Maternal multivitamin use and orofacial clefts in offspring

Teratology. 2001 Feb;63(2):79-86. doi: 10.1002/1096-9926(200102)63:2<79::AID-TERA1013>3.0.CO;2-3.


Background: Cleft lip with or without cleft palate (CLP) and cleft palate alone (CP) affect approximately 1 in 1000 infants and 1 in 2,500 infants, respectively. Studies of the relation between orofacial clefts and multivitamins or folic acid have been inconsistent.

Methods: We used data from a population-based case-control study involving 309 nonsyndromic cleft-affected births (222 with CLP, 87 with CP) and 3,029 control births from 1968 to 1980 to evaluate the relation between regular multivitamin use and the birth prevalence of orofacial clefts.

Results: We found a 48% risk reduction for CLP (odds ratio = 0.52, 95% confidence interval = 0.34-0.80) among mothers who used multivitamins during the periconceptional period or who started multivitamin use during the first postconceptional month, after controlling for several covariates. The risk reduction for CP was less than those for CLP (odds ratio = 0.81, 95% confidence interval = 0.44-1.52); however, a small number of CP cases limited interpretation. No risk reductions for CLP or CP were found for women who began multivitamin use in the second or third month after conception.

Conclusions: The magnitude of the risk reduction in our study is comparable to those of other recent studies; our study does not support the contention that only large dosages of folic acid are needed to prevent orofacial clefts. More studies are needed to test the effects of multivitamins and varying dosages of folic acid on the recurrence and/or occurrence of orofacial clefts to provide information needed to determine possible prevention strategies. Published 2001 Wiley-Liss, Inc.

MeSH terms

  • Case-Control Studies
  • Cleft Lip / epidemiology*
  • Cleft Lip / prevention & control
  • Cleft Palate / epidemiology*
  • Cleft Palate / prevention & control
  • Female
  • Folic Acid / administration & dosage*
  • Georgia / epidemiology
  • Humans
  • Pregnancy
  • Vitamins / administration & dosage*


  • Vitamins
  • Folic Acid