Folic acid supplements and risk for oral clefts in the newborn: a population-based study

Br J Nutr. 2015 Nov 14;114(9):1456-63. doi: 10.1017/S0007114515003013. Epub 2015 Sep 7.


Results from previous studies on maternal folic acid intake and infant oral clefts are inconclusive. The aim of the present study was to investigate the association between women's use of folic acid and/or multivitamin supplements and the risk for oral cleft in the newborn. We used data from the Medical Birth Registry of Norway based on all births in Norway from 1999 to 2013. A total of 528 220 women had 880 568 pregnancies, resulting in 896 674 live births and stillbirths, of which 1623 had oral clefts (isolated oral clefts, n 1311; non-isolated oral clefts, n 312). Altogether, 21·5% of women were vitamin supplement users before pregnancy. The birth prevalence of oral clefts was 1·81/1000 live births and stillbirths. Relative risks (RR) were estimated with log-binomial regression. For pregnancies with maternal use of vitamins, the adjusted RR for clefts overall was 0·90 (95% CI 0·79, 1·04). The adjusted RR for cleft palate only (n 586) was 0·84 (95% CI 0·66, 1·06) and that for cleft lip with or without cleft palate (n 1037) was 0·94 (95% CI 0·79, 1·13). Associations were stronger for cleft cases that occurred in combination with other malformations (adjusted RR 0·63; 95% CI 0·45, 0·88), although vitamin supplements provided no protection against isolated clefts (adjusted RR 0·98; 95% CI 0·84, 1·15). In conclusion, our study demonstrates no statistically significant association between vitamin use and isolated oral clefts. However, we found lower risk for oral clefts that occurred in combination with other malformations.

Keywords: CL(P) cleft lip with or without cleft palate; CPO cleft palate only; Epidemiology; Folic acid; Health promotion; MBRN Medical Birth Registry of Norway; MoBa Norwegian Mother and Child Cohort Study; Multivitamins; Oral clefts; RR relative risk; Reproduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cleft Lip / epidemiology*
  • Cleft Lip / prevention & control
  • Cleft Palate / epidemiology*
  • Cleft Palate / prevention & control
  • Cohort Studies
  • Dietary Supplements*
  • Female
  • Folic Acid / administration & dosage*
  • Humans
  • Infant, Newborn
  • Maternal Nutritional Physiological Phenomena*
  • Norway / epidemiology
  • Pregnancy
  • Risk Factors
  • Vitamins / administration & dosage
  • Young Adult


  • Vitamins
  • Folic Acid