Birth defects in Arkansas: Is folic acid fortification making a difference?

BACKGROUND: Since 1998, fortification of grain products with folic acid has been mandated in the United States, in an effort to reduce the prevalence of neural tube defects (NTDs). Published reports have shown a reduction in the prevalence of spina bifida since fortification was mandated, but no published studies have reported a reduction in birth defects, other than NTDs, that are postulated to be associated with folic acid deficiency. This study was performed to determine if fortification has reduced the prevalence of NTDs and other birth defects in Arkansas. METHODS: Using data from the Arkansas Reproductive Health Monitoring System, prevalences were computed for thirteen specific birth defects with prior evidence supporting a protective effect of folic acid or multivitamins. Prevalences were calculated using data for live births to Arkansas residents for 1993-2000. Exposure to folic acid fortification was classified by birth year as "pre-fortification" (1993-1995), "transition" (1996-1998) or "post-fortification" (1999-2000). Logistic regression analysis was used to compute crude and adjusted prevalence odds ratios comparing the identified time periods. RESULTS: Prevalences decreased between the pre- and post-fortification periods for spina bifida, orofacial clefts, limb reduction defects, omphalocele, and Down syndrome, but only the decrease in spina bifida was statistically significant (prevalence odds ratio 0.56; 95% confidence interval, 0.37, 0.83). CONCLUSION: In Arkansas, the prevalence of spina bifida has decreased since folic acid fortification of foods was implemented. Similar studies by other birth defects surveillance systems are needed to confirm a preventive effect of fortification for malformations other than spina bifida.     

Prevalence of spina bifida and anencephaly during the transition to mandatory folic acid fortification in the United States

BACKGROUND: In 1992, the United States Public Health Service recommended that all women of childbearing age consume 400 microg of folic acid daily. The Food and Drug Administration authorized the addition of synthetic folic acid to grain products in March 1996 with mandatory compliance by January 1998. The impact of these public health policies on the prevalence of neural tube defects needs to be evaluated. We sought to determine the prevalences of spina bifida and anencephaly during the transition to mandatory folic acid fortification. METHODS: Twenty-four population-based surveillance systems were used to identify 5,630 cases of spina bifida and anencephaly from 1995-99. Cases were divided into three temporal categories depending on whether neural tube development occurred before folic acid fortification (January 1995 to December 1996), during optional fortification (January 1997 to September 1998), or during mandatory fortification (October 1998 to December 1999). Prevalences for each defect were calculated for each time period. Data were also stratified by programs that did and did not ascertain prenatally diagnosed cases. RESULTS: The prevalence of spina bifida decreased 31% (prevalence ratio [PR] = 0.69, 95% confidence interval [CI] = 0.63-0.74) from the pre- to the mandatory fortification period and the prevalence of anencephaly decreased 16% (PR = 0.84, 95% CI = 0.75-0.95). Stratification by prenatal ascertainment did not alter results for spina bifida but did impact anencephaly trends. CONCLUSIONS: The decline in the prevalence of spina bifida was temporally associated with folic acid fortification of US grain supplies. The temporal association between fortification and the prevalence of anencephaly is unclear.     

Anencephaly and spina bifida among Hispanics: Maternal,sociodemographic, and acculturation factors in the National Birth Defects Prevention Study

BACKGROUND : We used data from the multisite National Birth Defects Prevention Study for expected delivery dates from October 1997 through 2003, to determine whether the increased risk in anencephaly and spina bifida (neural tube defects (NTDs)) in Hispanics was explained by selected sociodemographic, acculturation, and other maternal characteristics. METHODS : For each type of defect, we examined the association with selected maternal characteristics stratified by race/ethnicity and the association with Hispanic parents' acculturation level, relative to non‐Hispanic whites. We used logistic regression and calculated crude odds ratios (ORs) and their 95% confidence intervals (CIs). RESULTS : Hispanic mothers who reported the highest level of income were 80% less likely to deliver babies with spina bifida. In addition, highly educated Hispanic and white mothers had 76 and 35% lower risk, respectively. Other factors showing differing effects for spina bifida in Hispanics included maternal age, parity, and gestational diabetes. For spina bifida there was no significant elevated risk for U.S.–born Hispanics, relative to whites, but for anencephaly, corresponding ORs ranged from 1.9 to 2.3. The highest risk for spina bifida was observed for recent Hispanic immigrant parents from Mexico or Central America residing in the United States <5 years (OR = 3.28, 95% CI = 1.46–7.37). CONCLUSIONS : Less acculturated Hispanic parents seemed to be at highest risk of NTDs. For anencephaly, U.S.–born and English‐speaking Hispanic parents were also at increased risk. Finally, from an etiologic standpoint, spina bifida and anencephaly appeared to be etiologically heterogeneous from these analyses. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

Extremely high prevalence of neural tube defects in a 4-county area in Shanxi Province, China

BACKGROUND: In the past, northern China's Shanxi Province has reported the highest incidence of neural tube defects (NTDs) in the world. However, little is known about the epidemiology of NTDs in this area in recent years. METHODS: Data were collected from a population-based birth defects surveillance system in 4 counties that captures information on all live births, stillbirths of at least 20 weeks' gestation, and pregnancy terminations at any gestational age resulting from prenatal diagnosis of a birth defect. We also surveyed mothers of NTD case patients to determine their use of folic acid before and during early pregnancy. RESULTS: During 2003, 160 NTD cases were identified among 11,534 births (NTD birth prevalence = 138.7/10,000 births). The rates of anencephaly, spina bifida and encephalocele were 65.9, 58.1, and 14.7 per 10,000, respectively, and a female predominance was observed among anencephaly cases (male-to-female relative risk [RR], 0.49; 95% confidence interval [CI], 0.30-0.79), but not among spina bifida (RR, 0.90; 95% CI, 0.55-1.45) and encephalocele (RR, 1.03; 95% CI, 0.40-2.69) cases. The percentages of pregnancy termination following prenatal diagnosis of anencephaly, spina bifida, and encephalocele were 50%, 41.8%, and 35.3%, respectively. NTD birth prevalence tended to be higher among mothers aged <20 or > or =30 years (P = .06) and was markedly associated with lower levels of maternal education (P < .001). Among 143 NTD mothers, only 6 (4.2%) used folic acid supplements during the periconceptional period. CONCLUSIONS: The NTD birth prevalence rate in the study area is among the highest worldwide. Folic acid deficiency may be one important risk factor.     

Decline in the prevalence of neural tube defects following folic acid fortification and its cost-benefit in South Africa

BACKGROUND: In October 2003 South Africa embarked on a program of folic acid fortification of staple foods. We measured the change in prevalence of NTDs before and after fortification and assessed the cost benefit of this primary health care intervention. METHODS: Since the beginning of 2002 an ecological study was conducted among 12 public hospitals in four provinces of South Africa. NTDs as well as other birth defect rates were reported before and after fortification. Mortality data were also collected from two independent sources. RESULTS: This study shows a significant decline in the prevalence of NTDs following folic acid fortification in South Africa. A decline of 30.5% was observed, from 1.41 to 0.98 per 1,000 births (RR = 0.69; 95% CI: 0.49–0.98; p = .0379). The cost benefit ratio in averting NTDs was 46 to 1. Spina bifida showed a significant decline of 41.6% compared to 10.9% for anencephaly. Additionally, oro‐facial clefts showed no significant decline (5.7%). An independent perinatal mortality surveillance system also shows a significant decline (65.9%) in NTD perinatal deaths, and in NTD infant mortality (38.8%). CONCLUSIONS: The decrease in NTD rates postfortification is consistent with decreases observed in other countries that have fortified their food supplies. This is the first time this has been observed in a predominantly African population. The economic benefit flowing from the prevention of NTDs greatly exceeds the costs of implementing folic acid fortification. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.     

Effects of folic acid fortification on spina bifida prevalence in Brazil

BACKGROUND: To assess spina bifida birth prevalence changes after folic acid fortification of wheat and maize flours began in Brazil in June 2004. METHODS: Cross‐sectional study of Brazilian live births in 2004 and 2006. Spina bifida birth prevalence from the Live Births Information System (SINASC: Sistema de Informações sobre Nascidos Vivos) in a prefortified period was compared to a period fortified with folic acid in each state. Observed prevalence rates in 2004 were used to calculate the expected prevalence rates in 2006 under the null hypothesis that both were similar. The observed/expected (O/E) ratios were tested by two‐tailed Z‐test. To minimize ascertainment differences among states, the O/E ratio of each one of the 27 Brazilian states was adjusted for the number of births with the Mantel‐Haenszel statistic. RESULTS The reduction in spina bifida birth prevalence in 2006 was 39% (O/E = 0.61; 95% confidence interval [CI], 0.55‐0.67), and 40% (O/E = 0.60; 95% CI, 0.53–0.68), after adjusting for state birth number. This reduction was significant (p < 0.0001), and heterogeneous among states (χ² = 72.96; p < 0.0001). CONCLUSIONS: Using SINASC data, there was a significant reduction in spina bifida birth prevalence in Brazil, probably related to the folic acid food fortification program. Birth Defects Research (Part A) 2011. © 2011 Wiley‐Liss, Inc.     

NTD prevalences in central California before and after folic acid fortification

BACKGROUND: In many regions, NTD prevalences were already declining prior to folic acid fortification. This study examined whether the declining prefortification (1989–1996) NTD prevalences continued into the postfortification period (1998–2003) in selected California counties. METHODS: This population‐based study used vital statistics data and birth defects registry data that were actively ascertained from medical records. The study population included all live births and stillbirths delivered in central California counties from 1989 to 2003. Cases included deliveries with NTDs during the same time period. RESULTS: For all NTDs combined, the slopes indicated that NTD prevalence was decreasing by 7.5 (slope: ?7.5; 95% CI: ?12.4, ?2.5) cases per 100,000 deliveries per year before fortification, whereas NTD prevalence was no longer decreasing after fortification. Comparison of the difference in the two slopes indicated that the postfortification slope exceeded the prefortification slope by 12.6 (95% CI: 2.6, 22.6) cases per 100,000 deliveries per year. CONCLUSIONS: Annual NTD prevalences in central California did not continue to decrease after implementation of folic acid fortification. Birth Defects Research (Part A) 2008. © 2008 Wiley‐Liss, Inc.     

Application of the automated spatial surveillance program to birth defects surveillance data

BACKGROUND: Although many birth defects surveillance programs incorporate georeferenced records into their databases, practical methods for routine spatial surveillance are lacking. We present a macroprogram written for the software package R designed for routine exploratory spatial analysis of birth defects data, the Automated Spatial Surveillance Program (ASSP), and present an application of this program using spina bifida prevalence data for metropolitan Atlanta. METHODS: Birth defects surveillance data were collected by the Metropolitan Atlanta Congenital Defects Program. We generated ASSP maps for two groups of years that correspond roughly to the periods before (1994-1998) and after (1999-2002) folic acid fortification of flour. ASSP maps display census tract-specific spina bifida prevalence, smoothed prevalence contours, and locations of statistically elevated prevalence. We used these maps to identify areas of elevated prevalence for spina bifida. RESULTS: We identified a large area of potential concern in the years following fortification of grains and cereals with folic acid. This area overlapped census tracts containing large numbers of Hispanic residents. CONCLUSIONS: The potential utility of ASSP for spatial disease monitoring was demonstrated by the identification of areas of high prevalence of spina bifida and may warrant further study and monitoring. We intend to further develop ASSP so that it becomes practical for routine spatial monitoring of birth defects.     

Spina bifida and anencephaly in Scotland.

Data obtained from routine sources showed that from 1971 to 1982 the birth prevalences of spina bifida and anencephaly in Scotland fell. When known terminations after routine alpha fetoprotein screening were added to total births the adjusted birth prevalence could be calculated. In 1974-82 this fell by 40% for spina bifida (3 X 0-1 X 8) and 36% for anencephaly (2 X 2-1 X 4). These findings were compared with data on birth prevalences in England and Wales, Northern Ireland, and Glasgow. The fall in birth prevalences of spina bifida and anencephaly over the past decade appears to have been due both to a true fall in incidence as well as to increased screening and termination for these conditions.     

Interpreting changes in the epidemiology of anencephaly and spina bifida following folic acid fortification of the U.S. grain supply in the setting of long-term trends, Atlanta, Georgia, 1968-2003

BACKGROUND: The prevalence of anencephaly (AN) and spina bifida (SB) was declining long before fortification of enriched grains in the U.S. with folic acid. We examined whether changes in these defects surrounding fortification could be distinguished from preexisting trends. METHODS: We used data from the Metropolitan Atlanta Congenital Defects Program to identify three ascertainment periods: Period 1 (1968-1981), prenatal diagnoses rarely made; Period 2 (1981-1993), prenatal diagnoses made but not ascertained; Period 3 (1994-2003), prenatal diagnoses ascertained. We compared the annual percent change (APC) in AN and SB for each period using Poisson regression, then compared prevalences during each period for categories of pregnancy outcome, sex, race, gravidity, and maternal age. RESULTS: The prevalence of AN (N = 434) and SB (N = 663) declined during 1968-2003. The APCs in Periods 1, 2, and 3, respectively, were -6.9%, -2.9%, and -6.8% for AN, and -7.1%, -7.0%, and -6.2% for SB; 95% confidence intervals around the APCs for Periods 2 and 3 overlapped for both defects. Prevalence ratios (PRs) for females relative to males decreased for AN (2.3 in Period 1; 1.2 in Period 3); PRs for whites relative to blacks or African Americans decreased for both AN (2.7 in Period 1; 1.2 in Period 3) and SB (2.5 in Period 1; 1.1 in Period 3). CONCLUSIONS: Our analysis suggests that changes in AN and SB surrounding folic acid fortification (Period 3) could be part of preexisting trends. This must be considered when evaluating prevention efforts.     

Tracking the prevention of folic acid-preventable spina bifida and anencephaly

BACKGROUND: The fortification of wheat flour with folic acid prevents most cases of spina bifida and anencephaly by raising serum folate levels among women capable of bearing children, as does encouraging women to consume folic acid supplements prior to pregnancy. Unfortunately, surveillance is conducted in few countries where the need is greatest. METHODS: A method for assessing the prevention of these birth defects is presented that combines fortification program information with country case prevalence estimates. RESULTS: This approach suggests that about 70% of all cases could be prevented within a year of implementation of fortification programs, were it not for the inertia of regulatory agencies. CONCLUSIONS: Professional researchers and clinicians can help combat this situation by becoming advocates for child health in their respective countries.     

Proportion of neural tube defects attributable to known risk factors

BACKGROUND

Recognized risk factors for neural tube defects (NTDs) poorly predict population‐level NTD risk. However, the proportion of NTDs that can be attributed to these risk factors is uncertain.

METHODS

To determine the proportion of NTD cases that is attributable to known or suspected risk factors (i.e., female infant sex, family history of NTDs, and maternal Hispanic ethnicity, obesity, pregestational diabetes, gestational diabetes, low dietary folate intake, lack of folic acid supplementation, anticonvulsant use, and hot tub or sauna use), we estimated the adjusted population attributable fraction (aAF) for each factor, using the method of Eide and Geffler and data from the National Birth Defects Prevention Study.

RESULTS

Our analyses of these data indicate that the proportion of cases of spina bifida and anencephaly that can be attributed to known risk factors is 28% and 44%, respectively. For spina bifida, the factor with the greatest attributable fraction was maternal obesity (aAF, 10%), whereas for anencephaly it was Hispanic ethnicity (aAF, 15%).

CONCLUSION

Our analyses indicate that known risk factors account for <50% of NTD cases. Hence, the majority of NTD cases are attributable to, as yet, unidentified factors. These findings highlight the need for continued research to identify genetic and additional nongenetic risk factors for NTDs. Further, these findings suggest that strategies that aim to reduce the risk of NTDs associated with maternal Hispanic ethnicity and obesity may have the greatest impact on the population prevalence of these conditions. Birth Defects Research (Part A), 2013. © 2012 Wiley Periodicals, Inc.     

Associated malformations in cases with neural tube defects

Infants with neural tube defects (NTDs) may have other associated congenital defects. The reported incidence and the types of associated malformations vary between different studies. The purpose of this investigation was to assess the prevalence of associated malformations in a geographically defined population. The prevalences at birth of associated malformations in infants with NTDs were collected between 1979 and 2003 on all infants born in the area covered by the registry of congenital anomalies of Northeastern France in 334,262 consecutive births. Of the 360 infants with NTDs born during this period, 20.5 % had associated malformations. Associated malformations were more frequent in infants who had encephalocele (37.5 %) than in infants with anencephaly (11.8 %) or infants with spina bifida (23.7 %). Malformations in the face (oral clefts), in the musculoskeletal system, in the renal system, and in the cardiovascular system were the most common other anomalies. In conclusion the overall prevalence of malformations, which was one in five infants, emphasizes the need for a thorough investigation of infants with NTDs. A routine screening for other malformations especially facial clefts, musculoskeletal, renal and cardiac anomalies may need to be considered in infants with NTDs, and genetic counseling seems warranted in most of these complicated cases.     

High rates of neural tube defects in Ukraine

BACKGROUND: Oral consumption of synthetic folic acid can prevent neural tube defects (NTDs), which are some of the most severe congenital anomalies. The prevalence of NTDs in Ukraine and other countries of the former U.S.S.R. has not been well studied. We determined the prevalence of NTD-affected pregnancies in Northwestern Ukraine as background for policy decisions related to flour fortification in this country. METHODS: The Ukrainian-American Birth Defects Program was established in 1999 and conducts population- based surveillance of birth defects in several oblasts (states) of Ukraine. We determined the prevalence of NTDs in the Volyn and Rivne oblasts of Northwestern Ukraine for three years, 2000-2002. RESULTS: There were 75,928 births in the two oblasts in 2000-2002. There were 159 cases of NTDs among live births, stillbirths, and induced abortions. The prevalence of NTDs in the two oblasts in Northwestern Ukraine is 2.1 per 1000 births. CONCLUSIONS: The prevalence of NTD-affected pregnancies we found in Northwestern Ukraine is almost four times what it should be. This prevalence suggests that population folate deficiency is widespread in Ukraine. Universal folic acid fortification of flour milled in Ukraine is urgently needed to end this epidemic of birth defects. Such fortification would be expected to prevent folate deficiency anemia, heart attacks, and strokes.     

Feasibility of using the national hospital discharge survey to estimate the prevalence of selected birth defects

BACKGROUND: Nationally representative data on the prevalence of certain birth defects are largely unavailable. We evaluated the feasibility of using data from the National Hospital Discharge Survey (NHDS) to describe the prevalence of selected birth defects. METHODS: All live births recorded in the NHDS during 1999-2001 were included. The prevalence for selected birth defects was calculated using weighted ratio estimators. Prevalence ratios comparing the NHDS estimates to published national estimates from the National Birth Defects Prevention Network (NBDPN) were calculated. RESULTS: With the exception of common truncus, the NHDS prevalence for the selected defects was consistently lower than the NBDPN estimates. The prevalence ratios ranged from 0.38 for trisomy 18 and anopthalmia/micropthalmia to 1.16 for common truncus. The NHDS prevalence estimates for spina bifida without anencephaly (PR 0.89, 95% CI: 0.57-1.22) and gastroschisis/omphalocele (PR 0.94, 95% CF: 0.48-1.40) most closely approximated the NBDPN estimates. CONCLUSIONS: NHDS data underestimate the prevalence of most birth defects. Additional research is needed to determine whether NHDS estimates may be useful for evaluating trends in certain conditions. Surveillance systems employing active case-finding continue to provide more accurate estimates of birth defects prevalence.     

Decline of neural tube defects cases after a folic acid campaign in Nuevo León,México

BACKGROUND: Nuevo León is a state in northeastern Mexico, near the border of Texas. Mean mortality rate from 1996-98 due to anencephaly cases was 0.6/1,000. In 1999 a surveillance program for the registry and prevention of neural tube defects (NTD) cases was initiated. METHODS: Cases were obtained from hospitals and OB-GYN clinics by immediate notification, death certificates, or fetal death registries. Only isolated cases of NTD were included. In August 1999 a folic acid campaign was initiated with the free distribution of the vitamin to low-income women with a recommendation to take a 5.0-mg pill once a week. Number of cases and rates from 1999 to 2001 were compared (chi(2) test). RESULTS: After 2 years there has been a significant reduction in the number of cases and rates. In 1999 there were 95 NTD cases and in the years 2000 and 2001 there were only 59 and 55 respectively (P < 0.001). NTD rate decreased from 1.04/1,000 in 1999 to 0.58/1,000 in 2001. Anencephaly and spina bifida rates decreased from 0.55/1,000 to 0.29/1,000 and from 0.47/1,000 to 0.22/1,000 respectively, from 1999-2001. Decrease of female cases was higher than male cases for both phenotypes. CONCLUSION: After 2 years there was a 50% decrease in the incidence of anencephaly and spina bifida cases with a significant reduction of infant mortality and disability. These results encourage us to propose the use of a single tablet of 5.0-mg of folic acid per week as an alternative to supplementation on a daily basis.     

Neural tube defects among twin births.

To obtain accurate, unbiased rates of neural tube defects (NTDs) in twins, we conducted a population-based study that included live births and fetal deaths in Los Angeles County, California, ascertaining cases by multiple methods. Twenty-eight twin cases yielded a prevalence-at-birth of 1.6/1,000 twin births, which is significantly higher than the singleton prevalence of 1.1/1,000 births. In twins compared with singletons, the prevalences of both encephalocele and anencephaly are increased, whereas spina bifida is decreased. The twin case male/female sex ratio (.55) is lower than the singleton case sex ratio (.77). Concordance is relatively low at 3.7%, but appears to be higher than recently reported recurrence risks in other low prevalence areas. Stillbirths were most common among female cases and like-sex twins. Our study tends to support proposed etiologic theories associating NTDs with females or monozygotic twins, or both. There is increasing evidence that the etiology of NTDs may differ in high and low prevalence areas. We suggest also that twins and singletons may differ in their response to etiologic factors. The variations among anencephaly, spina bifida, and encephalocele in their association with twinning suggest that there may be different factors that influence the development of each specific NTD. The noted differences among the malformations also indicate that some of the variation among results of other studies of NTDs and twinning may be due to case ascertainment. Including spina bifida cases would decrease the proportion of twins in a study population, while including anencephalics would increase the proportion. Importantly, ascertaining fetal deaths would increase the proportion of anencephalics and case females, so studies of NTDs that do not include fetal deaths will show fewer twins than expected. On the basis of our findings and those of Layde et al., excluding encephaloceles will also decrease the number of twins among NTD cases. When investigating etiologic hypotheses for NTDs, these potential biases must be recognized.     

Recommendations for accelerating global action to prevent folic acid-preventable birth defects and other folate-deficiency diseases: meeting of experts on preventing folic acid-preventable neural tube defects

BACKGROUND: In April of 2003, The Micronutrient Initiative, in collaboration with several other organizations, convened a group of knowledgeable scientists and policy experts to discuss ways to accelerate the global pace at which countries implement effective and sustainable programs to prevent folic acid-preventable birth defects and other folate-deficiency diseases. Programs implemented to date by fewer than 40 countries have prevented only 10% of the estimated 240,000 annual cases of folic acid-preventable spina bifida and anencephaly. METHODS: Participants in this meeting summarized and presented scientific evidence showing that increased consumption of synthetic folic acid prevents a large proportion of spina bifida and anencephaly cases. They also reviewed related guidance and endorsement issued by national professional societies and advisory bodies as well as policies and programs implemented by some countries that have already demonstrated successful results in terms of reduced rates of neural tube defects and improved folate nutrition. CONCLUSIONS: The group formulated and discussed recommendations and strategies for increasing the pace of neural tube defect prevention globally. The recommendations and strategies are published here.     

Changes in the birth prevalence of selected birth defects after grain fortification with folic acid in the United States: findings from a multi-state population-based study

BACKGROUND: Observational studies and clinical trials have suggested that periconceptional use of folic acid can reduce the risk of birth defects other than neural tube defects (NTDs). Using data reported by states to the National Birth Defects Prevention Network, we examined whether folic acid fortification might have decreased the prevalence of other specific birth defects. METHODS: For each of 16 birth defect categories selected for study, birth prevalence for two time periods was calculated with data submitted from a number of states in 1995-1996 ("pre-fortification") and 1999-2000 ("post-fortification"). Changes in birth prevalence between the two time periods were assessed by calculating prevalence ratios and 95% confidence intervals for each defect, and compared by maternal race/ethnicity and availability of prenatally diagnosed cases. RESULTS: We confirmed previously reported reductions in the birth prevalence of NTDs. In addition, we found modest, yet statistically significant, decreases in the birth prevalence for transposition of the great arteries(12%), cleft palate only (12%), pyloric stenosis (5%), upper limb reduction defects (11%), and omphalocele (21%). More substantial subgroup decreases were observed for renal agenesis among programs that conduct prenatal surveillance (28%), for common truncus among Hispanics (45%), and for upper limb reduction defects among Hispanics (44%). There were modest yet significant increases in the prevalence of obstructive genitourinary defects (12%) and Down syndrome (7%), but not among programs conducting prenatal surveillance for these defects. CONCLUSIONS: These results suggest some modest benefit from the folic acid fortification on the prevalence of a number of non-NTD birth defects.     

Maternal flu or fever, medication use, and neural tube defects: a population-based case-control study in Northern China

BACKGROUND: Maternal exposure to flu or fever has been associated with increased risk for neural tube defects (NTDs); however, few studies have considered the effects of medications on the effects of flu or fever. We evaluated the effect of maternal flu or fever, medication use (antibiotics, antipyretics), and their joint effect on NTDs. METHODS: Data came from an ongoing population-based case-control study of infants with external malformations in northern China. The case group included 363 infants with NTDs identified between January 2003 and June 2005. Controls were 523 newborn infants without identified congenital anomalies matched by county, sex, maternal ethnic group, and the closest date of conception for infants with any major external malformation. Data were collected by a trained health worker through face-to-face interviews after delivery. RESULTS: NTD risks were significantly associated with maternal flu or fever (adjusted odds ratio [AOR] = 3.93, 95% CI: 2.48-6.23) and antipyretic use (AOR = 4.86, 95% CI: 1.33-17.78), but not with antibiotic use (AOR = 1.75, 95% CI: 0.91-3.38) after adjusting for potential confounders. NTD risk associated with maternal antipyretic use was markedly higher for anencephaly (AOR = 7.03, 95% CI: 1.70-29.04) than for spina bifida (AOR = 3.98, 95% CI: 0.95-16.74). Mothers with flu or fever who were also using antipyretics showed a markedly higher AOR for anencephaly (14.75 vs. 4.52), spina bifida (16.30 vs. 3.85), and all NTDs combined (13.91 vs. 4.04) than mothers with flu or fever who were not using antipyretics. Maternal antibiotics did not markedly change the effects of flu or fever on anencephaly (4.17 vs. 4.83), spina bifida (5.08 vs. 4.21), and all NTDs combined (5.05 vs. 4.29). CONCLUSIONS: Maternal flu or fever and antipyretic use during the periconceptional period increases the risk for NTDs. Maternal exposure to antipyretics together with flu or fever results in a markedly higher risk of NTDs than exposure to flu or fever alone.