Obesity raises the risk of neural tube defects approximately fourfold

Family Planning Perspectives, Sep/Oct 1996 by Remez, Lisa

Women who are obese at the time of conception are four times more likely to have an infant or fetus affected by neural tube defects than are leaner women. Findings from a multicenter case-control study conducted in the northeastern United States and Canada1 and from a California casecontrol analysis2 indicate that the risk of an affected pregnancy rises with increasing prepregnancy weight, regardless of whether folate intake is adequate. Thus, supplementation with folate, a B vitamin, does not appear to confer the same protection against neural tube defects in heavy women as it does in leaner women.

The Multicenter Study

The data for the multicenter study come from the Slone Epidemiology Unit Birth Defects Study, an ongoing surveillance program of birth defects initiated in the mid-1970s. The researchers examined data on the incidence of neural tube defects among live-born and stillborn infants in hospitals in Boston, Philadelphia and southeastern Ontario from 1988 to 1994. From 1990 onward, data were also collected on pregnancies with malformed fetuses that were terminated, and as of 1992 data on infants without malformations were collected to serve as controls.

In-home interviews were conducted within six months of the delivery or termination date and included questions on a variety of demographic, medical, reproductive and behavioral factors, as well as items on prepregnancy weight (and height, from 1992-1994), vitamin supplementation and dietary intake. For purposes of analysis, daily folate intake was estimated by combining the folic acid dose of any prenatal daily vitamin supplement and the folate content in 100 foods consumed prenatally.

The investigators examined 604 cases of neural tube defects (407 infants or fetuses with spina bifida, 136 with anencephaly and 61 with brain hernias). Controls consisted of 1,658 mothers of infants or fetuses with other major malformations not associated with obesity or folic acid intake and 93 mothers of infants with no major malformations. Relative risks of neural tube defects were estimated through logistic regression models that controlled for maternal age, maternal education, family income, birth status (whether the pregnancy ended either in a live birth or stillbirth or in an abortion), average daily folate intake (less than 400 mcg versus 400 mcg or more) and average calorie intake.

A prepregnancy maternal weight of less than 80 kg was not associated with any increased risk of neural tube defects when mothers of infants with such defects were contrasted with those whose infants had other malformations. However, weights above that level were increasingly related to the risk that a pregnancy would be diagnosed with neural tube defects: Net of all other factors, women who weighed 80-89 kg were nearly twice as likely to have an infant or fetus with neural tube defects (relative risk of 1.9) than were women of average weight (50-59 kg); these relative risks increased to 3.1 among women weighing 100-109 kg and to 4.0 among those weighing 110 kg or more. The same trend-increased weight associated with increased incidence, net of all factors-characterized the multivariate results for spina bifida and anencephaly, although not for hernias of the brain.

The investigators found that folate intake did not alter the probability of neural tube defects among obese women: No matter their daily folate intake, the relative risk of neural tube defects remained nearly three times as high among the offspring of women weighing 100 kg or more than among the infants or fetuses of women of average weight. Moreover, the protective effects of folate intake seemed to be nullified among very heavy women. While an average daily dose of 400 mcg or more lowered the risk of neural tube defects by 40% (compared with intake of less than 400 mcg) among women weighing less than 70 kg, adequate folate intake had no statistically significant impact on women who weighed 70 kg or more.

For 1992-1994, when data on height were available, the researchers examined the influence of body mass index on the risk of neural tube defects and contrasted 88 women having an infant or fetus diagnosed with neural tube defects with 317 control women whose infant or fetus had other malformations and the 93 with normal pregnancies. The risk rose steadily with increasing body mass: Women with the highest prepregnancy body mass index (32 kg/m2 or more) were nearly three times more likely than women of average body mass to have a pregnancy affected with neural tube defects (relative risk of 2.8).

The investigators considered the possibility of selection bias: Diagnostic techniques can be unreliable for obese women, so the incidence of neural tube defects (and resulting terminations) could be artificially elevated among leaner women. The distribution of therapeutic abortions was similar across all weight groups, however. The investigators observe that the lessened sensitivity of diagnosis among obese women may account for the unexpected strength of this association. They also rule out bias caused by errors in reporting dietary folate intake, since the majority of women who reported adequate levels took it as a vitamin supplement.