Anencephaly in Slovakia and Czech Republic: embryogenesis, risk factors, epidemiology and preventative approaches.

Anencephaly, a fatal anomaly of the central nervous system, belongs to the group of defects of the neural tube (NTDs). It is considered the most common congenital NTD, characterized by concurrent absence of a significant portion of the brain and cranial vault. This deformity occurs between days 23 and 26 after fertilization due to improper closure of the neural tube at its cranial end. Many genetic, epigenetic, and non-genetic factors (nutritional, environmental and geographical factors, parental socioeconomic status) contribute to the etiology of this disease. Despite significant advances in treatment and preventive measures, NTDs continue to pose a significant health and financial burden on patients and society as a whole. This study aimed to examine the incidence of anencephaly in Slovakia compared to the Czech Republic between 2012 and 2020. The authors seek to elucidate the reasons behind the higher incidence of this disease in Slovakia as compared to the Czech Republic, explore the male predominance of anencephaly in Slovakia, and investigate whether the prevention standards used in Slovakia differ from those employed in other countries (Tab. 1, Fig. 2, Ref. 129). Keywords: neural tube defects, anencephaly, risk factors, folic acid, food fortification.

Prevalence of neural tube defect and its identification during antenatal period: a cross-sectional study in eastern Indian state.

OBJECTIVE: To estimate the prevalence of neural tube defects among all birth outcomes in Odisha during 2016-2022. Additionally, to estimate the identification rate of neural tube defects during Pradhan Mantri Surakshit Matritva Abhiyan sessions. DESIGN: A population-based cross-sectional study with a household survey for neural tube defects using pictorial card as well as a hospital-based study for antenatal ultrasonography data. SETTING: The sample population was selected through multistage random sampling. In the first stage, one district from each zone was selected randomly. In the second stage, using simple random sampling, one community health centre and one urban primary health centre were selected from each district. In the third stage, the population from a block and ward were picked from the selected rural and urban settings, respectively. PARTICIPANTS: All married women in the reproductive age group (18-49 years) residing in these cluster villages in the selected districts were enrolled. RESULTS: The study surveyed 49 215 women and recorded 50 196 birth outcomes, including 49 174 live births, 890 stillbirths and 132 medical terminations of pregnancy. A total of 30 neural tube defect cases were detected. The overall prevalence rate of neural tube defect was 0.59 per 1000 birth outcomes. Spina bifida was the most prevalent neural tube defect with the prevalence of, followed by anencephaly and encephalocele. Despite 26 860 mothers receiving antenatal ultrasonography Pradhan Mantri Surakshit Matritva Abhiyan session, data on neural tube defects and other birth defects detected through these scans is unavailable. CONCLUSION: This study found a low prevalence of neural tube defect in Odisha, which is far lower compared with the older studies from India. There is an urgent need to strengthen the quality of antenatal care services provided under Pradhan Mantri Surakshit Matritva Abhiyan through better training regarding anomaly scans and better data keeping at public healthcare facilities. TRIAL REGISTRATION NUMBER: CTRI/2021/06/034487.

A global update on the status of prevention of folic acid-preventable spina bifida and anencephaly in year 2022.

BACKGROUND: Mandatory fortification of staple foods with folic acid is an effective public health strategy to prevent folic acid-preventable spina bifida and anencephaly (FAP SBA). We estimated the global proportion of FAP SBA prevented through mandatory folic acid fortification of cereal grains (i.e., wheat flour, maize flour, and rice). METHODS: We used year 2022 data from the Food Fortification Initiative to identify countries (n = 69) with mandatory fortification of grains that includes folic acid. Sixty-eight countries were eligible for analysis with complete data. Proportion of FAP SBA prevention was modeled assuming >150 mcg/day of folic acid fortification protects against FAP SBA, reducing post-fortification prevalence to a lowest achievable level of 0.5 cases per 1000 births. RESULTS: Our analysis found that a total of 63,520 cases of FAP SBA were prevented in the year 2022 in 68 countries implementing mandatory folic acid fortification of grains with folic acid. This translated to a 23.7% prevention of all possible FAP SBA prevention globally. An excess of 204,430 cases of FAPSBA still occurred in over 100 countries where mandatory staple food fortification with folic acid is not implemented. CONCLUSION: Our study showed that only a quarter of all FAP SBA cases were averted through mandatory folic acid fortification in the year 2022; many countries are not implementing the policy, resulting in a large proportion of FAP SBA cases that can be prevented. Fortification will help countries with achieving 2030 Sustainable Development Goals on neonatal- and under-five mortality, disability, stillbirths, and elective terminations prevention, from FAP SBA.

Anomalías congénitas frecuentes en Uruguay entre 2011 y 2014: importancia de un registro para la evaluación de las necesidades de salud / Frequent congenital anomalies in Uruguay in 2011-2014; importance of a medical record for health assessment / Anomalias congênitas frequentes no Uruguai entre 2011-2014, importância de um registro para avaliação das necessidades de saúde

Introducción: las anomalías congénitas (AC) son un problema de salud pública con impacto en la infancia, la mortalidad infantil (MI) y la discapacidad. En Uruguay, así como en otros países desarrollados, las AC y la prematuridad son las principales causas de MI. Objetivos: el objetivo de este trabajo fue analizar las anomalías más frecuentes en el país entre 2011 y 2014, y evaluar los factores de riesgo. Material y método: los datos se obtuvieron del Registro Nacional de Defectos Congénitos y Enfermedades Raras y Estadísticas Vitales del Ministerio de Salud Pública. Resultados: se determinó que prácticamente la mitad de los casos fueron: cardiopatías congénitas, síndrome de Down y defectos del tubo neural (anencefalia, encefalocele y mielomeningocele), representando 0,42% (812/191.820) y 2,85% (38/1334) de los nacidos vivos (NV) y de los óbitos fetales respectivamente. Las prevalencias por 10.000 NV y OF fueron: 38,52 y 149,93 para cardiopatías congénitas; 3,6 y 7,5 para síndrome de Down; 2,1 y 127,4 para defectos del tubo neural. La edad materna avanzada fue el principal factor de riesgo de síndrome de Down. Los factores de riesgo observados en las tres anomalías seleccionadas fueron: prematurez, depresión neonatal y bajo peso al nacer. Conclusiones: las anomalías congénitas en general y las seleccionadas en este trabajo en particular, constituyen una causa relevante de morbimortalidad en el período neonatal e infantil, plausibles de prevención. El diagnóstico temprano es fundamental para planificar servicios de salud especializados. Los resultados aquí presentados se pueden utilizar como línea de base para medir el impacto de las acciones de salud a nivel nacional.

Introduction: congenital anomalies (CA) are a public health problem with an impact on childhood, infant mortality (IM) and disability. In Uruguay, as well as in other developed countries, CA and prematurity are the main causes of IM. Objectives: analyze the most frequent anomalies in the country in 2011-2014 and evaluate risk factors. Material and methods: the data were obtained from the National Record of Congenital Defects and Rare Diseases and health statistics from the Ministry of Public Health. Results: it was determined that practically half of the cases were: congenital heart disease, Down syndrome and Neural Tube Defects (anencephaly, encephalocele and myelomeningocele), accounting for 0.42% (812/191,820) and 2.85% (38/1334) of live births and stillbirths respectively. The prevalence per 10,000 NV and stillbirths were: 38.52 and 149.93 for Congenital Heart Disease; 3.6 and 7.5 for Down Syndrome; 2.1 and 127.4 for neural tube defects. Advanced maternal age was the main risk factor for Down syndrome. The risk factors observed in the three selected anomalies were: prematurity, neonatal depression and low birth weight. Conclusions: congenital anomalies in general, and those selected in this study in particular, are a relevant cause of morbidity and mortality in newborns and infants, likely to be prevented. Early diagnosis is essential for planning specialized health services. The results presented in the present paper can be used as a baseline to measure the impact of health actions at national level.

Introdução: as anomalias congênitas (AC) são um problema de saúde pública com impacto na infância, na mortalidade infantil (MI) e na deficiência. No Uruguai, assim como em outros países desenvolvidos as AC e prematuridade são as principais causas de MI. Objetivos: analisar as anomalias mais frequentes no país, entre 2011-2014 e avaliar os fatores de risco. Material e métodos: os dados foram obtidos do Registro Nacional de Defeitos Congênitos e Doenças Raras e estatísticas vitais do Ministério da Saúde Pública. Resultados: determinou-se que praticamente a metade dos casos eram: cardiopatias congênitas, Síndrome de Down e Defeitos do tubo neural (anencefalia, encefalocele e mielomeningocele), representando 0,42% (812/191.820) e 2,85% (38/1334) de nascidos vivos-NV e natimortos, respectivamente. As prevalências por 10.000 NV e natimortos foram: 38,52 e 149,93 para Cardiopatia Congênita; 3,6 e 7,5 para Síndrome de Down; 2,1 e 127,4 para defeitos do tubo neural. A idade materna avançada foi o principal fator de risco para a síndrome de Down. Os fatores de risco observados nas três anomalias selecionadas foram: prematuridade, depressão neonatal e baixo peso ao nascer. Conclusões: as anomalias congênitas em geral e as selecionadas neste estudo em particular, constituem causa relevante de morbimortalidade no período neonatal e infantil, possível de ser prevenida. O diagnóstico precoce é fundamental para o planejamento de serviços de saúde especializados. Os resultados aqui apresentados podem ser usados como base para medir o impacto das ações de saúde realizadas a nível nacional.

Tendencia de los Defectos de Tubo Neural en el Estado de Hidalgo México del 2013-2018 / Trend of Neural Tube Defects in Hidalgo Mexico from 2013-2018

INTRODUCCIÓN: los Defectos de Tubo Neural (DTN) son defectos congénitos del sistema nervioso central resultado del cierre inadecuado en alguna zona del tubo neural, siendo los más frecuentes Anencefalia y Espina Bífida en sus diferentes variantes. En Latinoamérica y México se encuentran dentro de las principales causas de morbilidad y mortalidad infantil. MATERIAL Y MÉTODOS: Análisis de series de tiempo de casos y defunciones de DTN en Hidalgo del 2013-2018 generado a partir de la base de datos de la Dirección General de Vigilancia Epidemiológica de los Defectos del Tubo Neural y Craneofaciales proporcionada por la Secretaria de Salud del Estado de Hidalgo, se incluyeron 187 casos con DTN que nacieron y radican en el Estado. Se calcularon las tasas de mortalidad infantil específicas por DTN con el objetivo de identificar probables factores que incidan o incrementen dichas tendencias. RESULTADOS: la incidencia de DTN fue de 58.7 en el periodo estudiado, la Anencefalia es el más incidente 45% (84), seguido del Mielomeningocele 33% (62) él cual muestra una incidencia creciente. El 84% de la población estaba afiliada al Seguro Popular. Solo el 7.5% (14) de las madres de los casos consumieron ácido fólico tres meses previos al embarazo y el 55% (103) acudieron a 3 consultas prenatales o menos. CONCLUSIONES: Los DTN requieren de estudio y vigilancia permanente pues representan una causa importante de morbilidad y mortalidad en la infancia que afecta a los individuos que los padecen, sus familias, la sociedad y el sistema de salud, con esto se evitarían resultados negativos

INTRODUCTION: Neural Tube Defects (DTN) are congenital defects of the central nervous system resulting from an inadequate closure in some area of ​​the neural tube, the most frequent being Anencephaly and Spina Bifida in their different variants. In Latin America and Mexico, they are among the main causes of infant morbidity and mortality. MATERIAL AND METHODS: Analysis of time series of cases and deaths of DTN in Hidalgo from 2013-2018 generated from the database of the General Directorate of Epidemiological Surveillance of Neural Tube and Craniofacial Defects directly by the Ministry of Health of the State of Hidalgo, included 187 cases with DTN that were born and reside in the State. DTN specific infant mortality rates will be calculated in order to identify probable factors that influence or increase various trends. RESULTS: the incidence of DTN was 58.7 in the period studied, Anencephaly is the most incident 45% (84), followed by Myelomeningocele 33% (62), which shows an increasing incidence. 84% of the population was affiliated at the Seguro Popular. Only 7.5% (14) of the mothers of the cases consumed folic acid three months before the pregnancy and 55% (103) attended 3 or less prenatal visits. CONCLUSIONS: DTN are problems of study and permanent surveillance, since they represent an important cause of morbidity and mortality in childhood that affect the individuals who suffer, their families, society and the health system, this would avoid negative results

Prevalencia de defectos del tubo neural y estimación de casos evitados posfortificación en Argentina / Prevalence of neural tube defects and estimation of cases averted in the post-fortification period in Argentina

La ingesta periconcepcional de ácido fólico ha demostrado ser efectiva en la reducción de la frecuencia de defectos del tubo neural, y la fortificación de los alimentos ha sido una estrategia para incrementarla. Se presenta una actualización de la reducción de las prevalencias de defectos del tubo neural posfortificación en Argentina y la estimación de los casos evitados en el período 2005-2013 como consecuencia de esta intervención. Al comparar la prevalencia observada en el período posfortificación con la reportada en el período de prefortificación, se observa un descenso significativo de 66% para anencefalia y encefalocele, y de 47% para espina bífida. El número de casos evitados estimados fue mayor para anencefalia, seguido por espina bífida; encefalocele presentó el menor número de casos evitados, dado que la prevalencia de este defecto fue menor. El descenso de la prevalencia observado apoya los resultados de estudios previos sobre el efecto de la fortificación.

Periconceptional intake of folic acid has demonstrated to be effective to reduce the frequency of neural tube defects, and food fortification has been one of the strategies implemented to increase it. An update is herein presented on the reduced prevalence of neural tube defect cases in the post-fortification period in Argentina and an estimation of cases averted in the 2005-2013 period as a result of this intervention. When comparing the prevalence observed in the post-fortification period to that reported in the pre-fortification period, anencephaly and encephalocele decreased by 66%, and spina bifida, by 47%, which were significant reductions. The estimated number of cases averted was higher for anencephaly, followed by spina bifida; encephalocele showed the lowest number of cases averted given that the prevalence of this defect was smaller. The decrease observed in the prevalence supports findings from previous studies on the impact of fortification.

Feto Anencefálico: presentación de un caso y revisión de la entidad / Anencephalic fetus. A case p resentation and entity revision

Según la clasificación internacional de enfermedades, las malformaciones congénitas del Sistema Nervioso se pueden clasificar en: Anencefalia y malformaciones congénitas similares, Encefaloceles, Microcefalias, Hidrocefalias, Espina Bífida y otras malformaciones congénitas de la médula espinal. La Anencefalia se puede definir como un cierre defectuoso del neuroporo anterior durante la 4ta semana de gestación. En el momento de nacer, se denota como una masa de tejido degenerado que queda al descubierto. Esta afección es mortal en cuestión de horas o en algunas situaciones especiales días. Se presenta el caso del nacimiento de un feto anencefálico, en el Hospital Integral Comunitario en Caranavi, La Paz, Bolivia el 7 de Mayo del 2014, con el objetivo de identificar los factores asociados a esta entidad y hacer una revisión en la literatura reportada, para lo que se tomó en cuenta los artículos relacionados que circulan en la red en idioma Inglés y Español. Se concluye que hubo varios factores de riesgo relacionados con este tipo de malformación, reconocidos en la literatura revisada como: edad materna avanzada, no ingestión de acido fólico y factores ambientales adversos (manipulación de fertilizantes químicos). En la actualidad no existe cura ni tratamiento para esta entidad, solo la optimización de los servicios de atención prenatal incluyendo el programa de genética de detección precoz de malformaciones fetales, logrará disminuir el nacimiento de estos infantes(AU)

According to the international classification of diseases, the congenital malformations of the nervous system can be classified into: Anencephaly and similar congenital malformations, Encephalocele, Microcephalias, Hydrocephalias, Bifid Spina and other congenital malformations of the spinal cord. The Anencephalia can be defined as a defective closure of the previous neuropore during the 4th week of gestation. It is denoted at birth as a degenerate mass of tissue exposed. This condition is lethal in a few hours and in some special situations it can take days. It is presented the case of an anencephalic fetus, at the Community Integral Hospital in Caranavi, La Paz, Bolivia on May 7, 2014, with the aim of identifying the factors associated with this condition and making a literature revision, for which it was taken into account the related articles circulating on the net in English and Spanish language. It is concluded that there are several risk factors associated with this type of malformation, and they are recognized in the revised literatureas: the advanced maternal age, the non-taking of folic acid and the adverse environmental factors (handling of chemical fertilizers). There is no cure for this condition yet, only the optimization of prenatal care services,including the genetic program of early detection of fetal malformations will decrease these births(EU)

Characteristics of fetuses evaluated due to suspected anencephaly: a population-based cohort study in southern Brazil / Características de fetos avaliados por suspeita de anencefalia: um estudo de coorte de base populacional do Sul do Brasil

CONTEXT AND OBJECTIVE: Anencephaly is considered to be the most common type of neural tube defect. Our aim was to assess the clinical and gestational features of a cohort of fetuses with suspected anencephaly. DESIGN AND SETTING: Population-based retrospective cohort study in a referral hospital in southern Brazil. METHODS: The sample consisted of fetuses referred due to suspected anencephaly, to the Fetal Medicine Service of Hospital Materno Infantil Presidente Vargas, between January 2005 and September 2013. Clinical, radiological, pathological and survival data were gathered. RESULTS: Our sample was composed of 29 fetuses. The diagnosis of suspected anencephaly was made on average at 21.3 weeks of gestation. Seven fetuses had malformations that affected other organs, and these included oral clefts (n = 4) and congenital heart defects (n = 2). In 16 cases, there was termination of pregnancy (n = 12) or intrauterine death (n = 4). Regarding those who were born alive (n = 13), all of them died in the first week of life. After postnatal evaluation, the diagnosis of anencephaly was confirmed in 22 cases (75.9%). Other conditions included amniotic band disruption complex (6.9%), microhydranencephaly (6.9%), merocrania (3.4%) and holoprosencephaly (3.4%). CONCLUSIONS: Different conditions involving the cranial vault may be confused with anencephaly, as seen in our sample. However, these conditions also seem to have a poor prognosis. It seems that folic acid supplementation is not being properly performed. .

CONTEXTO E OBJETIVO: A anencefalia é considerada o tipo mais comum de defeito de fechamento do tubo neural. Nosso objetivo foi avaliar as características clínicas e gestacionais de uma coorte de fetos com suspeita de anencefalia. TIPO DE ESTUDO E LOCAL: Estudo de coorte retrospectivo de base populacional em um hospital de referência no sul do Brasil. MÉTODOS: A amostra foi composta por fetos encaminhados por suspeita de anencefalia ao Serviço de Medicina Fetal do Hospital Materno Infantil Presidente Vargas, no período de janeiro de 2005 a setembro de 2013. Foi realizada coleta de dados clínicos, radiológicos, patológicos e de sobrevida. RESULTADOS: Nossa amostra foi composta por 29 fetos. A suspeita do diagnóstico de anencefalia foi realizada em média com 21,3 semanas de gestação. Sete fetos apresentavam malformações que afetavam outros órgãos, e incluíram fendas orais (n = 4) e defeitos cardíacos congênitos (n = 2). Em 16 casos houve interrupção da gravidez (n = 12) ou morte intrauterina (n = 4). Daqueles que nasceram vivos (n = 13), todos morreram na primeira semana de vida. Após a avaliação pós-natal, o diagnóstico de anencefalia foi confirmado em 22 casos (75,9%). Outras condições incluíram o complexo disruptivo de banda amniótica (6,9%), microhidranencefalia (6,9%), merocrania (3,4%) e holoprosencefalia (3,4%). CONCLUSÕES: Diferentes condições que envolvem a calota craniana podem ser confundidas com a anencefalia, como verificado em nossa amostra. No entanto, estas também parecem ter um prognóstico pobre. A suplementação com ácido fólico parece não estar sendo realizada de forma adequada. .

Defectos congénitos en recién nacidos y fetos procedentes de interrupción del embarazo tras diagnóstico prenatal en el período 1982-2009 / Evolution of the frequency of congenital defects in newborn infants and fetuses from terminations of pregnancy after prenatal diagnosis in the period 1982-2009

Fundamento y objetivo: El estudio de la frecuencia de los defectos congénitos (DC) requiere incluir interrupciones voluntarias del embarazo (IVE) por DC y evaluar los factores que influyen en aquella. Pacientes y método: Serie consecutiva de 517 recién nacidos (RN) y 202 IVE con DC en 38.191 nacimientos entre 1982-2009. Resultados: La frecuencia media de RN con DC es 13,54‰ y la de RN + IVE por DC de 18,73‰. Los DC aislados suponen el 61,12% en RN y el 52,17% en IVE. El 18,37% de los DC en RN y el 40,58% en IVE son sindrómicos. La media de edad gestacional en IVE es 17,92 semanas. La frecuencia global de anencefalia es 2,62 y 6,77 por 10.000, respectivamente, en RN y en RN + IVE. La de la espina bífida es 3,14 y 5,99 por 10.000, respectivamente. La frecuencia global de síndrome de Down es 10,74 por 10.000 RN y 22,14 por 10.000 RN + IVE. El porcentaje de madres extranjeras en nuestra maternidad alcanza el 35,9% en 2009. La media de edad materna asciende significativamente a lo largo del tiempo. Conclusiones: Observamos una disminución estadísticamente significativa de DC en RN, pero no en su concepción. No detectamos prevención primaria de anencefalia ni espina bífida. El descenso de síndrome de Down en RN no alcanza significación estadística. La diversidad étnica y la mayor edad materna pueden estar modificando la frecuencia. El 53% de los casos (RN + IVE) con DC del trienio 2007-2009 fueron IVE. Se precisa el estudio completo de IVE por DC para ofrecer consejo reproductivo (AU)

Background and objective: The study of congenital defects (CD) must include termination of pregnancy (TOP) for CD and evaluate risk factors that modify their frequency. Patients and methods: Consecutive series of 517 newborn and 202 TOP with CD among 38,191 childbirths, between 1982-2009 years. Results: The mean frequency for newborns with CD is 13.54‰ and for newborn and TOP with CD is 18.73‰. Single CD are 61.12% in newborns and 52.17% in TOP. The 18.37% of CD in newborn and 40.58% of TOP are syndromic. Mean gestational age for TOP is 17.92 weeks. Overall frequency of anencephaly is 2.62‰ for newborns and 6.77 for 10,000 for newborns and TOP. Spina bifida is 3.14 for 10,000 newborns and 5.99 for 10,000 newborns and TOP. Overall frequency of Down syndrome (DS) is 10.74 for 10,000 newborns and 22.14 for 10,000 newborns and TOP. The percentage of foreign mothers was 35.9% in 2009 and the mean maternal age significantly increased in this period. Conclusion: We observe a significant decrease of CD in newborns but not in their conception. We have not detected primary prevention for neural tube defects. The decrease in DS in newborns is not statistically relevant but ethnic diversity and maternal aging may be modifying the frequency. The 53% of CD were TOP in the period 2007-2009. It is mandatory a complete study for CD in TOP in order to offer serious reproductive counseling (AU)

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.

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.

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.

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.

Defectos congénitos cráneo-encefálicos: variedades y respuesta a la fortificación de la harina con ácido fólico / Effect of flour folic acid fortification on the incidence of cranio encephalic congenital defects

Background: In Chile, flour is fortified with folic acid since 2000, and the incidence of neural tube defects has decreased. Cranio-encephalic congenital defects (CECD) have a wider clinical scope, includind classical neural tube defects (NTD) such as anencephalia and acrania, but also incorporating other defects. Therefore, the effects of folic acid fortification on the incidence of CECD could be different. Aim: To study the effect of folic acid fortification on the incidence of CECD. Material and methods: All prenatal diagnoses of CECD and cases registered locally in the Latin American Collaborative Study of Congenital Malformations (ECLAMC) were reviewed. The obtained data were crossed with all death certificates of newborns or stillborns of more than 500 g in the Sixth Region, in Central Chile. All cases were classified again in four subtypes, according to their phenotype. The incidences of all subtypes prior (1996-2000) and after folic acid supplementation (2001-2004), were compared. Results: Between 1996 and 2004, there were 64 cases of CEDC among 109,176 infants born alive. The global rate was 8.86 per 10,000 born alive in the period prior to fortification and 3.03 per 10,000 born alive after fortification. Comparing both periods, there was a 66 percent reduction in all CECD and a 77 and 100 percent reduction in subtypes A and B of CECD, respectively (p <0.05). No significant reductions in type C and D CECD, were observed. Conclusions: After the start of flour folic acid fortification, there was a global reduction in the incidence of CECD. However, only types A and B CECD, supposedly more responsive to folic acid, were reduced.

Análisis comparativo de las frecuencias de ciertos defectos congénitos y su evolución secular en 11 comunidades autónomas / Comparative analysis of the frequencies of diverse congenital birth defects and their time trends in 11 autonomous communities in Spain

Fundamento y objetivo: El conocimiento de la frecuencia de los distintos defectos congénitos a lo largo del tiempo y en las diferentes comunidades autónomas es importante, no sólo para cuantificar la magnitud del problema y planificar los recursos necesarios, sino para disponer de sistemas de vigilancia y analizar el impacto de las diversas actuaciones sanitarias. El objetivo de este trabajo ha sido analizar comparativamente en las 11 comunidades autónomas que participan en la REpIER (Red Epidemiológica de Investigación en Enfermedades Raras) las frecuencias de 6 tipos de defectos congénitos. Sujetos y métodos: Se han utilizado los datos del ECEMC (Estudio Colaborativo Español de Malformaciones Congénitas) correspondientes a las 11 autonomías que participan en la REpIER (Andalucía, Aragón, Canarias, Cantabria, Castilla-La Mancha, Cataluña, Comunidad de Madrid, Comunidad Valenciana, Extremadura, La Rioja y el Principado de Asturias), en el período 1980-2003. El ECEMC es un programa de investigación clínico-epidemiológico acerca de las causas de los defectos congénitos, estructurado como un sistema permanente de registro, con un diseño de tipo caso-control y de base hospitalaria. Los defectos estudiados han sido: anencefalia; espina bífida; labio leporino, con o sin fisura del paladar; sólo fisura del paladar; defectos por reducción de extremidades, y síndrome de Down en hijos de mujeres con más de 34 años. Para el análisis de la tendencia temporal en cada autonomía se ha utilizado la prueba de tendencia lineal (χ2con 1 grado de libertad) y la χ2 con k-2 grados de libertad para detectar desviaciones de la linealidad. Resultados: La distribución temporal de las frecuencias no es igual para todos los defectos estudiados ni en todas las comunidades. La mayor concordancia entre las 11 autonomías estudiadas se observa para la disminución secular del síndrome de Down en madres de más de 34 años, que es significativa en 8 comunidades. La anencefalia disminuye significativamente en 6 autonomías, y en otras 2 no se registró ningún caso. La espina bífida muestra descensos estadísticamente significativos en 6 circunscripciones autonómicas. La distribución secular de las frecuencias de los otros 3 tipos de malformaciones estudiadas no presenta tendencias significativas en la mayoría de las autonomías. Conclusiones: Desde que hay en España la posibilidad legal de realizar una interrupción voluntaria del embarazo tras la detección prenatal de anomalías, se observa un claro descenso de las frecuencias al nacimiento de los defectos para los que es posible el diagnóstico prenatal. Dicho descenso no ha sido igual en todas las comunidades, ni en lo que se refiere a su comienzo ni en cuanto a su intensidad, lo que puede estar poniendo de manifiesto, entre otros factores, diferencias en cuanto a la atención sanitaria

Background and objective: Knowledge of the frequency of the distinct congenital defects over time in the various Autonomous Communities in Spain is important, not only to quantify the scope of the problem and to plan the necessary resources, but also to have surveillance systems and analyze the impact of the diverse health interventions. The aim of this study was to analyze the comparative frequencies of 6 types of congenital defect in the 11 Autonomous Communities participating in the Epidemiological Network on Rare Disease Research (REpIER). Subjects and methods: We analyzed data from the Spanish Collaborative Study of Congenital Malformations (ECEMC) corresponding to the 11 Autonomous Communities participating in REpIER (Andalusia, Aragon, the Canary Islands, Cantabria, Castilla-La Mancha, Catalonia, the Autonomous Community of Madrid, the Autonomous Community of Valencia, Extremadura, La Rioja, and the Principality of Asturias) from 1980 to 2003. The ECEMC is a clinical-epidemiological research program on the causes of congenital defects, structured as a permanent registration system with a case-control design. The program is hospital-based. The defects studied were anencephaly, spina bifida, cleft lip with or without cleft palate, cleft palate only, limb reduction defects, and Down syndrome in infants born to mothers aged 34 years or older. To analyze the time trends in each Autonomous Community, the lineal trend test (chi-square with 1 degree of freedom) and chi-square with k-2 degrees of freedom to detect deviations from linearity were used. Results: The time trend of the frequencies was not the same for all the defects studied or for all the Autonomous Communities. The highest concordance between the 11 Autonomous Communities analyzed was observed in the decreasing secular trend for Down syndrome in infants born to mothers aged 34 years or older, which was statistically significant in 8 Autonomous Communities. The frequency of anencephaly significantly decreased in 6 Autonomous Communities, and in a further 2 no cases were registered. The frequency of spina bifida significantly decreased in 6 Autonomous Communities. The secular distribution of the frequencies of the other 3 types of malformations studied showed no significant trends in most of the regions. Conclusions: Since pregnancy terminations after prenatal detection of anomalies became legal in Spain, the frequency of prenatally diagnosable birth defects has clearly decreased. This decrease has not been equal in all the regions. Differences were found in the time the decreases began and in their intensity, which may reveal, among other factors, differences in health care

Anencefalia: presentación de un caso clínico / Anencephaly: a clinical case

La anencefalia es una malformación del sistema nervioso, causado por la falla del cierre del neuroporo anterior durante la embriogénesis. Su incidencia es de 1 en 1.000 embarazos en Estados Unidos. Los recién nacidos con anencefalia generalmente sobreviven sólo pocas horas o días, y excepcionalmente se han descrito casos de sobrevida de algunas semanas. Existen numeroso estudios que sugieren la existencia de factores genéticos y ambientales en la génesis de este trastorno, por ejemplo, mutaciones en el gen que codifica la enzima metilentetrahidrofolato reductasa, elevados niveles plasmáticos de homocisteína y bajos de folato en madres de niños con defectos del tubo neural y factores ambientales diversos. La mayoria de los casos son diagnosticados mediante ultrasonografía precozmente durante el embarazo (antes de las 20 semanas). Se presenta un caso clínico de recién nacido con anencefalia, en el Hospital de Salamanca, que tuvo una sobrevida excepcionalmente prolongada y se revisa el tema

Malformaciones congénitas y exposición a pesticidas / Congenital malformations and pesticide exposure

Background: Chronic pesticide exposure is a recognized risk for human health. The frequency of congenital malformations in exposed people, can be used for epidemiological studies assessing reproductive risk secondary to toxic exposure. Aim: To study the association between the incidence of congenital malformations and parent's exposure to pesticides. Material and methods: A prospective study of cases and controls. The exposure could be caused by occupational activities or residence around fumigated crops. The records of cases and controls from the surveillance carried out in the Hospital Regional de Rancagua were analyzed. This hospital is active member of a collaborative study of congenital malformations in Latin America. Results: In two years there was a total of 453 newborns (18 stillborn) with congenital malformations, with an incidence of 41.24 ä. Considering only children born alive, the paired analysis of cases and controls showed an association of congenital malformations with a history of maternal exposure, with an attributable fraction of 54.4 percent. Conclusions: These results, showing an association between pesticide exposure and congenital malformations, should be analyzed in the future by a logistic regression test