Effects Of Early-life Exposure Research Articles

Long-Term Effects of Childhood Exposure to War on Domestic Violence

AbstractThis paper highlights the scarring effects of early life exposure to civil war, by examining the impact of exposure to conflict in childhood on the incidence of domestic violence in adulthood among married women. To estimate these effects, we use a difference-in-differences model which exploits variation in exposure to Nigeria’s 30-month-long civil war by year of birth and ethnicity. Our results, based on the 2008 Nigerian Demographic Health Survey, show that women exposed to the war during childhood are more likely to be victims of domestic violence in adulthood compared to those not exposed to the war, with larger effects observed for those exposed at younger ages. Additionally, we explore the mechanisms through which exposure to civil war might affect domestic violence and find some support for both the normalisation of violence and weakened bargaining power hypotheses. Understanding the root causes of domestic violence is important given the high prevalence in developing countries and the deleterious consequences for women and their children.

Effects of Early Life Exposures to the Aryl Hydrocarbon Receptor Ligand TCDF on Gut Microbiota and Host Metabolic Homeostasis in C57BL/6J Mice.

Exposure to persistent organic pollutants (POPs) and disruptions in the gastrointestinal microbiota have been positively correlated with a predisposition to factors such as obesity, metabolic syndrome, and type 2 diabetes; however, it is unclear how the microbiome contributes to this relationship. This study aimed to explore the association between early life exposure to a potent aryl hydrocarbon receptor (AHR) agonist and persistent disruptions in the microbiota, leading to impaired metabolic homeostasis later in life. This study used metagenomics, nuclear magnetic resonance (NMR)- and mass spectrometry (MS)-based metabolomics, and biochemical assays to analyze the gut microbiome composition and function, as well as the physiological and metabolic effects of early life exposure to 2,3,7,8-tetrachlorodibenzofuran (TCDF) in conventional, germ-free (GF), and Ahr-null mice. The impact of TCDF on Akkermansia muciniphila (A. muciniphila) in vitro was assessed using optical density (OD 600), flow cytometry, transcriptomics, and MS-based metabolomics. TCDF-exposed mice exhibited lower abundances of A. muciniphila, lower levels of cecal short-chain fatty acids (SCFAs) and indole-3-lactic acid (ILA), as well as lower levels of the gut hormones glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), findings suggestive of disruption in the gut microbiome community structure and function. Importantly, microbial and metabolic phenotypes associated with early life POP exposure were transferable to GF recipients in the absence of POP carry-over. In addition, AHR-independent interactions between POPs and the microbiota were observed, and they were significantly associated with growth, physiology, gene expression, and metabolic activity outcomes of A. muciniphila, supporting suppressed activity along the ILA pathway. These data obtained in a mouse model point to the complex effects of POPs on the host and microbiota, providing strong evidence that early life, short-term, and self-limiting POP exposure can adversely impact the microbiome, with effects persisting into later life with associated health implications. https://doi.org/10.1289/EHP13356.

Long-term effects of early life rainfall shocks on foundational cognitive skills: Evidence from Peru

Global warming is changing precipitation patterns, particularly harming communities in low-and-middle income countries (LMICs). Whilst the long-term effects of being exposed to rainfall shocks early in life on school-achievement tests are well-established, there is little population-based evidence from LMICs on the mechanisms through which these shocks operate. Executive functions (EFs) are key for children’s learning abilities. This paper analyses the effects of early exposure to rainfall shocks on four foundational cognitive skills (FCSs), including EFs that have been found to be key predictors of educational success. These skills were measured via a series of tablet-based tasks administered in Peru as part of the Young Lives longitudinal study (YLS). We combine the YLS data with gridded data on monthly precipitation to generate monthly, community-level rainfall shock estimates. The key identification strategy relies on temporary climatic shocks being uncorrelated with other latent determinants of FCSs development. Our results show significant negative effects of early life exposure to rainfall shocks on EFs—especially, on working memory—measured in later childhood. We also find evidence of rainfall shocks decreasing households’ abilities to invest in human capital, which may affect both FCSs and domain-specific test scores. Finally, there is suggestive, but not conclusive, evidence that a conditional-cash-transfer program providing poor households with additional financial resources might partially offset the effects of the rainfall shocks.

Obesity risk in young adults from the Jerusalem Perinatal Study (JPS): the contribution of polygenic risk and early life exposure

Background/ObjectivesThe effects of early life exposures on offspring life-course health are well established. This study assessed whether adding early socio-demographic and perinatal variables to a model based on polygenic risk score (PRS) improves prediction of obesity risk.MethodsWe used the Jerusalem Perinatal study (JPS) with data at birth and body mass index (BMI) and waist circumference (WC) measured at age 32. The PRS was constructed using over 2.1M common SNPs identified in genome-wide association study (GWAS) for BMI. Linear and logistic models were applied in a stepwise approach. We first examined the associations between genetic variables and obesity-related phenotypes (e.g., BMI and WC). Secondly, socio-demographic variables were added and finally perinatal exposures, such as maternal pre-pregnancy BMI (mppBMI) and gestational weight gain (GWG) were added to the model. Improvement in prediction of each step was assessed using measures of model discrimination (area under the curve, AUC), net reclassification improvement (NRI) and integrated discrimination improvement (IDI).ResultsOne standard deviation (SD) change in PRS was associated with a significant increase in BMI (β = 1.40) and WC (β = 2.45). These associations were slightly attenuated (13.7–14.2%) with the addition of early life exposures to the model. Also, higher mppBMI was associated with increased offspring BMI (β = 0.39) and WC (β = 0.79) (p < 0.001). For obesity (BMI ≥ 30) prediction, the addition of early socio-demographic and perinatal exposures to the PRS model significantly increased AUC from 0.69 to 0.73. At an obesity risk threshold of 15%, the addition of early socio-demographic and perinatal exposures to the PRS model provided a significant improvement in reclassification of obesity (NRI, 0.147; 95% CI 0.068–0.225).ConclusionsInclusion of early life exposures, such as mppBMI and maternal smoking, to a model based on PRS improves obesity risk prediction in an Israeli population-sample.

Regression discontinuity design for the study of health effects of exposures acting early in life.

Regression discontinuity design (RDD) is a quasi-experimental approach to study the causal effect of an exposure on later outcomes by exploiting the discontinuity in the exposure probability at an assignment variable cut-off. With the intent of facilitating the use of RDD in the Developmental Origins of Health and Disease (DOHaD) research, we describe the main aspects of the study design and review the studies, assignment variables and exposures that have been investigated to identify short- and long-term health effects of early life exposures. We also provide a brief overview of some of the methodological considerations for the RDD identification using an example of a DOHaD study. An increasing number of studies investigating the effects of early life environmental stressors on health outcomes use RDD, mostly in the context of education, social and welfare policies, healthcare organization and insurance, and clinical management. Age and calendar time are the mostly used assignment variables to study the effects of various early life policies and programs, shock events and guidelines. Maternal and newborn characteristics, such as age, birth weight and gestational age are frequently used assignment variables to study the effects of the type of neonatal care, health insurance, and newborn benefits, while socioeconomic measures have been used to study the effects of social and welfare programs. RDD has advantages, including intuitive interpretation, and transparent and simple graphical representation. It provides valid causal estimates if the assumptions, relatively weak compared to other non-experimental study designs, are met. Its use to study health effects of exposures acting early in life has been limited to studies based on registries and administrative databases, while birth cohort data has not been exploited so far using this design. Local causal effect around the cut-off, difficulty in reaching high statistical power compared to other study designs, and the rarity of settings outside of policy and program evaluations hamper the widespread use of RDD in the DOHaD research. Still, the assignment variables' cut-offs for exposures applied in previous studies can be used, if appropriate, in other settings and with additional outcomes to address different research questions.

Impact of Maternal Smoking, Offspring Smoking, and Genetic Susceptibility on Crohn's Disease and Ulcerative Colitis.

The long-term impact of maternal smoking during pregnancy [MSDP] on the risk of Crohn's disease [CD] and ulcerative colitis [UC] in adult offspring remains uncertain. The present study aimed to investigate the individual and combined effects of early life exposure [MSDP], offspring personal behaviour [smoking], and genetic risk on the development of CD and UC in adult offspring. We conducted a prospective cohort study using UK Biobank data, including 334 083 participants recruited between 2006 and 2010, with follow-up until December 31, 2021. Multivariable Cox regression models were used to evaluate the associations of genetic factors, maternal and personal smoking, and their combination with CD and UC. Participants exposed to MSDP had an 18% increased risk of CD compared to those without MSDP (hazard ratio [HR] = 1.18, 95% confidence interval [CI] = 1.01-1.39). However, no significant association was found between MSDP and UC risk [HR = 1.03, 95% CI = 0.92-1.16]. Personal smoking increased the risk of CD and UC, and had a numerically amplified effect with MSDP. Participants with high genetic risk and MSDP had a 2.01-fold [95% CI = 1.53-2.65] and a 2.45-fold [95% CI = 2.00-2.99] increased risk of CD and UC, respectively, compared to participants without MSDP and with low genetic risk. Our prospective cohort study provides evidence that MSDP increases the risk of CD in adult offspring, whereas no evidence supports their causal association. Additionally, smoking and genetic susceptibility had a numerically amplified effect with MSDP on CD and UC, but the interaction lacked statistical significance.

Genetic Susceptibility to Neurotoxicity Related to Prenatal Inorganic Arsenic Exposure in Young Spanish Children.

We explored the influence of child and maternal single nucleotide polymorphisms (SNPs) in genes related to neurological function and arsenic metabolism (i.e., ABCA1, ABCB1, PON1, CYP3A, BDNF, GSTP1, MT2A, and APOE as well as AS3MT) on the association between prenatal arsenic (As) exposure and methylation efficiency and neuropsychological development in 4-5-year-old children. Participants were 549 mother-child pairs from the INMA (Environment and Childhood) Spanish Project. We measured inorganic arsenic (iAs) and the metabolites monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in urine samples collected during pregnancy. Neuropsychological development was assessed at the age of 4-5 years using the McCarthy Scales of Children's Abilities (MSCA). Several SNPs were determined in maternal and child DNA; AS3MT and APOE haplotypes were inferred. The median ∑As (sum of iAs, DMA, and MMA) was 7.08 μg/g creatinine. Statistically significant interactions for children's APOE haplotype were observed. Specifically, ε4-carrier children had consistently lower MSCA scores in several scales with increasing ∑As and MMA concentrations. These results provide evidence regarding the neurotoxic effects of early life exposure to As, observing that the APOE ε4 allele could make children more vulnerable to this exposure.

Urinary antibiotics concentrations, their related affecting factors and infant growth in the first 6 months of life: A prospective cohort study

Antibiotic exposure even in low-dose could have potential adverse health effects, especially during early life. There is a lack of data on antibiotic burdens in early infancy. We aim to assess antibiotic exposure in infants from birth to 6 months of age, their related affecting factors and the association between antibiotic exposure and infancy growth. Urine samples were collected at ages of 3 days, 42 days, 3 months and 6 months from 197 term-born Chinese infants. A total of 33 representative antibiotics were measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Urinary antibiotics were detectable in 69.4%, 63.2%, 75.0% and 84.3% of infants at ages of 3 days, 42 days, 3 and 6 months, respectively. The dominant antibiotic categories detected were: Preferred as Veterinary Antibiotics (PVAs), Human Antibiotics (HAs), and Veterinary Antibiotics (VAs). The detectable rates were 30.6%, 45.8%, 58.9%, and 81.4% for PVAs, 34.1%, 20.8%, 28.6%, and 45.1% for HAs, and 36.5%, 12.5%, 6.3%, and 5.9% for VAs, at age 3 days, 42 days, 3 and 6 months, respectively. Urinary concentrations of HAs and preferred as human antibiotics (PHAs) in newborns at age 3 days were not associated with maternal intrapartum antibiotic prophylaxis. Similarly, no associations were observed between urinary antibiotics concentration and antibiotics use in infants at age 42 days or 6 months. The numbers and concentrations of urine detectable antibiotics were similar between infants with exclusive breastfeeding and infants fed with formula or mixed-feeding at all ages of 42 days, 3 and 6 months. At age of 42 days, infants in the low tertile of total antibiotics concentration or with one antibiotic detected had higher weight-for-length Z score and greater head circumference, compared to infants with no antibiotics detected. No associations were found between urinary antibiotics and any of the infant anthropometric measures at age 6 months. In conclusion, urinary antibiotics were detectable in most infants during the first 6 months of life, and PVAs, HAs and VAs were the most commonly detected antibiotics. This suggested the possibility of a foods-originated antibiotics exposure in children. No strong nor consistent associations were found between urinary antibiotic concentration and infant growth at the first six months of life. Still, attention is needed on the adverse health effect of early life exposure to antibiotics in future studies.

Risk factors for anorexia nervosa: A population-based investigation of sex differences in polygenic risk and early life exposures.

To examine sex differences in risk factors for anorexia nervosa (AN). This population-based study involved 44,743 individuals (6,239 AN cases including 5,818 females and 421 males, and 38,504 controls including 18,818 females and 19,686 males) born in Denmark between May 1981 and December 2009. Follow-up began on the individual's sixth birthday and ended at AN diagnosis, emigration, death, or December 31, 2016, whichever occurred first. Exposures included socioeconomic status (SES), pregnancy, birth, and early childhood factors based on data from Danish registers, and psychiatric and metabolic polygenic risk scores (PRS) based on genetic data. Hazard ratios were estimated using weighted Cox proportional hazards models stratified by sex (assigned at birth), with AN diagnosis as the outcome. The effects of early life exposures and PRS on AN risk were comparable between females and males. Although we observed some differences in the magnitude and direction of effects, there were no significant interactions between sex and SES, pregnancy, birth, or early childhood exposures. The effects of most PRS on AN risk were highly similar between the sexes. We observed significant sex-specific effects of parental psychiatric history and body mass index PRS, though these effects did not survive corrections for multiple comparisons. Risk factors for AN are comparable between females and males. Collaboration across countries with large registers is needed to further investigate sex-specific effects of genetic, biological, and environmental exposures on AN risk, including exposures in later childhood and adolescence as well as the additive effects of exposures. Sex differences in the prevalence and clinical presentation of AN warrant examination of sex-specific risk factors. This population-based study indicates that the effects of polygenic risk and early life exposures on AN risk are comparable between females and males. Collaboration between countries with large registers is needed to further investigate sex-specific AN risk factors and improve early identification of AN.

The effects of exposure to high temperatures during pregnancy on adolescent mental health: Evidence from China

This paper provides the first study to explore the relationship between exposure to ambient temperatures during pregnancy and adolescent mental health in China. The results show that experiencing one more hot day relative to local historical contemporaneous average values during pregnancy significantly increases the likelihood of mental health disorders in adolescence. The impact is larger in the first and second trimesters. Individuals born in the northern region and whose mothers work in agriculture are more vulnerable to high temperatures. Prenatal exposure to hot days is more harmful to the mental health of older adolescents. Additionally, the adverse effects are similar for both men and women and individuals with rural and urban hukou. Biological effects, income effects, and human capital accumulation might be three operative channels of the impact. These findings add to the evidence on the lasting health effects of early life exposure to climatic shocks and call for policy interventions during pregnancy.

Early Life Exposure to Above Average Rainfall and Adult Mental Health*

AbstractWe study the effects of early life exposure to above average levels of rainfall on adult mental health. While we find no effect from prenatal exposure, postnatal positive rainfall shocks decrease average Center for Epidemiological Studies Depression (CESD) mental health scores by 13% and increase the likelihood of depression by 6%, a more than 26% increase relative to the mean. These effects are limited to females. We rule out prenatal stress and income shocks as pathways. Early life exposure to infectious diseases appears to play a limited role but further research is required.

The Long-Term Consequences of Early Life Exposure to Tsunami and Conflict on Adolescents in Sri Lanka.

The consequences for adolescent health due to early life exposure to natural disasters combined with war are not known. We collected data from adolescents aged 12-13 years in Sri Lanka whose mothers were pregnant during the Indian Ocean tsunami in 2004 in a tsunami-affected region (n = 22), conflict-affected region (n = 35), conflict-plus-tsunami-affected region (n = 29), or controls in areas unaffected by either (n = 24). Adjusted body mass index (BMI)-for-age z-scores were 1.3, 1.0 and 2.0 for conflict, tsunami, and conflict-plus-tsunami, respectively, compared with the control group. Greater skinfold thickness and higher diastolic blood pressure were found in adolescents born in the conflict zone but no differences were found in height, head circumference, and waist circumference, or blood results, with the exception of serum insulin. Being born after a natural disaster or during conflict was associated with increased BMI and body fat during adolescent, which are associated with longer-term risk of noncommunicable disease.

Exposure to bisphenol A or its phenolic analogs during early life induces different types of anxiety-like behaviors after maturity in male mice

Products used in daily life contain multiple chemicals capable of inducing endocrine disruption in animals, including humans. One such typical substance is bisphenol A (BPA). BPA has been widely used in epoxy resins and polycarbonate plastics and can exert several adverse effects. Furthermore, given their structural similarity to BPA, phenolic analogs of BPA, i.e., synthetic phenolic antioxidants (SPAs), are considered to exhibit similar toxicity; however, the effects of early SPA exposure on the adult central nervous system remain poorly clarified. In the present study, we aimed to evaluate and compare the neurobehavioral effects of early life exposure to BPA and two selected SPAs, 4,4'-butylidenebis (6-tert-butyl-m-cresol) (BB) and 2,2'-methylenebis (6-tert-butyl-p-cresol) (MB). We exposed mice to low levels of these chemicals through drinking water during prenatal and postnatal periods. Subsequently, we examined the adverse effects of these chemicals on the central nervous system using a mouse behavioral test battery, comprising the open field test, light/dark transition test, elevated plus-maze test, contextual/cued fear conditioning test, and prepulse inhibition test, at 12-13 weeks old. Based on the behavioral analysis, SPAs, like BPA, may cause affective disorders even at low doses, although qualitative differences were noted in anxiety-related behaviors. In conclusion, our findings could be valuable for clarifying the potential adverse developmental risks of SPA exposure in early life.

Adverse Effects of Black Carbon (BC) Exposure during Pregnancy on Maternal and Fetal Health: A Contemporary Review.

Black carbon (BC) is a major component of ambient particulate matter (PM), one of the six Environmental Protection Agency (EPA) Criteria air pollutants. The majority of research on the adverse effects of BC exposure so far has been focused on respiratory and cardiovascular systems in children. Few studies have also explored whether prenatal BC exposure affects the fetus, the placenta and/or the course of pregnancy itself. Thus, this contemporary review seeks to elucidate state-of-the-art research on this understudied topic. Epidemiological studies have shown a correlation between BC and a variety of adverse effects on fetal health, including low birth weight for gestational age and increased risk of preterm birth, as well as cardiometabolic and respiratory system complications following maternal exposure during pregnancy. There is epidemiological evidence suggesting that BC exposure increases the risk of gestational diabetes mellitus, as well as other maternal health issues, such as pregnancy loss, all of which need to be more thoroughly investigated. Adverse placental effects from BC exposure include inflammatory responses, interference with placental iodine uptake, and expression of DNA repair and tumor suppressor genes. Taking into account the differences in BC exposure around the world, as well as interracial disparities and the need to better understand the underlying mechanisms of the health effects associated with prenatal exposure, toxicological research examining the effects of early life exposure to BC is needed.

Effects of Lifetime Exposures to Environmental Contaminants on the Adult Gut Microbiome.

Emerging experimental evidence indicates that toxicant-induced alterations in gut microbiota composition and activity may affect host homeostasis. However, data from human studies are scarce; to our knowledge, no previous studies have quantified the association of lifetime exposure to environmental chemicals, across multiple time points, with the composition of the adult gut microbiome. Here we studied 124 individuals born in the Faroe Islands in 1986-1987 who were followed approximately every seven years from birth through age 28 years. Organochlorine compounds, including polychlorinated biphenyls (PCBs) and pesticides, perfluoroalkyl substances (PFAS), and mercury (Hg), were measured in cord blood and longitudinally in participants' blood. At age 28, the gut microbiome was assessed using shotgun metagenomic sequencing. Historical contaminant exposures had little direct effect on the adult gut microbiome, while a small number of fastidious anaerobes were weakly linked to recent PFAS/PFOS exposures at age 28. In this cohort, our findings suggest no lasting effects of early life exposures on adult gut microbial composition, but proximal exposures may contribute to gut microbiome alterations. The methods developed and used for this investigation may help in future identification of small but lasting impacts of environmental toxicant exposure on the gut microbiome.

Consequences of General Anesthesia in Infancy on Behavior and Brain Structure.

One in 7 children will need general anesthesia (GA) before the age of 3. Brain toxicity of anesthetics is controversial. Our objective was to clarify whether exposure of GA to the developing brain could lead to lasting behavioral and structural brain changes. A first study was performed in mice. The behaviors (fear conditioning, Y-maze, and actimetry) and brain anatomy (high-resolution magnetic resonance imaging) of 6- to 8-week-old Swiss mice exposed or not exposed to GA from 4 to 10 days old were evaluated. A second study was a complementary analysis from the preexisting APprentissages EXécutifs et cerveau chez les enfants d'âge scolaire (APEX) cohort to assess the replicability of our data in humans. The behaviors (behavior rating inventory of executive function, emotional control, and working memory score, Backward Digit Span, and Raven 36) and brain anatomy (high-resolution magnetic resonance imaging) were compared in 102 children 9 to 10 years of age exposed or not exposed to a single GA (surgery) during infancy. The animal study revealed chronic exacerbated fear behavior in the adult mice (95% confidence interval [CI], 4-80; P = .03) exposed to postnatal GA; this was associated with an 11% (95% CI, 7.5-14.5) reduction of the periaqueductal gray matter (P = .046). The study in humans suggested lower emotional control (95% CI, 0.33-9.10; P = .06) and a 6.1% (95% CI, 4.3-7.8) reduction in the posterior part of the right inferior frontal gyrus (P = .019) in the children who had been exposed to a single GA procedure. The preclinical and clinical findings of these independent studies suggest lasting effects of early life exposure to anesthetics on later emotional control behaviors and brain structures.

Does early life exposure to exogenous sources of reactive oxygen species (ROS) increase the risk of respiratory and allergic diseases in children? A longitudinal cohort study

BackgroundExcess reactive oxygen species (ROS) can cause oxidative stress damaging cells and tissues, leading to adverse health effects in the respiratory tract. Yet, few human epidemiological studies have quantified the adverse effect of early life exposure to ROS on child health. Thus, this study aimed to examine the association of levels of ROS exposure at birth and the subsequent risk of developing common respiratory and allergic diseases in children.Methods1,284 Toronto Child Health Evaluation Questionnaire (T-CHEQ) participants were followed from birth (born between 1996 and 2000) until outcome, March 31, 2016 or loss-to-follow-up. Using ROS data from air monitoring campaigns and land use data in Toronto, ROS concentrations generated in the human respiratory tract in response to inhaled pollutants were estimated using a kinetic multi-layer model. These ROS values were assigned to participants’ postal codes at birth. Cox proportional hazards regression models, adjusted for confounders, were then used to estimate hazard ratios (HR) with 95% confidence intervals (CI) per unit increase in interquartile range (IQR).ResultsAfter adjusting for confounders, iron (Fe) and copper (Cu) were not significantly associated with the risk of asthma, allergic rhinitis, nor eczema. However, ROS, a measure of the combined impacts of Fe and Cu in PM2.5, was associated with an increased risk of asthma (HR = 1.11, 95% CI: 1.02–1.21, p < 0.02) per IQR. There were no statistically significant associations of ROS with allergic rhinitis (HR = 0.96, 95% CI: 0.88–1.04, p = 0.35) and eczema (HR = 1.03, 95% CI: 0.98–1.09, p = 0.24).ConclusionThese findings showed that ROS exposure in early life significantly increased the childhood risk of asthma, but not allergic rhinitis and eczema.

Longitudinal effects of prenatal exposure to plastic-derived chemicals and their metabolites on asthma and lung function from childhood into adulthood.

Environmental exposure to phthalates and bisphenol A (BPA), chemicals used in the production of plastics, may increase risk for asthma and allergies. However, little is known about the long-term effects of early life exposure to these compounds. We investigated if prenatal exposure to these compounds was associated with asthma, allergy and lung function outcomes from early childhood into adulthood in a cohort study. Maternal serum samples collected from 846 pregnant women in the Raine Study were assayed for BPA and phthalate metabolites. The children of these women were followed up at 5, 13 and 22 years where spirometry and respiratory questionnaires were conducted to determine asthma and allergy status. Lung function trajectories were derived from longitudinal spirometry measurements. Multinomial logistic regression and weighted quantile sum regression was used to test associations of individual and chemical mixtures with asthma phenotypes and lung function trajectories. Effects of prenatal BPA and phthalates on asthma phenotypes were seen in male offspring, where BPA was associated with increased risk for persistent asthma, while mono-iso-butyl phthalate and mono-iso-decyl phthalate was associated with increased risk for adult asthma. Prenatal BPA had no effect on lung function trajectories, but prenatal phthalate exposure was associated with improved lung function. Prenatal BPA exposure was associated with increased likelihood of persistent asthma in males, while prenatal phthalate exposure was associated with increased likelihood of adult asthma in males. Results suggest that prenatal exposure to prenatal BPA and phthalates affect asthma risk, particularly in males, however lung function was not adversely affected.

Effects of early life exposure to home environmental factors on childhood allergic rhinitis: Modifications by outdoor air pollution and temperature.

There is growing evidence that allergic rhinitis (AR) is associated with indoor environmental factors, but their role in childhood AR during early life remains unclear. To investigate the association of preconceptional, prenatal, early postnatal, and current exposure to home environmental factors with childhood AR, and to further explore whether this association can be interacted by outdoor air pollution and temperature. A retrospective cohort study of 8689 preschool children was conducted during 2019-2020 in Changsha, China. A standard questionnaire was used to collect data on each family's health outcomes and home environments. We considered home environmental exposures during one year before conception, pregnancy, first year of life, and past year. Associations of indoor air pollution and allergens with AR were assessed by multiple logistic regression models. Pre-birth exposure to indoor air pollution emitted by new furniture or redecoration and dampness related allergen derived from mold/damp stains and mold/damp clothes or bedding during 1 year before conception and pregnancy was significantly associated with increased AR, with adjusted ORs (95% CI) ranging from 1.35 (1.05-1.75) to 1.87 (1.55-2.27). Childhood AR was also significantly related with post-birth exposure to dampness related indoor allergen including mold/damp stains and mold/damp clothes or bedding in first year and past year and pollen allergen including total and nonflowing plants in past year, with a range of ORs (95% CI) from 1.20 (1.01-1.42) to 1.79 (1.42-2.27). We identified that pre-birth, particularly in utero exposure to both indoor air pollution from renovation and dampness related allergens, played a key role in AR development compared to post-birth exposures, and accumulative effect was observed with the highest risk of AR. High exposure to traffic-related air pollution (TRAP) including outdoor PM2.5, NO2, CO, and O3, as well as living near traffic road not only significantly increased adverse effect of home environmental factors but also decreased protective effect of household dogs on childhood AR. Early life exposure to low temperature in pregnancy and high temperature in first year significantly increased AR risk of home environmental exposure. Sensitivity analysis indicated that some sub-groups were more susceptible to AR risk of home environmental exposure. Our study suggests that pre-birth exposure to home environmental factors played an important role in AR development and this effect can be interacted by TRAP and temperature, which supports a hypothesis of "(pre)fetal origin of childhood AR".

P06-10 The effects of early life exposure to acephate on sexual maturation in male and female mice

P06-10 The effects of early life exposure to acephate on sexual maturation in male and female mice