Folic acid supplements and perinatal mortality in China.

Introduction: Periconceptional use of multivitamins containing folic acid prevents external major birth defects, especially neural tube defects. We aimed to explore the effects of maternal folic acid supplementation alone on perinatal mortality with or without external major birth defects plus neural tube defects. Methods: From the China-US Collaborative Project for Neural Tube Defects Prevention, we identified 222, 303 singleton pregnancies with detailed information on periconceptional folic acid use, defined as folic acid supplementary before the last menstrual date until to the end of the first trimester. Perinatal mortality included stillbirths after 20 weeks' gestation and early neonatal deaths within 7 days of delivery. Results: Among the fetuses or infants of women who did not take folic acid, the rate of perinatal mortality was 2.99% and 1.62% at least 20 weeks' gestation in the northern and southern regions. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.85% and 1.39% in the northern and southern region. The estimated relative risk for perinatal mortality [adjusted risk ratio (RR), 0.72; 95% confidence interval (CI), 0.61- 0.85], stillbirth (adjusted RR, 0.78; 95% CI, 0.64-0.96), early neonatal mortality (adjusted RR, 0.61; 95% CI, 0.45-0.82), and neonatal death (adjusted RR, 0.64; 95% CI, 0.49-0.83) in northern China was significantly decreased in association with periconceptional folic acid supplementation. Compared with northern, there was a lesser effect in southern China. Conclusion: Periconceptional intake of 400μg folic acid daily reduces the overall risk perinatal mortality, as well as the risk from external major birth defects and neural tube defects, especially in northern China.