Understanding perspectives on neural tube defect management: insights from Jordanian parents.

INTRODUCTION: Neural tube defects (NTDs) represent a spectrum of heterogeneous birth anomalies characterized by the incomplete closure of the neural tube. In Jordan, NTDs are estimated to occur in approximately one out of every 1000 live births. Timely identification of NTDs during the 18-22 weeks of gestation period offers parents various management options, including intrauterine NTD repair and termination of pregnancy (TOP). This study aims to assess and compare parental knowledge and perceptions of these management modalities between parents of affected children and those with healthy offspring. MATERIALS AND METHODS: This retrospective case-control study was conducted at Jordan University Hospital (JUH) using telephone-administered questionnaires. Categorical variables were summarized using counts and percentages, while continuous variables were analyzed using mean and standard deviation. The association between exposure variables and outcomes was explored using binary logistic regression. Data analysis was performed using SPSS for Windows version 26 (SPSS Inc., Chicago, IL). RESULTS: The study sample comprised 143 participants, with 49.7% being parents of children with NTDs. The majority of NTD cases were associated with unplanned pregnancies, lack of folic acid supplementation, and postnatal diagnosis. Concerning parental knowledge of TOP in Jordan, 86% believed it to be legally permissible in certain situations. However, there was no statistically significant difference between cases and controls regarding attitudes toward TOP. While the majority of parents with NTD-affected children (88.7%) expressed a willingness to consider intrauterine surgery, this percentage decreased significantly (to 77.6%) after receiving detailed information about the procedure's risks and benefits (p = .013). CONCLUSIONS: This study represents the first case-control investigational study in Jordan focusing on parental perspectives regarding TOP versus intrauterine repair of myelomeningocele following a diagnosis of an NTD-affected fetus. Based on our findings, we urge the implementation of a national and international surveillance program for NTDs, assessing the disease burden, facilitating resource allocation toward prevention strategies, and promoting early diagnosis initiatives either by using newly suggested diagnostic biomarkers or early Antenatal ultrasonography.

Periconceptional folic acid usage and its associated factors in eastern Sudan: A cross-sectional study.

BACKGROUND: Several countries poorly adhere to the World Health Organization's recommendation of folic acid supplementation in the periconceptional period, especially in limited-resource settings. OBJECTIVE: The objective of this study was to investigate the prevalence of and the factors associated with folic acid usage in the periconceptional period among pregnant women at Gadarif Maternity Hospital in eastern Sudan. STUDY DESIGN: This is a cross-sectional study. METHODS: This study was conducted in eastern Sudan from April to September 2022. A total of 720 pregnant women in their first trimester were enrolled. The sociodemographic characteristics and clinical and obstetrical data of pregnant women in their first trimester were assessed using a face-to-face questionnaire. In addition, multivariate regression analysis was performed. RESULTS: In this study, the median (interquartile range) of the age and gravidity of the enrolled women was 26.3 (24.14-29.52) years and 2 (1-4), respectively. Of these 720 women, 423 (58.8%) used folic acid during the periconceptional period, while 27 (3.7%) women used folic acid in the preconceptional period. None of the investigated factors (age, residence, education, employment, body mass index, or gravidity) were associated with periconceptional use of folic acid. CONCLUSION: The study revealed a low prevalence of folic acid usage in preconceptional period among pregnant women in eastern Sudan. Additional efforts are needed to promote folic acid usage in the preconceptional period as well as in the first trimester.

Seasonal trend in the occurrence of myelomeningocele in nigeria: a hypothesis of climate-induced oxidative stress.

PURPOSE: Myelomeningocele is the most severe birth defect compatible with long-term survival. It accounts for 5.7% of neurological surgeries in Nigeria. However, the exact cause of this neural tube defect remains unidentified. This study aims to determine if seasonal variation is a potential environmental contributor. METHOD: This study prospectively recruited 242 children diagnosed with myelomeningocele at the University of Nigeria Teaching Hospital (UNTH), Enugu, Nigeria, between January 2010 and December 2022. Our primary outcome was the seasonal occurrence of myelomeningocele, while covariates included gender, birth order, maternal folic acid supplementation (FAS), and parental age. The estimated month of conception was derived from the mother's last menstrual period (LMP), and the occurrence of myelomeningocele across the various seasons in which these babies were conceived was assessed using the Lorenz curve and the Gini coefficient. RESULTS: 242 patients were studied with a male-to-female ratio of 1.26. The majority of cases were lumbosacral (93.4%), and none of the mothers commenced FAS before conception. The highest proportion of cases (39.7%) occurred during the hottest period of the dry season (January-March), while the lowest proportion (15.7%) occurred during the early wet season (April-June). The Gini index of 0.29, and the Gini coefficient derived from 100,000 Monte Carlo simulations of 0.24, indicate a significant variation in the distribution of myelomeningocele cases across different seasons of conception. CONCLUSION: The seasonal occurrence of myelomeningocele with a peak in January-March suggests a potential association with environmental factors including oxidative stress induced by solar radiation.

Hispanic Women's Perceptions of Neural Tube Defects and Folic Acid Supplementation: A Qualitative Study.

INTRODUCTION: In the United States, the prevalence of neural tube defects (NTDs) is higher among infants born to Hispanic women compared with those born to non-Hispanic women. The purpose of this study is to investigate perceptions of NTDs and the use of folic acid and folate as a preventive measure among Hispanic women. METHODS: Purposive sampling was used to recruit Hispanic women from a prenatal clinic in a Northeastern metropolitan city. In-depth interviews were conducted by native Spanish-speaking researchers using a semistructured interview guide. Thematic analysis was used to develop themes related to a priori domains. FINDINGS: The study sample consisted of 26 Hispanic women representing nine countries of origin. Four themes were revealed: dietary sources of folic acid, awareness of folic acid supplementation and fortification, preferences for receiving health information, and factors in decision-making concerning an NTD diagnosis. CONCLUSIONS: This study highlights the importance of early and targeted educational interventions sensitive to the cultural needs of this population. Results suggest that current NTD health education efforts may not be sufficient to increase our participants' knowledge of NTD. Additionally, the disparity may be multimodal, potentially influenced by insufficient understanding of prenatal folic acid use and the role of religiosity in decision-making during pregnancy. If Hispanic women are more likely to continue pregnancies affected by NTDs, this factor could be a part of NTD disparities. Exploring factors beyond supplementation and fortification that might influence rates of NTDs at birth in the U.S. Hispanic population can help to inform prevention efforts.

Clinical presentation and outcomes of neonates born with neural tube defects- an experience from a level III B NICU in Western India.

PURPOSE: Neural tube defects (NTDs) are one of the most common congenital anomalies and a cause of chronic disability. The study was done to study outcomes of neural tube defects admitted at a tertiary level neonatal intensive care unit (NICU) from 2018 to 2022, a period of 4 years that also coincided with the COVID pandemic. The secondary outcome was to study the clinical presentation, associated anomalies and epidemiological features. METHODS: It was a retrospective observational study; data of infants was obtained from medical records and analysis was done. RESULTS: Thirty-four neonates were enrolled, of which there were 16 (47%) males and 18 (53%) females. History of pre-pregnancy maternal folate intake was present in 4 (11.7%) cases. 33 (97%) babies were diagnosed with meningomyelocele (MMC) and one each had anencephaly, iniencephaly and encephalocele, of which one had frontal and two had occipital encephalocele. The median age of surgery was 16 days of life with primary repair being the most common procedure followed by MMC repair with VP shunt. Twenty babies (58.8%) were discharged successfully, while 9 (26.5%) expired and 5 (14.7%) were discharged against medical advice; which can be attributed to the financial problems of the patients in a developing country. The overall deaths in our series were four (26.5%) which is slightly higher than other studies which may be due to the fact that this study was conducted during the COVID era with lesser rates of folate supplementation, reduced access to prenatal diagnosis coupled with poor follow-up and compliance of patients post-surgical repair. CONCLUSION: This study emphasizes the importance of periconceptional folic acid supplementation, prenatal diagnosis, early surgery and meticulous follow-up as being pivotal to improving outcomes in children with NTDs.

Prevalence of neural tube defects in England prior to the mandatory fortification of non-wholemeal wheat flour with folic acid: a population-based cohort study.

OBJECTIVES: To determine the baseline trends in the total birth prevalence of neural tube defects (NTDs) in England (2000-2019) to enable the impact of folic acid fortification of non-wholemeal wheat flour to be monitored. DESIGN: Population-based, observational study using congenital anomaly (CA) registration data for England curated by the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS). SETTING: Regions of England with active registration in the time period. PARTICIPANTS: Babies that were liveborn or stillborn and pregnancies that resulted in a termination of pregnancy or a late miscarriage (20-23 weeks' gestation) with an NTD. MAIN OUTCOME MEASURES: Total birth prevalence of anencephaly, spina bifida and all NTDs in England. Poisson regression analysis was used to evaluate time trends with regional register as a random effect. The progress of national registration across England was assessed. RESULTS: There were 4541 NTD pregnancies out of 3 637 842 births in England; 1982 anencephaly and 2127 spina bifida. NTD prevalence was 12.5 (95% CI 12.1 to 12.9) per 10 000 total births. NTD prevalence per 10 000 total births was significantly higher in 2015-2019 (13.6, 95% CI 12.9 to 14.4) compared with 2010-2014 (12.1, 95% CI 11.7 to 12.5). An increasing trend in NTDs overall was detected (incidence rate ratio (IRR) 1.01, 1.00 to 1.02), although further analysis determined this effect was confined to 2015-2019 (compared against 2000-2004, IRR 1.14, 1.04 to 1.24). The birth prevalence of anencephaly reflected this pattern. The prevalence of spina bifida remained relatively stable over time. CONCLUSIONS: Baseline NTD prevalence for England has been established. National and standardised CA registration is in place, facilitating the systematic and consistent monitoring of pre-fortification and post-fortification NTD trends and evaluating the impact of fortification on NTD prevalence.

Determinants of neural tube defects among women who gave birth in hospitals in Eastern Ethiopia: evidence from a matched case control study.

INTRODUCTION: Neural tube defects (NTDs) are severe birth defects caused by nutritional, genetic or environmental factors. Because NTDs continue to have a significant health and economic impact on children and community at large, it is crucial to investigate potential risk factors in order to develop novel approaches to NTDs prevention. Determinants for the development of NTDs differ by country, region as well as within the country. The objective of this study was to identify the determinants of NTDs among newborns delivered in three hospitals found in eastern Ethiopia. METHODS: A hospital-based matched case-control study was conducted among 138 cases and 138 control women who delivered in three teaching hospitals in Eastern Ethiopia in 2021. Data were collected using a structured and pre-tested interviewer-administered questionnaire. Cases were mothers who delivered a neonate with any type of NTDs regardless of gestational age or fetal viability, whereas controls were mothers who delivered an apparently healthy newborn. Chi-square was used to assess the significant difference between the two groups. Conditional logistic regression model was used to generate adjusted odds ratio with its corresponding 95% confidence intervals and compare the two groups. RESULTS: Anencephaly (51.4%) and spinal bifida (34.1%) were the most frequently observed NTDs. None of study participants took preconception folic acid supplementation. Being a non-formal mothers (AOR = 0.34, 95% CI: 0.12-0.92, P = 0.034), rural residence, (AOR = 3.4, 95% CI: 1.18-9.78, P = 0.023), history of spontaneous abortion (AOR = 2.95, 95% CI: 1.15-7.55, P = 0.023), having severe anemia (AOR = 3.4, 95% CI: 1.17-9.87, P = 0.024), history of fever or cold (AOR = 2.75; 95% CI: 1.05-7.15, P = 0.038), and an exposure to various agro-chemicals (AOR = 3.39, 95% CI: 1.11-10.3, P = 0.032) were independent determinants of NTDs. CONCLUSION AND RECOMMENDATION: In this study, NTDs were associated to several determinant factors in the area, including residential area, history of spontaneous abortion, severe anemia, fever/cold, antibiotic use before or during early pregnancy, and exposure to agrochemicals. Addressing the identified determinants is critical in averting the incidence of NTDs in the study area. Moreover, more research is needed to investigate women's dietary practices as well as the practice of preconception folic acid supplementation for pregnant women in Ethiopia's current health care system.

Inequities in pre-pregnancy folic acid use in Central and South Auckland: secondary analysis from a postpartum contraception survey.

Introduction In Aotearoa New Zealand (NZ), there is inequity in rates of neural tube defects (NTDs). Among Maaori, NTD occur in 4.58/10 000 live births, and for Pacific peoples, it is 4.09/10 000 live births; this is compared to 2.81/10 000 live births for non-Maaori, non-Pacific peoples. Aim To describe self-reported pre-pregnancy folic acid supplementation and to determine the association between pregnancy intendedness, ethnicity, parity, maternal age, care provider and pre-pregnancy folic acid supplementation. Methods Secondary analysis of postpartum survey data collected at Te Whatu Ora Te Toka Tumai and Counties Manukau birthing facilities in 2020 was conducted. Descriptive analyses explored pregnancy intendedness and self-reported folic acid use by demographic variables. Multivariable logistic regression explored independent associations between demographic variables and folic acid use among intended pregnancies. Results In total, 398 participants completed the survey. The response rate was (140/149) 94% at Counties Manukau and (258/315) 82% at Te Toka Tumai. Pre-pregnancy supplementation was reported by 182 of 398 participants (46%). Use was higher among those who intended their pregnancy (151/262, 58%) compared to those who were 'pregnancy ambivalent' (9/33, 27%) or did not intend to become pregnant (22/103, 21%). Factors independently associated with supplementation among intended pregnancies included: 'Other ethnicity' (European, Middle Eastern, Latin American, African) compared to Maaori (aOR 5.3 (95% CI 1.3, 21.8)), age ≥30 years compared to Discussion Low rates of pre-pregnancy folic acid supplementation exist in Auckland with significant ethnic disparity. Mandatory fortification of non-organic wheat is important, but supplementation is still recommended to maximally reduce risk.

Birth prevalence and risk factors of neural tube defects in Ethiopia: a systematic review and meta-analysis.

OBJECTIVE: This study aims to estimate the prevalence of neural tube defects (NTDs) and to identify potential risk factors in the Ethiopian context. STUDY DESIGN: Systematic review and meta-analysis. STUDY PARTICIPANTS: A total of 611 064 participants were included in the review obtained from 42 studies. METHODS: PubMed (Medline), Embase and Cochrane Library databases in combination with other potential sources of literature were systematically searched, whereby studies conducted between January 2010 and December 2022 were targeted in the review process. All observational studies were included and heterogeneity between studies was verified using Cochrane Q test statistics and I2 test statistics. Small study effects were checked using Egger's statistical test at a 5% significance level. RESULT: The pooled prevalence of all NTDs per 10 000 births in Ethiopia was 71.48 (95% CI 57.80 to 86.58). The between-study heterogeneity was high (I2= 97.49%, p<0.0001). Birth prevalence of spina bifida (33.99 per 10 000) was higher than anencephaly (23.70 per 10 000), and encephalocele (4.22 per 10 000). Unbooked antenatal care (AOR 2.26, 95% CI (1.30 to 3.94)), preconception intake of folic acid (AOR 0.41, 95% CI (0.26 to 0.66)), having chronic medical illness (AOR 2.06, 95% CI (1.42 to 2.99)), drinking alcohol (AOR 2.70, 95% CI (1.89 to 3.85)), smoking cigarette (AOR 2.49, 95% CI (1.51 to 4.11)), chewing khat (AOR 3.30, 95% CI (1.88 to 5.80)), exposure to pesticides (AOR 3.87, 95% CI (2.63 to 5.71)), maternal age ≥35 (AOR 1.90, 95% CI (1.13 to 3.25)), maternal low educational status (AOR 1.60, 95% CI (1.13 to 2.24)), residing in urban areas (AOR 0.75, 95% CI (0.58 to 0.97))and family history of NTDs (AOR 2.51, 95% CI (1.36 to 4.62)) were associated with NTD cases. CONCLUSION: The prevalence of NTDs in Ethiopia is seven times as high as in other Western countries where prevention measures are put in place. Heredity, maternal and environmental factors are associated with a high prevalence of NTDs. Mandatory fortification of staple food with folic acid should be taken as a priority intervention to curb the burden of NTDs. To smoothen and overlook the pace of implementation of mass fortification, screening, and monitoring surveillance systems should be in place along with awareness-raising measures. PROSPERO REGISTRATION NUMBER: CRD42023413490.

Associations between maternal stressful life events experiences and risk of neural tube defects in offspring: a systematic review and meta-analysis.

OBJECTIVES: Multiple factors associated with neural tube defects (NTDs) risk have been identified, yet there is little evidence on the possible effects of maternal stressful life events. In this study, we aimed to investigate the association between stressful life events during the periconceptional period and risk of NTDs in offspring. METHODS: Relevant literature was searched in PubMed, Springer Link, ScienceDirect, and Cochrane Library up to July 2023. The pooled odds ratio (OR) and 95% confidence interval (CI) of NTDs risk with maternal stressful life events were estimated using a random effects model. Publication bias was assessed using Egger's regression asymmetry test and Begg's rank correlation test with Begg's funnel plot. RESULTS: Analysis results showed that mothers who experienced stressful life events during the periconceptional period were at greater risk of having NTDs offspring (OR: 1.37, 95% CI: 1.08-1.73) than those who did not. In subgroup analysis, the pooled OR was 1.37 (1.13-1.67) and 1.73 (0.36-8.32) for with and without adjusting for folic acid supplementation in each included study, while was 1.37 (1.13-1.67) and 1.64 (0.39-6.88) for exposure time of three months preconception until three months post conception and one year preconception until three months post conception, respectively. CONCLUSIONS: This study suggests that maternal stressful life events during the periconceptional period are significantly associated with higher NTDs risk in offspring. Tailored approaches for evaluating the risk and policy of NTDs among women of childbearing age should emphasize individual stressful experiences before and during early pregnancy.

National Diet and Nutrition Survey data reveal a decline in folate status in the United Kingdom population between 2008 and 2019.

BACKGROUND: Folate is essential for healthy growth and development. Fortification of foods with folic acid can improve folate status and reduce risk of neural tube defects (NTD). Following concern around folate status in the United Kingdom, the United Kingdom government announced in 2021 the intention to introduce mandatory folic acid fortification. OBJECTIVE: This study aimed to describe folate status in the United Kingdom population prior to the implementation of mandatory folic acid fortification of non-whole wheat (non-wholemeal) flour and to assess trends in folate status, including in females of reproductive age (FRA). METHODS: Data were from the United Kingdom National Diet and Nutrition Survey Rolling Program (2008-2019), a cross-sectional, nationally representative survey of children and adults aged 1.5+ (n = 5792 with folate result). Serum folate concentration was measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) and red blood cell (RBC) folate concentration by microbiological assay. Concentration data were compared against method-specific cut-offs and thresholds, and relationships were explored against demographic and lifestyle characteristics. RESULTS: RBC and serum folate concentration significantly decreased by ∼3 percentage points per year between 2008 and 2019 in all age/sex groups. Prevalence of deficiency (RBC folate < 305 nmol/L) was highest in children aged 11 to 18 y (17% in 2016-2019). The proportion of FRA below the cut-off for increased risk of NTD (RBC folate < 748 nmol/L) increased from 69% to 89% between 2008 and 2019. Ethnicity, smoking status, and income were significant determinants of RBC and serum folate concentrations. CONCLUSIONS: These data reveal a decline in population folate status in the United Kingdom between 2008 and 2019 and a high prevalence of folate deficiency. A high proportion of FRA had RBC folate concentrations below the cut-off for increased risk of NTD. These data provide information on folate status in a population not currently exposed to mandatory folic acid fortification and are essential to model and assess its impact.

"Prevalence and secular trend of neural tube defects in fetal deaths in Argentina, 1994-2019".

BACKGROUND: Fetal deaths are a major source of information on the epidemiology of neural tube defects (NTDs; anencephaly and myelomeningocele). We analyzed NTDs prevalence and secular trend using fetal death records between 1994 and 2019 in Argentina. MATERIALS AND METHODS: Data were obtained from the Department of Statistics and Information of the Ministry of Health (DEIS). Using the number of fetal deaths due to anencephaly and myelomeningocele, we estimated the proportion of all fetal deaths due to anencephaly, myelomeningocele, and NTDs (anencephaly + myelomeningocele) during pre- and post-fortification period in Argentina. We also estimated the ratio of fetal deaths due to anencephaly, myelomeningocele, and NTDs (anencephaly + myelomeningocele) to 10,000 live births. Secular trend in the outcomes was analyzed using a Poisson model and Joinpoint regression analysis. RESULTS: In the entire period analyzed, the NTD proportion on fetal deaths was 1.32. In 1994, NTDs accounted for 34.7% of congenital malformations fetal deaths (CM) and 1.7% of all fetal deaths, whereas in 2019, these percentages were 9.4% and 0.5%, respectively. NTDs present a negative secular trend (p < .05). The risk of fetal death due to anencephaly and myelomeningocele decreases between 2005 and 2019 by 67% and 51% respectively (p < .05) in comparison to the period between 1994 and 2004 before the effective fortification of wheat flour used in the food industry destined for the domestic market. DISCUSSION AND CONCLUSION: We found a significant decrease in the risk of all fetal deaths due to NTDs, particularly anencephaly, in Argentina over the study period, with most reduction observed during the mandatory flour fortification era (introduced in Argentina in 2002). The inclusion of fetal deaths in NTD surveillance, coupled or uncoupled with other pregnancy outcomes, is essential for monitoring preventive supplementation measures.

Periconceptional intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further reduce the risk of neural tube defects in offspring: a United States population-based case-control study of women meeting the folic acid recommendations.

BACKGROUND: Neural tube defects (NTDs) still occur among some women who consume 400 µg of folic acid for prevention. It has been hypothesized that intakes of methyl donors and other micronutrients involved in one-carbon metabolism may further protect against NTDs. OBJECTIVES: To investigate whether intakes of vitamin B6, vitamin B12, choline, betaine, methionine, thiamine, riboflavin, and zinc, individually or in combination, were associated with NTD risk reduction in offspring of women meeting the folic acid recommendations. METHODS: Data were from the National Birth Defects Prevention Study (United States population-based, case-control). We restricted deliveries between 1999 and 2011 with daily periconceptional folic acid supplementation or estimated dietary folate equivalents ≥400 µg. NTD cases were live births, stillbirths, or terminations affected by spina bifida, anencephaly, or encephalocele (n = 1227). Controls were live births without a major birth defect (n = 7095). We categorized intake of each micronutrient as higher or lower based on a combination of diet (estimated from a food frequency questionnaire) and periconceptional vitamin supplementation. We estimated NTD associations for higher compared with lower intake of each micronutrient, individually and in combination, expressed as odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age, race/ethnicity, education, and study center. RESULTS: NTD associations with each micronutrient were weak to modest. Greater NTD reductions were observed with concurrent higher-amount intakes of multiple micronutrients. For instance, NTD odds were ∼50% lower among participants with ≥4 micronutrients with higher-amount intakes than among participants with ≤1 micronutrient with higher-amount intake (adjusted OR: 0.53; 95% CI: 0.33, 0.86). The strongest reduction occurred with concurrent higher-amount intakes of vitamin B6, vitamin B12, choline, betaine, and methionine (adjusted OR: 0.26; 95% CI: 0.09, 0.77) compared with ≤1 micronutrient with higher-amount intake. CONCLUSIONS: Our findings support that NTD prevention, in the context of folic acid fortification, could be augmented with intakes of methyl donors and other micronutrients involved in folate metabolism.

Contribution of folic acid to human health and challenges of translating the science into effective policy: a call to action for the implementation of food fortification in Ireland.

Over 30 years ago it was proven beyond doubt that folic acid supplementation of mothers in early pregnancy protects against neural tube defects (NTD) in their babies. Such conclusive scientific evidence led to clear recommendations for women worldwide to take 0⋅4 mg/d folic acid before conceiving and in early pregnancy, but implementing these into effective policy has been problematic. As a result, there has been no change in the incidence of NTD in Ireland, the UK or any other European country over the 25-year period that the current strategy, recommending periconceptional folic acid supplements to women, has been in place. Thus preventable NTD are not being prevented. Notably, in September 2021, the UK government announced that starch is to be fortified with folic acid on a mandatory basis. A similar decision is now urgently needed in Ireland, where rates of NTD are among the highest in the world. A policy of mandatory folic acid fortification of food would be highly effective in preventing NTD because it reaches all women, including those who have not planned their pregnancy. International evidence shows that wherever such a policy has been introduced, it has proved to be effective in reducing rates of NTD in that country. Apart from preventing NTD, the driver of policy in the area, other potential health benefits across the lifecycle can be anticipated from folic acid fortification. Urgent action is needed on implementation of mandatory food fortification with folic acid in Ireland so that mothers and their babies can benefit.

Global strategies for the prevention of neural tube defects through the improvement of folate status in women of reproductive age.

INTRODUCTION: Neural tube defects represent a global public health problem, mainly in countries where effective prevention strategies are not yet in place. The global prevalence of neural tube defects is estimated at 18.6/10,000 (uncertainty interval: 15.3-23.0) live births, where ~ 75% of cases result in under-five mortality. Most of the mortality burden is in low- and middle-income countries. The main risk factor for this condition is insufficient folate levels in women of reproductive age. METHODS: This paper reviews the extent of the problem, including the most recent global information on folate status in women of reproductive age and the most recent estimates of the prevalence of neural tube defects. Additionally, we provide an overview of the available interventions worldwide to reduce the risk of neural tube defects by improving folate status in the population, including dietary diversification, supplementation, education, and fortification. RESULTS: Large-scale food fortification with folic acid is the most successful and effective intervention to reduce the prevalence of neural tube defects and associated infant mortality. This strategy requires the coordination of several sectors, including governments, the food industry, health services providers, the education sector, and entities that monitor the quality of the service processes. It also requires technical knowledge and political will. An international collaboration between governmental and non-governmental organizations is essential to succeed in saving thousands of children from a disabling but preventable condition. DISCUSSION: We propose a logical model for building a national-level strategic plan for mandatory LSFF with folic acid and explain the actions needed for promoting sustainable system-level change.

The impact of voluntary folate fortification of corn masa flour on US pregnancies complicated by neural tube defects.

INTRODUCTION: In 1996, the US Food and Drug Administration (FDA) mandated folic acid fortification for all enriched cereal grains. This resulted in a reduction of neural tube defect (NTD)-affected pregnancies. However, Hispanic women continued to be twice as likely to give birth to a child affected by NTD compared to non-Hispanic White women. Some hypotheses explaining this difference focus on cultural variation in dietary intake of cereal grains. In 2016, the FDA approved voluntary folic acid fortification for corn masa flour products to focus on the Hispanic diet staple. This study investigates rates of NTDs in predominantly Hispanic-populated zip codes before and after the voluntary fortification of corn masa flour with folic acid. METHODS: Normal pregnancies and those complicated by NTDs between 1/1/2016 and 9/30/2020 were identified using ICD-9 and ICD-10 codes in an all-payor claims database. The post-fortification period began 12 months after the fortification recommendation. The US Census data was used to stratify pregnancies in predominantly Hispanic zip codes (≥ 75% of households) vs. non-Hispanic zip codes. The causal impact of the FDA's recommendation was assessed by means of a Bayesian structural time series model. RESULTS: A total of 2,584,366 pregnancies were identified among females aged 15-50 years. Of these, 365,983 took place in predominantly Hispanic zip codes. Mean quarterly NTDs per 100,000 pregnancies did not significantly differ between predominantly Hispanic zip codes and predominantly non-Hispanic zip codes pre-FDA recommendation (184.5 vs. 175.6; p = 0.427), nor post-recommendation (188.2 vs. 185.9; p = 0.713). Rates of NTDs predicted to occur if no FDA recommendation had been made were compared to the actual rate post-recommendation: no significant difference was observed in predominantly Hispanic zip codes (p = 0.245) or overall (p = 0.116). CONCLUSIONS: Rates of neural tube defects were not significantly reduced in predominantly Hispanic zip codes following the 2016 FDA approval of voluntary folic acid fortification of corn masa flour. Further research and implementation of comprehensive approaches to advocacy, policy, and public health are necessary to decrease preventable congenital disease rates. Mandatory rather than voluntary fortification of corn masa flour products may achieve more substantial prevention of neural tube defects in at-risk US populations.

Neural tube defects: Prevalence, mortality, and maternal characteristics in two departmental hospitals in the northwestern region of Nicaragua, 2006-2018.

BACKGROUND: Congenital anomalies are the fifth most common cause of neonatal mortality in Nicaragua, and neural tube defects (NTDs) are the most common of all cases of lethality associated with a birth defect. Prevalence and mortality estimates are needed to propose effective intervention strategies that prevent NTDs over time. METHODS: A cross-sectional study was carried out in northwestern Nicaragua from January 2006 to December 2018. All cases of NTDs (anencephaly, spina bifida, and encephalocele) were registered in hospital surveillance systems, and the medical histories of the mothers and newborns were reviewed. Prevalence was calculated by considering the number of live births and stillbirths older than 20 weeks of gestation with NTDs, divided by the total number of live births and stillbirths in each study year. Neonatal mortality rate (NMR) for NTD, and case fatality for spina bifida was calculated. RESULTS: Two hundred fifty cases of NTDs were identified from 178,498 deliveries (177,316 live births and 1,182 stillbirths). The prevalence of NTDs during this time period was 14.01 (95% CI: 12.27-15.74) per 10,000 births. The prevalence of spina bifida (n = 140), anencephaly (n = 97), and encephalocele (n = 13) was 7.84, (95% CI: 6.54-9.14), 5.43 (95% CI: 4.30-6.45), and 0.73 (95% CI: 0.33-1.12) per 10,000 births, respectively. Mothers with fetus or newborns affected with NTDs did not use folic acid prior to conception, and 11% experienced periods of hyperthermia during the first trimester of pregnancy. NMR for NTDs was 0.55 per 1.000 livebirths. Case fatality for all NTDs and for spina bifida were 55% and 18%, respectively. CONCLUSION: The prevalence and mortality of NTDs in the northwestern region of Nicaragua present peaks and troughs during the study period. Spina bifida was the most frequent type of NTD. We believe that these findings could be of use by health policy makers to strengthen the primary prevention of NTDs in the region through the monitoring of the food fortification policy and folic acid supplementation to women of childbearing age. Additional etiologic studies of NTDs should be considered to identify additional prevention measures.

Neural tube defects: a review of global prevalence, causes, and primary prevention.

Neural tube defects (NTDs) are common birth defects and contribute to life-long disabilities, high medical care costs, and perinatal and child mortality. This review is a primer on prevalence, causes, and evidence-based prevention strategies for NTDs. The estimated average global prevalence of NTDs is two cases per 1000 births, amounting to approximately 214,000-322,000 affected pregnancies worldwide annually. Prevalence and associated adverse outcomes are disproportionately high in developing countries. NTDs have multiple risk factors including genetic and non-genetic (i.e., maternal nutritional status, pre-pregnancy diabetes, early pregnancy exposure to valproic acid (anti-epileptic medication), and a previous pregnancy affected by a NTD) factors. Maternal folate insufficiency before and during early pregnancy is the most common risk factor and is preventable. Folic acid (vitamin B9) is required for formation of the neural tube early in pregnancy, around 28 days after conception, when most women are unaware of their pregnancies. Current guidelines recommend that all women planning or capable of pregnancy take a daily supplement containing 400-800 µg of folic acid. Mandatory folic acid fortification of staple foods (e.g., wheat flour, maize flour, rice) is safe, economical, and the effective intervention for primary prevention of NTDs. Currently, about 60 countries are implementing mandatory folic acid fortification of staple foods, preventing just a quarter of all preventable NTD cases worldwide. There is an urgent need for active champions, including neurosurgeons and other healthcare providers, to generate political will and promote effective mandatory food fortification with folic acid, and reach equitable primary prevention of NTDs in all countries.

Integrated surveillance strategy to support the prevention of neural tube defects through food fortification with folic acid: the experience of Costa Rica.

PURPOSE: (1) To describe how Costa Rica implemented an integrated surveillance strategy of folate deficiency, neural tube defects (NTDs) prevalence, NTDs-associated infant mortality rate (NTDs-IMR), and folic acid food fortification (FAFF), to support with evidence NTDs prevention policies; (2) to disseminate updated data from monitoring programs. METHODS: We performed a cross-sectional analysis, using the databases of national surveillance systems for NTDs outcomes to compare NTDs-prevalence and NTDs-IMR observed in the pre-fortification (1987-1998) and post-fortification (2010-2020) periods. In addition, using data from FAFF monitoring program (2010-2020), means of folic acid concentration (mg/kg) and folic acid daily intake (µg/day) were calculated for each fortified food (corn and wheat flour, rice and milk), as well as its contribution to folic acid estimated average requirement (EAR). RESULTS: After FAFF Costa Rica showed a decrease of 84% in folic acid deficiency in women of childbearing age, as well as a 53% decrease in the prevalence of NTDs, falling from 11.82/10,000 to 5.52/10,000 livebirths. In addition, there was a 76% reduction in the NTDs-IMR from 77.01/100,000 to 18.66/100,000 livebirths. Between 2010 and 2020, all fortified foods provided an average contribution of 119% of the EAR of folic acid in the population. CONCLUSION: To reduce NTD risk, an integrated surveillance strategy is essential not only to base prevention strategies on evidence, but also to demonstrate their impact and improve interventions over time. The experience in Costa Rica provides evidence that this type of surveillance is feasible to be implemented in developing countries.

Prevented cases of neural tube defects and cost savings after folic acid fortification of flour in Brazil.

Anencephaly, encephalocele, and spina bifida are congenital neural tube defects and are the main causes of neonatal morbidity and mortality and impose a heavy economic burden on health systems. This study to estimates the direct costs of neural tube defects from the perspective of the Brazilian Ministry of Health, and the prevented cases and cost savings during the period in which mandatory folic acid fortification was in effect in the country (2010-2019). It is a top-down cost-of-illness oriented study based on the prevalence of the disorders in Brazil. Data were collected from the Brazilian Ministry of Health's outpatient and hospital information system databases. The direct cost was estimated from the total patient-years, allocated by age and type of disorder. Prevented cases and cost savings were determined by the difference in the prevalence of the disorders in the pre- and post-fortification periods based on the total number of births and the sum of outpatient and hospital costs during the period. The total cost of outpatient and hospital services for these disorders totaled R$ 92,530,810.63 (Int$ 40,565,896.81) in 10 years; spina bifida accounted for 84.92% of the total cost. Hospital costs were expressive of all three disorders in the first year of the patient's life. Between 2010 and 2019, mandatory folic acid fortification prevented 3,499 live births with neural tube defects and resulted in R$ 20,381,586.40 (Int$ 8,935,373.25) in hospital and outpatient cost savings. Flour fortification has proved to be a valuable strategy in preventing pregnancies with neural tube defects. Since its implementation, there has been a 30% decrease in the prevalence of neural tube defects and a 22.81% decrease associated in hospital and outpatient costs.