Postnatal Exposure Research Articles

Effect modifications of parents’ age at childbirth on association between ambient particulate matter and children obesity

BackgroundThere is limited evidence regarding the modifying effects of parents’ age at childbirth on the relationship between air pollution and obesity in plateau areas. This study aimed to explore the association between particulate matter (PM) and child obesity, specifically investigating whether parents’ age at childbirth could modify this relationship in the Tibetan plateau, China.MethodsSatellite-based random forest models were used to estimate the concentrations of PM2.5 (particulate matter with aerodynamic diameters ≤ 2.5 μm), PMc (particulate matter with aerodynamic diameters between 2.5 μm and 10 μm), and PM10 (particulate matter with aerodynamic diameters ≤ 10 μm). Linear and logistic regression models were employed to assess associations between PM exposure and obesity indicators, and effect estimates of PM across different particle sizes were compared.ResultsThe study comprised 2,015 children under five years old. Postnatal exposure to PM was positively associated with overweight and obesity (OWO), waist-to-hip ratio (WHR) and body mass index (BMI). Among these pollutants, PM10 exhibited the strongest association with BMI and OWO, whereas PMc showed the strongest association with WHR. An interquartile range (IQR) increase in PM2.5 (5.67 µg/m3), PMc (5.25 µg/m3), and PM10 (11.06 µg/m3) was positively associated with OWO (odd ratio [OR] for PM2.5 = 1.52, 95% confidence interval [CI] for PM2.5 = 1.24 to 1.85; OR for PMc = 1.50, 95% CI for PMc = 1.19 to 1.88; OR for PM10 = 1.56, 95% CI for PM10 = 1.25 to 1.96), respectively. Stratified analysis by parents’ age at childbirth indicated that the effects of PM on obesity indicators were more pronounced in the advanced age group.ConclusionsLong-term exposure to PM was positively associated with OWO, WHR, and BMI. Our findings also underscore the importance of examining the effects of ambient PM exposure on OWO, particularly in parents of advanced age at childbirth.

Impact of maternal high-fat diet on offspring gut microbiota during short-term high-fat diet exposure in mice.

Alterations in the gut microbiome have been linked to obesity, with maternal high-fat diet (HF) playing a role in shaping offspring microbiome composition. However, the sex-specific responses to maternal HF diet and the impact of subsequent dietary challenges remain unclear. This study investigated the effects of maternal HF diet on offspring gut microbiota structure and predicted functional profile in response to short-term postnatal HF diet exposure with a focus on sex-specific responses. Female and male offspring of maternal control (C) diet or maternal HF diet were weaned onto C diet or HF diet. Offspring were euthanized at 13 weeks of age and cecal contents were collected for bacterial taxonomic profiling. Maternal HF diet reduced α-diversity, notably in male offspring weaned onto HF diet. Sex-specific differences were observed in the gut microbial composition and predicted functional potential. Furthermore, the influence of maternal diet on bacterial community structure and functional potential varied depending on postnatal diet. Maternal HF diet led to increased relative abundance of Corynebacterium in female offspring and decreased abundance of Akkermansia and Roseburia in male offspring. These findings underscore the sexually dimorphic nature of maternal HF diet effects on gut microbiota composition and function, with implications for developmental programming and metabolic health.

Windows of susceptibility and joint effects of prenatal and postnatal ambient air pollution and temperature exposure on asthma and wheeze in Mexican children

IntroductionPrenatal and early-life exposure to air pollution and extreme temperatures are associated with childhood asthma and wheeze. However, potential windows of susceptibility and their sex-specific and interactive effects have not been fully elucidated. We aimed to identify critical windows of susceptibility and evaluate sex-specific effects in these associations, and evaluate exposure interactions. MethodsWe analyzed data from 468 mother–child pairs enrolled in the PROGRESS birth cohort in Mexico City. Daily residential levels of PM2.5, NO2, and temperature were generated from our validated spatiotemporally resolved models from conception to age 4 years. Childhood asthma and wheeze outcomes were collected at 4–6 and 7–8 years. Distributed lag nonlinear models (DLNMs) were used to identify susceptible windows for prenatal weekly-specific and postnatal monthly-specific associations of air pollution and temperature with respiratory outcomes adjusting for covariates. To evaluate sex-specific effects, DLNMs were stratified. Joint effects were assessed using relative excess risk due to interaction and attributable proportion. ResultsMid-gestation was a critical window for both PM2.5 (weeks 20–28, cumulative OR: 1.18 [95% CI: 1.01, 1.37]; weeks 19–26, cumulative OR: 1.18 [95% CI: 1.02, 1.36]) and NO2 (weeks 18–25, cumulative OR: 1.16 [95% CI: 1.02, 1.31]) exposure, associated with higher odds of wheeze. Postnatal exposure to PM2.5 and NO2 during the first year of life was also linked to higher odds of wheeze. The warmer and colder temperatures showed mixed effects on respiratory outcomes. We observed a synergistic interaction between high PM2.5 and high temperature exposure during the first year of life, associated with higher odds of current wheeze. The associations of prenatal air pollution and temperature exposure with respiratory outcomes were more pronounced in males. ConclusionsEarly-life air pollution exposure contributes to the development of childhood asthma and wheeze, while exposure to temperature showed mixed associations with respiratory outcomes.

Associations between pre- and post-natal exposure to phthalate and DINCH metabolites and gut microbiota in one-year old children

The gut microbiota is a collection of symbiotic microorganisms in the gastrointestinal tract. Its sensitivity to chemicals with widespread exposure, such as phthalates, is little known. We aimed to investigate the impact of perinatal exposure to phthalates on the infant gut microbiota at 12 months of age. Within SEPAGES cohort (Suivi de l’Exposition à la Pollution Atmosphérique durant la Grossesse et Effet sur la Santé), we assessed 13 phthalate metabolites and 2 di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) metabolites in repeated urine samples collected in pregnant women and their offspring. We obtained stool samples from 356 children at 12 months of age and sequenced the V3-V4 region of the 16S rRNA gene, allowing gut bacterial profiling. We used single-chemical (linear regressions) and mixture (BKMR, Bayesian Kernel Machine Regression) models to examine associations of phthalates and DINCH metabolites, with gut microbiota indices of α-diversity (specific richness and Shannon diversity) and the relative abundances of the most abundant microbiota phyla and genera. After correction for multiple testing, di(2-ethylhexyl) phthalate (ΣDEHP), diethyl phthalate (DEP) and bis(2-propylheptyl) phthalate (DPHP) metabolites 12-month urinary concentrations were associated with higher Shannon α-diversity of the child gut microbiota in single-chemical models. The multiple-chemical model (BKMR) suggested higher α-diversity with exposure to the phthalate mixture at 12 months, driven by the same phthalates. There were no associations between phthalate and DINCH exposure biomarkers at other time points and α-diversity after correction for multiple testing. ΣDEHP metabolites concentration at 12 months was associated with higher Coprococcus genus. Finally, ΣDEHP exposure at 12 months tended to be associated with higher phylum Firmicutes, an association not maintained after correction for multiple testing. Infancy exposure to phthalate might disrupt children's gut microbiota. The observed associations were cross-sectional, so that reverse causality cannot be excluded.

Prenatal tobacco and tobacco-Cannabis co-exposure and unpredictability in maternal anger/hostility: Implications for toddler reactivity

Tobacco and cannabis are frequently used together during pregnancy. However, relatively little is known about how co-use and related maternal risk factors impact toddler reactivity. One understudied risk factor is maternal experience of anger/hostility, despite evidence suggesting that individuals who use substances experience more anger/hostility. In addition, mood unpredictability in anger/hostility (MUA), a relatively novel construct, may be particularly important for mothers who use substances as they attempt to cut down or quit during pregnancy and may also impact toddler reactivity. Importantly, prenatal exposures may also impact toddler outcomes via continued postnatal exposure and infant reactivity. We examined a conceptual model linking prenatal tobacco and tobacco-cannabis co-use, maternal anger/hostility, and unpredictability in anger/hostility with toddler reactivity in a sample (N = 247 at recruitment, 190 at toddler age; N = 247 for model testing) of dyads recruited during the first trimester of pregnancy into a tobacco group (use of combustible cigarettes; including sub-group of women who also used cannabis) and a non-substance use group. Results indicated a direct effect of prenatal co-exposure on blunted toddler reactivity for males only. Mothers who used substances prenatally had the highest levels of anger/hostility and MUA. Prenatal anger/hostility and MUA were associated with higher reactivity at infancy which in turn, was associated with higher toddler reactivity. Prenatal co-exposure and higher prenatal maternal anger/hostility was associated with continued postnatal exposure to cannabis which in turn, was associated with higher reactivity at toddlerhood. Results highlight the importance of examining prenatal co-exposure and continued postnatal cannabis exposure as well as associated maternal risk factors such as anger/hostility and MUA for toddler developmental outcomes.

Association Between Ambient Air Pollution and Attention-Deficit/Hyperactivity Disorder (ADHD) in Children: A Systematic Review and Meta-Analysis.

The objective of this systematic review and meta-analysis was to assess the association between postnatal exposure to ambient air pollutants (particulate matter (PM)2.5, PM10, nitrogen dioxide (NO2)) and the risk of attention-deficit/hyperactivity disorder (ADHD) in children. Observational studies, including cohort, case-control, and cross-sectional designs, that examined the relationship between postnatal exposure to ambient air pollution and ADHD in children were included, while studies focusing on prenatal exposure or unrelated neurodevelopmental outcomes were excluded. A comprehensive search of databases including PubMed, Web of Science, Embase, and Ovid, last updated in May 2024, was conducted. The risk of bias in the selected studies was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools, with discrepancies resolved through discussion among four reviewers. A meta-analysis was performed, synthesizing results using hazard ratios (HR), odds ratios (OR), and risk ratios (RR) as effect sizes. Random effects models were applied in most analyses due to the expected variability between studies, while fixed effects models were employed where only two studies were available. A total of 25 studies were included, with sample sizes ranging from 174 to 35,103 children. The studies were conducted in different countries and varied in their design and pollutant exposure measurement methods. The meta-analysis demonstrated a significant association between PM2.5 exposure and ADHD, with moderate heterogeneity (I² = 74.2%). PM10 exposure was also significantly associated with ADHD, and the heterogeneity was reduced to 34.94% after excluding an influential outlier. NO2 exposure similarly showed a significant association with ADHD, with low heterogeneity (I² = 0%). Due to the limited number of studies per pollutant (ranging from two to six), publication bias was not assessed. Despite the significant findings, there were limitations, including moderate to high heterogeneity among studies and the small number of studies per pollutant, which restricted the ability to assess publication bias and impacted the robustness of the results. Differences in exposure measurement methods and study designs also contributed to variability in the findings. Nonetheless, the evidence suggests that postnatal exposure to ambient air pollutants, particularly PM2.5, PM10, and NO2, is significantly associated with an increased risk of ADHD in children. These results underscore the importance of conducting further large-scale, high-quality studies to explore these associations in greater depth and to elucidate the mechanisms underlying the link between air pollution and ADHD.

Ambient temperature exposure and rapid infant weight gain.

Childhood obesity is a major public health concern, and the global rate is rising. Rapid infant weight gain is a risk factor for later overweight. Studies have linked prenatal ambient temperature exposure to fetal growth, and preliminary evidence suggests postnatal exposure may be associated with infant weight gain. Using a population-based historical cohort study including 1100576 infants born 2011-2019, we assessed the relationship between prenatal and one-month postnatal ambient temperature exposure and rapid infant weight gain. We used a hybrid spatiotemporal model to assess temperatures at the family's recorded residence at birth. Repeated weight measurements between birth and 15 months were used to model the outcome using the SuperImposition by Translation and Rotation (SITAR) method. We employed generalized linear models and distributed lag models to estimate the association between prenatal and postnatal exposure and rapid infant weight gain, defined as the upper tertile of the SITAR growth velocity. Overall, higher ambient temperatures were associated with rapid infant weight gain. The cumulative adjusted relative risk for the highest exposure quintile during pregnancy compared with the lowest quintile was 1.33 [95% confidence interval (CI): 1.25, 1.40], and the corresponding association for the first postnatal month was 1.19 (95% CI: 1.15, 1.23). Exposure to high ambient temperature during early and mid-pregnancy, as well as the first postnatal month, was associated with rapid weight gain, while during late pregnancy, exposure to low temperatures was associated with this outcome. Prenatal and postnatal ambient temperatures are associated with rapid infant weight gain.

Cancer mortality risk in the Urals Cohort of Exposed Population Offspring

The objective of the study is to analyze solid cancer mortality and estimate the risk value of solid cancer mortality in the offspring of parents irradiated in the Southern Urals, depending on the dose to the parents' gonads as well as to conduct a preliminary assessment of the mortality risk from cancer of individual locations depending on the gonadal dose. The issue of the transgenerational effects of the human gonad exposure is still very important. There exists conclusive evidence of the presence of such effects in experimental animals. However, there is no proof of the existence of these effects in humans despite a great number of research on this subject. International scientific community and international organizations, UNSCEAR and ICRP being among them, regard this issue as the one that has not been solved yet and requires further studies. Urals Cohort of offspring of the population exposed on the Techa River and on the territory of the East Ural radioactive trace was established in the Urals research Center for Radiation medicine in 2022. The key feature of the cohort is the exclusion of the offspring with postnatal exposure. The size of the cohort as of September 2023 is 31,154 persons. The number of person-years over the whole follow-up period from 1950 through 2020 is 1 226 380. Mean dose to the gonads of mothers of all the cohort members is 41 mGy, to those of the fathers' — 35 mGy, mean combined gonad dose is 76 mGy. Over the whole follow-up period 3,774 deaths from all causes including 284 deaths from solid cancers were registered in the cohort. The mean age of the cohort members at the end of the follow-up period was 42 years. The risk of death was analyzed using Poisson regression by the programs of the EPICURE statistical software package. Three models of dose dependence were tested: linear, quadratic, and linear-quadratic models of paternal gonadal dose, maternal gonadal dose, and total gonadal dose. Mortality risk analysis of all solid cancers in the offspring cohort showed no statistically significant effect with parental gonadal dose (we have obtained positive although statistically insignificant values of solid cancers mortality risk) which is consistent with the results of other studies in human populations. At the same time, the analysis for the first time obtained a statistically significant linear dependence of the solid cancer mortality risk in offspring with father's age over 45 years depending on the dose to the father's gonads. The excess relative risk of death was 8.09/Gy, (0.51-22.93), p < 0.05. Also, for the first time, evidence of dose dependence of the mortality risk of lung cancer in male offspring on maternal gonadal dose, paternal gonadal dose, and combined gonadal dose was obtained. The values of excess relative risk of lung cancer and 95% confidence intervals according to the linear model were 5.39/Gy (0.46; 15.56) from paternal gonad dose, 4.36/Gy (0.15; 13.48) from maternal gonad dose, and - 3.95/Gy (0.55; 12.14) from combined gonad dose. Point risk estimates of lung cancer at this stage are characterized by wide confidence intervals and require additional studies to assess the influence of possible effect modifiers, but with a high degree of probability indicate the presence of dose dependence of this effect. Increasing the follow-up period and attained age, will increase the number of cancers in the future and will reduce dose response uncertainties and provide more accurate estimates of the risk of death in the offspring cohort.

A New Plant Active Polysaccharide from Nicotiana Improves the Lead-Led Impairment of Spatial Memory in Mice by Modulating the Gut Microbiota and IL-6.

Active polysaccharides from plants are broadly applied in the food and health industry. The purpose of this study is to identify a new plant active polysaccharide and to investigate its role in modulating spatial memory. Ultrasonics and DEAE-52 chromatography were used to separate and purify the plant active polysaccharide (PAP). Mice were exposed to 100 ppm of lead acetate from birth to 7 weeks old to establish the memory impairment model. PAPs with concentrations of 200 or 400 ppm were fed to the subject mice each day after weaning in a spatiotemporally separated fashion. At the end of the intervention, mice were examined using the Morris water maze test, microbiome sequencing, cytokine profiling and protein analysis. The derived active polysaccharide was constituted by β-anomeric carbon, indicating a new form of PAP. The PAP significantly ameliorates the memory impairment caused by postnatal lead exposure, as evidenced by the preferred coverage of the test mouse in the hidden platform, demonstrating salient neuroregulatory activity. In terms of the gut microbiome in response to PAP treatment, it was found that the 400 ppm PAP reversed the gut dysbiosis, producing a comparable structure to the intact animals, represented by the relative abundance of Firmicutes and Muribaculum, Desulfovibrio, etc. For cytokines, the PAP reversed the plasma levels of IL-6, suggesting an anti-inflammatory trend in the context of proinflammation caused by lead invasion. By injecting an IL-6 antagonist, Tocilizumab, into the deficient mice, the spatial memory was significantly repaired, which demonstrates the central roles of IL-6 in mediating the positive effect of the PAP. Finally, a histone modification mark, H3K27me3, was found to be potent in responding to the signals conveyed by the PAP. The PAP could improve the memory deficits by remodeling the gut-brain axis centered at the microbiota and IL-6, which is regarded as an important cytokine-modulating brain activity. This is an intriguing instance linking neuromodulation with the active polysaccharide, shedding light on the innovative applications of plant polysaccharides due to the scarcity of similar phenotypic connections.

Prenatal and postnatal cocaine exposure enhances the anxiety- and depressive-like behaviors in rats: An ontogenetic study.

Prenatal and postnatal exposure to drugs such as cocaine is a public health problem that causes deficits in brain development and function in humans and animals. One of the main effects of prenatal and postnatal cocaine exposure is increased vulnerability to developing the substance use disorder at an early age. Furthermore, the negative emotional states associated with cocaine withdrawal increase the fragility of patients to relapse into drug abuse. In this sense, prenatal and postnatal cocaine exposure enhanced the cocaine- and nicotine-induced locomotor activity and locomotor sensitization, and rats exposed prenatally to cocaine displayed an increase in anxiety- and depressive-like behaviors in adulthood (PND 60-70). Therefore, the objective of this study was to determine the effect of prenatal and postnatal cocaine exposure on anxiety- and depressive-like behaviors at different ages (30, 60, 90, and 120 days of age) in rats. The study was divided into two stages: prenatal and postnatal. In the prenatal stage, a group of pregnant female Wistar rats was administered daily from GD0 to GD21 cocaine (cocaine pre-exposure group), and another group of pregnant female rats was administered daily saline (saline pre-exposure group). In the postnatal stage, during lactation (PND0 to PND21), pregnant rats received administration of cocaine or saline, respectively. Of the litters resulting from the cocaine pre-exposed and saline pre-exposed pregnant female groups, only the male rats were used for the recording of the anxiety- and depressive-like behaviors at different postnatal ages (30, 60, 90, and 120 days), representative of adolescence, adult, adulthood, and old age. The study found that prenatal and postnatal cocaine exposure generated age-dependent enhancement in anxiety- and depressive-like behaviors, being greater in older adult (PND 120) rats than in adolescent (PND 30) or adults (PND 60-90) rats. This suggests that prenatal and postnatal cocaine exposure increases anxiety- and depressive-like behaviors, which may increase the vulnerability of subjects to different types of drugs in young and adult age.

Maternal exposure to smoking and wheezing phenotypes in children: a cohort study of the Japan Environment and Children’s Study

BackgroundPrevious studies have shown that prenatal maternal smoking and maternal secondhand smoke exposure during pregnancy were associated with an increased risk of wheezing and asthma development. However, few studies have examined the influence of different sources of tobacco exposure in different perinatal timeframes (preconception, prenatal, and postnatal) on wheezing phenotypes in children. Using national survey data from Japan, we investigated the effects of exposure to tobacco smoke during pregnancy on wheezing phenotypes in children before the age of 3 years.MethodsPregnant women who lived in the 15 regional centers in the Japan Environment and Children’s Study were recruited. We obtained information on prenatal and postnatal exposure to active and secondhand smoke (SHS) and wheeze development up to 3 years of age. Multiple logistic regression analysis was performed to determine the association between tobacco smoke exposure and wheezing phenotypes in children.ResultsWe analyzed 73,057 singleton births and identified four longitudinal wheezing phenotypes: never wheezing; early transient wheezing (wheezing by age 1 year but not thereafter); late-onset wheezing (wheezing by age 2–3 years but not beforehand); and persistent wheezing. Maternal smoking during pregnancy was significantly associated with early transient and persistent wheezing in children compared with no maternal smoking [early transient wheezing: 1–10 cigarettes per day, adjusted odds ratio (aOR) 1.43, 95% confidence interval (CI) 1.23–1.66; ≥ 11 cigarettes per day, aOR 1.67, 95% CI 1.27–2.20; persistent wheezing: 1–10 cigarettes per day, aOR 1.64, 95% CI 1.37–1.97; ≥ 11 cigarettes per day, aOR 2.32, 95% CI 1.70–3.19]. Smoking cessation even before pregnancy was also significantly associated with increased risk of early transient wheezing, late-onset wheezing, and persistent wheezing in children. Moreover, maternal exposure to SHS during pregnancy was significantly associated with increased risk of early transient and persistent wheezing compared with no such exposure.ConclusionsMaternal smoking before and throughout pregnancy was associated with wheeze development in children up to 3 years of age. It appears that smoking is detrimental compared to never smoking, regardless of whether individuals quit smoking before or after becoming aware of the pregnancy.

Postnatal Allergic Inhalation Induces Glial Inflammation in the Olfactory Bulb and Leads to Autism-Like Traits in Mice

Autism spectrum disorder (ASD) is one of the most prevalent neurodevelopmental disorders. To explore its pathophysiology, we investigated the association between neonatal allergic exposure and behavioral changes. Adult female C57BL/6J mice were immunized with adjuvant (aluminum hydroxide) or ovalbumin emulsified with adjuvant. After immunization, the mice were mated, and offspring were born at full term. The postnatal dams and infants were then simultaneously exposed to an allergen (ovalbumin) or vehicle via inhalation. After weaning, behavioral testing and histopathological analyses were conducted on male offspring. Compared with the vehicle-exposed offspring, the ovalbumin-exposed offspring had decreased sociability and increased repetitive behavior, thus representing an ASD-like phenotype in mice. Moreover, histopathological analyses revealed that the ovalbumin-exposed mice had increased astroglial, microglial, and eosinophilic infiltration in the olfactory bulb, as well as increased eosinophils in the nasal mucosa. The ovalbumin-exposed mice also had decreased dendritic spine density and a lower proportion of mature spines, suggesting the impairment of stimulus-induced synaptogenesis. In conclusion, postnatal allergic exposure induced an ASD-like phenotype, as well as allergic rhinitis, which was followed by glial inflammation in the olfactory bulb parenchyma.

Biospecimens in the HEALthy Brain and Child Development (HBCD) Study: Rationale and protocol

The HEALthy Brain and Child Development (HBCD) Study, a multi-site prospective longitudinal cohort study, will examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally and planned through early childhood. The longitudinal collection of biological samples from over 7000 birthing parents and their children within the HBCD study enables research on pre- and postnatal exposures (e.g., substance use, toxicants, nutrition), and biological processes (e.g., genetics, epigenetic signatures, proteins, metabolites) on neurobehavioral developmental outcomes. The following biosamples are collected from the birthing parent: 1) blood (i.e., whole blood, serum, plasma, buffy coat, and dried blood spots) during pregnancy, 2) nail clippings during pregnancy and one month postpartum, 3) urine during pregnancy, and 4) saliva during pregnancy and at in-person postnatal assessments. The following samples are collected from the child at in-person study assessments: 1) saliva, 2) stool, and 3) urine. Additionally, placenta tissue, cord blood, and cord tissue are collected by a subset of HBCD sites. Here, we describe the rationale for the collection of these biospecimens, their current and potential future uses, the collection protocol, and collection success rates during piloting. This information will assist research teams in the planning of future studies utilizing this collection of biological samples.

Prenatal exposure to PM2.5 led to impaired respiratory function in adult mice

BackgroundPM2.5 is a complex mixture, with water-soluble inorganic ions (WSII), mainly NH4+, SO42−, and NO3−, constituting major components. Early-life PM2.5 exposure has been shown to induce adverse health consequence but it is difficult to determine whether such an effect occurs prenatally (preconception, gestational) or postnatally in human studies. MethodsFour groups of C57BL/6 J mice were assigned to four exposure conditions: PM2.5 NO3−, PM2.5 SO42−, PM2.5 NH4+ and clean air, and exposure started at 4 weeks old. At 8 weeks old, mice bred within group. The exposure continued during gestation. After delivery, both the maternal and F1 mice (offspring) were kept in clean air without exposure to PM2.5. Respiratory function and pulmonary pathology were assessed in offspring mice at 8 weeks of age. In parallel, placenta tissue was collected for transcriptome profiling and mechanistic investigation. ResultsF1 mice in PM2.5 NH4+, SO42- and NO3− groups had 32.2 % (p=6.0e-10), 30.3 % (p=3.8e-10) and 16.9 % (p=5.7e-8) lower peak expiratory flow (PEF) than the clean air group. Importantly, the exposure-induced lung function decline was greater in male than female offspring. Moreover, exposure to PM2.5 WSII before conception and during gestation was linked to increased airway wall thickness and elevated pulmonary neutrophil and macrophage counts in the offspring mice. At the molecular level, the exposure significantly disrupted gene expression in the placenta, affecting crucial functional pathways related to sex hormone response and inflammation. ConclusionsPM2.5 WSII exposure during preconception and gestational period alone without post-natal exposure substantially impacted offspring’s respiratory function as measured at adolescent age. Our results support the paradigm of fetal origin of environmentally associated chronic lung disease and highlight sex differences in susceptibility to air pollution exposure.

Development and child health in a world of synthetic chemicals.

Chemical pollution is one of today's most significant threats to the developmental potential of children worldwide. Maternal exposure to toxicants can perturb sensitive windows of fetal development, indirectly through promoting antenatal disorders, abnormal placental adaptation, or directly through maternal-fetal transport. Current evidence clearly shows that persistent organic chemicals promote hypertensive disorders of pregnancy, placental abnormalities, and fetal growth restriction, whereas findings are less consistent for phthalates and bisphenols. Prospective birth cohorts strongly support a link between adverse neurodevelopmental outcomes and prenatal exposure to flame retardants and organophosphate pesticides. Emerging evidence reveals a potential association between in utero exposure to bisphenols and childhood behavioral disorders, while childhood metabolic health is more consistently associated with postnatal exposure to phthalates and bisphenols. IMPACT: Synthesizes emerging evidence linking modern forms of chemical pollution to antenatal disorders, fetal growth restriction and childhood disorders. Highlights potential developmental impacts of emerging pollutants of concern now ubiquitous in our environment but without regulatory restrictions.

Early Life Neuroimaging: The Generalizability of Cortical Area Parcellations Across Development.

The cerebral cortex comprises discrete cortical areas that form during development. Accurate area parcellation in neuroimaging studies enhances statistical power and comparability across studies. The formation of cortical areas is influenced by intrinsic embryonic patterning as well as extrinsic inputs, particularly through postnatal exposure. Given the substantial changes in brain volume, microstructure, and functional connectivity during the first years of life, we hypothesized that cortical areas in 1-to-3-year-olds would exhibit major differences from those in neonates and progressively resemble adults as development progresses. Here, we parcellated the cerebral cortex into putative areas using local functional connectivity gradients in 92 toddlers at 2 years old. We demonstrated high reproducibility of these cortical regions across 1-to-3-year-olds in two independent datasets. The area boundaries in 1-to-3-year-olds were more similar to adults than neonates. While the age-specific group parcellation fitted better to the underlying functional connectivity in individuals during the first 3 years, adult area parcellations might still have some utility in developmental studies, especially in children older than 6 years. Additionally, we provided connectivity-based community assignments of the parcels, showing fragmented anterior and posterior components based on the strongest connectivity, yet alignment with adult systems when weaker connectivity was included.

Gestational and postnatal exposure to wildfire smoke and prolonged use of respiratory medications in early life

As wildfire frequency and severity increases, smoke exposures will cause increasingly more adverse respiratory effects. While acute respiratory effects of smoke exposure have been documented in children, longer term sequelae are largely unstudied. Our objective here was to examine the association between gestational and postnatal exposure to wildfire smoke and prolonged use of prescription medication for respiratory conditions in early childhood. Using Merative MarketScan claims data, we created cohorts of term children born in western states between 1 January 2010-31 December 2014 followed for at least three years. Using NOAA Hazard Mapping System data, we determined the average number of days a week that >25% of the population in a metropolitan statistical area (MSA) was covered by smoke within each exposure period. The exposure periods were defined by trimester and two 12 week postnatal periods. Medication use was based on respiratory indication (upper respiratory, lower respiratory, or any respiratory condition) and categorized into outcomes of prolonged use (⩾30 d use) (PU) and multiple prolonged uses (at least two prolonged uses) (MPU). We used logistic regression models with random intercepts for MSAs adjusted for child sex, birth season, and birth year. Associations differed by exposure period and respiratory outcome, with elevated risk of MPU of lower respiratory medications following exposure in the third trimester and the first 12 postnatal weeks (RR 1.15, 95% CI 0.98, 1.35; RR 1.21, 95% CI 1.05, 1.40, respectively). Exposure in the third trimester was associated with an increase in MPU of any respiratory among males infants only (male RR 1.22, 95% CI 1.00, 1.50; female RR 0.93, 95% CI 0.66, 1.31). Through novel use of prescription claims data, this work identifies critical developmental windows in the 3rd trimester and first 12 postnatal weeks during which environmental inhalational disaster events may impact longer-term respiratory health.

Prenatal and Postnatal Exposure to Antibiotics and the Risk of Type 1 Diabetes in Finnish Children: A Registry-based Study

ObjectiveTo study whether prenatal and postnatal exposure to antibiotics is associated with the risk of type 1 diabetes in childhood. Study designA case-cohort study including 2,869 children diagnosed with type 1 diabetes by the end of 2009, born January 1, 1996, to December 31, 2008, in Finland and a reference cohort (n =74,263) representing 10% of each birth cohort. Exposure to antibiotics was assessed in different time periods. The data were derived from Special Reimbursement Register, Drug Prescription Register, and Population Register and analyzed with weighted Cox proportional hazards regression models. ResultsExposure to any antibiotics before or during pregnancy, in the neonatal ward, during the first year of life, or during the two first years of life, was not associated with the risk of type 1 diabetes in the offspring. Exposure to macrolides in the year preceding pregnancy (adjusted HR 1.17 [95% CI 1.02, 1.33]) and to sulfonamides and trimethoprim during pregnancy (adjusted HR 1.91 [1.07, 3.41]) was associated with an increased risk of type 1 diabetes in the offspring. Exposure to sulfonamides and trimethoprim during first two years of life was associated with decreased risk of type 1 diabetes (adjusted HR 0.84 [0.73, 0.97]). Number of antibiotic purchases among mothers or children was not associated with type 1 diabetes risk. ConclusionsPrenatal and postnatal exposure to antibiotics in general did not increase the risk of type 1 diabetes in the offspring. However, type of antibiotic and timing of exposure may play a role in type 1 diabetes risk.

Influences of quality of maternal care and environmental enrichment on associative memory function in rats with early life lead exposure.

Children in low socioeconomic status (SES) communities are at higher risk of exposure to lead (Pb) and potentially more severe adverse outcomes from Pb exposures. While the factors encompassing SES are complex, low SES households often have less enriching home environments and parent-child interactions. This study investigated the extent to which environmental/behavioral factors (quality of maternal care and richness of the postnatal environment) may modify adverse effects from Pb exposure. Long-Evans female rats were randomly assigned to Control (no Pb), Early Postnatal (EPN: birth through weaning), or Perinatal (PERI: 14 days pre-mating through weaning) Pb exposure groups. From postnatal days (PNDs) 2-9, maternal care behaviors were observed, and dams were classified as low or high maternal care based on amounts of licking/grooming and arched back nursing. At weaning, pups were randomly assigned to enriched or non-enriched environments. At PND 55, animals began trace fear conditioning and associative memory was tested on days 1, 2, and 10 postconditioning. Control offspring showed no significant effects of maternal care or enrichment on task performance. Females with EPN-Pb exposure and males with PERI-Pb exposure living in the non-enriched environment and having an LMC mother had significant memory impairments at days 2 and 10 that were not observed in comparably housed animals with HMC mothers. Enriched animals had no deficits, regardless of maternal care status. These results show the potential for modulatory influences of maternal care and housing environment on protecting against or reversing at least one aspect of Pb-induced cognitive/behavioral dysfunction.

P25-14 Renal disturbances after prenatal and postnatal exposure to a very low dose of glyphosate and its mixture with dicamba and 2-4-D

P25-14 Renal disturbances after prenatal and postnatal exposure to a very low dose of glyphosate and its mixture with dicamba and 2-4-D