RESUMEN

Ambient air pollution is a significant environmental risk factor for adverse pregnancy outcomes, including preterm birth. However, the impact of different pollutants across various regions and trimesters of pregnancy has not been fully investigated in Brazil. This study aimed to examine the associations between exposure to PM2.5, NO2, and O3 during different trimesters of pregnancy and the risk of preterm birth across five regions of Brazil. We used logistic regression models to estimate the odds ratios (OR) of preterm birth associated with PM2.5, NO2, and O3 adjusting for potential confounders such as maternal age, education, and socioeconomic status. Our study included over 9.9 million live births from 2001 to 2018, with data obtained from the Ministry of Health in Brazil. On average, for each 1-µg/m3 increase in PM2.5, we estimated a 0.26 % (95 % CI: 0.08-0.44 %) increase in the risk of preterm birth nationally in the first trimester. For NO2, each 1ppb increase was associated with a percentage increase in preterm birth risk of 7.26 % (95 % CI: 4.77-9.74 %) in the first trimester, 8.05 % (95 % CI: 5.73-10.38 %) in the second trimester, and 7.48 % (95 % CI: 5.25-9.72 %) in the third trimester. For O3, each 1ppb increase was associated with a percentage increase in preterm birth risk of 1.24 % (95 % CI: 0.29-2.18 %) in the first trimester, 1.51 % (95 % CI: 0.60-2.41 %) in the second trimester, and 0.72 % (95 % CI: -0.18-1.62 %) in the third trimester. This study highlights the significant impact of ambient air pollution on preterm birth risk in Brazil, with significant regional variations. Our findings underscore the need for targeted public health interventions to mitigate the effects of air pollution on pregnancy outcomes, particularly in the most affected regions.

Asunto(s)

Contaminantes Atmosféricos , Contaminación del Aire , Exposición Materna , Nacimiento Prematuro , Embarazo , Nacimiento Prematuro/epidemiología , Femenino , Brasil/epidemiología , Humanos , Contaminación del Aire/efectos adversos , Contaminación del Aire/estadística & datos numéricos , Contaminantes Atmosféricos/análisis , Adulto , Exposición Materna/estadística & datos numéricos , Exposición Materna/efectos adversos , Material Particulado/análisis , Adulto Joven , Ozono/análisis , Dióxido de Nitrógeno/análisis

RESUMEN

Although phthalate exposure has been linked with multiple adverse pregnancy outcomes, their underlying biological mechanisms are not fully understood. We examined associations between biomarkers of phthalate exposures and metabolic alterations using untargeted metabolomics in 99 pregnant women and 86 newborns [mean (SD) gestational age = 39.5 (1.5) weeks] in the PROTECT cohort. Maternal urinary phthalate metabolites were quantified using isotope dilution high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), while metabolic profiles in maternal and cord blood plasma were characterized via reversed-phase LC-MS. Multivariable linear regression was used in metabolome-wide association studies (MWAS) to identify individual metabolic features associated with elevated phthalate levels, while clustering and correlation network analyses were used to discern the interconnectedness of biologically relevant features. In the MWAS adjusted for maternal age and prepregnancy BMI, we observed significant associations between specific phthalates, namely, di(2-ethylhexyl) phthalate (DEHP) and mono(3-carboxypropyl) phthalate (MCPP), and 34 maternal plasma metabolic features. These associations predominantly included upregulation of fatty acids, amino acids, purines, or their derivatives and downregulation of ceramides and sphingomyelins. In contrast, fewer significant associations were observed with metabolic features in cord blood. Correlation network analysis highlighted the overlap of features associated with phthalates and those identified as differentiating markers for preterm birth in a previous study. Overall, our findings underscore the complex impact of phthalate exposures on maternal and fetal metabolism, highlighting metabolomics as a tool for understanding associated biological processes. Future research should focus on expanding the sample size, exploring the effects of phthalate mixtures, and validating identified metabolic features in larger, more diverse populations.

Asunto(s)

Metabolómica , Ácidos Ftálicos , Humanos , Femenino , Ácidos Ftálicos/orina , Embarazo , Adulto , Puerto Rico , Exposición Materna , Recién Nacido , Sangre Fetal/química , Sangre Fetal/metabolismo , Biomarcadores/sangre , Metaboloma , Exposición a Riesgos Ambientales

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental contaminants produced through the combustion of organic matter, with sources ranging from traffic pollution to diet. Although PAH exposure has been associated with adverse health effects, few studies have examined its impact on neurodevelopmental delay (NDD). Thus, our study aims to investigate the effect of prenatal PAH exposure on the odds of NDD. We measured 7 hydroxylated PAH metabolites in spot urine samples collected up to three times during pregnancy in the PROTECT birth cohort. NDD was identified using score cutoffs from the Ages and Stages Questionnaire, 3rd edition offered in Spanish, across five domains at 12, 24, 36, and 48 months. We utilized logistic regression and mixed effects logistic regression models to assess associations between prenatal PAH concentrations and NDD. Our results showed mostly lower odds of NDD with higher PAH exposure (p < 0.05). However, male children showed higher odds of NDD in relation to PAH exposure, particularly in the Fine Motor domain. For example, 1-hydroxypyrene was associated with 1.11 (1.01, 1.23) times odds of delay in fine motor function in male children versus 0.91 (0.82, 1.00) times odds in female children. Our preliminary sex-specific results suggest that PAH exposure may impact neurodevelopment in male children and prompt further investigation into the potential sex-specific mechanisms of PAHs on motor function.

Asunto(s)

Contaminantes Ambientales , Hidrocarburos Policíclicos Aromáticos , Efectos Tardíos de la Exposición Prenatal , Humanos , Hidrocarburos Policíclicos Aromáticos/toxicidad , Hidrocarburos Policíclicos Aromáticos/orina , Femenino , Embarazo , Masculino , Contaminantes Ambientales/orina , Puerto Rico , Preescolar , Exposición Materna/estadística & datos numéricos , Lactante , Trastornos del Neurodesarrollo/epidemiología , Trastornos del Neurodesarrollo/inducido químicamente , Desarrollo Infantil/efectos de los fármacos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Adulto

RESUMEN

Low birth weight (LBW) is a global health concern. While it is commonly associated with maternal health and behavior, exposure to ambient air pollution, can also play a role in contributing to LBW. In Brazil, where diverse environmental conditions and regional disparities exist, assessing the impact of ambient air pollution on LBW becomes particularly pertinent. To our knowledge, there is a gap in the existing literature, as no previous study has specifically investigated the relationship between ambient air pollution and LBW nationwide in Brazil. This study aims to fill this gap by examining the association between ambient air pollution and LBW in each trimester of pregnancy across the Brazilian states. In this work, birth data from January 1, 2001, to December 31, 2018 has been used. We utilized logistic regression models to estimate the odds ratio (OR) for low birth weight (LBW) associated with ambient air pollution (PM2.5, NO2, and O3) during each trimester of pregnancy (1st to 3rd trimester) across all 27 Brazilian states in our nationwide case-control study. We adjusted our model for several variables, including ambient temperature, relative humidity, and socioeconomic status (SES) variables at the individual level. We also conducted effect modification analyses by infant sex, mother's age, and the number of prenatal visits. Our study comprises over 10,213,144 birth records nationwide. Of these, 479,204 (4.92%) infants were included as cases of LBW. Our results indicate positive associations between PM2.5 and LBW, mainly in the Southern region. For example, in the state of Santa Catarina (South region), ORs were 1.003 (95% CI: 1.002, 1.004), 1.003 (95% CI: 1.002, 1.004), and 1.005 (95% CI: 1.003, 1.007) for the 1st, 2nd, and 3rd trimesters of exposure, respectively. NO2 had a robust association with LBW in the Northern and Northeastern states, including the state of Amapá (North region, where the Amazon Forest is located) with ORs of 1.377 (95% CI: 1.010, 1.878), 1.390 (95% CI: 1.020, 1.894), and 1.747 (95% CI: 1.297, 2.352) for the 1st, 2nd, and 3rd trimesters of exposure, respectively. Similarly, O3 had a robust association in the North and Midwest states, as observed in the state of Amapá with ORs of 1.033 (95% CI: 1.012, 1.054), and 1.033 (95% CI: 1.013, 1.053) for the 2nd, and 3rd trimesters, respectively. In the stratified analysis, boys were more vulnerable than girls, and the lower number of prenatal visits was associated with higher OR. Our findings are essential to the development of guidelines to prevent maternal exposure and protection of newborns in Brazil. This study provides valuable insights for region-specific strategies to improve maternal and neonatal health.

Asunto(s)

Contaminantes Atmosféricos , Contaminación del Aire , Recién Nacido de Bajo Peso , Exposición Materna , Material Particulado , Humanos , Brasil , Contaminación del Aire/estadística & datos numéricos , Femenino , Embarazo , Recién Nacido , Contaminantes Atmosféricos/análisis , Material Particulado/análisis , Adulto , Exposición Materna/estadística & datos numéricos , Masculino , Estudios de Casos y Controles , Ozono/análisis , Adulto Joven , Oportunidad Relativa , Dióxido de Nitrógeno/análisis , Modelos Logísticos

RESUMEN

Aim: Childhood maltreatment (CM) may affect not only directly exposed individuals but also their offspring. However, the underlying biological mechanisms remain unclear. microRNAs (miRNAs) may play a regulatory role in this process. This study investigates the relationship between maternal exposure to CM and miRNA expression in maternal and perinatal tissues.Methods: We enrolled 43 pregnant women and assessed their CM exposure. We collected maternal blood, cord blood and placental tissue samples during childbirth and performed miRNA profiling using next generation sequencing.Results: Maternal CM was inversely associated with hsa-miR-582-3p levels in cord blood. Pathway analysis revealed that this miRNA regulates genes involved in intrauterine development.Conclusion: Our findings highlight the potential impact of maternal CM exposure on offspring epigenetic mechanisms.

---

Child maltreatment (CM) includes physical, sexual and emotional abuse, as well as physical and emotional neglect. CM not only harms those directly exposed but can also negatively impact their offspring. However, the biological reasons behind this are not well understood. To explore this further, our study investigates how CM affects the biology of pregnant women and their newborns through changes in small regulatory molecules called microRNAs (miRNAs). We recruited 43 pregnant women and assessed their exposure to CM. During childbirth, we collected blood samples from the mothers, blood from the umbilical cord and placental samples. We then analyzed the levels of miRNAs in these samples using advanced sequencing technology. We observed that more severe maternal exposure to CM was associated with lower levels of a miRNA named hsa-miR-582-3p in umbilical cord blood. This miRNA regulates genes involved in fetal development in utero and has been linked to spontaneous preterm birth. It may also influence immunologic and stress-related processes. Thus, newborns of mothers who had been exposed to CM may be more vulnerable to adverse effects on their brain development and overall health. Despite our small sample size, our study highlights the importance of addressing CM as an intergenerational concern and provides new insights into the biological mechanisms through which maternal CM can affect offspring.

Asunto(s)

Sangre Fetal , Exposición Materna , MicroARNs , Humanos , Femenino , Sangre Fetal/metabolismo , MicroARNs/genética , MicroARNs/sangre , Embarazo , Adulto , Exposición Materna/efectos adversos , Maltrato a los Niños , Placenta/metabolismo , Epigénesis Genética , Niño

RESUMEN

Maternal exposure to extreme ambient temperature during pregnancy has been proposed as a potential risk factor for birth defects. Comprehensive investigations on this association remain limited, particularly in low- and middle-income countries. This study aims to examine the association between ambient temperature exposure during pregnancy and the risk of birth defects in Brazil, contributing to the broader understanding of environmental influences on birth outcomes. Using a large dataset of over 11 million live birth records, we analyzed 12 categories of birth defects, encompassing a time frame from 2001 to 2018. Ambient temperature data were assigned at the municipality level. For the exposure assessment, we considered two biologically driven pregnancy stages by dividing the gestational period into two specific windows: the first trimester (from week 1 to week 12) and the second trimester (from week 13 to week 28). We employed a two-stage case-control design. In the first stage, we applied a conditional logistic regression model to estimate the odds ratio (OR) for specific birth defects and each of the five Brazilian regions (North, Northeast, Midwest, Southeast, and South). The model was adjusted for potential confounding variables, including PM2.5, relative humidity, and socioeconomic status. Temporal trends were addressed using time-stratified sampling. In the second stage, we used mixed-effects meta-analysis to pool region-specific estimates. Our analysis revealed a significant association between maternal exposure to higher ambient temperatures during the first trimester and an increased risk of specific birth defect categories, including those affecting the genital organs (OR = 1.08, 95% CI: 1.02; 1.14), digestive system (OR = 1.12, 95% CI: 1.06; 1.19); circulatory system (OR = 1.08, 95% CI: 1.01; 1.17); eyes, ears, face, and neck (OR = 1.08, 95% CI: 1.02; 1.15); benign neoplasms tumors (OR = 1.17, 95% CI: 1.03; 1.32), musculoskeletal system (OR = 1.03, 95% CI: 1.01; 1.05); and other congenital anomalies (OR = 1.22, 95% CI: 1.15; 1.29). The associations with respiratory system, nervous system, and chromosomal anomalies were null. These findings have significant implications for public health policies aimed at mitigating the impact of environmental factors on birth outcomes, both in Brazil and globally.

Asunto(s)

Anomalías Congénitas , Exposición Materna , Humanos , Femenino , Brasil/epidemiología , Embarazo , Exposición Materna/efectos adversos , Exposición Materna/estadística & datos numéricos , Estudios de Casos y Controles , Recién Nacido , Anomalías Congénitas/epidemiología , Temperatura , Adulto , Factores de Riesgo

RESUMEN

OBJECTIVE: To evaluate the influence of environmental factors and prematurity relating to juvenile dermatomyositis (JDM), its course and refractoriness to treatment. METHODS: A case-control study with 35 patients followed up at a tertiary hospital and 124 healthy controls, all residents of São Paulo. Patients were classified according to monocyclic, polycyclic or chronic disease courses and refractoriness to treatment. The daily concentrations of pollutants (inhalable particulate matter-PM10, sulfur dioxide-SO2, nitrogen dioxide-NO2, ozone-O3 and carbon monoxide-CO) were provided by the Environmental Company of São Paulo. Data from the population were obtained through a questionnaire. RESULTS: Fifteen patients had monocyclic courses, and 19 polycyclic/chronic courses. Eighteen patients were refractory to treatment. Maternal occupational exposure to inhalable agents (OR = 17.88; IC 95% 2.15-148.16, p = 0.01) and exposure to O3 in the fifth year of life (third tertile > 86.28µg/m3; OR = 6.53, IC95% 1.60-26.77, p = 0.01) were risk factors for JDM in the multivariate logistic regression model. The presence of a factory/quarry at a distance farther than 200 meters from daycare/school (OR = 0.22; IC 95% 0.06-0.77; p = 0.02) was a protective factor in the same analysis. Prematurity, exposure to air pollutants/cigarette smoke/sources of inhalable pollutants in the mother's places of residence and work during the gestational period were not associated with JDM. Prematurity, maternal exposure to occupational pollutants during pregnancy as well as patient's exposure to ground-level pollutants up to the fifth year of life were not associated with disease course and treatment refractoriness. CONCLUSION: Risk factors for JDM were maternal occupational exposure and exposure to O3 in the fifth year of life.

Asunto(s)

Dermatomiositis , Exposición Profesional , Material Particulado , Humanos , Dermatomiositis/etiología , Femenino , Estudios de Casos y Controles , Masculino , Factores de Riesgo , Material Particulado/análisis , Material Particulado/efectos adversos , Niño , Brasil/epidemiología , Exposición Profesional/efectos adversos , Exposición Profesional/análisis , Embarazo , Ozono/análisis , Ozono/efectos adversos , Exposición Materna/efectos adversos , Monóxido de Carbono/análisis , Dióxido de Nitrógeno/análisis , Dióxido de Nitrógeno/efectos adversos , Dióxido de Azufre/análisis , Dióxido de Azufre/efectos adversos , Preescolar , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Modelos Logísticos , Nacimiento Prematuro

RESUMEN

Early life phthalates exposure has been associated with adverse respiratory outcomes. However, evidence linking prenatal phthalates exposure and childhood lung function has been inconclusive. Additionally, few studies have examined phthalates exposure as a mixture and explored sexually dimorphic associations. We aimed to investigate sex-specific associations of prenatal phthalates mixtures with childhood lung function using the PROGRESS cohort in Mexico (N = 476). Prenatal phthalate concentrations were measured in maternal urine collected during the 2nd and 3rd trimesters. Children's lung function was evaluated at ages 8-13 years. Individual associations were assessed using multivariable linear regression, and mixture associations were modeled using repeated holdout WQS regression and hierarchical BKMR; data was stratified by sex to explore sex-specific associations. We identified significant interactions between 2nd trimester phthalates mixture and sex on FEV1 and FVC z-scores. Higher 2nd trimester phthalate concentrations were associated with higher FEV1 (ß = 0.054, 95 %CI: 0.005, 0.104) and FVC z-scores (ß = 0.074, 95 % CI: 0.024, 0.124) in females and with lower measures in males (FEV1, ß = -0.017, 95 %CI: -0.066, 0.026; FVC, ß = -0.014, 95 %CI: -0.065, 0.030). This study indicates that prenatal exposure to phthalates is related to childhood lung function in a sex-specific manner.

Asunto(s)

Pulmón , Ácidos Ftálicos , Efectos Tardíos de la Exposición Prenatal , Humanos , Ácidos Ftálicos/orina , Ácidos Ftálicos/toxicidad , Femenino , Niño , México , Masculino , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Adolescente , Pulmón/efectos de los fármacos , Pulmón/fisiopatología , Exposición Materna/efectos adversos , Contaminantes Ambientales/orina , Contaminantes Ambientales/toxicidad , Pruebas de Función Respiratoria

RESUMEN

OBJECTIVE: To identify the prevalence of contamination by pesticides and their metabolites in the milk of lactating mothers in Latin America. METHODS: In this systematic review, the PubMed, LILACS, Embase, and Scopus databases were searched up to January 2022 to identify observational studies. The Mendeley software was used to manage these references. The risk of bias assessment was evaluated according to the checklist for prevalence studies and writing design, by the Prisma guidelines. RESULTS: This study retrieved 1835 references and analyzed 49 studies. 69.38% of the analyzed studies found a 100% prevalence of breast milk contamination by pesticides among their sample. Main pesticides include dichlorodiphenyltrichloroethane (DDT) and its isomers (75.51%), followed by the metabolite dichlorodiphenyldichloroethylene (DDE) (69.38%) and hexachlorocyclohexane (HCH) (46.93%). This study categorized most (65.30%) studies as having a low risk of bias. CONCLUSIONS: This review shows a high prevalence of pesticide contamination in the breast milk of Latin American women. Further investigations should be carried out to assess contamination levels in breast milk and the possible effects of these substances on maternal and child health.

Asunto(s)

Lactancia , Leche Humana , Plaguicidas , Humanos , Leche Humana/química , Femenino , América Latina , Plaguicidas/análisis , Residuos de Plaguicidas/análisis , Prevalencia , DDT/análisis , Exposición Materna/efectos adversos

RESUMEN

BACKGROUND: Metal(oid)s have been cross-sectionally associated with lung function outcomes in childhood but there is limited data on their combined effects starting in utero. Child sex may further modify these effects. OBJECTIVE: Examine associations between in utero and early life exposure to metals assessed via novel dentine biomarkers and childhood lung function and explore effect modification by child sex. METHODS: Analyses included 291 children enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a longitudinal birth cohort study in Mexico City. Weekly dentine levels of arsenic (As), cadmium (Cd), cobalt (Co), copper (Cu), manganese (Mn), nickel (Ni), and lead (Pb) were measured from 15 weeks pre-birth to 15 weeks post birth in deciduous children's teeth. Lung function was tested at ages 8-14 years and then modeled as age, height and sex adjusted z-scores. Associations were modeled using lagged weighted quantile sum (LWQS) regression to evaluate the potential for a time-varying mixture effect adjusting for maternal age and education at enrollment and exposure to environmental tobacco smoke in pregnancy. Models were also stratified by sex. RESULTS: We identified a window of susceptibility at 12-15 weeks pre-birth in which the metal mixture was associated with lower FVC z-scores in children aged 8-14 years. Cd and Mn were the largest contributors to the mixture effect (70 %). There was also some evidence of effect modification by sex, in which the mean weights and weighted correlations over the identified window was more evident in males when compared to females. In the male stratum, Cd, Mn and additionally Pb also dominated the mixture association. CONCLUSIONS: Prenatal metal(oid) exposure was associated with lower lung function in childhood. These findings underscore the need to consider both mixtures and windows of susceptibility to fully elucidate effects of prenatal metal(oid) exposure on childhood lung function.

Asunto(s)

Efectos Tardíos de la Exposición Prenatal , Humanos , Niño , Femenino , México , Masculino , Embarazo , Adolescente , Metales/análisis , Metaloides/análisis , Contaminantes Ambientales , Pulmón/efectos de los fármacos , Diente/efectos de los fármacos , Exposición Materna/estadística & datos numéricos , Estudios Longitudinales , Metales Pesados/análisis , Pruebas de Función Respiratoria

RESUMEN

Particulate matter is a type of air pollution that consists of fine particles with a diameter <2.5 µm (PM2.5), which can easily penetrate the respiratory system and enter the bloodstream, increasing health risks for pregnant women and their unborn babies. Recent reports have suggested that there is a positive association between PM2.5 exposure and adverse pregnancy outcomes. However, most evidence of this relationship comes from Western countries. Thus, the objective of this study was to evaluate the association between PM2.5 exposure during pregnancy and birth outcomes among pregnant women in Colombia. This study included 542,800 singletons born in 2019 to Colombian women, aged 15+ years, residing in 981 municipalities. Data on parental, child and birth characteristics were extracted from anonymized live birth records. Satellite-based estimates of monthly PM2.5 concentrations at the surface level were extracted for each municipality from the Atmospheric Composition Analysis Group (ACAG). PM2.5 exposure during pregnancy was indicated by the monthly average of PM2.5 concentrations across the pregnancy duration for the municipality where the child was born. The associations of municipality-level PM2.5 concentration during pregnancy with pre-term birth (PTB) and low birth weight (LBW) were tested in separate two-level logistic regression models, with babies nested within municipalities. The prevalence of PTB and LBW were 8.6 % and 8.3 %, respectively. The mean PM2.5 concentration across the 981 municipalities was 18.26 ± 3.30 µg/m3, ranging from 9.11 to 31.44 µg/m3. Greater PM2.5 concentration at municipality level was associated with greater odds of PTB (1.05; 95%CI: 1.04-1.06) and LBW (1.04; 95%CI: 1.03-1.05), after adjustment for confounders. Our findings provide new evidence on the association between PM2.5 on adverse pregnancy outcomes from a middle-income country.

Asunto(s)

Contaminantes Atmosféricos , Recién Nacido de Bajo Peso , Exposición Materna , Material Particulado , Resultado del Embarazo , Material Particulado/análisis , Femenino , Embarazo , Colombia/epidemiología , Humanos , Exposición Materna/estadística & datos numéricos , Contaminantes Atmosféricos/análisis , Resultado del Embarazo/epidemiología , Adulto , Adulto Joven , Adolescente , Contaminación del Aire/estadística & datos numéricos , Nacimiento Prematuro/epidemiología , Recién Nacido

RESUMEN

Tributyltin (TBT) is the chemical substance commonly used worldwide to prevent biofouling of vessels. Due to its ability to bioaccumulate and biomagnify, even after being banned, significant concentrations of TBT can be detected in sediment, affecting marine and human life. Although studies have shown that direct exposure to TBT alters physiological parameters in mammals, the relationship between exposure to TBT during pregnancy and lactation, considered critical windows for metabolic programming, has not been fully elucidated. Our hypothesis is that offspring whose mothers were exposed to TBT during critical stages of development may exhibit dysfunctions in endocrine-metabolic parameters. We used pregnant Wistar rats that were divided into groups and received the following treatments from gestational day 7 until the end of lactation by intragastric gavage: vehicle (ethanol 0.01%; Control), low TBT dose (100 ng/kg of body weight (bw)/day; TBT100ng) and high TBT dose (1000 ng/kg bw/day; TBT1000ng). Dams and offspring at birth and weaning (21 days old) were studied. Maternal exposure to TBT promoted dose-dependent changes in dams. The findings for adiposity, milk composition and lipid profile were more pronounced in TBT100 ng dam; however, thyroid morphology was altered in TBT1000 ng dam. Female offspring were differentially affected by the dose of exposure. At birth, females in the TBT100ng group had low body weight, lower naso-anal length (NAL), and higher plasma T4, and at weaning, females in the TBT100ng group had lower insulin and leptin levels. Females in the TBT1000ng group had lower NAL at birth and lower leptinemia and weight of white adipose tissue at weaning. Male offspring from TBT groups showed high T3 at birth, without biometric alterations at birth or weaning. Despite these findings, both sexes exhibited dose-dependent morphological changes in the thyroid gland. Thus, maternal exposure to TBT constitutes an important route of contamination for both dams and offspring.

Asunto(s)

Lactancia , Exposición Materna , Efectos Tardíos de la Exposición Prenatal , Ratas Wistar , Glándula Tiroides , Compuestos de Trialquiltina , Animales , Femenino , Compuestos de Trialquiltina/toxicidad , Ratas , Embarazo , Masculino , Glándula Tiroides/efectos de los fármacos , Lactancia/efectos de los fármacos , Animales Recién Nacidos , Disruptores Endocrinos/toxicidad , Leche/química , Leche/metabolismo

RESUMEN

BACKGROUND/AIM: Heavy metals are known to induce oxidative stress and inflammation, and the association between metal exposure and adverse birth outcomes is well established. However, there lacks research on biomarker profiles linking metal exposures and adverse birth outcomes. Eicosanoids are lipid molecules that regulate inflammation in the body, and there is growing evidence that suggests associations between plasma eicosanoids and pregnancy outcomes. Eicosanoids may aid our understanding of etiologic birth pathways. Here, we assessed associations between maternal blood metal concentrations with eicosanoid profiles among 654 pregnant women in the Puerto Rico PROTECT birth cohort. METHODS: We measured concentrations of 11 metals in whole blood collected at median 18 and 26 weeks of pregnancy, and eicosanoid profiles measured in plasma collected at median 26 weeks. Multivariable linear models were used to regress eicosanoids on metals concentrations. Effect modification by infant sex was explored using interaction terms. RESULTS: A total of 55 eicosanoids were profiled. Notably, 12-oxoeicosatetraenoic acid (12-oxoETE) and 15-oxoeicosatetraenoic acid (15-oxoETE), both of which exert inflammatory activities, had the greatest number of significant associations with metal concentrations. These eicosanoids were associated with increased concentrations of Cu, Mn, and Zn, and decreased concentrations of Cd, Co, Ni, and Pb, with the strongest effect sizes observed for 12-oxoETE and Pb (ß:-33.5,95 %CI:-42.9,-22.6) and 15-oxoETE and Sn (ß:43.2,95 %CI:11.4,84.1). Also, we observed differences in metals-eicosanoid associations by infant sex. Particularly, Cs and Mn had the most infant sex-specific significant associations with eicosanoids, which were primarily driven by female fetuses. All significant sex-specific associations with Cs were inverse among females, while significant sex-specific associations with Mn among females were positive within the cyclooxygenase group but inverse among the lipoxygenase group. CONCLUSION: Certain metals were significantly associated with eicosanoids that are responsible for regulating inflammatory responses. Eicosanoid-metal associations may suggest a role for eicosanoids in mediating metal-induced adverse birth outcomes.

Asunto(s)

Eicosanoides , Exposición Materna , Humanos , Femenino , Eicosanoides/sangre , Embarazo , Puerto Rico , Adulto , Exposición Materna/estadística & datos numéricos , Contaminantes Ambientales/sangre , Metales Pesados/sangre , Adulto Joven , Metales/sangre

RESUMEN

Autism Spectrum Disorder (ASD) belongs to the group of neurodevelopmental disorders, and has a high prevalence, affecting 1 in 100 children according to data from the World Health Organization (WHO). To be diagnosed with ASD, the child must have persistent deficits in communication and social interactions, and restricted and repetitive patterns of behavior, interests, or activities. Despite its prevalence, the etiology of ASD is still uncertain, with multifactorial characteristics, including those associated with the gestational period, where maternal exposure to biological, chemical, or physical hazards occurs, some of which have already been proposed as causes of ASD outcomes. Since pregnancy requires a balance between the maternal-fetal binomial, the breakdown of this balance caused by such environmental hazards can lead to altered fetal neurodevelopment, including ASD. With this firmly in mind, this review aims to compile the most recent data on the gestational causes that may be associated with the development of ASD to help health professionals identify risk factors and act for the prevention and management of ASD.

Asunto(s)

Trastorno del Espectro Autista , Trastornos del Neurodesarrollo , Niño , Embarazo , Femenino , Humanos , Trastorno del Espectro Autista/epidemiología , Trastorno del Espectro Autista/etiología , Trastorno del Espectro Autista/diagnóstico , Factores de Riesgo , Exposición Materna , Causalidad

RESUMEN

Previously, we found that the ultraviolet filter benzophenone-3 (BP3) causes fetal growth restriction in mice when is applied when implantation occurs (first week of gestation). However, whether BP3 can affect gestation and fertility after implantation period is unknown. We aimed to study the effects on reproductive physiology of the offspring caused by perinatal exposure to BP3. C57BL/6 pregnant mice were dermally exposed to 50 mg BP3/kg bw.day or olive oil (vehicle) from gestation day 9 (gd9) to postnatal day 21 (pnd1). We observed no differences in mother's weights, duration of gestation, number of pups per mother, onset of puberty or sex ratio. The weights of the pups exposed to benzophenone-3 were transiently lower than those of the control. Estrous cycle was not affected by perinatal exposure to BP3. Besides, we performed a fertility assessment by continuous breeding protocol: at 10 weeks of age, one F1 female and one F1 male mouse from each group was randomly chosen from each litter and housed together for a period of 6 months. We noticed a reduction in the number of deliveries per mother among dams exposed to BP3 during the perinatal period. To see if this decreased fertility could be associated to an early onset of oocytes depletion, we estimated the ovarian reserve of germ cells. We found reduced number of oocytes and primordial follicles in BP3. In conclusion, perinatal exposure to BP3 leads to a decline in the reproductive capacity of female mice in a continuous breeding protocol linked to oocyte depletion.

Asunto(s)

Benzofenonas , Ratones Endogámicos C57BL , Oocitos , Efectos Tardíos de la Exposición Prenatal , Animales , Femenino , Benzofenonas/toxicidad , Benzofenonas/administración & dosificación , Embarazo , Masculino , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Oocitos/efectos de los fármacos , Ratones , Fertilidad/efectos de los fármacos , Protectores Solares/toxicidad , Exposición Materna/efectos adversos

RESUMEN

A previous study using miRNA sequencing revealed that exposure to a mixture of phthalates during pregnancy and lactation dysregulated rno-miR-184 and rno-miR-141-3p in the ventral prostate (VP) of offspring. Here, rno-miR-184 and rno-miR-141-3 expressions were obtained by RT-qPCR in the VP of F1 males as well as in F2 offspring, aiming to establish a relationship with possible oncogenic targets through in silico analyses with multigenerational approach. Additionally, some targets were measured by western blots to highlight a possible relationship between the deregulated miRNAs and some of their targets. VP samples from rats exposed to a mixture of phthalates maternally during pregnancy and lactation (GD10 to PND21-F1) and VP from offspring (F2) were examined. The phthalate mixture at both concentrations (20 µg and 200 mg/kg/day) increased the expression of both miRNAs in the F1 (PND22 and 120) and F2 (descendants of F1-treated males) prostate. Target prediction analysis revealed that both microRNAs are responsible for modulating the expression and synthesis of 40 common targets. A phthalate target association analysis and the HPA database showed an interesting relationship among these possible miRNAs modulated targets with prostate adenocarcinoma and other oncogenic processes. Western blots showed alteration in P63, P53, WNT5, and STAT3 expression, which are targeted by the miRNAs, in the VP of F1/F2 males. The data draw attention to the epigenetic modulation in the prostate of descendants exposed to phthalates and adds to one of the few currently found in the literature to point to microRNAs signature as biomarkers of exposure to plasticizers.

Asunto(s)

MicroARNs , Ácidos Ftálicos , Efectos Tardíos de la Exposición Prenatal , Neoplasias de la Próstata , MicroARNs/genética , MicroARNs/metabolismo , Masculino , Animales , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Femenino , Ácidos Ftálicos/toxicidad , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/genética , Exposición Materna/efectos adversos , Próstata/efectos de los fármacos , Próstata/patología , Ratas Wistar , Ratas , Simulación por Computador

RESUMEN

Illicit drug use is a serious and complex public health problem, not only due to the severity of the health damage but also to the social implications, such as marginalization and drug trafficking. Currently, cocaine (COC) is among the most abused drugs worldwide with about 22 million users. Drug abuse has also been found in women during the pregnancy period, which has shed light on a new group for epidemiology. The diagnosis of COC use in these cases usually depends largely on the mother's reports, which in several cases omit or deny consumption. Therefore, considering physical-chemical methods of sample preparation and exposure biomarkers, the development of analytic toxicological methods can help to confirm drug use during pregnancy. Thus, the objective of the present work was to develop an analytical method based on dispersive liquid-liquid microextraction for the determination of COC analytes, using umbilical cord tissue as an alternative biological matrix, and detection by gas chromatography coupled to mass spectrometry. Therefore, after optimization, the dispersive liquid-liquid microextraction method was fully validated for quantification of COC, benzoylecgonine, cocaethylene, ecgonine, ecgonine methyl ester and norcocaine. The limits of detection were between 15 and 25 ng/g, the limits of quantification were 30 ng/g for ecgonine and 25 ng/g for the other analytes. Linearity ranged from the limits of quantification to 1,000 ng/g. Coefficients of variation for intra-assay precision were <18.5%, inter-assay was <8.75% and bias was <16.4% for all controls. The developed method was applied in 10 suspected positive samples, based on the mother's report and maternal urine screening and confirmation. COC, benzoylecgonine, ecgonine and ecgonine methyl ester were quantified in four umbilical cords with concentrations that ranged from 39.6 to 420.5 ng/g.

Asunto(s)

Cocaína , Cromatografía de Gases y Espectrometría de Masas , Microextracción en Fase Líquida , Intercambio Materno-Fetal , Detección de Abuso de Sustancias , Cordón Umbilical , Humanos , Cocaína/análogos & derivados , Cocaína/análisis , Femenino , Embarazo , Cordón Umbilical/química , Detección de Abuso de Sustancias/métodos , Límite de Detección , Reproducibilidad de los Resultados , Exposición Materna

RESUMEN

This study analyzed how glyphosate exposure in the gestational period affects vascular function in their female offspring and whether oxidative stress is involved in this effect. To this, pregnant Wistar rats were exposed through drinking water to 0.2% of a glyphosate commercial formulation, and we analyzed the response to acetylcholine and phenylephrine in the aorta from offspring of Glyphosate-based herbicide (O-GBH) and controls (O-CON) rats at six months of age. Relaxation to acetylcholine was reduced in O-GBH than in O-CON. Acute Indomethacin and Apocynin increased relaxation to acetylcholine in O-GBH. The aorta from O-GBH was hyperactive to phenylephrine; the preincubation with N-nitro-L-arginine methyl ester (L-NAME) increased contraction to phenylephrine more in O-CON than O-GBH. TEMPOL similarly reduced phenylephrine response, and L-NAME prevented this effect. The TBARS and GSH levels were increased in O-GBH than in O-CON. Results reinforce the concept that oxidative stress during the perinatal period contributes to the development of vascular changes in adulthood. Results also reveal that oxidative stress parameters altered, and the current levels considered safe for exposure to Glyphosate deserve further investigation, especially in the female gender.

Asunto(s)

Glifosato , Herbicidas , Embarazo , Humanos , Ratas , Animales , Femenino , Herbicidas/toxicidad , Ratas Wistar , NG-Nitroarginina Metil Éster , Exposición Materna/efectos adversos , Acetilcolina , Glicina/toxicidad , Fenilefrina/toxicidad

RESUMEN

Prenatal fine particulate matter (PM2.5) and maternal psychological functioning have been associated with child cognitive outcomes, though their independent and joint impacts on earlier behavioral outcomes remains less studied. We used data from 382 mother-child pairs from a prospective birth cohort in Mexico City. Temperament was measured at 24 months using the Carey Toddler Temperament Scale (TTS). Exploratory factor analysis (EFA) was used to update the factor structure of the TTS. During pregnancy, mothers completed the Crisis in Family Systems-Revised, Edinburgh Depression Scale, pregnancy-specific anxiety scale, and the Perceived Stress Scale. Pregnancy PM2.5 was assessed using estimates from a satellite-based exposure model. We assessed the association between prenatal maternal stress and PM2.5 on temperament, in both independent and joint models. Quantile g-computation was used to estimate the joint associations. Models were adjusted for maternal age, SES, education, child sex, and child age. In EFA, we identified three temperament factors related to effortful control, extraversion, and negative affect. Our main results showed that higher levels of PM2.5 and several of the maternal psychological functioning measures were related to both effortful control and negative affect in the child, both individually and as a mixture. For instance, a one quartile increase in the prenatal mixture was associated with higher negative affect scores in the child (0.34, 95% CI: 0.16, 0.53). We observed modification of these associations by maternal SES, with associations seen only among lower SES participants for both effortful control (-0.45, 95% CI: -0.70, -0.20) and negative affect outcomes (0.60, 95% CI: 0.35, 0.85). Prenatal PM2.5 and maternal psychological functioning measures were associated with toddler temperament outcomes, providing evidence for impacts of chemical and non-chemical stressors on early child health.

Asunto(s)

Material Particulado , Efectos Tardíos de la Exposición Prenatal , Estrés Psicológico , Temperamento , Humanos , Femenino , Embarazo , Material Particulado/análisis , Efectos Tardíos de la Exposición Prenatal/psicología , Preescolar , Adulto , Masculino , México/epidemiología , Estudios Prospectivos , Contaminantes Atmosféricos/análisis , Exposición Materna/efectos adversos , Adulto Joven

RESUMEN

BACKGROUND: Pesticide exposure may affect young children's neurodevelopment, but only few cohort studies have addressed possible effects of non-organophosphate pesticides. OBJECTIVE: We evaluated associations between prenatal current-use pesticide exposure and neurodevelopmental outcomes among 1-year-old children from the Infants' Environmental Health (ISA) birth cohort. METHODS: To determine prenatal pesticide exposure, we measured biomarkers of pyrimethanil, chlorpyrifos, synthetic pyrethroids, and 2,4-D in urine samples among 355 women, 1-3 times during pregnancy. One-year post-partum, we evaluated children's neurodevelopment with the Bayley Scales of Infant and Toddler Development 3rd edition (BSID-III). We assessed associations between exposures and neurodevelopmental outcomes (composite and z-scores) using single-chemical linear regression models adjusted for possible confounders (maternal education, parity, sex, gestational age at birth, child age, HOME-score, location of assessment, biomarkers of mancozeb), and studied effect-modification by sex. We evaluated non-linear associations of multiple pesticide exposures with Bayesian kernel machine regression (BKMR). RESULTS: We found higher prenatal urinary 2,4-D concentrations were associated with lower language (ßper ten-fold increase = -2.0, 95 % confidence interval (CI) = -3.5, -0.5) and motor (ßper ten-fold increase = -2.2, 95 %CI = -4.2, -0.1) composite scores among all children. Also, higher chlorpyrifos exposure [measured as urinary 3,5,6-trichloro-2-pyridinol (TCPy)] was associated with lower cognitive composite scores (ßper ten-fold increase = -1.9, 95 %CI = -4.7, 0.8), and lower motor composite scores among boys (ßper ten-fold increase = -3.8, 95 % CI = -7.7, 0.1) but not girls (ßper ten-fold increase = 2.3, 95 %CI = -1.6, 6.3, pINT = 0.11). Finally, higher pyrimethanil was associated with lower language abilities among girls, but not boys. Pyrethroid metabolite concentrations did not explain variability in BSID-III composite scores. Associations were similar for BSID-III z-scores, and we found no evidence for non-linear associations or mixture effects. DISCUSSION: Prenatal exposure to common-use pesticides may affect children's neurodevelopment at 1-year of age, some effects may be sex-specific.

Asunto(s)

Desarrollo Infantil , Plaguicidas , Efectos Tardíos de la Exposición Prenatal , Humanos , Femenino , Embarazo , Lactante , Plaguicidas/orina , Plaguicidas/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/epidemiología , Masculino , Desarrollo Infantil/efectos de los fármacos , Costa Rica , Exposición Materna/efectos adversos , Cohorte de Nacimiento , Contaminantes Ambientales/orina , Adulto , Estudios de Cohortes , Adulto Joven