVE: We tested the hypothesis that poor maternal 25-hydroxyvitamin D [25(OH)D] is associated with increased risk of placental vascular pathology. DESIGN: Maternal serum 25(OH)D was measured at ≤26 wk of gestation in a random subcohort of term, singleton infants in the Collaborative Perinatal Project (1959-1966; n = 2048). A dichotomous vascular construct was created from the presence of any of 12 pathologies identified on placental examinations, including evidence of placental abruption, infarction, hypoxia, decidual vasculopathy, or thrombosis of fetal vessels (n = 240 cases). RESULTS: The relation between 25(OH)D and vascular pathology was modified by infant sex (P = 0.003). A maternal 25(OH)D concentration ≥80 compared with <50 nmol/L was associated with 49% lower risk of pathology in boys [adjusted OR (95% CI): 0.27, 0.95] after conditioning on study site. No associations were observed between maternal 25(OH)D and pathology in mothers with female offspring. Subsequent analyses showed that, in pregnancies with a female fetus, vascular pathology was associated with a reduced birth-weight z score when the mother's 25(OH)D concentration was <30 nmol/L (β: -0.73; 95% CI: -1.17, -0.30). No association was observed between pathology and birth weight in mothers of female offspring with 25(OH)D concentrations ≥30 nmol/L or in boys, regardless of maternal 25(OH)D status. CONCLUSIONS: Our findings suggest complex relations between vitamin D, placental vascular pathology, and birth weight that differ by infant sex. Maternal vitamin D status may be beneficial for male and female offspring through different mechanisms.