Drug and environmental factors associated with adverse pregnancy outcomes. Part II: Improvement with folic acid.
OBJECTIVE
To provide a comprehensive review of periconceptional folic acid supplementation and factors affecting folate supplementation trials.


METHODS
A MEDLINE search was conducted through December 1997. Additional sources were obtained from Current Contents and citations from the references obtained. Search terms included folate, folic acid, neural tube defect, spina bifida, and anencephaly.


METHODS
Relevant animal and human studies examining the effects of folate were reviewed.


METHODS
Data collected included: type of study, folate dosing, dietary folate intake, serum and red blood cell folate concentrations, type of defect(s) studied, vitamin usage, parental risk factors, factors affecting trial results.


RESULTS
Nine key factors have been identified that affect outcomes of folic acid supplementation trials. Daily doses of 0.8 mg decreased the occurrence and doses of 4 mg decreased the recurrence of neural tube defects in randomized clinical trials. Since lower folic acid doses were effective in nonrandomized trials, research is needed to determine the lowest effective dosage. Other benefits involving pregnancy outcome are suggested.


CONCLUSIONS
Women of childbearing age should take a daily folic acid supplement to reduce the risk of pregnancies resulting in infants with a neural tube defect and other potential adverse pregnancy outcomes. Further health benefits from folic acid supplementation are reviewed in Part III of this series.
College of Pharmacy, University of Iowa, Iowa City 52242, USA.
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Van Dyke
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D000818:Animals; D019587:Dietary Supplements; D064420:Drug-Related Side Effects and Adverse Reactions; D004785:Environmental Pollutants / Q000009:adverse effects*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D016239:MEDLINE; D009436:Neural Tube Defects / Q000139:chemically induced / Q000517:prevention & control; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced* / Q000517:prevention & control*; D011256:Pregnancy Outcome; D016032:Randomized Controlled Trials as Topic
D004785:Environmental Pollutants; D005492:Folic Acid