Trend and burden of neural tube defects among cohort of pregnant women in Ethiopia: Where are we in the prevention and what is the way forward?

INTRODUCTION: Neural tube defect is one of the top five most serious birth defects in the world. In Ethiopia an accurate estimate of the trend and burden of neural tube defects is still unknown. There hasn't been much research done on the prevalence and trend of neural tube defects in Eastern Ethiopia. To complement previous efforts of studies, the purpose of this study is to estimate the trend and burden of neural tube defects in Eastern Ethiopia as well as to investigate the epidemiological implications of the findings. METHODS: A facility-based retrospective cohort study was carried out from cohort pregnant women who delivered in selected hospitals. File records of all babies who were found to have neural tube defects could be reached between 2017 and 2019. A structured checklist was used to collect data. The incidence of each case was calculated by dividing the number of cases per year by the total number of live births in each hospital. To determine the linear trend of neural tube defects over time, linear trend of Extended Mantel-Haenszel chi-square was performed. Data were presented using frequencies and percentages. Data were analyzed using SPSS for windows version 25. RESULTS: A total of 48,750 deliveries were recorded during the three years of the study considered for analyses with 522 women having neural tube defect giving an incidence rate of 107.5 per 10,000 live births in the three years. The most common types of neural tube defects found in the area were anencephaly and spina bifida accounting for 48.1% and 22.6%, respectively. The distribution of neural tube defects varied across the study hospitals, with Adama Medical College Hospital having the highest proportion (46.6%). Over half of the mothers (56.7%) live in cities. Mothers in the age group 25-34 (46.9%) and multigravida mothers had higher proportions (64.4%).of neural tube defects. None of the mothers took folic acid before conception, and only 19% took iron folic acid supplementation during their pregnancy. CONCLUSION AND RECOMMENDATION: The findings showed that an increasing trend and burden of neural tube defects and preconception folic acid supplementation is insignificant in the region which showed that where we are in the prevention of neural tube defects. The finding suggests that preconception folic acid supplementation in conjunction with health care services should be considered to reduce the risk of neural tube defects in the region. Aside from that, intensive prevention efforts for long-term folate intake through dietary diversification and appropriate public health interventions are required. Furthermore, data must be properly recorded in order to address disparities in neonatal death due to neural tube defects, and the determinants of neural tube defects should be investigated using large scale prospective studies with biomarkers.

Predicted Effects and Cost-Effectiveness of Wheat Flour Fortification for Reducing Micronutrient Deficiencies, Maternal Anemia, and Neural Tube Defects in Yaoundé and Douala, Cameroon.

BACKGROUND: Policy makers aiming to reduce micronutrient deficiencies (MNDs) and their health effects must choose among alternative definitions of impact when evaluating cost-effectiveness. OBJECTIVE: Estimate the cost-effectiveness of a mandatory wheat flour fortification program for reducing cases of MNDs (iron, zinc, folate, vitamin B12), anemia and neural tube defects (NTDs) averted, and disability-adjusted life years (DALYs) averted in urban Cameroon. METHODS: A 13-year predictive model was developed, including a 3-year start-up period and 10 years of program activity. Costs were estimated using historical program budgets. Effects were calculated based on observed changes in prevalence of MND and anemia 1 year postfortification and predicted reductions in NTDs based on NTD burden and wheat flour intake. Total DALYs averted were estimated for anemia and NTDs. RESULTS: The program cost ∼$2.4 million over 13 years and averted an estimated ∼95 000 cases of maternal anemia and ∼83 500 cases of iron deficiency among children after 1 year. Cost/case-year averted for MNDs ranged from $0.50 for low plasma folate to $3.30 for iron deficiency and was $2.20 for maternal anemia. The program was predicted to avert 1600 cases of NTDs over 10 years at ∼$1500 per case averted. Estimated cost/DALY averted was $50 for NTDs and $115 for anemia. CONCLUSIONS: In Cameroon, cost-effectiveness of wheat flour fortification varied by the measure of impact employed, but was classified as "very cost-effective" for all outcomes using World Health Organization criteria. Policy makers and their advisors must determine how best to use information on program costs and benefits to inform their decisions.

Effectiveness of Folic Acid Supplementation Recommendations among Polish Female Students from the Podkarpackie Region.

Adequate folic acid supplementation during the preconception period is an important element in the primary prevention of neural tube defects (NTDs). This study aims to study the effectiveness of folic acid supplementation recommendations among women of childbearing age, and to assess and characterise their awareness about this public health measure. The cross-sectional study included women (N = 1285) aged 22.27 ± 4.6 years old on average. Some of the results were obtained on a subgroup of women (N = 1127) aged 21.0 ± 2.1. This study was performed using a questionnaire. The analysis was performed with the use of a logistic regression model, chi-square test for independence and odds ratio (OR). According to the results, only 13.9% of women supplement folic acid, and 65.3% of them do so daily. A total of 91.1% of the respondents were not aware of its recommended dose and 43% did not know the role it plays in the human body. Among women who do not currently supplement folic acid (N = 1052), 52.4% declared doing so while planning their pregnancy. Women's awareness about the role of folic acid in NTD prevention (OR = 4.58) and the information they got from physicians (OR = 1.68) are key factors that increased the odds of the women taking folic acid before pregnancy. There is therefore a need for more information and education campaigns to raise awareness about folic acid.

Reducing the Burden of Anemia and Neural Tube Defects in Low- and Middle-Income Countries: An Analysis to Identify Countries with an Immediate Potential to Benefit from Large-Scale Mandatory Fortification of Wheat Flour and Rice.

Using a predetermined set of criteria, including burden of anemia and neural tube defects (NTDs) and an enabling environment for large-scale fortification, this paper identifies 18 low- and middle-income countries with the highest and most immediate potential for large-scale wheat flour and/or rice fortification in terms of health impact and economic benefit. Adequately fortified staples, delivered at estimated coverage rates in these countries, have the potential to avert 72.1 million cases of anemia among non-pregnant women of reproductive age; 51,636 live births associated with folic acid-preventable NTDs (i.e., spina bifida, anencephaly); and 46,378 child deaths associated with NTDs annually. This equates to a 34% reduction in the number of cases of anemia and 38% reduction in the number of NTDs in the 18 countries identified. An estimated 5.4 million disability-adjusted life years (DALYs) could be averted annually, and an economic value of 31.8 billion United States dollars (USD) generated from 1 year of fortification at scale in women and children beneficiaries. This paper presents a missed opportunity and warrants an urgent call to action for the countries identified to potentially avert a significant number of preventable birth defects, anemia, and under-five child mortality and move closer to achieving health equity by 2030 for the Sustainable Development Goals.

Social Inequalities in Prenatal Folic Acid Supplementation: Results from the ELFE Cohort.

Most professional and international organizations recommend folic acid supplementation for women planning pregnancy. Various studies have shown high levels of non-compliance with this recommendation. This study aimed to identify sociodemographic characteristics related to this compliance. The analyses were based on 16,809 women from the French nationwide ELFE cohort (Etude Longitudinale Française depuis l'Enfance). Folic acid supplementation was assessed at delivery, and sociodemographic characteristics were collected at two months postpartum. The association between sociodemographic characteristics and compliance with recommendations on folic acid supplementation (no supplementation, periconceptional supplementation, and supplementation only after the periconceptional period) was examined using multivariate multinomial logistic regression. Only 26% of French women received folic acid supplementation during the periconceptional period, 10% of women received supplementation after the periconceptional period, and 64% received no supplementation. Young maternal age, low education level, low family income, multiparity, single parenthood, maternal unemployment, maternal overweight, and smoking during pregnancy were related to lower likelihood of folic acid supplementation during the periconceptional period compared to no supplementation. These associations were not explained by unplanned pregnancy. Immigrant and underweight women were more likely to receive folic acid supplementation after the periconceptional period. Our study confirms great social disparities in France regarding the compliance with the recommendations on folic acid supplementation.

Improved micronutrient status and health outcomes in low- and middle-income countries following large-scale fortification: evidence from a systematic review and meta-analysis.

BACKGROUND: Micronutrient malnutrition is highly prevalent in low- and middle-income countries (LMICs) and disproportionately affects women and children. Although the effectiveness of large-scale food fortification (LSFF) of staple foods to prevent micronutrient deficiencies in high-income settings has been demonstrated, its effectiveness in LMICs is less well characterized. This is important as food consumption patterns, potential food vehicles, and therefore potential for impact may vary substantially in these contexts. OBJECTIVES: The aim of this study was to determine the real-world impact of LSFF with key micronutrients (vitamin A, iodine, iron, folic acid) on improving micronutrient status and functional health outcomes in LMICs. METHODS: All applicable published/unpublished evidence was systematically retrieved and analyzed. Studies were not restricted by age or sex. Meta-analyses were performed for quantitative outcomes and results were presented as summary RRs, ORs, or standardized mean differences (SMDs) with 95% CIs. RESULTS: LSFF increased serum micronutrient concentrations in several populations and demonstrated a positive impact on functional outcomes, including a 34% reduction in anemia (RR: 0.66; 95% CI: 0.59, 0.74), a 74% reduction in the odds of goiter (OR: 0.26; 95% CI: 0.16, 0.43), and a 41% reduction in the odds of neural tube defects (OR: 0.59; 95% CI: 0.49, 0.70). Additionally, we found that LSFF with vitamin A could protect nearly 3 million children per year from vitamin A deficiency. We noted an age-specific effect of fortification, with women (aged >18 y) attaining greater benefit than children, who may consume smaller quantities of fortified staple foods. Several programmatic/implementation factors were also reviewed that may facilitate or limit program potential. CONCLUSIONS: Measurable improvements in the micronutrient and health status of women and children are possible with LSFF. However, context and implementation factors are important when assessing programmatic sustainability and impact, and data on these are quite limited in LMIC studies.

Real-World Cost Effectiveness of Mandatory Folic Acid Fortification of Bread-Making Flour in Australia.

BACKGROUND: In 2009, mandatory folic acid fortification of bread-making flour was introduced in Australia to reduce the birth prevalence of preventable neural tube defects (NTDs) such as spina bifida. Before the introduction of the policy, modelling predicted a reduction of 14-49 NTDs each year. OBJECTIVE: Using real-world data, this study provides the first ex-post evaluation of the cost effectiveness of mandatory folic acid fortification of bread-making flour in Australia. METHODS: We developed a decision tree model to compare different fortification strategies and used registry data to quantify the change in NTD rates due to the policy. We adopted a societal perspective that included costs to industry and government as well as healthcare and broader societal costs. RESULTS: We found 32 fewer NTDs per year in the post-mandatory folic acid fortification period. Mandatory folic acid fortification improved health outcomes and was highly cost effective because of the low intervention cost. The policy demonstrated improved equity in outcomes, particularly in birth prevalence of NTDs in births from teenage and indigenous mothers. CONCLUSIONS: This study calculated the value of mandatory folic acid fortification using real-world registry data and demonstrated that the attained benefit was comparable to the modelled expected benefits. Mandatory folic acid fortification (in addition to policies including advice on supplementation and education) improved equity in certain populations and was effective and highly cost effective for the Australian population.

[Folic Acid Intake Among Women in Berlin According to Their Socio-Economic Status]. / Folsäure-Einnahme bei Berliner Frauen in Abhängigkeit vom sozioökonomischen Status.

INTRODUCTION: The intake of folic acid before and during pregnancy is known to reduce the risk of neural tube defects. Many pregnant women do take folic acid at some point during their pregnancy. Very few of them start taking supplements before conception as recommended. The aim of this study was to find out more about the supplementation behavior among pregnant women and postpartum women in Berlin. METHODS: Pregnant women and postpartum women were asked to anonymously fill in a questionnaire about potential folic acid intake. We conducted a logistic regression analysis to identify independent predictors of folic acid intake during pregnancy. RESULTS: 90.7% (n=1069) of women did take folic acid at some point during their pregnancy, 37.8% (n=445) before conception as advised. Women are more likely to take folic acid before conception when they have planned their pregnancy, when they are better educated, earn more money and are older. Non-German(-speaking) women took significantly less folic acid than German women. Education, income and planning of the pregnancy were identified as independent predictors of folic acid intake prior to conception. CONCLUSION: Almost two thirds of pregnant women do not take folic acid when they need it most, especially those women who do not make much money, are not well educated, are young, and/or have not planned their pregnancy. Additionally, the supplementation rate is lower among non-German women and/or women who do not speak any German.

Reducing inequities in preventable neural tube defects: the critical and underutilized role of neurosurgical advocacy for folate fortification.

Neural tube defects (NTDs) are one of the greatest causes of childhood mortality and disability-adjusted life years worldwide. Global prevalence at birth is approximately 18.6 per 10,000 live births, with more than 300,000 infants with NTDs born every year. Substantial strides have been made in understanding the genetics, pathophysiology, and surgical treatment of NTDs, yet the natural history remains one of high morbidity and profound impairment of quality of life. Direct and indirect costs of care are enormous, which ensures profound inequities and disparities in the burden of disease in countries of low and moderate resources. All indices of disease burden are higher for NTDs in developing countries. The great tragedy is that the majority of NTDs can be prevented with folate fortification of commercially produced food. Unequivocal evidence of the effectiveness of folate to reduce the incidence of NTDs has existed for more than 25 years. Yet, the most comprehensive surveys of effectiveness of implementation strategies show that more than 100 countries fail to fortify, and consequently only 13% of folate-preventable spina bifida is actually prevented. Neurosurgeons harbor a disproportionate, central, and fundamental role in the management of NTDs and enjoy high standing in society. No organized group in medicine can speak as authoritatively or convincingly. As a result, neurosurgeons and organized neurosurgery harbor disproportionate potential to advocate for more comprehensive folate fortification, and thereby prevent the most common and severe birth defect to impact the human nervous system. Assertive, proactive, informed advocacy for folate fortification should be a central and integral part of the neurosurgical approach to NTDs. Only by making the prevention of dysraphism a priority can we best address the inequities often observed worldwide.

Ácido fólico 400mcg em associação a vitamina E 10mg para prevenção de distúrbios do tubo neural relacionados à deficiência de ácido fólico em mulheres que estejam em idade fértil / Folic acid 400mcg in combination with vitamin E 10mg for prevention of neural tube disorders related to folic acid deficiency in women who are of childbearing age

CONTEXTO: Os defeitos do tubo neural são defeitos congênitos severos do sistema nervoso central que se originam durante a embriogênese, entre o 18º e 28º dias após a fertilização. Referem-se à fusão incompleta ou fechamento defeituoso da região mediana dorsal do embrião e podem ser divididos em cranianos e espinhais. Os mais comuns são anencefalia, as encefaloceles e a espinha bífida. As características clínicas associadas a essas deformidades variam bastante, principalmente com relação à severidade. Lesões abertas que afetam o cérebro (anencefalia, craniorraquisquise) são invariavelmente letais antes, no momento ou pouco tempo após o nascimento. As encefaloceles também podem ser letais a depender da extensão do dano cerebral relacionado à protrusão (herniação). Casos de espinha bífida aberta são compatíveis com a sobrevivência após o nascimento, entretanto o comprometimento neurológico resultante do local afetado pode traduzir-se em perda sensorial, incapacidade de andar e incontinência. O tratamento principal para as encefaloceles e para a espinha bífida é o cirúrgico, quando possível. No Brasil a prevalência de todos os defeitos do tubo neural no período de 2005 a 2007 foi de 24,3 por 10.000 nascimentos. Uma importante intervenção médica é a prevenção de defeitos do tubo neural por meio da suplementação periconcepcional com ácido fólico. O Ministério da Saúde por meio do Programa Nacional de Suplementação de Ferro (PNSF) e da Política Nacional de Alimentação e Nutrição (PNAN) (Portaria nº 1.977, de 12 de setembro de 2014) recomenda em Manual de Condutas Gerais do Programa Nacional de Suplementação de Ferro que a suplementação com ácido fólico deve ser iniciada pelo menos 30 dias antes da data em que se planeja engravidar para a prevenção da ocorrência de defeitos do tubo neural e deve ser mantida durante toda a gestação para a prevenção da anemia. TECNOLOGIA: Ácido fólico 400 mcg em associação a acetato de dextroalfatocoferol (vitamina E) 10 mg. PERGUNTA: O DTN-Fol® é uma opção eficaz, segura e econômica para a prevenção de defeitos do tubo neural (DTN) associados à deficiência de ácido fólico em mulheres que estejam em idade fértil ou que desejam engravidar em comparação com as opções disponibilizada pelo Sistema Único de Saúde? EVIDÊNCIAS CIENTÍFICAS: Atualmente não há estudos nos quais se comparem de forma direta os efeitos da suplementação periconcepcional com ácido fólico isoladamente com os da suplementação com ácido fólico em associação com vitamina E na prevenção de defeitos do tubo neural ou em outros importantes desfechos relacionados à gestação e maternidade. Em revisão sistemática de estudos controlados e randomizados de boa qualidade apontou-se efeito benéfico da utilização preconcepcional de ácido fólico na prevenção de defeitos do tubo neural independentemente da associação desse composto a outras vitaminas e sais minerais. Após a publicação dos estudos controlados randomizados nos quais se demonstra efeito protetor da suplementação com ácido fólico, foram conduzidos vários estudos observacionais e de casocontrole, nos quais, em sua maioria, obtém-se resultados que corroboram os estudos clínicos, observando-se o efeito protetor do ácido fólico tanto proveniente de programas de fortificação alimentar quanto da suplementação direta. Em revisão sistemática de boa qualidade metodológica não se identificou efeito benéfico da suplementação periconcepcional com vitamina E em importantes desfechos relacionados à gestação, à maternidade e à saúde do feto. Em função da comprovação do efeito protetor do ácido fólico grande quantidade de países, por meio de seus órgãos sanitários, recomendam a suplementação periconcepcional com esse composto. Em nenhum país recomenda-se a suplementação com vitamina E de forma específica. AVALIAÇÃO ECONÔMICA: A análise de custo-minimização apresentada pelo demandante não foi considerada adequada para o contexto apresentado porque, de acordo com as evidências avaliadas nesse parecer, não se deve considerar as tecnologias em análises intercambiáveis, não se justificando uma suplementação em nível populacional com vitamina E. Outra questão diz respeito ao preço do ácido fólico isolado utilizado, o preço fábrica da tabela CMED, que é mais alto que o valor praticado de fato no SUS, quando se avaliam registros de compras recentes. O que se observa na prática é que a tecnologia em análise é mais cara que o ácido fólico isolado, não se justificando uma análise de custo-minimização. AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Uma possível incorporação da associação entre ácido fólico e vitamina E causaria um aumento de gasto incremental de R$ 6.928.122,00 no primeiro ano e um gasto acumulado incremental nos três anos de R$ 68.254.800,30. RECOMENDAÇÃO INICIAL DA CONITEC: A recomendação inicial da Comissão Nacional de Incorporação de Tecnologias no SUS, na 66ª reunião ordinária no dia 10 de maio de 2018, foi por unanimidade não incorporar a associação entre ácido fólico (400 mcg) e vitamina E (10 mg) (DTN-FOL®), entendendo que apesar de ser forte a recomendação da utilização adequada de ácido fólico periconcepcional para a prevenção de defeitos do tubo neural, não há evidências sobre o efeito da utilização periconcepcional da associação entre ácido fólico e vitamina E ou de vitamina E isolada em desfechos relacionados a defeitos do tubo neural. Além disso, uma possível incorporação da referida associação estaria relacionada a um aumento de gastos para o SUS. CONSULTA PÚBLICA: A consulta pública nº 29/2018, publicada no diário oficial da união de 25/05/2018, foi realizada entre os dias 26/05/2018 e 14/06/2018. Foram recebidas 82 contribuições, sendo 9 pelo formulário para contribuições técnico-científicas e 73 pelo formulário para contribuições sobre experiência ou opinião de pacientes, familiares, amigos ou cuidadores de pacientes, profissionais de saúde ou pessoas interessadas no tema. Após apreciação das contribuições encaminhadas pela consulta pública, o plenário da CONITEC entendeu que não houve nem um fato novo e suficiente para alterar a conduta atual do Ministério da Saúde que é a da utilização de ácido fólico na concentração de 400 mcg no período periconcepcional para prevenção de defeitos do tubo neural, não entendendo que a associação obrigatória com vitamina E, apesar de segura, traria algum benefício adicional. Dessa forma, mantém a recomendação inicial desfavorável à incorporação da associação fixa entre ácido fólico e vitamina E. Reforça-se que o medicamento DTN-FOL® é eficaz e seguro, entretanto de composição muito específica, com apenas um produtor nacional em contexto de utilização do ácido fólico em escala nacional para prevenção de defeitos do tubo neural, como política pública em saúde. RECOMENDAÇÃO FINAL DA CONITEC: Os membros da CONITEC presentes na 69ª reunião ordinária, no dia 01 de agosto de 2018, deliberaram, por unanimidade, por recomendar a não incorporação ao SUS da associação entre ácido fólico (400 mcg) e acetato de dextroalfatocoferol (vitamina E) 10 mg para prevenção de defeitos do tubo neural relacionados à deficiência de ácido fólico em mulheres em idade fértil. Foi assinado o Registro de Deliberação nº 359/2018. Decisão: Não incorporar o ácido fólico 400 mcg + acetato de dextroalfatocoferol 10 mg para prevenção de distúrbios do tubo neural relacionados a deficiência de ácido fólico, para mulheres em idade fértil no âmbito do Sistema Único de Saúde ­ SUS

Understanding the consumption of folic acid during preconception, among Pakistani, Bangladeshi and white British mothers in Luton, UK: a qualitative study.

BACKGROUND: To review the similarities and differences in Pakistani, Bangladeshi and White British mothers health beliefs (attitudes, knowledge and perceptions) and health behaviour regarding their consumption of folic acid pre-conception, to reduce the risk of neural tube defects. METHODS: Our study used a descriptive qualitative research approach, implementing face-to-face focus group discussions with Pakistani, Bangladeshi or White British mothers (normal birth outcomes and mothers with poor birth outcomes) and semi-structured interviews or focus groups with service providers using semi-structured topic guides. This method is well suited for under researched areas where in-depth information is sought. There were three sample groups: 1. Pakistani, Bangladeshi and White British mothers with normal birth outcomes (delivery after 37 weeks of gestation, in the preceding 6 to 24 months, weighing 2500 g and living within a specified postcode area in Luton, UK). 2. Pakistani Bangladeshi and white British bereaved mothers who had suffered a perinatal mortality (preceding 6 to 24 months, residing within a specificied postcode area). 3. Healthcare professionals working on the local maternity care pathway (i.e. services providing preconception, antenatal, antepartum and postpartum care). Transcribed discussions were analysed using the Framework Analysis approach. RESULTS: The majority of mothers in this sample did not understand the benefits or optimal time to take folic acid pre-conception. Conversely, healthcare professionals believed the majority of women did consume folic acid, prior to conception. CONCLUSIONS: There is a need to increase public health awareness of the optimal time and subsequent benefits for taking folic acid, to prevent neural tube defects.

Improving maternal folate status to prevent infant neural tube defects: working group conclusions and a framework for action.

As infectious disease control programs achieve increasing success, further reductions in child mortality in low- and middle-income countries (LMICs) will require focused prevention strategies for birth defects and other noninfectious diseases. Neural tube defects (NTDs) can cause early death or lifelong disability. Preventing NTDs provides a feasible, significant opportunity to decrease the toll of birth defects and contribute to further reducing child mortality globally. The Micronutrient Forum convened a technical consultation on Folate Status in Women and Neural Tube Defects Prevention to develop a roadmap to inform and prioritize investments in NTD prevention in LMICs; help guide implementation efforts in terms of the feasibility of interventions and the potential for acceleration; and identify research and knowledge gaps. Here, we describe the impetus for and approach to the consultation and present the conclusions and a framework for developing a roadmap for action to accelerate NTD prevention in LMICs. The framework (1) provides options for action on folate status assessment; (2) outlines a way forward to develop and implement a time-bound global action plan for NTD prevention; and (3) identifies common impediments to NTD prevention, broad strategies to overcome or minimize these impediments, and basic building blocks necessary to accelerate action.

Community approval required for periconceptional adolescent adherence to weekly iron and/or folic acid supplementation: a qualitative study in rural Burkina Faso.

BACKGROUND: Iron deficiency remains a prevalent adolescent health problem in low income countries. Iron supplementation is recommended but improvement of iron status requires good adherence. OBJECTIVES: We explored factors affecting adolescent adherence to weekly iron and/or folic acid supplements in a setting of low secondary school attendance. METHODS: Taped in-depth interviews were conducted with participants in a randomised, controlled, periconceptional iron supplementation trial for young nulliparous women living in a rural, malaria endemic region of Burkina Faso. Participants with good, medium or poor adherence were selected. Interviews were transcribed and analysed thematically. RESULTS: Thirty-nine interviews were conducted. The community initially thought supplements were contraceptives. The potential benefits of giving iron supplementation to unmarried "girls" ahead of pregnancy were not recognised. Trial participation, which required parental consent, remained high but was not openly admitted because iron supplements were thought to be contraceptives. Unmarried non-school attenders, being mobile, were often sent to provide domestic labour in varied locations. This interrupted adherence - as did movement of school girls during vacations and at marriage. Field workers tracked participants and trial provision of free treatment encouraged adherence. Most interviewees did not identify health benefits from taking supplements. CONCLUSIONS: For success, communities must be convinced of the value of an adolescent intervention. During this safety trial, benefits not routinely available in iron supplementation programmes were important to this low income community, ensuring adolescent participation. Nevertheless, adolescents were obliged to fulfil cultural duties and roles that interfered with regular adherence to the iron supplementation regime. TRIAL REGISTRATION: Trial Registration at clinicaltrials.gov : NCT01210040.

The investment case for folic acid fortification in developing countries.

There is compelling evidence that neural tube defects can be prevented through mandatory folic acid fortification. Why, then, is an investment case needed? At the core of the answer to this question is the notion that governments and individuals have limited resources for which there are many competing claims. An investment case compares the costs and benefits of folic acid fortification relative to alternative life-saving investments and informs estimates of the financing required for implementation. Our best estimate is that the cost per death averted through mandatory folic acid fortification is $957 and the cost per disability-adjusted life year is $14.90. Both compare favorably to recommended life-saving interventions, such as the rotavirus vaccine and insecticide-treated bed nets. Thus, there is a strong economic argument for mandatory folic acid fortification. Further improvements to these estimates will require better data on the costs of implementing fortification and on the costs of improving compliance where regulations are already in place.

Folate status in women of reproductive age as basis of neural tube defect risk assessment.

Reliable folate status data for women of reproductive age (WRA) to assess global risk for neural tube defects (NTDs) are needed. We focus on a recent recommendation by the World Health Organization that a specific "optimal" red blood cell (RBC) folate concentration be used as the sole indicator of NTD risk within a population and discuss how to best apply this guidance to reach the goal of assessing NTD risk globally. We also emphasize the importance of using the microbiologic assay (MBA) as the most reliable assay for obtaining comparable results for RBC folate concentration across time and countries, the need for harmonization of the MBA through use of consistent key reagents and procedures within laboratories, and the requirement to apply assay-matched cutoffs for folate deficiency and insufficiency. To estimate NTD risk globally, the ideal scenario would be to have country-specific population-based surveys of RBC folate in WRA determined utilizing a harmonized MBA, as was done in recent studies in Guatemala and Belize. We conclude with guidance on next steps to best navigate the road map toward the goal of generating reliable folate status data on which to assess NTD risk in WRA in low- and middle-income countries.

Do Italian pregnant women use periconceptional folate supplementation?

INTRODUCTION: Deficiency of folic acid (FA) has been identified as a risk factor for neural tube defects (NTDs) as well as other congenital anomalies. Thus, periconceptional folate supplementation is recommended for all women planning to get pregnant. METHODS: We conducted a KAP (knowledge, attitude, practice) survey to investigate the use of FA and its appropriateness. The survey included a sample of 562 women who delivered in the Lazio region between 2013 and 2014. Two logistic regression analyses were performed to evaluate the association between the characteristics of participating women and both the information received on FA intake and its use. RESULTS: The prevalence of periconceptional FA assumption was 19.4% although 82.2% of the interviewed women had planned their pregnancies. CONCLUSIONS: It shows that more periconceptional counseling is needed to increase women's awareness on the opportunity of FA supplementation.

[Investigation on folic acid supplementation status among Chinese women in the first trimester of pregnancy].

OBJECTIVE: To investigate folic acid (FA) supplementation status among Chinese rural reproductive women in their early pregnancy, and to provide evidence for the evaluation of FA supplementation project from national basic public health services. METHODS: The data on intake status of FA supplementation from "National Free Preconception Health Examination Project (NFPHEP)" database between January 1, 2010 and December 31, 2012 was used and analyzed.A total of 902 270 women who achieved follow-up during early pregnancy from 220 pilot counties of 31 provinces were recruited. RESULTS: From 2010 to 2012, the rate of FA intake among women recuited were 73.58% (134 131/182 289), 75.88% (329 288/433 970) and 76.53% (218 896/286 011), respectively, which increased year by year (χtrend(2)=13 371.8, P<0.001). Among 682 315 women who took FA, 350 738(51.40%) women began to take FA 3 months before amenorrhea; 130 683 (19.15%) women began to take FA 1-2 months before amenorrhea, and 200 894 (29.44%) began to take FA after amenorrhea.Among 682 315 women who took FA, 645 310 (94.58%) women took it regularly, and 342 418 (50.18%) women took FA in a standardized way. CONCLUSIONS: The status of FA intake among Chinese rural women in the first trimester of pregnancy was good, and 75.62% (682 315/902 270) of them took FA.It is also important for basic public health services to improve the rate of FA intake and increase the rate of taking FA in a standardized way in Chinese rural pregnant women.

Long term trends in prevalence of neural tube defects in Europe: population based study.

STUDY QUESTION: What are the long term trends in the total (live births, fetal deaths, and terminations of pregnancy for fetal anomaly) and live birth prevalence of neural tube defects (NTD) in Europe, where many countries have issued recommendations for folic acid supplementation but a policy for mandatory folic acid fortification of food does not exist? METHODS: This was a population based, observational study using data on 11,353 cases of NTD not associated with chromosomal anomalies, including 4162 cases of anencephaly and 5776 cases of spina bifida from 28 EUROCAT (European Surveillance of Congenital Anomalies) registries covering approximately 12.5 million births in 19 countries between 1991 and 2011. The main outcome measures were total and live birth prevalence of NTD, as well as anencephaly and spina bifida, with time trends analysed using random effects Poisson regression models to account for heterogeneities across registries and splines to model non-linear time trends. SUMMARY ANSWER AND LIMITATIONS: Overall, the pooled total prevalence of NTD during the study period was 9.1 per 10,000 births. Prevalence of NTD fluctuated slightly but without an obvious downward trend, with the final estimate of the pooled total prevalence of NTD in 2011 similar to that in 1991. Estimates from Poisson models that took registry heterogeneities into account showed an annual increase of 4% (prevalence ratio 1.04, 95% confidence interval 1.01 to 1.07) in 1995-99 and a decrease of 3% per year in 1999-2003 (0.97, 0.95 to 0.99), with stable rates thereafter. The trend patterns for anencephaly and spina bifida were similar, but neither anomaly decreased substantially over time. The live birth prevalence of NTD generally decreased, especially for anencephaly. Registration problems or other data artefacts cannot be excluded as a partial explanation of the observed trends (or lack thereof) in the prevalence of NTD. WHAT THIS STUDY ADDS: In the absence of mandatory fortification, the prevalence of NTD has not decreased in Europe despite longstanding recommendations aimed at promoting peri-conceptional folic acid supplementation and existence of voluntary folic acid fortification. FUNDING, COMPETING INTERESTS, DATA SHARING: The study was funded by the European Public Health Commission, EUROCAT Joint Action 2011-2013. HD and ML received support from the European Commission DG Sanco during the conduct of this study. No additional data available.

Few Danish pregnant women follow guidelines on periconceptional use of folic acid.

INTRODUCTION: Approximately 60-70 pregnancies are affected by neural tube defects (NTD) in Denmark annually. Folic acid (FA) deficiency can cause NTD. Periconceptional FA supplementation reduces the risk of NTD by up to 70-80%. Danish women planning pregnancy are recommended 0.4 mg of FA daily from at least one month before planned conception and continuing throughout the first 12 weeks of pregnancy. The aim of the present study was to examine the knowledge about and use of FA supplementation among Danish pregnant women. METHODS: From 11 October 2012 to 15 November 2012, all women attending for a routine nuchal translucency scan were given a questionnaire regarding their knowledge and use of FA supplementation during their current pregnancy. RESULTS: A total of 462 women answered the questionnaire. 95% had taken FA supplements at some point during their pregnancy, but only 10.4% as recommended. More than 80% stated knowledge about recommendations before the current pregnancy. Positive predictors of knowledge were: age > 30 years, multiparity, Danish origin and education > 3 years. CONCLUSION: Despite national recommendations on periconceptional FA supplementation, our study showed that women do not follow these recommendations. Especially women with a low socio-economic status were likely to lack knowledge about FA supplementation in relation to pregnancy. There is a need for revision of the existing national recommendations and for other initiatives aiming to improve women's intake of FA, including FA fortification of flour and/or other food products. FUNDING: not relevant. TRIAL REGISTRATION: The study was approved by the Danish Data Protection Agency (No.: 01855 HVH-2012-044).

Predicting folic acid intake among college students.

PURPOSE: Annually in the United States, approximately 3,000 babies are born with neural tube defects (NTDs). Folic acid supplementation can reduce NTDs by 50% to 70%. Despite recommendations for folic acid intake, only 30% of women ages 18 to 24 report folic acid supplementation and 6% have knowledge of when to take folic acid. There is little information regarding lifestyle factors that correlate with consuming folic acid. The purpose was to describe folic acid consumption among college students; and explore the relationship between folic acid intake and the variables of: age, gender, year in college, alcohol and tobacco use, and vitamin supplement intake. STUDY DESIGN AND METHODS: This was a descriptive study with secondary analysis of data from 1,921 college-aged student participants in North Carolina who took part in a pretest/posttest-designed intervention to increase folic acid consumption and knowledge. Surveys included demographic, lifestyle, folic acid knowledge, and consumption questions adapted from the Centers for Disease Control and Prevention questionnaire. Quantitative analyses included descriptive statistics and logistic regression. RESULTS: Of the 1,921 college students, 83.3% reported taking a vitamin supplement, but only 47.6% stated that the vitamin contained folic acid. A relationship was found between age, year in school, gender, and vitamin intake. Lifestyle variables were not significant predictors of folic acid consumption. CLINICAL IMPLICATIONS: Identification of variables associated with folic acid intake, marketing, and education can be focused to increase supplementation levels, and ultimately reduce the number of NTDs.