Birth Prevalence Of Neural Tube Defects Research Articles

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

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. 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. 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. 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. 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.

Periconceptional folic acid supplementation and sex difference in prevention of neural tube defects and their subtypes in China: results from a large prospective cohort study.

BackgroundFolic acid (FA) supplementation is known to prevent neural tube defects (NTDs). We examined whether this preventive effect differs by the sex of the infant.MethodsData were gathered from a large population-based cohort study in China that evaluated the effects of FA supplementation on NTDs. All births at 20 complete gestational weeks, including live births, stillbirths, and pregnancy terminations, and all NTDs, regardless of gestational age, were recorded. In a northern China province, a total of 30,801 singleton live births to women whose use of FA supplements during the first trimester was known at the time were included in the study. The birth prevalence of NTDs was classified by sex, subtype, and maternal FA supplementation. Male to female rate ratios [RR] and their 95% confidence intervals [CI] were calculated.ResultsA total of 106 NTDs cases were recorded. The overall prevalence of NTDs was 2.5‰ among males and 4.4‰ among females; NTDs were less prevalent among males than among females (RR, 0.58; 95% CI, 0.54–0.63). There was a higher prevalence of anencephaly (RR, 0.34; 95% CI, 0.27–0.43) and spina bifida (RR, 0.73; 95% CI, 0.63–0.84) among females. However, FA supplementation led to significantly greater decreases in the rates of anencephaly (4.8‰) and total NTDs (7.6‰) in females than in males (1.6‰ and 2.8‰, respectively).ConclusionsFA supplementation successfully reduces the prevalence of NTDs in both male and female infants, although we found a significantly greater decrease in anencephaly and total NTDs in females than in males. How the protective effects of FA supplementation affect the sexes differently needs to be studied further.

Estimates of global and regional prevalence of neural tube defects for 2015: a systematic analysis.

Neural tube defects (NTDs) are associated with substantial mortality, morbidity, disability, and psychological and economic costs. Many are preventable with folic acid, and access to appropriate services for those affected can improve survival and quality of life. We used a compartmental model to estimate global and regional birth prevalence of NTDs (live births, stillbirths, and elective terminations of pregnancy) and subsequent under-5 mortality. Data were identified through web-based reviews of birth defect registry databases and systematic literature reviews. Meta-analyses were undertaken where appropriate. For 2015, our model estimated 260,100 (uncertainty interval (UI): 213,800-322,000) NTD-affected birth outcomes worldwide (prevalence 18.6 (15.3-23.0)/10,000 live births). Approximately 50% of cases were elective terminations of pregnancy for fetal anomalies (UI: 59,300 (47,900-74,500)) or stillbirths (57,800 (UI: 35,000-88,600)). Of NTD-affected live births, 117,900 (∼75%) (UI: 105,500-186,600) resulted in under-5 deaths. Our systematic review showed a paucity of high-quality data in the regions of the world with the highest burden. Despite knowledge about prevention, NTDs remain highly prevalent worldwide. Lack of surveillance and incomplete ascertainment of affected pregnancies make NTDs invisible to policy makers. Improved surveillance of all adverse outcomes is needed to improve the robustness of total NTD prevalence estimation, evaluate effectiveness of prevention through folic acid fortification, and improve outcomes through care and rehabilitation.

Congenital Malformations of the Central Nervous System in Rural Western Honduras: A 6-Year Report on Trends.

Central nervous system (CNS) malformations, including neural tube defects (NTDs), are the second most common type of birth defects worldwide and are major causes of childhood disability and mortality. We report the first analysis of birth prevalence in Western Honduras of CNS malformations including NTDs over 6 consecutive years. Data from all patients with congenital CNS malformations and total live births for the period 2010-2015 were obtained through institution and regional registries from all 3 public referral hospitals in Western Honduras, representing 67 municipalities. Cases were identified using the International Classification of Diseases, Tenth Revision CNS malformation codes. Birth prevalence was calculated as cases per 10,000 live births. From 123,903 live births, 275 cases of CNS malformations were identified (54% females, 58% NTDs). Six-year birth prevalence of CNS malformations was 13.9-31.1. Spina bifida variants and anencephaly represented 80% and 19% of reported NTDs, respectively. Total 6-year prevalence of NTDs in Western Honduras was 7.0-17.4 over years studied. In 6 municipalities, average prevalence was >30 (maximum 49.0). This is the first study reporting disease burden of CNS malformations in Western Honduras. The nationwide birth prevalence of NTDs in rural Honduras may have decreased since the implementation of prenatal health policies in 2005. However, we identified regions with unexpectedly elevated prevalence, indicating high regional prevalence that could be targeted for improved preventive efforts, ultimately decreasing the burden of these conditions.

Prevalence of neural tube defects in a rural area of north india from 2001 to 2014: A population-based survey.

Neural tube defects (NTDs) are one of the commonest birth defects. There was paucity of community-based data on occurrence of NTDs in India, especially from rural parts of the country. Against this background, the current study was carried out with main objectives to determine the prevalence of NTDs and its specific types (anencephaly, spina bifida and encephalocele) in a rural community setting over the time period 2001 to 2014. This was a community-based cross-sectional study carried out in 28 villages of Ballabgarh Tehsil of Faridabad district in north India (population ∼ 96,000). A household survey was undertaken by trained multi-purpose workers who enquired ever-married women about history of conception with outcome as NTD during the study period. The probable case of NTD was determined using a colored pictorial card with photographs of different types of NTDs. These cases were confirmed by doctors. A total of 26,946 live births occurred during the years 2001 to 2014. A total of 140 confirmed cases of NTDs were identified. The live birth prevalence of NTDs was 24.1 per 10,000 live births (95% confidence interval, 18.8-30.6). The birth prevalence of NTDs for the years 2008 to 2014 was 50.8 (95% confidence interval, 39.9-63.8) per 10,000 live and stillbirths. The most common type of NTD was found to be spina bifida followed by anencephaly and encephalocele. We found high prevalence of NTDs in rural community settings from north India for years 2001 to 2014.Birth Defects Research 109:203-210, 2017.© 2016 Wiley Periodicals, Inc.

A Mixed-Method Study to Determine the Benefits of Periconceptional Folic Acid Supplementation and Effects of Folic Acid Deficiency in Mothers on Birth Outcomes.

BackgroundEvidence from high income countries shows mothers who are supplemented with folic acid in their periconceptional period and early pregnancy have significantly reduced adverse outcomes like birth defects. However, in India there is a paucity of data on association of birth defects and folic acid supplementation. We identified a few important questions to be answered using separate scientific methods and then planned to triangulate the information.ObjectiveIn this paper, we describe the protocol of our study that aims to determine the association of folic acid and pregnancy outcomes like neural tube defects (NTDs) and orofacial clefts (OFCs). We decided to fill the gaps in knowledge from India to determine public health consequences of folic acid deficiency and factors influencing dietary and periconceptional consumption of folic acid.MethodsThe proposed study will be carried out in five stages and will examine the questions related to folic acid deficiency across selected locations in South and North India. The study will be carried out over a period of 4 years through the hierarchical evidence-based approach. At first a systematic review was conducted to pool the current birth prevalence of NTDs and orofacial clefts OFCs in India. To investigate the population prevalence, we plan to use the key informant method to determine prevalence of NTDs and OFCs. To determine the normal serum estimates of folic acid, iron, and vitamin B12 among Indian women (15-35 years), we will conduct a population-based, cross-sectional study. We will further strengthen the evidence of association between OFCs and folic acid by conducting a hospital-based, case-control study across three locations of India. Lastly, using qualitative methods we will understand community and health workers perspective on factors that decide the intake of folic acid supplements.ResultsThis study will provide evidence on the community prevalence of birth defects and prevalence folic acid and vitamin B12 deficiency in the community. The case-control study will help understand the association of folic acid deficiency with OFCs.ConclusionsThe results from this study are intended to strengthen the evidence base in childhood disability for planning and policy initiatives.

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...

Peru's national folic acid fortification program and its effect on neural tube defects in Lima

OBJECTIVE: To evaluate the impact of Peru's national folic acid fortification program on folic acid content in wheat flour, and the effect on birth prevalence of neural tube defects (NTDs) in Lima, and to compare the program's legislative requirements with international standards. METHODS: Bread was sampled from six sites across Peru and tested for folic acid. Data were obtained from the largest obstetric hospital in Lima on the prevalence of births (live and still) with NTDs during both the pre-fortification period (2004-2005) and post-fortification years (2007-2008). RESULTS: Folic acid content in the sampled bread met national legislative requirements but was less than one-half of the level recommended for Peru by the World Health Organization (WHO) (2.6 mg/kg wheat flour). Birth prevalence of NTDs was 18.4/10 000 in the pre-fortification period and 20.0/10 000 during post-fortification years. Relative risk for NTDs after fortification was 1.02 (95% confidence interval 0.77-1.35, P = 0.90). CONCLUSIONS: Peruvian legislative requirements for folic acid fortification are below international (WHO) recommendations; birth prevalence of NTDs in Lima is higher than international benchmarks; and no decrease in NTDs following fortification of flour with folic acid (according to Peruvian national standards) was observed. As increasing the level of folic acid in flour remains the most sustainable way of preventing NTDs, it is recommended that Peru increase its folic acid fortification requirements to meet those recommended by WHO (2.6 mg/kg).

Peru's national folic acid fortification program and its effect on neural tube defects in Lima

To evaluate the impact of Peru's national folic acid fortification program on folic acid content in wheat flour, and the effect on birth prevalence of neural tube defects (NTDs) in Lima, and to compare the program's legislative requirements with international standards. Bread was sampled from six sites across Peru and tested for folic acid. Data were obtained from the largest obstetric hospital in Lima on the prevalence of births (live and still) with NTDs during both the pre-fortification period (2004-2005) and post-fortification years (2007-2008). Folic acid content in the sampled bread met national legislative requirements but was less than one-half of the level recommended for Peru by the World Health Organization (WHO) (2.6 mg/kg wheat flour). Birth prevalence of NTDs was 18.4/10 000 in the pre-fortification period and 20.0/10 000 during post-fortification years. Relative risk for NTDs after fortification was 1.02 (95% confidence interval 0.77-1.35, P = 0.90). Peruvian legislative requirements for folic acid fortification are below international (WHO) recommendations; birth prevalence of NTDs in Lima is higher than international benchmarks; and no decrease in NTDs following fortification of flour with folic acid (according to Peruvian national standards) was observed. As increasing the level of folic acid in flour remains the most sustainable way of preventing NTDs, it is recommended that Peru increase its folic acid fortification requirements to meet those recommended by WHO (2.6 mg/kg).

The use of a Toolkit for health needs assessment on neural tube defects in Argentina.

Health needs assessment (HNA) is a commonly used process for those working in public health. The PHG Foundation has developed a Toolkit to provide users with a stepwise approach for undertaking a HNA on birth defects. We report the findings from using the Toolkit to examine needs in relation to policies and programs, services, and interventions for neural tube defects (NTDs) in Argentina. The trend over the last few decades is one of decline in infant mortality from nutritional and infectious causes, thus further increasing the relative importance of birth defects. The observed prevalence of NTDs is consistent with that reported internationally. Since 2002 folic acid fortification (FAF) has been mandatory by law, and different studies have shown at least a 50% decrease in the birth prevalence of NTDs after FAF. In Argentina, there is inequity between the public and non-public health sectors. The birth prevalence of NTDs seems lower in the non-public sector, possibly as a result of better nutritional status of women, higher access to folic acid supplementation, and earlier prenatal diagnosis followed by termination of pregnancy (ToP) in non-public hospitals. Although illegal, ToP is believed to be widespread, with better access for people of higher socioeconomic status. Through the process of HNA, we identified several unmet needs regarding registration of cases, public and professional education, legislation, and organization of care pathways. In our experience, the Toolkit brought together people working on the same issue, and it engaged and motivated experts and stakeholders to work together to tackle the problem.

Metabolic Signature of Pregnant Women with Neural Tube Defects in Offspring

Neural tube defects (NTDs) are one of the most common types of birth defects, affecting approximately 1 of every 1000 pregnancies in the United States and an estimated 300 000 newborns worldwide each year. The metabolic signature of pregnant women with NTDs in offspring has not previously been characterized. In this paper, we report a profiling study that characterized the serum metabolome of 101 pregnant women affected with NTDs in offspring in comparison with 143 pregnant women with normal pregnancy outcomes in Lvliang prefecture, the area with the highest birth prevalence of NTDs in China. A serum metabonomic study was also conducted to identify significantly altered metabolites associated with di-n-butyl phthalate (DBP)-induced teratogenesis in mice. The metabolic signature of NTD in pregnant women is characterized by the impaired mitochondrial respiration, neurotransmitter γ-aminobutyric acid, and methionine cycle. Of interest, consistent findings from DBP-induced teratogenesis in mice demonstrated increased succinate and decreased fumarate, suggesting an inhibited succinic dehydrogenase implicated in the defective mitochondria. The characteristic disruption of maternal metabolism offers important insights into metabolic mechanisms underlying human NTDs as well as potential preventive strategies.

Prevalence of neural tube defects in Australia prior to mandatory fortification of bread‐making flour with folic acid

To establish baseline prevalence of neural tube defects (NTDs) prior to mandatory folic acid fortification in Australia. Retrospective population based study. Data from the Australian Congenital Anomalies Monitoring System, for 1998-2005 were used to calculate birth prevalence including live/stillbirths of at least 20 weeks gestation or 400 g birthweight. Total prevalence and trends of NTD including terminations of pregnancy (TOPs) before 20 weeks were established using data from South Australia, Victoria and Western Australia because of the incomplete ascertainment in other states. The birth prevalence of NTDs from 1998-2005, was 5/10,000 births. The total prevalence including TOPs was 13/10,000 births. A 26% declining trend in total prevalence was seen from 1992-2005, but the main decline occurred prior to 1998. Women who were Indigenous, socially disadvantaged, young, living in remote areas and had multiple gestations were more likely to give birth to babies with NTDs. The prevalence of NTD has been stable since 1998. Reporting of the birth prevalence alone underestimates the actual prevalence of NTD. From a public health perspective, future monitoring of NTD following implementation of fortification of bread-making flour with folic acid should include a mixed methods approach; reporting birth prevalence on national data and total prevalence on tri-state data.

Changes in the birth prevalence of selected birth defects after grain fortification wiht folic acid in the United States: Findings from a multi-state population-based study

Observational studies and clinical trials have suggested that periconceptional use of folic acid can reduce the risk of birth defects other than neural tube defects (NTDs). Using data reported by states to the National Birth Defects Prevention Network, we examined whether folic acid fortification might have decreased the prevalence of other specific birth defects. For each of 16 birth defect categories selected for study, birth prevalence for two time periods was calculated with data submitted from a number of states in 1995-1996 ("pre-fortification") and 1999-2000 ("post-fortification"). Changes in birth prevalence between the two time periods were assessed by calculating prevalence ratios and 95% confidence intervals for each defect, and compared by maternal race/ethnicity and availability of prenatally diagnosed cases. We confirmed previously reported reductions in the birth prevalence of NTDs. In addition, we found modest, yet statistically significant, decreases in the birth prevalence for transposition of the great arteries(12%), cleft palate only (12%), pyloric stenosis (5%), upper limb reduction defects (11%), and omphalocele (21%). More substantial subgroup decreases were observed for renal agenesis among programs that conduct prenatal surveillance (28%), for common truncus among Hispanics (45%), and for upper limb reduction defects among Hispanics (44%). There were modest yet significant increases in the prevalence of obstructive genitourinary defects (12%) and Down syndrome (7%), but not among programs conducting prenatal surveillance for these defects. These results suggest some modest benefit from the folic acid fortification on the prevalence of a number of non-NTD birth defects.

Neural tube defects: is a decreasing prevalence associated with a decrease in severity?

Objective: Severe neural tube defects (NTDs) tend to occur with disproportionate frequency in areas of high prevalence. The objective of our study was to determine the birth prevalence of NTDs during a 25-year period at a single institution based in an area of high prevalence for NTDs and to investigate if a decreasing prevalence resulted in a change in the type of NTDs. Study design: All cases of NTD affected births born at the Coombe Women's Hospital during the interval 1975–1999 were reviewed. There were 171,260 births at the Coombe Women's Hospital between 1975 and 1999. During this interval, there were 522 NTD affected births. Results: From 1975 until 1999 the prevalence of NTDs significantly decreased ( P < 0.0001). This transition from high to low prevalence was associated with a significant decrease in severe forms of NTDs ( P < 0.0001). This decreasing trend in rate and severity of NTD affected births was most dramatic prior to either food fortification or periconceptual folic acid supplementation. Conclusions: Our transition from high to low prevalence for NTDs has been associated with a significant decrease in severe forms of NTDs.

Does prenatal screening for 5,10-methylenetetrahydrofolate reductase (MTHFR) mutations in high-risk neural tube defect pregnancies make sense?

Despite the fact that neural tube defects (NTDs) are the most common congenital malformations of the central nervous system, investigators have yet to identify responsible gene(s). Research efforts have been productive in the identification of environmental factors, such as periconceptional folic acid supplementation, that modulate risk for the development of NTDs. Studies of the folic acid biosynthetic pathway led to the discovery of an association between elevated levels of homocysteine and NTD risk. Researchers subsequently identified single nucleotide polymorphisms in the gene coding for the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR). Association studies suggested it was a potential risk factor for NTDs, because the thermolabile form of the enzyme led to elevated homocysteine concentrations when folic acid intake is low. Numerous studies analyzing MTHFR variants have resulted in positive associations with increased NTD risk only in certain populations, suggesting that these variants are not large contributors to the etiology of NTDs. With our limited understanding of the genes involved in regulating NTD susceptibility, the paucity of data on how folic acid protects the developing embryo, as well as the observed decrease in birth prevalence of NTDs following folic acid supplementation and food fortification, it makes little sense for prospective parents to be tested for MTHFR variants, or for variants of other known folate pathway genes.

Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects.

Daily consumption of 400 microg of folic acid before conception and during early pregnancy dramatically reduces the occurrence of neural tube defects (NTDs). Before food fortification, however, only an estimated 29% of US reproductive-aged women were taking a supplement containing 400 microg of folic acid daily. The US Food and Drug Administration authorized addition of folic acid to enriched grain products in March 1996, with compliance mandatory by January 1998. To evaluate the impact of food fortification with folic acid on NTD birth prevalence. National study of birth certificate data for live births to women in 45 US states and Washington, DC, between January 1990 and December 1999. Birth certificate reports of spina bifida and anencephaly before fortification (October 1995 through December 1996) compared with after mandatory fortification (October 1998 through December 1999). The birth prevalence of NTDs reported on birth certificates decreased from 37.8 per 100 000 live births before fortification to 30.5 per 100 000 live births conceived after mandatory folic acid fortification, representing a 19% decline (prevalence ratio [PR], 0.81; 95% confidence interval [CI], 0.75-0.87). During the same period, NTD birth prevalence declined from 53.4 per 100 000 to 46.5 per 100 000 (PR, 0.87; 95% CI, 0.64-1.18) for women who received only third-trimester or no prenatal care. A 19% reduction in NTD birth prevalence occurred following folic acid fortification of the US food supply. However, factors other than fortification may have contributed to this decline.

Quantifying the Decline in the Birth Prevalence of Neural Tube Defects in England and Wales

In England and Wales there has been a large decline in the birth prevalence of neural tube defects (NTDs) from the early 1970s (reported rates of about 3.2 per 1000 births) to the present (0.1 per 1000 births in 1997). The reported number of terminations of NTD pregnancies increased from 0.02 per 1000 in 1970 to 0.66 per 1000 in 1997, much too small an increase to explain the decline in NTD births. Some underreporting of NTD terminations is recognised. We estimated its extent using 1976‐80 data on reported central nervous system (CNS) defect terminations and NTD births in an analysis in which the true total number of NTD pregnancies during this short period was assumed to have either remained constant or else to have been changing by a constant amount per year. The estimate was that 56% of NTD terminations were not reported as such and this fitted the data well. In 1997 the estimated birth prevalence of NTDs was 0.14 per 1000 births, a fall of 96% since 1970. This 96% was apportioned as 40% due to antenatal screening and termination of pregnancy and 56% due to a decline in incidence. Over the period 1970‐97 there was an increase in dietary folate, and this will have at least in part caused the decline in incidence of NTDs. (J Med Screen 1999;6:182‐185)

Similarities in the epidemiology of neural tube defects and coronary heart disease: is homocysteine the missing link?

It is hypothesised that a single aetiological pathway could explain both the strong ecological association between the birth prevalence of neural tube defects (NTD) and coronary heart disease (CHD) mortality...

East Ireland 1980-1994: epidemiology of neural tube defects.

STUDY OBJECTIVE: The objective of the study was to describe the epidemiology of neural tube defects (NTD) in the eastern region of Ireland using the EUROCAT register of congenital malformations....

Quantifying the decline in the birth prevalence of neural tube defects in England and Wales

In England and Wales there has been a large decline in the birth prevalence of neural tube defects (NTDs) from the early 1970s (reported rates of about 3.2 per 1000 births) to the present (0.1 per 1000 births in 1997). The reported number of terminations of NTD pregnancies increased from 0.02 per 1000 in 1970 to 0.66 per 1000 in 1997, much too small an increase to explain the decline in NTD births. Some underreporting of NTD terminations is recognised. We estimated its extent using 1976-80 data on reported central nervous system (CNS) defect terminations and NTD births in an analysis in which the true total number of NTD pregnancies during this short period was assumed to have either remained constant or else to have been changing by a constant amount per year. The estimate was that 56% of NTD terminations were not reported as such and this fitted the data well. In 1997 the estimated birth prevalence of NTDs was 0.14 per 1000 births, a fall of 96% since 1970. This 96% was apportioned as 40% due to antenatal screening and termination of pregnancy and 56% due to a decline in incidence. Over the period 1970-97 there was an increase in dietary folate, and this will have at least in part caused the decline in incidence of NTDs.