Vitamin K supplementation during pregnancy for improving outcomes: a systematic review and meta-analysis

Design: randomized or quasi-randomized controlled trials assessing antenatal VK supplementation. Participants: pregnant women from high-income countries (US, UK, Netherlands, Japan; one South Africa trial excluded); late gestation with varying gestational ages; mostly healthy; total participants 21,493 mother–newborn pairs across six trials (three RCTs and three quasi-randomized).

VK regimens during pregnancy included: oral vitamin K1 (phylloquinone) 1 mg/day until delivery (some trials used 4 weeks); oral VK1 20 mg/day for 7–10 days before birth; intramuscular VK1 50 mg given 4–12 hours before delivery; for women on anticonvulsants from ~36 weeks, parenteral or oral VK1 dosing such as 10 mg intramuscular daily for 2–7 days and 10 mg VK1 daily thereafter; vitamin K2 regimens; sometimes used within multivitamin formulations; routes: oral or intramuscular.

Results: Neonatal bleeding not significantly reduced by antenatal VK (RR 1.16; 95% CI 0.59–2.29; P=0.67). Maternal plasma VK1 increased with VK (MD 2.46 ng/mL; 95% CI 0.98–3.93; P=0.001). Other VK-related outcomes showed improvements (cord serum VK1, breast milk VK1 and VK2, VK-dependent factors), but overall evidence quality was very low. Conclusion: Antenatal VK increases maternal VK1 status and some transfer markers but does not demonstrate a clear reduction in neonatal bleeding; routine antenatal VK solely to prevent neonatal bleeding is not supported; more high-quality trials are needed.

Six older trials (1951–1993) with high or unclear risk of bias; small samples in many trials; heterogeneity in dose, route, and gestational age; outcomes inconsistently assessed; data largely from high-income settings; results dominated by two large trials; no data on perinatal death or maternal bleeding; potential publication bias.