Effects and safety of periconceptional folate supplementation for preventing birth defects
- PMID: 20927767
- PMCID: PMC4160020
- DOI: 10.1002/14651858.CD007950.pub2
Effects and safety of periconceptional folate supplementation for preventing birth defects
Update in
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Effects and safety of periconceptional oral folate supplementation for preventing birth defects.Cochrane Database Syst Rev. 2015 Dec 14;2015(12):CD007950. doi: 10.1002/14651858.CD007950.pub3. Cochrane Database Syst Rev. 2015. PMID: 26662928 Free PMC article. Review.
Abstract
Background: It has been reported that neural tube defects can be prevented with periconceptional folic acid supplementation. The effects of different doses, forms and schemes of folate supplementation for the prevention of other birth defects and maternal and infant outcomes are unclear.
Objectives: This review updates and expands a previous Cochrane Review assessing the effects of periconceptional supplementation with folic acid to reduce neural tube defects (NTDs). We examined whether folate supplementation before and during early pregnancy can reduce neural tube and other birth defects (including cleft palate) without causing adverse outcomes for mothers or babies.
Search strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2010). Additionally, we searched the international clinical trials registry platform and contacted relevant organisations to identify ongoing and unpublished studies.
Selection criteria: We included all randomised or quasi-randomised trials evaluating the effect of periconceptional folate supplementation alone, or in combination with other vitamins and minerals, in women independent of age and parity.
Data collection and analysis: We assessed trials for methodological quality using the standard Cochrane criteria. Two authors independently assessed the trials for inclusion, one author extracted data and a second checked for accuracy.
Main results: Five trials involving 6105 women (1949 with a history of a pregnancy affected by a NTD and 4156 with no history of NTDs) were included. Overall, the results are consistent in showing a protective effect of daily folic acid supplementation (alone or in combination with other vitamins and minerals) in preventing NTDs compared with no interventions/placebo or vitamins and minerals without folic acid (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.15 to 0.52). Only one study assessed the incidence of NTDs and the effect was not statistically significant (RR 0.08, 95% CI 0.00 to 1.33) although no events were found in the group that received folic acid. Folic acid had a significant protective effect for reoccurrence (RR 0.32, 95% CI 0.17 to 0.60). There is no statistically significant evidence of any effects on prevention of cleft palate, cleft lip, congenital cardiovascular defects, miscarriages or any other birth defects. There were no included trials assessing the effects of this intervention on maternal blood folate or anaemia at term.We found no evidence of short-term side effects.
Authors' conclusions: Folic acid, alone or in combination with vitamins and minerals, prevents NTDs but does not have a clear effect on other birth defects.
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References
References to studies included in this review
-
- Czeizel A, Fritz G. Randomized trial of periconceptional vitamins. JAMA. 1989;262:1634.
-
- Czeizel A, Rode K. Trial to prevent first occurrence of neural tube defects by periconceptional multivitamin supplementation. Lancet. 1984;2(8393):40. - PubMed
-
- Czeizel AE. Controlled studies of multivitamin supplementation on pregnancy outcomes. Annals of the New York Academy of Sciences. 1993;678:266–75. - PubMed
-
- Czeizel AE. Limb-reduction defects and folic acid supplementation. Lancet. 1995;345(8954):932. - PubMed
-
- Czeizel AE. Nutritional supplementation and prevention of congenital abnormalities. Current Opinion in Obstetrics & Gynecology. 1995;7(2):88–94. - PubMed
References to studies excluded from this review
-
- Atukorala TM, de Silva LD, Dechering WH, Dassenaeike TS, Perera RS. Evaluation of effectiveness of iron-folate supplementation and anthelminthic therapy against anemia in pregnancy - a study in the plantation sector of Sri Lanka. American Journal of Clinical Nutrition. 1994;60(2):286–92. - PubMed
-
- Bailey LB, Berry RJ. Folic acid supplementation and the occurrence of congenital heart defects, orofacial clefts, multiple births, and miscarriage. American Journal of Clinical Nutrition. 2005;81(5):1213S–17S. - PubMed
-
- Binns C, Scott J, Nwafor N, Graham K, Oddy W, Lee A, et al. Which mothers take folic acid and folate containing foods? Asia Pacific Journal of Clinical Nutrition. 2006;15(3):335–40. - PubMed
-
- Oddy WH, Miller M, Payne JM, Serna P, Bower CI. Awareness and consumption of folate-fortified foods by women of childbearing age in Western Australia. Public Health Nutrition. 2007;10(10):989–95. - PubMed
-
- Botto LD, Lisi A, Bower C, Canfield MA, Dattani N, De Vigan C, et al. Trends of selected malformations in relation to folic acid recommendations and fortification: an international assessment. Birth Defects Research. 2006;76(10):693–705. - PubMed
References to ongoing studies
-
- Javois L. [accessed 21 March 2006];Birth defects treatment and prevention program: oral cleft prevention program (ongoing trial) ClinicalTrials.gov http://clinicaltrials.gov/
Additional references
-
- Berry RJ, Li Z, Erickson JD, Li S, Moore CA, Wang H, et al. Prevention of neural-tube defects with folic acid in China. China-U.S. collaborative project for neural tube defect prevention. New England Journal of Medicine. 1999;341(20):1485–90. - PubMed
-
- Berry RJ, Bailey L, Mulinare J, Bower C. Folic Acid Working Group. Fortification of flour with folic acid. Food Nutrition Bulletin. 2010;31(Suppl 1):S22–35. - PubMed
-
- Botto LD, Lisi A, Bower C, Canfield MA, Dattani N, De Vigan C, et al. Trends of selected malformations in relation to folic acid recommendations and fortification: an international assessment. Birth Defects Research Part A. Clinical and Molecular Teratology. 2006;76:693–705. - PubMed
-
- Botto LD, Yang Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. American Journal of Epidemiology. 2000;151(9):862–77. - PubMed
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