Tocolytic magnesium sulfate exposure and risk of cerebral palsy among children with birth weights less than 1,750 grams.

The authors examined the relation between intrapartum magnesium sulfate exposure and risk of cerebral palsy in a case-control study of low birth weight children designed to control for confounding by the clinical indications for magnesium in pregnancy. Case children (n = 97) included all singleton children with cerebral palsy who were born in 1985-1989 in Atlanta, Georgia with a birth weight less than 1,750 g and whose mothers had not had a hypertension-related disease during pregnancy. Control children (n = 110) were randomly selected from the infant survivors using identical selection criteria. Data on magnesium sulfate exposure, labor and delivery, and infant characteristics were abstracted from hospital records. The authors found no association between exposure to magnesium sulfate and cerebral palsy risk (odds ratio = 0.9; 95% confidence interval: 0.3, 2.6) either in all children or in subgroups with varying likelihoods for exposure to magnesium. However, the association did vary by birth weight, with a protective effect being seen in children born weighing less than 1,500 g and an elevated risk in children with birth weights of 1,500 g or more; all confidence intervals included 1.0 except for the combined <1,500 g group. Several ongoing randomized clinical trials of magnesium and cerebral palsy may shed more definitive light on this relation.

Doubling the number of women consuming vitamin supplement pills containing folic acid: an urgently needed birth defect prevention complement to the folic acid fortification of cereal grains.

The major known environmental causes of birth defects are ancient agents that have been in the environment for centuries but have been only recently discovered-rubella, alcohol, and folic acid deficiency. In the United States, we have made great progress in preventing congenital rubella syndrome. We also have a great opportunity to prevent spina bifida and anencephaly (SBA) by increasing the number of women who daily consume vitamin supplements containing folic acid. Even with the recently announced grain fortification regulations, there are 45 million women unprotected from an SBA-affected pregnancy. This article suggests that a substantial educational campaign could, over a 5-year period, double the number of women consuming folic acid supplement pills and make a substantial contribution toward preventing SBA.

5,10 Methylenetetrahydrofolate reductase genetic polymorphism as a risk factor for neural tube defects.

Persons with a thermolabile form of the enzyme 5,10 methylenetetrahydrofolate reductase (MTHFR) have reduced enzyme activity and increased plasma homocysteine which can be lowered by supplemental folic acid. Thermolability of the enzyme has recently been shown to be caused by a common mutation (677C-->T) in the MTHFR gene. We studied 41 fibroblast cultures from NTD-affected fetuses and compared their genotypes with those of 109 blood specimens from individuals in the general population. 677C-->T homozygosity was associated with a 7.2 fold increased risk for NTDs (95% confidence interval: 1.8-30.3; p value: 0.001). These preliminary data suggest that the 677C-->T polymorphism of the MTHFR gene is a risk factor for spina bifida and anencephaly that may provide a partial biologic explanation for why folic acid prevents these types of NTD.

More folic acid for everyone, now.

Research during the last 5 years has made it clear that people who do not take folic acid supplements are at increased risk for functional folate deficiency, which has been proven to cause spina bifida and anencephaly and also has been associated with an increased risk for occlusive cardiovascular disease. The overriding folate policy issue is how to increase dramatically the folate consumption of 75% of the population who are now consuming 0.4 mg of folic acid in a supplement. The most expeditious way to increase consumption is through fortification of a food staple. Public health programs are also needed to educate people about the vital importance of increased consumption of folic acid vitamin supplements and of food rich in natural folates. It is urgent that fortification of cereal-grain products be implemented now. The level proposes by FDA would accomplish some prevention, but much more prevention would occur if the fortification were 2.5 times that level. Fortification at the higher level would prevent about 1000 spina bifida and anencephaly birth defects each year and perhaps as many as 50,000 premature deaths each year from coronary disease. Available data have not demonstrated that increasing consumption of folic acid by 0.1 to 0.25 mg of folic acid a day is harmful. If a policy needs to be established on the assumption that people who take vitamin supplements could be harmed, a good policy option ia available; require that all folic acid vitamin supplements also contain 0.4 mg of vitamin B-12.

Prevention of folic acid-preventable spina bifida and anencephaly.

The results of the British Medical Research Council's randomized controlled trial proved that folic acid can prevent spina bifida and anencephaly. The trial provided critical scientific data upon which to base public health policy for preventing folic acid-preventable spina bifida and anencephaly. Within weeks of publication of the results, the Centers for Disease Control and Prevention in the US developed and issued guidelines for women who had had a pregnancy affected by spina bifida or anencephaly. A year later, the US Public Health Service issued the recommendation that all women of child-bearing age who are capable of becoming pregnant should consume 0.4 mg of folic acid per day. The Public Health Service needed a year to make inferential judgements about dose, target groups, safety, timing of ingestion, and existing and proposed vitamin and drug policies and regulations. Current policy discussions concern whether to permit manufacturers of vitamins or food products to claim that folic acid will prevent folic acid-preventable spina bifida and anencephaly and whether to allow a food staple to be fortified with folic acid.