To determine the effect of preconceptional folate supplementation on perinatal mortality and morbidity.
In a cohort of 38,033 singleton pregnancies preconceptional folate supplementation was prospectively recorded in the first trimester of pregnancy.Perinatal mortality was defined as stillbirth after 20 weeks or neonatal death within first 28 days of life, both in the absence of chromosomal or congenital abnormalities. Neonatal morbidity was self-reported. The association between folate supplementation and perinatal mortality and morbidity was adjusted for maternal characteristics (age, race/ethnicity, parity, BMI, and smoking) and complications of pregnancy (chronic hypertension, preeclampsia, pre and gestational diabetes, placenta previa and placental abruption).
Preconceptional folate supplementation for >= 1 year, but not less, was associated with a 40% reduction of perinatal mortality (RR, 95% CI = 0.63, 0.42-0.95; p=0.027). BMI negatively interacted with the effect of folate. Thus adjustement for interaction with BMI and other maternal characteristics showed stronger risk reduction of perinatal mortality (adjusted RR, 95% CI = 0.15, 0.03-0.73; p=0.019). Pulmonary complications were the only neonatal morbidity significantly associated with preconceptional folate supplementation (adjusted RR, 95% CI = 0.81, 0.68-0.97; p=0.022). Adjustment for complications of pregnancy did not have a material effect but adjustment for duration of pregnancy eliminated entirely the associations between folate supplementation and perinatal mortality and morbidity (p=0.3 and p=0.1, respectively).
Preconceptional folate supplementation is associated with 40-80% reduction in perinatal mortality and its effect increases with decreasing BMI. Folate supplementation reduces only the risk of neonatal pulmonary morbidity. Preconceptional folate supplementation decreases perinatal mortality and morbidity specifically by reducing risk of preterm birth rather than representing general good health and pregnancy outcome.
© 2008 Mosby, Inc. Published by Elsevier Inc. All rights reserved.