Vitamin D insufficiency among Danish pregnant women-Prevalence and association with adverse obstetric outcomes and placental vitamin D metabolism.

Abstract

In pregnancy, vitamin D deficiency is associated with increased risk of fetal growth restriction and preeclampsia. The underlying mechanisms are not known, but placental dysfunction is believed to play a role. In a Danish population, where health authorities recommend a 10µg/day vitamin D supplement during pregnancy, we explored current use of vitamin D supplements and vitamin D status. In term placentas, alterations in vitamin D metabolism and placental growth, evaluated by the key placental growth factor pregnancy-associated plasma protein-A (PAPP-A), and their relation to vitamin D insufficiency were investigated. We included 225 randomly selected pregnant women attending a nuchal translucency scan at gestational weeks 11-14. Information on use of vitamin D supplements and body mass index (BMI) at inclusion was obtained using self-reported questionnaires. Plasma 25-hydroxyvitamin D was measured at inclusion and correlated with pregnancy outcomes and placental biology, as judged by expression of PAPP-A and enzymes involved in vitamin D metabolism (CYP24A1, CYP27B1) in term placentas. Vitamin D supplements were used by 92% of the women, but 42% were vitamin D insufficient (plasma 25-hydroxyvitamin D <75nmol/L). Eleven women with singleton pregnancies developed fetal growth restriction or preeclampsia. In this small subset, first-trimester mean plasma 25-hydroxyvitamin D was lower in women who developed fetal growth restriction (43±33nmol/L; n=3; P=.006) and there was a tendency towards lower plasma 25-hydroxyvitamin D among women who developed preeclampsia (65±19nmol/L; n=8; P=.08) in third trimester compared with uncomplicated pregnancies (79±22nmol/L; n=187). In term placentas, PAPP-A expression was lower among participants with first-trimester vitamin D insufficiency (P=.009; n=30) but no correlation was found between plasma 25-hydroxyvitamin D and mRNA expression of CYP24A1 (P=.67) and CYP27B1 (P=.34). BMI was negatively correlated with plasma 25-hydroxyvitamin D (P=.03) and positively correlated with placental mRNA expression of CYP24A1 (P=.003; n=30). Despite high compliance with official guidelines regarding vitamin D supplements, vitamin D insufficiency was frequent and the findings indicate that vitamin D insufficiency may affect placental growth. High BMI was associated with vitamin D insufficiency and increased placental vitamin D turnover, but further investigations are needed.