Rate Of Neural Tube Defects Research Articles

Bayesian mapping of neural tube defects prevalence in Heshun County, Shanxi Province, China during 1998∼2001

Objective: To estimate the prevalence rates of neural tube defects (NTDs) in Heshun County, Shanxi Province, China by Bayesian smoothing technique. Methods: A total of 80 infants in the study area who were diagnosed with NTDs were analyzed. Two mapping techniques were then used. Firstly, the GIS software ArcGIS was used to map the crude prevalence rates. Secondly, the data were smoothed by the method of empirical Bayes estimation. Results: The classical statistical approach produced an extremely dishomogeneous map, while the Bayesian map was much smoother and more interpretable. The maps produced by the Bayesian technique indicate the tendency of villages in the southeastern region to produce higher prevalence or risk values. Conclusions: The Bayesian smoothing technique addresses the issue of heterogeneity in the population at risk and it is therefore recommended for use in explorative mapping of birth defects. This approach provides procedures to identify spatial health risk levels and assists in generating hypothesis that will be investigated in further detail.

Fetal Alert Network: Surveying congenital anomalies

Fetal Alert Network: Surveying congenital anomalies

Prevalence of neural tube defects in economically and socially deprived area of China

This paper aims to understand the situation and epidemiology trend of neural tube defects in Guizhou province, China from 1996 to 2004. Pregnant women from 17 hospitals in Guizhou province were chosen for investigation of perinatal infants from January 1996 to December 2004. Of 1,208 birth defect cases studied in this 9-year period, a total of 122 cases were identified as neural tube defects (NTD), making up a 10.10% of the total birth defects. The average prevalence rate of NTD was 12.21 per 10,000 births; however, there is no significant difference between the genders. In this study, the age of mothers during pregnancy was shown to be one of the major factors affecting the prevalence rate of NTD and the differences between infants with or without NTD and the usage of folic acid as a supplement during pregnancy were found to be statistical significant. NTD was found to be the most common and serious form of human birth defect in Guizhou province. For prevention, folic acid supplement is thought to be efficacious in inhibiting NTD, and thus, it is essential for people in socially deprived areas to effectively reduce the prevalence of NTD in China.

Efeito da fortificação com ácido fólico na redução dos defeitos do tubo neural

Neural tube defects are congenital malformations that occur during initial fetal development, leading to anencephaly and spina bifida; folic acid deficiency is the most important risk factor identified to date. Brazil has one of the world's highest neural tube defect rates. Food consumption surveys among pregnant Brazilian women showed a high rate of inadequate folic acid intake (< 0.6 mg/day). In 2004, the National Health Surveillance Agency (ANVISA) mandated the fortification of corn meal and wheat flour with folic acid (0.15 mg/100g). The National Family Budget Survey estimated the average amount of bread/flour products available in households as 106.1g/day (contributing with 0.16 mg folic acid/day). However, while in the South of the country the supply was 144 g/day, in the North and Central West it barely reached 70 g/day. Folic acid food fortification is mandatory in some 40 countries, but only four have assessed this strategy. The existing studies have all shown a significant impact, ranging from 19 to 78%. Folic acid fortification is an undeniably important intervention for primary prevention, and neural tube defects can now be considered a preventable epidemic.

Developmental and Genetic Outcomes in Children Conceived Through Assisted Reproductive Technologies

After completing this article, readers should be able to: 1. Describe the outcomes of assisted reproductive technologies (ART) for singleton, twin, and other multiple births. 2. Describe the role of fertility in adverse outcomes seen with ART births. 3. Review the association of birth defects with ART. 4. Delineate the association of disease of genomic imprinting with ART. 5. Describe the relationship between ART and the subsequent incidence of neurodevelopmental sequelae. In the 1977 ruling “Carey v. Population Services International,” the United States Supreme Court ruled that the decision to bear children is constitutionally protected. (1) Significant interest already had been shown in the development and improvements of in vitro fertilization (IVF) for infertile couples. The first human pregnancy and human birth using IVF were reported by Steptoe and Edwards in the United Kingdom. (2) Their work resulted in the first baby born via reproductive technologies, Louise Brown, born on July 25, 1978, at Oldham General Hospital in Oldham, United Kingdom. (3) She was born via a planned cesarean section, and her birthweight was 2.61 kg. The first successful viable IVF in the United States was performed by Jones and Seager-Jones in 1981 in Norfolk, Virginia. (4) Assisted reproductive technologies (ART) have seen a recent surge in popularity. The Centers for Disease Control and Prevention (CDC) reported that 122,872 cycles of ART were initiated in 2003, resulting in the delivery of 48,756 neonates, (5) accounting for approximately 1% of all neonates delivered in the United States. The percentage is higher in many countries, including Denmark, where it is estimated that 5% of all deliveries are with the assistance of ART. (6) Couples pursue ART for myriad reasons, including tubal transport factors, ovulatory dysfunction, uterine factors, endometriosis, male- and female-specific factors, and when a cause of infertility is unknown. (5) It would be very …

Weekly Administration of Folic Acid and Epidemiology of Neural Tube Defects

In 1999, a folic acid campaign for prevention of neural tube defects was started in Nuevo León, México, with the recommendation of taking a 5000 -mcg tablet of folic acid per week. The purpose of this study was to compare the epidemiology of neural tube defects after four years of the campaign. Cases of anencephaly, spina bifida, and encephalocele (ICD Q00, Q01, Q05, 10th Ed.) from public and private hospitals were registered by immediate notification, death certificates, and fetal death registries. Comparisons of neural tube defects rates, phenotype distribution of cases, and sex ratios, registered before and after the folic acid campaign, were done using the Student's t Test and Chi square test. There was a 50% reduction in the incidence of anencephaly and spina bifida cases from 93 in 1999 (1.04x1000) to 46 in the year 2003 (0.56x1000) (p<0.001). Spina bifida cases declined up to 70% in 2002 and anencephaly cases up to 50% in 2003. In 1999, overall, the ratio (females: males) was 0.66 with female excess; the sex ratio was similar for anencephaly and spina bifida cases. In the year 2000, female cases showed a significant reduction for both spina bifida and anencephaly (75% and 56% respectively); the sex ratio was 0.57 with a greater male excess for both phenotypes. Weekly administration of 5000 mcg of folic acid reduces the incidence of neural tube defects 50%, primarily spina bifida, with a higher reduction of female cases.

Are the recommendations on the prevention of neural tube defects working?

Many studies showed that reduction by an estimated 80% or more of neural tube defects (NTD) by consumption of folic acid from before conception is achievable. The objectives of this study were to evaluate the effectiveness of recommendations on folic acid aimed at reducing the occurrence of NTD in our region. Cases of NTD were ascertained among liveborn infants, stillbirths, and terminations of pregnancy. Incidences and trends in rates of NTD before and after 1992 (the year of the first recommendations) and before and after 1995 (the year of local recommendations) were obtained. The results showed that the issuing of recommendations on folic acid was followed by no detectable improvement in the trends of incidence of NTD. The rates of NTD per 10,000 were before 1992 9.07, from 1993 to 1995 8.14, and after 1995 10.62, respectively. The incidence rate ratios (IRRs) were not different from 1.00. In conclusion new cases preventable by folic acid continue to accumulate. Recommendations alone did not influence trends in NTD in our country up to 11 years after the confirmation of the effectiveness of folic acid in clinical trials. New strategies are needed.

Pre-administration of Ganoderma lucidum spore reduces incidence of neural tube defects induced by retinoic acid in pregnant mice

To explore whether pre-administration of Ganoderma lucidum spore (GASP) can reduce incidence of neural tube defects (NTDs) induced by all-trans retinoic acid (ATRA) in pregnant mice. Twenty pregnant mice were randomly divided into four groups: normal control group, solvent-treated group, ATRA-induced group, and GASP-treated plus ATRA-induced group. GASP solution, which was prepared with solvent (sodium carboxymethyl cellulose), was fed to the pregnant mice in the GASP-treated plus ATRA-induced group twice a day from embryo (E) 0 d to E10.5 d. The same dose of solvent was given to the pregnant mice in the solvent-treated group. At E7.75 d, ATRA (50 mg/kg) was given to the pregnant mice in both ATRA-induced group and GASP-treated plus ATRA-induced group for single time. Embryos were sampled from pregnant mice at E10.5 d. Then the incidence rate of NTDs in mouse embryo was calculated and the crown-rump length of mouse embryo was measured. The positive rate of nestin expression and the distribution of cell cycle of embryonic neural tube neuroepithelial cells were detected by histochemical staining technique and flow cytometry respectively. Reverse transcription-polymerase chain reaction method was used to detect the gene expressions of cyclin-dependent protein kinase 2 (Cdk2) and Cdk4 mRNAs. The incidence rates of NTDs in mouse embryos in the ATRA-induced group and the GASP-treated plus ATRA-induced group were 79.41% and 21.67% respectively, while the crown-rump length of mouse embryos in these two groups were (3.62+/-1.27) mm and (5.84+/-0.92) mm respectively. The positive rate of nestin expression in embryonic neural tube neuroepithelial cells of mouse embryo at E10.5 d in the ATRA-induced group was 32.44%, while that in the GASP-treated plus ATRA-induced group was 77.65%. The cell cycle of embryonic neural tube neuroepithelial cells was obviously arrested at G(0)/G(1) phase in the ATRA-induced group as compared with that in the GASP-treated plus ATRA-induced group. The Cdk4 mRNA was transcripted at a high level in embryonic neural tube in the GASP-treated plus ATRA-induced group, but the Cdk2 mRNA was not detected in this group. Pre-administration of GASP can reduce the incidence of NTDs induced by ATRA in pregnant mice.

Birth defects surveillance in Ukraine: a process

Birth defects (BD) surveillance using international standards was introduced in Ukraine by a network of five BD centers located in northwestern, central and southern regions. BD centers provide resources to access current and comprehensive information and to nurture partnerships with physicians, administrators, parental support groups, educators, and humanitarian assistance organizations. One outcome was the vigorous and popular website International BD Information Systems (IBIS). The network is now incorporated as OMNI-Net Ukraine. The program has documented high prevalence rates of neural tube defects (NTD); fetal alcohol effects (FAE); and idiopathic developmental retardation among orphans that prompted prevention and amelioration initiatives. Further program objectives include: universal folic acid flour fortification, as recommended by the Ukrainian Academy of Medicine; continued research on methods to reduce FAE in collaboration with partners from California; opening other early infant stimulation centers funded by local authorities, modeled on those in Rivne and Lutsk; and linking BD prevention with bioethical considerations, which is a topic of interest in Ukraine in part enhanced by the effects of Chornobyl.

Primary prevention of neural tube defects with folate in Western Australia: the value of the Western Australian Birth Defects Registry

This paper reviews the role of the Western Australian Birth Defects Registry in the primary prevention of neural tube defects. The Registry provides complete and up-to-date information on all neural tube defects (NTD), including terminations of pregnancy. These data have been used to determine a baseline rate of NTD and to monitor trends in NTD over time, when health promotion of folic acid supplement use and voluntary fortification of food with folate were introduced. The register has also been used to investigate NTD in special populations (Indigenous infants in Australia) and as a sampling frame for case control studies. The data derived from these studies have been used to assist in assessing whether mandatory food fortification in Australia is indicated to prevent NTD.

Neural tube defects and associated anomalies in a fetal and perinatal autopsy series

Neural tube defects (NTDs) are congenital malformations of the central nervous system (CNS) secondary to abnormal closure of the neural tube during embryonic development. This study provides information on NTD rate, distribution, associated morphologic anomalies and organ weights in a Danish fetal and perinatal autopsy series during a 16 year period. The data were extracted from the autopsy reports of a consecutive series of 1984 fetal and perinatal autopsies from the Copenhagen area performed in the period 1989-2004. Registered parameters included: The location and morphology of the NTD, associated morphological anomalies, and organ weights. Organ weights were evaluated according to new fetal autopsy standards and grouped as low, normal or high. Ninety-seven NTD cases were found (4.9%): Spina bifida (38 cases), cephalocele (17 cases) and anencephaly (42 cases). 63% of NTD cases had associated morphologic anomalies. Among the most common were hydrocephalus, NTD in another region, and anomalies in the urogenital system. 58% of the NTD cases had abnormal weight of one or more organs. Most notable was low adrenal weight not only in anencephalic fetuses but also in cases with cephalocele, suggesting a possible association.

Folic acid awareness and supplementation among Texas women of childbearing age

Objective. Neural tube defects (NTDs) affect about seven of every 10,000 deliveries in Texas. To reduce the risk for NTDs, women are encouraged to supplement with 400 mcg folic acid daily during their reproductive years. This study examines folic acid awareness, knowledge, and supplementation practices among women of childbearing age (WCBA), including residents of Texas–Mexico border as well as women of Hispanic origin/ethnicity, populations that have NTD rates up to three times higher than the national average. Methods. We conducted a statewide multistage sample telephone survey among Texas women of childbearing age in 2001. In total 1,196 women age 18 to 44 were interviewed. Results. About 78% of WCBA knew about folic acid, 28% knew that folic acid prevents birth defects, and 25% knew to take folic acid before pregnancy. The prevalence of daily folic acid supplementation among all women of childbearing age was 33%. Education was the strongest predictor of folic acid awareness followed by race/ethnicity and age. Significant predictors of daily folic acid supplementation were education and ethnicity. Conclusions. Our findings suggest the need for more emphases on strategies to improve the level of folic acid supplementation among low educated women, and race ethnic minority populations.

Improvements in the Status of Folate and Cobalamin in Pregnant Newfoundland Women Are Consistent with Observed Reductions in the Incidence of Neural Tube Defects

Historically, the province of Newfoundland and Labrador had one of the highest rates of neural tube defects (NTDs) in North America (1976-1991: 3.2/1000 births), which could be partially explained by the sub-optimal status of folate and cobalamin in this population. In order to gain evidence of the impact of folate fortification programs, as well as prenatal education programs, a cross-sectional study was conducted to obtain data on the folate and cobalamin status of pregnant Newfoundland women in the post-folate fortification era. Additionally, the rates of NTDs were determined. Blood samples were collected during the first prenatal clinic (at approximately 16 weeks gestation) from 365 pregnant women in Newfoundland in 2002. Samples were analyzed for serum folate, cobalamin and homocysteine. In addition, rates of neural tube defects were calculated from data collected from the Provincial Medical Genetics Program, Newfoundland. Data were compared to historical data from a similar population of pregnant women in Newfoundland. The status of both folate and cobalamin has significantly improved (p<0.0001) in the post-fortification era, concurrent with a significant reduction in the number of neural tube defects (NTDs), from 4.67 (years 1992-1996) to 1.01 (years 1998-2002) per 1000 total births. These data provide evidence that both folate and cobalamin status of pregnant Newfoundland women have improved since 1997. The data for cobalamin provide evidence that strategies in addition to folate fortification programs are contributing to the improvements of poor water-soluble vitamin status in this population, thus providing a partial explanation for the dramatic reductions in NTD rates observed since 1995.

Improvements in the Status of Folate and Cobalamin in Pregnant Newfoundland Women Are Consistent with Observed Reductions in the Incidence of Neural Tube Defects

Historically, the province of Newfoundland and Labrador had one of the highest rates of neural tube defects (NTDs) in North America (1976–1991: 3.2/1000 births), which could be partially explained by the sub-optimal status of folate and cobalamin in this population. In order to gain evidence of the impact of folate fortification programs, as well as prenatal education programs, a cross-sectional study was conducted to obtain data on the folate and cobalamin status of pregnant Newfoundland women in the post-folate fortification era. Additionally, the rates of NTDs were determined. Blood samples were collected during the first prenatal clinic (at approximately 16 weeks gestation) from 365 pregnant women in Newfoundland in 2002. Samples were analyzed for serum folate, cobalamin and homocysteine. In addition, rates of neural tube defects were calculated from data collected from the Provincial Medical Genetics Program, Newfoundland. Data were compared to historical data from a similar population of pregnant women in Newfoundland. The status of both folate and cobalamin has significantly improved (p<0.0001) in the post-fortification era, concurrent with a significant reduction in the number of neural tube defects (NTDs), from 4.67 (years 1992–1996) to 1.01 (years 1998–2002) per 1000 total births. These data provide evidence that both folate and cobalamin status of pregnant Newfoundland women have improved since 1997. The data for cobalamin provide evidence that strategies in addition to folate fortification programs are contributing to the improvements of poor water-soluble vitamin status in this population, thus providing a partial explanation for the dramatic reductions in NTD rates observed since 1995.

Trends of selected malformations in relation to folic acid recommendations and fortification: An international assessment

Two crucial issues relative to the benefits and impact of folic acid in the prevention of birth defects are whether supplementation recommendations alone, without fortification, are effective in reducing the population-wide rates of neural tube defects (NTDs), and whether such policies can reduce the occurrence of other birth defects. Using data from 15 registries, we assessed rates and trends of 14 major defects, including NTDs, in areas with official recommendations or fortification to assess the effectiveness of recommendations and fortification on a wide range of major birth defects. We evaluated surveillance data through 2003 on major birth defects from population-based registries from Europe, North America, and Australia. All included ascertainment of pregnancy terminations (where legal). Trends before and after policies or fortification were assessed via Poisson regression and were compared via rate ratios. Significant changes in trends were seen for NTDs in areas with fortification but not in areas with supplementation recommendations alone. For other major birth defects, there was an overall lack of major trend changes after recommendations or fortification. However, some significant declines were observed for select birth defects in individual areas. Recommendations alone remain an ineffective approach in translating the known protective effect of folic acid in population-wide decline in NTD rates. Fortification appears to be effective in reducing NTDs. The effect on other birth defects remains unclear.

A population‐based case–control study of risk factors for neural tube defects in four high‐prevalence areas of Shanxi province, China

Shanxi province in Northern China has one of the highest reported prevalence rates of neural tube defects (NTD) in the world. To explore the risk factors for NTDs in Shanxi province, we carried out a population-based case-control study in four selected counties with prevalence rates >10 per 1000 births during 2003. Using a multi-logistic regression model analysis (alpha = 0.10), 158 NTD cases were compared with 226 control mothers. Maternal factors significantly associated with increased risk for an NTD were a primary school education or lower (adjusted odds ratio [OR] 2.32, 95% confidence interval [CI] 1.09, 4.97); a history of a previous birth defect-affected pregnancy (adjusted OR 5.27, 95% CI 0.98, 28.37); history of a fever or 'cold' (adjusted OR 3.36, 95% CI 1.68, 6.72); use of analgesic and antipyretic drugs (adjusted OR 4.89, 95% CI 0.92, 25.97); daily passive exposure to cigarette smoke (adjusted OR 1.60, 95% CI 0.94, 2.73); poor ventilation during heating (adjusted OR 3.91, 95% CI 0.75, 20.81); and consumption of >or= six meals per week containing pickled vegetables (adjusted OR 3.86, 95% CI 1.11, 13.47) during pregnancy. Factors which appeared to be protective were meat consumption one to three times per week (adjusted OR 0.62, 95% CI 0.37, 1.06), or >or= four times per week (adjusted OR 0.28, 95% CI 0.11, 0.77); and legume consumption >or= six times per week (adjusted OR 0.39, 95% CI 0.17, 0.89). Differences in risk were found between the two most common phenotypes, anencephaly and spina bifida. Most of the environmental factors had stronger positive and negative associations with risk for anencephaly rather than spina bifida, whereas history of a previous birth defect-associated pregnancy, as well as legume consumption, were more strongly associated with the risk for spina bifida than for anencephaly. The findings suggest that aetiological heterogeneity may exist between anencephaly and spina bifida.

A decreasing rate of neural tube defects following the recommendations for periconceptional folic acid supplementation

Neural tube defects (NTDs) are the most common birth defects, resulting in severe mortality and morbidity. In 1995, the supplementation of folic acid periconceptionally was officially recommended in Germany. The impact of the recommendations on the rate of NTDs was assessed. An active surveillance system was established in the northern Rhine area. From 1996, all departments of obstetrics were asked to report cases of NTDs in all abortions, live births and stillbirths. Compliance with the recommendations was evaluated in a sample of mothers who delivered at the Department of Obstetrics of Düsseldorf University in 2001. From 1996-2003, 520 NTDs were reported. Compared to the rate of NTDs in 1996 (10.5/10,000), the average incidence in the years 1997 to 2003 dropped (6.8/10,000). The intake of folic acid, as recommended, was low among the general population (21.1%). Active surveillance data on the rate of NTDs are compatible with the maximum decrease of about 20% to be expected from data on the implementation of the recommendations. A much greater decrease in NTDs should be the challenge for the future.

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.

International Retrospective Cohort Study of Neural Tube Defects in Relation to Folic Acid Recommendations: Are the Recommendations Working?

This retrospective cohort study was planned to determine whether recommendations to take folic acid have in fact lessened the risk of neural tube defects. Recommendations typically include eating a healthy diet and takingfolic acid supplements when planning pregnancy or throughout the childbearing years. In a few countries, including the United States, flour is fortified so that much of the population will receive at least a small supplemental amount of folic acid. Many governments promote the use of supplements because folic acid is inexpensive, safe, and easy to use. The authors acquired information on more than 13 million births from 13 birth defects registries in Norway that monitored rates of neural tube defects from 1988 to 1998. Cases of anencephaly and spina bifida totaled 8636. Rates of defects were stable during the 10-year monitoring interval in most areas. There were no evident changes in rates of defects after local recommendations were issued. Comparable findings were obtained when analyzing anencephaly and spina bifida separately and combined. Folic acid use in Europe is, in general, low; in Norway, it is approximately 10%. In China, intensive educational efforts and a high rate of planned pregnancies probably are responsible for the effectiveness of a public health campaign to promote the use of folic acid supplements. Rates of folic acid use generally follow economic and educational trends. Fortifying flour with folic acid holds promise for delivering some folic acid to a large part of the population, crossing social and economic barriers. Blood folate levels have increased rapidly where this practice is followed. It is estimated that thousands of neural tube defects occurring since 1992 could have been prevented.

Reduction of birth prevalence rates of neural tube defects after folic acid fortification in Chile

To verify whether the decreasing neural tube defects birth prevalence rates in Chile are due to folic acid fortification or to pre-existing decreasing trends, we performed a population survey using a network of Estudio Colaborativo Latino Americano de Malformaciones Congenitas (ECLAMC, Latin American Collaborative Study of Congenital Malformations) maternity hospitals in Chile, between the years 1982 and 2002. Within each maternity hospital, birth prevalence rates of spina bifida and anencephaly were calculated from two pre-fortification periods (1982-1989 and 1990-2000), and from one fortified period (2001-2002). There was no historical trend for spina bifida birth prevalence rates before folic acid fortification, and there was a 51% (minimum 27%, maximum 66%) decrease in the birth prevalence rates of this anomaly in the fortified period. The relative risks of spina bifida were homogeneous among hospitals in the two period comparisons. There was no historical trend for the birth prevalence of anencephaly comparing the two pre-fortified periods, but the relative risks were heterogeneous among hospitals in this comparison. There was a 42% (minimum 10%, maximum 63%) decrease in the birth prevalence rate of anencephaly in the fortified period as compared with the immediately pre-fortified period, with homogeneous relative risks among hospitals. Within the methodological constraints of this study we conclude that the birth prevalence rates for both spina bifida and anencephaly decreased as a result of folic acid fortification, without interference of decreasing secular trends.