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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.

bullet Overall, vitamin users had 35% lower risk, but college-educated women and Latina mothers had much less benefit than other groups.
bullet 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 acid25% of the daily level recommended for women of childbearing age.

reference information PDF file English Spanish

DELVING DEEPER INTO FOLIC ACID METABOLISM

Taking vitamins does not eliminate the risk for neural tube defectswhy 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:

bullet 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. reference information
bullet Methionine synthase: The 15% of babies who carried an altered form of this gene did not have a higher risk for spina bifida. reference information
bullet FR-: We found no variation in the folate receptor alpha (FR-) gene, responsible for folic acid transport into cells. reference information
bullet BHMT: Babies who have variants of the BHMT/BHMT2 gene do not have a higher risk for oral clefts.reference information


OBESITY DOUBLES RISK

We found obese women had nearly 2 times higher risk for neural tube defectsa 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:

bullet Folic acid intake: Women who were obesewhether or not they used vitaminsstill had a greater risk than non-obese women for neural tube defects.
bullet Weight reduction diets: Those who dieted in the months just before or after conception did not have a higher risk.
bullet 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 geneticlinked 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.

reference information PDF file English Spanish

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DOWNLOADABLE STUDY SUMMARIES
bullet English
PDF file Neural Tube Defects and
Obesity
PDF file Neural Tube Defects: The
Impact of Prenatal Diagnosis
on Rates
PDF file Neural Tube Defects: Who's at
Risk?
PDF file Nitrates & Neural Tube
Defects
PDF file Pesticides and Birth Defects
PDF file Vitamins & Neural Tube
Defectswho Benefits?
bullet Spanish
PDF file Los Defectos del Tubo
Cerebromedular y Las
Vitaminas-¿A Quién
Benefician?)
PDF file Defectos del tubo neural.
¿Quiénes corren el riesgo?
PDF file Los Defectos del Tubo Neural Y la Obesidad
PDF file Los Pesticidas y Los Defectos
de Nacimiento

OTHER EXPOSURES

bullet 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. reference information
bullet 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. reference information
bullet Electromagnetic flelds. No clearcut association was seen between neural tube defects and using electric bed heating devices: electric blankets, mattress pads or waterbed heaters. reference information
bullet 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. reference information
bullet 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. reference information PDF file
bullet 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. reference information PDF file (English Spanish)
bullet

Smoking. Parents' smoking did not increase risk for neural tube defects. reference information

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. reference information

bullet 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. reference information
bullet Stress. Stressful life eventsdivorce, job loss or death of someone closewere reported 30% to 50% more commonly by mothers of affected infants. reference information PDF file
bullet 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. reference information
bullet

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. reference information

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. reference information

Having a low quality diet is associated with increased NTD risk among women who did not take multivitamins or eat cereal regularly before pregnancy. reference information

Diets rich in choline and betaine may have the same protective effect as folic acid in preventing NTDs. reference information

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