Sensitive Time Window Research Articles

Anti-inflammatory diet mitigate cardiovascular risks due to particulate matter exposure in women during pregnancy: A perspective cohort study from China

BackgroundParticulate matter (PM) exposure during pregnancy may increase cardiovascular risk (CVR). However, the specific time windows of exposure contributing to this association and the potential biological mechanisms underlying it remain unclear. ObjectiveTo determine the sensitive time window for CVR related to PM exposure. We investigated whether levels of inflammatory biomarkers mediate the relationship between PM exposure and CVR, and examined the potential impact of an anti-inflammatory diet on this association. MethodsFrom 2015 to 2021, 9294 pregnant women from three Hefei hospitals were included. We used a 1 × 1 km satellite dataset to assess PM1, PM2.5, and PM10 exposure. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured as inflammatory biomarkers. The empirical dietary inflammatory pattern (EDIP) score, based on a validated food frequency questionnaire. The CVR score was calculated using five clinical metrics based on American Heart Association criteria. ResultsWe found a significant association between PM exposure and increased CVR score, especially during the 2nd to 8th weeks of the first trimester. For every increase of 10-μg/m3 of PM1, PM2.5, and PM10, there was an associated increase in CVR of 0.51 (95%CI: 0.21, 082), 0.25 (95% CI: 0.11 to 0.39), and 0.29 (95% CI: 0.09 to 0.37), respectively. Mediation analysis revealed that the proportion of the association between PM1, PM2.5, and PM10 exposure and CVR mediated by inflammatory biomarkers was 24.3%, 22.4%, and 20.1%, respectively. Stratified analyses showed no positive correlation between PM exposure and CVR in the anti-inflammatory diet (low EDIP) group. The β coefficients were 0.52 for PM1 (95% CI: -0.06 to 1.11), 0.31 for PM2.5 (95% CI: -0.04 to 0.79), and 0.25 for PM10 (95% CI: -0.03 to 0.54). ConclusionsPM exposure, particularly during weeks 2–8 of pregnancy, correlates with CVR, partly mediated by levels of inflammatory biomarkers. An anti-inflammatory diet mitigates CVR associated with PM exposure.

Inhibition of striatal indirect pathway during second postnatal week leads to long-lasting deficits in motivated behavior.

Schizophrenia is a neuropsychiatric disorder with postulated neurodevelopmental etiology. Genetic and imaging studies have shown enhanced dopamine and D2 receptor occupancy in the striatum of patients with schizophrenia. However, whether alterations in postnatal striatal dopamine can lead to long-lasting changes in brain function and behavior is still unclear. Here, we approximated striatal D2R hyperfunction in mice via designer receptor-mediated activation of inhibitory Gi-protein signaling during a defined postnatal time window. We found that Gi-mediated inhibition of the indirect pathway (IP) during postnatal days 8-15 led to long-lasting decreases in locomotor activity and motivated behavior measured in the adult animal. In vivo photometry further showed that the motivational deficit was associated with an attenuated adaptation of outcome-evoked dopamine levels to changes in effort requirements. These data establish a sensitive time window of D2R-regulated striatal development with long-lasting impacts on neuronal function and behavior.

Prenatal exposure to PM2.5 and its composition on child growth trajectories in the first two years: A prospective birth cohort study

The findings on the relationship between prenatal exposure to particulate matter with aerodynamic diameter ≤2.5 μm (PM2.5) and its constituent and children's growth trajectories are inconsistent. This association's sensitive exposure time window and possible gender differences remain unclear. Our aim was to determine the association between prenatal exposure to PM2.5 and its component and children's growth trajectories by the age of two. From 2015 to 2021, 6407 mother-infant pairs were enrolled in the study. The PM2.5 include sulfate (SO42−), nitrate (NO3−), ammonium (NH4+), organic matter (OM), and black carbon (BC), from the ChinaHighAirPollutants (CHAP) datasets. Children were followed at birth, 1, 3, 6, 9, 12, 18, and 24 months. Population-based and individual-based methods were used to simulate child growth trajectories: slow growth, normal growth, and rapid growth. The distributed lags modeling was used to identify sensitive time windows for the effects of prenatal exposure to PM2.5 and its components on child growth. Sex-stratified analyses estimated sex differences. Median concentrations [interquartile ranges (IQRs)] were 57.46(17.3), 10.59(3.8), 14.26(4.4), 8.69(2.8), 13.05(3.4), and 2.53(0.7) μg/m3 for PM2.5, SO42−, NO3−, NH4+, OM, and BC, respectively. Compared with the normal growth trajectory group, exposure to PM2.5 was significantly associated with a higher risk of rapid growth trajectory in boys (ORs with 95% CI for the entire, first trimester, and second trimester of pregnancy, respectively: 1.016[1.006,1.025], 1.007[1.002,1.011], 1.007[1.002,1.011]). Exposure to PM2.5 was significantly associated with a higher risk of slow growth trajectory in girls (ORs with 95% CI for the entire, second trimester, and third trimester of pregnancy, respectively: 1.010 [1.001,1.018], 1.006 [1.001,1.011], 1.007 [1.002,1.012]). Prenatal PM2.5 and its composition exposure was positively associated with BMI peak in boys (βs with 95% CI for PM2.5, SO42−, NO3−, NH4+, OM, BC: 0.004[0.000,0.007], 0.025[0.006,0.044], 0.012[0.002,0.023], 0.022[0.004,0.039], 0.016[0.001,0.031], 0.082[0.005,0.159]), and not statistically significant in girls. We observed a more pronounced BC effect in our cohort. Prenatal exposure to PM2.5 and its component, especially at 10–22 weeks of gestation, is associated with a higher risk of rapid growth in boys and a risk of slow growth in girls.

Maternal Exposure to Environmental Air Pollution and Premature Rupture of Membranes: Evidence from Southern China.

BACKGROUND Exposure to air pollution (AP) during pregnancy is associated with pre-labor rupture of membranes (PROM). However, there is limited research on this topic, and the sensitive exposure windows remain unclear. The present study assessed the association between AP exposure and the risk of PROM, as well as seeking to identify the sensitive time windows. MATERIAL AND METHODS This retrospective study analyzed 4276 pregnant women's data from Tongling Maternal and Child Health Hospital from 2020 to 2022. We obtained air pollution data, including particulate matter (PM) with an aerodynamic diameter of ≤2.5 μm (PM₂․₅), particulate matter with an aerodynamic diameter of ≤10 μm (PM₁₀), nitrogen dioxide (NO₂), and ozone (O₃), from the Tongling Ecology and Environment Bureau. Demographic information was extracted from medical records. We employed a distributed lag model to identify the sensitive exposure windows of prenatal AP affecting the risk of PROM. We conducted a sensitivity analysis based on pre-pregnancy BMI. RESULTS We found a significant association between prenatal exposure to AP and increased PROM risk after adjusting for confounders, and the critical exposure windows of AP were the 6th to 7th months of pregnancy. In the underweight group, an increase of 10 µg/m³ in PM₂․₅ was associated with a risk of PROM, with an odds ratio (OR) of 1.48 (95% CI: 1.16, 1.89). Similarly, a 10 µg/m³ increase in PM₁₀ was associated with a risk of PROM, with an OR of 1.45 (95% CI: 1.05, 1.77). CONCLUSIONS Prenatal exposure to AP, particularly during months 6-7 of pregnancy, is associated with an increased risk of PROM. This study extends and strengthens the evidence on the association between prenatal exposure to AP and the risk of PROM, specifically identifying the critical exposure windows.

Prenatal particulate matter exposure is linked with neurobehavioural development in early life

BackgroundEarly life exposure to ambient particulate matter (PM) may negatively affect neurobehavioral development in children, influencing their cognitive, emotional, and social functioning. Here, we report a study on prenatal PM2.5 exposure and neurobehavioral development focusing on different time points in the first years of life. MethodsThis study was part of the ENVIRONAGE birth cohort that follows mother-child pairs longitudinally. First, the Neonatal Behavioral Assessment Scale (NBAS) was employed on 88 newborns aged one to two months to assess their autonomic/physiological regulation, motor organisation, state organisation/regulation, and attention/social interaction. Second, our study included 393 children between the ages of four and six years, for which the Strengths and Difficulties Questionnaire (SDQ) was used to assess the children's emotional problems, hyperactivity, conduct problems, peer relationship, and prosocial behaviour. Prenatal PM2.5 exposure was determined using a high-resolution spatial-temporal method based on the maternal address. Multiple linear and multinomial logistic regression models were used to analyse the relationship between prenatal PM2.5 exposure and neurobehavioral development in newborns and children, respectively. ResultsA 5 μg/m³ increase in first-trimester PM2.5 concentration was associated with lower NBAS range of state cluster scores (−6.11%; 95%CI: −12.00 to −0.23%; p = 0.04) in one-to-two-month-old newborns. No other behavioural clusters nor the reflexes cluster were found to be associated with prenatal PM2.5 exposure. Furthermore, a 5 μg/m³ increment in first-trimester PM2.5 levels was linked with higher odds of a child experiencing peer problems (Odds Ratio (OR) = 3.89; 95%CI: 1.39 to 10.87; p = 0.01) at ages four to six. Additionally, a 5 μg/m³ increase in second-trimester PM2.5 concentration was linked to abnormal prosocial behaviour (OR = 0.49; 95%CI: 0.25 to 0.98; p = 0.04) at four to six years old. No associations were found between in utero PM2.5 exposure and hyperactivity or conduct problems. ConclusionsOur findings suggest that prenatal exposure to PM may impact neurobehavioural development in newborns and preschool children. We identified sensitive time windows during early-to-mid pregnancy, possibly impacting stage changes in newborns and peer problems and prosocial behaviour in children.

Shrinking Alpine chamois: higher spring temperatures over the last 27 years in Switzerland are linked to a 3 kg reduction in body mass of yearlings.

Although climate change is considered to be partly responsible for the size change observed in numerous species, the relevance of this hypothesis for ungulates remains debated. We used body mass measurements of 5635 yearlings (i.e. 1.5 years old) of Alpine chamois (Rupicapra rupicapra) harvested in September in the Swiss Alps (Ticino canton) from 1992 to 2018. In our study area, during this period, yearlings shrank by ca 3 kg while temperatures between May and July rose by 1.7°C. We identified that warmer temperatures during birth and the early suckling period (9 May to 2 July in the year of birth) had the strongest impact on yearling mass. Further analyses of year-detrended mass and temperature data indicate that this result was not simply due to changes in both variables over years, but that increases in temperature during this particularly sensitive time window for development and growth are responsible for the decrease in body mass of yearling chamois. Altogether, our results suggest that rising temperatures in the Alpine regions could significantly affect the ecology and evolution of this wild ungulate.

Prenatal air pollution, fetal β-cell dysfunction and neurodevelopmental delay

BackgroundEmerging evidence has reported significant associations of prenatal air pollution exposure with neurodevelopmental delay in offspring. Sensitive exposure windows and the modifiable factor remain elusive. ObjectiveWe aim to identify sensitive windows of air pollution during pregnancy on neurodevelopmental delay, and examine whether cord blood C-peptide mediates the relationship. MethodsThis study included 7438 mother-newborn pairs in Hefei, China, from 2015 to 2021. Weekly exposure to particulate matter of aerodynamic diameter <2.5 µm, 10 µm (PM2.5, PM10), nitrogen dioxide (NO2) and carbon monoxide (CO) was estimated at regulatory air monitoring stations in Hefei. Denver Developmental Screening Test-II and the Gesell Developmental Schedules were applied to assess the neurodevelopmental delay in children 6–36 mon of age. Distributed lag nonlinear models examined sensitive time windows of prenatal air pollutants exposure. Mediation analysis estimated the mediating role of cord blood C-peptide. ResultsThe sensitive PM2.5, PM10, NO2, and CO exposure windows associated with neurodevelopmental delay were throughout pregnancy. Weekly air pollutants exposure was related to higher neurodevelopmental delay risks [cumulative odds ratio (OR): 1.40(1.29,1.53) in PM2.5 (per 10 μg/m3), 1.40(1.28,1.53) in PM10 (per 10 μg/m3), 1.41(1.30,1.52) in CO (per 0.1 mg/m3), and 1.49(1.29,1.72) in NO2 (per 5 μg/m3)]. Mediation analysis indicated 18.3 % contributions of cord C-peptide to the relationship [average mediation effect: 0.04(0.01.0.06); average direct effect: 0.15(0.07.0.25)]. Conclusions: Exposure to air pollution throughout pregnancy is linked to neurodevelopmental delay mediated by poorer fetal β-cell function. Screening and treatment of abnormal glucose metabolism in infants could benefit the prevention of air pollution-associated neurodevelopment delay.

Is tuberous sclerosis complex-associated autism a preventable and treatable disorder?

Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in the TSC1 and TSC2 genes, causing overactivation of the mechanistic (previously referred to as mammalian) target of rapamycin (mTOR) signaling pathway in fetal life. The mTOR pathway plays a crucial role in several brain processes leading to TSC-related epilepsy, intellectual disability, and autism spectrum disorder (ASD). Pre-natal or early post-natal diagnosis of TSC is now possible in a growing number of pre-symptomatic infants. We searched PubMed for peer-reviewed publications published between January 2010 and April 2023 with the terms "tuberous sclerosis", "autism", or "autism spectrum disorder"," animal models", "preclinical studies", "neurobiology", and "treatment". Prospective studies have highlighted that developmental trajectories in TSC infants who were later diagnosed with ASD already show motor, visual and social communication skills in the first year of life delays. Reliable genetic, cellular, electroencephalography and magnetic resonance imaging biomarkers can identify pre-symptomatic TSC infants at high risk for having autism and epilepsy. Preventing epilepsy or improving therapy for seizures associated with prompt and tailored treatment strategies for autism in a sensitive developmental time window could have the potential to mitigate autistic symptoms in infants with TSC.

The association between newborn cord blood steroids and ambient prenatal exposure to air pollution: findings from the ENVIRONAGE birth cohort

Knowledge of whether prenatal exposure to ambient air pollution disrupts steroidogenesis is currently lacking. We investigated the association between prenatal ambient air pollution and highly accurate measurements of cord blood steroid hormones from the androgenic pathway.This study included 397 newborns born between the years 2010 and 2015 from the ENVIRONAGE cohort in Belgium of whom six cord blood steroid levels were measured: 17α-hydroxypregnenolone, 17α-hydroxyprogesterone, dehydroepiandrosterone, pregnenolone, androstenedione, and testosterone. Maternal ambient exposure to PM2.5 (particles with aerodynamic diameter ≤ 2.5 μm), NO2, and black carbon (BC) were estimated daily during the entire pregnancy using a high-resolution spatiotemporal model. The associations between the cord blood steroids and the air pollutants were tested and estimated by first fitting linear regression models and followed by fitting weekly prenatal exposures to distributed lag models (DLM). These analyses accounted for possible confounders, coexposures, and an interaction effect between sex and the exposure. We examined mixture effects and critical exposure windows of PM2.5, NO2 and BC on cord blood steroids via the Bayesian kernel machine regression distributed lag model (BKMR-DLM).An interquartile range (IQR) increment of 7.96 µg/m3 in PM2.5 exposure during pregnancy trimester 3 was associated with an increase of 23.01% (99% confidence interval: 3.26–46.54%) in cord blood levels of 17α-hydroxypregnenolone, and an IQR increment of 0.58 µg/m³ in BC exposure during trimester 1 was associated with a decrease of 11.00% (99% CI: -19.86 to -0.012%) in cord blood levels of androstenedione. For these two models, the DLM statistics identified sensitive gestational time windows for cord blood steroids and ambient air pollution exposures, in particular for 17α-hydroxypregnenolone and PM2.5 exposure during trimester 3 (weeks 28–36) and for androsterone and BC exposure during early pregnancy (weeks 2–13) as well as during mid-pregnancy (weeks 18–26). We identified interaction effects between pollutants, which has been suggested especially for NO2.Our results suggest that prenatal exposure to ambient air pollutants during pregnancy interferes with steroid levels in cord blood. Further studies should investigate potential early-life action mechanisms and possible later-in-life adverse effects of hormonal disturbances due to air pollution exposure.

Prenatal and postnatal exposure to heavy metals in PM2.5 and autism spectrum disorder

Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders, and its incidence is increasing over time. Although several environmental factors have been suspected to be risk factors for ASD, studies on the effects of airborne heavy metals on newly developed ASD are still limited. We conducted a large birth cohort study of 168,062 live term births in Taichung during 2004–2011 to assess the association of heavy metals in particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) with ASD, and identify sensitive time windows during prenatal and postnatal periods. Heavy metals, including arsenic (As), cadmium (Cd), mercury (Hg), and lead (Pb) in PM2.5, were estimated using the Weather Research and Forecasting/Chem (WRF/Chem), inserted from the top 75 emission sources for the module. The association between childhood ASD and 4 metals were analyzed from pregnancy to 9 months after birth. The Cox proportional hazard model with a distributed lag nonlinear model (DLNM) was used to estimate the association between heavy metals in PM2.5 and ASD. We identified 666 incident ASD cases in 168,062 participants. A positive association between Hg and ASD was found at 9 months after birth (Hazard Ratio: 1.63; 95% CI: 1.13–2.36). According to the DLNM, there was an increased risk of exposure to Hg during 10–25 weeks after birth, and decreased risk of exposure to Hg during gestational weeks 4–6. Exposure to As and Hg on the risk of ASD were significantly stronger in low birth weight infants (<2500 g) than in those of birth weight ≥2500 g during postnatal period. Postnatal exposure to Hg in PM2.5 may associate with increased ASD incidence. Infants with low birth weight and exposure to As and Hg in PM2.5 are more likely to develop ASD.

Low-dose Bisphenol A exposure alters the functionality and cellular environment in a human cardiomyocyte model

Early embryonic development represents a sensitive time-window during which the foetus might be vulnerable to the exposure of environmental contaminants, potentially leading to heart diseases also later in life. Bisphenol A (BPA), a synthetic chemical widely used in plastics manufacturing, has been associated with heart developmental defects, even in low concentrations. This study aims to investigate the effects of environmentally relevant doses of BPA on developing cardiomyocytes using a human induced pluripotent stem cell (hiPSC)-derived model. Firstly, a 2D in vitro differentiation system to obtain cardiomyocytes from hiPSCs (hiPSC-CMs) have been established and characterised to provide a suitable model for the early stages of cardiac development. Then, the effects of a repeated BPA exposure, starting from the undifferentiated stage throughout the differentiation process, were evaluated. The chemical significantly decreased the beat rate of hiPSC-CMs, extending the contraction and relaxation time in a dose-dependent manner. Quantitative proteomics analysis revealed a high abundance of basement membrane (BM) components (e.g., COL4A1, COL4A2, LAMC1, NID2) and a significant increase in TNNC1 and SERBP1 proteins in hiPSC-CMs treated with BPA. Network analysis of proteomics data supported altered extracellular matrix remodelling and provided a disease-gene association with well-known pathological conditions of the heart. Furthermore, upon hypoxia-reoxygenation challenge, hiPSC-CMs treated with BPA showed higher rate of apoptotic events. Taken together, our results revealed that a long-term treatment, even with low doses of BPA, interferes with hiPSC-CMs functionality and alters the surrounding cellular environment, providing new insights about diseases that might arise upon the toxin exposure. Our study contributes to the current understanding of BPA effects on developing human foetal cardiomyocytes, in correlation with human clinical observations and animal studies, and it provides a suitable model for New Approach Methodologies (NAMs) for environmental chemical hazard and risk assessment.

Prenatal exposure to environmental air pollution and psychosocial stress jointly contribute to the epigenetic regulation of the serotonin transporter gene in newborns.

Antenatal exposures to maternal stress and to particulate matter with an aerodynamic diameter of less than 2.5 μm (PM2.5) have been independently associated with developmental outcomes in early infancy and beyond. Knowledge about their joint impact, biological mechanisms of their effects and timing-effects, is still limited. Both PM2.5 and maternal stress exposure during pregnancy might result in altered patterns of DNA methylation in specific stress-related genes, such as the serotonin transporter gene (SLC6A4 DNAm), that might, in turn, influence infant development across several domains, including bio-behavioral, cognitive and socio-emotional domains. Here, we investigated the independent and interactive influence of variations in antenatal exposures to maternal pandemic-related stress (PRS) and PM2.5 onSLC6A4 DNAmlevels in newborns. Mother-infant dyads (N = 307) were enrolled at delivery during the COVID-19 pandemic. Infants' methylation status was assessed in 13 CpG sites within the SLC6A4gene's region (chr17:28562750-28562958) in buccal cells at birth and women retrospectively report on PRS. PM2.5 exposure throughout the entire gestation and at each gestational trimester was estimated using a spatiotemporal model based on residential address. Among several potentially confounding socio-demographic and health-related factors, infant's sex was significantly associated with infants' SLC6A4 DNAm levels, thus hierarchical regression models were adjusted for infant's sex. Higher levels of SLC6A4 DNAm at 6 CpG sites werefound in newborns born to mothers reporting higherlevels of antenatal PRS and greater PM2.5exposureacross gestation, while adjusting for infant's sex. These effectswere especially evident when exposure toelevated PM2.5 occurred during the second trimester ofpregnancy. Several important brain processes (e.g., synaptogenesis and myelination) occur during mid-pregnancy, potentially making the second trimester a sensitive time window for the effects of stress-related exposures. Understanding the interplay between environmental and individual-level stressors has important implications for the improvement of mother-infant health during and after the pandemic.

Association between exposure to air pollution during preconception and risk of gestational diabetes mellitus: The role of anti-inflammatory diet

BackgroundRegarding the association between the sensitive time-windows of air pollution (AP) exposure and gestational diabetes mellitus (GDM), epidemiological findings are inconsistent. The dietary inflammatory potential has been implicated in the development of GDM, but it is unclear whether an anti-inflammatory diet during pregnancy reduces the association between AP and GDM. ObjectiveWe aimed to characterize the sensitive time-windows of AP to GDM risk. Further, to verify whether a maternal anti-inflammatory diet can reduce the risk of AP-induced GDM, by inhibiting inflammation. MethodsA total of 8495 pregnant women were included between 2015 and 2021 in the Maternal & Infants Health in Hefei study. Weekly mean AP exposure to fine particles (PM2.5 and PM10), SO2, and NO2 was estimated from the data of Hefei City Ecology and Environment Bureau. High-sensitivity C-reactive protein (hs-CRP) concentrations were measured to evaluate systemic inflammation. The empirical dietary inflammatory pattern (EDIP) score based on a validated food frequency questionnaire was used to assess the dietary inflammatory potential of pregnant women.Logistic regression models with distributed lags were used to identify the sensitive time-window for the effect of AP on GDM. Mediation analysis estimated the mediated effect of hs-CRP, linking AP with GDM. Stratified analysis was used to investigate the potential effect of anti-inflammatory diet on GDM risk. ResultsThe increased risks of GDM were found to be positively associated with exposure to PM2.5 (OR = 1.11, 95% CI:1.07–1.15), PM10 (OR = 1.12, 95% CI:1.09–1.16), and SO2 (OR = 1.42, 95% CI:1.25–1.60) by distributed lag models, and the critical exposure windows were 21st to 28th weeks of preconception. The proportion of association between PM2.5, PM10, and SO2 with GDM mediated by hs-CRP was 25.9%, 21.1%, and 19.4%, respectively, according to mediation analysis. In the stratified analyses by EDIP, the association between AP and GDM was not statistically significant among women those with anti-inflammatory diets. ConclusionsExposure to AP, especially in 21st to 28th week of preconception, is associated with risk of GDM, which is partly mediated by hs-CRP. Adherence to the anti-inflammatory dietary pattern may reduce the risk of AP-induced GDM.

Prenatal Exposure to Air Pollution and Pre-Labor Rupture of Membranes in a Prospective Cohort Study: The Role of Maternal Hemoglobin and Iron Supplementation.

Exposure to air pollution in prenatal period is associated with prelabor rupture of membranes (PROM). However, the sensitive exposure time windows and the possible biological mechanisms underlying this association remain unclear. We aimed to identify the sensitive time windows of exposure to air pollution for PROM risk. Further, we examined whether maternal hemoglobin levels mediate the association between exposure to air pollution and PROM, as well as investigated the potential effect of iron supplementation on this association. From 2015 to 2021, 6,824 mother-newborn pairs were enrolled in the study from three hospitals in Hefei, China. We obtained air pollutant data [particulate matter (PM) with aerodynamic diameter (), PM with aerodynamic diameter (), sulfur dioxide (), and carbon monoxide (CO)] from the Hefei City Ecology and Environment Bureau. Information on maternal hemoglobin levels, gestational anemia, iron supplementation, and PROM was obtained from medical records. Logistic regression models with distributed lags were used to identify the sensitive time window for the effect of prenatal exposure to air pollutant on PROM. Mediation analysis estimated the mediated effect of maternal hemoglobin in the third trimester, linking prenatal air pollution with PROM. Stratified analysis was used to investigate the potential effect of iron supplementation on PROM risk. We found significant association between prenatal exposure to air pollution and increased PROM risk after adjusting for confounders, and the critical exposure windows of , , and CO were the 21th to 24th weeks of pregnancy. Every increase in and , increase in , and increase in CO was associated with low maternal hemoglobin levels [ (95% confidence interval (CI): , ), (95% CI: , ), (95% CI: , ), and (95% CI: , ), respectively] in the third trimester. The proportion of the association between air pollution and PROM risk mediated by hemoglobin levels was 20.61% [average mediation effect (95% CI): 0.02 (0.01, 0.05); average direct effect (95%): 0.08 (0.02, 0.14)]. The PROM risk associated with exposure to low-medium air pollution could be attenuated by maternal iron supplementation in women with gestational anemia. Prenatal exposure to air pollution, especially in the 21st to 24th weeks of pregnancy, is associated with PROM risk, which is partly mediated by maternal hemoglobin levels. Iron supplementation in anemia pregnancies may have protective effects against PROM risk associated with exposure to low-medium air pollution. https://doi.org/10.1289/EHP11134.

In Utero Exposure to Air Pollutants and Mitochondrial Heteroplasmy in Neonates.

Mitochondria are sensitive to oxidative stress, which can be caused by traffic-related air pollution. Placental mitochondrial DNA (mtDNA) mutations have been previously linked with air pollution. However, the relationship between prenatal air pollution and cord-blood mtDNA mutations has been poorly understood. Therefore, we hypothesized that prenatal particulate matter (PM2.5) and NO2 exposures are associated with cord-blood mtDNA heteroplasmy. As part of the ENVIRONAGE cohort, 200 mother-newborn pairs were recruited. Cord-blood mitochondrial single-nucleotide polymorphisms were identified by whole mitochondrial genome sequencing, and heteroplasmy levels were evaluated based on the variant allele frequency (VAF). Outdoor PM2.5 and NO2 concentrations were determined by a high-resolution spatial-temporal interpolation method based on the maternal residential address. Distributed lag linear models were used to determine sensitive time windows for the association between NO2 exposure and cord-blood mtDNA heteroplasmy. A 5 μg/m3 increment in NO2 was linked with MT-D-Loop16311T>C heteroplasmy from gestational weeks 17-25. MT-CYTB14766C>T was negatively associated with NO2 exposure in mid pregnancy, from weeks 14-17, and positively associated in late pregnancy, from weeks 31-36. No significant associations were observed with prenatal PM2.5 exposure. This is the first study to show that prenatal NO2 exposure is associated with cord-blood mitochondrial mutations and suggests two critical windows of exposure in mid-to-late pregnancy.

Maternal Sleep Problems in the Periconceptional Period and the Impact on Health of Mother and Offspring: A Systematic Review.

Knowledge of the impact of sleep problems in the periconceptional period is scarce. Since this period is the most sensitive time window for embryonic and placental development, we aim to study the impact of maternal sleep problems in the periconceptional period on both mother and offspring. We systematically searched various databases up until September 2021 for studies reporting on maternal sleep in the periconceptional period and any outcome in mother and offspring. We included observational studies describing maternal sleep problems in the periconceptional period and associations with either maternal and/or offspring outcomes. The search produced 8596 articles, of which we selected 27 studies. Some associations were found between sleep problems and lower fertility, more hypertensive disorders, more mood disorders in mothers, higher risk of preterm birth and low birth weight, and more sleep and behavior problems in offspring, with associations with maternal mood disorders being most consistent. This systematic review shows that maternal sleep problems in the periconceptional period are associated with a higher risk of various adverse outcomes in both mother and offspring, although not consistently. It shows that good sleep during pregnancy is crucial, starting as early as before conception, especially for maternal mood. Therefore, it is important for clinicians to pay attention to sleep problems in the periconceptional period and provide adequate treatment for potential sleep problems, even before pregnancy.

Povidone iodine exposure alters the immune response and microbiota of the gill and skin in koi carp, Cyprinus carpio

Povidone‑iodine (PVP-I) is a disinfectant widely used to prevent and treat bacterial diseases in fish. The use of PVP-I may disturb the microbial community on the fish body surface and thereby facilitate pathogen invasion. We aimed to assess the effects of PVP-I on the immune system and bacterial communities of skin and gill in Cyprinus carpio. Fish were disinfected with 7.5 mL/m3 of PVP-I (1%) for 30 min, and then skin and gill tissues were sampled on days 0, 1, 3, 7, and 14 for the determination of immunity parameters and characterization of surface bacterial communities. Control fish were not disinfected. The results indicated that exposure to PVP-I decreased the activities of gill lysozyme on day 1, and significantly increased the activities of gill SOD and Na-ATPase on day 7. The activity of skin SOD was enhanced on day 3. The PVP-I bath enhanced the mRNA expression of lysozyme, sod, and cat in the gill but decreased lysozyme on days 1–7 and sod on days 7–14 in the skin. The mRNA expression of tight junction proteins was enhanced in both gill and skin tissue. PVP-I decreased gill bacterial richness on days 3 and 7, and reduced bacterial diversity on day 7. The gill microbiota on day 7 was remarkably separate from the control. The skin microbiota on days 1 and 3 was significantly separated from that of the control. In summary, PVP-I elicited shifts in the immune response and changes in the surface microbiota of fish, and the sensitive time windows of microbial fluctuation after PVP-I treatment were three days in the skin and seven days in the gill.

Gene-environment interactions in Alzheimer disease: the emerging role of epigenetics.

With the exception of a few monogenic forms, Alzheimer disease (AD) has a complex aetiology that is likely to involve multiple susceptibility genes and environmental factors. The role of environmental factors is difficult to determine and, until a few years ago, the molecular mechanisms underlying gene-environment (G × E) interactions in AD were largely unknown. Here, we review evidence that has emerged over the past two decades to explain how environmental factors, such as diet, lifestyle, alcohol, smoking and pollutants, might interact with the human genome. In particular, we discuss how various environmental AD risk factors can induce epigenetic modifications of key AD-related genes and pathways and consider how epigenetic mechanisms could contribute to the effects of oxidative stress on AD onset. Studies on early-life exposures are helping to uncover critical time windows of sensitivity to epigenetic influences from environmental factors, thereby laying the foundations for future primary preventative approaches. We conclude that epigenetic modifications need to be considered when assessing G × E interactions in AD.

Post-partum Women’s Anxiety and Parenting Stress: Home-Visiting Protective Effect During the COVID-19 Pandemic

ObjectivesThe COVID-19 pandemic resulted in a particularly adverse and stressful environment for expecting mothers, possibly enhancing feelings of anxiety and parenting stress. The present work assesses mothers' anxiety levels at delivery and parenting stress after 3 months as moderated by home-visiting sessions.MethodsWomen (n = 177) in their second or third trimester of pregnancy during the COVID-19 lockdown were enrolled in northern Italy and split into those who did and did not receive home visits. After 3 months, the association between anxiety at delivery and parenting stress was assessed with bivariate correlations in the whole sample and comparing the two groups.ResultsHigher anxiety at birth correlated with greater perceived stress after 3 months. Mothers who received at least one home-visiting session reported lower parenting stress at 3 months than counterparts who did not receive home visits.Conclusions for PracticeThe perinatal period is a sensitive time window for mother-infant health, especially during a critical time like the COVID-19 pandemic. We suggest that home-visiting programs could be beneficial during global healthcare emergencies to promote maternal well-being after delivery.

The acute effect and lag effect analysis between exposures to ambient air pollutants and spontaneous abortion: a case-crossover study in China, 2017–2019

IntroductionRecent studies demonstrated that living in areas with high ambient air pollution may have adverse effects on pregnancy outcomes, but few studies have investigated its association with spontaneous abortion. Further investigation is needed to explore the acute effect and lag effect of air pollutants exposure on spontaneous abortion.ObjectiveTo investigate the acute effect and lag effect between exposure to ambient air pollutants and spontaneous abortion.MethodsResearch data of spontaneous abortion were collected from the Chongqing Health Center for Women and Children (CQHCWC) in China. The daily ambient air pollution exposure measurements were estimated for each woman using inverse distance weighting from monitoring stations. A time-stratified, case-crossover design combined with distributed lag linear models was applied to assess the associations between spontaneous pregnancy loss and exposure to each of the air pollutants over lags 0–7 days, adjusted for temperature and relative humidity.ResultsA total of 1399 women who experienced spontaneous pregnancy loss events from November 1, 2016, to September 30, 2019, were selected for this study. Maternal exposure to particulate matter 2.5 (PM2.5), particle matter 10 (PM10) nitrogen dioxide (NO2), and sulfur dioxide (SO2) exhibited a significant association with spontaneous abortion. For every 20 μg/m3 increase in PM2.5, PM10, NO2, and SO2, the RRs were 1.18 (95% CI: 1.06, 1.34), 1.12 (95% CI, 1.04–1.20), 1.15 (95% CI: 1.02, 1.30), and 1.92 (95% CI: 1.18, 3.11) on lag day 3, lag day 3, lag day 0, and lag day 3, respectively. In two-pollutant model combined with PM2.5 and PM10, a statistically significant increase in spontaneous abortion incidence of 18.0% (RR = 1.18, 95% CI: 1.06, 1.32) was found for a 20 μg/m3 increase in PM2.5 exposure, and 11.2% (RR = 1.11, 95% CI: 1.03, 1.20) for a 20 μg/m3 increase in PM10 exposure on lag day 3, similar to single-pollutant model analysis.ConclusionMaternal exposure to high levels of PM2.5, PM10, NO2, and SO2 during pregnancy may increase the risk of spontaneous abortion for acute effects and lag effects. Further research to explore sensitive exposure time windows is needed.