Hokkaido birth cohort study on environment and children's health: cohort profile 2021

BACKGROUND@#The Hokkaido Study on Environment and Children's Health is an ongoing study consisting of two birth cohorts of different population sizes: the Sapporo cohort and the Hokkaido cohort. Our primary objectives are to (1) examine the effects that low-level environmental chemical exposures have on birth outcomes, including birth defects and growth retardation; (2) follow the development of allergies, infectious diseases, and neurobehavioral developmental disorders, as well as perform a longitudinal observation of child development; (3) identify high-risk groups based on genetic susceptibility to environmental chemicals; and (4) identify the additive effects of various chemicals, including tobacco.@*METHODS@#The purpose of this report is to provide an update on the progress of the Hokkaido Study, summarize recent results, and suggest future directions. In particular, this report provides the latest details from questionnaire surveys, face-to-face examinations, and a collection of biological specimens from children and measurements of their chemical exposures.@*RESULTS@#The latest findings indicate different risk factors of parental characteristics on birth outcomes and the mediating effect between socioeconomic status and children that are small for the gestational age. Maternal serum folate was not associated with birth defects. Prenatal chemical exposure and smoking were associated with birth size and growth, as well as cord blood biomarkers, such as adiponectin, leptin, thyroid, and reproductive hormones. We also found significant associations between the chemical levels and neuro development, asthma, and allergies.@*CONCLUSIONS@#Chemical exposure to children can occur both before and after birth. Longer follow-up for children is crucial in birth cohort studies to reinforce the Developmental Origins of Health and Disease hypothesis. In contrast, considering shifts in the exposure levels due to regulation is also essential, which may also change the association to health outcomes. This study found that individual susceptibility to adverse health effects depends on the genotype. Epigenome modification of DNA methylation was also discovered, indicating the necessity of examining molecular biology perspectives. International collaborations can add a new dimension to the current knowledge and provide novel discoveries in the future.

Cafeteria diet in breastfeeding dams promotes anxiolytic effects, accumulation of adipose tissue, and impacts offspring development / La dieta de la cafetería en las madres que amamantan promueve los efectos ansiolíticos y la acumulación de tejido adiposo, y afecta el desarrollo de la descendencia

The aim of this study was to evaluate the nutritional and behavioral effects of a cafeteria diet in dams during the breastfeeding period and in their offspring from weaning until early adulthood (70 days old). Pregnant Wistar rats were fed a chow diet until delivery. Postnatally (D0), litters were culled to 8 pups and lactating dams received control (CTRL n= 6) or cafeteria (CAF n= 6) diets and water ad libitum. At the end of the breastfeeding period, male offspring were placed in individual boxes receiving the same treatment from their respective dams (CTRL or CAF) until adulthood (70 days). All nutritional and behavioral evaluations were performed with the dams (n= 12) during the breastfeeding phase and with the male offspring (n= 24) after weaning to adulthood. CAF dams demonstrated a lower caloric and protein intake; higher intake of fats; loss of weight; greater accumulation of adipose tissue; and an anxiolytic effect. CAF male offspring showed lower caloric intake; higher intake of fats; and accumulation of adipose tissue. In addition, these animals continued to have decreased body weight, body length and tibia-femur length in relation to CTRL. In dams, a cafeteria diet promoted alterations in body composition and anxiety, and in offspring the diet resulted in adequate development.

El objetivo de este estudio fue evaluar los efectos nutricionales y de comportamiento de la dieta de la cafetería en las madres durante el período de lactancia materna y en su descendencia desde el destete hasta la edad adulta temprana (70 días de edad). Ratas Wistar embarazadas fueron alimentadas con una dieta estándar hasta el parto. Postnatalmente (D0), las camadas se ajustaron en 8 crías y las madres lactantes recibieron las dietas control (CTRL n= 6) o cafetería (CAF n= 6) además de agua ad libitum. Al final del período de lactancia materna, las proles machos fueron colocados en cajas individuales recibiendo el mismo tratamiento de sus respectivas madres (CTRL o CAF) hasta la edad adulta (70 días). Todas las evaluaciones nutricionales y comportamentales se realizaron con las madres (n= 12) durante la fase de lactancia y con la prole masculina (n= 24) después del destete hasta la edad adulta. Las madres CAF demostraron una menor ingesta calórica y proteica; mayor ingestión de grasas; pérdida de peso; mayor acumulación de tejido adiposo; y un efecto ansiolítico. La prole masculina CAF presentó menor consumo calórico; mayor ingestión de grasas; y la acumulación de tejido adiposo. Además, estos animales presentaron menor peso corporal, longitud corporal, y longitud de la tibia-fémur, en relación a CTRL. En las madres, la dieta de cafetería promovió cambios en la composición corporal y ansiedad, y en la prole la dieta comprometió el desarrollo adecuado.

Exposición a contaminantes provenientes de termoeléctricas a carbón y salud infantil: ¿Cuál es la evidencia internacional y nacional? / Exposure to contaminants from coal-fired thermoelectric plants and children's health: what is the international and national evidence?

Resumen: Las centrales termoeléctricas (CTE) a carbón representan un riesgo para la salud de las comunidades expuestas. Se realizó una revisión de la literatura científica nacional e internacional enfocada en los efectos en salud de niños y la exposición a emisiones al aire provenientes de CTE a carbón. Se inclu yeron 21 artículos para su revisión en texto completo, donde se midieron efectos en salud infantil relacionados a presencia de biomarcadores de exposición y efecto, daños perinatales, neuroconductuales y respiratorios principalmente. La exposición a emisiones de CTE a carbón en el embarazo se asoció a niños con bajo peso y muy bajo peso al nacer, menor talla, menor diámetro de Circunfe rencia del Cráneo (CC) y prematuridad; el diámetro de CC aumentó en recién nacidos después del cierre de CTE. Se encontraron menor coeficiente de desarrollo (CD) y coeficiente intelectual (CI) en niños expuestos a emisiones de CTE a carbón comparados con no expuestos; CD aumentó cuando la central fue cerrada. Por otro lado, vivir en zonas con fuentes de emisión de mercurio (asociadas a CTE y plantas de cemento que funcionan con carbón) se asoció con mayor riesgo de autismo. En salud respiratoria, los artículos fueron consistentes en reportar menor función pulmonar en niños residentes en zonas expuestas a fuentes de combustión de carbón comparados con grupos de niños no expuestos. Es muy necesario abrir el debate en Chile sobre los riesgos controlables a los que se enfrenta la población infantil a consecuencia de plantas generadoras de energía instaladas en Chile.

Abstract: Coal-fired power plants (CFPP) represent a health risk to the exposed communities. A review of national and international scientific literature was made focused on the health effects on children and exposure to air emissions from CFPP. Twenty-one articles were included for full-text review, where effects on child health mainly related to the biomarkers presence of exposure and effect, pe rinatal, neurobehavioral and respiratory damages were measured. Exposure to CFPP emissions in pregnancy was associated with low birth weight and very low birth weight, shorter height, smaller head circumference (HC) diameter, and prematurity; the HC diameter increased in newborns after the CFPP closure. Lower coefficient of development (CD) and intelligence quotient (IQ) were found in children exposed to CFPP emissions compared with unexposed ones; CD increased when the plant was closed. On the other hand, living in areas with mercury emission sources (associated with CFPP and cement plants that work with coal) was associated with an increased risk of autism. In respira tory health, the articles were consistent with reporting lower pulmonary function in children living in areas exposed to coal combustion sources compared with groups of unexposed children. There is a great need to open the debate in Chile on the controllable risks faced by the child population as a result of power generation plants located in Chile.

Influencia de contaminantes ambientales en la gestación humana: causante de patologías en el adulto / Influence of environmental pollutants on human gestation: cause of adult pathologies

Resumen: En el presente articulo se revisan los mecanismos del imprinting epigenético mediante el cual se producen los efectos diferidos generados por la exposición prenatal o infantil temprana a agentes químicos contaminantes. Se revisaron las bases de datos Pubmed y Embase para identificar estudios publicados entre 2005 y 2018, junto a artículos considerados pioneros en este ámbito. Se incluyeron además, datos generados en nuestro Laboratorio. Como fuente de información secundaria se citan normas chilenas de concentraciones de algunos contaminantes en agua potable publicados por el Ministerio de Salud de Chile. Se describen cambios en la metilación de diversos genes causados por exposición prenatal o infantil temprana a algunos contaminantes ambientales relevantes en Chile: arsénico, plomo, ftalatos y fenoles, y se mencionan algunas de las enfermedades orgánicas y cambios neuroconductuales que se desarrollan más tarde en la vida como consecuencia de dichas exposi ciones. Se sugiere que un mayor conocimiento de los factores ambientales y una mejor educación de la población, permitirían una protección más adecuada de embarazadas y lactantes, en especial durante las ventanas de susceptibilidad y que los pediatras y obstetras, serían los profesionales mejor indicados para desarrollar estas acciones. Se sugiere además la necesidad de adecuar normas am bientales y aumentar la fiscalización de contaminantes y sus fuentes, para prevenir el deterioro de la salud de las futuras generaciones.

Abstract: This review explains the epigenetic imprinting mechanisms by which the delayed effects generated by prenatal or early childhood exposure to chemical pollutants are produced. Pubmed and Embase databases were reviewed to identify studies published between 2005 and 2018, along with articles considered pioneers in this field. We also included data generated in our Laboratory. As a source of secondary information, Chilean standards on concentrations of some pollutants in drinking water published by the Ministry of Health of Chile are cited. Changes are described in the methylation of diverse genes caused by prenatal or early childhood exposure to some relevant environmental po llutants in Chile such as arsenic, lead, phenols, and phthalates, and some of the organic diseases and neurobehavioral changes that occur later in life as a consequence of these exposures are mentioned. We suggest that a wider knowledge of environmental factors and better education of the population would allow a more adequate protection of pregnant women and infants especially during the win dows of susceptibility, and that pediatricians and obstetricians would be in the best position to deve lop these actions. We also suggest the need to adapt environmental standards and increase the control of pollutants and their sources to prevent health deterioration of future generations.

Are there differences in birth weight according to sex and associations with maternal exposure to air pollutants? A cohort study / Existem diferenças no peso ao nascer de acordo com sexo e associações com exposição materna a poluentes do ar? Estudo de coorte

ABSTRACT CONTEXT AND OBJECTIVE: Several effects of exposure to air pollutants on human health are known. The aim of this study was to identify whether exposure of pregnant women to air pollutants contributes towards low birth weight and which sex is more affected. DESIGN AND SETTING: Longitudinal study using data on newborns from mothers living in São José do Rio Preto (SP) who were exposed to air pollutants in 2012-2013. METHODS: A hierarchical model on three levels was built using maternal and newborn variables and environmental concentrations of particulate matter, ozone and nitrogen dioxide in quartiles. Preterm new-borns, twins and newborns with birth defects were excluded and exposure windows of 30, 60 and 90 days before delivery were considered. RESULTS: 8,948 newborns were included: 4,491 males (50.2%) and 4,457 females (49.8%); 301 newborns presented low birth weight (3.4%). The mean weight differed between males (3281.0 g) and females (3146.4 g) (P < 0.001). Exposure to ozone was significantly associated with low birth weight in both sexes in the 30-day window (odds ratio, OR = 1.38) and 90-day window (OR = 1.48); and among females, in the 30-day window (OR = 1.58) and 90-day window (OR = 1.59). Exposure to particulate matter had a paradoxical protective effect. No association was found among male newborns. CONCLUSIONS: Female newborns showed greater susceptibility to maternal exposure to air pollutants. Studies on low birth weight in relation to maternal exposure to air pollutants should deal with males and females separately.

RESUMO CONTEXTO E OBJETIVO: São vários os efeitos da exposição a poluentes do ar na saúde humana. O objetivo deste estudo foi identificar se a exposição da gestante contribui para o baixo peso ao nascer e qual o sexo mais acometido. TIPO DE ESTUDO: Estudo longitudinal com dados de recém-nascidos de mães residentes em São José do Rio Preto (SP) com exposição a poluentes do ar em 2012 e 2013. MÉTODOS: Foi construído modelo hierarquizado em três níveis com variáveis maternas, do recém-nascido e concentrações de material particulado, ozônio e dióxido de nitrogênio, em quartis. Foram excluídos recém-nascidos prematuros, gemelares ou com malformações e consideradas janelas de exposição de 30, 60 e 90 dias anteriores ao parto. RESULTADOS: Foram incluídos 8.948 recém-nascidos, 4.491 do sexo masculino (50,2%) e 4.457 do feminino (49,8%), e identificados 301 recém-nascidos com baixo peso (3,4%). Os pesos médios foram diferentes entre o sexo masculino (3.281,0 g) e o feminino (3.146,4 g) (P < 0,001). Exposição ao ozônio esteve associada significativamente ao baixo peso ao nascer em ambos os sexos nas janelas de 30 dias (odds ratio, OR = 1,38) e 90 dias (OR = 1,48) e, no sexo feminino, nas janelas de 30 dias (OR = 1,58) e 90 dias (OR =1,59). Exposição ao material particulado teve efeito protetor paradoxal. Não houve associação no sexo masculino. CONCLUSÕES: Houve maior susceptibilidade do sexo feminino aos poluentes a partir da exposição materna. Estudos sobre baixo peso ao nascer segundo exposição materna a poluentes do ar devem separar sexo masculino e feminino.

Tabaquismo materno como un factor posiblemente implicado en el desarrollo de la obesidad infantil / Possible effects of maternal smoking during pregnancy on the development of childhood obesity

El tabaquismo es la adicción al tabaco provocada principalmente por diversos componentes activos y tóxicos como la nicotina. El consumo de cigarrillo durante la gestación puede provocar desprendimiento de placenta, placenta previa, embarazo ectópico y aborto espontáneo, como también inducir alteraciones en el feto. En la presente revisión de la literatura se recopiló información en bases de datos como Pub-Med, Embase y Google Académico, concerniente a los posibles efectos del tabaquismo materno durante la gestación sobre el desarrollo de la obesidad infantil. Fueron seleccionados 38 artículos escritos en el idioma inglés y español, publicados a partir de año de 1988 hasta el año 2015, que incluyeron metaanálisis, artículos originales, y revisiones de tema. Se encontró que la exposición al humo del tabaco durante la gestación ha sido ampliamente descrita como un factor de riesgo para la manifestación de alteraciones en el desarrollo fetal como retardo del crecimiento intrauterino y bajo peso al nacer. Además, se ha asociado ampliamente con trastornos del desarrollo infantil en etapas avanzadas, como preescolares y escolares, manifestados en un aumento del índice de masa corporal con respecto al percentil adecuado para la edad; incremento de la incidencia de sobrepeso y obesidad en el infante. Se concluye que la exposición al humo del cigarrillo durante la gestación se relaciona con alteraciones en el crecimiento del niño y en el desarrollo de enfermedades prevalentes asociadas a la obesidad.

Most smokers use tobacco regularly because they are addicted to various active and toxic compounds such as nicotine. Cigarette smoking during pregnancy can cause abruption, placenta previa, ectopic pregnancy and spontaneous abortion, as well as induce alterations in the fetus. In this review, information was collected in databases such as PubMed, Embase and Google Scholar, concerning the possible effects of maternal smoking during pregnancy on the development of childhood obesity. Thirty-eigth articles written in English and Spanish published from year 1988 to 2015, which included meta-analysis, original articles and reviews were selected topic. It was found that exposure to cigarette smoke during pregnancy has been widely described as a risk factor for alterations in fetal development such as intrauterine growth retardation and low birth weight. In addition, it has been widely associated with disorders of child development in advanced stages, preschool and school age: increased body mass index regarding the appropriate percentile for age, and increase in childhood overweight and obesity. It is concluded that exposure to cigarette smoke during pregnancy is associated with changes in child growth and development of prevalent diseases associated with obesity.

O que sabemos das alterações auditivas centrais em crianças expostas ao álcool na gestação? Revisão sistemática / What we know of the central auditory disorders in children exposed to alcohol during pregnancy? Systematic review

RESUMO Objetivo Identificar os efeitos da ingestão de álcool na gestação sobre o sistema nervoso auditivo central em relação aos seus possíveis diagnósticos, Síndrome Fetal do Álcool, Síndrome Fetal do Álcool Parcial, Distúrbios ao Nascimento Relacionados ao Álcool e Distúrbio do Neurodesenvolvimento Relacionado ao Álcool, sua extensão e o método de avaliação auditiva. Estratégia de pesquisa Busca sistemática e integrativa nas bases de dados PubMed, LILACS e SciELO, com os termos em português e inglês “síndrome fetal do álcool”, “desordens relacionadas ao uso do álcool” associadas a “audição”. Critérios de seleção Dos 123 resumos identificados, foram seis selecionados, publicados até maio de 2015. Análise dos dados Foram elencados tópicos a serem respondidos, caracterização da casuística; o diagnóstico decorrente da exposição fetal nas crianças; método de avaliação auditiva; e resultados descritos. Resultados Entre as avaliações comportamentais, foram utilizados os testes dicóticos verbais com sílabas e com sentenças e o teste fala com ruído. Entre os testes eletrofisiológicos, no Potencial Evocado Auditivo de Tronco Encefálico, foi detectada alteração de sincronia neural, e no Potencial Evocado Auditivo de Longa Latência – P300, valores de latência precoces. Conclusão Existem evidências de que as crianças e adultos jovens expostos ao álcool na gestação apresentam sinais de comprometimento do sistema nervoso auditivo central, mas não foi possível caracterizar essas alterações nos diferentes subtipos diagnósticos do espectro. As vias auditivas corticais foram as mais investigadas e o método eletrofisiológico o mais utilizado, com um resultado inesperado em dois deles, a latência precoce da N2 e da P300.

ABSTRACT Purpose To identify the effects of alcohol intake during pregnancy on the central auditory nervous system in relation to their possible diagnosis, Fetal Alcohol Syndrome, partial Fetal Alcohol Syndrome, Alcohol-Related Birth Defects and Alcohol-Related Neurodevelopmental Disorder, his extension and the hearing assessment method. Research strategy Systematic and integrative review searched the databases PubMed, LILACS and SciELO, with terms in Portuguese and English “fetal alcohol syndrome”, “alcohol-related disorders” associated with “hearing”. Selection criteria: We identified 123 abstracts, six were selected and published until May 2015. Data analysis Were listed topics to be answered, characterization of the sample; the diagnosis result of fetal exposure; method of hearing assessment and described results. Results Among the behavioral assessments, Verbal Dichotic Tests with syllables and sentences and Speech in Noise Test, were used. Among the electrophysiological tests, the Brainstem Auditory Evoked Potential was detected change neural synchrony, and Long-Latency Auditory Evoked Potential – P300, early latency values. Conclusion There is evidence that children exposed to alcohol in utero present central auditory nervous system involvement signals, but it was not possible to identify the influence of different subtypes and their losses. Cortical auditory pathways were the most investigated and the electrophysiological method as used with an unexpected result in two of them, early N2 and P300 latency.

Autonomic and Renal Alterations in the Offspring of Sleep-Restricted Mothers During Late Pregnancy

OBJECTIVES: Considering that changes in the maternal environment may result in changes in progeny, the aim of this study was to investigate the influence of sleep restriction during the last week of pregnancy on renal function and autonomic responses in male descendants at an adult age. METHODS: After confirmation of pregnancy, female Wistar rats were randomly assigned to either a control or a sleep restriction group. The sleep-restricted rats were subjected to sleep restriction using the multiple platforms method for over 20 hours per day between the 14th and 20th day of pregnancy. After delivery, the litters were limited to 6 offspring that were designated as offspring from control and offspring from sleep-restricted mothers. Indirect measurements of systolic blood pressure (BPi), renal plasma flow, glomerular filtration rate, glomerular area and number of glomeruli per field were evaluated at three months of age. Direct measurements of cardiovascular function (heart rate and mean arterial pressure), cardiac sympathetic tone, cardiac parasympathetic tone, and baroreflex sensitivity were evaluated at four months of age. RESULTS: The sleep-restricted offspring presented increases in BPi, glomerular filtration rate and glomerular area compared with the control offspring. The sleep-restricted offspring also showed higher basal heart rate, increased mean arterial pressure, increased sympathetic cardiac tone, decreased parasympathetic cardiac tone and reduced baroreflex sensitivity. CONCLUSIONS: Our data suggest that reductions in sleep during the last week of pregnancy lead to alterations in cardiovascular autonomic regulation and renal morpho-functional changes in offspring, triggering increases in blood pressure.

Insulin-like growth factor (IgF)-I, IgF binding protein-3, and prostate cancer: correlation with gleason score

Introduction Non-androgenic growth factors are involved in the growth regulation of prostate cancer (PCa). Objective This is the first Brazilian study to correlate, in a population of patients operated for PCa, PSA, total testosterone, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) with Gleason score and to compare with a control group with benign prostate hyperplasia (BPH). Materials and Methods This retrospective single-center study included 49 men with previously diagnosed PCa and 45 with previously diagnosed BPH. PSA, testosterone, IGF-I, IGFBP-3 were determined in both groups. Results PSA and IGFBP-3 levels were significantly higher in the PCa group as compared to the BPH group (p<0.001 and p=0.004, respectively). There was a significant difference when we compared the PSA before surgery (p<0.001) and at the inclusion in the study (p<0.001) and IGFBP3 (0.016) among patients with Gleason <7, ≥7 and BPH. In the PCa group, PSA, testosterone, IGF-I and IGFBP-3 levels were comparable between Gleason <7 and ≥7. Conclusions Our data suggest that in localized PCa, the quantification of PSA and, not of IGF-1, may provide independent significant information in the aggressiveness. IGFBP-3 could be a biochemical marker of disease control in PCa patients. .

Effect of maternal diabetes on female offspring / Efeito do diabetes materno na prole feminina

Objective To evaluate the effect of maternal diabetes on the blood pressure and kidney function of female offspring, as well as if such changes exacerbate during pregnancy. Methods Diabetes mellitus was induced in female rats with the administration of streptozotocin in a single dose, one week before mating. During pregnancy, blood pressure was measured through plethysmography. On the 20th day of pregnancy, the animals were placed for 24 hours in metabolic cages to obtain urine samples. After the animals were removed from the cages, blood samples were withdrawn. One month after pregnancy, new blood and urine sample were collected. Kidney function was evaluated through proteinuria, plasma urea, plasma creatinine, creatinine excretion rate, urinary flow, and creatinine clearance. Results The female offspring from diabetic mothers showed an increase in blood pressure, and a decrease in glomerular filtration rate in relation to the control group. Conclusion Hyperglycemia during pregnancy was capable of causing an increase in blood pressure and kidney dysfunction in the female offspring. .

Objetivo Avaliar o efeito do diabetes materno sobre a pressão arterial e a função renal da prole feminina, bem como verificar se as alterações observadas se exacerbam durante a prenhez. Métodos O diabetes mellitus foi induzido em ratas com a administração de estreptozocina em dose única, uma semana antes do cruzamento. Durante a prenhez, foram feitas medidas da pressão arterial por pletismografia. No 20o dia da prenhez, os animais foram colocados durante 24 horas em gaiolas metabólicas para obtenção de amostras de urina. Após a retirada dos animais das gaiolas, foram obtidas amostras de sangue. Um mês após a prenhez, foram obtidas novas amostras de sangue e urina para as determinações. A função renal foi avaliada por meio de proteinúria, ureia plasmática, creatinina plasmática, carga excretada de creatinina, fluxo urinário e clearance de creatinina. Resultados As fêmeas da prole de mães diabéticas apresentaram elevação da pressão arterial e redução do ritmo de filtração glomerular em relação ao grupo controle. Conclusão A hiperglicemia durante a gestação foi capaz de causar elevação da pressão arterial e disfunção renal na prole de sexo feminino. .

Maternal smoking during pregnancy and birth defects in children: a systematic review with meta-analysis / El tabaquismo materno durante el embarazo y las malformaciones congénitas en niños: una revisión sistemática y meta-análisis / Tabagismo materno na gestação e malformações congênitas em crianças: uma revisão sistemática com meta-análise

This systematic review aimed to investigate the association between maternal smoking during pregnancy and birth defects in children. We performed an electronic search of observational studies in the databases ovid MEDLINE (1950 to April 2010), LILACS and SciELO. We included 188 studies with a total of 13,564,914 participants (192,655 cases). Significant positive associations were found between maternal smoking and birth defects in the following body systems: cardiovascular (OR: 1.11; 95%CI: 1.03-1.19), digestive (OR: 1.18; 95%CI: 1.07-1.30), musculoskeletal (OR: 1.27; 95%CI: 1.16-1.39) and face and neck (OR: 1.28; 95%CI: 1.19-1.37). The strength of association between maternal smoking and birth defects measured by the OR (95%CI) is significantly related to the amount of cigarettes smoked daily (χ2 = 12.1; df = 2; p = 0.002). In conclusion, maternal smoking during pregnancy is associated with congenital malformations in children and this association is dose-dependent.

Esta revisión sistemática se encargó de investigar la asociación entre el tabaquismo materno durante el embarazo y las malformaciones congénitas en los niños. Se realizó una búsqueda electrónica de los estudios de observación en las bases de datos de ovid MEDLINE (1950 hasta abril de 2010), LILACS y SciELO. 188 estudios con 13.564.914 participantes se incluyeron en esta revisión. Se encontraron asociaciones positivas significativas entre el tabaquismo materno y malformaciones de los sistemas: cardiovascular (OR: 1,11; IC95%: 1.03-1.19), digestivo (OR: 1,18; IC95%: 1,07-1,30), musculoesqueléticos (OR: 1,27; IC95%: 1,16-1,39) y de cara y cuello (OR: 1,28; IC95%: 1,19-1,37). La fuerza de la asociación entre el tabaquismo materno y los defectos de nacimiento, medidos por el OR (IC95%) está significativamente relacionada con la cantidad de cigarrillos fumados diariamente (χ2 = 12,1; p = 0,002). Llegamos a la conclusión de que el tabaquismo materno durante el embarazo se asocia con un mayor riesgo de malformaciones congénitas en los niños y esta asociación es dosis-dependiente.

Esta revisão sistemática teve como objetivo investigar a associação entre fumo materno na gestação e as malformações congênitas em crianças. Uma busca eletrônica dos estudos observacionais foi realizada nas bases de dados ovid MEDLINE (1950 até abril de 2010), SciELO e LILACS. Foram incluídos nesta revisão 188 estudos com um total de 13.564.914 participantes (192.655 casos). Foram encontradas associações positivas significativas entre fumo materno e malformações dos sistemas: cardiovascular (OR: 1,11; IC95%: 1,03-1,19), digestivo (OR: 1,18; IC95%: 1,07-1,30), musculoesquelético (OR: 1,27; IC95%: 1,16-1,39) e face e pescoço (OR: 1,28; IC95%: 1,19-1,37). A força de associação entre fumo materno e malformações medida pelo OR (IC95%) está relacionada significativamente com a quantidade diária de cigarros consumidos (χ2 = 12,1; df = 2; p = 0,002). Concluímos que fumo materno na gestação está associado com maior risco de malformações congênitas em crianças e essa associação é dose-dependente.

Prenatal exposure to tobacco and alcohol are associated with chronic daily headaches at childhood: A population-based study / Tabagismo e ingestão alcoólica pré-natal estão associados à cefaleia crônica diária na infância: um estudo de base populacional

The influence of prenatal events on the development of headaches at childhood has not been investigated and is the scope of our study. Of 2,173 children identified as the target sample, consents and analyzable data were provided by 1,440 (77 percent). Parents responded to a standardized questionnaire with a validated headache module and specific questions about prenatal exposures. Odds of chronic daily headache (CDH) were significantly higher when maternal tabagism was reported. When active and passive smoking were reported, odds ratio (OR) of CDH were 2.29 [95 percent confidence intervals (CI)=1.6 vs. 3.6)]; for active tabagism, OR=4.2 (95 percent CI=2.1-8.5). Alcohol use more than doubled the chance of CDH (24 percent vs. 11 percent, OR=2.3, 95 percent CI=1.2-4.7). In multivariate analyses, adjustments did not substantially change the smoking/CDH association. Prenatal exposure to tobacco and alcohol are associated with increased rates of CDH onset in preadolescent children.

A influência de eventos pré-natais na fisiopatogenia das cefaleias na infância ainda não foi investigada e é o objetivo desse estudo. Da amostra-alvo de 2.173 crianças, um consentimento pós-informado e dados suficientes para as análises foram obtidos de 1.440 (77 por cento). Os pais responderam a um questionário padrão com um módulo de cefaleia validado na população brasileira e questões específicas sobre antecedentes pré-natais. O risco de cefaleia crônica diária (CCD) foi significativamente maior nas crianças cujas mães fumaram durante a gestação. Quando presentes tabagismo ativo e passivo, o risco (OR) de CCD foi de 2,29 [intervalo de confiança (IC) de 95 por cento=1,6-3,6)]; para tabagismo ativo, OR=4,2 (IC 95 por cento=2,1-8,5). O uso de álcool durante a gestação dobrou o risco de CCD (24 por cento vs. 11 por cento, OR=2,3, IC 95 por cento=1,2-4,7). Nas análises multivariadas, os ajustes não modificaram, substancialmente a associação entre tabagismo materno durante a gestação e CCD. A exposição pré-natal ao tabaco e ao álcool encontra-se associada à CCD de início na infância.

Effects of prenatal stress on male offspring sexual maturity

Prenatal stimulations have been shown to have long-term effects on at reproductive activity. We evaluated the influence of the prenatal stress on the hypothalamic-pituitary-gonad (HPG) axis in male offsprings from mothers with high number of offsprings per litter (HNL) and low number of offsprings per litter (LNL) after hypothesizing that the number of offsprings per litter may modify the effect of the prenatal stress on the HPG of adult offsprings. Pregnant Wistar rats were used for this study. Immobilization (IMO) stress was used, 30 min, 3 times per week, from the 5th to 21st day of pregnancy. The weight of adrenal and gonads, and the corticosterone (COR), testosterone (TES) and luteinizing hormone (LH) plasmatic levels were analyzed in the male offspring at 30, 45 and 70 days of age. The offspring males coming from LNL showed a decrease in testicle weight and TES levels, without changes in the plasmatic LH levels. However, the offspring of HNL showed a decrease of LH levels. It is possible to conclude that in LNL prenatal stress would produce alterations to gonadal level, while in HNL the effect of stress would be evident at pituitary level.

Consumo de cafeína e de alimentos - fonte de cafeína e prematuridade: um estudo caso - controle / Caffeine intake and food sources of caffeine and prematurity: a case - control study

A cafeína (1,3,7-trimetilxantina) é um alcalóide que facilmente atravessa a barreira placentária podendo interferir no crescimento e desenvolvimento das células fetais e comprometer a oxigenação fetal. Considerando o amplo consumo de alimentos que contêm cafeína no Brasil, o objetivo do estudo foi avaliar a associação entre o consumo total de cafeína e de alimentos-fonte de cafeína com a prematuridade. Um estudo caso-controle de 140 casos (recém-nascidos com idade gestacional inferior a 37 semanas de gestação) e 162 controles (recém-nascidos com 37 semanas ou mais) avaliou o consumo de cafeína durante a gravidez. Para se medir o consumo utilizou-se um questionário de freqüência alimentar, semi-quantitativo, baseado nos seguintes alimentos: café, chá mate e chocolate em pó. O consumo total de cafeína e de alimentos-fonte de cafeína durante a gravidez não foram associados à prematuridade, com a maioria das mulheres tendo consumido menos que 300mg/dia. O consumo de cafeína observado no presente estudo não suporta recomendações contra o consumo de cafeína em gestantes brasileiras.