Early-Pregnancy Vitamin D Deficiency and Risk of Preterm Birth Subtypes

Obstetrics & Gynecology
Feb 2015
Citations:143
Influential Citations:10
Observational Studies (Human)
82
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Methods
Case-cohort study (EVITA) of pregnant women delivering singleton live-born infants at Magee-Womens Hospital, Pittsburgh. Eligible: 12,861 women with prenatal aneuploidy screening at ≤20 weeks. Random subcohort: 2,327; all remaining preterm birth cases: 922; total analytic dataset: 1,126 cases plus 2,327 subcohort. Serum 25-hydroxyvitamin D measured by LC-MS. Outcomes: preterm birth <37 weeks and <34 weeks, with spontaneous and indicated subtypes. Gestational age by obstetric estimates. Data from 1999–2010. Analyses used multivariable models with sampling weights; vitamin D modeled categorically and with restricted cubic splines; adjustments for race/ethnicity, prepregnancy BMI, education, marital status, parity, smoking, season and gestational age at sampling, assay batch, and year of delivery; effect modification by race/ethnicity and BMI tested.
Results
Higher early-pregnancy 25(OH)D status is associated with lower risk of preterm birth. Adjusted risk for preterm birth <37 weeks: <50 vs ≥75 nmol/L: 1.8 (1.3–2.6); 50–74.9 vs ≥75: 1.4 (1.1–1.8). For preterm birth <34 weeks: <50 vs ≥75: 2.1 (1.3–3.6); 50–74.9 vs ≥75: 2.2 (1.4–3.4). Risk declines as 25(OH)D rises to ~90 nmol/L and then plateaus. Findings are similar for spontaneous and indicated preterm birth and do not vary by race/ethnicity. Conclusion: Vitamin D sufficiency in early pregnancy is associated with lower preterm birth risk; these observational data support conducting well-powered randomized trials to determine causality and optimal supplementation strategies in pregnancy.
Limitations
Observational design limits causal inference; potential residual confounding; serum 25-hydroxyvitamin D measured once in early pregnancy and reflects total, not bioavailable, vitamin D; lack of additional vitamin D metabolism markers (e.g., binding protein) and detailed phenotypic data; generalizability may be limited to similar hospital populations.

Abstract

OBJECTIVE: To estimate the association between maternal 25-hydroxyvitamin D concentrations and risk of preterm birth subtypes. METHODS: We performed a case–cohort study using data and banked samples from patients at a teaching hospital in Pittsburgh,...