Folic Acid-Fortified Iodized Salt and Serum Folate Levels in Reproductive-Aged Women of Rural India: A Nonrandomized Controlled Trial.

Importance: India has a disproportionately high prevalence of neural tube defects, including spina bifida and anencephaly (SBA), causing a high number of stillbirths, elective pregnancy terminations, and child mortality; India contributes a large proportion of the global burden of SBA. Thirty years after folic acid was shown to be effective in reducing SBA prevalence, only about one-quarter of such births are prevented globally through cereal grain fortification. Objective: To determine the association of folic acid-fortified iodized salt with serum folate concentrations among nonpregnant and nonlactating women of reproductive age. Design, Setting, and Participants: This nonrandomized controlled trial using a preintervention and postintervention design was conducted in 4 rural villages in Southern India from July 1 to November 30, 2022. All households in the villages agreed to participate in the study. Preintervention and postintervention serum folate levels were analyzed among study participants at baseline and after 4 months, respectively. Intervention: Consumption of approximately 300 µg/d of folic acid using double fortified salt (folic acid plus iodine). Median serum folate concentrations were assessed at baseline and 4 months. Main Outcomes and Measures: Change in median serum folate levels between baseline and study end point as the primary outcome of the study. Results: A total of 83 nonpregnant nonlactating women aged 20 to 44 years (mean [SD] age, 30.9 [5.1] years) were eligible for the study and provided serum samples for analysis at baseline and the end point of the intervention. The median serum folate concentration increased from 14.6 (IQR, 11.2-20.6) nmol/L at baseline to 54.4 (IQR, 43.5-54.4) nmol/L at end of study, a 3.7-fold increase from baseline to study end point. Two-tailed Wilcoxon signed rank test showed the median difference in preintervention and postintervention serum folate concentrations to be highly significant (P < .001). The participants found the salt acceptable in color and taste. Conclusions and Relevance: Use of folic acid-fortified iodized salt was associated with increased serum folate concentrations in women of reproductive age. This novel evidence can inform public health policy to accelerate SBA prevention. Trial Registration: ClinicalTrials.gov Identifier: NCT06174883.

Folic acid prescription practice for high-risk prevention of spina bifida at a tertiary care hospital in Addis Ababa, Ethiopia.

PURPOSE: Mothers who have had a pregnancy affected by spina bifida are advised to take 4-5 mg/day folic acid pills to prevent recurrence. The folic acid prescription pattern was examined for high-risk mothers whose children received spina bifida surgery in an urban Ethiopian hospital. METHODS: Data were analyzed from a large Ethiopian urban tertiary care hospital that provided spina bifida care. General practitioners recorded 5 mg/day folic acid prescriptions administered to mothers of infants with spina bifida born between January 2019 and June 2022. RESULTS: Among 500 baby-mother pairs, 340 (68%) received a 120-day prescription for 5 mg/day folic acid pills. Of these 340 mothers, 331 (97%) received their folic acid prescription at their child's first or second patient encounter. Almost all mothers (94%) had documentation of only one prescription for the study duration. The percentage of mothers receiving at least one prescription varied by the baby's year of birth (2019:75%; 2020:92%; 2021:46%; Jan 2022 -June 2022:79%). CONCLUSION: This prioritization of spina bifida recurrence prevention demonstrates feasibility for other healthcare centers in low-income countries. Sustained funds to provide women with free folic acid pills can favor high compliance and uptake of this prevention intervention.

Neural tube defects as a cause of death among stillbirths, infants, and children younger than 5 years in sub-Saharan Africa and southeast Asia: an analysis of the CHAMPS network.

BACKGROUND: Neural tube defects are common birth defects resulting in severe morbidity and mortality; they can largely be prevented with periconceptional maternal intake of folic acid. Understanding the occurrence of neural tube defects and their contribution to mortality in settings where their burden is highest could inform prevention and health-care policy. We aimed to estimate the mortality attributed to neural tube defects in seven countries in sub-Saharan Africa and southeast Asia. METHODS: This analysis used data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network and health and demographic surveillance systems from South Africa, Mozambique, Bangladesh, Kenya, Mali, Ethiopia, and Sierra Leone. All stillbirths and infants and children younger than 5 years who died, who were enrolled in CHAMPS, whose families consented to post-mortem minimally invasive tissue sampling (MITS) between Jan 1, 2017, and Dec 31, 2021, and who were assigned a cause of death by a determination of cause of death panel as of May 24, 2022, were included in this analysis, regardless the cause of death. MITS and advanced diagnostic methods were used to describe the frequency and characteristics of neural tube defects among eligible deaths, identify risk factors, and estimate the mortality fraction and mortality rate (per 10 000 births) by CHAMPS site. FINDINGS: Causes of death were determined for 3232 stillbirths, infants, and children younger than 5 years, of whom 69 (2%) died with a neural tube defect. Most deaths with a neural tube defect were stillbirths (51 [74%]); 46 (67%) were neural tube defects incompatible with life (ie, anencephaly, craniorachischisis, or iniencephaly) and 22 (32%) were spina bifida. Deaths with a neural tube defect were more common in Ethiopia (adjusted odds ratio 8·09 [95% CI 2·84-23·02]), among female individuals (4·40 [2·44-7·93]), and among those whose mothers had no antenatal care (2·48 [1·12-5·51]). Ethiopia had the highest adjusted mortality fraction of deaths with neural tube defects (7·5% [6·7-8·4]) and the highest adjusted mortality rate attributed to neural tube defects (104·0 per 10 000 births [92·9-116·4]), 4-23 times greater than in any other site. INTERPRETATION: CHAMPS identified neural tube defects, a largely preventable condition, as a common cause of death among stillbirths and neonatal deaths, especially in Ethiopia. Implementing interventions such as mandatory folic acid fortification could reduce mortality due to neural tube defects. FUNDING: Bill & Melinda Gates Foundation.

Barriers and facilitators to the implementation of mandatory folate fortification as an evidence-based policy to prevent neural tube defects.

BACKGROUND: Neural tube defects continue to be one of the main congenital malformations affecting the development of the nervous system and a significant cause of disability and disease burden to individuals living with these conditions. Mandatory food fortification with folic acid is, by far, one of the most efficacious, safe, and cost-effective interventions to prevent neural tube defects. However, most countries fail to effectively fortify staple foods with folic acid, impacting public health and healthcare systems and generating dismal disparities. AIM: This article discusses the main barriers and facilitators for implementing mandatory food fortification as an evidence-based policy to prevent neural tube defects worldwide. METHODS: A comprehensive review of the scientific literature allowed the identification of the determinant factors acting as barriers or facilitators for the reach, adoption, implementation, and scaling up of mandatory food fortification with folic acid as an evidence-based policy. RESULTS: We identified eight barriers and seven facilitators as determinant factors for food fortification policies. The identified factors were classified as individual, contextual, and external, inspired by the Consolidated Framework for Implementation of Research (CFIR). We discuss mechanisms to overcome obstacles and seize the opportunities to approach this public health intervention safely and effectively. CONCLUSIONS: Several determinant factors acting as barriers or facilitators influence the implementation of mandatory food fortification as an evidence-based policy worldwide. Notoriously, policymakers in many countries may lack knowledge of the benefits of scaling up their policies to prevent folic acid-sensitive neural tube defects, improve the health status of their communities, and promote the protection of many children from these disabling but preventable conditions. Not addressing this problem negatively affects four levels: public health, society, family, and individuals. Science-driven advocacy and partnerships with essential stakeholders can help overcome the barriers and leverage the facilitators for safe and effective food fortification.

Employment Status in the United States and Use of Long-Acting Reversible Contraception or Moderately Effective Contraception before and after the Affordable Care Act: National Survey of Family Growth 2006-2010 and 2015-2017.

Employment status has been previously associated with contraceptive use among women of reproductive age. We assessed the association between employment status and method of contraception among US women of reproductive age, before and after the implementation of the Affordable Care Act (ACA) passed in 2010. We conducted a cross-sectional study using data from the National Survey of Family Growth (NSFG): 2006-2010 survey for our pre-ACA analysis and 2015-2017 survey for post-ACA analysis. We combined the use of moderately-effective or long-acting reversible contraceptives (LARC) as the main study outcome. Multivariable logistic regression was used to estimate adjusted prevalence odds ratios (aPOR) and 95% confidence intervals (CI). Our study included 5,572 women pre-ACA and 2,340 women post-ACA. Pre-ACA, non-Hispanic white women who were employed were significantly more likely to use moderately-effective or LARC contraceptives (aPOR = 1.66; 95% CI = 1.28, 2.14), but post-ACA, this association was non-significant (aPOR = 0.94; 95% CI = 0.67, 1.33). Findings were not significant for other race/ethnic groups in either time frame. Our study shows that being employed was no longer associated with contraceptive method during a post-ACA time period among non-Hispanic white women. Modifications to the ACA should be scrutinized to further evaluate the impact it may have on women's access to moderately-effective or LARC contraception.

A case study of ReachAnother Foundation as a change champion for developing spina bifida neurosurgical care and advocating for primary prevention in Ethiopia.

Spina bifida is a serious birth defect affecting the central nervous system, characterized by incomplete closure of the neural tube. Ethiopia has a very high prevalence of spina bifida, affecting about 40 cases per 10,000 births. Babies born with spina bifida require early closure surgery, done within the first 2-3 days after birth. Some babies need repeat surgeries to address complications, including hydrocephalus. Without medical care, babies have a high risk of death within the first 5 years of their life. Neurosurgical capacity for spina bifida closure surgery at birth is a relatively new development in Ethiopia. ReachAnother Foundation, a not-for-profit organization based in OR, USA, started work in Ethiopia in 2009 and has been instrumental in training neurosurgeons and improving treatment for spina bifida and hydrocephalus. Along with the development of neurosurgical care, the Foundation has invested in training multi-disciplinary teams to conduct patient aftercare and has launched a platform for improved patient outcomes research. As of year 2022, they support six spina bifida "Centers of Excellence" nationwide and are continuously advocating for primary prevention of spina bifida through mandatory fortification of staple foods in Ethiopia. This paper describes ReachAnother's efforts in Ethiopia in a short interval of time, benefiting numerous patients and families with spina bifida and anencephaly. We document this as a case study for other countries to model where resources are limited and the prevalence of spina bifida and hydrocephalus is high, especially in Asia and Africa.

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.

Factors Associated with Transfer Distance from Birth Hospital to Repair Hospital for First Surgical Repair among Infants with Myelomeningocele in California.

OBJECTIVE: The objective of our study was to examine factors associated with distance to care for first surgical repair among infants with myelomeningocele in California. STUDY DESIGN: A total of 677 eligible cases with complete geocoded data were identified for birth years 2006 to 2012 using data from the California Perinatal Quality Care Collaborative linked to hospital and vital records. The median distance from home to birth hospital among eligible infants was 9 miles, and from birth hospital to repair hospital was 15 miles. We limited our analysis to infants who lived close to the birth hospital, creating two study groups to examine transfer distance patterns: "lived close and had a short transfer" (i.e., lived <9 miles from birth hospital and traveled <15 miles from birth hospital to repair hospital; n = 92), and "lived close and had a long transfer" (i.e., lived <9 miles from birth hospital and traveled ≥15 miles from birth hospital to repair hospital; n = 96). Log-binomial regression was used to estimate crude and adjusted risk ratios (aRRs and 95% confidence intervals (CIs). Selected maternal, infant, and birth hospital characteristics were compared between the two groups. RESULTS: We found that low birth weight (aRR = 1.44; 95% CI = 1.04, 1.99) and preterm birth (aRR = 1.41; 95% CI = 1.01, 1.97) were positively associated, whereas initiating prenatal care early in the first trimester was inversely associated (aRR = 0.64; 95% CI = 0.46, 0.89) with transferring a longer distance (≥15 miles) from birth hospital to repair hospital. No significant associations were noted by maternal race-ethnicity, socioeconomic indicators, or the level of hospital care at the birth hospital. CONCLUSION: Our study identified selected infant factors associated with the distance to access surgical care for infants with myelomeningocele who had to transfer from birth hospital to repair hospital. Distance-based barriers to care should be identified and optimized when planning deliveries of at-risk infants in other populations. KEY POINTS: · Low birth weight predicted long hospital transfer distance.. · Preterm birth was associated with transfer distance.. · Prenatal care was associated with transfer distance..

Early Neonatal Mortality among Babies Born with Spina Bifida in Finland (2000-2014).

OBJECTIVE: We examined early neonatal mortality risk, temporal trends, and selected infant and maternal factors associated with early neonatal mortality among all spina bifida-affected live births in Finland. STUDY DESIGN: We linked multiregistry population-based data from the national registers in Finland for infants born with spina bifida from 2000 to 2014. Early neonatal mortality was defined as death in 0 to 6 days after birth. Early neonatal mortality risk and 95% confidence intervals (CI) was estimated by using the Poisson approximation of binomial distribution. Poisson regression was used to examine temporal trend in early neonatal mortality from 2000 to 2014 for spina bifida cases and all births in Finland. Selected infant and maternal characteristics were compared between cases that experienced early neonatal mortality and cases that did not. Exact logistic regression was used to estimate unadjusted odds ratios (uORs) and 95% confidence intervals (CIs). RESULTS: A total of 181 babies were born alive with spina bifida in Finland during the study period; 61% had isolated spina bifida. Pooling all study years, 7.2% (95% CI: 4.2-12.4%) of all live-born cases experienced early neonatal death. There was a significant increase in early neonatal mortality among spina bifida births over the study period (p < 0.0001). Low gestational age (<37 weeks; uOR = 6.96; 95% CI: 1.86-29.01), cases occurring as a part of a syndrome (uOR = 125.67; 95% CI: 14.90 to >999.999), and advanced maternal age at gestation (≥35 years; uOR = 5.33; 95% CI: 1.21-21.87) were positively associated with early neonatal mortality. CONCLUSION: Using national data from Finland, we found high early neonatal mortality with increasing trend over birth period spanning 15 years (2000-2014), and unadjusted positive associations with some infant and maternal factors. Future studies should pool data from Nordic countries to increase study size allowing multivariable analysis. KEY POINTS: · Early neonatal mortality in babies affected by spina bifida is 7% in Finland.. · Early neonatal mortality trend showed a significant increase from 2000 to 2014.. · Low gestational age, syndrome case status, and advanced maternal age increased early neonatal mortality risk in spina bifida..

National Mandatory Grain Fortification Legislation Decreases Anemia Prevalence among Nonpregnant Women of Reproductive Age: Findings from Multiple Demographic and Health Surveys.

BACKGROUND: Two billion people are affected by anemia globally, mostly including women of reproductive age (WRA) and those residing in low- and middle-income countries (LMICs). Large national population-representative studies examining the impact of national grain fortification policies on the prevalence of anemia among WRA are lacking from recent years. OBJECTIVES: We aimed to determine whether mandatory national grain fortification policies reduce the prevalence of anemia among nonpregnant WRA. METHODS: We examined national food fortification policy characteristics from the Global Fortification Data Exchange (GFDx) database and anemia prevalence data from the Demographic and Health Surveys (DHSs). In total, 21 LMICs, with and without national grain fortification policies, completing ≥2 DHSs between 2000 and 2018, met study eligibility. We applied the difference-in-differences approach to compare changes in the prevalence of anemia among WRA in 10 countries with and 11 countries without fortification between each DHS year. Odds ratios (ORs) and average marginal effects, along with 95% confidence intervals (CIs) were calculated, adjusting for individual-, household-, and country-level factors. RESULTS: Our analytic study sample included 96,334 and 874,984 WRA in countries with and without fortification, respectively. Overall, countries with fortification showed 27% decreased odds of anemia (adjusted OR: 0.73; 95% CI: 0.63, 0.85) and a 7.47-percentage-point decrease in the mean anemia prevalence (average marginal effect: -7.47; 95% CI: -11.03, -3.92) from the pre- to the postfortification period, compared with countries without fortification, after controlling for selected individual-, household-, and country-level factors. CONCLUSIONS: Our findings, using nationally representative DHS data and applying a recommended analytic method to measure policy effectiveness, suggest significant reductions in anemia prevalence in WRA in countries with mandatory grain fortification compared with those without. Implementing national mandatory grain fortification in LMICs would effectively reduce anemia resulting from micronutrient deficiencies among WRA.

Prevalence and mortality among children with anorectal malformation: A multi-country analysis.

PURPOSE: We examined the total prevalence, trends in prevalence, and age-specific mortality among individuals with anorectal malformation (ARM) METHODS: We conducted a retrospective cohort study using data from 24 population- and hospital-based birth defects surveillance programs affiliated with the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) from 18 countries and for births from 1974 to 2014. We estimated pooled and program-specific total prevalence per 10,000 total births. Poisson regression was used to assess time trends in prevalence from 2001 to 2012 when most programs contributed data. We calculated selected age-specific proportions of deaths, stratified by case status RESULTS: The pooled total prevalence of ARM was 3.26 per 10,000 total births (95% Confidence Interval = 3.19, 3.32) for birth years 1974-2014. About 60% of cases were multiple or syndromic. Prevalence of multiple, syndromic, and stillborn cases decreased from 2001 to 2012. The first week mortality proportion was 12.5%, 3.2%, 28.3%, and 18.2% among all, isolated, multiple, and syndromic cases, respectively CONCLUSIONS: ARM is relatively rare, with multiple and syndromic cases showing decreasing prevalence during the study period. Mortality is a concern during the first week of life, and especially among multiple and syndromic cases. Our descriptive epidemiological findings increase our understanding of geographic variation in the prevalence of ARM and can be used to plan needed clinical services. Exploring factors influencing prevalence and mortality among individuals with ARM could inform future studies.

The role of neurosurgeons in global public health: the case of folic acid fortification of staple foods to prevent spina bifida.

OBJECTIVE: The global neurosurgery movement arose at the crossroads of unmet neurosurgical needs and public health to address the global burden of neurosurgical disease. The case of folic acid fortification (FAF) of staple foods for the prevention of spina bifida and anencephaly (SBA) represents an example of a new neurosurgical paradigm focused on public health intervention in addition to the treatment of individual cases. The Global Alliance for the Prevention of Spina Bifida-F (GAPSBiF), a multidisciplinary coalition of neurosurgeons, pediatricians, geneticists, epidemiologists, food scientists, and fortification policy experts, was formed to advocate for FAF of staple foods worldwide. This paper serves as a review of the work of GAPSBiF thus far in advocating for universal FAF of commonly consumed staple foods to equitably prevent SBA caused by folic acid insufficiency. METHODS: A narrative review was performed using the PubMed and Google Scholar databases. RESULTS: In this review, the authors describe the impact of SBA on patients, caregivers, and health systems, as well as characterize the multifaceted requirements for proper spina bifida care, including multidisciplinary clinics and the transition of care, while highlighting the role of neurosurgeons. Then they discuss prevention policy approaches, including supplementation, fortification, and hybrid efforts with folic acid. Next, they use the example of FAF of staple foods as a model for neurosurgeons' involvement in global public health through clinical practice, research, education and training, and advocacy. Last, they describe mechanisms for involvement in the above initiatives as a potential academic tenure track, including institutional partnerships, organized neurosurgery, neurosurgical expert groups, nongovernmental organizations, national or international governments, and multidisciplinary coalitions. CONCLUSIONS: The role of neurosurgeons in caring for children with spina bifida extends beyond treating patients in clinical practice and includes research, education and training, and advocacy initiatives to promote context-specific, evidence-based initiatives to public health problems. Promoting and championing FAF serves as an example of the far-reaching, impactful role that neurosurgeons worldwide may play at the intersection of neurosurgery and public health.

Prepregnancy exposure to dietary arsenic and congenital heart defects.

INTRODUCTION: Arsenic crosses the placenta and accumulates in fetal tissues. In the United States, diet is the predominant route of arsenic exposure, but epidemiologic data are sparse regarding this exposure and development of birth defects. Using data from a large case-control study, we explored associations between maternal dietary arsenic exposure and congenital heart defects (CHDs), the most prevalent birth defects. METHODS: We used maternal self-reported dietary assessments and arsenic concentration estimates in food items to estimate average daily exposure to dietary arsenic during the year before pregnancy for mothers of 10,446 unaffected control children and 6,483 case children diagnosed with CHDs. Using tertiles of dietary exposure to total arsenic (all species) and inorganic arsenic, we applied logistic regression analysis to estimate associations for middle and high tertiles, compared with the low tertile. RESULTS: Positive associations (odds ratio [OR] ≥ 1.2) for total arsenic were observed in both tertiles for perimembranous ventricular septal defect (VSD) and high tertile only for double outlet right ventricle-transposition of the great arteries (DORV-TGA), partial anomalous pulmonary venous return (PAPVR), and tricuspid atresia. Positive associations were also observed in both tertiles (tricuspid atresia) and high tertile only (DORV-TGA, conoventricular VSD, PAPVR, and pulmonary atresia) for inorganic arsenic. Most remaining associations were near or below unity. DISCUSSION: Exploration of maternal dietary exposure to total and inorganic arsenic and CHDs produced few positive associations but was limited by available food item concentrations. Future research requires expanded collection of dietary data, improved estimates of concentrations, and consideration of nondietary sources of arsenic exposure.

A global update on the status of prevention of folic acid-preventable spina bifida and anencephaly in year 2020: 30-Year anniversary of gaining knowledge about folic acid's prevention potential for neural tube defects.

BACKGROUND: Spina bifida and anencephaly are major neural tube defects largely preventable through maternal periconceptional intake of folic acid. We estimated the global proportion of folic acid-preventable spina bifida and anencephaly (FAP SBA) prevented through mandatory folic acid fortification of cereal grains, including wheat flour, maize flour, and rice, at the end of year 2020, a time point marking the 30th anniversary of the publication of landmark British Medical Research Council (MRC) study providing unequivocal knowledge on folic acid's FAP SBA prevention potential. METHODS: The Food Fortification Initiative database was used to identify countries with mandatory fortification policies with folic acid added to cereal grains. We examined the status of FAP SBA prevention assuming mandatory folic acid fortification at 200 mcg/day of folic acid protects against FAP SBA and reduces their prevalence to a minimum achievable rate of 0.5 cases/1000 live births. RESULTS: Our analysis showed that 61,680 FAP SBA cases were prevented in the year 2020 through mandatory folic acid fortification of cereal grains in 58 countries, translating to 22% prevention of total possible FAP SBA prevention globally. Many countries in Africa, Asia, and Europe are yet to implement fortification. In 2020, 30 years after the MRC study was published, 218,270 preventable FAP SBA cases still occurred globally. CONCLUSION: Global prevention efforts for FAP SBA are inadequate even after three decades of knowledge on their prevention. Universal mandatory fortification of staples should be urgently implemented to prevent thousands of FAP SBA and associated elective terminations, stillbirths, and child mortality.

Global and regional prevalence of disabilities among children and adolescents: Analysis of findings from global health databases.

Objective: The United Nations' Sustainable Development Goals (SDGs) require population-based data on children with disabilities to inform global policies and intervention programs. We set out to compare the prevalence estimates of disabilities among children and adolescents younger than 20 years as reported by the world's leading organizations for global health statistics. Methods: We purposively searched the disability reports and databases of the United Nations Children's Fund (UNICEF), the World Health Organization (WHO), the World Bank and the Global Burden of Diseases (GBD) Study. We analyzed the latest disability data reported by these organizations since 2015. We examined the methodologies adopted in generating the reported prevalence estimates and evaluated the degree of agreement among the data sources using Welch's test of statistical difference, and the two one-sided t-test (TOST) for statistical equivalence. Results: Only UNICEF and GBD provided the most comprehensive prevalence estimates of disabilities in children and adolescents. Globally, UNICEF estimated that 28.9 million (4.3%) children aged 0-4 years, 207.4 million (12.5%) children aged 5-17 years and 236.4 million (10.1%) children aged 0-17 years have moderate-to-severe disabilities based on household surveys of child functional status. Using the UNICEF estimated prevalence of 10.1%, approximately 266 million children aged 0-19 years are expected to have moderate-to-severe disabilities. In contrast, GBD 2019 estimated that 49.8 million (7.5%) children aged under 5 years, 241.5 million (12.6%) children aged 5-19 years and 291.3 million (11.3%) children younger than 20 years have mild-to-severe disabilities. In both databases, Sub-Saharan Africa and South Asia accounted for more than half of children with disabilities. A comparison of the UNICEF and GBD estimates showed that the overall mean prevalence estimates for children under 5 years were statistically different and not statistically equivalent based on ±3 percentage-point margin. However, the prevalence estimates for children 5-19 years and < 20 years were not statistically different and were statistically equivalent. Conclusion: Prevalence estimates of disabilities among children and adolescents generated using either functional approach or statistical modeling appear to be comparable and complementary. Improved alignment of the age-groups, thresholds of disability and the estimation process across databases, particularly among children under 5 years should be considered. Children and adolescents with disabilities will be well-served by a variety of complementary data sources to optimize their health and well-being as envisioned in the SDGs.

Cerebral palsy and developmental intellectual disability in children younger than 5 years: Findings from the GBD-WHO Rehabilitation Database 2019.

Objective: Children with developmental disabilities are associated with a high risk of poor school enrollment and educational attainment without timely and appropriate support. Epidemiological data on cerebral palsy and associated comorbidities required for policy intervention in global health are lacking. This paper set out to report the best available evidence on the global and regional prevalence of cerebral palsy (CP) and developmental intellectual disability and the associated "years lived with disability" (YLDs) among children under 5 years of age in 2019. Methods: We analyzed the collaborative 2019 Rehabilitation Database of the Global Burden of Disease (GBD) Study and World Health Organization for neurological and mental disorders available for 204 countries and territories. Point prevalence and YLDs with 95% uncertainty intervals (UI) are presented. Results: Globally, 8.1 million (7.1-9.2) or 1.2% of children under 5 years are estimated to have CP with 16.1 million (11.5-21.0) or 2.4% having intellectual disability. Over 98% resided in low-income and middle-income countries (LMICs). CP and intellectual disability accounted for 6.5% and 4.5% of the aggregate YLDs from all causes of adverse health outcomes respectively. African Region recorded the highest prevalence of CP (1.6%) while South-East Asia Region had the highest prevalence of intellectual disability. The top 10 countries accounted for 57.2% of the global prevalence of CP and 62.0% of the global prevalence of intellectual disability. Conclusion: Based on this Database, CP and intellectual disability are highly prevalent and associated with substantial YLDs among children under 5 years worldwide. Universal early detection and support services are warranted, particularly in LMICs to optimize school readiness for these children toward inclusive education as envisioned by the United Nations' Sustainable Development Goals.

Relationship between achieving Sustainable Development Goals and promoting optimal care and prevention of birth defects globally.

Birth defects affect eight million newborns annually worldwide. About 8% of global under-5 mortality is attributable to birth defects. The United Nations (UN) Sustainable Development Goals (SDGs) have set 17 global goals for human growth and development to be achieved by 2030 using multi-sectorial approaches. The third goal (SDG-3) focuses on ensuring healthy lives and promoting well-being; achieving SDG-3 improves birth defects care and prevention. However, we aimed to show how achieving other SDGs also influence optimal care and prevention of birth defects. SDGs focused on poverty reduction, access to nutritious food, universal health coverage, equitable education, gender equality, environment, inclusivity through infrastructure innovation, and strengthening social justice is crucial to addressing social determinants of health for individuals and families affected by birth defects. Understanding birth defects in the context of several relevant SDGs will allow practitioners, researchers, and policymakers to leverage the momentum generated by SDGs and make a case for commitment and allocation of funding and resources for advancing birth defects surveillance, care, and prevention. SDGs are built on principles of equity and social justice and we urge policy-makers to approach birth defects using various SDGs as a catalyst. The synergy between several SDGs helps to optimize birth defect outcomes and prevention. Our effort to present a more comprehensive look at various SDGs and their relationship with birth defects is parallel to several other health advocacy groups conducting a similar mapping exercise, thus bringing to the forefront millions of lives that are impacted by birth defects worldwide.

Maternal cigarette smoking and alcohol consumption and congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) occurs when abnormal diaphragm development allows herniation of abdominal organs into the thoracic cavity. Its etiopathogenesis is not well understood, but cigarette smoking and alcohol exposure may impact diaphragm development. Using data from a large, population-based case-control study, we examined associations between maternal cigarette smoking and alcohol consumption and CDH in offspring. METHODS: We analyzed maternal interview reports of cigarette smoking and alcohol consumption during early pregnancy for 831 children with CDH and 11,416 children without birth defects with estimated dates of delivery during 1997-2011. Generalized linear mixed effects models with a random intercept for study site were used to estimate associations between measures of exposure to smoking (any, type, frequency, duration) and alcohol (any, quantity, frequency, variability, type) for all CDH combined and selected subtypes (Bochdalek and Morgagni). RESULTS: Mothers of 280 (34.0%) case and 3,451 (30.3%) control children reported early pregnancy exposure to cigarette smoking. Adjusted odds ratios for all CDH were increased for any (1.3; 95% confidence interval 1.1-1.5), active (1.3, 1.0-1.7), and passive (1.4, 1.1-1.7) smoking. Early pregnancy alcohol consumption was reported by mothers of 286 (34.9%) case and 4,200 (37.0%) control children; odds were near the null for any consumption (0.9, 0.8-1.1) and consumption with (0.9, 0.7, 1.1) or without (0.9, 0.8, 1.1) binging. Estimates for smoking and alcohol tended to be higher for Bochdalek CDH and Morgagni CDH than those for all CDH. CONCLUSIONS: Findings suggest that maternal early pregnancy exposure to cigarette smoking, but less so to alcohol consumption, contributes to CDH. These findings need to be replicated in additional large studies that use systematic case ascertainment and classification, detailed exposure assessment, and examine subtype-specific associations.

A Multicountry Analysis of Prevalence and Mortality among Neonates and Children with Bladder Exstrophy.

OBJECTIVE: Bladder exstrophy (BE) is a rare but severe birth defect affecting the lower abdominal wall and genitourinary system. The objective of the study is to examine the total prevalence, trends in prevalence, and age-specific mortality among individuals with BE. STUDY DESIGN: We conducted a retrospective cohort study. Data were analyzed from 20 birth defects surveillance programs, members of the International Clearinghouse for Birth Defects Surveillance and Research in 16 countries. Live births, stillbirths, and elective terminations of pregnancy for fetal anomaly (ETOPFA) diagnosed with BE from 1974 to 2014. Pooled and program-specific prevalence of BE per 100,000 total births was calculated. The 95% confidence intervals (CI) for prevalence were estimated using Poisson approximation of binomial distribution. Time trends in prevalence of BE from 2000 to 2014 were examined using Poisson regression. Proportion of deaths among BE cases was calculated on the day of birth, day 2 to 6, day 7 to 27, day 28 to 364, 1 to 4 years, and ≥5 years. Mortality analysis was stratified by isolated, multiple, and syndromic case status. RESULTS: The pooled total prevalence of BE was 2.58 per 100,000 total births (95% CI = 2.40, 2.78) for study years 1974 to 2014. Prevalence varied over time with a decreasing trend from 2000 to 2014. The first-week mortality proportion was 3.5, 17.3, and 14.6% among isolated, multiple, and syndromic BE cases, respectively. The majority of first-week mortality occurred on the first day of life among isolated, multiple, and syndromic BE cases. The proportion of first-week deaths was higher among cases reported from programs in Latin America where ETOPFA services were not available. CONCLUSIONS: Prevalence of BE varied by program and showed a decreasing trend from 2000 to -2014. Mortality is a concern among multiple and syndromic cases, and a high proportion of deaths among cases occurred during the first week of life. KEY POINTS: · Total prevalence of BE was 2.58 per 100,000 births.. · Prevalence decreased from 2000 to 2014.. · The first-week mortality was 9.3%..