title: Folic acid use and nonsyndromic orofacial clefts in China: a prospective cohort study.
abstract: BACKGROUND
  Questions remain about the effectiveness, dose, and timing of folic acid in preventing orofacial clefts. Case-control studies report conflicting results. There have been no cohort studies of orofacial clefts and the use of folic acid without other vitamins.
  
  
  METHODS
  In a prospective cohort of 240,244 women enrolled between 1993 and 1995 in 1 northern and 2 southern provinces in China, we examined the risk of nonsyndromic cleft lip with or without cleft palate (CL/P) and cleft palate alone (CP) in relation to maternal use of 400 μg of folic acid without other vitamins.
  
  
  RESULTS
  Daily use of 400 μg of folic acid without other vitamins, started before the last menstrual period (LMP), was associated with reduced risk of CL/P with adjusted rate ratio (aRR) of 0.69 (95% confidence interval = 0.55-0.87). The greatest reduction in risk was observed in the north among daily users who began taking folic acid pills before LMP (aRR = 0.21 [0.10-0.44]); in the south there was marginal reduction in risk (aRR = 0.81 [0.63-1.05]). No evidence of reduced CL/P risk was observed among women who started folic acid pills on or after their LMP. No persuasive evidence for reduction in CP risk was seen with folic acid pill use at any time.
  
  
  CONCLUSIONS
  Daily maternal consumption of 400 μg of folic acid without other vitamins, started before mother's LMP, was associated with a reduced risk of CL/P in babies born in a high-prevalence region of China.
authors.affiliation: Department of Pediatrics, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Ann
authors.initials: A
authors.lastname: Chao
authors.forename: Zhu
authors.initials: Z
authors.lastname: Li
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Moore
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Liu
authors.forename: Jianghui
authors.initials: J
authors.lastname: Zhu
authors.forename: J David
authors.initials: JD
authors.lastname: Erickson
authors.forename: Ling
authors.initials: L
authors.lastname: Hao
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Berry
mesh_terms: D000293:Adolescent; D000328:Adult; D002681:China; D002971:Cleft Lip / Q000517:prevention & control*; D002972:Cleft Palate / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D016015:Logistic Models; D008297:Male; D011159:Population Surveillance; D011247:Pregnancy; D011295:Prenatal Care; D011446:Prospective Studies; D012306:Risk; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000627:therapeutic use*; D055815:Young Adult; D016903:Drug Monitoring
chemical_list: D014803:Vitamin B Complex; D005492:Folic Acid