Association of light-to-moderate alcohol drinking in pregnancy with preterm birth and birth weight: elucidating bias by pooling data from nine European cohorts.

Women who drink light-to-moderately during pregnancy have been observed to have lower risk of unfavourable pregnancy outcomes than abstainers. This has been suggested to be a result of bias. In a pooled sample, including 193 747 live-born singletons from nine European cohorts, we examined the associations between light-to-moderate drinking and preterm birth, birth weight, and small-for-gestational age in term born children (term SGA). To address potential sources of bias, we compared the associations from the total sample with a sub-sample restricted to first-time pregnant women who conceived within six months of trying, and examined whether the associations varied across calendar time. In the total sample, drinking up to around six drinks per week as compared to abstaining was associated with lower risk of preterm birth, whereas no significant associations were found for birth weight or term SGA. Drinking six or more drinks per week was associated with lower birth weight and higher risk of term SGA, but no increased risk of preterm birth. The analyses restricted to women without reproductive experience revealed similar results. Before 2000 approximately half of pregnant women drank alcohol. This decreased to 39% in 2000-2004, and 14% in 2005-2011. Before 2000, every additional drink was associated with reduced mean birth weight, whereas in 2005-2011, the mean birth weight increased with increasing intake. The period-specific associations between low-to-moderate drinking and birth weight, which also were observed for term SGA, are indicative of bias. It is impossible to distinguish if the bias is attributable to unmeasured confounding, which change over time or cohort heterogeneity.

Prenatal exposure to hexachlorobenzene (HCB) and reproductive effects in a multicentre birth cohort in Spain.

OBJECTIVE: To investigate the possible association between birth size or gestational length and maternal serum concentrations of hexachlorobenzene (HCB) in a population exposed to background levels. METHODS: A total of 1568 mother-child pairs recruited in three Spanish areas (INMA Project) from 2004 to 2008 participated in the study. Multivariate analysis was performed between birth weight and length, weeks of gestation, preterm birth or small for gestational age and HCB concentrations in maternal serum. RESULTS: The median concentration of HCB was 45.45 ng/g lipids. No association was found between HCB exposure levels and birth weight (ß: -50.42 [-109.88; 9.04]), birth length (ß: -0.07 [-0.32; 0.18]), gestation age (HR: 1.07 [0.94; 1.22]), small for gestational age (OR: 0.95 [0.56; 1.61]) and preterm birth (OR: 0.60 [0.29; 1.28]). Results remain similar after adjustment for other organochlorines. CONCLUSION: Our findings support the idea that exposure to low levels of HCB does not affect the intrauterine growth nor the duration of gestation.

Dietary and sociodemographic determinants of bisphenol A urine concentrations in pregnant women and children.

Bisphenol A (BPA) exposure during early life may have endocrine-disrupting effects, but the dietary and sociodemographic predictors of BPA exposure during pregnancy and childhood remain unclear. Our aim was to evaluate the correlations between, and sociodemographic and dietary predictors of, serial urinary BPA concentrations measured during pregnancy and childhood in a Spanish birth cohort study. BPA was measured in two spot urine samples collected from 479 women during the first and third trimester of pregnancy and in one urine sample from their 4-year old children (n=130). Average dietary intakes were reported in food frequency questionnaires during the first and third pregnancy trimester and at age 4years. Multivariate mixed models and linear regression models were used to estimate associations between sociodemographic and dietary factors and BPA concentrations. A small, but statistically significant correlation was found between serial maternal BPA concentrations measured during pregnancy (r=0.17). Pregnant women who were younger, less-educated, smoked, and who were exposed to second-hand tobacco smoke (SHS) had higher BPA concentrations than others. BPA concentrations were also higher in children exposed to SHS. High consumption of canned fish during pregnancy was associated with 21% [GM ratio=1.21; 95%CI 1.02, 1.44] and 25% [GM ratio=1.25; 95%CI 1.05, 1.49] higher urinary BPA concentrations in the first and third pregnancy trimester, respectively, compared to the lowest consumption group. This study suggests that canned fish may be a major source of BPA during pregnancy in Spain, a country of high canned fish consumption. Further evaluation of specific BPA exposure sources in the sociodemographic group of younger women who smoke, are exposed to SHS, and have a low educational level is needed. Studies identifying sources of exposure would benefit from repeat BPA measurements and questionnaires specifically focused on dietary and packaging sources.

Prenatal exposure to organochlorine pesticides and TSH status in newborns from Southern Spain.

OBJECTIVE: To investigate the association between prenatal exposure to organochlorine pesticides (OCPs) and thyroid-stimulating hormone (TSH) levels in male newborns. METHODS: Exposure to 17 OCPs was analyzed in 220 placentas from a male birth cohort in Southern Spain, and TSH was measured in the umbilical cord blood. OCP concentrations were quantified by gas chromatography and mass spectrometry. Multivariate regression analysis was conducted to examine the association between pesticide exposure and neonatal TSH levels, adjusting for confounders. RESULTS: Newborn boys with higher exposure to endrin in placenta had higher odds of TSH cord blood levels ≥ 5 mU/L (80th percentile) (OR=2.05; 95% CI=1.01, 4.18; p=0.05), whereas higher prenatal exposure to endosulfan-sulfate was associated with lower odds of TSH ≥ 5 mU/L (OR=0.36; 95% CI=0.17, 0.77; p=0.008). A marginally significant negative association was found between TSH and hexachlorobenzene levels (ß=-0.15; 95% CI=-0.31, 0.02; p=0.09), and exposure to p,p'-DDE showed a marginally-significant higher odds of TSH ≥ 5 mU/L (OR=1.32; 95% CI=0.95, 1.83; p=0.09). No association was found between TSH and the remaining pesticides. CONCLUSIONS: Early exposure to certain environmental chemicals with endocrine-disruption activity may interfere with neonatal thyroid hormone status; however, the pattern of interference is not yet clearly elucidated.

[Studies conducted in Spain on concentrations in humans of persistent toxic compounds]. / Estudios realizados en España sobre concentraciones en humanos de compuestos tóxicos persistentes.

No systematic review is available on studies conducted in Spain on human concentrations of persistent toxic substances (PTS). The objectives were: to identify studies conducted in Spain in the past 30 years that determined concentrations in humans of dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethane (DDE), hexachlorobenzene (HCB), hexachlorocyclohexane (HCH) and polychlorinated biphenyls (PCBs); and to summarize the main characteristics and results of each study. Studies are highly heterogeneous and most lack population representativeness. Concentrations of DDT and DDE might have decreased moderately in the last 20 years. Numerous fluctuations are apparent in levels of HCB, HCHs and PCBs, in some instances compatible with some stagnation. There are enormous differences in levels detected across and within studies: PTS concentrations of some individuals may be over 200-fold higher than those of others. The actual magnitude of human contamination by PTS and their trends across Spain -as well as the geographic and social heterogeneity- remain largely unknown.

Estudios realizados en España sobre concentraciones en humanos de compuestos tóxicos persistentes / Studies conducted in Spain on concentrations in humans of persistent toxic compounds

Aunque en España se han realizado estudios sobre concentraciones en medios biológicos humanos de compuestos tóxicos persistentes (CTP) desde hace varias décadas, no se ha llevado a cabo una revisión sistemática. Los objetivos fueron: a) identificar los estudios realizados en España en los últimos30 años que hubiesen determinado concentraciones en humanos de diclorodifeniltricloroetano (DDT), diclorodifenildicloroeteno (DDE), hexaclorobenceno (HCB), hexaclorociclohexanos (HCH) y policlorobifenilos (PCB), y b) sintetizar las principales característicasy resultados de cada estudio. Los estudios son sumamenteheterogéneos y la mayoría carece de representatividad poblacional. Las concentraciones de DDT y DDE parecenhaber decrecido moderadamente en los últimos 20 años. Haynumerosas fluctuaciones en los valores de HCB, HCH y PCB,en algún caso compatibles con un estancamiento. Se observan grandes diferencias en los valores detectados en los distintos estudios y dentro de un mismo grupo: las concentraciones de CTP de algunos individuos pueden llegar a ser más de 200 veces superiores a los de otros. La magnitud real de la contaminación humana por CTP y sus tendencias a lo largo del territorio español, así como su diversidad geográfica y social, siguen siendo ampliamente desconocidas

No systematic review is available on studies conducted inSpain on human concentrations of persistent toxic substances (PTS). The objectives were: to identify studies conducted in Spain in the past 30 years that determined concentrations in humans of dichlorodiphenyltrichloroethane (DDT), dichlorodiphenyldichloroethane (DDE), hexachlorobenzene(HCB), hexachlorocyclohexane (HCH) and polychlorinated biphenyls (PCBs); and to summarize the main characteristics and results of each study. Studies are highly heterogeneous and most lack population representativeness. Concentrationsof DDT and DDE might have decreased moderately in the last 20 years. Numerous fluctuations are apparent in levels of HCB, HCHs and PCBs, in some instances compatible with some stagnation. There are enormous differences in levels detected across and within studies: PTS concentrations of some individualsmay be over 200-fold higher than those of others. Theactual magnitude of human contamination by PTS and theirtrends across Spain –as well as the geographic and social heterogeneity– remain largely unknown

[Air pollutant exposure during pregnancy and fetal and early childhood development. Research protocol of the INMA (Childhood and Environment Project)]. / Exposición a contaminantes atmosféricos durante el embarazo y desarrollo prenatal y neonatal: protocolo de investigación en el proyecto INMA (Infancia y Medio Ambiente).

INTRODUCTION: The INMA (INfancia y Medio Ambiente [Spanish for Environment and Childhood]) project is a cooperative research network. This project aims to study the effects of environment and diet on fetal and early childhood development. This article aims to present the air pollutant exposure protocol during pregnancy and fetal and early childhood development of the INMA project. METHODS: The information to assess air pollutant exposure during pregnancy is based on outdoor measurement of air pollutants (nitrogen dioxide [NO2], volatile organic compounds [VOC], ozone, particulate matter [PM10, PM2,5 ] and of their composition [polycyclic aromatic hydrocarbons]); measurement of indoor and personal exposure (VOC and NO2); urinary measurement of a biological marker of hydrocarbon exposure (1-hydroxypyrene); and data gathered by questionnaires and geographic information systems. These data allow individual air pollutant exposure indexes to be developed, which can then be used to analyze the possible effects of exposure on fetal development and child health. CONCLUSION: This protocol and the type of study allow an approximation to individual air pollutant exposure to be obtained. Finally, the large number of participants (N = 4,000), as well as their geographic and social diversity, increases the study's potential.

Exposición a contaminantes atmosféricos durante el embarazo y desarrollo prenatal y neonatal: protocolo de investigación en el proyecto INMA (Infancia y Medio Ambiente) / Air pollutant exposure during pregnancy and fetal and early childhood development. Research protocol of the INMA [Childhood and Environment Project]

Introducción: El proyecto INMA (Infancia y Medio Ambiente) es una red de investigación cooperativa que tiene como objetivos estudiar los efectos del medio ambiente y la dieta en el desarrollo fetal e infantil. El objetivo de este artículo es presentar el protocolo de exposición a contaminantes atmosféricos durante el embarazo y desarrollo prenatal y neonatal en el proyecto INMA. Métodos: La información para la evaluación de la exposición a contaminación atmosférica durante el embarazo se basa en mediciones de contaminantes atmosféricos en el exterior (dióxido de nitrógeno [NO2], compuestos orgánicos volátiles [COV], ozono, partículas [PM10, PM2,5] y su composición [hidrocarburos aromáticos policíclicos]), medición de contaminantes de exposición individual (en el interior de la vivienda y captadores personales [COV y NO2]), determinación de un marcador biológico de exposición a hidrocarburos (1-hidroxipireno), en información recogida mediante cuestionarios y en la utilización de sistemas de información geográfica. Esta información permite elaborar índices de exposición individual a contaminación atmosférica con los que analizar su posible relación con el desarrollo fetal y la salud del recién nacido. Discusión: El protocolo que se presenta y el tipo de estudio permiten obtener una aproximación a la exposición individual a contaminantes atmosféricos. Por último, el elevado número de participantes (n = 4.000), así como la heterogeneidad de las características ambientales y sociodemográficas, acrecienta el potencial del estudio

Introduction: The INMA (INfancia y Medio Ambiente [Spanish for Environment and Childhood]) project is a cooperative research network. This project aims to study the effects of environment and diet on fetal and early childhood development. This article aims to present the air pollutant exposure protocol during pregnancy and fetal and early childhood development of the INMA project. Methods: The information to assess air pollutant exposure during pregnancy is based on outdoor measurement of air pollutants (nitrogen dioxide [NO2], volatile organic compounds [VOC], ozone, particulate matter [PM10, PM2,5 ] and of their composition [polycyclic aromatic hydrocarbons]); measurement of indoor and personal exposure (VOC and NO2); urinary measurement of a biological marker of hydrocarbon exposure (1-hydroxypyrene); and data gathered by questionnaires and geographic information systems. These data allow individual air pollutant exposure indexes to be developed, which can then be used to analyze the possible effects of exposure on fetal development and child health. Conclusion: This protocol and the type of study allow an approximation to individual air pollutant exposure to be obtained. Finally, the large number of participants (N = 4,000), as well as their geographic and social diversity, increases the study's potential

Medida de contaminantes del agua y usos del agua durante el embarazo en un estudio de cohortes en España / Measurement of drinking water contaminants and water use activities during pregnancy in a cohort study in Spain

Objetivos: La evidencia que hay no permite establecer causalidad entre la exposición a subproductos de la cloración (SPC) durante la gestación y los efectos reproductivos. Los trihalometanos, uno de los subproductos de la cloración, son muy prevalentes en algunas zonas españolas. En el marco del estudio INMA (INfancia y Medio Ambiente) se describe: 1) los hábitos personales de uso y consumo de agua, y 2) el valor de trihalometanos en el agua de las zonas de estudio. Métodos: Estudio de cohortes de seguimiento de mujeres embarazadas en Valencia (n=800), Sabadell (n=800), País Vasco (n=600), Asturias (n=500) y Granada (n=700). Con entrevistas en el tercer trimestre del embarazo se obtiene información personal acerca del origen y cantidad de agua consumida, frecuencia de ducha, baño y asistencia a piscinas. Se toman muestras de agua para analizar los trihalometanos. Resultados: El origen del agua consumida dentro y fuera de casa es la embotellada (el 82 y el 94%, respectivamente). El agua para cocinar es principalmente municipal (91%). El 98,2% de las mujeres embarazadas toman preferentemente duchas 6,8 veces/semana durante 11,7min. Un 58,5% de las mujeres se bañan en piscinas durante el embarazo, en promedio 9,4 veces/mes en piscinas descubiertas en verano y 3,1 veces/mes en cubiertas el resto del año, durante 32,6 y 21,7min, respectivamente. Los valores medios de trihalometanos oscilan entre 4g/l en la provincia de Granada y 117g/l en Sabadell. Conclusión: Los resultados provisionales sugieren que las principales vías de exposición a trihalometanos durante el embarazo son la absorción dérmica y la inhalación, y la ingestión es una vía poco relevante (AU)

Objectives: Exposure to chlorination by-products during pregnancy has been associated with reproductive outcomes but the evidence remains inconclusive. Levels of trihalomethanes, the most prevalent chlorination by-products, are high in some areas of Spain. Within the framework of a follow-up study in pregnant women, we describe: 1) the personal habits of water use and consumption, and 2) trihalomethane levels in the drinking water of the study areas. Methods: We performed a follow-up cohort study in pregnant women in Valencia (n=800), Sabadell (n=800), the Basque Country (n=600), Asturias (n=500), and Granada (n=700). Interviews were conducted in the third trimester of pregnancy to obtain individual information on the sources and amounts of drinking water, and on the frequency of showering, bathing, and swimming pool attendance. Water samples were collected to analyze trihalomethane levels. Results: The main source of drinking water was bottled water, both inside and outside the home (82% and 94% of the women, respectively). Drinking water for cooking was mainly municipal (91%). Women preferred to take showers (98.2%) and did so, on average, 6.8 times/week for 11.7 minutes. A total of 58.5% of the women went to swimming pools during pregnancy, on average 9.4 times/month to outdoor swimming pools in the summer and 3.1 times/month the rest of the year for 32.6 and 21.7 minutes, respectively. Average trihalomethane levels ranged from 4 g/l in the province of Granada to 117 g/l in Sabadell. Conclusion: These preliminary results suggest that the main routes of trihalomethane exposure during pregnancy are dermal absorption and inhalation. Ingestion is a minor exposure route (AU)

Hiperalgesia postoperatoria: de la molécula a la práctica clínica

El dolor postoperatorio representa en nuestros días uno de los retos no resuelto para el anestesiólogo. Estudios recientes, en los que se involucraron alrededor de 20000 pacientes, se evidenció que 41 por ciento de todos los pacientes quirúrgicos sufrían de dolor moderado a severo en la sala de recuperación y 24 por ciento las consecuencias de un alivio inadecuado. Desafortunadamente, el control del dolor postoperatorio agudo no ha mejorado de forma significativa en la última década incrementándose paralelamente la incidencia del dolor crónico posterior a procedimientos quirúrgicos. Se propone definir los conceptos de hiperalgesia en el paciente quirúrgico, así como los principios fisiológicos. Se realizó una revisión de la literatura sobre el tema, en el cual se aborda la problemática de la hiperalgesia del paciente quirúrgico. Se describen sus ventajas y la posibilidad de evitar complicaciones. Se concluye que los estudios en la última década plantean que la HP ocurre en el postoperatorio inmediato como consecuencia de la nocicepción quirúrgica como también por medicamentos (particularmente opioides). La HP basada en síntomas clínicos solos es difícil de diagnosticar pero, la introducción y adaptación de PSC a la práctica clínica representa un método válido. Estudios demuestran la efectividad de la profilaxis y tratamiento de la HP; sin embargo, se necesitan más para esclarecer el rol de esta en el dolor agudo y crónico postoperatorio(AU)

Lack of activity of cadmium in in vitro estrogenicity assays.

Prompted by reports about strong estrogenic effects of cadmium, attempts were made to reproduce these observations using the yeast estrogen screen (YES) and the E-Screen assays. For the first time, possible activation of the Src/MAPK pathway was also investigated. In the YES, only a slight activation (10% of a maximal effect) of the estrogen receptor alpha (ERalpha) was observed at cadmium concentrations between 5 x 10(-7) M and 5 x 10(-6) M. In the E-Screen assay, carried out by two laboratories, the heavy metal was without observable cell proliferative effects when tested in the range between 6 x 10(-11) M and 1 x 10(-5) M. However, in both assays, cadmium led to a reduction of the effects of 17beta-estradiol (E2). Treatment of MCF-7 human breast cancer cells with 1 x 10(-7) M cadmium failed to induce phosphorylation of Src and the MAP kinases Erk1 and Erk2-effects shown to occur with E2 and epidermal growth factor (EGF). In summary, we were unable to confirm the strong estrogenicity of cadmium reported recently by a number of laboratories. This apparent absence of effects in our hands is not due to a lack of uptake of the metal or to effective protection against cadmium by high levels of glutathione or metallothionein, since toxicity and an antagonism of E2 responses were observed both in the YES and the E-Screen.

[Measurement of drinking water contaminants and water use activities during pregnancy in a cohort study in Spain]. / Medida de contaminantes del agua y usos del agua durante el embarazo en un estudio de cohortes en España.

OBJECTIVES: Exposure to chlorination by-products during pregnancy has been associated with reproductive outcomes but the evidence remains inconclusive. Levels of trihalomethanes, the most prevalent chlorination by-products, are high in some areas of Spain. Within the framework of a follow-up study in pregnant women, we describe: 1) the personal habits of water use and consumption, and 2) trihalomethane levels in the drinking water of the study areas. METHODS: We performed a follow-up cohort study in pregnant women in Valencia (n = 800), Sabadell (n = 800), the Basque Country (n = 600), Asturias (n = 500), and Granada (n = 700). Interviews were conducted in the third trimester of pregnancy to obtain individual information on the sources and amounts of drinking water, and on the frequency of showering, bathing, and swimming pool attendance. Water samples were collected to analyze trihalomethane levels. RESULTS: The main source of drinking water was bottled water, both inside and outside the home (82% and 94% of the women, respectively). Drinking water for cooking was mainly municipal (91%). Women preferred to take showers (98.2%) and did so, on average, 6.8 times/week for 11.7 minutes. A total of 58.5% of the women went to swimming pools during pregnancy, on average 9.4 times/month to outdoor swimming pools in the summer and 3.1 times/month the rest of the year for 32.6 and 21.7 minutes, respectively. Average trihalomethane levels ranged from 4 microg/l in the province of Granada to 117 microg/l in Sabadell. CONCLUSION: These preliminary results suggest that the main routes of trihalomethane exposure during pregnancy are dermal absorption and inhalation. Ingestion is a minor exposure route.

[The Environment and Childhood Research Network ("INMA" network): study protocol]. / La Red de Investigación "Infancia y Medio Ambiente" (Red INMA): protocolo de estudio.

Increasingly greater evidence exists as to the influence which diet and exposure to low doses of toxic substances during the prenatal stage and early childhood has on health and well-being throughout later stages of life. Following the WHO and European Union recommendations in 2003, the Cooperative Environment and Childhood Research Network was set up to study the effects of the environment and diet on fetal and early childhood development in different geographical areas of Spain. This Network integrates different multidisciplinary research groups and is comprised of six cohorts--three pre-existing and three de novo--which will follow up prospectively 3,600 pregnant women, from the start of pregnancy up to age 4-6 years of the child. This network's general objectives are: (1) To describe individual exposure to toxic substances in the environment during gestation and early childhood. (2) To evaluate the effects of exposure to toxic substances and diet on fetal and early childhood development. (3) To evaluate the interaction among toxic, nutritional and genetic factors in fetal and early childhood development. The follow-up is done every three months during gestation, at birth, at age one and up to age four or six. The information is gathered by means of questionnaires, clinical data, physical examinations, echographs, biomarkers and environmental measurements. The general characteristics of the network and a description of the current situation of each one of the cohorts are provided in this study.

La Red de Investigación «Infancia y Medio Ambiente» (Red INMA): protocolo de estudio / The environment and childhood research network («INMA» network): study protocol

Cada vez existe mayor evidencia de la influencia de la dieta y dela exposición a dosis bajas de tóxicos durante la etapa prenatal y primerainfancia sobre la salud y el bienestar en etapas posteriores de lavida. Siguiendo las recomendaciones de la OMS y de la Unión Europeaen el año 2003 se constituyó la Red de Investigación CooperativaInfancia y Medio Ambiente para estudiar los efectos del medioambiente y la dieta en el desarrollo fetal e infantil en diversas zonasgeográficas en España. La Red integra diversos grupos multidisciplinaresde investigación y está constituida por seis cohortes, trespreexistentes y tres de novo, que seguirán de forma prospectiva a3.600 mujeres embarazadas, desde el inicio del embarazo hasta los 4-6 años del niño. Los objetivos generales de la red son: (1) Describirla exposición individual a tóxicos ambientales durante la gestación yla primera infancia. (2) Evaluar los efectos de la exposición a tóxicosy de la dieta en el desarrollo fetal e infantil. (3) Evaluar la interacciónentre factores tóxicos, nutricionales y genéticos en el desarrollo fetale infantil. El seguimiento se realiza en cada trimestre de la gestación,al nacimiento, al año y hasta los cuatro o seis años del niño. La información se recoge mediante cuestionarios, datos clínicos, exploración física, ecografías, biomarcadores y mediciones ambientales. Eneste trabajo se presentan las características generales de la red y sedescribe la situación actual de cada una de las cohortes

Increasingly greater evidence exists as to the influence whichdiet and exposure to low doses of toxic substances during the prenatalstage and early childhood has on health and well-being throughoutlater stages of life. Following the WHO and European Unionrecommendations in 2003, the Cooperative Environment and ChildhoodResearch Network was set up to study the effects of the environmentand diet on fetal and early childhood development in differentgeographical areas of Spain. This Network integrates differentmultidisciplinary research groups and is comprised of six cohorts -three pre-existing and three de novo - which will follow up prospectively3,600 pregnant women, from the start of pregnancy up to age4-6 years of the child. This network's general objectives are: (1) Todescribe individual exposure to toxic substances in the environmentduring gestation and early childhood. (2) To evaluate the effects ofexposure to toxic substances and diet on fetal and early childhooddevelopment. (3) To evaluate the interaction among toxic, nutritionaland genetic factors in fetal and early childhood development. Thefollow-up is done every three months during gestation, at birth, atage one and up to age four or six. The information is gathered bymeans of questionnaires, clinical data, physical examinations, echographs,biomarkers and environmental measurements. The generalcharacteristics of the network and a description of the current situationof each one of the cohorts are provided in this study