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Cited by 358Folate and B Vitamins ResearchPharmacological Effects and Toxicity StudiesSpinal Dysraphism and Malformations

Effects and safety of periconceptional folate supplementation for preventing birth defects

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De-Regil, Luz Maria, Fernández-Gaxiola, Ana C, Dowswell, Therese, Peña-Rosas, Juan Pablo·2010·Cochrane Database of Systematic Reviews
DOI 10.1002/14651858.cd007950.pub2PMC PMC4160020
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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the international clinical trials registry platform and contacted relevant organisations to identify ongoing and unpublished studies.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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  • Early initiation (ideally before conception) of folic acid supplements decreases the risk for congenital malformations such as neural tube defects.

    “Although we found no difference in adverse pregnancy outcomes between women who started folic acid supplements before or during the pregnancy, it is widely evidenced that early initiation (ideally before conception) of folic acid supplements does decrease the risk for congenital malformations such as neural tube defects [52].”

    From Associations between periconceptional lifestyle behaviours and adverse pregnancy outcomes (2021) · cites this paper as [52]

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Cited by

Sorted by citations

Authors
De-Regil, L. M., Fernández-Gaxiola, A. C., Dowswell, T., & Peña-Rosas, J. P.
Affiliations
  • World Health Organization (CH)
  • Instituto Nacional de Salud Pública (MX)
  • University of Liverpool (GB)
Venue
Cochrane Database of Systematic Reviews
Publisher
John Wiley & Sons, Ltd
Published
2010-10-06
Issue
10
Pages
CD007950-CD007950
ISSN
1361-6137 (ISSN-L)
DOI
10.1002/14651858.cd007950.pub2
PMC
PMC4160020
OpenAlex
W4210985169
Cited by
358
References
4
Citations by year
2026: 6 · 2025: 8 · 2024: 13 · 2023: 8 · 2022: 17 · 2021: 20 · 2020: 17 · 2019: 13 · 2018: 18 · 2017: 31 · 2016: 51 · 2015: 37 · 2014: 42 · 2013: 36 · 2012: 28
Type
reference entry
Language
en
Update notices
new_version (2015-12-14)
Open access
Locations
  • Cochrane Database of Systematic Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute for Health and Care Research (CPGS02)
Topics
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Spinal Dysraphism and Malformations
Keywords
folic acid, neural tube defects, congenital malformations, cleft palate, cleft lip, miscarriage, maternal outcomes, infant outcomes, anemia in pregnancy, adverse effects, contraception
MeSH terms
Female, Folic Acid, Humans, Infant, Neural Tube Defects, Pregnancy, Vitamin B Complex, Randomized Controlled Trials as Topic, Dietary Supplements

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