A self-sustaining layer of early-life-origin B cells drives steady-state IgA responses in the adult gut.

The adult immune system consists of cells that emerged at various times during ontogeny. We aimed to define the relationship between developmental origin and composition of the adult B cell pool during unperturbed hematopoiesis. Lineage tracing stratified murine adult B cells based on the timing of output, revealing that a substantial portion originated within a restricted neonatal window. In addition to B-1a cells, early-life time-stamped B cells included clonally interrelated IgA plasma cells in the gut and bone marrow. These were actively maintained by B cell memory within gut chronic germinal centers and contained commensal microbiota reactivity. Neonatal rotavirus infection recruited recurrent IgA clones that were distinct from those arising by infection with the same antigen in adults. Finally, gut IgA plasma cells arose from the same hematopoietic progenitors as B-1a cells during ontogeny. Thus, a complex layer of neonatally imprinted B cells confer unique antibody responses later in life.

Biomonitoring of Dietary Mycotoxin Exposure and Associated Impact on the Gut Microbiome in Nigerian Infants.

Mycotoxins are toxic chemicals that adversely affect human health. Here, we assessed the influence of mycotoxin exposure on the longitudinal development of early life intestinal microbiota of Nigerian neonates and infants (NIs). Human biomonitoring assays based on liquid chromatography tandem mass spectrometry were applied to quantify mycotoxins in breast milk (n = 68) consumed by the NIs, their stool (n = 82), and urine samples (n = 15), which were collected longitudinally from month 1-18 postdelivery. Microbial community composition was characterized by 16S rRNA gene amplicon sequencing of stool samples and was correlated to mycotoxin exposure patterns. Fumonisin B1 (FB1), FB2, and alternariol monomethyl ether (AME) were frequently quantified in stool samples between months 6 and 18. Aflatoxin M1 (AFM1), AME, and citrinin were quantified in breast milk samples at low concentrations. AFM1, FB1, and ochratoxin A were quantified in urine samples at relatively high concentrations. Klebsiella and Escherichia/Shigella were dominant in very early life stool samples (month 1), whereas Bifidobacterium was dominant between months 3 and 6. The total mycotoxin levels in stool were significantly associated with NIs' gut microbiome composition (PERMANOVA, p < 0.05). However, no significant correlation was observed between specific microbiota and the detection of certain mycotoxins. Albeit a small cohort, this study demonstrates that mycotoxins may influence early life gut microbiome composition.

Inactivation of common airborne antigens by perfluoroalkyl chemicals modulates early life allergic asthma.

Allergic asthma, driven by T helper 2 cell-mediated immune responses to common environmental antigens, remains the most common respiratory disease in children. Perfluorinated chemicals (PFCs) are environmental contaminants of great concern, because of their wide application, persistence in the environment, and bioaccumulation. PFCs associate with immunological disorders including asthma and attenuate immune responses to vaccines. The influence of PFCs on the immunological response to allergens during childhood is unknown. We report here that a major PFC, perfluorooctane sulfonate (PFOS), inactivates house dust mite (HDM) to dampen 5-wk-old, early weaned mice from developing HDM-induced allergic asthma. PFOS further attenuates the asthma protective effect of the microbial product lipopolysaccharide (LPS). We demonstrate that PFOS prevents desensitization of lung epithelia by LPS, thus abolishing the latter's protective effect. A close mechanistic study reveals that PFOS specifically binds the major HDM allergen Der p1 with high affinity as well as the lipid A moiety of LPS, leading to the inactivation of both antigens. Moreover, PFOS at physiological human (nanomolar) concentrations inactivates Der p1 from HDM and LPS in vitro, although higher doses did not cause further inactivation because of possible formation of PFOS aggregates. This PFOS-induced neutralization of LPS has been further validated in primary human cell models and extended to an in vivo bacterial infection mouse model. This study demonstrates that early life exposure of mice to a PFC blunts airway antigen bioactivity to modulate pulmonary inflammatory responses, which may adversely affect early pulmonary health.

Early-life exposure to ambient air pollutants and kidney function in adolescents: a cohort study based on the 'Children of 1997' Hong Kong birth cohort.

OBJECTIVES: Air pollution is increasingly linked to impaired kidney function in adults. However, little is known about how early-life exposure to air pollutants affects kidney function in adolescents. STUDY DESIGN: Cohort study. METHODS: We leveraged data from the 'Children of 1997' Hong Kong population-representative birth cohort (N = 8327). Residential exposure to average ambient levels of four air pollutants, including inhalable particle (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), and nitrogen monoxide (NO), during in utero, infancy, and childhood periods was estimated using the inverse distance weighting. Kidney function was assessed using estimated glomerular filtration rate (eGFR) calculated from age-adjusted equations for adolescents. Generalized linear regression was used to examine the association of air pollutant exposure in each period with kidney function at 17.6 years. Two-pollutant models tested the robustness of the association. RESULTS: Of the 3350 participants included, 51.4% were boys. Exposure to PM10 was associated with poorer kidney function. Each interquartile range increment in PM10 was inversely associated with eGFR (ß: -2.933, 95% confidence interval -4.677 to -1.189) in utero, -2.362 (-3.992 to -0.732) infancy, -2.708 (-4.370 to -1.047) childhood, and -2.828 (-4.409 to -1.247) overall. Exposure to PM10 and SO2in utero had a stronger inverse association with kidney function in males. The associations were robust to PM10 exposure in two-pollutant models. CONCLUSIONS: Our findings suggest that early-life exposure to ambient PM10 and SO2 is associated with reduced kidney function in adolescents, especially exposure in utero.

Being Breastfed in Infancy and Risk of Colorectal Cancer and Precursor Lesions.

BACKGROUND & AIMS: Emerging evidence implicates the importance of perinatal and early-life exposures in colorectal cancer (CRC) development. However, it remains unclear whether being breastfed in infancy is associated with CRC risk in adult life, particularly early adulthood. METHODS: We prospectively investigated the association between history of being breastfed and risk of CRC and its precursor lesions among 66,634 women 46-93 years of age from the Nurses' Health Study and 92,062 women 27-68 years of age from the Nurses' Health Study II. Cox regression and logistic regression for clustered data were used to estimate hazard ratios for CRC and odds ratios for CRC precursors, respectively. RESULTS: During 3.5 million person-years of follow-up, we identified 1490 incident cases of CRC in 2 cohorts. Having been breastfed was associated with a 23% (95% confidence interval [CI], 10% to 38%) increased risk of CRC. The risk of CRC increased with duration of being breastfed (Ptrend < .001). These findings were validated using breastfeeding information from the mothers of a subset of participants. Among younger participants from the Nurses' Health Study II, a significant association was observed between being breastfed and increased risk of high-risk adenomas under 50 years of age (odds ratio, 1.46; 95% CI, 1.16 to 1.83). Consistently, having been breastfed was associated with increased risk of CRC among participants ≤55 years of age (hazard ratio, 1.38; 95% CI, 1.06 to 1.80). CONCLUSIONS: Being breastfed in infancy was associated with increased risk of CRC in adulthood, including among younger adults. However, further research is needed to understand the underlying biological mechanisms, as this association does not establish causation.

Improved ambient air quality is associated with decreased prevalence of childhood asthma and infancy shortly after weaning is a sensitive exposure window.

BACKGROUND: The urban ambient air quality has been largely improved in the past decade. It is unknown whether childhood asthma prevalence is still increasing in ever top-ranking city of Shanghai, whether the improved air quality is beneficial for children's asthma and what time window of exposure plays critical roles. METHODS: Using a repeat cross-sectional design, we analyzed the association between early life exposure to particles and wheezing/asthma in each individual and combined surveys in 2011 and 2019, respectively, in 11,825 preschool children in Shanghai. RESULTS: A significantly lower prevalence of doctor-diagnosed asthma (DDA) (6.6% vs. 10.5%, p < 0.001) and wheezing (10.5% vs. 23.2%, p < 0.001) was observed in 2019 compared to 2011. Exposure to fine particulate matter (PM2.5 ), coarse particles (PM2.5-10 ) and inhalable particles (PM10 ) was decreased in 2019 by 6.3%, 35.4%, and 44.7% in uterus and 24.3%, 20.2%, and 31.8% in infancy, respectively. Multilevel log-binomial regression analysis showed exposure in infancy had independent association with wheezing/DDA adjusting for exposure in uterus. For each interquartile range (IQR) increase of infancy PM2.5 , PM2.5-10 and PM10 exposure, the odds ratios were 1.39 (95% confidence interval (CI): 1.24-1.56), 1.51 (95% CI:1.15-1.98) and 1.53 (95% CI:1.27-1.85) for DDA, respectively. The distributed lag non-linear model showed the sensitive exposure window (SEW) was 5.5-11 months after birth. Stratified analysis showed the SEWs were at or shortly after weaning, but only in those with <6 months of exclusive breastfeeding. CONCLUSIONS: Improved ambient PM benefits in decreasing childhood asthma prevalence. We firstly reported the finding of SEW to PM at or closely after weaning on childhood asthma.

Arsenic Ingested Early in Life Is More Readily Absorbed: Mechanistic Insights from Gut Microbiota, Gut Metabolites, and Intestinal Morphology and Functions.

Early-life arsenic (As) exposure is a particular health concern. However, it is unknown if As ingested early in life is more readily absorbed from the gastrointestinal (GI) tract, i.e., higher in oral bioavailability. Here, weanling (3-week) and adult (6-week-old) female mice were exposed to arsenate in the diet (10 µg g-1) over a 3-week period with As oral bioavailability estimated using As urinary excretion as the bioavailability endpoint. The As urinary excretion factor was 1.54-fold higher in weanling mice compared to adult mice (82.2 ± 7.29 versus 53.1 ± 3.73%), while weanling mice also showed 2.28-, 1.50-, 1.48-, and 1.89-fold higher As concentration in small intestine tissue, blood, liver, and kidneys, demonstrating significantly higher As oral bioavailability of early-life exposure. Compared to adult mice, weanling mice significantly differed in gut microbiota, but the difference did not lead to remarkable differences in As biotransformation in the GI tract or tissue and in overall gut metabolite composition. Although the expression of several metabolites (e.g., atrolactic acid, hydroxyphenyllactic acid, and xanthine) was up-regulated in weanling mice, they had limited ability to elevate As solubility in the intestinal tract. Compared to adult mice, the intestinal barrier function and intestinal expression of phosphate transporters responsible for arsenate absorption were similar in weanling mice. However, the small intestine of weanling mice was characterized by more defined intestinal villi with greater length and smaller width, providing a greater surface area for As to be absorbed across the GI barrier. The results highlight that early-life As exposure can be more readily absorbed, advancing the understanding of its health risk.

Combined effect of preconceptional and prenatal exposure to air pollution and temperature on childhood pneumonia: A case-control study.

Mounting evidence have linked ambient air pollution and temperature with childhood pneumonia, but it is unclear whether there is an interaction between air pollution and temperature on childhood pneumonia. We aim to assess the combined effect of ambient air pollution and temperature exposure during preconception and pregnancy on pneumonia by a case-control study of 1510 children aged 0-14 years in Changsha, China. We obtained the data of childhood pneumonia from XiangYa Hospital electrical records. We estimated personal exposure to outdoor air pollution (PM10, SO2 and NO2) by inverse distance weighted (IDW) method and temperature indicators. Multiple logistic regression models were used to evaluate associations of childhood pneumonia with air pollution, temperature (T), and diurnal temperature variation (DTV). We found that exposure to industry-related air pollution (PM10 and SO2) during preconception and pregnancy were associated with childhood pneumonia, with ORs (95% CI) of 1.72 (1.48-1.98) and 2.96 (2.50-3.51) during 1 year before pregnancy and 1.83 (1.59-2.11) and 3.43 (2.83-4.17) in pregnancy. Childhood pneumonia was negatively associated with T exposure during 1 year before pregnancy and pregnancy, with ORs (95% CI) of 0.57 (0.41-0.80) and 0.85 (0.74-0.98). DTV exposure during pregnancy especially during the 1st and 2nd trimesters significantly increased pneumonia risk, with ORS (95% CI) of 1.77 (1.19-2.64), 1.47 (1.18-1.83), and 1.37 (1.07-1.76) respectively. We further observed interactions of PM10 and SO2 exposure with low T and high DTV during conception and pregnancy in relation to childhood pneumonia. This study suggests that there were interactions air pollution with temperature and DTV on pneumonia development.

Evidence for an association of prenatal exposure to particulate matter with clinical severity of Autism Spectrum Disorder.

Early-life exposure to air pollutants, including ozone (O3), particulate matter (PM2.5 or PM10, depending on diameter of particles), nitrogen dioxide (NO2) and sulfur dioxide (SO2) has been suggested to contribute to the etiology of Autism Spectrum Disorder (ASD). In this study, we used air quality monitoring data to examine whether mothers of children with ASD were exposed to high levels of air pollutants during critical periods of pregnancy, and if higher exposure levels may lead to a higher clinical severity in their offspring. We used public data from the Portuguese Environment Agency to estimate exposure to these pollutants during the first, second and third trimesters of pregnancy, full pregnancy and first year of life of the child, for 217 subjects with ASD born between 2003 and 2016. These subjects were stratified in two subgroups according to clinical severity, as defined by the Autism Diagnostic Observational Schedule (ADOS). For all time periods, the average levels of PM2.5, PM10 and NO2 to which the subjects were exposed were within the admissible levels defined by the European Union. However, a fraction of these subjects showed exposure to levels of PM2.5 and PM10 above the admissible threshold. A higher clinical severity was associated with higher exposure to PM2.5 (p = 0.001), NO2 (p = 0.011) and PM10 (p = 0.041) during the first trimester of pregnancy, when compared with milder clinical severity. After logistic regression, associations with higher clinical severity were identified for PM2.5 exposure during the first trimester (p = 0.002; OR = 1.14, 95%CI: 1.05-1.23) and full pregnancy (p = 0.04; OR = 1.07, 95%CI: 1.00-1.15) and for PM10 (p = 0.02; OR = 1.07, 95%CI: 1.01-1.14) exposure during the third trimester. Exposure to PM is known to elicit neuropathological mechanisms associated with ASD, including neuroinflammation, mitochondrial disruptions, oxidative stress and epigenetic changes. These results offer new insights on the impact of early-life exposure to PM in ASD clinical severity.

Early life exposure to outdoor air pollution and indoor environmental factors on the development of childhood allergy from early symptoms to diseases.

BACKGROUND: The prevalence of childhood allergies has increased during past decades leading to serious hospitalization and heavy burden worldwide, yet the key factors responsible for the onset of early symptoms and development of diagnosed diseases are unclear. OBJECTIVE: To explore the role of early life exposure to ambient air pollution and indoor environmental factors on early allergic symptoms and doctor diagnosed allergic diseases. METHODS: A retrospective cohort study of 2598 preschool children was conducted at 36 kindergartens in Changsha, China from September of 2011 to February of 2012. A questionnaire was developed to survey each child's early onset of allergic symptoms (wheeze and rhinitis-like symptoms) and doctor diagnosis of allergic diseases (asthma and rhinitis) as well as home environments. Each mother's and child's exposures to ambient air pollutants (PM10, SO2, and NO2) and temperature were estimated for in utero and postnatal periods. The associations of early symptoms and diagnosed diseases with outdoor air pollution and indoor environmental variables were examined by logistic regression models. RESULTS: Childhood early allergic symptoms (33.9%) including wheeze (14.7%) and rhinitis-like symptoms (25.4%) before 2 years old were not associated with outdoor air pollution exposure but was significantly associated with maternal exposure of window condensation at home in pregnancy with ORs (95% CI) of 1.33 (1.11-1.59), 1.30 (1.01-1.67) and 1.27 (1.04-1.55) respectively, and was associated with new furniture during first year after birth with OR (95% CI) of 1.43 (1.02-2.02) for early wheeze. Childhood diagnosed allergic diseases (28.4%) containing asthma (6.7%) and allergic rhinitis (AR) (7.2%) were significantly associated with both outdoor air pollutants (mainly for SO2 and NO2) during first 3 years and indoor new furniture, redecoration, and window condensation. We found that sex, age, parental atopy, maternal productive age, environmental tobacco smoke (ETS), antibiotics use, economic stress, early and late introduction of complementary foods, and outdoor air pollution modified the effects of home environmental exposure in early life on early allergic symptoms and diagnosed allergic diseases. CONCLUSION: Our study indicates that early life exposure to indoor environmental factors plays a key role in early onset of allergic symptoms in children, and further exposure to ambient air pollution and indoor environmental factors contribute to the later development of asthma and allergic rhinitis.

Prenatal and childhood exposure to per-/polyfluoroalkyl substances (PFASs) and its associations with childhood overweight and/or obesity: a systematic review with meta-analyses.

BACKGROUND: Per-/polyfluoroalkyl substances (PFASs) are persistent organic pollutants and suspected endocrine disruptors. OBJECTIVE: The aim of this work was to conduct a systematic review with meta-analysis to summarise the associations between prenatal or childhood exposure to PFASs and childhood overweight/obesity. METHODS: The search was performed on the bibliographic databases PubMed and Embase with text strings containing terms related to prenatal, breastfeeding, childhood, overweight, obesity, and PFASs. Only papers describing a biomonitoring study in pregnant women or in children up to 18 years that assessed body mass index (BMI), waist circumference (WC), or fat mass in children were included. When the estimates of the association between a PFAS and an outcome were reported from at least 3 studies, a meta-analysis was conducted; moreover, to correctly compare the studies, we developed a method to convert the different effect estimates and made them comparable each other. Meta-analyses were performed also stratifying by sex and age, and sensitivity analyses were also performed. RESULTS: In total, 484 and 779 articles were retrieved from PubMed and Embase, respectively, resulting in a total of 826 articles after merging duplicates. The papers included in this systematic review were 49: 26 evaluating prenatal exposure to PFASs, 17 childhood exposure, and 6 both. Considering a qualitative evaluation, results were conflicting, with positive, negative, and null associations. 30 papers were included in meta-analyses (19 prenatal, 7 children, and 4 both). Positive associations were evidenced between prenatal PFNA and BMI, between PFOA and BMI in children who were more than 3 years, and between prenatal PFNA and WC. Negative associations were found between prenatal PFOS and BMI in children who were 3 or less years, and between PFHxS and risk of overweight. Relatively more consistent negative associations were evidenced between childhood exposure to three PFASs (PFOA, PFOS, and PFNA) and BMI, in particular PFOS in boys. However, heterogeneity among studies was high. CONCLUSION: Even though heterogeneous across studies, the pooled evidence suggests possible associations, mostly positive, between prenatal exposure to some PFASs and childhood BMI/WC; and relatively stronger evidence for negative associations between childhood exposure to PFASs and childhood BMI.

Early-life cadmium exposure elevates susceptibility to allergic asthma in ovalbumin-sensitized and challenged mice.

Increasing evidence have demonstrated that early-life exposure to environmental toxicants elevates risk of allergic asthma. Cadmium (Cd) is widely present in the environment. The purposes of this study were to evaluate the impact of early-life Cd exposure on susceptibility to ovalbumin (OVA)-evoked allergic asthma. Newly weaned mice were subjected to a low concentration of CdCl2 (1 mg/L) by drinking water for 5 consecutive weeks. Penh value, an index of airway obstruction, was increased in OVA-stimulated and challenged pups. Abundant inflammatory cells were observed in the lung of OVA-exposed pups. Goblet cell hyperplasia and mucus secretion were shown in the airway of OVA-stimulated and challenged pups. Early-life Cd exposure exacerbated OVA-evoked airway hyperreactivity, Goblet cell hyperplasia and mucus secretion. The in vitro experiments showed that mucoprotein gene MUC5AC mRNA was upregulated in Cd-exposed bronchial epithelial cells. Mechanistically, endoplasmic reticulum (ER) stress-related molecules GRP78, p-eIF2α, CHOP, p-IRE1α and spliced XBP-1 (sXBP-1) were elevated in Cd-subjected bronchial epithelial cells. The blockade of ER stress, using chemical inhibitor 4-PBA or sXBP-1 siRNA interference, attenuated Cd-induced MUC5AC upregulation in bronchial epithelial cells. These results indicate that early-life Cd exposure aggravates OVA-induced allergic asthma partially through inducing ER stress in bronchial epithelial cells.

The final 28 Days:Prenatal exposure to air pollution and child anthropometric outcomes.

This study examines the health consequences of prenatal exposure to air pollution by combining child health data from an original survey with the Air Pollution Index (API) from official Chinese statistics. Our results show that exposure to air pollution in late trimester (four-week windows before delivery) is negatively associated with health outcomes in children in the short and long terms. One standard deviation increase in the API in the final 28 days before delivery decreased birth weight and length by 0.388 and 0.458, respectively, in z-scores and lowered the weight-for-age and height-for-age by 0.370 and 0.441, respectively, in z-scores at 13-15 years post-exposure. Although the timing of exposure and its consequences have been the subject of debate in existing literature, our results focus on four-week windows and demonstrate that exposure during the late pregnancy period may have adverse health effects on children. We conducted analyses that accounted for potential covariates and omitted variables, and our results remain robust and statistically significant. We also found gender heterogeneous effects that girls are more vulnerable to fetal air pollution exposure than boys. Our findings uncover fetal and child health risks regarding air pollution and reinforce the importance of policies for mitigating air pollution in developing countries.

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.

The association between early-life famine exposure and adulthood obesity on the risk of dyslipidemia.

BACKGROUND AND AIMS: The joint effect of famine exposure and adulthood obesity on risk of dyslipidemia remains unclear. Thus, we aim to explore the joint effect of famine exposure and adulthood obesity on the risk of dyslipidemia, and the potential effect of adult general or abdominal obesity on the association between famine exposure and dyslipidemia. METHODS AND RESULTS: We conducted a community-based cohort study in 8880 subjects aged 40 years or older. Participants were divided into nonexposed, fetal-exposed, childhood-exposed, adolescent-exposed according to birth date. General obesity and abdominal obesity were defined according to body mass index (BMI: overweight≥24.0 kg/m2, obesity≥28.0 kg/m2) and waist-to-hip ratio (WHR, men/women: moderate≥0.90/0.85, high≥0.95/0.90). Dyslipidemia was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. Compared with nonexposed participants, fetal-exposed individuals had significantly increased risk of dyslipidemia (OR:1.24, 95%CI: 1.03-1.50) in the whole study. Significant increased risk of dyslipidemia related to famine exposure was observed in women [ORs (95%CIs) were 1.36 (1.05-1.76) and 1.70 (1.22-2.37) for the fetal and childhood-exposed group, respectively] but not in men. Moreover, both general and central obesity had significant multiplicative interactions with famine exposure for the risk of dyslipidemia (P for interaction = 0.0001 and < 0.0001, respectively). Significant additive interaction was found between famine exposure and WHR on risk of dyslipidemia in women, with the relative excess risk due to interaction (RERI) and 95% CI of 0.43 (0.10-0.76). CONCLUSION: Coexistence of early-life undernutrition and adulthood obesity was associated with a higher risk of dyslipidemia in later life.

Effect of prenatal and postnatal exposure to home renovation on the risk of common cold in preschool children.

Common cold is usually considered to be associated with outdoor climate, but the evidence linking with indoor environmental factors is lacking. The role of indoor renovations during which critical timing window on childhood common cold remains unclear. Therefore, we investigated the effect of exposure to new furniture and/or redecoration during prenatal and postnatal periods on the occurrence and duration of common cold in preschool children. We conducted a retrospective cohort study of 39 782 children aged 3-6 years in seven cities of China. The occurrence and duration of common cold in children, and their lifetime exposures to indoor new furniture and redecoration (including pregnancy, the first year of life, and after one year old) were assessed using a questionnaire administered by the parents. Associations between high frequency (>5 colds) and long duration (≥2 weeks per cold) of common cold during past 12 months and exposure to indoor new furniture/redecoration were examined by logistic regression models in terms of odds ratio (OR) and 95% confidence interval (CI). We found that the prevalence of high frequency and long duration of common cold in preschool children in China were, respectively, 9.2% and 11.9%. Frequent common cold was significantly associated with exposure to indoor new furniture/redecoration during pregnancy, first year, and after 1 year old, respectively, with the ORs (95% CI) = 1.25 (1.12-1.39), 1.11 (1.00-1.25), and 1.09 (1.01-1.18). Furthermore, childhood long duration per cold was associated with exposure to indoor new furniture/redecoration during pregnancy with OR (95% CI) of 1.14 (1.03-1.25) but not with postnatal exposure. We identified that prenatal exposure to home renovation was more critical than postnatal exposure for an increased risk of high frequency and long duration of common cold. Sensitivity analysis showed that the association between prenatal exposure to indoor renovations and the risk of childhood common cold was consistent and robust, and the associations were modified by some personal and indoor environmental factors. Our findings indicated that prenatal and postnatal exposure to home renovation played an important role in the risk of childhood common cold, supporting the hypothesis of "fetal origin of childhood infection."

Oral administration of TiO2 nanoparticles during early life impacts cardiac and neurobehavioral performance and metabolite profile in an age- and sex-related manner.

BACKGROUND: Nanoparticles (NPs) are increasingly incorporated in everyday products. To investigate the effects of early life exposure to orally ingested TiO2 NP, male and female Sprague-Dawley rat pups received four consecutive daily doses of 10 mg/kg body weight TiO2 NP (diameter: 21 ± 5 nm) or vehicle control (water) by gavage at three different pre-weaning ages: postnatal day (PND) 2-5, PND 7-10, or PND 17-20. Cardiac assessment and basic neurobehavioral tests (locomotor activity, rotarod, and acoustic startle) were conducted on PND 20. Pups were sacrificed at PND 21. Select tissues were collected, weighed, processed for neurotransmitter and metabolomics analyses. RESULTS: Heart rate was found to be significantly decreased in female pups when dosed between PND 7-10 and PND 17-20. Females dosed between PND 2-5 showed decrease acoustic startle response and when dosed between PND 7-10 showed decreased performance in the rotarod test and increased locomotor activity. Male pups dosed between PND 17-20 showed decreased locomotor activity. The concentrations of neurotransmitters and related metabolites in brain tissue and the metabolomic profile of plasma were impacted by TiO2 NP administration for all dose groups. Metabolomic pathways perturbed by TiO2 NP administration included pathways involved in amino acid and lipid metabolism. CONCLUSION: Oral administration of TiO2 NP to rat pups impacted basic cardiac and neurobehavioral performance, neurotransmitters and related metabolites concentrations in brain tissue, and the biochemical profiles of plasma. The findings suggested that female pups were more likely to experience adverse outcome following early life exposure to oral TiO2 NP than male pups. Collectively the data from this exploratory study suggest oral administration of TiO2 NP cause adverse biological effects in an age- and sex-related manner, emphasizing the need to understand the short- and long-term effects of early life exposure to TiO2 NP.

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

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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".

Early-life exposure to submicron particulate air pollution in relation to asthma development in Chinese preschool children.

BACKGROUND: Emerging research suggested an association of early-life particulate air pollution exposure with development of asthma in childhood. However, the potentially differential effects of submicron particulate matter (PM; PM with aerodynamic diameter ≤1 µm [PM1]) remain largely unknown. OBJECTIVE: This study primarily aimed to investigate associations of childhood asthma and wheezing with in utero and first-year exposures to size-specific particles. METHODS: We conducted a large cross-sectional survey among 5788 preschool children aged 3 to 5 years in central China. In utero and first-year exposures to ambient PM1, PM with aerodynamic diameter less than or equal to 2.5 µm, and PM with aerodynamic diameter less than or equal to 10 µm at 1 × 1-km resolution were assessed using machine learning-based spatiotemporal models. A time-to-event analysis was performed to examine associations between residential PM exposures and childhood onset of asthma and wheezing. RESULTS: Early-life size-specific PM exposures, particularly during pregnancy, were significantly associated with increased risk of asthma, whereas no evident PM-wheezing associations were observed. Each 10-µg/m3 increase in in utero and first-year PM1 exposure was accordingly associated with an asthma's hazard ratio in childhood of 1.618 (95% CI, 1.159-2.258; P = .005) and 1.543 (0.822-2.896; P = .177). Subgroup analyses suggest that short breast-feeding duration may aggravate PM-associated risk of childhood asthma. Each 10-µg/m3 increase in in utero exposure to PM1, for instance, was associated with a hazard ratio of 2.260 (1.393-3.666) among children with 0 to 5 months' breast-feeding and 1.156 (0.721-1.853) among those longer breast-fed. CONCLUSIONS: Our study added comparative evidence for increased risk of childhood asthma in relation to early-life PM exposures, highlighting stronger associations with ambient PM1 than with PM with aerodynamic diameter less than or equal to 2.5 µm and PM with aerodynamic diameter less than or equal to 10 µm.

Early Life Short-Term Exposure to Polychlorinated Biphenyl 126 in Mice Leads to Metabolic Dysfunction and Microbiota Changes in Adulthood.

Early life exposure to environmental pollutants may have long-term consequences and harmful impacts on health later in life. Here, we investigated the short- and long-term impact of early life 3,3',4,4',5-pentacholorobiphenyl (PCB 126) exposure (24 µg/kg body weight for five days) in mice on the host and gut microbiota using 16S rRNA gene sequencing, metagenomics, and 1H NMR- and mass spectrometry-based metabolomics. Induction of Cyp1a1, an aryl hydrocarbon receptor (AHR)-responsive gene, was observed at 6 days and 13 weeks after PCB 126 exposure consistent with the long half-life of PCB 126. Early life, Short-Term PCB 126 exposure resulted in metabolic abnormalities in adulthood including changes in liver amino acid and nucleotide metabolism as well as bile acid metabolism and increased hepatic lipogenesis. Interestingly, early life PCB 126 exposure had a greater impact on bacteria in adulthood at the community structure, metabolic, and functional levels. This study provides evidence for an association between early life environmental pollutant exposure and increased risk of metabolic disorders later in life and suggests the microbiome is a key target of environmental chemical exposure.