Discoveries and Data: Specific Conditions

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anencephaly
bias
diabetes
folic acid
gene
neural tube defects
protective factor
risk factor
spina bifida

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PROTECTIVE EFFECT SEEN WITH FOLIC ACID

Our studies have contributed to the growing awareness that taking multivitamins containing folic acid around the time of conception reduces risk for neural tube defects.

	Overall, vitamin users had 35% lower risk, but college-educated women and Latina mothers had much less benefit than other groups.

	Among women who did not take multivitamins, those consuming fortified cereal had lower risks. One bowl of vitamin-fortified cereal contains at least 0.1 milligrams of folic acid—25% of the daily level recommended for women of childbearing age.

English Spanish

DELVING DEEPER INTO FOLIC ACID METABOLISM

Taking vitamins does not eliminate the risk for neural tube defects—why do some pregnancies benefit while others do not? The search to understand how supplements alter risk has has focused on a number of genes that influence the developing baby's folic acid metabolism. Variant forms of these genes can lower folic acid levels, particularly if the mother does not take multivitamins containing folic acid. Among babies who inherited variant genes and whose mothers did not use multivitamins, we found:

	MTHFR: About 1 in 6 babies had the genetic type "TT" of methylenetetrahydrofolate reductase (MTHFR); this variant was more common in Latino infants. Babies with type "TT" had a modest increase in spina bifida risk.

	Methionine synthase: The 15% of babies who carried an altered form of this gene did not have a higher risk for spina bifida.

	FR-: We found no variation in the folate receptor alpha (FR-) gene, responsible for folic acid transport into cells.

	BHMT: Babies who have variants of the BHMT/BHMT2 gene do not have a higher risk for oral clefts.

OBESITY DOUBLES RISK

We found obese women had nearly 2 times higher risk for neural tube defects—a finding since replicated by the Program and other researchers. The association was more pronounced for spina bifida (open spine) than for anencephaly (absence of the brain).

Nutritional and other factors didn't explain the study results:

	Folic acid intake: Women who were obese—whether or not they used vitamins—still had a greater risk than non-obese women for neural tube defects.

	Weight reduction diets: Those who dieted in the months just before or after conception did not have a higher risk.

	Diabetes: Mothers with insulin-dependent diabetes have greater risk for neural tube defects, but excluding diabetics from our analysis did not change results.

Will losing weight eliminate the extra risk seen among obese women? Not necessarily. There may be an underlying factor-nutritional, metabolic or even genetic—linked to both obesity and neural tube defects; if so, weight loss alone might not correct this factor. We caution women to consult their physicians before attempting to lose weight; an unsupervised diet actually could increase risk by eliminating nutrients such as folic acid.

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DOWNLOADABLE STUDY SUMMARIES


	English

Neural Tube Defects and Obesity Neural Tube Defects: The Impact of Prenatal Diagnosis on Rates Neural Tube Defects: Who's at Risk? Nitrates & Neural Tube Defects Pesticides and Birth Defects Vitamins & Neural Tube Defects—who Benefits?

	Spanish

Los Defectos del Tubo Cerebromedular y Las Vitaminas-¿A Quién Benefician?) Defectos del tubo neural. ¿Quiénes corren el riesgo? Los Defectos del Tubo Neural Y la Obesidad Los Pesticidas y Los Defectos de Nacimiento

OTHER EXPOSURES

	Corticosteroids. Use of drugs such as cortisone and prednisone to treat asthma, autoimmune diseases and to reduce inflammation did not alter risk for neural tube defects.

	Drugs. Using cocaine, amphetamines/ speed or marijuana was associated with reduced risk. This may be due to reporting differences (mothers of affected infants may be reluctant to admit using drugs), more miscarriages among drug-exposed pregnancies or some other bias. Father's drug use didn't increase risk.

	Electromagnetic flelds. No clearcut association was seen between neural tube defects and using electric bed heating devices: electric blankets, mattress pads or waterbed heaters.

	Hazardous waste sites. Women who lived within 1/4 mile of a Superfund site during the first 3 months of pregnancy had a 2 times greater risk of of having babies with neural tube defects.

	Nitrates. High levels of nitrates in drinking water from groundwater sources was linked to higher risk for anencephaly but not for spina bifida. There was no increased risk for nitrates from diet or medications.

	Pesticides. Household gardening caused a modest risk increase in some types of defects, as did living within 1/4 mile of agricultural crops. However, we saw no increased risk among mothers with the pesticide exposures we had expected to be most intense: occupational contact and self-applied home pest control. (English Spanish)

	Smoking. Parents' smoking did not increase risk for neural tube defects. Women who smoked during pregnancy, did not use vitamins and whose babies had at least one variant of the NOS3 gene were 4 times more likely to have babies with oral clefts.

	Social and economic factors. The more indicators of low socioeconomic status (such as lower income, less education), the higher the risk for neural tube defects. Residing in a low-SES neighborhood increased risk as well.

	Stress. Stressful life events—divorce, job loss or death of someone close—were reported 30% to 50% more commonly by mothers of affected infants.

	Vitamin A. High doses of vitamin A induce birth defects in laboratory animals; however, we found no higher risk for neural tube defects among mothers who took vitamin A supplements during pregnancy.

	Diet & Nutrition. Women who consume foods with a high sucrose or high glycemic index value around the time of conception and during early pregnancy have an increased risk for neural tube defects. Women who diet during their first trimester of pregnancy, particularly those who also use diuretics, may be more likely to have a baby with a neural tube defect. Having a low quality diet is associated with increased NTD risk among women who did not take multivitamins or eat cereal regularly before pregnancy. Diets rich in choline and betaine may have the same protective effect as folic acid in preventing NTDs.