title: 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.
abstract: Associations between vitamin D and pregnancy outcomes have been inconsistent.
  
  
  
  We described the distribution of 25-hydroxyvitamin D3 [25(OH)D3], 3-epi-25(OH)D3, and 25(OH)D2 in early pregnancy and investigated associations with pre-eclampsia and small-for-gestational-age (SGA) birth, which are indicative of uteroplacental dysfunction.
  
  
  
  The SCOPE (Screening for Pregnancy Endpoints) Ireland prospective pregnancy cohort study included 1768 well-characterized low-risk, nulliparous women resident at 52°N. Serum 25(OH)D3, 3-epi-25(OH)D3, and 25(OH)D2 were quantified at 15 wk of gestation with the use of a CDC-accredited liquid chromatography-tandem mass spectrometry method.
  
  
  
  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)D3, which was detectable in 99.9% of samples, was 2.6 ± 1.6 nmol/L. Determinants of 3-epi-25(OH)D3 were 25(OH)D3 (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)D2 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.
  
  
  
  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. The SCOPE pregnancy cohort was registered at www.anzctr.org.au as ACTRN12607000551493.
authors.affiliation: Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences, The Irish Centre for Fetal and Neonatal Translational Research, and m.kiely@ucc.ie.
authors.forename: Mairead E
authors.initials: ME
authors.lastname: Kiely
authors.affiliation: Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences.
authors.forename: Joy Y
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: Cork Centre for Vitamin D and Nutrition Research, School of Food and Nutritional Sciences.
authors.forename: Michael
authors.initials: M
authors.lastname: Kinsella
authors.affiliation: The Irish Centre for Fetal and Neonatal Translational Research, and Departments of Epidemiology and Public Health and.
authors.forename: Ali S
authors.initials: AS
authors.lastname: Khashan
authors.affiliation: The Irish Centre for Fetal and Neonatal Translational Research, and Obstetrics and Gynecology, University College Cork, Cork, Ireland.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Kenny
mesh_terms: D000328:Adult; D002112:Calcifediol / Q000097:blood; D019587:Dietary Supplements; D005260:Female; D006801:Humans; D007236:Infant, Small for Gestational Age; D007494:Ireland; D010920:Placenta / Q000503:physiopathology*; D011225:Pre-Eclampsia / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control; D011247:Pregnancy; D011256:Pregnancy Outcome; D015995:Prevalence; D011446:Prospective Studies; D012307:Risk Factors; D014599:Uterus / Q000503:physiopathology*; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood* / Q000627:therapeutic use; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications* / Q000517:prevention & control; D014815:Vitamins / Q000097:blood / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D014815:Vitamins; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D002112:Calcifediol
keywords: 25-hydroxyvitamin D; pre-eclampsia; pregnancy; small for gestational age; vitamin D