Apparent Prevention of Neural Tube Defects by Periconceptional Vitamin Supplementation

Smithells, R. W.; Sheppard, Sheila; Schorah, C. J.; Seller, MaryJ.; Nevin, N. C.; Harris, R. Alan; Read, Andrew P.; Fielding, D W

doi:10.1097/00006254-198210000-00011

Cited by 25 publications

(28 citation statements)

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“…Many different lines of evidence suggest the protective effect of folate consumption, including descriptive epidemiology, case‐control studies, cohort studies, and randomized and nonrandomized intervention studies (Table 3) (51, 53–75). While a majority of studies have shown a protective effect of folate supplementation, some have failed to demonstrate an effect.…”

Section: Prevention Of Ntds: the Folate Storymentioning

confidence: 99%

Epidemiology of Neural Tube Defects

2003

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Summary: Neural tube defects (NTDs)-malformations secondary to abnormal neural tube closure between the third and fourth weeks of gestational age-have a complex and imperfectly understood etiology in which both genetic and environmental factors appear to be involved. A number of specific chromosomal or single-gene disorders, presumably not affected by environmental influences, are associated with the development of NTDs, but such syndromal cases account for a small proportion of NTDs in live-born infants. Analysis of recurrence patterns within families and of twin-concordance data provides evidence of a genetic influence in nonsyndromal cases, but factors such as socioeconomic status and geographic area (independent of race or ethnicity) are also associated with variations in the incidence of NTDs. The prevalence at birth of both anencephaly and spina bifida has decreased, but the advent of antenatal diagnosis and elective termination of affected pregnancies has undermined the reliability of birth prevalence rate as an estimate of incidence. Some occupational and other exposures, including maternal use of antiepileptic drugs (AEDs), are associated with increased risk for NTDs. Among women who have had an NTD-affected pregnancy, recurrence risk is markedly higher than the risk for a first NTD-affected pregnancy in the general population. There is strong evidence, overall, for a protective effect of adequate folate consumption. In some high-risk groups, however, such as women taking AEDs, folate supplementation has not been proven to reduce NTD risk.

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Section: Prevention Of Ntds: the Folate Storymentioning

confidence: 99%

Epidemiology of Neural Tube Defects

2003

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“…These findings led Smithells et al to propose a randomized, placebo‐controlled, double‐blind study of periconceptional nutrient supplementation and NTD recurrence. However, their initial proposal was rejected by two institutional ethics review committees (Smithells et al,1981); thus, Smithells et al conducted a non‐randomized intervention study without a placebo control, using a multivitamin preparation providing 360 μg of folic acid daily. All women participating in the study had a previous NTD‐affected pregnancy; thus, this study addressed prevention of NTD recurrence , rather than first occurrence .…”

Section: Introductionmentioning

confidence: 99%

Teratology: From science to birth defects prevention

Rasmussen

Erickson

Reef

et al. 2008

Birth Defects Research

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One of the goals of birth defects research is to better understand risk or preventive factors for birth defects so that strategies for prevention can be developed. In this article, we have selected four areas of birth defects research that have led to the development of prevention strategies. These areas include rubella virus as a cause of congenital rubella syndrome, folic acid as a preventive factor for neural tube defects, cytomegalovirus infection as a cause of birth defects and developmental disabilities, and alcohol as a cause of fetal alcohol spectrum disorders. For each of these areas, we review key clinical and research findings that led to the identification of the risk or preventive factor, milestones in the development of prevention strategies, and the progress made thus far toward prevention.

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“…This discovery prompted Smithells and his team to conduct a trial of periconceptional supplementation where women who had experienced at least one prior NTD pregnancy were offered a multivitamin that included 0.36 mg folic acid. The strong evidence of the vitamins' protective effect prevented the ethics committee from approving a double‐blind placebo study; however, a significant reduction in NTDs was observed in the group of women taking the supplement (Smithells et al, ). Subsequent studies by Smithells and many other researchers have confirmed this protective effect, and we now know that supplemental folic acid intake can reduce the incidence of NTDs by up to 70% (reviewed in Ross, ).…”

Section: Introductionmentioning

confidence: 99%