Vitamin D and Preterm Birth
Preterm birth (before 37 weeks) is a leading cause of infant mortality and long-term morbidity worldwide. Maternal vitamin D deficiency has been examined as a modifiable risk factor, with observational associations that supplementation trials partly confirm.
Observational associations
Multiple cohort studies find lower maternal 25(OH)D associated with higher rates of preterm birth. A 2015 meta-analysis reported adjusted OR ~1.3 for deficient vs sufficient women. The MUSC study (Wagner 2016) found each 10 ng/mL increase in maternal 25(OH)D was associated with 40% reduction in early preterm delivery (< 32 weeks).
RCT evidence
- Wagner NICHD trial (2011) — 494 pregnant women; 4,400 IU/day cholecalciferol vs 400 IU/day. No difference in preterm birth rate in the primary analysis but strong dose-response signal in secondary analysis.
- MUSC Charleston (2013) — expanded 2011 trial; women achieving 25(OH)D > 40 ng/mL had 60% lower risk of preterm birth.
- Meta-analyses (Palacios 2019 Cochrane) — pooled trials show reduction in preterm birth with vitamin D vs placebo (RR ~0.7), moderate-certainty evidence.
Mechanism
Vitamin D regulates immune responses at the maternal-fetal interface, modulates inflammation (which is causally linked to premature membrane rupture and preterm labour), and affects placental development. Vitamin D deficiency correlates with bacterial vaginosis and cervicovaginal infection, both preterm-labour risk factors.
Preterm infant vitamin D
Preterm infants have very low body stores of vitamin D at birth (most vitamin D accrual is in the third trimester). Prevention of preterm rickets and metabolic bone disease of prematurity requires:
- 200–400 IU/kg/day vitamin D in preterm infants < 1,500 g (ESPGHAN 2010, US paediatric guideline).
- Preterm formulas or breastmilk fortifiers deliver vitamin D at higher concentrations than standard products.
- Calcium and phosphorus supplementation is also critical — vitamin D alone won't prevent metabolic bone disease in very preterm babies.
Practical guide
- Preconception and first-trimester: test 25(OH)D and correct to ≥ 30 ng/mL (some obstetricians target 40+).
- Continue 1,000–4,000 IU/day cholecalciferol throughout pregnancy. See pregnancy page.
- History of previous preterm birth: aggressive vitamin D correction is one of several evidence-based interventions (progesterone, cervical cerclage as indicated).
- Postpartum breastfeeding: see maternal 6,400 IU/day option in the infants page.