Maternal multivitamin use and orofacial clefts in offspring.

BACKGROUND: Cleft lip with or without cleft palate (CLP) and cleft palate alone (CP) affect approximately 1 in 1000 infants and 1 in 2,500 infants, respectively. Studies of the relation between orofacial clefts and multivitamins or folic acid have been inconsistent. METHODS: We used data from a population-based case-control study involving 309 nonsyndromic cleft-affected births (222 with CLP, 87 with CP) and 3,029 control births from 1968 to 1980 to evaluate the relation between regular multivitamin use and the birth prevalence of orofacial clefts. RESULTS: We found a 48% risk reduction for CLP (odds ratio = 0.52, 95% confidence interval = 0.34-0.80) among mothers who used multivitamins during the periconceptional period or who started multivitamin use during the first postconceptional month, after controlling for several covariates. The risk reduction for CP was less than those for CLP (odds ratio = 0.81, 95% confidence interval = 0.44-1.52); however, a small number of CP cases limited interpretation. No risk reductions for CLP or CP were found for women who began multivitamin use in the second or third month after conception. CONCLUSIONS: The magnitude of the risk reduction in our study is comparable to those of other recent studies; our study does not support the contention that only large dosages of folic acid are needed to prevent orofacial clefts. More studies are needed to test the effects of multivitamins and varying dosages of folic acid on the recurrence and/or occurrence of orofacial clefts to provide information needed to determine possible prevention strategies. Published 2001 Wiley-Liss, Inc.

Folic acid and preconceptional care.

If all women capable of becoming pregnant consumed 400 µg (0.4 mg) of the B vitamin folic acid daily before conception and during the first trimester, the annual number of neural-tube birth defect (NTD)-affected pregnancies in this country could be reduced by 50% to 70%. Despite this important relationship, most women are not aware that folic acid prevents NTDs, and folic acid supplementation rates remain low. If folic acid consumption is to succeed as a public health intervention on a societal scale, physicians who care for reproductive-age women must become informed about the folic acid-NTD prevention linkage. Next, they must be encouraged to counsel patients about the need to consume sufficient folic acid before conception. Studies reveal that few physicians have adequate knowledge of the appropriate timing and dosage of folic acid supplementation. Studies also show that women are more likely to get important folic acid information not from their physicians but from other sources. This article provides information about ways in which physicians can improve their folic acid knowledge and education practices.

Multivitamin use and mortality in a large prospective study.

To determine the relation between multivitamin use and death from heart disease, cerebrovascular disease, and cancer, the authors examined a prospective cohort of 1,063,023 adult Americans in 1982-1989 and compared the mortality of users of multivitamins alone; vitamin A, C, or E alone; and multivitamin and vitamin A, C, or E in combination with that of vitamin nonusers by using multivariate Cox proportional hazard models. Multivitamin users had heart disease and cerebrovascular disease mortality risks similar to those of nonusers, whereas combination users had mortality risks that were 15% lower than those of nonusers. Multivitamin and combination use had minimal effect on cancer mortality overall, although mortality from all cancers combined was increased among male current smokers who used multivitamins alone (relative risk (RR) = 1.13, 95% confidence interval (CI): 1.05, 1.23) or in combination with vitamin A, C, or E (RR = 1.16, 95% CI: 1.06, 1.26), but decreased in male combination users who had never (RR = 0.86, 95% CI: 0.74, 0.99) or had formerly (RR = 0.90, 95% CI: 0.82, 0.98) smoked. No such associations were seen in women. These observational data provide limited support for the hypothesis that multivitamin use in combination with vitamin A, C, or E may reduce heart disease and cardiovascular disease mortality, but add to concerns raised by randomized studies that some vitamin supplements may adversely affect male smokers.

Occurrence of congenital heart defects in relation to maternal mulitivitamin use.

The purpose of this study was to assess the relation between maternal multivitamin use and risk for cardiac defects in the offspring, using a population-based approach. The Atlanta Birth Defects Case-Control study is a population-based case-control study of infants born between 1968 and 1980 to mothers residing in metropolitan Atlanta, Georgia. The 958 case infants with nonsyndromic cardiac defects were actively ascertained from multiple sources. The 3,029 infants without birth defects (control infants) were selected from birth certificates by stratified random sampling. Periconceptional multivitamin use, defined as reported regular use of multivitamins from 3 months before pregnancy through the first 3 months of pregnancy, was contrasted with no use during the same time period. Periconceptional multivitamin use was associated with a reduced risk for nonsyndromic cardiac defects in the offspring (odds ratio (OR) = 0.76; 95% confidence interval (Cl): 0.60, 0.97). The risk reduction was strongest for outflow tract defects (OR = 0.46; 95% Cl 0.24, 0.86) and ventricular septal defects (OR = 0.61; 95% Cl: 0.38, 0.99). No risk reduction was evident when multivitamin use was begun after the first month of pregnancy. If these associations are causal, the results suggest that approximately one in four major cardiac defects could be prevented by periconceptional multivitamin use.

Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention.

BACKGROUND AND METHODS: Periconceptional administration of folic acid can reduce a woman's risk of having a fetus or infant with a neural-tube defect. As part of a public health campaign conducted from 1993 to 1995 in an area of China with high rates of neural-tube defects (the northern region) and one with low rates (the southern region), we evaluated the outcomes of pregnancy in women who were asked to take a pill containing 400 microg of folic acid alone daily from the time of their premarital examination until the end of their first trimester of pregnancy. RESULTS: Among the fetuses or infants of 130,142 women who took folic acid at any time before or during pregnancy and 117,689 women who had not taken folic acid, we identified 102 and 173, respectively, with neural-tube defects. Among the fetuses or infants of women who registered before their last menstrual period and who did not take any folic acid, the rates of neural-tube defects were 4.8 per 1000 pregnancies of at least 20 weeks' gestation in the northern region and 1.0 per 1000 in the southern region. Among the fetuses or infants of the women with periconceptional use of folic acid, the rates were 1.0 per 1000 in the northern region and 0.6 per 1000 in the southern region. The greatest reduction in risk occurred among the fetuses or infants of a subgroup of women in the northern region with periconceptional use who took folic acid pills more than 80 percent of the time (reduction in risk, 85 percent as compared with the fetuses or infants of women who registered before their last menstrual period and who took no folic acid; 95 percent confidence interval, 62 to 94 percent) [corrected]. In the southern region the reduction in risk among the fetuses or infants of women with periconceptional use of folic acid was also significant (reduction in risk, 41 percent; 95 percent confidence interval, 3 to 64 percent). CONCLUSIONS: Periconceptional intake of 400 microg of folic acid daily can reduce the risk of neural-tube defects in areas with high rates of these defects and in areas with low rates.

Elevated rates of severe neural tube defects in a high-prevalence area in northern China.

In the northern provinces of China, the birth prevalence rate of neural tube defects (NTDs) is among the highest in the world-at about 6 per 1,000 births in rural areas. A unique population-based birth defects surveillance system in which photographs are taken of infants with selected external birth defects was implemented in two provinces in northern China and two provinces in southern China where NTD rates approximate those in the United States. In the period from March 1992 through December 1993, 660 infants with NTDs were identified by the surveillance project from a birth cohort of 251,567. We compared data from the two surveillance areas in China with data from a low-prevalence area in the United States to determine if the pattern of NTD types differs. Based on birth prevalence rates of NTDs from the Metropolitan Atlanta Congenital Defects Program, the observed to expected ratios for two types of NTDs are markedly increased at 80.8 for craniorachischisis and 25.0 for iniencephaly. Rates of these two NTDs in the southern provinces are increased to a lesser degree with observed to expected ratios of 7.1 for craniorachischisis and 2.7 for iniencephaly. The pattern of NTDs in northern China shows an increase in types that are rare in low-prevalence areas such as metropolitan Atlanta. Increased awareness of varying patterns of NTDs in different populations may have important implications for identifying etiologic and pathogenetic mechanisms of NTDs.

Does periconceptional multivitamin use reduce the risk for limb deficiency in offspring?

There is accumulating evidence that periconceptional multivitamin use may prevent the occurrence of some birth defects other than neural tube defects. Using data from the population-based Atlanta Birth Defects Case-Control Study, we investigated the possible association between periconceptional multivitamin use and the occurrence of limb deficiency. We examined the periconceptional use of multivitamins among mothers of 117 babies with nonsyndromic limb deficiency who were liveborn or stillborn to residents of metropolitan Atlanta from 1968 to 1980 and among mothers of 3,029 control babies born without birth defects who were randomly selected through birth certificates. We found that children whose mothers were periconceptional multivitamin users had a lower risk of having a limb deficiency [odds ratio (OR) = 0.47; 95% confidence interval (CI) = 0.23-0.97]. This protective effect, however, was mostly seen for transverse limb deficiency (OR = 0.30; 95% CI = 0.07-1.32) and not for longitudinal deficiency (including preaxial and postaxial deficiencies; OR = 1.03; 95% CI = 0.17-4.30). Adjustment for potential confounding factors did not change these findings. We found a trend of decreasing risk for all transverse limb deficiencies with earlier vitamin use. These data indicate that mothers' periconceptional multivitamin use may reduce the risk for some types of limb deficiency among their offspring. In addition, because we did not find the protective effect for all types of limb deficiency, the data may also indicate causal heterogeneity of limb deficiencies.

Periconceptional multivitamin use and the occurrence of conotruncal heart defects: results from a population-based, case-control study.

OBJECTIVE: The preventive efficacy of the periconceptional use of multivitamins is well established for neural tube defects, much less so for other birth defects. We conducted a population-based, case-control study to assess the effects of multivitamin use on the risk for conotruncal defects, a group of severe heart defects that includes transposition of the great arteries, tetralogy of Fallot, and truncus arteriosus. METHODS: From the population-based Atlanta Birth Defects Case-Control Study, we identified 158 case infants with conotruncal defects and 3026 unaffected, randomly chosen control infants, born from 1968 through 1980 to mothers residing in metropolitan Atlanta. Periconceptional multivitamin use was defined as reported regular use from 3 months before conception through the third month of pregnancy. We present the results of the crude analysis, because the multivariate model yielded essentially identical results. RESULTS: Mothers who reported periconceptional multivitamin use had a 43% lower risk of having infants with conotruncal defects (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.33 to 1.00) than did mothers who reported no use. The estimated relative risk was lowest for isolated conotruncal defects (OR, 0.41; 95% CI, 0.20 to 0.84) compared with those associated with noncardiac defects (OR, 0.91; 95% CI, 0.33 to 2.52) or a recognized syndrome (OR, 1.82; 95% CI, 0.31 to 10.67). Among anatomic subgroups of defects, transposition of the great arteries showed the greatest reduction in risk (OR, 0.36; 95% CI, 0.15 to 0.89). CONCLUSIONS: Periconceptional multivitamin use is associated with a reduced risk for conotruncal defects. These findings could have major implications for the prevention of these birth defects.

Is maternal obesity a risk factor for anencephaly and spina bifida?

To determine whether the risk of having an infant with anencephaly or spina bifida is greater among obese women than among average-weight women, we compared 307 Atlanta-area women who gave birth to a liveborn or stillborn infant with anencephaly or spina bifida (case group) with 2,755 Atlanta-area women who gave birth to an infant without birth defects (control group). The infants of control women were randomly selected from birth certificates and frequency-matched to the case group by race, birth hospital, and birth period from 1968 through 1980. After adjusting for maternal age, education, smoking status, alcohol use, chronic illness, and vitamin use, we found that, compared with average-weight women, obese women (pregravid body mass index greater than 29) had almost twice the risk of having an infant with spina bifida or anencephaly (odds ratio = 1.9; 95% confidence limits = 1.1, 3.4). A woman's risk increased with her body mass index: adjusted odds ratios ranged from 0.6 (95% confidence limits = 0.3, 2.1) for very underweight women to 1.9 for obese women.

The surveillance of birth defects: the usefulness of the revised US standard birth certificate.

To assess the sensitivity and positive predictive value of birth defects reported on the 1989 revision of the US Standard Birth Certificate, a population of 76,862 Atlanta-area births during 1989 and 1990 was used as the basis for comparing 771 birth certificates that reported birth defects with 2428 live-born infant records in a birth defects registry that uses multiple sources of case ascertainment. Only 14% of birth defects in the registry records were reported on birth certificates. After the analysis was restricted to defects recognizable at birth, the sensitivity and positive predictive value of the birth certificates were 28% and 77%, respectively. Birth certificates underestimate birth defect rates and should be used cautiously for birth defect surveillance and epidemiological studies.

Does periconceptional multivitamin use reduce the risk of neural tube defects associated with other birth defects? data from two population-based case-control studies.

The role of periconceptional folic acid in the prevention of neural tube defects (NTDs) is well established. However, it is not clear whether a protective effect exists for the subset of nonsyndromic NTD with other "unrelated" major structural birth defects (NTD-multiples). This question is important to investigate because of shared pathogenetic mechanisms between NTD and other types of birth defects, and because of the epidemiologic differences that have been shown between NTD-multiples and NTD-singles. We analyzed data from two population-based case-control studies of NTDs, Atlanta 1968-1980, and California 1989-1991, to assess whether periconceptional multivitamin use reduces the risk of NTD-multiples. Maternal vitamin histories were assessed for 47 and 65 NTD-multiples cases and 3,029 and 539 control babies in Atlanta, and California, respectively. There was a substantial risk reduction associated with periconceptional multivitamin use (-3 to +3 months) for NTD-multiples (pooled odds ratio = 0.36, 95% C.I. 0.18-0.72) that persisted after adjustment for maternal race/ethnicity and education. Also, no specific types of NTDs or NTDs with specific defects explained the risk reduction with vitamin use. These data suggest that multivitamins reduce the risk of nonsyndromic NTD cases associated with other major birth defects. The implication of this finding for the role of vitamins in the prevention of non-NTD birth defects should be further explored.

Prevention of folic acid-preventable spina bifida and anencephaly.

The results of the British Medical Research Council's randomized controlled trial proved that folic acid can prevent spina bifida and anencephaly. The trial provided critical scientific data upon which to base public health policy for preventing folic acid-preventable spina bifida and anencephaly. Within weeks of publication of the results, the Centers for Disease Control and Prevention in the US developed and issued guidelines for women who had had a pregnancy affected by spina bifida or anencephaly. A year later, the US Public Health Service issued the recommendation that all women of child-bearing age who are capable of becoming pregnant should consume 0.4 mg of folic acid per day. The Public Health Service needed a year to make inferential judgements about dose, target groups, safety, timing of ingestion, and existing and proposed vitamin and drug policies and regulations. Current policy discussions concern whether to permit manufacturers of vitamins or food products to claim that folic acid will prevent folic acid-preventable spina bifida and anencephaly and whether to allow a food staple to be fortified with folic acid.