Preconceptional Folate Supplementation and the Risk of Spontaneous Preterm Birth

Abstract

Listen

Translate article

A number of studies have reported an association between low concentrations of serum folate and preterm birth. Folate supplementation during pregnancy increased the length of pregnancy in some but not all clinical trials. This cohort study investigated whether preconceptional folate supplementation (as ascertained by patient questionnaire in the first trimester of pregnancy) lowers the risk of spontaneous preterm birth. The investigators analyzed data collected from a cohort of 34,480 low-risk singleton pregnancies in women enrolled in a previous prospective cohort study on Down syndrome screening conducted at 15 US centers between 1999 and 2002. Duration of pregnancy was estimated by ultrasound measurement in the first trimester. Spontaneous preterm birth was defined as preterm birth between 20 and 37 weeks with no medical or obstetrical complications that constituted indications for delivery. The effects of the duration of preconceptional folate supplementation of ≥1 year (long-term), < year and the effect of no supplementation on risk of spontaneous preterm birth were compared using time-to-event analysis. Data were subjected to analysis with multivariable logistic regression. Compared to women who did not take a folate supplement, the risk of spontaneous preterm delivery between 20 and 28 weeks was 70% lower in women who took folate supplements for a year or longer before pregnancy (0.27% vs 0.04%); the hazard ratio was 0.22, with a 95% confidence interval of 0.08 to 0.61, P = 0.004. Long-term folate supplementation reduced the risk between 28 and 32 weeks by over 50% (0.38% vs 0.18%) (hazard ratio, 0.45; 95% confidence interval, 0.24-0.83, P = 0.010). Supplementation had no significant effect on the risk of spontaneous preterm birth beyond 32 weeks. Adjustment for maternal variables (age, body mass index, race and ethnicity, educational level, marital status, smoking, parity and history of prior preterm birth) did not affect the association between long-term folate and risk of spontaneous preterm birth but did eliminate the association found in unadjusted analysis between duration of preconceptional folate supplementation less than one year and risk. These findings suggest that preconceptional folate supplementation for a year or longer may substantially reduce the risk of early spontaneous preterm birth. The risk is lower with longer duration of folate supplementation before pregnancy. The beneficial effect of folic acid does not appear to be associated with other complications of pregnancy such as preeclampsia, small for gestational age infant, placental abruption, or nonspontaneous preterm birth.