Low choline levels in pregnant women raise babies' risk for brain and spinal-cord defects, study shows

- By Erin Digitale

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Gary Shaw

A newborn’s risk for brain and spinal-cord defects rises if the mother has low blood levels of the nutrient choline during pregnancy, researchers at the Stanford University School of Medicine have discovered.

The scientists used a collection of 180,000 blood samples from pregnant California women to look for risk factors for two neural tube birth defects: anencephaly, a lethal condition in which the brain and skull do not develop, and spina bifida, a spinal-cord malformation that causes paralysis and lifelong disability. Neural tube defects have become less common since the 1996 decision to fortify the U.S. food supply with folic acid, a B-vitamin shown to prevent the defects, but they have not disappeared.

“Families whose infants die or suffer permanent disability from NTDs still feel the burden of these defects,” said Gary Shaw, DrPH, professor of neonatology and primary author of the new research, which will appear Aug. 14 in Epidemiology.

About 500 pregnancies per year are affected by neural tube defects in California alone, noted Shaw. “We’re keen on understanding what risk factors explain the continued disease.”

Shaw’s study targeted a group of nutrients suspected to promote brain and spinal-cord development. In early pregnancy, a sealed tube forms along the embryo’s back that later grows into the brain and spinal cord. Neural tube defects occur if the tube does not seal correctly. Based on prior research on folic acid, scientists believe that development of the neural tube may depend on a specific biochemical pathway that requires several vitamins and essential nutrients to operate properly. Shaw’s team measured blood levels of 13 of these nutrients in two groups of women who participated in California’s prenatal birth-defect screening program.

From 180,000 pregnant women screened between 2003 and 2005, the researchers identified 80 whose pregnancies were affected by neural tube defects. Their blood samples were compared to 409 samples randomly selected from among the women whose infants had no structural birth defects.

Choline, an essential nutrient found in egg yolks, soy, wheat germ and meats, was the only nutrient measured whose blood levels were linked to risk of neural tube defects.

“As choline levels went up, risk went down,” Shaw said. Risk for neural tube defects was 2.4 times higher in women with the lowest blood choline levels compared to women with average blood choline levels. The highest blood choline levels were associated with the lowest risk. A previous study by Shaw’s group showed that consumption of choline-rich foods was associated with lower risk for neural tube defects, but this is the first study to evaluate blood levels of choline and NTD risk.

Shaw’s work provides a promising target for future clinical trials on neural tube defect prevention, said Louanne Hudgins, MD, division chief of medical genetics at Lucile Packard Children’s Hospital, who did not participate in the study. Hudgins, who is also a professor of pediatric genetics at the medical school, regularly counsels families facing prenatal diagnoses of neural tube defects. “You can’t change an individual’s genetic predisposition to these defects. But nutrition components to NTD risk are ripe for therapy,” she said.

Shaw cautioned that the blood samples tested were obtained between the 15th and 18th week of pregnancy, well after formation of the neural tube, which seals around the sixth week of pregnancy. Future research will be needed to examine blood choline levels in early pregnancy, he said. Researchers also need to test whether choline supplements given in early pregnancy reduce the rates of neural tube defects. Right now, prenatal multivitamins contain little or no choline.

For women who want to become pregnant, “the best source for choline is still eating a variety of foods,” Shaw concluded. Women of reproductive age should also follow U.S. Public Health Service recommendations to take a multivitamin containing other nutrients previously shown to promote healthy pregnancies, he said.

The study was funded by grants from the U.S. Centers for Disease Control and Prevention, the National Institute of Neurological Disorders and Stroke, and the Foundation to Promote Research into Functional Vitamin B12 Deficiency.

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