Early prenatal exposure to air pollutants and congenital heart disease: a nested case-control study

BACKGROUND@#Congenital heart disease (CHD) is one of the most common congenital malformations in humans. Inconsistent results emerged in the existed studies on associations between air pollution and congenital heart disease. The purpose of this study was to evaluate the association of gestational exposure to air pollutants with congenital heart disease, and to explore the critical exposure windows for congenital heart disease.@*METHODS@#The nested case-control study collected birth records and the following health data in Tianjin Women and Children's Health Center, China. All of the cases of congenital heart disease from 2013 to 2015 were selected matching five healthy controls for each case. Inverse distance weighting was used to estimate individual exposure based on daily air pollution data. Furthermore, the conditional logistic regression with distributed lag non-linear model was performed to identify the association between gestational exposure to air pollution and congenital heart disease.@*RESULTS@#A total of 8,748 mother-infant pairs were entered into the analysis, of which 1,458 infants suffered from congenital heart disease. For each 10 µg/m3 increase of gestational exposure to PM2.5, the ORs (95% confidence interval, 95%CI) ranged from 1.008 (1.001-1.016) to 1.013 (1.001-1.024) during the 1st-2nd gestation weeks. Similar weak but increased risks of congenital heart disease were associated with O3 exposure during the 1st week and SO2 exposure during 6th-7th weeks in the first trimester, while no significant findings for other air pollutants.@*CONCLUSIONS@#This study highlighted that gestational exposure to PM2.5, O3, and SO2 had lag effects on congenital heart disease. Our results support potential benefits for pregnancy women to the mitigation of air pollution exposure in the early stage, especially when a critical exposure time window of air pollutants may precede heart development.

Research progress on the relationship between air pollution and gestational diabetes / 中华预防医学杂志

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and has serious implications for the health of mothers and their offspring. In recent years, studies have confirmed that air pollution is one of the main risk factors for diabetes, and there is increasing evidence that air pollution exposure is closely related to the occurrence of gestational diabetes. However, current studies on the association between air pollutant exposure and the incidence of gestational diabetes are inconsistent, and the window period of pollutant exposure is still unclear. Limited mechanistic studies suggest that airborne particulate matter and gaseous pollutants may affect GDM through multiple mechanisms, including inflammation, oxidative stress, disruption of adipokine secretion, and imbalance of intestinal flora. This review summarizes the relationship between air pollutant exposure and the incidence of GDM in recent years, as well as the possible molecular mechanism of the occurrence and development of GDM caused by air pollutants, in order to provide scientific basis for preventing pollutant exposure, reducing the risk of GDM, improving maternal and fetal outcomes and improving the quality of the birth population.

Gene-environment interactions related to maternal exposure to environmental and lifestyle-related chemicals during pregnancy and the resulting adverse fetal growth: a review

BACKGROUND@#There are only limited numbers of reviews on the association of maternal-child genetic polymorphisms and environmental and lifestyle-related chemical exposure during pregnancy with adverse fetal growth. Thus, this article aims to review: (1) the effect of associations between the above highlighted factors on adverse fetal growth and (2) recent birth cohort studies regarding environmental health risks.@*METHODS@#Based on a search of the PubMed database through August 2021, 68 epidemiological studies on gene-environment interactions, focusing on the association between environmental and lifestyle-related chemical exposure and adverse fetal growth was identified. Moreover, we also reviewed recent worldwide birth cohort studies regarding environmental health risks.@*RESULTS@#Thirty studies examined gene-smoking associations with adverse fetal growth. Sixteen maternal genes significantly modified the association between maternal smoking and adverse fetal growth. Two genes significantly related with this association were detected in infants. Moreover, the maternal genes that significantly interacted with maternal smoking during pregnancy were cytochrome P450 1A1 (CYP1A1), X-ray repair cross-complementing protein 3 (XRCC3), interleukin 6 (IL6), interleukin 1 beta (IL1B), human leukocyte antigen (HLA) DQ alpha 1 (HLA-DQA1), HLA DQ beta 1 (HLA-DQB1), and nicotinic acetylcholine receptor. Fetal genes that had significant interactions with maternal smoking during pregnancy were glutathione S-transferase theta 1 (GSTT1) and fat mass and obesity-associated protein (FTO). Thirty-eight studies examined the association between chemical exposures and adverse fetal growth. In 62 of the 68 epidemiological studies (91.2%), a significant association was found with adverse fetal growth. Across the studies, there was a wide variation in the analytical methods used, especially with respect to the genetic polymorphisms of interest, environmental and lifestyle-related chemicals examined, and the study design used to estimate the gene-environment interactions. It was also found that a consistently increasing number of European and worldwide large-scale birth cohort studies on environmental health risks have been conducted since approximately 1996.@*CONCLUSION@#There is some evidence to suggest the importance of gene-environment interactions on adverse fetal growth. The current knowledge on gene-environment interactions will help guide future studies on the combined effects of maternal-child genetic polymorphisms and exposure to environmental and lifestyle-related chemicals during pregnancy.

Effect of maternal exposure to lipopolysaccharide during pregnancy on allergic asthma in offspring in mice / 中华儿科杂志

Objective: To investigate the effect of maternal exposure to lipopolysaccharide during pregnancy on allergic asthma in offspring in mice. Methods: Animal experimental research was carried out from June 2019 to June 2021.Pregnant C57BL/6J mice were randomly divided into 2 groups by intraperitoneal injection with 7 μg/kg lipopolysaccharide (LPS) or phosphate buffered saline (PBS) at day 15.5 of gestation. After birth, 6 offspring were randomly chosen from each group at the age of 4 weeks, and stimulated with house dust mites (HDM) or PBS, further divided into 4 groups, such as LPS+PBS group, LPS+HDM group, PBS+PBS group, PBS+HDM group, with 3 mice in each group. The cough and wheezing were observed, the histological changes in lung tissue were examined after HE staining, and the expression of inflammatory factors including interleukin (IL)-4, IL-6, IL-17A, IL-23, interferon (IFN)-α and IFN-β in the lung tissue were detected by high-throughput liquid protein chip detection. T test or rank sum test was used for the comparison among these groups. Results: The asthma-like airway inflammation was more obvious in PBS+HDM group after stimulated by HDM than that in PBS+PBS group, nevertheless, this manifestation in LPS+HDM group was milder than that in PBS+HDM group. HE staining showed that inflammatory cell aggregation in the lung tissue in PBS+HDM group was significantly higher than that in PBS+PBS group (4.0 (3.5, 4.0) vs. 0 (0, 0.5), Z=2.02, P=0.043), while it was much lower in LPS+HDM group compared to PBS+HDM group (1.0 (0.5, 1.5) vs. 4.0 (3.5, 4.0), Z=1.99, P=0.046). High-throughput liquid protein chip detection of lung tissue showed that IL-6, IL-23 and IFN-β levels were significantly higher in PBS+HDM group when compared to those in PBS+PBS group ((114±3) vs. (94±4) ng/L, (210±4) vs. (173±7) ng/L, (113±2) vs. (94±4) ng/L, t=4.37, 4.84, 3.96, all P<0.05), while the levels of IL-6, IL-23, IFN-α, IFN-β in LPS+HDM group were significantly lower than those in PBS+HDM group ((87±5) vs. (114±3) ng/L, (171±7) vs. (210±4) ng/L, (16.1±0.6) vs. (20.9±0.3) ng/L, (95±1) vs. (113±2) ng/L, t=5.07, 5.07, 7.28, 7.47, all P<0.05). Conclusions: Prenatal low dose LPS exposure can reduce offspring's airway inflammatory reactions and prevent the development of allergic disease. Maternal infection during pregnancy may affect the occurrence and development of allergic asthma in offspring.

Prenatal pyrethroid pesticides exposure and neurodevelopment of 2-year-old children: a birth cohort study / 中华预防医学杂志

Objective: To investigate the influence and critical windows of prenatal exposure to pyrethroid pesticides (PYRs) on neurodevelopment of 2-year-old children. Methods: The subjects of this study were derived from the Xuanwei Birth Cohort. A total of 482 pregnant women who participated in the rural district of Xuanwei birth cohort from January 2016 to December 2018 were included. Maternal urinary concentrations of PYRs metabolites during 8-12 gestational weeks, 20-23 gestational weeks and 32-35 gestational weeks were measured with ultra high performance liquid chromatography system coupled with a tandem mass spectrometry detector. Child neurodevelopment was evaluated with the Bayley Scales of Infant and Toddler Development-Third Edition at 2 years of age. Multivariate linear regression models and binary logistic regression models were used to assess the association between PYRs exposure during pregnancy and children's neurodevelopment. Results: A total of 360 mother-child pairs had complete data on maternal urinary PYRs metabolites detection and children's neurodevelopment assessment. The detection rate of any one PYRs metabolites during the first, second and third trimester were 93.6% (337/360), 90.8% (327/360) and 94.2% (339/360), respectively. The neurodevelopmental scores of Cognitive, Language, Motor, Social-Emotional, and Adaptive Behavior of 2-year-old children were (102.3±18.9), (100.2±16.3), (102.0±20.3), (107.8±23.3) and (85.8±18.6) points, respectively. After controlling for confounding factors, 4-fluoro-3-phenoxybenzoic acid (4F3PBA, one of PYRs metabolites) exposure in the first trimester reduced Motor (β=-5.02, 95%CI: -9.08, -0.97) and Adaptive Behavior (β=-4.12, 95%CI:-7.92, -0.32) scores of 2-year-old children, and increased risk of developmental delay of adaptive behavior (OR=2.07, 95%CI:1.13-3.82). Conclusion: PYRs exposure during the first trimester of pregnancy may affect neurodevelopment of 2-year-old children, and the first trimester may be the critical window.

Living frisbees: riesgos de patologías mentales en niños y niñas expuestos a thc durante su gestación / Living frisbees: risks of mental pathologies in boys and girls exposed to thc during their pregnancy

La Cannabis sativa es una planta que contiene componentes psicoactivos (principalmente tetrahidrocannabinol) y actualmente corresponde a la droga ilícita más consumida a nivel mundial. Además, desde el área de la salud mental, ha habido un creciente interés en evaluar la relación entre el consumo de marihuana y el desarrollo de trastornos mentales. En este contexto, considerando tanto este creciente aumento en su consumo a nivel mundial y el interés por conocer si está involucrada en la patogénesis de patologías de la esfera psiquiátrica, es clave analizar qué posibles riesgos de desarrollar patologías mentales presentan aquellos niños expuestos al tetrahidrocannabinol durante la gestación. A partir de esta situación, el objetivo de este FRISBEEs es determinar si los niños/as expuestos a THC durante su gestación tienen un mayor riesgo de patologías mentales, en comparación a aquellos niños no expuestos durante su gestación. Los materiales y métodos utilizados para responder esta pregunta fueron obtenidos a partir de una búsqueda bibliográfica en dos bases de datos, donde se analizó la evidencia disponible, y se seleccionó el estudio primario titulado "Maternal tobacco, cannabis and alcohol use during pregnancy and risk of adolescent psychotic symptoms in offspring", ya que era el que más se aproximaba a poder responder nuestra pregunta clínica. Este se analizó de forma crítica, llegando al resultado de que el estudio no fue concluyente en establecer una asociación entre el uso de cannabis y síntomas psicóticos. Como conclusión, dado que no se pudo llegar a establecer una asociación entre el uso de cannabis y el desarrollo de patologías mentales, se debería realizar más investigación sobre el tema dado la magnitud del consumo de cannabis a nivel mundial, para así poder llegar a conclusiones clínicas basadas en la evidencia y poder dar recomendaciones clínicas a las pacientes embarazadas.

Cannabis sativa is a plant that contains psychoactive components (mainly tetrahydrocannabinol) and currently corresponds to the most widely consumed illicit drug worldwide. In addition, from the area of mental health, there has been a growing interest in evaluating the relationship between marijuana use and the development of mental disorders. In this context, considering both this growing increase in its consumption worldwide and the interest in knowing if it is involved in the pathogenesis of pathologies in the psychiatric sphere, it is essential to analyze what possible risks of developing mental pathologies present those children exposed to tetrahydrocannabinol during gestation. Based on this situation, the objective of this FRISBEEs is to determine whether children exposed to THC during their pregnancy have a greater risk of mental pathologies, compared to those children not exposed during their pregnancy. The materials and methods used to answer this question were obtained from a bibliographic search in two databases, where the available evidence was analyzed, and the primary study entitled "Maternal tobacco, cannabis and alcohol use during pregnancy and risk of adolescent psychotic symptoms in offspring ", as he was the closest to answering our clinical question. This was critically analyzed, reaching the result that the study was not conclusive in establishing an association between the use of cannabis and psychotic symptoms. In conclusion, given that it was not possible to establish an association between the use of cannabis and the development of mental pathologies, more research should be carried out on the subject given the magnitude of cannabis use worldwide, in order to reach conclusions. evidence-based clinics and to be able to give clinical recommendations to pregnant patients

Effects of prenatal tobacco smoke on cerebellum histomorphological changes at critical developmental stages in CD-1 mice / Efectos del humo de tabaco en los cambios histomorfológicos del cerebelo en las etapas críticas del desarrollo prenatal en ratones CD-1

SUMMARY: In this study the consequences of prenatal exposure to tobacco smokes on the histo-morphological changes of cerebellum was assessed by comparing the smoker mice to the nonsmoker mice. A total of 30 pregnant cd-1 mice were divided into three groups of 10 mice each and with two replicates per group (5 mice each). Following acclimation for five days, the mice were placed in a special modified smoking machine for 2 hours per day over a two- and three-week period for group two and group three, respectively. Group one was considered as a control group. Mice in the control group were exposed simultaneously to fresh air from the room, while those in the treatment groups were exposed to tobacco smoke from six commercial filter cigarettes, containing 0.8 mg of nicotine, 10 mg of tar, and 10 mg of carbon monoxide, for three 1-hour exposure periods every day for three weeks. The mice in the control group were exposed to room air for three 1-hour periods every day for the same period of three weeks. The results from this study showed a correlation between maternal smoking and histological changes in Neuron purkinjense (Purkinje cells) of the cerebellum. They also showed that prenatal smoking period may have caused more damage in the histology and structure of Neuron purkinjense in some juvenile mice. An increased incidence of morphology damage of the cerebellum's Neuron purkinjense' structures was also observed in fetuses with prolonged exposure to tobacco smoking. Exposure of in utero maternal smoking may interfere with brain biological development parameters, giving rise to structural abnormalities of the cerebellum. This study concluded that tobacco smoke exposure to pregnant mice may affect neurodevelopment which may induce behavioural changes as a result of reduced cerebellar size and function.

RESUMEN: Se evaluaron los efectos producidos por la exposición prenatal al humo de tabaco en ratones expuestos y no expuestos y los cambios histomorfológicos observados en el cerebelo en ambos grupos. Un total de 30 ratones cd-1 preñados se dividieron en tres grupos de 10 ratones cada uno y con dos réplicas por grupo (5 ratones cada uno). Después de la aclimatación durante cinco días, los ratones se colocaron en una máquina de fumar modificada, especial durante 2 horas al día, durante un período de dos y tres semanas para el grupo dos y el grupo tres, respectivamente. El grupo uno se consideró como grupo control. Los ratones del grupo de control fueron expuestos simultáneamente al aire limpio de la habitación, mientras que los grupos de tratamiento fueron expuestos al humo de tabaco de seis cigarrillos comerciales, que contenían 0,8 mg de nicotina, 10 mg de alquitrán y 10 mg de monóxido de carbono. durante tres períodos de 1 hora diariamente, durante tres semanas. Los ratones del grupo de control se expusieron al aire ambiente durante tres períodos de 1 hora todos los días durante el mismo período de tres semanas. Los resultados de este estudio mostraron una correlación entre el tabaquismo materno y los cambios histológicos en las neuronas purkinjenses (células de Purkinje). Se observó además que el período de tabaquismo prenatal puede haber causado mayor daño en la histología y estructura de las neuronas purkinjenses en algunos ratones jóvenes. También se observó una mayor incidencia de daño morfológico de las estructuras de las neuronas purkinjenses del cerebelo en fetos con exposición prolongada al tabaquismo. La exposición al tabaquismo materno en el útero puede interferir con los parámetros de desarrollo biológico del cerebro, dando lugar a anomalías estructurales del cerebelo. Este estudio concluyó que la exposición al humo del tabaco en ratones preñados puede afectar el desarrollo neurológico, lo que puede inducir cambios de comportamiento como resultado de la reducción del tamaño y la función del cerebelo.

Air pollution and children's health-a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter

BACKGROUND@#Particulate matter (PM), a major component of ambient air pollution, accounts for a substantial burden of diseases and fatality worldwide. Maternal exposure to PM during pregnancy is particularly harmful to children's health since this is a phase of rapid human growth and development.@*METHOD@#In this review, we synthesize the scientific evidence on adverse health outcomes in children following prenatal exposure to the smallest toxic components, fine (PM@*RESULTS@#Maternal exposure to fine and ultrafine PM directly and indirectly yields numerous adverse birth outcomes and impacts on children's respiratory systems, immune status, brain development, and cardiometabolic health. The biological mechanisms underlying adverse effects include direct placental translocation of ultrafine particles, placental and systemic maternal oxidative stress and inflammation elicited by both fine and ultrafine PM, epigenetic changes, and potential endocrine effects that influence long-term health.@*CONCLUSION@#Policies to reduce maternal exposure and health consequences in children should be a high priority. PM

Maternal metal concentration during gestation and pediatric morbidity in children: an exploratory analysis

BACKGROUND@#The majority of studies linking exposure to metals with certain health outcomes focus on known toxic metals. Alternatively, this study assesses the extent to which exposure to a wider range of metals during gestation is associated with childhood morbidity.@*METHODS@#We analyzed the concentrations of 25 metals found in urine samples of 111 pregnant women of Arab-Bedouin origin collected prior to birth. In addition, we collected medical records on their offspring for six years following birth, including every interaction with HMOs, local hospitals, and pharmacies.@*RESULTS@#The main types of morbidities diagnosed and treated during this period were preterm births, malformations, asthma-like morbidity, cardiovascular and behavioral problems, and obesity. Multivariable analysis showed that offspring born before term were more likely to have been exposed to elevated maternal concentrations of zinc, thallium, aluminum, manganese, and uranium, all with adjusted relative risk above 1.40 for an increase by each quintile. Likewise, children with asthma had been exposed to higher levels of magnesium, strontium, and barium at gestation, while behavioral outcomes were associated with elevated biometals, i.e., sodium, magnesium, calcium, selenium, and zinc, as well as higher levels of lithium, cobalt, nickel, strontium, cadmium, vanadium, arsenic, and molybdenum. A heatmap of adjusted relative risk estimates indicates the considerable implications that exposure to metals may have for preterm birth and developmental outcomes.@*CONCLUSIONS@#The current study shows that perinatal exposure to metals is adversely associated with pediatric morbidity. Further such analyses on additional samples are warranted.

Effects of maternal exposure to arsenic on social behavior and related gene expression in F2 male mice

BACKGROUND@#Arsenic is a developmental neurotoxicant. It means that its neurotoxic effect could occur in offspring by maternal arsenic exposure. Our previous study showed that developmental arsenic exposure impaired social behavior and serotonergic system in C3H adult male mice. These effects might affect the next generation with no direct exposure to arsenic. This study aimed to detect the social behavior and related gene expression changes in F2 male mice born to gestationally arsenite-exposed F1 mice.@*METHODS@#Pregnant C3H/HeN mice (F0) were given free access to tap water (control mice) or tap water containing 85 ppm sodium arsenite from days 8 to 18 of gestation. Arsenite was not given to F1 or F2 mice. The F2 mice were generated by mating among control F1 males and females, and arsenite-F1 males and females at the age of 10 weeks. At 41 weeks and 74 weeks of age respectively, F2 males were used for the assessment of social behavior by a three-chamber social behavior apparatus. Histological features of the prefrontal cortex were studied by ordinary light microscope. Social behavior-related gene expressions were determined in the prefrontal cortex by real time RT-PCR method.@*RESULTS@#The arsenite-F2 male mice showed significantly poor sociability and social novelty preference in both 41-week-old group and 74-week-old group. There was no significant histological difference between the control mice and the arsenite-F2 mice. Regarding gene expression, serotonin receptor 5B (5-HT 5B) mRNA expression was significantly decreased (p < 0.05) in the arsenite-F2 male mice compared to the control F2 male mice in both groups. Brain-derived neurotrophic factor (BDNF) and dopamine receptor D1a (Drd1a) gene expressions were significantly decreased (p < 0.05) only in the arsenite-F2 male mice of the 74-week-old group. Heme oxygenase-1 (HO-1) gene expression was significantly increased (p < 0.001) in the arsenite-F2 male mice of both groups, but plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG) and cyclooxygenase-2 (COX-2) gene expression were not significantly different. Interleukin-1β (IL-1β) mRNA expression was significantly increased only in 41-week-old arsenite-F2 mice.@*CONCLUSIONS@#These findings suggest that maternal arsenic exposure affects social behavior in F2 male mice via serotonergic system in the prefrontal cortex. In this study, COX-2 were not increased although oxidative stress marker (HO-1) was increased significantly in arsnite-F2 male mice.

Inflammatory state and autism-like behavioral phenotype of offspring induced by maternal exposure to low-dose chemical mixtures during pregnancy in mice / 浙江大学学报·医学版

To investigate the effects of maternal exposure to 13 chemicals mixture (CM) during pregnancy on pregnancy outcome and health status of maternal/offspring mice. C57BL/6 pregnant mice were given drinking water containing carbaryl dimethoate glyphosate methomyl methyl parathion triadimefon aspartame sodium benzoate calcium disodium ethylene diamine tetra-acetate ethylparaben butylparaben bisphenol A and acacia gum The effects of CM exposure on pregnancy outcome, health status of dams/offspring, levels of circulating inflammatory cytokines in dams/offspring and emotional related behaviors of offspring were evaluated. CM exposure during pregnancy had no significant effect on pregnancy outcome, liver function, body weight of the dams in late pregnancy and uterine/ovarian weight after delivery, however, it led to an increase in maternal serum IFN-γ level （<0.05）. CM exposure during pregnancy had no significant effect on the liver function of offspring, but increased the serum IFN-γ, prefrontal cortex IFN-γ, and TNF-α and hippocampus IFN-γ levels in the offspring（all <0.01）. In addition, the offspring of CM group showed significant abnormal emotion-related (autism-like) behaviors in adulthood, especially in male offspring. Low dose CM exposure during pregnancy may induce inflammation status in dams/offspring, and lead to autism-like behaviors in offspring, indicating the potential effects of low dose CM exposure on human maternal and infant health.

Impact of maternal exposure to wood smoke pollution on fetal lung morphology in a rat model / Impacto de la exposición materna a la contaminación por humo de leña en la morfología pulmonar fetal en un modelo de rata

SUMMARY: Residential heating with wood is an important source of ambient air pollution. Evidence links air pollution to serious health effects such as respiratory and cardiovascular mortality and morbidity. We hypothesized that prenatal exposure to wood smoke pollution causes morphological changes in the development of the rat lung, leading to altered lung structure and function during later life. We presumed that analysis of the fetal lung stereology provides novel insights into the underlying processes mediating particulate matter associated developmental changes and damage. The objective of the study was to investigate the effects of exposure during gestational period to wood smoke pollution on lung fetal morphology. To test this, pregnant rats were exposed during pregestational and gestational periods to wood smoke pollution. Complete lungs samples were obtained from 24 fetus from healthy female G3 rats subjected to cesarean at 19 days post-fecundation. The lungs were prepared for histological and stereological analysis. The volume fraction of terminal bronchioles VV [tb, lung] and volume fraction of parenchyma VV [par, lung], surface density of terminal bronchioles SV [tb, lung] as well as numerical density of bronchiolar exocrinocytes NA [ec,lung] were calculated by light microscopy. Statistical analysis detected significant differences between groups in volume density VV [tb, lung; %] (p=0.0012) and surface density SV [tb, lung; mm2/mm3] (p<0.0001) of the terminal bronchioles. However, it did not show differences between groups in the stereological parameter volume density VV [par, lung; %] (p=0.0838) and numerical density of bronchiolar exocrinocytes NA [ec,lung; nº/mm2] (p=0.0705). The analysis of the evidence obtained indicates that exposure to environmental pollution was affects lung maturation, and particularly the proportion and area of terminal bronchioles in the fetal lung. In conclusion, maternal exposure to wood smoke pollution during pregnancy was associated with a decrease in the lower conducting airways of lungs, which, according to urban pollution studies, could be related to early childhood lower respiratory illness. The public health implications of this study are that reducing or avoiding exposure to wood smoke is important before and during pregnancy.

RESUMEN: La calefacción residencial con leña es una fuente importante de contaminación ambiental. La evidencia vincula la contaminación del aire con graves efectos sobre la salud, como la mortalidad y la morbilidad respiratoria y cardiovascular. Hipotetizamos que la exposición prenatal a la contaminación por humo de leña causa cambios en el desarrollo del pulmón de rata, lo que conduce a una morfo-función pulmonar alteradas durante la vida posterior, creemos que el análisis de la estereología pulmonar fetal proporcionará nuevos conocimientos sobre los procesos subyacentes que median esos cambios. El objetivo del estudio fue investigar los efectos de la exposición prenatal a la contaminación ambiental por humo de leña sobre la morfología pulmonar fetal. Ratas preñadas fueron expuestas durante los períodos pregestacional y gestacional a la contaminación por humo de leña. En fetos de 19 días post-fecundación fue obtenido el pulmón para análisis histológico y estereológico. Fue determinado la fracción de volumen de bronquiolos terminales VV [tb, pulmón], fracción de volumen del parénquima VV [par, pulmón], densidad superficial de los bronquiolos terminales SV [tb, pulmón] así como la densidad numérica de exocrinocitos NA [ec, pulmón]. El análisis estadístico detectó diferencias significativas entre grupos en la densidad de volumen V [tb, pulmón; %] (p=0,0012) y densidad superficial SV [tb, pulmón; mm2/mm3] (p<0,0001) de los bronquiolos terminales. Sin embargo, no demostró diferencias entre grupos en la densidad de volumen VV [par, pulmón; %] (p=0,0838) y numérica de exocrinocitos bronquiolares NA [ec, pulmón; nº / mm ] (p=0,0705). El análisis de la evidencia obtenida indica que la exposición a la contaminación ambiental afectó la maduración pulmonar, y particularmente la proporción y área de bronquiolos terminales en el pulmón fetal. En conclusión, la exposición materna a la contaminación por humo de leña durante la gestación se asoció a una disminución de las vías respiratorias conductoras de aire en pulmón, lo que, según estudios de contaminación urbana, podría estar relacionado con enfermedades de las vías respiratorias inferiores en la primera infancia. Las implicaciones para la salud pública de este estudio son que reducir o evitar la exposición al humo de leña es importante previo y durante la gestación. Por otro lado, la contaminación por humo de leña tiene un gran impacto en la salud pública que, en teoría, es posible prevenir.

Exposure to wood smoke pollution during pre-gestational period of rat has effects on placenta volume and fetus size / La exposición a la contaminación por humo de leña durante el período pregestacional de la rata tiene efectos sobre el volumen de la placenta y el tamaño del feto

SUMMARY: Studies in humans showed that prenatal exposure to urban air pollution (AP) influences fetal development, and increases the incidence of adverse pregnancy outcomes and some diseases in postnatal life. However, most of these were performed in environments where the main source of environmental particulate matters (PM) emission is diesel combustion by motor vehicles and industries, thereby ignoring the effects produced by wood smoke pollution. We hypothesized that morphological changes in the placenta could contribute to the reduction in fetal size associated with different periods of exposure to AP produced by wood smoke pollution prior to and during pregnancy. The objective of the study was to investigate the quantitative effects of long-term exposure to environmental levels of wood smoke pollution on the macroscopic and microscopic morphology of the placenta in rats. To test this, pregnant rats were exposed during pregestational and gestational periods to wood smoke pollution in indoor and outdoor environments. At 19 days of gestation, the placentas were obtained by caesarean and were prepared for histological, planimetric and stereological analysis. The volume and proportions of the placental compartments were estimated. In addition, stereological estimators in fetal capillaries were calculated in the labyrinth region. Crown rump length, fetus weight and litter weight were influenced by pregestational and gestational exposure periods. Exposure to wood smoke pollution during pregestational period has significant effect on the volume of the placenta, and consequently on fetal height. In conclusion, this study demonstrated that long-term outdoor exposure to wood smoke pollution from residential heating affects fetal health, decreasing the absolute volume of the entire placenta and the placental interface between the mother and fetus, decreasing the total volume of blood vessels present in the labyrinth region ofthe placenta and affecting the size of the fetus.

RESUMEN: Estudios en humanos demostraron que la exposición prenatal a la polución del aire urbano influye en el desarrollo fetal y aumenta la incidencia de resultados adversos de la gestación y algunas enfermedades postnatales. Sin embargo, la mayoría de ellos fueron realizados en entornos donde la principal fuente de emisión de material particulado, fue la combustión de petróleo por vehículos a motor e industrias, ignorando los efectos producidos por el humo de leña producido por la calefacción intradomiciliaria. Hipotetizamos respecto a que los cambios de la placenta contribuirían a la disminución del tamaño fetal relacionado a los períodos de exposición al humo de leña durante los periodos pregestacional y gestacional. El objetivo del estudio fue investigar los efectos cuantitativos de la exposición al humo de leña sobre la morfología macroscópica y microscópica en placenta de ratas. Para probar esto, ratas preñadas fueron expuestas durante los períodos pregestacional y gestacional a la contaminación por humo de leña en ambientes interiores y exteriores. A los 19 días de gestación, las placentas fueron obtenidas por cesárea y fueron preparadas para un análisis histológico, planimétrico y estereológico. Fue estimado el volumen absoluto y las proporciones de los compartimentos placentarios. Además, fueron calculados estimadores estereológicos en capilares fetales del laberinto y trofoblasto. La longitud, el peso del feto y el peso de la camada fueron influenciados por los períodos de exposición pregestacional y gestacional. La exposición a la contaminación por humo de leñá durante el período pregestacional tuvo un efecto significativo en el volumen de la placenta y, en consecuencia, en la altura del feto. En conclusión, este estudio demostró que la exposición a largo plazo al humo de leña afecta la salud del feto, disminuyendo el volumen absoluto de la placenta, además, afecta la interfaz placentaria entre la madre y feto, disminuyendo el volumen total de vasos sanguíneos presentes en la región del laberinto placentario y por consecuente afectando el tamaño del feto.

Prevalencia de factores de riesgo ambientales prenatales en niños con trastorno del espectro autista controlados en un hospital de niños / Prevalence of prenatal environmental risk factors in children with autism spectrum disorder monitored in a children's hospital

INTRODUCCIÓN: El Trastorno del Espectro Autista (TEA) afecta al 1% de los niños y se ha demostrado que una de sus principales causas se debe a factores ambientales prenatales que afectan al feto durante el periodo gestacional. El objetivo fue estimar la prevalencia de factores de riesgo (FR) prenatales en niños con TEA menores de 8 años que se controlan en un Hospital de niños. MÉTODOS: Se realizó un estudio transversal descriptivo. Se aplicó una encuesta a los padres o tutores de los niños durante la espera a su control. Se realizó un análisis descriptivo de los datos. RESULTADOS: Participaron 76 madres de niños con TEA. Entre los niños predominó el sexo masculino, mediana de edad de 5,4 años, la mayoría puede hablar sin dificultad (78%) y un 28% tenía diagnóstico de alguna enfermedad crónica. La prevalencia de FR prenatales encontrados en este estudio es similar a las reportadas en otros estudios especialmente la edad de los padres, los años de educación materna, los abortos previos y el diagnóstico de enfermedades en el embarazo. Sin embargo, la prevalencia de factores como el embarazo de alto riesgo, el consumo materno de fármacos durante el embarazo, el parto prematuro y el consumo de tabaco y drogas durante el embarazo, fueron muy superiores en este estudio comparado con otros estudios, y podrían estar relacionadas con el diagnóstico de TEA en la infancia. CONCLUSIÓN: A partir de estos hallazgos, se establece una base para realizar estudios comparativos en el futuro.

INTRODUCTION: Autistic Spectrum Disorder (ASD) affects 1% of children and it has been shown that one of its main causes is due to prenatal factors that affect the fetus during the gestational period. The objective was to estimate the prevalence of prenatal risk factors (RF) in children with ASD under 8 years of age who are monitored in a Children's Hospital. METHODS: A descriptive cross-sectional study was carried out. A survey was applied to the parents or guardians of the children during the wait for their control. A descriptive analysis of the data was carried out. RESULTS: 76 mothers of children with ASD participated. The male sex predominated, the average age was 5.4 years, the majority could speak without difficulty (78%) and 28% had a diagnosis of a chronic disease. The prevalence of prenatal RF found in this study is similar to that reported in other studies, especially the age of the parents, the years of maternal education, previous abortions and the diagnosis of diseases in pregnancy. However, the prevalence of factors such as high-risk pregnancy, maternal consumption of medicines during pregnancy, preterm delivery and tobacco and drug use during pregnancy were much higher in this study compared to other studies, and could be related to the diagnosis of ASD in childhood. CONCLUSION: Based on these findings, a basis for comparative studies in the future is established.

Maternal exposure to benzene and toluene and preterm birth. A longitudinal study

ABSTRACT BACKGROUND: Exposure to air pollutants has several effects on human health, including during pregnancy. OBJECTIVE: To identify whether exposure to benzene and toluene among pregnant women contributes to preterm delivery. DESIGN AND SETTING: Longitudinal study using data on newborns from mothers living in São José dos Campos (SP) in 2016, who had been exposed to benzene and toluene. METHODS: A logistic regression model with three hierarchical levels was constructed using maternal variables relating to newborns, and using benzene and toluene concentrations in quartiles. Occurrences of cesarean births, twins or malformations were excluded. Maternal exposure windows of 5, 10, 15, 30, 60 and 90 days prior to delivery were considered. RESULTS: Out of the 9,562 live births, 3,671 newborns were included and 343 newborns were born at less than 37 weeks of gestation (9.3%). The average birth weight was 3,167.2 g. Exposure to benzene and toluene was significantly associated (P = 0.04) with preterm delivery in the five-day window. There was no association in any of the other exposure windows. CONCLUSIONS: It was possible to identify that maternal exposure to benzene and toluene has an acute effect on preterm delivery.

Maternal exposure to alcohol and low birthweight: A systematic review and meta-analysis / Exposição maternal ao álcool e baixo peso ao nascer: revisão sistemática e metanálise

Abstract Objective To investigate the relationship between maternal exposure to alcohol and low birthweight (LBW). Methods The literature search was performed in January 2017 using the following electronic databases: Medline, Embase, LILACS, SciELO, Web of Science, Scopus, CINHAL, Proquest, and PsychInfo. The search strategy used the following terms: alcohol drinking, binge drinking, alcohol-related disorders, alcoholism, alcohol addiction/ use/abuse/consumption, light/moderate/social/low drinking, low birthweight, case-control studies, retrospective studies, and cohort studies. No restrictions regarding language or publication date were considered. The literature search yielded 2,383 articles, and after screening and eligibility assessment, 39 articles were included in the systematic review, and 38 studies were included in the meta-analysis. Results Maternal alcohol consumption was associated with LBWamong retrospective cohort studies (relative risk [RR] = 1.37; 95%CI [confidence interval]:1.10-1.77; I2 = 98.4%; p < 0.01). Prospective cohort studies (RR = 1.11; 95%CI: 0.98-1.25; I2 = 81.5%; p < 0.01), and case-control studies (odds ration [OR] = 1.16; 95%CI: 0.68-1.97; I2 = 61.2%; p = 0.05) showed no association between alcohol and LBW.No publication bias was identified, and the meta-regression showed that the sample size influenced the high heterogeneity among retrospective cohort studies. The subgroup analysis showed differences in association between groups when compared by sample size, type of adjustment, or crude measures and publication year. Conclusions We have not found an association between alcohol consumption during gestation and LBW in the analysis in all of the subgroups. In addition, we have found a high heterogeneity between the primary studies, which is related to methodological differences in the conduction of these studies.

Resumo Objetivo Investigar a associação entre a exposição maternal ao álcool e o baixo peso ao nascer. Método A busca na literatura ocorreu em janeiro de 2017 nas seguintes bases de dados eletrônicas: Medline, Embase, LILACS, SciELO, Web of Science, Scopus, CINHAL, Proquest, e PsychInfo. A estratégia de busca utilizou os seguintes termos: alcohol drinking, binge drinking, alcohol-related disorders, alcoholism, alcohol addiction/use/ abuse/consumption, light/moderate/social/low drinking, low birthweight, case-control studies, retrospective studies, e cohort studies. Não houve restrição de idioma e ano de publicação. A busca na literatura identificou 2.383 artigos, e depois de analisados conforme os critério de elegibilidade, foram incluídos na revisão sistemática 39 estudos, e 38 estudos foram incluídos na metanálise. Resultados A amostra foi composta por 497.023 gestantes. O consumo materno de álcool foi associado ao baixo peso ao nascer entre os estudos de coorte retrospectiva (risco relativo [RR] = 1,37; IC [intervalo de confiança] 95%: 1,10-1,77; I2 = 98,4%; p < 0,01). Os estudos de coorte prospectiva (RR = 1,11; IC95%: 0,98-1,25; I2 = 81,5%; p < 0,01) e caso-controle (razão de chances [OR, na sigla em inglês] = 1,16; IC95%: 0,68-1,97; I2 = 61,2%; p = 0,05) não apresentaram associação entre o consumo e o desfecho. Não foi identificado viés de publicação, e a metarregressão mostrou que o tamanho da amostra influenciou a heterogeneidade entre os estudos de coorte prospectiva. Na análise por subgrupo, houve diferenças entre os grupos por tamanho de amostra, por tipo de ajuste e por ano de publicação. Conclusão Não encontramos associação entre o consumo e o baixo peso ao nascer em todas as análises por subgrupo. Além disso, encontramos alta heterogeneidade entre os estudos primários, e isto se deve possivelmente às diferenças metodológicas na condução destes estudos.

Uso de medicamentos antidepressivos na amamentação: avaliação da conformidade das bulas com fontes bibliográficas baseadas em evidências científicas / Use of antidepressants during breastfeeding: evaluating drug package inserts conformity with science-based bibliographical sources / Uso de medicamentos antidepresivos durante la lactancia: evaluación de la conformidad de los prospectos, respecto a fuentes bibliográficas basadas en evidencias científicas

O objetivo deste artigo foi avaliar a conformidade entre as recomendações de uso de medicamentos antidepressivos durante a amamentação, presentes em bulas, e as recomendações de fontes bibliográficas baseadas em evidências científicas. Foram avaliadas as bulas padrão de 23 antidepressivos com registro ativo no Brasil. A presença de contraindicação do uso do antidepressivo durante a amamentação foi comparada com as informações presentes no manual técnico do Ministério da Saúde, no livro Medications and Mothers' Milk e nas bases de dados LactMed, Micromedex e UpToDate. Na maioria das bulas (62,5%), o antidepressivo é contraindicado na amamentação. Entre as fontes bibliográficas, esse percentual variou de 0% a 25%. O estudo aponta para baixa conformidade entre bulas e fontes bibliográficas, alertando sobre a necessidade de revisão do conteúdo e forma de apresentação das informações presentes nas bulas dos antidepressivos no Brasil.

This article sought to evaluate the conformity between recommendations regarding antidepressant use during breastfeeding found in drug package inserts with recommendations from science-based bibliographic sources. We evaluated the standard drug package inserts of 23 antidepressants with active registration in Brazil. The presence of contraindications of antidepressant use during breastfeeding was compared with information present in the Brazilian Ministry of Health technical manual, the book Medications and Mothers' Milk and on the databases LactMed, Micromedex and UpToDate. In most drug package inserts (62.5%), antidepressants are contraindicated during breastfeeding. Among bibliographical sources, that percentage varied between 0% and 25%. The study shows a low conformity between drug package inserts and bibliographical sources, alerting to the need for revising the content and presentation of information present in antidepressant drug package inserts in Brazil.

El objetivo de este artículo fue evaluar la conformidad entre las recomendaciones de uso de medicamentos antidepresivos durante la lactancia, presentes en prospectos, y las recomendaciones de fuentes bibliográficas, basadas en evidencias científicas. Se evaluaron los prospectos estándar de 23 antidepresivos con registro activo en Brasil. La presencia de contraindicaciones en el consumo de antidepresivos durante la lactancia se comparó con la información presente en el manual técnico del Ministerio de la Salud, en el libro Medications and Mothers' Milk, y en las bases de datos LactMed, Micromedex y UpToDate. En la mayoría de los prospectos (62,5%), el antidepresivo está contraindicado durante la lactancia. Entre las fuentes bibliográficas el porcentaje varió de 0% a 25%. El estudio señala la escasa conformidad entre prospectos y fuentes bibliográficas, alertando sobre la necesidad de revisión del contenido, así como de la forma de presentación de la información que aparece en los prospectos de los antidepresivos en Brasil.

Protective effect of omega 3 and vitamin D in preventing lung-tissue damage of newborn rats exposed to cigarette smoke during intrauterine period / Efecto protector de omega 3 y vitamina D en la prevención del daño en el tejido pulmonar de ratas recién nacidas expuestas al humo del cigarrillo durante el período intrauterino

SUMMARY: This study aimed to investigate the toxic effects of cigarette smoke exposure on lung and the protective role of Omega 3 and Vitamin D against these toxic effects biochemically and histologically. 28 pregnant Wistar Albino rats were divided into four groups. The first group was control group; the second group was exposed to smoke of 10 cigarette by puff device 2 hours/day after pregnancy; the third group was exposed to cigarette smoke together with Omega 3 (0.5 mg/kg/day) and the fourth group was exposed to cigarette smoke together with vitamin D (42 microgram/kg/day). Finally, lung tissue sections of the newborn rats were stained with Hemotoxilen eosine and Masson tricromite. Malondialdehyde (MDA) and Fluorescent Oxidation Products (FOU) levels were measured. Fetal weights and the number of fetuses were significantly lower in the group received only cigarette smoke (both p<0.001). Histopathologically, pulmonary volume, number of developed alveols and parenchyma elasticity decreased significantly, meanwhile interstitial tissue increased, elastin and collagen did not develop adequately. Histopathologic changes significantly decreased in the group given Omega 3 and Vitamin D. Statistically, MDA and FOU levels were found to be higher in the group exposed to cigarette smoke compared to the control group, and MDA and FOU levels were lower in the group given Omega 3 along with cigarette smoke (p<0.001). Cigarette smoke caused histologically significant damage to fetal lung tissue, oxidative stress and increased MDA and FOU levels. This damage was significantly reduced with Omega 3 and Vitamine D supplementation. Omega 3 is an important antioxidant; vitamin D has no significant antioxidant effect.

RESUMEN: Este estudio tuvo como objetivo investigar los efectos tóxicos de la exposición al humo de cigarrillo en el pulmón, y el papel protector de Omega 3 y la Vitamina D contra esos efectos. 28 ratas Wistar albino preñadas fueron separadas en cuatro grupos. El primer grupo grupo control; el segundo grupo estuvo expuesto al humo de 10 cigarrillos por dispositivo de inhalación 2 horas / día después de la preñez; el tercer grupo se expuso al humo del cigarrillo junto con Omega 3 (0,5 mg / kg / día) y el cuarto grupo se expuso al humo del cigarrillo junto con vitamina D (42 microgramos / kg / día). Secciones de tejido pulmonar de las ratas recién nacidas se tiñeron con Hematoxilina Eosina y tricrómico de Masson. Se midieron los niveles de malondialdehído (MDA) y productos de oxidación fluorescente (POF). Los pesos fetales y el número de fetos fueron significativamente más bajos en el grupo que recibió solamente humo de cigarrillo (ambos p <0,001). Histopatológicamente, el volumen pulmonar, el número de alveolos desarrollados y la elasticidad del parénquima disminuyeron significativamente; mientras que el tejido intersticial aumentó y la elastina y el colágeno no se desarrollaron adecuadamente. Los cambios histopatológicos disminuyeron significativamente en el grupo que recibió Omega 3 y Vitamina D. Estadísticamente, se encontró que los niveles de MDA y POF eran más altos en el grupo expuesto al humo de cigarrillo en comparación con el grupo control, además los niveles de MDA y POF fueron más bajos en el grupo que recibió Omega 3 junto con el humo del cigarrillo (p <0,001). El humo del cigarrillo causó daños histológicamente significativos en el tejido pulmonar fetal, el estrés oxidativo y el aumento de los niveles de MDA y FOU. Este daño se redujo significativamente con los suplementos de Omega 3 y Vitamina D. El omega 3 es un importante antioxidante; la vitamina D no tiene ningún efecto antioxidante significativo.

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.

Burden of Mild Mental Retardation attributed to prenatal methylmercury exposure in Amazon: local and regional estimates / Carga de Retardo Mental Leve atribuída à exposição pré-natal ao metilmercúrio na Amazônia: estimativas local e regional

Abstract The gold rush in the Amazon Region caused an increase of mercury (Hg) levels in the environment, and, consequently, raised human exposure. Once released into aquatic systems, Hg could generate methylmercury (MeHg), an extremely toxic compound, which is accumulated through trophic chains. Several studies have provided evidences of the brain sensitivity to MeHg, as well as, of the fetus vulnerability during pregnancy. The main objective of this study was to estimate the Mild Mental Retardation (MMR) in Amazonian populations, caused by prenatal exposure to MeHg, using the methodology proposed by Poulin (2008), which quantifies the environmental burden of disease. The estimates of the MMR burden, attributed to prenatal MeHg exposure, were based on the calculation of Disability-Adjusted Life Years (DALY), which were obtained from MMR incidence rate in the studied populations. At the local level, the MMR incidence rate calculations were based on primary data of MeHg exposure of riverine women at childbearing age. The MMR incidence rate was equal to 5.96/1,000 infants, which would result in 2.0 IQ points loss in 34.31% of the newborns. The estimated DALY/1,000 infants was equal to 71.2, while the DALY was 576. For the regional estimates, different exposure scenarios were created. The calculated DALY varied from 3,256 to 65,952 per year.

Resumo A corrida pelo ouro na Amazônia elevou os níveis de mercúrio (Hg) no ambiente e, consequentemente, aumentou a exposição humana. Uma vez liberado em sistemas aquáticos, o Hg pode gerar metilmercúrio (MeHg), um composto tóxico que se acumula ao longo de cadeias tróficas. Vários estudos têm gerado evidências sobre a sensibilidade do cérebro ao MeHg, bem como sobre a vulnerabilidade do feto durante a gravidez. O principal objetivo deste trabalho foi estimar a carga de Retardo Mental Leve (RML) em populações amazônicas, causada pela exposição pré-natal ao MeHg, utilizando a metodologia proposta por Poulin (2008). As estimativas de RML, atribuída à exposição ao MeHg pré-natal, foram baseadas no cálculo dos Anos de Vida Ajustados por Incapacidade (DALY), que foi desenvolvido a partir de taxa de incidência RML nas populações estudadas. Em nível local, o cálculo da taxa de incidência RML baseou-se em dados primários sobre a exposição ao MeHg em mulheres ribeirinhas em idade fértil. A taxa de incidência RML foi igual a 5,96/1.000 nascidos, o que resulta na perda de 2,0 pontos de QI em 34,31% dos nascidos. A estimativa de DALY/1.000 nascidos foi igual a 71,2, enquanto o DALY foi de 576. Para as estimativas regionais, foram criados diferentes cenários de exposição. Os DALYs calculados variaram de 3.256 a 65.952 por ano.