Joseph Mulinare

Trends in the postfortification prevalence of spina bifida and anencephaly in the United States

BACKGROUND The prevalence of NTDs in the US declined significantly after mandatory folic acid fortification; however, it is not known if the prevalence of NTDs has continued to decrease in recent years relative to the period immediately following the fortification mandate. METHODS Population-based data from 21 birth defects surveillance systems were used to examine trends in the birth prevalence of spina bifida and anencephaly during 1999-2000, 2001-2002, and 2003-2004. Prevalence data were stratified by non-Hispanic White, non-Hispanic Black, and Hispanic race or ethnicity. Prevalence ratios were calculated by dividing the birth prevalences during the later time periods (2001-2002 and 2003-2004) by the birth prevalences during 1999-2000. RESULTS During 1999-2004, 3,311 cases of spina bifida and 2,116 cases of anencephaly were reported. Hispanic infants had the highest prevalences of NTDs for all years. For all infants, the combined birth prevalences of spina bifida and anencephaly decreased 10% from the 1999-2000 period to the 2003-2004 period. The decline in spina bifida (3%) was not significant; however the decline in anencephaly (20%) was statistically significant. CONCLUSIONS While the prevalences of spina bifida and anencephaly in the United States have declined since folic acid fortification in the food supply began, these data suggest that reductions in the prevalence of anencephaly continued during 2001-2004 and that racial and ethnic and other disparities remain.

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.

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.

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.

Is maternal obesity a risk factor for anencephaly and spina bifida

&NA; 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 Atlantaarea 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 womans 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.

Do multivitamin or folic acid supplements reduce the risk for congenital heart defects? Evidence and gaps.

Congenital heart defects are among the most common congenital anomalies and are the leading cause of infant death due to congenital anomalies. Except for a few known measures, effective primary prevention is not yet feasible for most heart anomalies. Recent reports have associated the use of multivitamin supplements around the time of conception and during early pregnancy with a reduced risk for heart defects in the offspring. We review and discuss the evidence and suggest a framework for further investigation in this area. Published 2003 Wiley‐Liss, Inc.

Fortification of flour with folic acid

Background After randomized, controlled trials established that consumption of folic acid before pregnancy and during the early weeks of gestation reduces the risk of a neural tube defect (NTD)-affected pregnancy, the United States Public Health Service recommended in 1992 that all women capable of becoming pregnant consume 400 μg folic acid daily. In 1998, folic acid fortification of all enriched cereal grain product flour was fully implemented in the United States and Canada. Objective To provide guidance on national fortification of wheat and maize flours to prevent 50 to 70% of the estimated 300,000 NTD-affected pregnancies worldwide. Methods An expert workgroup reviewed the latest evidence of effectiveness of folic acid flour fortification and the safety of folic acid. Results Recent estimates show that in the United States and Canada, the additional intake of about 100 to 150 μg/day of folic acid through food fortification has been effective in reducing the prevalence of NTDs at birth and increasing blood folate concentrations in both countries. Most potential adverse effects associated with folic acid are associated with extra supplement use not mandatory fortification. Fortification of wheat flour has a proven record of prevention in other developed countries. In 2009, 51 countries had regulations written for mandatory wheat flour fortification programs that included folic acid. Conclusions NTDs remain an important cause of perinatal mortality and infantile paralysis worldwide. Mandatory fortification of flour with folic acid has proved to be one of the most successful public health interventions in reducing the prevalence of NTD-affected pregnancies. Most developing countries have few, if any, common sources of folic acid, unlike many developed countries, which have folic acid available from ready-to-eat cereals and supplements. Expanding the number of developed and developing countries with folic acid flour fortification has tremendous potential to safely eliminate most folic acid-preventable NTDs.

Reevaluating the Benefits of Folic Acid Fortification in the United States: Economic Analysis, Regulation, and Public Health

Before a 1996 US regulation requiring fortification of enriched cereal-grain products with folic acid, 3 economic evaluations projected net economic benefits or cost savings of folic acid fortification resulting from the prevention of pregnancies affected by a neural tube defect. Because the observed decline in neural tube defect rates is greater than was forecast before fortification, the economic gains are correspondingly larger. Applying both cost-benefit and cost-effectiveness analytic techniques, we estimated that folic acid fortification is associated with annual economic benefit of 312 million dollars to 425 million dollars. The cost savings (net reduction in direct costs) were estimated to be in the range of 88 million dollars to 145 million dollars per year.

Maternal fever, multivitamin use, and selected Birth defects: Evidence of interaction?

Background. Multivitamin use has been associated with lower risks for some birth defects. We evaluated whether multivitamin use modified birth defect risks associated with febrile illness, a common and possibly teratogenic exposure. Methods. From the population-based Atlanta Birth Defects Case-Control Study (1968–1980) we selected seven defects (neural tube defects, cleft lip and palate, cardiac outflow tract defects, ventricular septal defects, atrial septal defects, omphalocele, and limb deficiencies) because of their inverse relation with multivitamin supplement use documented in previous analyses. We defined four exposure categories from combinations of multivitamin use (periconceptional use compared with no use) and febrile illness (early pregnancy compared with no illness). The reference category was no multivitamin use and no illness. Results. Febrile illness with no multivitamin use was associated with generally increased risk for the seven defects and the combined group (odds ratio = 2.1, 1.7, 1.5, 1.9, 2.9, 4.4, 3.3, and 2.3, respectively). With multivitamin use, however, the risk estimates associated with febrile illness were generally lower (odds ratio = 0.6, 1.1, 0.0, 1.5, 0.0, 0.8, 0.0, and 0.8, respectively). Some of the associated 95% confidence intervals included one. Conclusions. The pattern of findings suggests that multivitamin use might decrease the risk associated with febrile illness.

Tobacco smoke exposure and decreased serum and red blood cell folate levels: data from the Third National Health and Nutrition Examination Survey

The aim of this cross-sectional study was to determine the effects of smoke exposure on serum and red blood cell folate levels. Data collected as part of the Third National Health and Nutrition Examination Survey were analyzed. Serum and red blood cell folate levels were measured in active smokers and nonsmokers with high, moderate, and low exposure to environmental tobacco smoke. After adjusting for dietary intake of folate and other covariates, we found that both smokers and nonsmokers with high smoke exposure had lower red blood cell folate levels than did nonsmokers with low smoke exposure (-86 nmol/l [95% confidence interval, CI, -101 to -71 nmol/l] for smokers; -50 nmol/l [95% CI -69 to -31 nmol/l] for nonsmokers with high smoke exposure, compared with nonsmokers with low smoke exposure). Similarly, after adjustment of dietary intake of folate and other covariates, the log serum folate level also was decreased (-0.29 log nmol/l [95% CI -0.33 to -0.25 log nmol/l] for smokers; -0.16 log nmol/l [95% CI -0.20 to -0.12 log nmol/l] for nonsmokers with high smoke exposure, compared with nonsmokers with low smoke exposure). Tobacco smoke exposure is associated with decreased folate levels, which may be a mechanism for some of the health effects of active and passive smoking.