Vitamin D status is associated with uteroplacental dysfunction indicated by pre-eclampsia and small-for-gestational-age birth in a large prospective pregnancy cohort in Ireland with low vitamin D status

Background: Associations between vitamin D and pregnancy outcomes have been inconsistent. Objectives: We described the distribution of 25-hydroxyvitamin D-3 [25(OH)D-3], 3-epi-25(OH)D-3, and 25(OH)D-2 in early pregnancy and investigated associations with pre-eclampsia and small-for-gestational-age (SGA) birth, which are indicative of uteroplacental dysfunction. Design: The SCOPE (Screening for Pregnancy Endpoints) Ireland prospective pregnancy cohort study included 1768 well-characterized low-risk, nulliparous women resident at 52 degrees N. Serum 25(OH)D-3, 3-epi-25(OH)D-3, and 25(OH)D-2 were quantified at 15 wk of gestation with the use of a CDC-accredited liquid chromatographytandem mass spectrometry method. Results: The mean +/- SD total 25(OH)D concentration was 56.7 +/- 25.9 nmol/L, and 17% and 44% of women had 25(OH)D concentrations <30 and <50 nmol/L, respectively. The prevalence of pre-eclampsia was 3.8%, and 10.7% of infants were SGA. There was a lower risk of pre-eclampsia plus SGA combined (13.6%) at 25(OH)D concentrations >75 nmol/L (adjusted OR: 0.64; 95% CI: 0.43, 0.96). The main predictors of 25(OH) D were the use of vitamin D-containing supplements (adjusted mean difference: 20.1 nmol/L; 95% CI: 18.5, 22.7 nmol/L) and summer sampling (adjusted mean difference: 15.5 nmol/L; 95% CI: 13.4, 17.6 nmol/L). Non-Caucasian ethnicity (adjusted mean difference: -19.3 nmol/L; 95% CI: -25.4, -13.2 nmol/L) and smoking (adjusted mean difference: -7.0 nmol/L; 95% CI: -10.5, -3.6 nmol/L) were negative predictors of 25(OH)D. The mean +/- SD concentration of 3-epi-25(OH)D-3, which was detectable in 99.9% of samples, was 2.6 +/- 1.6 nmol/L. Determinants of 3-epi-25(OH)D-3 were 25(OH)D-3 (adjusted mean difference: 0.052 nmol/L; 95% CI: 0.050, 0.053 nmol/L) and maternal age (adjusted mean difference: -0.018 nmol/L; 95% CI: -0.026, -0.009 nmol/L). The mean +/- SD concentration of 25(OH)D-2 was 3.1 +/- 2.7 nmol/L, which was present in all samples. No adverse effects of 25(OH)D concentrations >125 nmol/L were observed. Conclusions: In the first report to our knowledge of CDC-accredited 25(OH) D data and pregnancy outcomes from a large, clinically validated, prospective cohort study, we observed a protective association of a 25(OH)D concentration >75 nmol/L and a reduced risk of uteroplacental dysfunction as indicated by a composite outcome of SGA and pre-eclampsia. Well-designed, adequately powered randomized controlled trials are required to verify this observation.