Healthy Beginnings: Nutrition's Role in Preventing Birth Defects

An Interview with James L. Mills, M.D.

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A native New Yorker, James L. Mills, M.D., arrived on the National Institutes of Health (NIH) campus in 1979, committed to improving scientific understanding of neonatology and birth defects. While climbing the ranks to chief of the Pediatric Epidemiology Section of the National Institute of Child Health and Human Development, Dr. Mills has studied the relationship between birth defects and diabetes, vitamins, obesity, caffeine as well as many non-dietary variables such as drug use and contraception methods. In this interview with Food Insight, Dr. Mills discusses recent nutrition-related research on the prevention of neural tube defects, low birth weight and other adverse birth outcomes.

What is the incidence of birth defects today in the United States?

The risk for major malformations among the general population today is around two percent. Certain segments of the population, however, such as women with insulin-dependent diabetes and those who have given birth previously to a child with neural tube defects, have an increased risk of delivering malformed babies compared to the general population. In both of these latter instances, metabolic or nutritional factors are certainly important.

Can women with insulin-dependent diabetes reduce their risk of having children with birth defects?

Women who have insulin-dependent diabetes at the time they become pregnant have a two-to-three times greater risk of having malformed babies than other women. These malformations can affect the central nervous system, heart, kidneys and other organs. Unfortunately, the biochemical mechanisms or causes of such malformations are not yet known. But practically speaking, the risk of malformations can be reduced considerably with good metabolic control prior to the time the embryo's organs start developing. So if a woman with insulin-dependent diabetes has her blood sugar well-controlled before she gets pregnant, her risk of delivering a malformed baby as well as miscarriage is much, much lower.

What is a neural tube defect (NTD)?

In simple terms, a neural tube defect is a malformation of the brain or spinal cord (neurological system) during embryonic development. Infants born with spina bifida, where the spinal cord is exposed, can grow to adulthood but usually suffer from paralysis or other disabilities. Babies born with anencephaly, where most or all of the brain is missing, usually die shortly after birth. These NTDs make up about five percent of all U.S. birth defects each year.

Can NTDs be prevented?

In 1991, the British Medical Research Trial reported that women with a previously NTD-affected child, who took folic acid or multivitamins with folic acid before and during early pregnancy, had a reduced risk of having other NTD-affected children than those who took multivitamins without folate or no vitamins. A subsequent Hungarian study in women who never had NTD-affected children found that those who received vitamins containing folic acid were less likely than those taking placebos to have children with NTDs. Based on these and other findings, the U.S. Public Health Service recommended that all women of childbearing age take 0.4 milligrams (mg) of folic acid per day.

What government action has been taken?

The Food and Drug Administra-tion (FDA) has proposed fortifying the food supply with 140 micrograms of folic acid per 100 grams of grain including pasta, rice, cornmeal, flour and other grain products. This is estimated to prevent up to one-half or 2,000 NTDs annually. But there's been considerable debate on both sides of the proposal, including from the Centers for Disease Control, which is advocating a higher level of fortification. One argument against such higher levels is that those at increased risk due to poor diets are likely to get the least amount of supplementation from food, while those who don't need it at all are going to consume the largest amounts. Furthermore, folic acid can mask pernicious anemia, a condition resulting from vitamin B-12 deficiency. If this condition is not properly treated, it can cause permanent neurological damage.

What is your opinion on this issue?

I agree with FDA's recommendation for more conservative levels of fortification. The number of people at risk for pernicious anemia and for neurological damage is much higher than the anticipated number of NTD cases to be prevented. At this point, we're unsure what upper level of fortification is safe, and we'd be exposing some 260 million people through the food supply. If a problem does occur, how will we discover if it's related? Everyone in the country will have been exposed, so there will be no control or comparison groups. It'll also be difficult to quantify the exact benefits of folate fortification, because the NTD rate has been declining due to prenatal diagnosis and termination of such pregnancies.

Is NICHD conducting any research on folic acid and birth defects?

We're conducting a study of folic acid intake and birth defects with the Irish Health Research Board. Blood samples taken from pregnant women in Dublin will be analyzed to study the relationship of folic acid and pregnancy outcome. In Ireland multivitamin use is uncommon. So there's less concern about getting the specimens before prenatal care begins, which is necessary to avoid the possible confounding effects of vitamins taken after an NTD occurs. We hope to have results from this study within a year.

What other perinatal vitamins have been studied recently?

In the early 1990s, several reports from England showed that children receiving intramuscular shots of vitamin K shortly after birth had a higher risk of developing leukemia than those who received the vitamin orally or not at all. These reports were taken very seriously, since every U.S. newborn in the last 20 years or so has received vitamin K shots to prevent life-threatening hemorrhagic disease. Working with Mark Klebanoff, M.D., of NICHD, we examined U.S. infant birth records from the time the vitamin K prophylactic measures were introduced. Children in the study were followed for seven years after birth. Our results, published in the New England Journal of Medicine, showed that there was no difference in the cancer rates of children who received the vitamin K shots and those who did not. A second study in Sweden also confirmed the U.S. findings.

How do non-nutritive substances like caffeine affect pregnancy outcomes?

We published a study last year in the Journal of the American Medical Association (JAMA), which showed no association between moderate caffeine consumption and adverse pregnancy outcomes such as miscarriage, low birth weight and short gestation. While it confirmed other research on prenatal exposure to caffeine over the last decade, our study had several distinct advantages. First, women who were trying to become pregnant were recruited within 21 days of conception, which is before most people identify pregnancies or collect information on pregnancy exposures. Second, on each of their seven clinic visits, the women were interviewed about their caffeine consumption, including the quantity they consumed and from what sources. Third, we identified all the miscarriages occurring from three weeks after conception up to delivery. The data were not biased by women who had had a miscarriage and were asked retrospectively about their dietary or other habits.

Wasn't another study published recently contradicting your findings?

Claire Infante-Rivard, M.D., of Montreal's McGill University, published a study in a December 1993 issue of JAMA, which showed a relationship between caffeine intake and miscarriage. There are several problems with the study that could explain the contradiction in findings. First, information on women's caffeine consumption was collected only after they had miscarried, which is subject to recall bias. Second, there's a significant chance they missed many women with spontaneous abortions who did not go to the hospital. Third, there was no attempt to assess the volume of coffee or other beverages consumed, which, in turn, would make it difficult to calculate the amount of caffeine consumed.

Is it safe for pregnant women to consume caffeine in moderation?

Yes, I continue to stand by my previous conclusion that 300 mg of caffeine - or two or three cups of coffee daily - is not associated with spontaneous abortion, preterm delivery or any adverse effects on the fetus. Moreover, we did not find any association between intakes of caffeine over 300 mg and adverse effects; but the number of study subjects consuming the higher amounts was too small to be certain that there was no risk.

U.S. Infant Deaths Due to Birth Defects 1990 Birth defects accounted for 21.5 percent of all infant deaths in the U.S. in 1990. Of these, the largest proportion (32 pecent) were due to heart defects. The following chart outlines other birth defects that contributed to infant mortality.

Heart		32%
Respiratory		14%
Nervous System		13%
Chromosomal		12%
Other		29%

For more information see Healthy Eating During Pregnancy

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Reprinted from the International Food Information Council Foundation