Genetic susceptibility for retinopathy of prematurity and its associated comorbidities.

BACKGROUND: Retinopathy of prematurity (ROP) is one of the leading cause of child blindness. Preterm newborns of very low gestational age (GA) and very low birth weight are at the greatest risk. Our objective was to evaluate the role of genetic variants associated with ROP risk and its comorbidities in an Argentinian sample of premature infants. METHODS: A sample of 437 preterm infants <33 weeks GA, born at a maternity hospital in Tucumán, Argentina, 2005-2010, was analyzed. Environmental factors, perinatal outcomes, and fourteen single nucleotide polymorphisms associated with ROP were evaluated, comparing ROP with non-ROP newborns. A lasso logistic regression was performed to select variables; then, a conditional logistic regression was used to identify ROP maternal and perinatal risk factors adjusting by maternal and gestational ages, respectively. RESULTS: ROP maternal risk factors were alcohol intake, periodontal infections, and severe stress. Respiratory distress, sepsis, and intracranial hemorrhage were the ROP perinatal risk factors. Markers rs186085 of EPAS1 and rs427832 of AGTR1 were significantly associated with ROP newborns. CONCLUSION: We identified three maternal and three perinatal risk factors associated with ROP. Genes EPAS1 and AGTR1, involved in angiogenesis and vascularization, were identified to be of risk for ROP. IMPACT: Genetic and environmental risk factors associated with ROP and its comorbidities are evaluated in a Latin American population. Genes EPAS1 and AGTR1, involved in angiogenesis and vascularization, were identified to be of risk for ROP. Three maternal and three perinatal risk factors associated with ROP were also identified. A matrix of significant relationships among genetic markers and comorbidities is presented. Reported data may help develop more effective preventive measures for ROP in the Latin American region.

Indirect Effects of Neighbourhood Socioeconomic Status on Preterm Birth Risk in an Argentine Population.

BACKGROUND: Preterm birth (PTB) is the main condition related to perinatal morbimortality worldwide. The aim of this study was to determine the indirect effects of neighbourhood socioeconomic status (NSES) on the risk of spontaneous PTB. METHODS: We carried out a retrospective case-control study including sociodemographic and obstetric data of multigravid women who gave birth at a maternity hospital in Tucumán, Argentina, between 2005 and 2010: 949 women without previous PTB nor pregnancy loss who delivered at term and 552 who had spontaneous PTB. NSES was estimated from the Unsatisfied Basic Needs index of census data. Variables selected through penalised regressions were used to create a data-driven Bayesian network; then, pathways were identified and mediation analyses performed. RESULTS: Maternal age less than 20 years mediated part of the protective effect of high NSES on spontaneous PTB [natural indirect effect (NIE) -0.0125, 95% confidence interval (CI) (-0.0208, -0.0041)] and on few prenatal visits (< 5) [NIE - 0.0095, 95% CI (-0.0166, -0.0025)]. These pathways showed greater sensitivity to unobserved confounders that affect the variables mediator-outcome in the same direction, and exposure-mediator in the opposite direction. They did not show sensitivity to observed potential confounders, nor to the parameterization used to define NSES. Meanwhile, urinary tract infections showed a trend in mediating the effect of low NSES on spontaneous PTB [NIE 0.0044, 95% CI (-0.0006, 0.0093), P 0.0834]. CONCLUSIONS: High NSES has protective indirect effects on spontaneous PTB risk, mainly associated with a lower frequency of teenage pregnancy.

Gene-environment interactions and preterm birth predictors: A Bayesian network approach.

Preterm birth (PTB) is the main condition related to perinatal morbimortality worldwide. The aim of this study was to identify gene-environment interactions associated with spontaneous PTB or its predictors. We carried out a retrospective case-control study including parental sociodemographic and obstetric data as well as newborn genetic variants of 69 preterm and 61 at term newborns born at a maternity hospital from Tucumán, Argentina, between 2005 and 2010. A data-driven Bayesian network including the main PTB predictors was created where we identified gene-environment interactions. We used logistic regressions to calculate the odds ratios and confidence intervals of the interactions. From the main PTB predictors (nine exposures and six genetic variants) we identified an interaction between low neighbourhood socioeconomic status and rs2074351 (PON1, genotype GG) variant that was associated with an increased risk of toxoplasmosis (odds ratio 12.51, confidence interval 95%: 1.71 - 91.36). The results of this exploratory study suggest that structural social disparities could influence the PTB risk by increasing the frequency of exposures that potentiate the risk associated with individual characteristics such as genetic traits. Future studies with larger sample sizes are necessary to confirm these findings.

Prevalencia del bajo peso al nacer en un escenario de depresión económica en Argentina / Prevalence of low birth weight in a scenario of economic depression in Argentina

Introducción. El bajo peso al nacer (BPN) es considerado un indicador general de salud por su relación con complicaciones en la vida del recién nacido y por ser una de las primeras causas de mortalidad infantil. Es multifactorial y, entre sus determinantes, se incluyen los socioeconómicos. Objetivo. Evaluar el impacto de la desigualdad económica sobre la prevalencia del BPN, cuantificando el efecto diferencial según edad y educación materna y nivel de atención. Población y métodos. Estudio epidemiológico de diseño transversal, en el cual se analizaron los nacimientos ocurridos en Argentina desde 2001 a 2013 con datos obtenidos del Registro Nacional de los nacimientos, perteneciente a la Dirección de Estadísticas e Información en Salud (DEIS). Se estudió la variación temporal de la prevalencia de recién nacidos con BPN (< 2500 gramos) y su relación con indicadores demográficos y socioeconómicos. Se evaluó su asociación a través de modelos de regresión logística. Resultados. Se incluyeron 9 001 960 nacimientos. Se observó un incremento en la prevalencia de recién nacidos con BPN durante la crisis económica de 2001 -de un 6% en 2002 y un 7% en 2003-. Fue heterogéneo y tuvo mayor impacto en hospitales públicos (razón de prevalencia -RP-= 1,03) y madres adolescentes (RP= 1,07) y ningún impacto sobre la educación materna baja (RP= 0,99). Conclusiones. El impacto de la desigualdad socioeconómica sobre la prevalencia de bajo peso fue significativo y heterogéneo, más importante en hospitales públicos y madres en edades extremas.

Introduction. Low birth weight (LBW) is considered a general indicator of health because it is related to complications in the life of a newborn infant and is one of the leading causes of infant mortality. It is a multifactorial indicator, and its determinants include socioeconomic factors. Objective. To assess the impact of economic inequality on the prevalence of LBW by quantifying its differential effect by maternal age, level of maternal education, and level of care. Population and methods. Epidemiological, cross-sectional study that analyzed all births occurred in Argentina between 2001 and 2013 based on data provided by the National Registry of births, corresponding to the Health Statistics and Information Department. The temporal variation in the prevalence of LBW newborn infants (< 2500 grams) and its relation to demographic and socioeconomic indicators were studied. Its association was assessed using logistic regression models. Results. A total of 9 001 960births were included. The prevalence of LBW newborn infants during the 2001 economic crisis increased -6% in 2002 and 7% in 2003- The impact was heterogeneous and higher on public hospitals (--1;PR--3; = 1.03) and adolescent mothers (PR=1.07), but no impact was observed on a low level of maternal education (PR= 0.99). Conclusions. The impact of socioeconomic inequality on the prevalence of LBW was significant and heterogeneous, especially on public hospitals and mothers at the extremes of maternal age.

ECLAMC Study: prevalence patterns of hypospadias in South America: multi-national analysis over a 24-year period

ABSTRACT Objective To evaluate prevalence trends of hypospadias in South-America it is essential to perform multicenter and multinational studies with the same methodology. Herein we present systematic data as part of an international multicenter initiative evaluating congenital malformations in South America over a 24-year period. Materials and Methods A nested case-control study was conducted using the Latin American Collaborative Study of Congenital Malformations (ECLAMC), between January 1989 and December 2012. Cases were stratified as isolated (IH) and non-isolated hypospadias (NIH). Global prevalence was calculated and discriminated by country. Associations between birth weight and gestational age, and NIH distribution by associated abnormality and severity of hypospadias, were analyzed. Results A total of 159 hospitals from six countries participated, reporting surveillance on 4.020.384 newborns. A total of 4.537 hypospadias cases were detected, with a global prevalence of 11.3/10.000 newborns. Trend analyses showed in Chile, Brazil and Uruguay a statistically significant increase in prevalence. Analysis of severity and associated anomalies did not to find an association for distal cases, but did for proximal (RR=1.64 [95% CI=1.33-2.03]). Conclusion This is one of only a few Latin American multicenter studies reporting on the epidemiology of hypospadias in South America in the last two decades. Our data adds to evidence suggesting an increase in some countries in the region at different times. There were also variations in prevalence according to severity. This study adds to literature describing associated anomalies at a hospital-based level.

Determinantes sociales adversos y riesgo para anomalías congénitas seleccionadas / Adverse social determinants and risk for congenital anomalies

Introducción. Diferentes trabajos han relacionando condiciones sociales adversas a nivel familiar y regional con resultados perinatales (mortalidad neonatal, bajo peso y prematuridad), sin embargo, pocos estudiaron el efecto de la pobreza sobre anomalías congénitas. Objetivo. Evaluar el riesgo de ocurrencia de 25 anomalías congénitas y determinantes sociales adversos según el nivel socioeconómico de la familia y de la región. Población y métodos. Estudio caso-control exploratorio, en el que se utilizaron datos del Estudio Colaborativo Latinoamericano de Malformaciones Congénitas (ECLAMC). La muestra consistió en 3786 recién nacidos vivos con una única malformación y 13 344 controles, seleccionados entre 546 129 nacimientos, ocurridos en 39 hospitales de Argentina durante el período 1992-2001. Se estimaron los riesgos (OR) directos, indirectos (a través de la región de residencia) y la interacción entre el nivel socioeconómico individual y residencial para cada uno de los 25 defectos congénitos. Resultados. Los defectos labio leporino con/sin paladar hendido (OR= 1,43) y comunicación interventricular (OR= 1,38) mostraron un riesgo significativamente mayor en el nivel socioeconómico más bajo. Los niveles socioeconómicos bajos se asociaron de manera significativa con una mayor frecuencia de consanguinidad parental, ancestros nativos, edad materna menor de 19 años, más de 4 embarazos, bajo número de visitas prenatales y residencia en regiones desfavorables. Conclusión. La fisura labial con o sin paladar hendido y los defectos del tabique interventricular estuvieron asociados significativamente con un nivel socioeconómico más bajo. La falta de planificación familiar, de control prenatal y la exposición a agentes ambientales o teratógenos pueden explicar estos hallazgos.

Introduction. Different studies have related familiar and regional adverse social conditions to perinatal outcome (neonatal mortality, low birth weight and prematurity); however, few studies have studied the effect of poverty on congenital anomalies. Objective. To assess the hazard ratio of 25 congenital anomalies and adverse social determinants as per the socioeconomic level of families and regions. Population and methods. Exploratory, case-control study using data from the Latin-American Collaborative Study of Congenital Malformations (Estudio Colaborativo Latinoamericano deMalformaciones Congenitas, ECLAMC). The sample consisted of 3786live newborninfantswitha singlemalformation and 13 344 controls selected among 546 129 births occurred in 39 hospitals from Argentina in the 19922001 period. Both direct and indirect (residence) risks (OR) were estimated, together with the interaction between the individual and residential socioeconomic levels for each of the 25 congenital anomalies. Results.Cleft lip with/without cleft palate (OR= 1.43) and ventricular septal defect (OR= 1.38) showed a significantly higher risk in the lower socioeconomic level. Low socioeconomic levels were significantly associated with a higher frequency of parental sibship (blood relationship); native descent; maternal age younger than 19 years old; more than four pregnancies; a low number of antenatal care visits; and residence in deprived regions. Conclusion. Cleft lip with/without cleft palate and ventricular septal defects were significantly associated with a lower socioeconomic level. Lack of family planning and antenatal care; and exposure to environmental or teratogenic agents may account for these findings.

Determinantes sociales adversos y riesgo para anomalías congénitas seleccionadas / Adverse social determinants and risk for congenital anomalies

Introducción. Diferentes trabajos han relacionando condiciones sociales adversas a nivel familiar y regional con resultados perinatales (mortalidad neonatal, bajo peso y prematuridad), sin embargo, pocos estudiaron el efecto de la pobreza sobre anomalías congénitas. Objetivo. Evaluar el riesgo de ocurrencia de 25 anomalías congénitas y determinantes sociales adversos según el nivel socioeconómico de la familia y de la región. Población y métodos. Estudio caso-control exploratorio, en el que se utilizaron datos del Estudio Colaborativo Latinoamericano de Malformaciones Congénitas (ECLAMC). La muestra consistió en 3786 recién nacidos vivos con una única malformación y 13 344 controles, seleccionados entre 546 129 nacimientos, ocurridos en 39 hospitales de Argentina durante el período 1992-2001. Se estimaron los riesgos (OR) directos, indirectos (a través de la región de residencia) y la interacción entre el nivel socioeconómico individual y residencial para cada uno de los 25 defectos congénitos. Resultados. Los defectos labio leporino con/sin paladar hendido (OR= 1,43) y comunicación interventricular (OR= 1,38) mostraron un riesgo significativamente mayor en el nivel socioeconómico más bajo. Los niveles socioeconómicos bajos se asociaron de manera significativa con una mayor frecuencia de consanguinidad parental, ancestros nativos, edad materna menor de 19 años, más de 4 embarazos, bajo número de visitas prenatales y residencia en regiones desfavorables. Conclusión. La fisura labial con o sin paladar hendido y los defectos del tabique interventricular estuvieron asociados significativamente con un nivel socioeconómico más bajo. La falta de planificación familiar, de control prenatal y la exposición a agentes ambientales o teratógenos pueden explicar estos hallazgos.(AU)

Introduction. Different studies have related familiar and regional adverse social conditions to perinatal outcome (neonatal mortality, low birth weight and prematurity); however, few studies have studied the effect of poverty on congenital anomalies. Objective. To assess the hazard ratio of 25 congenital anomalies and adverse social determinants as per the socioeconomic level of families and regions. Population and methods. Exploratory, case-control study using data from the Latin-American Collaborative Study of Congenital Malformations (Estudio Colaborativo Latinoamericano deMalformaciones Congenitas, ECLAMC). The sample consisted of 3786live newborninfantswitha singlemalformation and 13 344 controls selected among 546 129 births occurred in 39 hospitals from Argentina in the 19922001 period. Both direct and indirect (residence) risks (OR) were estimated, together with the interaction between the individual and residential socioeconomic levels for each of the 25 congenital anomalies. Results.Cleft lip with/without cleft palate (OR= 1.43) and ventricular septal defect (OR= 1.38) showed a significantly higher risk in the lower socioeconomic level. Low socioeconomic levels were significantly associated with a higher frequency of parental sibship (blood relationship); native descent; maternal age younger than 19 years old; more than four pregnancies; a low number of antenatal care visits; and residence in deprived regions. Conclusion. Cleft lip with/without cleft palate and ventricular septal defects were significantly associated with a lower socioeconomic level. Lack of family planning and antenatal care; and exposure to environmental or teratogenic agents may account for these findings.(AU)

Consumo y exposición al humo de tabaco en mujeres embarazadas de Ecuador / Smoking and exposure to tobacco smoke among pregnant women in Ecuador

OBJETIVOS: Determinar la frecuencia de tabaquismo y exposición ambiental al humo de tabaco en mujeres embarazadas de Ecuador y describir los perfiles sociodemográficos asociados con esos factores de riesgo perinatal. MÉTODOS: Estudio descriptivo transversal mediante una encuesta aplicada a mujeres de 18 a 46 años con más de 3 meses de embarazo que asistieron entre octubre de 2004 y septiembre de 2005 a sus consultas de seguimiento en siete servicios de maternidad de seis ciudades de Ecuador. Se analizaron los datos demográficos y de exposición medioambiental (variables independientes) y su relación con el hábito de fumar cigarrillos y la exposición ambiental al humo de tabaco. RESULTADOS: De las 746 mujeres analizadas, 53,3 por ciento había fumado ocasionalmente y 4,3 por ciento había fumado habitualmente; de estas, 75,0 por ciento había dejado de fumar antes o durante el embarazo. De las encuestadas, 12,9 por ciento estuvo expuesta con frecuencia o siempre al humo de tabaco en ambientes cerrados. Tener mayor educación (11 años o más) y un nivel socioeconómico medio o alto, ser caucásica y considerar aceptable que las mujeres de su comunidad fumen se asoció significativa y directamente con el hábito de fumar cigarrillos (P < 0,001). En general, 12,9 por ciento de las mujeres estuvo expuesta al humo de tabaco y esto se asoció significativamente con ser soltera y cohabitar con fumadores o trabajadores vinculados con la industria del tabaco (P < 0,001). CONCLUSIONES: Se deben diseñar e implementar medidas específicas dirigidas no solo a estimular el abandono de este hábito en las embarazadas, sino también a prevenir que las mujeres en edad reproductiva comiencen a fumar y controlar el entorno fumador en el hogar.

OBJECTIVES: To determine the frequency of smoking and second-hand smoke exposure among pregnant women in Ecuador and to describe the sociodemographic profiles associated with these perinatal risk factors. METHODS: A cross-sectional descriptive study using a survey of women 18-46 years of age who were more than three months pregnant and attended follow-up consultations in seven maternity clinics in six cities in Ecuador between October 2004 and September 2005. Demographics and environmental exposure (independent variables) data and their relationship to cigarette smoking and secondhand-smoke exposure were analyzed. RESULTS: Of the 746 women studied, 53.3 percent had smoked occasionally, and 4.3 percent, regularly; of these, 75 percent had quit smoking before or during pregnancy. Of the respondents, 12.9 percent were frequently or always exposed to secondhand smoke indoors. Having more education (11 or more years), being in the middle or upper socioeconomic classes, being Caucasian, and it being considered acceptable for women in the community to smoke were significantly and directly associated with cigarette smoking (P < 0.001). Overall, 12.9 percent of women were being exposed to secondhand smoke and this was significantly associated with being single and cohabiting with smokers or employees connected to the tobacco industry (P < 0.001). CONCLUSIONS: Specific measures must be designed and implemented to not only encourage smoking cessation during pregnancy, but also to prevent women of reproductive age from taking up smoking and to limit smoking in the home environment.

Adverse social determinants and risk for congenital anomalies. / Adverse social determinants and risk for congenital anomalies.

INTRODUCTION: Different studies have related familiar and regional adverse social conditions to perinatal outcome (neonatal mortality, low birth weight and prematurity); however, few studies have studied the effect of poverty on congenital anomalies. OBJECTIVE: To assess the hazard ratio of 25 congenital anomalies and adverse social determinants as per the socioeconomic level of families and regions. POPULATION AND METHODS: Exploratory, case-control study using data from the Latin-American Collaborative Study of Congenital Malformations (Estudio Colaborativo Latinoamericano de Malformaciones Congenitas, ECLAMC). The sample consisted of 3786 live newborn infants with a single malformation and 13,344 controls selected among 546,129 births occurred in 39 hospitals from Argentina in the 1992-2001 period. Both direct and indirect (residence) risks (OR) were estimated, together with the interaction between the individual and residential socioeconomic levels for each of the 25 congenital anomalies. RESULTS: Cleft lip with/without cleft palate (OR= 1.43) and ventricular septal defect (OR= 1.38) showed a significantly higher risk in the lower socioeconomic level. Low socioeconomic levels were significantly associated with a higher frequency of parental sibship (blood relationship); native descent; maternal age younger than 19 years old; more than four pregnancies; a low number of antenatal care visits; and residence in deprived regions. CONCLUSION: Cleft lip with/without cleft palate and ventricular septal defects were significantly associated with a lower socioeconomic level. Lack of family planning and antenatal care; and exposure to environmental or teratogenic agents may account for these findings.