Maternal supplemental and dietary zinc intake and the occurrence of neural tube defects in California.

The authors investigated the association between maternal preconceptional supplemental and dietary zinc intake and risk of neural tube defects (NTDs) in a population-based case-control study conducted between 1989 and 1991 in California. Cases were 430 NTD-affected fetuses/infants, and controls were 429 randomly selected non-malformed infants. Mothers reported their preconceptional use of vitamin, mineral, and food supplements, and completed a 98-item food frequency questionnaire. Increased total preconceptional zinc intake was associated with a reduced risk for NTDs (quintile 5 vs. quintile 1, odds ratio (OR) = 0.65, 95% confidence interval (CI) 0.43, 0.99). Phytate intake, a constituent of the diet known to impede zinc absorption, appeared to modify the zinc - NTD association. In addition, increased servings of animal products, the most bioavailable food source of zinc, was associated with a reduced risk for NTDs (quintile 5 vs. quintile 1, OR = 0.49, 95% CI 0.32, 0.76). Risk estimates for zinc intake were changed little after controlling for multiple sociodemographic factors and total folate intake, but were attenuated after controlling for nutrients highly correlated with dietary sources of zinc, such as protein. In sum, the analyses indicate that risk of NTDs in infants and fetuses decreased with increasing maternal preconceptional zinc intake. However, it remains unclear whether increased zinc intake, or another nutrient or combination of nutrients highly correlated with zinc intake in the diet, is causally associated with reduced NTD risk.

Maternal occupational and hobby chemical exposures as risk factors for neural tube defects.

In a case-control study, we investigated whether occupational and nonoccupational (hobbies) chemical exposures to women in the periconceptional period increased their risk for having neural tube defect-affected pregnancies. Women were asked about occupational tasks and hobbies performed during the 3 months before through 3 months after conception. Based on her reported occupational tasks and hobbies, an industrial hygienist assigned a priori defined exposure categories to each task and hobby. The exposure categories included 74 chemical groups, 9 "end-use" chemical groups, and organic solvents. Face-to-face interviews were conducted with mothers of 538 (88% of eligible) infants or fetuses with neural tube defect and mothers of 539 (88%) randomly selected, nonmalformed, live-born infants from a population-based 1989-1991 cohort of California births (N = 703,518). Our results suggested that maternal exposures in the periconceptional period to a variety of chemicals associated with occupational and nonoccupational activities did not contribute substantially to risk of neural tube defects in offspring. We observed no effect estimate greater than 2.0 for maternal exposures to the chemical agent groups studied. We did not observe substantially elevated risks associated with maternal exposures to any of the end-use chemical groups or to organic solvents. Considering occupational exposures only among women who worked did not substantially alter results. Adjustment for maternal vitamin use, race/ethnicity, or education level also did not substantially alter the observed associations.

Energy and nutrient intakes and health practices of Latinas and white non-Latinas in the 3 months before pregnancy.

OBJECTIVE: To describe the health practices and energy and nutrient intakes from diet and supplements of foreign- and US-born Latinas and white non-Latinas in the 3 months before pregnancy. DESIGN: A descriptive study in which data were obtained retrospectively from 2 questionnaires: an interviewer-administered questionnaire on the subject's medical, reproductive, family, occupational, and lifestyle history and a subject-administered (and interviewer-assisted) 100-item food frequency questionnaire. SUBJECTS/SETTING: A population-based sample of California women (n = 462) who gave birth between 1989 and 1991 to single, live-born infants. One third of women were Latinas, of whom 58.1% were foreign born. STATISTICAL ANALYSES: Means, standard deviations, and percentiles were computed for energy and nutrient intakes of the total population and for white non-Latinas; US-born Latinas; and foreign-born Latinas. One-way analysis of variance was used to compare group means. RESULTS: Mean and median energy intake in all ethnic groups exceeded 2,000 kcal/day, although less than half of the population consumed 5 servings of fruit and vegetables per day. For iron, half of the women were below the Recommended Dietary Allowance. In contrast to the dietary intake of white non-Latinas and US-born Latinas, foreign-born Latinas had the lowest contribution of fat to total energy intake and the highest dietary intake of carbohydrate, cholesterol, fiber, grain products, protein foods, folate, vitamin C, iron, and zinc. CONCLUSIONS: A woman's ethnicity, as well as whether her place of birth was within or outside of the United States, may be predictors of her dietary and health practices before pregnancy. Vitamin, mineral, and food supplementation and consumption of cold breakfast cereal may be avenues for improving perinatal micronutrient intake.

Maternal illness, including fever and medication use as risk factors for neural tube defects.

We investigated if selected maternal illnesses or medications used during the periconceptional period increased risk of having neural tube defect (NTD)-affected pregnancies. We used a population-based case-control study of fetuses and liveborn infants with NTDs among 1989-1991 California births. In-person interviews were conducted with mothers of 538 (88% of eligible) NTD cases and 539 (88%) nonmalformed controls, usually within 5 months of delivery. A maternal fever or febrile illness episode in the first trimester was associated with an increased risk for having a NTD-affected pregnancy, odds ratio (OR) = 1.91 (95% confidence interval, 1.35-2.72) for fever and OR = 2.02 (1.20-3.43) for febrile illness. Risk estimates were not substantially altered after adjustment for maternal age, race/ethnicity, education, vitamin use, and body mass index. Other reported illnesses were generally not associated with risks of 1.5 or greater, or were too infrequent to adequately estimate risk. An OR of 1.5 or greater was observed for maternal use of guaifenesin, OR = 2.04 (0.79-5.28), and an OR of 0.5 or less was observed for maternal use of calcium-containing medicines, OR = 0.38 (0.14-1.03). Our findings are consistent with previous reports that suggested elevated NTD risks from maternal fever. We could not discriminate, however, whether the increased risks observed for maternal fever were indicative of a causal relation or due to reporting bias. Our findings suggest that many of the illnesses common to reproductive-aged women and the medications commonly used to treat them during pregnancy, except, perhaps, for those illnesses that are febrile-related, do not appear to substantially contribute to the occurrence of NTDs in the population.

Risk for neural tube defect-affected pregnancies among women of Mexican descent and white women in California.

OBJECTIVES: This study investigated a previously reported 50% or more increased risk for neural tube defect-affected pregnancies among Latina women compared with White women. METHODS: Data were derived from a population-based case-control study of fetuses and live-born infants with neural tube defects in a 1989-through-1991 California birth cohort. Interviews were conducted with mothers of 538 (88% of eligible) infants/fetuses with neural tube defects and mothers of 539 (88%) nonmalformed control infants. RESULTS: The risk for a neural tube defect-affected pregnancy was approximately twice as high among women of Mexican descent than among White women (odds ratio = 1.9, 95% confidence interval [CI] = 1.5, 2.8). The odds ratio for Mexico-born Mexican women compared with White women was 2.4 (95% CI = 1.7, 3.2), whereas the risk for US-born women of Mexican and other racial/ethnic descent was not substantially higher than that for Whites. The higher risk among Mexico-born Mexican women was not attributable to differences in numerous studied parental characteristics and exposures. CONCLUSIONS: Given that nearly 20% of all California births are to Mexico-born Mexican women, the increased risks observed are relevant to the population burden of neural tube defects.

Is dietary intake of methionine associated with a reduction in risk for neural tube defect-affected pregnancies?

Results from experimental animals and other laboratory data have suggested a role for methionine, an essential amino acid, in normal closure of the neural tube. We hypothesized that women who had higher dietary intakes of methionine would be at lower risk for neural tube defect (NTD)-affected pregnancies. Data were derived from a population-based case-control study of fetuses and liveborn infants with NTDs among a 1989-1991 California birth cohort. Interviews, which included a 100-item food frequency questionnaire, were conducted with mothers of 424 NTD cases and 440 nonmalformed controls. Risk for having an NTD-affected pregnancy was estimated according to quartiles (established from intakes among control mothers) of average daily maternal dietary intake of methionine in the 3 months before conception. We observed an approximately 30-40% reduction in NTD-affected pregnancies among women whose average daily dietary intake of methionine was above the lowest quartile of intake (> 1,341.86 mg/ day). These reductions in NTD risk were observed for both anencephaly and spina bifida; remained after adjustment for maternal race/ethnicity and education; and were observed irrespective of maternal level of folate intake. Although we were unable to establish whether the observed reductions in NTD risk were attributable to maternal periconceptional methionine intake or to another highly correlated nutrient, these data add to the growing body of evidence that maternal diet plays a role in neural tube closure.

Parental recreational drug use and risk for neural tube defects.

The authors investigated whether maternal or paternal periconceptional use of recreational drugs increased the risk of having neural tube defect (NTD)-affected pregnancies using a population-based case-control study of fetuses and liveborn infants with NTDs among 1989-1991 California births. Face-to-face interviews were conducted with mothers of 538 (88% of eligible) NTD cases and 539 (88%) nonmalformed controls, usually within 5 months of delivery. Periconceptional maternal use of cocaine (odds ratio (OR) = 0.74, 95% confidence interval (CI) 0.40-1.4), amphetamines/speed (OR = 0.68, 95% CI 0.39-1.2), or marijuana (OR = 0.64, 95% CI 0.43-0.95) or preconceptional use of alcohol as < 1 drink/day (OR = 0.80, 95% CI 0.62-1.0) or > or = 1 drink/day (OR = 0.69, 95% CI 0.42-1.2) or of cigarettes as < 1 pack/day (OR = 0.90, 95% CI 0.65-1.2) or > or = 1 pack/day (OR = 0.59, 95% CI 0.36-0.96) did not increase the risk for delivering NTD-affected offspring. Risks were not substantially altered after adjustment for maternal age, race/ethnicity, vitamin use, education, and household income. Increased NTD risk was also not generally associated with paternal drug use. The authors could not discern whether the decreased risks observed for these maternal exposures reflected a true association or were due to reporting bias, a disproportionate number of drug-exposed NTD cases among spontaneous abortuses that could not be ascertained, or some other bias.

Impact of prenatal diagnosis and elective termination on prevalence and risk estimates of neural tube defects in California, 1989-1991.

The authors examined the impact of prenatal diagnosis and elective termination of neural tube defect (NTD)-affected pregnancies on NTD prevalence and risk estimates. Prevalence data were actively ascertained and were derived from a population-based 1989-1991 cohort of California births. Included were 664 singleton infants/fetuses with an NTD. The birth prevalence (livebirths and stillbirths only) was 48.4% of the total prevalence (including elective terminations) for anencephaly and 70.2% for spina bifida. The authors also used in-person interview data from mothers of 538 of the ascertained NTD cases and mothers of 539 randomly selected nonmalformed control infants to examine maternal/infant characteristics. Compared with women who delivered liveborn/stillborn infants with an NTD, women who electively terminated NTD-affected pregnancies were disproportionately white, were more highly educated, had higher incomes, and used vitamins containing folic acid more often. For factors associated with elective terminations, risk estimates appeared biased when only liveborn and stillborn infants were included among cases compared with analyses in which all clinically recognized NTD-affected pregnancies were included.

Risk of neural tube defect-affected pregnancies among obese women.

OBJECTIVE: To investigate the risk for neural tube defect (NTD)-affected pregnancies among obese women (ie, women with a body mass index [BMI] > 29kg/m2) compared with women of average prepregnancy weight. DESIGN: Population-based case-control study. SETTING: All hospitals in 55 of 58 counties in California. PARTICIPANTS: In-person interviews were conducted with mothers of 538 (88% of eligible) NTD cases (including fetuses and infants electively terminated, stillborn, or born alive) and with mothers of 539 nonmalformed controls (88%) within an average of 5 months from the term delivery date. MAIN OUTCOME MEASURES: The risk of an NTD-affected pregnancy among obese women. RESULTS: Compared with women whose BMI was less than or equal to 29 kg/m2, an increased risk for NTD-affected pregnancy was observed among obese women (odds ratio, 1.9; 95% confidence interval, 1.3 to 2.9). The increased risk was not attributable to maternal nonuse of a vitamin containing folic acid, diabetes, use of diet pills, lower dietary folate intake, or an NTD-pregnancy history. Adjustment for maternal age, education, gravidity, use of vitamins, and use of alcohol did not change the odds ratio. The risk associated with maternal obesity was greater for spina bifida and for other less prevalent NTDs than for anencephaly. CONCLUSION: Because as many as 10% of women may be obese periconceptionally, the observed twofold increased risk is relevant to the population burden of NTDs.

Surveillance for anencephaly and spina bifida and the impact of prenatal diagnosis--United States, 1985-1994.

PROBLEM/CONDITION: The reported prevalence of anencephaly and spina bifida in the United States has steadily declined since the late 1960s. During this time, the ability to diagnose these defects prenatally has progressed rapidly. Many U.S. birth defects surveillance systems ascertain defects only among live-born infants or among infants and fetuses beyond a certain gestational age, thus excluding defects among pregnancies prenatally diagnosed as being affected by a neural tube defect (NTD) and electively terminated before the gestational age limit. The impact of prenatal diagnosis and subsequent pregnancy termination on the reported prevalence of anencephaly and spina bifida in the United States has not been well established. However, assessment of this impact is crucial to the use of surveillance data to monitor trends in the occurrence of NTDs and the effectiveness of interventions for these defects (e.g., increased consumption of folic acid). REPORTING PERIOD: This report presents data from birth defects surveillance systems in six states over different time periods: Arkansas, 1985-1989; California, 1989-1991; Georgia, 1990-1991; Hawaii, 1988-1994; Iowa, 1985-1990; and South Carolina, 1992-1993. DESCRIPTION OF SYSTEMS: Population-based data about a) live-born and stillborn infants with anencephaly and spina bifida and b) pregnancies electively terminated after prenatal diagnosis of these defects were analyzed from the Arkansas Reproductive Health Monitoring System; the California Birth Defects Monitoring Program; CDC's Metropolitan Atlanta Congenital Defects Program; the Iowa Birth Defects Registry, the University of Iowa, and the Iowa Department of Public Health; and the Greenwood Genetic Center in South Carolina. Data also were analyzed from the Hawaii Birth Defects Monitoring Program, which includes data for some women who were not residents of the state. The systems differed in the size and racial/ethnic composition of the populations studied, the surveillance methods used, the completeness of ascertainment, and the availability and utilization of prenatal testing and pregnancy termination. RESULTS AND INTERPRETATION: Among all pregnancies ascertained in which the infant or fetus had anencephaly or spina bifida, the percentages that were electively terminated ranged from 9% in Arkansas to 42% in Atlanta and Hawaii, with a corresponding increase in the adjusted prevalence of these defects compared with the prevalence at birth. In each system, pregnancies associated with anencephaly were terminated more frequently than were those associated with spina bifida. These data indicate that the impact of prenatal diagnosis and subsequent pregnancy termination on the prevalence at birth of anencephaly and spina bifida differs among geographic areas and populations. Comprehensive surveillance for these defects requires inclusion of pregnancies that are prenatally diagnosed and then terminated. ACTIONS TAKEN: CDC will use these data to promote the inclusion of prenatally diagnosed and terminated pregnancies in estimates of the prevalence of anencephaly and spina bifida generated by birth defects surveillance programs in the United States. Including such pregnancies is crucial to the ability of these programs to monitor trends accurately and to establish the effectiveness of interventions, including the use of folic acid, for these defects.

Periconceptional vitamin use, dietary folate, and the occurrence of neural tube defects.

With a case-control study, we investigated whether periconceptional intake of supplemental or dietary folate reduced the risk of having a neural tube defect (NTD)-affected pregnancy. Mothers of 549 (88% of eligible) cases and 540 (88%) controls were interviewed in person about vitamin supplements used in either the 3 months before or the 3 months after conception and also about usual diet in the 3 months before conception. Women with any use of a folic acid-containing vitamin in the 3 months before conception had a lower risk of having an NTD-affected pregnancy [odds ratio (OR) = 0.65; 95% confidence interval (CI) = 0.45-0.94]. ORs were similar for 3 levels (< 0.4, 0.4-0.9, and > 0.9 mg per day) of average daily intake of folic acid. Any level of use in the first 3 months after conception resulted in a lowered risk as well (OR = 0.60; 95% CI = 0.46-0.79). Reduced risks were less marked for Hispanics and were not observed among women who graduated from college. Modest reduced risks were noted among non-vitamin users whose estimated daily dietary intake of folate was more than 0.227 mg. We observed decreasing risk with increasing folate intake from combined dietary sources and vitamin supplements. A reduction in NTD risk associated with folate intake is consistent with other studies; however, the reduced risk may be particular to subsets of the population, primarily non-Hispanic women and women whose education does not exceed high school.

A population-based study of gastroschisis: demographic, pregnancy, and lifestyle risk factors.

Gastroschisis, an abdominal wall defect, most often occurs in infants of young mothers. To identify risk factors for gastroschisis, we conducted a case-control study in the population surveyed by the California Birth Defects Monitoring Program (CBDMP). From structured questionnaire data, we compared sociodemographic, reproductive, and lifestyle factors for 110 mothers of infants with gastroschisis with those for 220 age-matched mothers of normal infants. Univariate matched-pair analysis showed significant associations of gastroschisis with mother's education, yearly family income, marital status, a history of mother's mother smoking, mother's father's absence from home during the mother's youth, more than one elective abortion, a short interval between menarche and first pregnancy, siblings from different fathers, and use of either a recreational drug (either cocaine, amphetamine, marijuana, or LSD), alcohol, or tobacco during the trimester preceding pregnancy. For cocaine, amphetamine, and marijuana, use of more than one drug showed a stronger association than single drug use. The association was stronger if both parents used drugs. Although many variables were correlated, odds ratios (OR) were significant (95% confidence intervals) in multivariate conditional logistic analysis for: yearly family income < $10,000 [OR = 4.34 (1.54, 12.22)] or $10,000-$49,999 [OR = 3.93 (1.43, 10.80)]; mother's mother's smoking status not known [OR = 3.99 (1.66, 9.56)]; mother's father's absence from home during her youth [OR = 3.11 (1.14, 8.46)]; and drug use by mother [OR = 2.21 (1.21, 4.03)], father [OR = 1.66 (1.02, 2.69)], or both [OR = 3.05 (1.48, 6.28)]. The best predictive model explained 32% of the deviance. Young, socially disadvantaged women with a history of substance use were at highest risk for a child with a gastroschisis.

Cerebral palsy in four northern California counties, births 1983 through 1985.

To examine the impact of demographic shifts and changes in perinatal medicine on the distribution of cerebral palsy (CP), we investigated characteristics of affected children in a large, recent population-based American cohort study. Children with moderate or severe congenital CP born in four northern California counties in 1983 through 1985 and surviving to age 3 years were identified through records of state service agencies and clinical examination or record review by a single physician. We compared information from birth certificates for 192 children with CP and 155,636 survivors without CP born in those counties in the same period. Children with birth weights < 2500 gm contributed 47.4% of the CP in this population; those < 1000 gm, who were 0.20% of survivors, contributed 7.8%. Children with birth weights of 4000 to 4500 gm were at lowest risk. Among singletons, prevalence of CP was lowest (0.92/1000) in infants born to women aged 25 to 34 years, and was significantly higher in children whose mothers were 40 years or older (3.3/1000), especially if they were high in parity (6.9/1000). Children of teenaged mothers or fathers were at somewhat increased risk of CP. Early gestational age at birth was also an important independent risk factor. Prevalence of CP was slightly higher in black children, apparently related to a greater tendency to be low in birth weight. The time during pregnancy when prenatal care began was similar for children with CP and for the general population. For the 95% of children born weighing > or = 2500 gm, birth in a hospital lacking a special care nursery was not associated with increased risk of CP. Almost 8% of CP occurred in children born weighing < 1000 gm, a group that produced few survivors in the past; 28.1% occurred in children born weighing < 1500 gm. Neither early initiation of prenatal care nor, for that large majority of neonates weighing > 1500 gm, delivery at a hospital with specialized facilities was associated with a lower risk of CP.