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

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

Spina bifida folate fortification in Brazil, update 2022: a cross-sectional study.

INTRODUCTION: Despite improving maternal-child indicators in Brazil, congenital malformations are still the second cause of mortality in the first years of life. This work aims to compare statistical data before and after flour fortification with folic acid (FA) in Brazil. METHODS: A cross-sectional Brazilian-population-based study compares the spina bifida (SB) rates pre- and post-fortification of the flour with folate. Data collected from the public database of the Live Birth Information System (SINASC/SUS) was performed. The period 1999-2004 (pre-fortification) was compared with 2005-2010 (post-maize and wheat fortification with FA), and another analysis comparing 2005-2010 and 2011-2020 (cassava flour fortification) was performed. The estimator was the prevalence ratio (PRR); the confidence interval selected was 95%. We used a random effects analysis model and inverse variance. RESULTS: The review showed a tendency to decrease the PRR after flour fortification; however, there is no statistical significance between studies. DATASUS data analysis comparing 5 years before and 5 years after mandatory maize and wheat flour fortification demonstrated a rate ratio of 1.05 (95% CI 0.99-1.1; p = 0.075). Furthermore, comparing 10 years after additional cassava flour folate fortification, the rate ratio increased to 1.4 (95% CI 1.34-1.45; p < 0.01). CONCLUSION: This study demonstrated an increase in SB after FA fortification. Possible explanations rely on national registry improvement, not fortified staple food, or further unidentified causes. Moreover, suggestions can be made for creating a mandatory registry for malformations, inspecting the concentrations of FA in the flour, and fortifying all food.

Changes in Spina Bifida Lesion Level after Folic Acid Fortification in the US.

OBJECTIVE: To assess whether the severity of cases of spina bifida changed after the institution of mandatory folic acid fortification in the US. STUDY DESIGN: Six active population-based birth defects programs provided data on cases of spina bifida for 1992-1996 (prefortification period) and 1999-2016 (postfortification period). The programs contributed varying years of data. Case information included both a medical record verbatim text description of the spina bifida diagnosis and spina bifida codes (International Classification of Diseases, Clinical Modification, or a modified birth defects surveillance coding system). Comparing the prefortification and postfortification periods, aORs for case severity (upper-level lesions [cervical, thoracic] vs lower-level lesions [lumbar, sacral]) and prevalence ratios (PRs) were estimated. RESULTS: A total of 2593 cases of spina bifida (out of 7 816 062 live births) met the inclusion criteria, including 573 cases from the prefortification period and 2020 cases from the postfortification period. Case severity decreased by 70% (aOR, 0.30; 95% CI, 0.26-0.35) between the fortification periods. The decrease was most pronounced for non-Hispanic White mothers. Overall spina bifida prevalence declined by 23% (PR, 0.77; 95% CI, 0.71-0.85), with similar reductions seen across the early, mid, and recent postfortification periods. A statistically significant decrease in upper-level lesions occurred in the postfortification period compared with the prefortification period (PR, 0.28; 95% CI, 0.22-0.34), whereas the prevalence of lower-level lesions remained relatively similar (PR, 0.94; 95% CI, 0.84-1.05). CONCLUSIONS: The severity of spina bifida cases decreased after mandatory folic acid fortification in the US. Further examination is warranted to better understand the potential effect of folic acid on spina bifida severity.

Guía de Práctica Clínica Disrafias Espinales 2017 / Guide of Clinical Practice Spinal Dystrophies 2017

Objetivo general: Generar recomendaciones basadas en la mejor evidencia disponible acerca de la prevención, tratamiento y rehabilitación de disrafias espinales en recién nacidos

Espina bífida, prevención, diagnóstico y manejo prenatal / Spina bifida, prevention, prenatal diagnosis and management

Esta revisión de la literatura intenta actualizar conceptos en relación al diagnóstico, prevención y manejo prenatal de la espina bífida. La espina bífida corresponde a la malformación más común secundaria a defectos de cierre del tubo neural. Los recién nacidos con esta condición requieren cirugía en los primeros días de vida y presentas diversos grados de secuelas. En EE.UU afecta a 3,4 por 10.000 nacidos vivos. En Chile, después dela fortificación de la harina con ácido fólico la incidencia de espina bífida es de 3,9 por 10.000 nacidos, 40 por ciento menos que en la etapa pre- fortificación. El diagnóstico puede sospecharse precozmente con ecografía entre 11 y 14 semanas con la evaluación de translucencia intracraneana y confirmarse en el segundo trimestre con este mismo método, buscando signos clásicos. Son útiles estudios complementarios con ecografía 3D y RNM para definir de mejor manera el pronóstico y enfrentamiento. Al tratamiento tradicional quirúrgico postnatal se agrega en los últimos años, en casos seleccionados, la alternativa de cirugía antenatal, con resultados positivos que superarían al tratamiento postnatal. En Chile existe experiencia ya con 26 casos de cirugía fetal de espina bífida. No existe consenso total respecto a la vía de parto más adecuada, aunque la tendencia es hacia la resolución por cesárea.

This literature review attempts to update concepts regarding the diagnosis, prevention and management of prenatal spina bifida. Spina bifida is a congenital malformation resulting from defects in neural tube closure. Infants with this condition require surgery in the first days of their life and show varying degrees of sequelae. In the US affects 3.4 per 10,000 live births. In Chile, after fortification of flour with folic acid incidence of spina bifida is 3.9 per 10,000 births, 40 percent less than in the pre- stage fortification. The diagnosis maybe suspected early by an ultrasound between 11 and 14 weeks with the evaluation of intracranial translucency and confirmed in the second quarter with the same method, looking for classic signs. They are useful complementary studies with 3D ultrasound and MRI to better define prognosis and confrontation. The traditional postnatal surgical treatment is added in recent years, in selected cases, the alternative of antenatal surgery with positive results that exceed the postnatal treatment. In Chile there and experience with 26 cases of fetal surgery for spina bifida. There is no complete consensus regarding the most appropriate route of delivery, although the trend is toward resolution by cesarean section.

[Effects of wheat flour fortification with folic acid on the prevalence of neural tube defects in Chile]. / Resultados del Programa de Prevención de Defectos de Tubo Neural en Chile mediante la fortificación de la harina con ácido fólico: Período 2001-2010.

BACKGROUND: Congenital malformations (CMF) have an important role in infant mortality. Neural tube defects (NTD) have great relevance from both social and public health points of view. The ECLAMC (Collaborative Latin American Study of Congenital Malformations) maintains in Chile an epidemiological surveillance of CMF prevalence rate at birth since 1969. AIM: To assess the effect of wheat flour folic acid fortification on the prevalence of NTD. PATIENTS AND METHODS: Only Anencephaly, Spina bifida and Cephalocele were considered as NTD. All children born in the maternities incorporated to ECLAMC between 1969 and 1999 were considered as belonging to the pre folic acid fortification period and those who were born from 2001 to 2010 were considered as belonging to the post fortification period. RESULTS: The NTD prevalence rate at birth in the pre fortification period was 17.03/10,000. In the second period, there were 291,996 births and among them, 280 newborns were affected by a form of NTD (9.59 in 10,000 births). This represents a 44% decrease (p < 0.01). Anencephaly rate fell from 7.16/10,000 to 3.67/10,000, representing a 49% lower rate (p < 0.01). Spina bifida rate decreased from 8.61/10,000 to 4.49/10,000, representing a 48% lower rate (p < 0.01). Cephalocele had a 20% non-significant reduction. CONCLUSIONS: Wheat flour fortification with folic acid reduced by 44% the prevalence rate of NTD at birth. This means that NTDs were prevented in 185 Chilean newborns each year.

Resultados del Programa de Prevención de Defectos de Tubo Neural en Chile mediante la fortificación de la harina con ácido fólico: Período 2001-2010 / Effects of wheat flour fortification with folic acid on the prevalence of neural tube defects in Chile

Background: Congenital malformations (CMF) have an important role in infant mortality. Neural tube defects (NTD) have great relevance from both social and public health points of view. The ECLAMC (Collaborative Latin American Study of Congenital Malformations) maintains in Chile an epidemiological surveillance of CMF prevalence rate at birth since 1969. Aim: To assess the effect of wheat flour folic acid fortification on the prevalence of NTD. Patients and Methods: Only An encephaly, Spina bifida and Cephalocele were considered as NTD. All children born in the maternities incorporated to ECLAMC between 1969 and 1999 were considered as belonging to the pre folic acid fortification period and those who were born from 2001 to 2010 were considered as belonging to the post fortification period. Results: The NTD prevalence rate at birth in the pre fortification period was 17.03/10,000. In the second period, there were 291,996 births and among them, 280 newborns were affected by a form of NTD (9.59 in 10,000 births). This represents a 44% decrease (p < 0.01). Anencephaly rate fell from 7.16/10,000 to 3.67/10,000, representing a 49% lower rate (p < 0.01). Spina bifida rate decreased from 8.61/10,000 to 4.49/10,000, representing a 48% lower rate (p < 0.01). Cephalocele had a 20% non-significant reduction. Conclusions: Wheat flour fortification with folic acid reduced by 44% the prevalence rate of NTD at birth. This means that NTDs were prevented in 185 Chilean newborns each year.

[Prevalence and spatial distribution of neural tube defects in São Paulo State, Brazil, before and after folic acid flour fortification]. / Prevalência e distribuição espacial de defeitos do tubo neural no Estado de São Paulo, Brasil, antes e após a fortificação de farinhas com ácido fólico.

This cross-sectional study analyzed the prevalence and spatial distribution of neural tube defects before and after folic acid flour fortification. The study used the Information System on Live Births (SINASC) and presented prevalence rates according to maternal characteristics with odds ratios (OR) and 95% confidence intervals (95%CI). Polynomial regression was used in time trend analysis and empirical Bayesian smoothed maps for spatial analysis. Total prevalence of neural tube defects decreased by 35%, from 0.57/1,000 to 0.37/1,000 live births after fortification (OR = 0.65; 95%CI: 0.59-0.72). There was a reduction among newborns of mothers with the following characteristics: all age groups (except < 15 years), more than three years of schooling, and seven or more prenatal visits. There was a reduction over time and in most of São Paulo State, except in a few municipalities (counties) located in the western region of the State. Other factors may have contributed to the observed decline, but the results corroborate flour fortification as an important measure to prevent neural tube defects. Further research is needed to elucidate the lack of a decline in neural tube defects in the western part of São Paulo State.

Prevalência e distribuição espacial de defeitos do tubo neural no Estado de São Paulo, Brasil, antes e após a fortificação de farinhas com ácido fólico / Prevalence and spatial distribution of neural tube defects in São Paulo State, Brazil, before and after folic acid flour fortification / Prevalencia y distribución espacial de defectos del tubo neural en el Estado de São Paulo, Brasil, antes y después del enriquecimiento de harinas con ácido fólico

Estudo transversal que analisou prevalência e distribuição espacial de defeitos do tubo neural, antes e após a fortificação das farinhas de trigo e milho com ácido fólico no Estado de São Paulo, Brasil, com uso do Sistema de Informações sobre Nascidos Vivos (SINASC). São apresentadas prevalências segundo características maternas por meio de odds ratio (OR) e intervalos de 95% de confiança (IC95%). Para análise temporal e espacial, foram utilizados, respectivamente, regressão polinomial e mapas com suavização bayesiana empírica. A prevalência diminuiu 35%, de 0,57 para 0,37 por mil nascidos vivos após a fortificação (OR = 0,65; IC95%: 0,59-0,72). Verificou-se redução para mulheres de todas as idades (exceto < 15 anos), com mais de três anos de estudo e sete consultas ou mais de pré-natal. Confirmou-se redução temporal na maior parte do estado, exceto alguns municípios do oeste. Outros aspectos podem ter contribuído para o declínio observado, porém os resultados reiteram a fortificação de farinhas como medida importante para prevenção de defeitos do tubo neural. Outras análises devem ser realizadas para justificar resultado inverso no oeste paulista.

This cross-sectional study analyzed the prevalence and spatial distribution of neural tube defects before and after folic acid flour fortification. The study used the Information System on Live Births (SINASC) and presented prevalence rates according to maternal characteristics with odds ratios (OR) and 95% confidence intervals (95%CI). Polynomial regression was used in time trend analysis and empirical Bayesian smoothed maps for spatial analysis. Total prevalence of neural tube defects decreased by 35%, from 0.57/1,000 to 0.37/1,000 live births after fortification (OR = 0.65; 95%CI: 0.59-0.72). There was a reduction among newborns of mothers with the following characteristics: all age groups (except < 15 years), more than three years of schooling, and seven or more prenatal visits. There was a reduction over time and in most of São Paulo State, except in a few municipalities (counties) located in the western region of the State. Other factors may have contributed to the observed decline, but the results corroborate flour fortification as an important measure to prevent neural tube defects. Further research is needed to elucidate the lack of a decline in neural tube defects in the western part of São Paulo State.

Estudio transversal que analizó la prevalencia y distribución espacial de defectos del tubo neural, antes y después del enriquecimiento de las harinas de trigo y maíz con ácido fólico en el Estado de Sao Paulo, Brasil, con el uso del Sistema de Información sobre Nacidos Vivos (SINASC). Se presentaron prevalencias, según características maternas, mediante odds ratio (OR) e intervalos de un 95% de confianza (IC95%). Para un análisis temporal y espacial, fueron utilizados, respectivamente, regresión polinomial y mapas con suavizamiento bayesiano empírico. La prevalencia disminuyó un 35%, de 0,57 a 0,37 por mil nacidos vivos tras el enriquecimiento (OR = 0,65; IC95%: 0,59-0,72). Se verificó la reducción en mujeres de todas las edades (excepto < 15 años), con más de tres años de estudio y siete consultas o más de carácter prenatal. Se confirmó la reducción temporal en la mayor parte del estado, excepto algunos municipios del oeste. Otros aspectos pueden haber contribuido al declive observado, no obstante, los resultados reiteran el enriquecimiento de harinas como una medida importante para la prevención de defectos en el tubo neural. Otros análisis deben ser realizados para justificar el resultado inverso en el oeste paulista.

Asociación inversa entre asma y defectos del tubo neural: estudio ecológico binacional / Inverse association between asthma and neural tube defects: a binational ecological study

OBJETIVO: Los donadores de metilo como el ácido fólico previenen defectos del tubo neural (DTN), pero estudios recientes sugieren que también favorecen el desarrollo de asma. En este trabajo exploramos una posible asociación ecológica entre DTN y asma. MATERIAL Y MÉTODOS: Se consultaron bases de datos de México y EUA para obtener información sobre distribución geográfica (por estado) y tendencia temporal (por año) de DTN y asma. RESULTADOS: Los estados con menor frecuencia de DTN tuvieron mayor frecuencia de asma, tanto en México (rS=-0.48, p=0.005) como en EUA (rS=-0.39, p=0.005). Las tendencias temporales también mostraron correlación inversa en México (1997-2007, rS=-0.73, p=0.01) y EUA (1979-1998, rS=-0.91, p<0.001). CONCLUSIONES: En ambos países la frecuencia de asma correlacionó de forma inversa con la frecuencia de DTN, tanto en distribución geográfica como en tendencias anuales, apoyando la posibilidad de que la ingestión de donadores de metilo en la dieta o como suplementos esté influyendo sobre la frecuencia de asma.

OBJECTIVE: Dietary intake of methyl donors such as folic acid prevents neural tube defects (NTD), but recent studies showed that it might also favor the development of asthma. In this work a possible ecological association between NTD and asthma was explored. MATERIAL AND METHODS: Data bases from Mexico and the United States (US) were reviewed to obtain information about geographical distribution (by state) and temporal trends (by year) of NTD and asthma. RESULTS: Those states with the lowest frequency of NTD had the highest frequency of asthma, both in Mexico (rS=-0.48, p=0.005) and US (rS=-0.39, p=0.005). Temporal trends also showed an inverse correlation in Mexico (1997-2007, rS=-0.73, p=0.01) and US (1979-1998, rS=-0.91, p<0.001). CONCLUSIONS: In both countries the frequency of asthma inversely correlated with the frequency of NTD, both in geographical distribution and annual trends, giving support to the possibility that methyl donors intake in diet or supplements is influencing the asthma frequency.

[Inverse association between asthma and neural tube defects: a binational ecological study]. / Asociación inversa entre asma y defectos del tubo neural: estudio ecológico binacional.

OBJECTIVE: Dietary intake of methyl donors such as folic acid prevents neural tube defects (NTD), but recent studies showed that it might also favor the development of asthma. In this work a possible ecological association between NTD and asthma was explored. MATERIAL AND METHODS: Data bases from Mexico and the United States (US) were reviewed to obtain information about geographical distribution (by state) and temporal trends (by year) of NTD and asthma. RESULTS: Those states with the lowest frequency of NTD had the highest frequency of asthma, both in Mexico (rS=-0.48, p=0.005) and US (rS=-0.39, p=0.005). Temporal trends also showed an inverse correlation in Mexico (1997-2007, rS=-0.73, p=0.01) and US (1979-1998, rS=-0.91, p<0.001). CONCLUSIONS: In both countries the frequency of asthma inversely correlated with the frequency of NTD, both in geographical distribution and annual trends, giving support to the possibility that methyl donors intake in diet or supplements is influencing the asthma frequency.

[Impact of the fortification of food with folic acid on neural tube defects in Costa Rica]. / Impacto de la fortificación de alimentos con ácido fólico en los defectos del tubo neural en Costa Rica.

OBJECTIVE: Evaluate the impact of the fortification of food with folic acid on prevalence trends for neural tube defects (NTD) and the infant mortality rate (IMR) associated with this disorder in Costa Rica. METHODS: The surveillance data from the Congenital Disease Registry Center and the Central American Population Center were analyzed. The neural tube defects considered were anencephaly, spina bifida, and encephalocele. The trends from 1987-2009, as well as the differences in prevalence and mortality rates prior to and up to 12 years after food fortification with folic acid, were examined (95% confidence interval [CI]). The contribution of fortification to the decrease in the overall IMR was determined. RESULTS: During 1987-1997, prior to the period of food fortification with folic acid, NTD prevalence was 12/10 000 births (95% CI: 11.1-12.8), whereas in 2009 prevalence was 5.1/10 000 births (3.3-6.5). The IMR associated with NTD was 0.64/1 000 births (46-0.82) in 1997 and 0.19/1 000 births (0.09-9.3) in 2009. There were significant decreases in the IMR associated with NTD and the prevalence of NTD: 71%, and 58%, respectively (P < 0.05). The overall IMR decreased from 14.2/1 000 births in 1997 to 8.84/1 000 births in 2009 (P < 0.05). The decrease in the IMR associated with NTD contributed to an 8.8% decrease in the overall IMR from 1997 to 2009. CONCLUSIONS: Food fortification with folic acid caused a decrease in NTD at birth and the IMR associated with this malformation during the 1997-2009 period. It also led to a decrease in the overall IMR. There is a temporal relationship between the introduction of fortification policies and the decrease in prevalence and mortality associated with NTD. This intervention should be promoted in Latin American and Caribbean countries where it has not yet been implemented.

Impacto de la fortificación de alimentos con ácido fólico en los defectos del tubo neural en Costa Rica / Impact of the fortification of food with folic acid on neural tube defects in Costa Rica

OBJETIVO: Evaluar el impacto de la fortificación de alimentos con ácido fólico en las tendencias de las prevalencias de los defectos del tubo neural (DTN) y la tasa de mortalidad infantil (TMI) por este trastorno en Costa Rica. MÉTODOS: Se analizaron los datos de vigilancia del Centro de Registro de Enfermedades Congénitas y el Centro Centroamericano de Población. Se consideraron defectos del tubo neural la anencefalia, la espina bífida y el encefalocele. Se examinaron las tendencias durante 1987-2009, así como las diferencias de tasas (intervalo de confianza [IC] 95 por ciento) de prevalencia y mortalidad antes de la fortificación de alimentos con ácido fólico y hasta 12 años después de su implementación. Se determinó el aporte de la fortificación al descenso en la TMI general. RESULTADOS: En 1987-1997, previo al período de fortificación de alimentos con ácido fólico, la prevalencia de DTN fue de 12/10 000 nacidos (IC95 por ciento: 11,1-12,8), mientras que en 2009 fue de 5,1/10 000 nacidos (3,3-6,5). La TMI por DTN en 1997 fue de 0,64/1 000 nacimientos (46-0,82) y en 2009 de 0,19/1 000 (0,09-0,3). La TMI por DTN y su prevalencia disminuyeron en forma significativa, 71 por ciento y 58 por ciento respectivamente (P < 0,05). La TMI general disminuyó de 14,2/1 000 nacidos en 1997 a 8,84/1 000 en 2009 (P < 0,05). El descenso en la TMI por DTN contribuyó a una caída de 8,8 por ciento en la TMI general entre 1997 y 2009. CONCLUSIONES: La fortificación de alimentos con ácido fólico provocó una reducción de DTN al nacimiento y de la TMI por esta malformación durante el período 1997-2009, así como también el descenso de la TMI general. Existe relación de temporalidad entre el inicio de las políticas de fortificación y el descenso de la prevalencia y mortalidad por DTN. Se debe pro-mover esta intervención en los países de América Latina y el Caribe donde todavía no ha sido implementada.

OBJECTIVE: Evaluate the impact of the fortification of food with folic acid on prevalence trends for neural tube defects (NTD) and the infant mortality rate (IMR) associated with this disorder in Costa Rica. METHODS: The surveillance data from the Congenital Disease Registry Center and the Central American Population Center were analyzed. The neural tube defects considered were anencephaly, spina bifida, and encephalocele. The trends from 1987-2009, as well as the differences in prevalence and mortality rates prior to and up to 12 years after food fortification with folic acid, were examined (95 percent confidence interval [CI]). The contribution of fortification to the decrease in the overall IMR was determined. RESULTS: During 1987-1997, prior to the period of food fortification with folic acid, NTD prevalence was 12/10 000 births (95 percent CI: 11.1-12.8), whereas in 2009 prevalence was 5.1/10 000 births (3.3-6.5). The IMR associated with NTD was 0.64/1 000 births (46-0.82) in 1997 and 0.19/1 000 births (0.09-9.3) in 2009. There were significant decreases in the IMR associated with NTD and the prevalence of NTD: 71 percent, and 58 percent, respectively (P < 0.05). The overall IMR decreased from 14.2/1 000 births in 1997 to 8.84/1 000 births in 2009 (P < 0.05). The decrease in the IMR associated with NTD contributed to an 8.8 percent decrease in the overall IMR from 1997 to 2009. CONCLUSIONS: Food fortification with folic acid caused a decrease in NTD at birth and the IMR associated with this malformation during the 1997-2009 period. It also led to a decrease in the overall IMR. There is a temporal relationship between the introduction of fortification policies and the decrease in prevalence and mortality associated with NTD. This intervention should be promoted in Latin American and Caribbean countries where it has not yet been implemented.

Effects of folic acid fortification on spina bifida prevalence in Brazil.

BACKGROUND: To assess spina bifida birth prevalence changes after folic acid fortification of wheat and maize flours began in Brazil in June 2004. METHODS: Cross-sectional study of Brazilian live births in 2004 and 2006. Spina bifida birth prevalence from the Live Births Information System (SINASC: Sistema de Informações sobre Nascidos Vivos) in a prefortified period was compared to a period fortified with folic acid in each state. Observed prevalence rates in 2004 were used to calculate the expected prevalence rates in 2006 under the null hypothesis that both were similar. The observed/expected (O/E) ratios were tested by two-tailed Z-test. To minimize ascertainment differences among states, the O/E ratio of each one of the 27 Brazilian states was adjusted for the number of births with the Mantel-Haenszel statistic. RESULTS The reduction in spina bifida birth prevalence in 2006 was 39% (O/E = 0.61; 95% confidence interval [CI], 0.55-0.67), and 40% (O/E = 0.60; 95% CI, 0.53-0.68), after adjusting for state birth number. This reduction was significant (p < 0.0001), and heterogeneous among states (χ(2) = 72.96; p < 0.0001). CONCLUSIONS: Using SINASC data, there was a significant reduction in spina bifida birth prevalence in Brazil, probably related to the folic acid food fortification program.

Folic acid flour fortification: impact on the frequencies of 52 congenital anomaly types in three South American countries.

The aim of the present investigation was to search for a reduction in birth prevalence estimates of 52 selected types of congenital anomalies, associated with folic acid fortification programs in Chile, Argentina, and Brazil. The material included 3,347,559 total births in 77 hospitals of the three countries during the 1982-2007 period: 596,704 births (17 hospitals) in Chile, 1,643,341 (41 hospitals) in Argentina, and 1,107,514 (19 hospitals) in Brazil. We compared pre- and post-fortification rates within each hospital and the resulting Prevalence Rate Ratios (PRRs) were pooled by country. Statistically significant reductions in birth prevalence estimates after fortification were observed for neural tube defects (NTDs), septal heart defects, transverse limb deficiencies, and subluxation of the hip. However, only the reduction of NTDs appeared to be associated with folic acid fortification and not due to other factors, because of its consistency among the three countries, as well as with previously published reports, and its strong statistical significance. Among the NTDs, the maximum prevalence reduction was observed for isolated cephalic (cervical-thoracic) spina bifida, followed by caudal (lumbo-sacral) spina bifida, anencephaly, and cephalocele. This observation suggests etiologic and pathogenetic heterogeneity among different levels of spina bifida, as well as among different NTD subtypes. We concluded that food fortification with folic acid prevents NTDs but not other types of congenital anomalies.

[Effects of folic acid fortification in the rates of malformations at birth in Chile]. / Efecto de la fortificación de la harina con ácido fólico sobre la evolución de las tasas de prevalencia al nacimiento de malformaciones congénitas en los hospitales chilenos del ECLAMC.

BACKGROUND: The effects of folic acid fortification on neural tube defects is well known. Other reports show a beneficial effect of the fortification on orofacial clefts, urinary malformations and defects caused by limb reduction. AIM: To determine the changes in prevalence of congenital malformations after the start of flour folic acid fortification in Chile. MATERIAL AND METHODS: The rates of 22 malformations occurring in the maternity of the University of Chile Clinical Hospital and other Chilean hospitals participating in the Latin American Collaborative Study of Congenital Malformations (ECLAMC) were compared before and after the start of flour folic acid fortification. RESULTS: After the start of folic acid fortification a significant reduction in the rates of anencephalia, spina bifida and diaphragmatic hernia, was observed. The rates of all other malformations remained stable or increased. The rates of all malformations at the University of Chile Clinical Hospital had a steady increase until 2005 and were significantly higher than in the rest of hospitals participating in ECLAMC. CONCLUSIONS: Folic acid fortification was associated with an expected reduction in rates of spina bifida and anencephalia and an unexpected reduction in the rates of diaphragmatic hernia.

Cost-effectiveness of a folic acid fortification program in Chile.

OBJECTIVE: Periconceptional intake of folic acid reduces the risk of neural tube defects (NTDs), a frequent birth defect that can cause significant infant mortality and disability. In Chile, fortification of wheat flour with folic acid has resulted in significant reduction in the risk of anencephaly and spina bifida. We investigated the cost-effectiveness implications of this policy. METHODS: We conducted an ex-post economic analysis of this intervention. Estimates of the effect of fortification in decreasing NTDs and deaths were derived from a prospective evaluation. The costs of fortification and provision of medical care to children with spina bifida in Chile were based on primary data collection. FINDINGS: The intervention costs per NTD case and infant death averted were I$ 1200 and 11,000, respectively. The cost per DALY averted was I$ 89, 0.8% of Chile's GDP per capita. Taking into account averted costs of care, fortification resulted in net cost savings of I$ 2.3 million. CONCLUSION: Fortification of wheat flour with folic acid is a cost-effective intervention in Chile, a middle income country in the post-epidemiological transition. This result supports the continuation of the Chile fortification program and constitutes valuable information for policy makers in other countries to consider.

Efecto de la fortificación de la harina con ácido fólico sobre la evolución de las tasas de prevalencia al nacimiento de malformaciones congénitas en los hospitales chilenos del ECLAMC / Effects of folic acid fortification in the rates of malformations at birth in Chile

Background: The effects of folic acid fortification on neural tube defects is well known. Other reports show a beneficial effect of the fortification on orofacial clefts, urinary malformations and defects caused by limb reduction. Aim: To determine the changes in prevalence of congenital malformations after the start of flour folic acid fortification in Chile. Material and methods: The rates of 22 malformations occurring in the maternity of the University of Chile Clinical Hospital and other Chilean hospitals participating in the Latin American Collaborative Study of Congenital Malformations (ECLAMC) were compared before and after the start of flour folic acid fortification. Results: After the start of folic acid fortification a significant reduction in the rates of anencephalia, spina bifida and diaphragmatic hernia, was observed. The rates of all other malformations remained stable or increased. The rates of all malformations at the University of Chile Clinical Hospital had a steady increase until 2005 and were significantly higher than in the rest of hospitals participating in ECLAMC. Conclusions: Folic acid fortification was associated with an expected reduction in rates of spina bifida and anencephalia and an unexpected reduction in the rates of diaphragmatic hernia.