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.

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.