Folic Acid Prevention of NTDs PDF

AMERICAN ACADEMY OF PEDIATRICS Committee on Genetics Folic Acid for the Prevention of Neural Tube Defects ABSTRACT. The American Academy of Pediatrics...

AMERICAN ACADEMY OF PEDIATRICS Committee on Genetics Folic Acid for the Prevention of Neural Tube Defects ABSTRACT. The American Academy of Pediatrics en- for women who have had a previous NTD-affected dorses the US Public Health Service (USPHS) recommen- pregnancy. dation that all women capable of becoming pregnant consume 400 mg of folic acid daily to prevent neural tube WOMEN WITH NO HISTORY OF A PREVIOUS defects (NTDs). Studies have demonstrated that pericon- NTD-AFFECTED PREGNANCY ceptional folic acid supplementation can prevent 50% or more of NTDs such as spina bifida and anencephaly. For Of children with an NTD, 95% are born to couples women who have previously had an NTD-affected preg- with no family history of these defects. Evidence to nancy, the Centers for Disease Control and Prevention date suggests that supplementation with a multivi- (CDC) recommends increasing the intake of folic acid to tamin containing 400 (0.4 mg) mg of folic acid pre- 4000 mg per day beginning at least 1 month before con- vents the occurrence of.50% of NTDs when it is ception and continuing through the first trimester. Im- taken before conception and continued throughout plementation of these recommendations is essential for the first trimester of pregnancy.5 The USPHS recom- the primary prevention of these serious and disabling birth defects. Because fewer than 1 in 3 women consume mends that all women of childbearing age who are the amount of folic acid recommended by the USPHS, capable of becoming pregnant take 400 mg of folic the Academy notes that the prevention of NTDs depends acid daily.5 Implementing this recommendation may on an urgent and effective campaign to close this preven- provide the opportunity for primary prevention of tion gap. 50% or more of these serious disabling birth defects. Regular and ongoing ingestion of folic acid by women of childbearing age is necessary because ap- ABBREVIATIONS. NTDs, neural tube defects; USPHS, US Public Health Service; CDC, Centers for Disease Control and Prevention; proximately half of the pregnancies in the United MRC, Medical Research Council; IOM, Institute of Medicine; AAP, States are unplanned,6 and neural tube closure oc- American Academy of Pediatrics. curs during the first 4 weeks of gestation.7 Despite the publication of the USPHS recommendation in September 1992, a 1998 poll showed that 70% of BACKGROUND women aged 18 to 45 years still are not following the N eural tube defects (NTDs) are among the USPHS recommendation.8 most common birth defects contributing to infant mortality and serious disability. WOMEN WHO HAVE HAD A PREVIOUS NTDs, which include anencephaly, spina bifida, and NTD-AFFECTED PREGNANCY encephalocele, occur in approximately 1 of 1000 Among US couples who have had a child with an births in the United States.1 An estimated 4000 preg- NTD, the recurrence risk is 2% to 3% in subsequent nancies are affected with NTDs each year. More than pregnancies.9 In 1991, the Medical Research Council one third of these pregnancies are spontaneously lost (MRC) Vitamin Study Group reported the results of or electively terminated; thus, about 2500 infants per a well-designed, prospective, randomized trial of fo- year are born with an NTD. The results of 2 random- lic acid supplementation for the prevention of NTDs ized controlled trials and several observational stud- in pregnancies of women who had a previous child ies showed that 50% or more of NTDs can be pre- with an NTD, and the CDC published its recommen- vented if women consume a folic acid– containing dations for consumption of 4000 (4 mg) mg of folic supplement before and during the early weeks of acid.4 The results of the MRC study conclusively pregnancy2,3 in addition to the folate in their diet. demonstrated that a daily dosage of 4000 mg of folic Based on a synthesis of these data, the US Public acid, in addition to folate in the diet, before and Health Service (USPHS) and Centers for Disease during early pregnancy resulted in a 71% reduction Control and Prevention (CDC) recommendations of recurrence of NTDs. The addition of other vita- were developed.4,5 Because the evidence for folic acid mins to the dosage of folic acid did not reduce the prevention evolved over time, there are two separate risk further. Use of multivitamins without folic acid recommendations: one for women who have no his- did not result in a reduced risk for NTDs. The MRC tory of a previous NTD-affected pregnancy and one study did not explore the possible benefit of a dosage lower than 4000 mg of folic acid. However, an earlier nonrandomized study conducted in the United The recommendations in this statement do not indicate an exclusive course Kingdom suggested that a lower dosage, 360 mg of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate. daily, resulted in a comparable reduction of recur- PEDIATRICS (ISSN 0031 4005). Copyright © 1999 by the American Acad- rence of NTDs.10 Although adverse maternal or fetal emy of Pediatrics. effects of a daily 4000 mg dosage of folic acid were PEDIATRICS Vol. 104 No. 2 August 1999 325 Downloaded from http://publications.aap.org/pediatrics/article-pdf/104/2/325/843981/325.pdf by Univ Of South Alabama user  not detected by the MRC study, the small size of the multivitamin preparations. Folic acid tablets in a study groups precluded detection of uncommon ad- 1000 mg dose are available by prescription only. This verse effects. preparation is most frequently utilized by women who are taking 4000 mg because of a previous NTD- FOLATE AND FOLIC ACID affected pregnancy. Folic acid, also known as pteroylmonoglutamic In March 1996, the Food and Drug Administration acid, is a synthetic compound used in dietary sup- mandated that enriched cereal-grain products be for- plements and fortified foods. The term folate includes tified with 140 mg of folic acid per 100 g of flour.15 all compounds that have the vitamin properties of This measure increases the proportion of women folic acid—including folic acid and naturally occur- who consume the USPHS-recommended daily dos- ring compounds in food.11 The average diet in the age of 400 mg of folic acid only an additional 3%, United States contains 200 mg of naturally occurring because this fortification level will provide the aver- food folate, which is less bioavailable than folic ac- age woman only an additional 100 mg of folic acid id.12 Additional intake of foods rich in folate could per day (unpublished data, 1992). raise the average intake, but it has not been demon- strated that increased consumption of food folate RECOMMENDATIONS would prevent NTDs as effectively as a daily vitamin 1. Prevention for Women With No History of a Pre- supplement containing 400 mg of folic acid. A small vious NTD-Affected Pregnancy. The American comparison study suggests that blood folate concen- Academy of Pediatrics (AAP) endorses the trations are increased much more by folic acid sup- USPHS recommendation that all women of child- plementation than by naturally occurring food folate bearing age who are capable of becoming preg- in the diet.13 Economic and social circumstances may nant should consume 400 (0.4 mg) mg of folic acid make an adequate increase in dietary folate difficult daily. Because of the high rate of unplanned preg- or unlikely, and the behavioral change required nancies in the United States, the AAP encourages among a large fraction of women may take years to efforts at devising a program of food fortification achieve. to provide all women a daily intake of 400 mg of Folic acid is a water-soluble vitamin that has no folic acid. In the absence of optimal fortification, known toxicity. However, higher doses of folic acid the AAP encourages women to consume 400 mg of can correct the anemia of vitamin B12 deficiency (per- folic acid daily in addition to eating a healthy diet. nicious anemia), which might be an important clue to At present, the most convenient, inexpensive, and the presence of vitamin B12 deficiency in some in- direct way to meet the recommended dosage is by stances. Folic acid does not prevent the neurologic taking a multivitamin containing 400 mg of folic consequences of vitamin B12 deficiency, and, for this acid, but efforts to increase the availability of folic reason, the USPHS recommendation cautioned that acid-only supplements should be encouraged for intake of folate should be not.1000 mg per day. women who prefer not to take multivitamins. Be- However, the Institute of Medicine (IOM) Food and cause the risk for NTDs is not totally eliminated Nutrition Board recently set the tolerable upper in- by folic acid use, routine prenatal screening for take limit of synthetic folic acid at 1000 mg, thus NTDs is still advisable. eliminating food folate from the calculation.14 Be- 2. Prevention for Women Who Have Had a Previous cause pernicious anemia rarely occurs before the age NTD-Affected Pregnancy. Women with a history of 50 years, it is likely to be rare among women of a previous pregnancy resulting in a fetus with consuming folic acid during the reproductive years. an NTD should be advised of the results of the Folic acid has been consumed by about a quarter of MRC study. During times in which a pregnancy is all women for many years and extensively during not planned, these high-risk women should con- later pregnancy without apparent adverse effects; sume 4000 (4 mg) mg of folic acid per day. How- however, studies that definitively address the ques- ever, they should be offered treatment with 4000 tion of maternal and fetal safety of folic acid are not mg of folic acid per day starting 1 month before available. the time they plan to become pregnant and The IOM Food and Nutrition Board’s recom- throughout the first 3 months of pregnancy, un- mended dietary allowance (RDA) for folate is 400 mg less contraindicated. Women should be advised for adults and 600 mg for pregnant women.14 To not to attempt to achieve the 4000 mg daily dosage reduce the risk for NTDs, the IOM recommended of folic acid by taking over-the-counter or pre- that women capable of becoming pregnant consume scription multivitamins containing folic acid be- 400 mg of folic acid daily from fortified foods, vita- cause of the possibility of ingesting harmful levels min supplements, or a combination of the two. This of other vitamins, for example, Vitamin A.17 It is in addition to the naturally occurring folate ob- should be noted that 4000 mg of folic acid did not tained from a varied diet.14 The majority of multivi- prevent all NTDs in the MRC study. Therefore, tamin preparations contain 400 mg of folic acid. high-risk patients should be cautioned that folic These preparations are available over the counter acid supplementation does not preclude the need and are already being taken by about 30% of non- for counseling or consideration of prenatal testing pregnant women aged 18 to 45 years in the United for NTDs. States.8 Tablets containing folic acid alone are avail- 3. Prevention for Other High-Risk Persons. No inter- able over the counter in dosages up to 800 mg but the vention or observational studies address prevention availability is very limited when compared with for other high-risk persons. Women with a close 326 FOLIC ACID FOR THE PREVENTION OF NEURAL TUBE DEFECTS Downloaded from http://publications.aap.org/pediatrics/article-pdf/104/2/325/843981/325.pdf by Univ Of South Alabama user  relative (eg, sibling, niece, or nephew) who has an Consultant NTD (risk is approximately 0.3% to 1.0%), women Sechin Cho, MD with type 1 diabetes mellitus (risk is approximately 1%), women with seizure disorders being treated with valproic acid or carbamazepine (risk is approx- REFERENCES imately 1%), and women or their partners who have 1. Centers for Disease Control and Prevention. Surveillance for anenceph- an NTD (risk may be 2% to 3%)18 and are planning aly and spina bifida and the impact of prenatal diagnosis. United States, 1985–1994. MMWR. 1996;44(SS-4):1–13 a pregnancy should discuss with their physician the 2. MRC Vitamin Study Research Group. 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