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.     

Heterogeneity of neural tube defects in Europe: the significance of site of defect and presence of other major anomalies in relation to geographic differences in prevalence.

In the period 1980-1987, neural tube defects were two to three times more prevalent in populations covered by EUROCAT registries in the United Kingdom and Ireland (UKI) than in Continental Europe and Malta (CEM). 1864 NTD cases in a total population of 580,000 births in UKI and 455 cases in a population of 380,000 births in CEM were analysed to find if there were differences in the ratio of prevalence rates between UKI and CEM according to site of the defect and association with non-central nervous system (CNS) anomalies. The prevalence rate ratio was high for anencephaly with accompanying spina bifida, iniencephaly, and upper spina bifida, and low for encephalocele, lower spina bifida, and anencephaly without other neural tube defects. There was a greater female excess for anencephaly with accompanying spina bifida, iniencephaly, and upper spina bifida than for other defects in both geographic areas. There was a female excess for encephalocele in UKI but a male excess in CEM. Certain sites (anencephaly with accompanying spina bifida, iniencephaly, and encephalocele) were more likely to have accompanying non-CNS anomalies. The prevalence rate ratio of multiply malformed NTD was in general lower than for isolated NTD but showed the same pattern by site. The prevalence rate ratio was high for multiply malformed anencephaly with accompanying spina bifida, iniencephaly, and upper spina bifida. The sex ratio was similar between isolated and multiply malformed cases when site of the defect is taken into account. It is concluded that the geographic prevalence pattern and sex ratio differ according to site of NTD but do not differ substantially according to whether NTD is isolated or associated with non-CNS anomalies.     

Clinical, genetic, and epidemiological factors in neural tube defects.

We examined clinical, genetic, and epidemiologic factors among 512 probands with nonsyndromal neural tube defects (NTDs). Data were analyzed after grouping the probands in four different ways with respect to pathological features and putative pathogenic mechanisms. Apparently unrelated congenital anomalies occurred more frequently among probands with craniorachischisis (62%), encephalocele (30%), or multiple NTDs (25%) than among probands with anencephaly (14.7%) or spina bifida (10.1%) (P much less than .0001). Unrelated congenital anomalies occurred less often among probands with low spina bifida (6.7%) than among probands with high spina bifida (19.5%). NTDs were seen in 7.8% of the siblings of probands with high spina bifida but in only 0.7% of the siblings of probands with low spina bifida, in 2.2% of the siblings of anencephalic probands, and in none of the siblings of probands with craniorachischisis, encephalocele, or multiple NTDS (P less than .001). In all 16 families in which two siblings had NTDs, both had either defects of the type associated with abnormal primary neurulation or defects of the type associated with abnormal canalization. High spina bifida and multiple NTDs were found more frequently than expected among the Sikh probands (P less than .02). The frequency of non-NTD congenital anomalies was higher among siblings of Sikh probands (8.8%) than among siblings of other probands (2.4%) (P less than .05). This excess was due to the occurrence of hydrocephalus without spina bifida in four of 68 siblings of Sikh probands.     

Genetic heterogeneity in neural tube defects.

In 1985-1987, the authors attempted to ascertain all cases of confirmed neural tube defects (NTD) in California and Illinois, not only among live-born infants (postnatal) but also cases ascertained during pregnancy (prenatal). Mothers of both prenatal and postnatal NTD cases were interviewed within 5 months. Among postnatal NTD cases, 14.9% (45/303) had anomalies not ordinarily associated with NTD. The frequency of non-NTD related anomalies was 9.4% (5/53) in anencephaly, 0/3 in craniorachischisis, 22.9% (8/35) in encephalocele, 14.5% (27/186) in spina bifida, 20% (1/5) in multiple NTD cases and 19% (4/21) in other NTDs. However, relatively few postnatal NTD cases had known multiple malformation patterns; Meckel-Gruber syndrome was the most common, with 2 postnatal cases, and 3 additional prenatal cases. Maternal age, paternal age and birth order in postnatal cases were 26.7 +/- 5.4 SD, 28.9 +/- 5.8 and 2.8 +/- 1.8, respectively. These characteristics were similar in prenatal NTD cases (27.9 +/- 6.0, 30.1 +/- 6.3, 2.5 +/- 1.5, respectively). We also found no differences in parental ages among different types of NTD. Frequency of prior spontaneous abortion differed neither between postnatal NTD (9.3%) and postnatal controls (8.1%), nor between prenatal NTD (10.7%) and prenatal control (8.7%). Loss rates in the pregnancy immediately prior to the index NTD cases were not significantly higher than in control subjects. The high frequency of non-NTD associated malformations (14.9%) indicates the caution must be exercised before assuming that a given NTD case is polygenic-multifactorial in etiology, especially cases of encephalocele.     

Effects of inositol supplementation in a cohort of mothers at risk of producing an NTD pregnancy

Neural tube defects (NTDs), most commonly spina bifida and anencephaly, can be prevented with periconceptional intake of folic acid in about 70% of cases. Recurrence of NTDs despite supplementation of high dose of folic acid further suggests that a proportion of NTD cases might be resistant to folic acid. Moreover, heterogeneity of NTDs has been suggested in animal studies, indicating that only some sub-type of NTDs should be considered sensitive to folate intake. Inositol isomers (particularly myo- and chiro-inositol) can prevent folate-resistant NTDs in the curly-tail mutant mouse, suggesting that some cases of human NTDs might benefit from inositol supplementation. In humans, lower inositol blood concentration was found in pregnant women carrying NTD fetuses, whereas a periconceptional combination therapy with folic acid associated with inositol has been linked to normal live births, despite high NTD recurrence risk. Fifteen pregnancies from 12 Caucasian women from different parts of Italy with at least one previous NTD-affected pregnancy underwent periconceptional combined myo-inositol and folic acid supplementation. Maternal serum α-feto-protein levels were found in the normal range, and normal results on ultrasound examination were found in all the pregnancies that followed. No collateral effects or intense uterine contractions were demonstrated in this pilot study in any of the pregnancies after inositol supplementation, and seventeen babies were born without any type of NTD.     

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.     

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.     

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. Birth Defects Research (Part A), 2008. © 2008 Wiley‐Liss, Inc.     

Proctalgia fugax: a cause of marital dysharmony.

A survey of the records of all hospitals with obstetric services in Nova Scotia revealed that during 1980-84 there were 122 pregnancies involving a neural tube defect. The mean rate was 2/1000 births. Of the affected fetuses or infants 54% had spina bifida, 35% had anencephaly and 11% had encephalocele. The records showed that in the early part of the period studied at least one prenatal ultrasonographic examination had been performed in 60% of the pregnancies; in 1984 the rate was 74%. When examinations done before 16 weeks'' gestation were excluded, the overall detection rates at the first ultrasonographic examination were 100% for anencephaly and 73% for spina bifida and encephalocele; the rates improved toward the end of the study period.     

Mouse mutants with neural tube closure defects and their role in understanding human neural tube defects

BACKGROUND: The number of mouse mutants and strains with neural tube closure defects (NTDs) now exceeds 190, including 155 involving known genes, 33 with unidentified genes, and eight "multifactorial" strains. METHODS: The emerging patterns of mouse NTDs are considered in relation to the unknown genetics of the common human NTDs, anencephaly, and spina bifida aperta. RESULTS: Of the 150 mouse mutants that survive past midgestation, 20% have risk of either exencephaly and spina bifida aperta or both, parallel to the majority of human NTDs, whereas 70% have only exencephaly, 5% have only spina bifida, and 5% have craniorachischisis. The primary defect in most mouse NTDs is failure of neural fold elevation. Most null mutations (>90%) produce syndromes of multiple affected structures with high penetrance in homozygotes, whereas the "multifactorial" strains and several null-mutant heterozygotes and mutants with partial gene function (hypomorphs) have low-penetrance nonsyndromic NTDs, like the majority of human NTDs. The normal functions of the mutated genes are diverse, with clusters in pathways of actin function, apoptosis, and chromatin methylation and structure. The female excess observed in human anencephaly is found in all mouse exencephaly mutants for which gender has been studied. Maternal agents, including folate, methionine, inositol, or alternative commercial diets, have specific preventative effects in eight mutants and strains. CONCLUSIONS: If the human homologs of the mouse NTD mutants contribute to risk of common human NTDs, it seems likely to be in multifactorial combinations of hypomorphs and low-penetrance heterozygotes, as exemplified by mouse digenic mutants and the oligogenic SELH/Bc strain.     

Spina bifida phenotypes in infants or fetuses of obese mothers

BACKGROUND: A twofold or greater risk of neural tube defect (NTD)-affected pregnancy has been associated with prepregnant obesity, where obesity was defined as body mass index (BMI) of >29 kg/m(2). Risks have been more elevated for spina bifida than for anencephaly. METHODS: We investigated whether finer phenotypic classifications of spina bifida, in combination with other factors, were associated with a BMI of >29 kg/m(2). Data were derived from a case-control study of fetuses and infants with NTDs among 1989-1991 California births. Interviews were conducted with mothers of 277 spina bifida cases and 517 nonmalformed controls. RESULTS: Women with a BMI of >29 kg/m(2) compared with those 29 kg/m(2) compared with males whose mothers were 相似文献   

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.     

Morphological study of the removed fetus after therapeutic abortion for echographic anomalies (apropos of 42 cases)

In 42 cases, fetal abnormalities were diagnosed by obstetric ultrasonography and the pregnancy was terminated. The malformations included: anencephaly (22), severe hydrocephaly (4, one with a spina bifida), encephalocele and meningocele (2) amniotic band syndrome (4; a correct prenatal diagnosis was performed during the second trimester in two cases), major anterior abdominal wall defects (2), Pena-Shokeir syndrome type I? (I), severe renal abnormalities (2), conjoined twins, dicephalus type (2), cystic hygroma and hydrops fetalis (2), osteogenesis imperfecta, type II (I). Thus, there were 23 fetuses with a polygenetically determined status; five fetuses could be affected by an autosomal recessive disorder.     

A familial association between twinning and upper-neural tube defects.

An increased twinning rate has been observed in the near relatives (sibs, parents, and aunts and uncles) of probands with neural tube defects (NTDs) occurring at the level of the 11th thoracic vertebra and above (upper NTDs). The twin rate was more than double that of the near relatives of probands with lower NTDs and of those of probands with Mendelian disorders (the controls). The excess twinning was same sex and can therefore consist of either MZ or same-sex DZ twins. Furthermore, upper-NTD families with twins had a higher NTD-sibling occurrence rate than did families without twins. These findings, if corroborated, may imply an etiology common to twinning and NTDs and can perhaps be applied in counseling NTD families.     

Gestational duration, and fetal and infant mortality for twins vs singletons.

The aim of this research was to study fetal and infant mortality in Sweden between 1973 and 1996 in twins vs singletons in relation to gestational duration. Analysis was of fetal and infant mortality based on the number of pregnancies at risk as the denominator rather than the number of deliveries each week. The analysis was based on information stored at the Medical Birth Registry (MBR), the National Board of Health and Welfare, Stockholm. The MBR keeps records on virtually all pregnancies (> 99%) regarding delivery and neonatal information, and for infant mortality up to 1 year of age. During the study period, 2,206,738 singleton and 52,658 twin births were registered. Risk evaluation was made as odds ratio (OR) with a 95% confidence interval. The material was stratified according to parity, maternal age, year of delivery, and delivery unit. Results showed the OR for twin births before 34 weeks gestation was 6 to 8-fold increased compared with singletons. The OR for fetal mortality was increased in all gestational weeks, and like-sexed twins had a consistently poorer prognosis compared to unlike-sexed. Between 1989-96, unlike-sexed twins had a fetal mortality approaching that of singletons. In conclusion, real progress in reduction of infant mortality in twins may be impossible until the high incidence of preterm births can be decreased. Hypothetically, about 100 twin labors would have to be induced to avoid one fetal death in like-sexed twin pregnancies.     

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.     

Twinning rates in a rural area of Bangladesh

In this study we investigate the incidence of twin births over a period of 16 years in a rural area of Bangladesh using data from the Demographic Surveillance System of the International Centre for Diarrhoeal Disease Research. Over the study period twinning rates fluctuated between 7.8 and 11.2 per 1000 live births. The twinning rate was strongly correlated with maternal age; the rate for mothers over 35 years of age was about 3 times higher than for mothers younger than 20 years. The variation in twinning rate with maternal age is due to the variation in dizygotic twinning; the rate of monozygotic twinning is almost constant for all ages. Twinning rates were higher in the treatment area than in the comparison area after controlling for maternal age and parity. The rates were lower for monozygotic twinning and higher for dizygotic twinning in the treatment area than in the comparison area. Seasonality was observed for both twins and singletons, but the peak for twinning precedes that for singleton births by more than a month.     

与神经管畸形相关的基因学研究进展

神经管畸形（neural tube defects,NTDs）是指由于在胚胎发育过程中,神经管闭合不全所引起的一组出生缺陷,包括无脑儿、脊柱裂、脑积水、脑或脑脊膜膨出等,其危害极大,严重影响患儿的生理发育和生活质量,给家庭和社会带来沉重的精神压力和经济负担。大多数研究认为神经管畸形是多因素多基因的遗传疾病,是遗传、环境、营养因素共同作用、交互影响的结果,目前还不能用一种单一原因解释该疾病的发生。本文主要从导致神经管畸形发生的叶酸代谢酶基因多态性、神经管形态学方面的相关基因研究等做一综述。     

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.     

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.