Time trends in the prevalence and epidemiological characteristics of neural tube defects in Liaoning Province, China, 2006-2015: A population-based study.

To evaluate the time trends in the prevalence of neural tube defects and all their subtypes as well as to identify the epidemiological characteristics of these malformations documented in the Liaoning Province of northeast China from 2006 to 2015. This was a population-based observational study using data from 3,248,954 live births as well as from 6217 cases of neural tube defects, 1,600 cases of anencephaly, 2,029 cases of spina bifida, 404 cases of encephalocele, and 3,008 cases of congenital hydrocephalus from 14 cities in Liaoning Province from 2006 to 2015. All analyses were conducted using SPSS software. During the observational period, the prevalence of neural tube defects, anencephaly, spina bifida, encephalocele, and congenital hydrocephalus was 19.1, 4.9, 6.2, 1.2, and 9.3 per 10,000 live births, respectively. Significantly decreasing trends were observed in the prevalence of all these malformations except for encephalocele. Notably, relatively higher prevalence rates were found in isolated compared with non-isolated malformations, with significant differences in selected characteristics (e.g., prognosis status, gestational age, and birth weight) between isolated and non-isolated cases of these malformations. The prevalence of neural tube defects showed a downward trend in Liaoning Province from 2006 to 2015. However, more attention should be focused on non-isolated cases in the future because of the severe clinical manifestations. Future prevention efforts should be strengthened to reduce the risk of these malformations, especially the non-isolated subtype, in areas with high prevalence.

When folic acid fails: Insights from 20 years of neural tube defect surveillance in South Carolina.

Neural tube defects (NTDs) are the most common of the severe malformations of the brain and spinal cord. Increased maternal intake of folic acid (FA) during the periconceptional period is known to reduce NTD risk. Data from 1046 NTD cases in South Carolina were gathered over 20 years of surveillance. It was possible to determine maternal periconceptional FA use in 615 NTD-affected pregnancies. In 163 occurrent (26.9%) and two recurrent (22%) NTD cases, the mothers reported periconceptional FA use. These women were older and more likely to be white. Maternal periconceptional FA usage was reported in 40.4% of cases of spina bifida with other anomalies but in only 25.2% of isolated spina bifida cases (P = 0.02). This enrichment for associated anomalies was not noted among cases of anencephaly or of encephalocele. Among the 563 subsequent pregnancies to mothers with previous NTD-affected pregnancies, those taking FA had a 0.4% NTD recurrence rate, but the recurrence without FA was 8.5%. NTDs with other associated findings were less likely to be prevented by FA, suggesting there is a background NTD rate that cannot be further reduced by FA. Nonetheless, the majority (73.9%) of NTDs in pregnancies in which the mothers reported periconceptional FA use were isolated NTDs of usual types. Cases in which FA failed in prevention of NTDs provide potential areas for further study into the causation of NTDs. The measures and techniques implemented in South Carolina can serve as an effective and successful model for prevention of NTD occurrence and recurrence.

Estimate of the potential impact of folic acid fortification of corn masa flour on the prevention of neural tube defects.

BACKGROUND: Hispanics in the US have a higher prevalence of neural tube defect (NTD) -affected pregnancies than non-Hispanic whites, and lower median total folic acid (FA) intake. FA fortification of corn masa flour (CMF) is a policy-level intervention for NTD prevention; however, the impact on NTD prevalence has not been estimated. METHODS: We developed a model to estimate the percentage reduction in prevalence of spina bifida and anencephaly (NTDs) that could occur with FA fortification of CMF. Model inputs included estimates of the percentage reduction in United States NTD prevalence attributed to FA fortification of enriched cereal grain products (1995-1996 vs. 1998-2002), the increase in median FA intake after enriched cereal grain product fortification, and the estimated increase in median FA intake that could occur with CMF fortification at the same level as enriched cereal grain products (140 µg/100 g). We used Monte Carlo simulation to quantify uncertainty. We stratified analyses by racial/ethnic group and rounded results to the nearest 10. RESULTS: We estimated CMF fortification could prevent 30 Hispanic infants from having spina bifida (95% uncertainty interval: 0, 80) and 10 infants from having anencephaly (95% uncertainty interval: 0, 40) annually. The estimated impact among non-Hispanic whites and blacks was smaller. CONCLUSION: CMF fortification with FA could prevent from 0 to 120 infants, with the most likely value of approximately 40, from having spina bifida or anencephaly among Hispanics, the population most likely to benefit from the proposed intervention. While this estimated reduction is unlikely to be discernible using current birth defect surveillance methods, it still suggests an important benefit to the target population.

Prevalence and trends of selected congenital malformations in New York State, 1983 to 2007.

BACKGROUND: Major birth defects result in high infant mortality and morbidity. It is important to evaluate the burden of birth defects and trends for future intervention and public health improvement. Using the New York State (NYS) Congenital Malformations Registry data, we examined the prevalence and trends of birth defects among children in NYS during 25 years of surveillance. METHODS: Children who had any of the 21 selected birth defects and were born to NYS residents between 1983 and 2007 were selected. The prevalence of each defect was characterized by demographic and birth factors, and the prevalence ratio was calculated. Live births of NYS residents for the same birth year period were used as the denominators for calculating the prevalence. The prevalence trends of birth defects were analyzed by maternal age and race/ethnicity. RESULTS: Compared with non-Hispanic whites, we detected 33%, 21%, and 37% higher prevalence of encephalocele, lower limb deficiencies and omphalocele among non-Hispanic blacks, respectively, and 22% higher prevalence of gastroschisis among Hispanics. Increasing trends of gastroschisis and Down syndrome among non-Hispanic blacks and decreasing trends of spina bifida and limb deficiencies were observed in NYS. CONCLUSION: The findings from this study suggest the existence of racial disparities among children with selected birth defects in NYS. The increasing trends of gastroschisis and Down syndrome observed in NYS are consistent with nationwide trends.

The role of ethnicity and culture on functional status in children with spina bifida.

PURPOSE: Spina bifida is a common cause of pediatric disability and more prevalent in the Hispanic population. Significant health disparities exist in minority populations. Culturally adapted health interventions have been attempted in conditions such as pediatric asthma with improvement. This study aims to explore the influence of ethnicity and culture with regards to functional status and care satisfaction. METHODS: Study participants were recruited from the Children's Hospital Colorado Spinal Defects Clinic. Demographics and past medical and surgical history were obtained via chart review. A questionnaire assessed ethnicity, acculturation, self-care, mobility, bowel and bladder function, and care satisfaction. RESULTS: A total of 70 subjects with spina bifida were included in the statistical analysis. There was no difference in PEDI self-care and mobility scores between ethnicities. The Hispanic group had higher urinary incontinence rates, higher percentage with bladder accidents, and lower satisfaction with bladder management. Regarding bowel function, the Hispanic group had lower satisfaction rates and a trend towards lower bowel continence. CONCLUSIONS: Further work is needed to understand the social and cultural differences between Hispanic and Non-Hispanic children and their families that impact bowel and bladder continence and care satisfaction. Once identified, culturally sensitive interventions may be implemented that can alleviate these apparent health disparities.

Improved survival among children with spina bifida in the United States.

OBJECTIVE: To evaluate trends in survival among children with spina bifida by race/ethnicity and possible prognostic factors in 10 regions of the United States. STUDY DESIGN: A retrospective cohort study was conducted of 5165 infants with spina bifida born during 1979-2003, identified by 10 birth defects registries in the United States. Survival probabilities and adjusted hazard ratios were estimated for race/ethnicity and other characteristics using the Cox proportional hazard model. RESULTS: During the study period, the 1-year survival probability among infants with spina bifida showed improvements for whites (from 88% to 96%), blacks (from 79% to 88%), and Hispanics (from 88% to 93%). The impact of race/ethnicity on survival varied by birth weight, which was the strongest predictor of survival through age 8. There was little racial/ethnic variation in survival among children born of very low birth weight. Among children born of low birth weight, the increased risk of mortality to Hispanics was approximately 4-6 times that of whites. The black-white disparity was greatest among children born of normal birth weight. Congenital heart defects did not affect the risk of mortality among very low birth weight children but increased the risk of mortality 4-fold among children born of normal birth weight. CONCLUSIONS: The survival of infants born with spina bifida has improved; however, improvements in survival varied by race/ethnicity, and blacks and Hispanics continued to have poorer survival than whites in the most recent birth cohort from 1998-2002. Further studies are warranted to elucidate possible reasons for the observed differences in survival.

Working towards a risk prediction model for neural tube defects.

BACKGROUND: Several risk factors have been consistently associated with neural tube defects (NTDs). However, the predictive ability of these risk factors in combination has not been evaluated. METHODS: To assess the predictive ability of established risk factors for NTDs, we built predictive models using data from the National Birth Defects Prevention Study, which is a large, population-based study of nonsyndromic birth defects. Cases with spina bifida or anencephaly, or both (n = 1239), and controls (n = 8494) were randomly divided into separate training (75% of cases and controls) and validation (remaining 25%) samples. Multivariable logistic regression models were constructed with the training samples. The predictive ability of these models was evaluated in the validation samples by assessing the area under the receiver operator characteristic curves. An ordinal predictive risk index was also constructed and evaluated. In addition, the ability of classification and regression tree (CART) analysis to identify subgroups of women at increased risk for NTDs in offspring was evaluated. RESULTS: The predictive ability of the multivariable models was poor (area under the receiver operating curve: 0.55 for spina bifida only, 0.59 for anencephaly only, and 0.56 for anencephaly and spina bifida combined). The predictive abilities of the ordinal risk indexes and CART models were also low. CONCLUSION: Current established risk factors for NTDs are insufficient for population-level prediction of a women's risk for having affected offspring. Identification of genetic risk factors and novel nongenetic risk factors will be critical to establishing models, with good predictive ability, for NTDs.

Applying a knowledge-to-action framework for primary prevention of spina bifida in tropical Africa.

Maternal periconceptual folate supplementation reduces the incidence of neural tube defects; however, in settings where population-level food fortification is not available, it is not clear how best to promote this prevention strategy. Guided by a knowledge-to-action methodology, we used mixed quantitative and qualitative methods to define the local disease burden, then designed, implemented and evaluated a culturally tailored educational intervention in eastern Democratic Republic of Congo, where resource limitations and threats to human security contribute to restricted capacity for the prevention and management of congenital malformations. A descriptive case series of 27 patients undergoing surgery for spina bifida demonstrated a short-term mortality of 15% and long-term disability in survivors. A survey of knowledge, attitudes and practices demonstrated a low level of folate awareness (53%) among women of reproductive age. Focus group discussions revealed exotic aetiologic views, significant gender issues and several barriers to folate use. A culturally tailored radio broadcast and an educational video were designed and produced locally based on qualitative and quantitative findings. Evaluation of the video documented high levels of viewer satisfaction and unequivocal knowledge gain (P ≤ 0.001). We conclude that spina bifida poses a significant burden on affected patients and their families in the African context, but folate is underutilized as a prevention strategy. Patient education through video media results in increased awareness and understanding of spina bifida and folate, a first step in empowering women to reduce the risk of spina bifida in their children in the absence of population-wide food fortification.

Spina bifida subtypes and sub-phenotypes by maternal race/ethnicity in the National Birth Defects Prevention Study.

Spina bifida refers to a collection of neural tube defects, including myelomeningocele, meningocele, and myelocele (SB(M) ), as well as lipomyelomeningocele and lipomeningocele (SB(L) ). Maternal race/ethnicity has been associated with an increased risk for spina bifida among offspring. To better understand this relationship, we evaluated different spina bifida subtypes (SB(M) vs. SB(L) ) and sub-phenotypes (anatomic level or presence of additional malformations) by maternal race/ethnicity using data from the National Birth Defects Prevention Study. This study is a large, multisite, population-based study of nonsyndromic birth defects. Prevalence estimates were obtained using data from spina bifida cases (live births, fetal deaths, and elective terminations) and total live births in the study regions. From October 1997 through December 2005, 1,046 infants/fetuses with spina bifida were delivered, yielding a prevalence of 3.06 per 10,000 live births. Differences in the prevalences of SB(M) vs. SB(L) , isolated versus non-isolated SB(M) , and lesion level in isolated SB(M) among case offspring were observed by maternal race/ethnicity. Compared to non-Hispanic (NH) White mothers, offspring of Hispanic mothers had higher prevalences of each subtype and most sub-phenotypes, while offspring of NH Black mothers generally had lower prevalences. Furthermore, differences in race/ethnicity among those with isolated SB(M) were more pronounced by sex. For instance, among male offspring, the prevalence of isolated SB(M) was significantly higher for those with Hispanic mothers compared to NH White mothers [prevalence ratio (PR): 1.55, 95% confidence interval: 1.23-1.95]. These findings provide evidence that certain spina bifida subtypes and sub-phenotypes may be etiologically distinct.

Health care expenditures among children with and those without spina bifida enrolled in Medicaid in North Carolina.

BACKGROUND: National data on health care use among children with special needs are limited and do not address children with spina bifida (SB). One recent study examined health care costs during 2003 among privately insured individuals with SB. Our objective was to compare health care use and expenditures among publicly insured children with SB to children without a major birth defect and among children with SB with and without hydrocephalus. METHODS: Data from the North Carolina Birth Defects Monitoring Program and Medicaid were linked to identify continuously enrolled children with SB (case children) and children without a major birth defect (control children) born from 1995 to 2002. Medicaid expenditures per child for medical, inpatient, outpatient, dental, well-child care, developmental/behavioral services, and home health for those aged 0 to 4 years old were calculated for case and control children and for case children with and without hydrocephalus. RESULTS: Of 373 case children who survived infancy, 205 (55%) were enrolled in Medicaid. Expenditures were assessed for 144 case and 5674 control children aged 0 to 4 years old continuously enrolled in Medicaid. During infancy, mean expenditure was $33,135 per child with SB and $3900 per unaffected child. The biggest relative expenditures were for developmental/behavioral services (82 times higher for case than control child [$1401 vs. $17]) and home health services (20 times higher [$821 vs. $41]). Average expenditure for an infant with SB and hydrocephalus was 2.6 times higher than an infant with SB without hydrocephalus ($40,502 vs. $15,699). CONCLUSIONS: Expenditure comparisons by SB subtype are important for targeting health care resources.

Twenty-five-year survival of children with birth defects in New York State: a population-based study.

BACKGROUND: Few studies have been conducted on long-term survival of children with major birth defects because of a lack of longitudinal birth defects surveillance data. The objective of this study was to conduct a 25-year survival analysis among children in New York born with major defects by survival age, birth defect category, and other possible contributing factors. METHODS: A cohort was constructed containing children born in 1983 to 2006 with selected major birth defects. Deaths among the study cohort were identified by matching the children to their death certificates. The survival probability was estimated by Kaplan-Meier methods. Cox proportional hazards regression was used to examine the effect of the risk factors on survival. RESULTS: A total of 9112 deaths were identified among 57,002 live births with selected birth defects between 1983 and 2006. The overall 25-year survival probability of the study cohort was 82.51% (95% confidence interval, 82.11-82.89%). The estimated survival probability was comparable to that reported from previous studies regarding individual defects including spina bifida, encephalocele, atrioventricular septal defects, tracheoesophageal fistula and esophageal atresia or stenosis, renal agenesis or dysgenesis, lower limb reduction, diaphragmatic hernia, abdominal wall defects, and Down syndrome. Sex, low birth weight for gestational age, existence of multiple birth defects (nonisolated), and maternal age and nativity were identified as risk factors. CONCLUSION: Using the statewide, population-based birth defects surveillance data in New York State, the survival experience of the study cohort was examined across all survival time periods by individual birth defect of interest. Several risk factors that affect survival were identified.

Cultural considerations in the care of children with spina bifida.

Spina bifida occurs when the neural tube fails to close during early fetal development, resulting in a range of neural tube defects (NTDs). The cause of spina bifida is not fully understood, but scientists believe that NTDs are the result of genetic and environmental factors acting simultaneously. The Centers for Disease Control reports that spina bifida and other NTDs occur more frequently in some ethnic groups, such as Hispanic people, than in others. The United States is increasingly multicultural and diverse, and it is becoming more difficult to categorize individuals into a single racial/ethnic group. This article uses the term ethnicity as defined by the Institute of Medicine and avoids using race unless part of a particular study.

Associations of ethnicity and SES with IQ and achievement in spina bifida meningomyelocele.

OBJECTIVES: We evaluated whether the phenotypic pattern of higher verbal than nonverbal IQ in children with spina bifida meningomyelocele (SBM) is consistent across subgroups differing in ethnicity and SES. We also explored the relation of cognitive and academic performance. METHODS: Non-Hispanic White (n = 153) and Hispanic (n = 80) children with SBM received the Stanford Binet Test of Intelligence-IV and achievement subtests of the Woodcock-Johnson. Parents completed questionnaires assessing the family environment [socioeconomic status (SES), resources, and educational opportunities]. RESULTS: Multivariate analysis revealed that Hispanic children with lower SES had lower verbal than nonverbal scores. Hispanic children with higher SES and non-Hispanic White children demonstrated the reverse pattern. Verbal and nonverbal IQ interacted to predict reading and math performance. CONCLUSIONS: Lower SES is associated with lower verbal IQ in economically disadvantaged Hispanic children with SBM. Academic achievement is largely correlated with verbal IQ, but children with lower verbal IQ may partially compensate with higher nonverbal ability.

A Mexican American mother's experience in the neonatal intensive care unit.

BACKGROUND: Most parents would agree that the admission of an infant to the neonatal intensive care unit (NICU) is stressful. Existing research is focused on white mothers, with little known about the experiences of Spanish-speaking, Mexican American mothers who have an infant in the NICU. PURPOSE: The purpose of this qualitative case study was to describe the experiences of a Spanish-speaking, Mexican American mother whose infant had been in the NICU. METHODS: Qualitative description was used to conduct this study. One Spanish-speaking, Mexican American mother who had an infant in the NICU was recruited through purposive sampling. An in-depth interview was conducted, audio-recorded, and transcribed verbatim. Conventional content analysis was used to analyze the data. FINDINGS: Analysis of the data revealed that the experience of a Spanish-speaking, Mexican American mother who had an infant in the NICU was one of uncertainty, involvement, trust, and anticipating discrimination.

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.

Are birth defects among Hispanics related to maternal nativity or number of years lived in the United States?

BACKGROUND: Literature on the risk of birth defects among foreign- versus U.S.-born Hispanics is limited or inconsistent. We examined the association between country of birth, immigration patterns, and birth defects among Hispanic mothers. METHODS: We used data from the National Birth Defects Prevention Study and calculated odds ratios (ORs) and 95% confidence intervals and assessed the relationship between mothers' country of birth, years lived in the United States, and birth defects among 575 foreign-born compared to 539 U.S.-born Hispanic mothers. RESULTS: Hispanic mothers born in Mexico/Central America were more likely to deliver babies with spina bifida (OR = 1.53) than their U.S.-born counterparts. Also, mothers born in Mexico/Central America or who were recent United States immigrants (< or =5 years) were less likely to deliver babies with all atrial septal defects combined, all septal defects combined, or atrial septal defect, secundum type. However, Hispanic foreign-born mothers who lived in the United States for >5 years were more likely to deliver babies with all neural tube defects combined (OR = 1.42), spina bifida (OR = 1.89), and longitudinal limb defects (OR = 2.34). Foreign-born mothers, regardless of their number of years lived in the United States, were more likely to deliver babies with anotia or microtia. CONCLUSIONS: Depending on the type of birth defect, foreign-born Hispanic mothers might be at higher or lower risk of delivering babies with the defects. The differences might reflect variations in predisposition, cultural norms, behavioral characteristics, and/or ascertainment of the birth defects.

The prevalence and predictors of anencephaly and spina bifida in Texas.

Texas shares a 1255-mile border with Mexico and encompasses a variety of ecosystems, industries and other potential environmental exposures. The Texas Birth Defects Registry is an active surveillance system which covers all pregnancy outcomes (livebirths, fetal deaths and elective pregnancy terminations). This study describes the occurrence and the predictors of neural tube defects (anencephaly and spina bifida) in Texas between 1999 and 2003. Birth prevalence, crude and adjusted prevalence ratios and 95% confidence intervals were calculated using Poisson regression, for each defect, by fetal/infant sex, delivery year and maternal sociodemographic characteristics. Among approximately 1.8 million livebirths, a total of 1157 neural tube defects cases were ascertained by the Registry, resulting in an overall prevalence of 6.33 cases per 10 000 livebirths. The prevalences of anencephaly and spina bifida were 2.81 and 3.52 per 10 000 livebirths respectively. Prevalences of both defects were highest in Hispanics, among mothers living along the border with Mexico, among women of higher parity and among mothers who were 40+ years of age. In addition, the prevalence of each defect was higher among women with no record of prenatal care and among women with less than 7 years of education. Hispanic ethnicity was an important predictor for anencephaly, along with sex, maternal age, parity and border residence. However, only border residence and delivery year were significant predictors for spina bifida.

Racial/ethnic differences in the birth prevalence of spina bifida - United States, 1995-2005.

In 1992, the U.S. Public Health Service recommended that all women of childbearing age consume 400 microg of folic acid daily to help prevent pregnancies affected by neural tube defects (NTDs) such as spina bifida. Subsequently, the Food and Drug Administration mandated adding folic acid to all enriched cereal grain products by January 1998. During October 1998--December 1999, the birth prevalence of spina bifida in the United States decreased 22.9% compared with 1995--1996; however, by 2003--2004, no further decrease had been observed. Notably, the prevalence of NTD-affected pregnancies remained higher among Hispanic women than among women in other racial/ethnic populations. To update previously reported data and assess racial/ethnic differences, CDC analyzed birth certificate data for four periods during 1995--2005. This report summarizes the results of that analysis, which indicated that from the early postfortification period, 1999--2000, to the most recent period of analysis, 2003--2005, the prevalence of spina bifida declined 6.9%, from 2.04 to 1.90 per 10,000 live births (prevalence ratio [PR] = 0.93; 95% confidence interval [CI] = 0.87--1.00). Among infants with non-Hispanic black mothers, prevalence fell 19.8%, from 2.17 to 1.74 per 10,000 live births (PR = 0.80; CI = 0.67--0.96), while prevalence among infants with non-Hispanic white and Hispanic mothers remained nearly constant. Additional public health efforts targeting women with known risk factors (e.g., obesity and certain genetic factors) likely are needed to further reduce the prevalence of spina bifida in the United States.

Genetic polymorphisms in the thioredoxin 2 (TXN2) gene and risk for spina bifida.

TXN2 encodes human thioredoxin 2, a small redox protein important in cellular antioxidant defenses, as well as in the regulation of apoptosis. Txn2 knockout mice fail to complete neural tube closure by E10.5 and die in utero. We hypothesized that genetic variation in human TXN2 gene may alter the function of the encoded protein in a manner associated with an increased risk for neural tube defects (NTDs). A DNA re-sequencing effort of the human TXN2 gene was taken. After a variation in the promoter was identified, the transcriptional activity of different alleles was investigated. The possible association between these variations and the risk of spina bifida was further evaluated in a subset of samples obtained from a large population-based case-control study in California in two different ethnicity groups, non-Hispanic white and Hispanic white. We identified a novel promoter insertion polymorphism located 9 base pairs upstream of the transcription start site of exon 1(-9 insertion). The GA, G and GGGA insertions were associated with a marked decrease of transcriptional activity when overexpressed in both U2-OS (an osteosarcoma cell line) and 293 cells (derived from human embryonic kidney). Further analysis revealed that the GA insertion was associated with increased spina bifida risk for Hispanic whites. Our study revealed a novel Ins/Del polymorphism in the human TXN2 gene proximal promoter region that altered the transcriptional activity and is associated with spina bifida risk. This polymorphism may be a genetic modifier of spina bifida risk in this California population.

Characteristics of a spina bifida population including North American Caucasian and Hispanic individuals.

BACKGROUND: Meningomyelocele (MM) is a common human birth defect. MM is a disorder of neural development caused by contributions from genes and environmental factors that result in the NTD and lead to a spectrum of physical and neurocognitive phenotypes. METHODS: A multidisciplinary approach has been taken to develop a comprehensive understanding of MM through collaborative efforts from investigators specializing in genetics, development, brain imaging, and neurocognitive outcome. Patients have been recruited from five different sites: Houston and the Texas-Mexico border area; Toronto, Canada; Los Angeles, California; and Lexington, Kentucky. Genetic risk factors for MM have been assessed by genotyping and association testing using the transmission disequilibrium test. RESULTS: A total of 509 affected child/parent trios and 309 affected child/parent duos have been enrolled to date for genetic association studies. Subsets of the patients have also been enrolled for studies assessing development, brain imaging, and neurocognitive outcomes. The study recruited two major ethnic groups, with 45.9% Hispanics of Mexican descent and 36.2% North American Caucasians of European descent. The remaining patients are African-American, South and Central American, Native American, and Asian. Studies of this group of patients have already discovered distinct corpus callosum morphology and neurocognitive deficits that associate with MM. We have identified maternal MTHFR 667T allele as a risk factor for MM. In addition, we also found that several genes for glucose transport and metabolism are potential risk factors for MM. CONCLUSIONS: The enrolled patient population provides a valuable resource for elucidating the disease characteristics and mechanisms for MM development.