Environmental Causes
Posted on March 22nd, 2007
Vitamins [including Folic Acid]
Folic acid supplements and risk of facial clefts: Norwegian Study
[Abstract]1
Objective: To explore the role of folic acid supplements, dietary folates, and multivitamins in the prevention of facial clefts.
Design: National population based case-control study.
Setting: Infants born 1996-2001 in Norway.
Participants: 377 infants with cleft lip with or without cleft palate; 196 infants with cleft palate alone; 763 controls.
Main outcome measures: Association of facial clefts with maternal intake of folic acid supplements, multivitamins, and folates in diet.
Results: Folic acid supplementation during early pregnancy (≥400 µg/day) was associated with a reduced risk of isolated cleft lip with or without cleft palate after adjustment for multivitamins, smoking, and other potential confounding factors (adjusted odds ratio 0.61, 95% confidence interval 0.39 to 0.96). Independent of supplements, diets rich in fruits, vegetables, and other high folate containing foods reduced the risk somewhat (adjusted odds ratio 0.75, 0.50 to 1.11). The lowest risk of cleft lip was among women with folate rich diets who also took folic acid supplements and multivitamins (0.36, 0.17 to 0.77). Folic acid provided no protection against cleft palate alone (1.07, 0.56 to 2.03).
Conclusions: Folic acid supplements during early pregnancy seem to reduce the risk of isolated cleft lip (with or without cleft palate) by about a third. Other vitamins and dietary factors may provide additional benefit.
Reduction in orofacial clefts following folic acid fortification of the U.S. grain supply
[Abstract]2
BACKGROUND:
Folic acid fortification in the United States became mandatory January 1, 1998, to reduce the occurrence of neural tube defects (NTDs). We evaluated the impact of folic acid fortification on orofacial clefts using United States birth certificate data for 45 states and the District of Columbia.
METHODS:
Prevalence ratios (PRs) were calculated comparing orofacial cleft prevalence among births prefortification (1/1990-12/1996) and postfortification (10/1998-12/2002), based on fortification status at conception. The JoinPoint Regression Program and exponentially weighted moving average charts (EWMA) were used to assess the timing of any statistically significant changes in prevalence. Data were stratified by maternal race/ethnicity, age, smoking, and timing of prenatal care.
RESULTS:
Orofacial clefts declined following folic acid fortification (PR = 0.94; 95% CI: 0.92-0.96). The EWMA chart flagged a significant decrease in the fourth quarter of 1998. The JoinPoint graph had one change in slope, with a significant quarterly percent change (-0.34) between 1996 and 2002. The decline in orofacial clefts occurred in non-Hispanic Whites but not other racial/ethnic groups, nonsmokers but not women who reported smoking during pregnancy, and women who received prenatal care in the first trimester but not women who began receiving care later in pregnancy.
CONCLUSION:
Folic acid fortification in the United States was associated with a small decrease in orofacial cleft prevalence, with the timing of the decline consistent with the introduction of fortification. The decline is much smaller than that observed for NTDs, but nonetheless suggests an additional benefit of this public health intervention.
Extracts:
Orofacial clefts were reported on the birth certificates of 85.2 per 100,000 births during the period before folic acid fortification (1990-1996). This prevalence dropped to 80.2 per 100,000 births after folic acid fortification became mandatory (October 1998-December 2002) in the United States.
Women who reported smoking during pregnancy had a higher prevalence of infants with orofacial clefts than did women who did not report smoking during pregnancy both before fortification (119.0 vs. 82.2 per 100,000 live births) and after fortification (125.3 vs. 78.3 per 100,000 live births). Comparing data before and after folic acid fortification, the prevalence of orofacial clefts increased among infants whose mothers smoked during pregnancy, and declined significantly among infants whose mothers reported no use of tobacco during pregnancy.
NIH - Moderate doses of vitamin A do not pose risk of birth defects.
Date: July 22, 19973
Taking daily doses of 8-10,000 IU of vitamin A during pregnancy does not appear to cause birth defects, according to a study by the National Institute of Child Health and Human Development (NICHD) (chief investigator James Mills). The study also showed that it is very rare for women to take more than 10,000 IU of vitamin A each day. Dr. Mills added to the report that because few of the women in the study took large doses of vitamin A (more than 25,000 IU) it was not possible to ascertain whether large doses of the vitamin could cause birth defects.
The study compared 935 women pregnant with a child having a birth defect to 573 women pregnant with babies with no birth defect. 387 women in the former group were pregnant with a child having a cranial neural crest defect, a major class of birth defect resulting in cleft palate, facial abnormalities and heart valve abnormalities.
The study was carried out at Northwestern University in Chicago, Illinois, and at the California Public Health Foundation in Berkeley2 and appeared in the July, 1997 issue of the American Journal of Obstetrics and Gynecology.
Teratogenicity of high vitamin A intake
Date: November 1995
[Summary]4
A study of 22,748 pregnant women in the United States, published in the New England Journal of Medicine, November 1995, indicated that women who take more than 10,000 IUs of vitamin A run more than twice (2.4) the risk of giving birth to a baby with a birth defect (including cleft lip, cleft palate, heart disease) as do women taking a daily dosage of 5,000 IUs. Women taking 20,000 IUs were four times more likely to give birth to children with birth defects. Another interpretation on these figures was that 56 of 57 babies born to women consuming large amounts of vitamin A had no birth defects. The increased frequency of defects was concentrated among the babies born to women who had consumed high levels of vitamin A before the 7th week of gestation.
The study recommended that pregnant women either limit their daily consumption of vitamin A to 4-8,000 IUs, or alternatively, take beta-carotene. Beta-carotene is thought not to cause birth defects, as high beta-carotene intake does not elevate vitamin A levels in the body enough to pose a problem with respect to birth defects. The body only converts beta-carotene to vitamin A as needed.
The study was conducted by the Boston University School of Medicine between October 1984 and June 1987. Of the 22,748 women, 339 had birth defects; 121 of these babies had defects originating in the cranial neural crest, one of these defects being cleft palate.
Proviso: There was much criticism of this report, generally to the effect that the risk of vitamin A overdose was overstated. Only 1.4% of the women in the study took supplements exceeding 10,000 IU a day.
- Allen J Wilcox et al. Folic acid supplements and risk of facial clefts: national population based case-control study. BMJ 2007;334:464 (3 March). Available online http://www.bmj.com [verified 27 May 2007] SEE ALSO irishhealth.com [↩]
- Mahsa M. Yazdy, Margaret A. Honein, Jian Xing. Reduction in orofacial clefts following folic acid fortification of the U.S. grain supply. Birth Defects Research Part A: Clinical and Molecular Teratology, January 2007, 79 (1): 16-23. Published Online: 19 Dec 2006. Available at: http://www3.interscience.wiley.com/cgi-bin/jissue/114039049 [accessed 28 May 2007] [↩]
- Mills, J., Simpson, J., Cunningham, G., et al., Vitamin A and birth defects. American Journal of Obstetrics and Gynecology, 1997 177 (1): 31-36. News release available at http://www.nichd.nih.gov/new/releases/vitama.cfm [verified 22 March 2007] [↩]
- Rothman, Kenneth J., Moore, Lynn L., Singer, Martha R., et al., Teratogenicity of High Vitamin A Intake. The New England Journal of Medicine, November 23, 1995, 333 (21): 1369-73. Abstract available at http://content.nejm.org/content/vol333/issue21/index.shtml [verified 22 March 2007] Summary available at http://www.journalclub.org/vol1/a2.html [verified 22 March 2007] [↩]
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