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.

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.

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.

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.

The cost-effectiveness of mandatory folic acid fortification in Australia.

The Australian government recently introduced mandatory folic acid fortification of bread to reduce the incidence of neural tube defects (NTDs). The economic evaluation of this policy contained a number of limitations. This study aimed to address the limitations and to reconsider the findings. Cost-effectiveness analysis was used to assess the cost and benefits of mandatory versus voluntary folic acid fortification. Outcomes measures were quality-adjusted life-years (QALYs), life-years gained (LYG), avoided NTD cases, and additional severe neuropathy cases. Costs considered included industry costs and regulatory costs to the government. It was estimated that mandatory fortification would prevent 31 NTDs, whereas an additional 14 cases of severe neuropathy would be incurred. Overall, 539 LYG and 503 QALYs would be gained per year of mandatory compared with voluntary fortification. Mandatory fortification was cost-effective at A$10,723 per LYG and at A$11,485 per QALY. Probabilistic sensitivity analysis showed that at A$60,000 and A$151,000 per QALY, the probability that mandatory fortification was the most cost-effective strategy was 79% and 85%, respectively. Threshold analysis of loss of consumer choice indicated that with a compensation value above A$1.21 [assuming a willingness to pay (WTP) threshold of A$60,000 per QALY] or A$3.19 (assuming a WTP threshold of A$151,000 per statistical life-year) per capita per year mandatory fortification would not be cost-effective. Mandatory fortification was found to be cost-effective; however, inclusion of the loss of consumer choice can change this result. Even with mandatory fortification, mean folate intake will remain below the recommended NTD preventive level.

Ex-ante evaluation of biotechnology innovations: the case of folate biofortified rice in China.

In order to valorize novel biotechnology innovations, there is a need to evaluate ex-ante their market potential. A case in point is biofortification, i.e. the enhancement of the micronutrient content of staple crops through conventional or genetic breeding techniques. In a recent article in Nature Biotechnology, for example, De Steur et al. (2010) demonstrated the large potential consumer health benefits of folate biofortified rice as a means to reduce folate deficiency and Neural-Tube Defects. By focusing on a Chinese high-risk region of Neural-Tube Defects, the current study defines the potential cost-effectiveness of this genetically modified crop where the need to improve folate intake levels is highest. Building on the Disability-Adjusted Life Years (DALY) approach, both the potential health impacts and costs of its implementation are measured and benchmarked against similar innovations. The results show that this transgenic crop could be a highly cost-effective product innovation (US$ 120.34 - US$ 40.1 per DALY saved) to alleviate the large health burden of folate deficiency and reduce the prevalence of neural-tube birth defects. When compared with other biofortified crops and target regions, folate biofortified rice in China has a relatively high health impact and moderate cost-effectiveness. This research further supports the need for, and importance of ex-ante evaluation studies in order to adequately market and, thus, valorize biotechnology innovations. Although the cost-effectiveness analysis enables to illustrate the market potential of innovative agricultural biotechnology research, further research is required to address policy issues on transgenic biofortification, such as biosafety regulatory requirements.

[Peri-pregnancy folic acid supplementation must be improved]. / Foliumzuursuppletiebeleid bij zwangerschap werkt, maar moet beter.

The correct usage of folic acid (FA) supplements to prevent neural tube defects (NTDs) increased from 28% in 1996 to 50% in 2005 and remained stable until 2009. Recent data from national birth defect registries show a decrease of NTD prevalence from 13.2 (per 10,000) in 1997 to 8.3 in 2005 and stabilization up to 2009. It is estimated that between 2005 and 2009 FA supplementation prevented 583 NTD cases. The medical costs thus averted are € 75 M. If the correct usage of FA were to be increased to 70%, another 34 cases per year could be prevented. Part of the gain from continued prevention and other averted costs should be invested beforehand in the promotion of FA supplement usage.

Factors contributing to the success of folic acid public health campaigns.

BACKGROUND: Studies in the 1990s have found that periconceptional dietary folate, supplementation of folic acid or supplemental multivitamins containing folic acid, help prevent neural tube defect (NTDs) if taken at the right time. This literature review assesses the extant folic acid public health campaigns literature and identifies some common variables used in folic acid consumption campaign evaluations. METHODS: This review was part of a larger study that searched PUBMED, PsycINFO and Embase from 1976 to 2010 to identify articles related to the psychosocial and economic impact of NTDs (especially spina bifida) on patients and caregivers. RESULTS: Awareness of folic acid levels prior to conception improved post-campaign from 6 to 41%. Knowledge about consumption and correct periconceptional use of folic acid also improved. However, in most studies more than 50% of women did not take folic acid as prescribed. Many factors were associated with or without taking folic acid post-campaign, including incomplete outreach, prior awareness and knowledge, closeness to pregnancy, demographics and other personal characteristics. CONCLUSIONS: Sustained campaigning to maintain awareness about and promote periconceptional consumption of folic acid in order to reduce the incidence of NTDs is clearly needed. Additional initiatives could complement existing public health strategies.

Cost-effectiveness of mandatory folate fortification v. other options for the prevention of neural tube defects: results from Australia and New Zealand.

OBJECTIVE: To provide input to Australian and New Zealand government decision making regarding an optimal strategy to reduce the rate of neural tube defects (NTD). DESIGN: Standard comparative health economic evaluation techniques were employed for a set of intervention options for promoting folate/folic acid consumption in women capable of or planning a pregnancy. Evidence of effectiveness was informed by the international literature and costs were derived for Australia and New Zealand. RESULTS: Population-wide campaigns to promote supplement use and mandatory fortification were the most effective at reducing NTD, at an estimated 36 and 31 fewer cases per annum respectively for Australia and New Zealand, representing an 8 % reduction in the current annual NTD rate. Population-wide and targeted approaches to increase supplement use were cost-effective, at less than $AU 12,500 per disability-adjusted life year (DALY) averted ($US 9893, pound 5074), as was extending voluntary fortification. Mandatory fortification was not cost-effective for New Zealand at $AU 138,500 per DALY ($US 109 609, pound 56,216), with results uncertain for Australia, given widely varying cost estimates. Promoting a folate-rich diet was least cost-effective, with benefits restricted to impact on NTD. CONCLUSIONS: Several options for reducing NTD appear to fall well within accepted societal cost-effectiveness norms. All estimates are subject to considerable uncertainty, exacerbated by possible interactions between interventions, including impacts on currently effective strategies. The Australian and New Zealand governments have decided to proceed with mandatory fortification; it is hoped they will support a rigorous evaluation which will contribute to the evidence base.

A cost-effectiveness analysis of folic acid fortification policy in the United States.

OBJECTIVE: To quantify the health and economic outcomes associated with changes in folic acid consumption following the fortification of enriched grain products in the USA. DESIGN: Cost-effectiveness analysis. SETTING: Annual burden of disease, quality-adjusted life years (QALY) and costs were projected for four steady-state strategies: no fortification, or fortifying with 140, 350 or 700 microg folic acid per 100 g enriched grain. The analysis considered four health outcomes: neural tube defects (NTD), myocardial infarctions (MI), colon cancers and B12 deficiency maskings. SUBJECTS: The US adult population subgroups defined by age, gender and race/ethnicity, with folate intake distributions from the National Health and Nutrition Examination Surveys (1988-1992 and 1999-2000), and reference sources for disease incidence, utility and economic estimates. RESULTS: The greatest benefits from fortification were predicted in MI prevention, with 16 862 and 88 172 cases averted per year in steady state for the 140 and 700 microg fortification levels, respectively. These projections were between 6261 and 38 805 for colon cancer and 182 and 1423 for NTD, while 15-820 additional B12 cases were predicted. Compared with no fortification, all post-fortification strategies provided QALY gains and cost savings for all subgroups, with predicted population benefits of 266 649 QALY gained and $3.6 billion saved in the long run by changing the fortification level from 140 microg/100 g enriched grain to 700 microg/100 g. CONCLUSIONS: The present study indicates that the health and economic gains of folic acid fortification far outweigh the losses for the US population, and that increasing the level of fortification deserves further consideration to maximise net gains.

Economic evaluation of a neural tube defect recurrence-prevention program.

BACKGROUND: Women with a pregnancy affected by a neural tube defect (NTD) are encouraged to take folic acid prior to a subsequent pregnancy, but it is unknown whether organized attempts to identify and counsel such women to prevent recurrent NTDs are cost effective. METHODS: Data from the South Carolina recurrence-prevention program for October 2001-September 2002 were analyzed between October 2002 and December 2003 to calculate costs. Cost-effectiveness modeling of the program during 1992-2006 was conducted during 2007. Results were calculated for three scenarios based on recurrence risk, supplement use, and the effectiveness of folic acid in preventing recurrences. For each scenario, quality-adjusted life years (QALYs) were calculated separately using prevented NTD-affected live births; prevented NTD-affected births (including fetal deaths); and all prevented NTD-affected pregnancies. RESULTS: The prevention program cost approximately $155,000 per year in 2003 dollars to protect 35 pregnancies and prevent approximately one NTD. The direct costs associated with an NTD depend on type and outcome, but are approximately $560,000 in 2003 dollars for a live birth with spina bifida. The base-case cost-effectiveness ratio was $39,600 per QALY gained from avoided NTD-affected live births and stillbirths, and $14,700 per QALY gained from the avoidance of all NTD-affected pregnancies. The baseline NTD recurrence risk and the use of folic acid supplements by women who are at high risk for an NTD-affected pregnancy were influential parameters. CONCLUSIONS: The South Carolina NTD recurrence-prevention program appears comparable in cost effectiveness to other preventive services. Other states might consider including NTD recurrence prevention in birth defect-prevention programs.

Decline in the prevalence of neural tube defects following folic acid fortification and its cost-benefit in South Africa.

BACKGROUND: In October 2003 South Africa embarked on a program of folic acid fortification of staple foods. We measured the change in prevalence of NTDs before and after fortification and assessed the cost benefit of this primary health care intervention. METHODS: Since the beginning of 2002 an ecological study was conducted among 12 public hospitals in four provinces of South Africa. NTDs as well as other birth defect rates were reported before and after fortification. Mortality data were also collected from two independent sources. RESULTS: This study shows a significant decline in the prevalence of NTDs following folic acid fortification in South Africa. A decline of 30.5% was observed, from 1.41 to 0.98 per 1,000 births (RR = 0.69; 95% CI: 0.49-0.98; p = .0379). The cost benefit ratio in averting NTDs was 46 to 1. Spina bifida showed a significant decline of 41.6% compared to 10.9% for anencephaly. Additionally, oro-facial clefts showed no significant decline (5.7%). An independent perinatal mortality surveillance system also shows a significant decline (65.9%) in NTD perinatal deaths, and in NTD infant mortality (38.8%). CONCLUSIONS: The decrease in NTD rates postfortification is consistent with decreases observed in other countries that have fortified their food supplies. This is the first time this has been observed in a predominantly African population. The economic benefit flowing from the prevention of NTDs greatly exceeds the costs of implementing folic acid fortification.

Economic evaluation of folic acid food fortification in The Netherlands.

BACKGROUND: Folic acid intake before and during pregnancy reduces neural tube defects (NTD). Therefore, several countries have enriched bulk food with folic acid resulting in a 26-48% decrease in the prevalence of NTDs. In 2000, the Dutch Health Council advised against folic acid enrichment based on literature research; yet formal cost-effectiveness information was absent. We designed our study to estimate cost-effectiveness of folic acid food fortification in the Netherlands. METHOD: Prevalence of NTD at birth, life-time costs of care, and folic acid fortification costs were estimated using Dutch registrations, Dutch guidelines for costing, (inter)national literature and expert opinions. Both net cost per discounted life year gained and net cost per discounted quality adjusted life year (QALY) gained were estimated for the base case and sensitivity analyses. RESULTS: In the base case and most sensitivity analyses, folic acid enrichment was estimated to be cost-saving. Bulk food fortification with folic acid remains cost-effective as long as enrichment costs do not exceed euro5.5 million (threshold at euro20 000 per QALY). CONCLUSION: Our model suggests that folic acid fortification of bulk food to prevent cases of NTD in newborns might be a cost-saving intervention in the Netherlands. Additionally, besides the evidence that folic acid reduces the number of NTDs, there are indications that folic acid is associated with the prevention of other birth defects, cardiovascular diseases and cancer. Our model did not yet include these possibly beneficial effects.

Preconception care: preliminary estimates of costs and effects of smoking cessation and folic acid supplementation.

OBJECTIVE: To assess costs and effectiveness of preconception counseling for all women planning pregnancy in The Netherlands with regard to folic acid supplementation and smoking cessation counseling. STUDY DESIGN: Costs and effects were estimated based on 200,000 women approached yearly and uptake rates of 50% and 75%. Effectiveness and potential savings were based on hospital costs of neural tube defects, low birth weight, very low birth weight and perinatal death attributable to maternal smoking. RESULTS: Total costs were estimated at dollar 5.1 million and dollar 7.2 million at uptake rates of 50% and 75%, respectively. If 50% of women would seek preconception counseling, 22 neural tube defects, 98 low-birth-weight infants, 10 very-low-birth-weight infants and 7 perinatal deaths could be avoided. At 75% uptake, 33 neural tube defects, 146 low- and 15 very-low-birth-weight infants, and 11 perinatal deaths could be avoided. CONCLUSION: Net costs of preconception counseling amount to dollar 3.7 million and dollar 5.0 million when considering cases prevented and subsequent potential savings in costs of neural tube defects and smoking-related morbidity only. However, in light of many other preventable adverse outcomes and the potential of preconception counseling to prevent significant lifetime costs for affected children, the net costs may ultimately result in a favorable cost-savings balance. Moreover, the importance of a healthy child cannot be expressed in terms of costs and savings alone.

Folic acid fortification of grain: an economic analysis.

OBJECTIVES: The purpose of this study was to compare the economic costs and benefits of fortifying grain with folic acid to prevent neural tube defects. METHODS: A cost-benefit analysis based on the US population, using the human capital approach to estimate the costs associated with preventable neural tube defects, was conducted. RESULTS: Under a range of assumptions about discount rates, baseline folate intake, the effectiveness of folate in preventing neural tube defects, the threshold dose that minimizes risk, and the cost of surveillance, fortification would likely yield a net economic benefit. The best estimate of this benefit is $94 million with low-level (140 micrograms [mcg] per 100 g grain) fortification and $252 million with high-level (350 mcg/100 g) fortification. The benefit-to-cost ratio is estimated at 4.3:1 for low-level and 6.1:1 for high-level fortification. CONCLUSIONS: By averting costly birth defects, folic acid fortification of grain in the United States may yield a substantial economic benefit. We may have underestimated net benefits because of unmeasured costs of neural tube defects and unmeasured benefits of higher folate intake. We may have overestimated net benefits if the cost of neurologic sequelae related to delayed diagnosis of vitamin B12 deficiency exceeds our projection.