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In this study, associations between prenatal exposure to fine particulate matter (PM2.5) from 9 sources and development of autism spectrum disorder (ASD) were assessed in a population-based retrospective pregnancy cohort in southern California. The cohort included 318,750 mother-child singleton pairs. ASD cases (N = 4559) were identified by ICD codes. Source-specific PM2.5 concentrations were estimated from a chemical transport model with a 4 × 4 km2 resolution and assigned to maternal pregnancy residential addresses. Cox proportional hazard models were used to estimate the hazard ratios (HR) of ASD development for each individual source. We also adjusted for total PM2.5 mass and in a separate model for all other sources simultaneously. Increased ASD risk was observed with on-road gasoline (HR [CI]: 1.18 [1.13, 1.24]), off-road gasoline (1.15 [1.12, 1.19]), off-road diesel (1.08 [1.05, 1.10]), food cooking (1.05 [1.02, 1.08]), aircraft (1.04 [1.01, 1.06]), and natural gas combustion (1.09 [1.06, 1.11]), each scaled to standard deviation increases in concentration. On-road gasoline and off-road gasoline were robust for other pollutant groups. PM2.5 emitted from different sources may have different impacts on ASD. The results also identify PM source mixtures for toxicological investigations that may provide evidence for future public health policies.

Polychlorinated biphenyls (PCBs) and their metabolites are linked to developmental neurotoxicity, but their levels in the gestational and lactational environment remain unexplored. This study investigated the effects of dietary exposure to the Fox River Mixture (FRM) on serum levels of PCBs and their metabolites in female C57BL/6 J mice. Mice were exposed to 0.1, 1.0, or 6.0 mg/kg body weight/day of FRM beginning two weeks before mating and throughout gestation and lactation. Serum samples collected from the dams at weaning were analyzed using gas chromatograph-tandem mass spectrometry and nontarget liquid chromatography-high resolution mass spectrometry. Results showed complex and dose-dependent differences in PCB and metabolite profiles. Untargeted metabolomics revealed alterations in metabolites involved in glucuronidation. Network analysis suggested disturbances in heme and amino acid metabolism associated with higher chlorinated PCBs. These findings suggested that PCBs and metabolites present in the gestational and lactation environment of mice may contribute to developmental neurotoxicity in rodents.

Pregnancy is a time of high metabolic coordination, as maternal metabolism adapts to support the growing fetus. Many of these changes are coordinated by the placenta, a critical fetal endocrine organ and the site of maternal-fetal crosstalk. Dysregulation in maternal and placental metabolism during pregnancy has been linked to adverse outcomes, including altered neurodevelopment. Autism spectrum disorder (ASD) is a neurodevelopmental disorder linked to metabolic alterations in both children and their mothers. Prenatal environmental exposures have been linked to risk of ASD through dysregulated maternal, placental, and fetal metabolism. In this review, we focus on recent studies investigating the associations between prenatal metabolism in the maternal-placental-fetal unit and the impact of prenatal environmental exposures to phthalates and micronutrients on ASD risk. By identifying the mechanisms through which phthalates and other ubiquitous endocrine disrupting chemicals influence development, and how nutritional interventions can impact those mechanisms, we can identify promising ways to prevent suboptimal neurodevelopment.

Purpose of reviewDepression during the perinatal or antenatal period affects at least 1 in 10 women worldwide, with long term health implications for the mother and child. Concurrently, there is increasing evidence associating maternal exposure to per- and poly-fluoroalkyl substances (PFAS) to adverse pregnancy outcomes. We reviewed the body of evidence examining both the associations between PFAS exposure and perturbations in the maternal metabolome, and the associations between the maternal metabolome and perinatal/antenatal depression. Through this, we sought to explore existing evidence of the perinatal metabolome as a potential mediation pathway linking PFAS exposure and perinatal/antenatal depression.Recent findingsThere are few studies examining the metabolomics of PFAS exposure-specifically in pregnant women-and the metabolomics of perinatal/antenatal depression, let alone studies examining both simultaneously. Of the studies reviewed (N = 11), the majority were cross sectional, based outside of the US, and conducted on largely homogenous populations. Our review identified 23 metabolic pathways in the perinatal metabolome common to both PFAS exposure and perinatal/antenatal depression. Future studies may consider findings from our review to conduct literature-derived hypothesis testing focusing on fatty acid metabolism, alanine metabolism, glutamate metabolism, and tyrosine metabolism when exploring the biochemical mechanisms conferring the risk of perinatal/antenatal depression due to PFAS exposure. We recommend that researchers also utilize heterogenous populations, longitudinal study designs, and mediation approaches to elucidate key pathways linking PFAS exposures to perinatal/antenatal depression.

PURPOSE OF REVIEW: Environmental chemical exposures may disrupt child development, with long-lasting health impacts. To date, U.S. studies of early environmental exposures have been limited in size and diversity, hindering power and generalizability. With harmonized data from over 60,000 participants representing 69 pregnancy cohorts, the National Institutes of Healths Environmental influences on Child Health Outcomes (ECHO) Program is the largest study of U.S. childrens health. Here, we: (1) review ECHO-wide studies of chemical exposures and maternal-child health; and (2) outline opportunities for future research using ECHO data. RECENT FINDINGS: As of early 2024, in addition to over 200 single-cohort (or award) papers on chemical exposures supported by ECHO, ten collaborative multi-cohort papers have been made possible by ECHO data harmonization and new data collection. Multi-cohort papers have examined prenatal exposure to per- and polyfluoroalkyl substances (PFAS), phthalates, phenols and parabens, organophosphate esters (OPEs), metals, melamine and aromatic amines, and emerging contaminants. They have primarily focused on describing patterns of maternal exposure or examining associations with maternal and infant outcomes; fewer studies have examined later child outcomes (e.g., autism) although follow up of enrolled ECHO children continues. The NICHDs Data and Specimen Hub (DASH) database houses extensive ECHO data including over 470,000 chemical assay results and complementary data on priority outcome areas (pre, peri-, and postnatal, airway, obesity, neurodevelopment, and positive health), making it a rich resource for future analyses. ECHOs extensive data repository, including biomarkers of chemical exposures, can be used to advance our understanding of environmental influences on childrens health. Although few published studies have capitalized on these unique harmonized data to date, many analyses are underway with data now widely available.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) have been linked to adverse birth outcomes that have been reported to be induced by oxidative stress, but few epidemiological studies to date have evaluated associations between urinary PAH metabolites and oxidative stress biomarkers in pregnancy and identified critical periods for these outcomes and PAH exposures in pregnancy. METHODS: A cohort of pregnant women was recruited early in pregnancy from antenatal clinics at the University of California Los Angeles during 2016-2019. We collected urine samples up to three times during pregnancy in a total of 159 women enrolled in the cohort. A total of 7 PAH metabolites and 2 oxidative stress biomarkers [malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG)] were measured in all available urine samples. Using multiple linear regression models, we estimated the percentage change (%) and 95% confidence interval (CI) in 8-OHdG and MDA measured at each sample collection time per doubling of PAH metabolite concentrations. Furthermore, we used linear mixed models with a random intercept for participant to estimate the associations between PAH metabolite and oxidative stress biomarker concentrations across multiple time points in pregnancy. RESULTS: Most PAH metabolites were positively associated with both urinary oxidative stress biomarkers, MDA and 8-OHdG, with stronger associations in early and late pregnancy. A doubling of each urinary PAH metabolite concentration increased MDA concentrations by 5.8-41.1% and 8-OHdG concentrations by 13.8-49.7%. Linear mixed model results were consistent with those from linear regression models for each gestational sampling period. CONCLUSION: Urinary PAH metabolites are associated with increases in oxidative stress biomarkers during pregnancy, especially in early and late pregnancy.

ImportanceResearch on fetal epigenetic programming suggests that the intrauterine environment can have long-term effects on offspring disease susceptibility.ObjectiveTo examine the association between prenatal maternal occupation and child epigenetic age acceleration (EAA) among a farmworker community.Design, setting, and participantsThis cohort study included participants in the Center for the Health Assessment of Mothers and Children of Salinas, a prospective, Latino, prebirth cohort. Pregnant women were recruited from October 1, 1999, to October 1, 2000, from 6 community clinics in California's Salinas Valley agricultural region. Participants were 18 years or older, English or Spanish speaking, Medicaid eligible, and at 20 weeks' gestation or earlier at enrollment. Mother-child pairs who had blood DNA methylation measured at the ages of 7, 9, and 14 years were included. Data were analyzed from July 2021 to November 2023.ExposuresPrenatal maternal occupation was ascertained through study interviews conducted during prenatal visits and shortly after delivery.Main outcomes and measuresChild EAA at 7, 9, and 14 years of age was estimated using DNA methylation-based epigenetic age biomarkers. Three EAA measures were calculated: the Horvath EAA, skin and blood EAA, and intrinsic EAA. Linear mixed-effects models were used to estimate longitudinal associations of prenatal maternal occupation and child EAA, adjusting for confounders and prenatal organophosphate pesticide exposure.ResultsAnalyses included 290 mother-child pairs (mean [SD] maternal age at delivery, 26.5 [5.2] years; 152 [52.4%] female infants); 254 mothers (87.6%) were born in Mexico, 33 (11.4%) in the US, and 3 (1.0%) in other countries; and 179 families (61.7%) were below the federal poverty line during pregnancy. Mothers reported engaging in several types of work during pregnancy, including agricultural fieldwork (90 [31.0%]), other agricultural work (40 [13.8%]), nonagricultural work (53 [18.3%]), or no work (107 [36.9%]). Children whose mothers worked in agricultural fields during pregnancy had a mean of 0.66 (95% CI, 0.17-1.15) years of greater Horvath EAA, 0.62 (95% CI, 0.31-0.94) years of greater skin and blood EAA, and 0.45 (95% CI, 0.07-0.83) years of greater intrinsic EAA compared with children whose mothers did not work during pregnancy.Conclusions and relevanceIn this cohort study, prenatal maternal agricultural fieldwork was associated with accelerated childhood epigenetic aging independent of organophosphate pesticide exposure. Future research on which factors related to agricultural fieldwork accelerate aging in the next generation can inform targeted prevention programs and policies that protect children's health.

BackgroundMaternal solvent exposure has been suspected to increase offspring cancer risk. The study aimed to evaluate the associations between maternal residential exposure to solvents from industrial pollution during pregnancy and childhood cancer.MethodsThe present study included 15,744 cancer cases (aged 0-19 years at diagnosis) identified from California Cancer Registry and 283,141 controls randomly selected from California Birth Registry (20:1 frequency-matched by birth year: 1998-2016). We examined industrial releases of tetrachloroethylene and 1,1,1-trichloroethane within 3 km of the birth address, while we used a 5 km buffer for carbon disulfide. We calculated the total exposure from all linked Toxic Release Inventory sites during each index pregnancy and assigned "ever/never" and "high/low exposed/unexposed" exposure, using median values. We performed quadratic decay models to estimate cancer risks associated with maternal solvent exposure in pregnancy.Results1,1,1-Trichloroethane was associated with rhabdomyosarcoma (adjusted Odds Ratio (aOR): 1.96; 95% Confidence Interval (CI): 1.16, 3.32) in the "ever exposed" group. Ever exposure to carbon disulfide was associated with increased risks of medulloblastoma (OR = 1.85, 95% CI 1.01, 3.40) and ependymoma (OR = 1.63, 95% CI 0.97, 2.74).ConclusionsOverall, our findings suggested maternal residential exposure to solvents from industrial sources might be associated with elevated childhood cancer risks.

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

BACKGROUND: Wildfires in the Western United States are a growing and significant source of air pollution that is eroding decades of progress in air pollution reduction. The effects on preterm birth during critical periods of pregnancy are unknown. METHODS: We assessed associations between prenatal exposure to wildland fire smoke and risk of preterm birth (gestational age

BACKGROUND: Epidemiological findings regarding the association of particulate matter ≤2.5 μm (PM2.5) exposure with hypertensive disorders in pregnancy (HDP) are inconsistent; evidence for HDP risk related to PM2.5 components, mixture effects, and windows of susceptibility is limited. We aimed to investigate the relationships between HDP and exposure to PM2.5 during pregnancy. METHODS AND FINDINGS: A large retrospective cohort study was conducted among mothers with singleton pregnancies in Kaiser Permanente Southern California from 2008 to 2017. HDP were defined by International Classification of Diseases-9/10 (ICD-9/10) diagnostic codes and were classified into 2 subcategories based on the severity of HDP: gestational hypertension (GH) and preeclampsia and eclampsia (PE-E). Monthly averages of PM2.5 total mass and its constituents (i.e., sulfate, nitrate, ammonium, organic matter, and black carbon) were estimated using outputs from a fine-resolution geoscience-derived model. Multilevel Cox proportional hazard models were used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of PM2.5 constituents. The distributed lag model was applied to estimate the association between monthly PM2.5 exposure and HDP risk. This study included 386,361 participants (30.3 ± 6.1 years) with 4.8% (17,977/373,905) GH and 5.0% (19,381/386,361) PE-E cases, respectively. In single-pollutant models, we observed increased relative risks for PE-E associated with exposures to PM2.5 total mass [adjusted hazard ratio (HR) per interquartile range: 1.07, 95% confidence interval (CI) [1.04, 1.10] p < 0.001], black carbon [HR = 1.12 (95% CI [1.08, 1.16] p < 0.001)] and organic matter [HR = 1.06 (95% CI [1.03, 1.09] p < 0.001)], but not for GH. The population attributable fraction for PE-E corresponding to the standards of the US Environmental Protection Agency (9 μg/m3) was 6.37%. In multi-pollutant models, the PM2.5 mixture was associated with an increased relative risk of PE-E ([HR = 1.05 (95% CI [1.03, 1.07] p < 0.001)], simultaneous increase in PM2.5 constituents of interest by a quartile) and PM2.5 black carbon gave the greatest contribution of the overall mixture effects (71%) among all individual constituents. The susceptible window is the late first trimester and second trimester. Furthermore, the risks of PE-E associated with PM2.5 exposure were significantly higher among Hispanic and African American mothers and mothers who live in low- to middle-income neighborhoods (p < 0.05 for Cochrans Q test). Study limitations include potential exposure misclassification solely based on residential outdoor air pollution, misclassification of disease status defined by ICD codes, the date of diagnosis not reflecting the actual time of onset, and lack of information on potential covariates and unmeasured factors for HDP. CONCLUSIONS: Our findings add to the literature on associations between air pollution exposure and HDP. To our knowledge, this is the first study reporting that specific air pollution components, mixture effects, and susceptible windows of PM2.5 may affect GH and PE-E differently.

Maternal use of e-cigarette (e-cig) aerosols poses significant risks to fetal brain development, potentially increasing susceptibility to neurodevelopmental disorders in later life. However, the underlying mechanisms remain incompletely understood. This study aimed to understand the effects of fetal e-cig exposure on DNA methylome and transcriptomic changes in the neonatal brain. Pregnant rats were exposed to e-cig aerosols, and neonatal brains (5 males and 5 females/group) from both control and e-cig-exposed groups were used for experimental analysis. Results indicated that prenatal e-cig exposure altered site-specific DNA methylation patterns at both CpG and CH (non-CpG) sites, predominantly in intergenic and intronic regions, with sex dimorphism in methylation and gene expression changes. Gene ontology analysis revealed that e-cig exposure not only affected neuron projection development and axonogenesis but also altered pathways related to neurodegeneration and long-term depression. These findings provide novel insights into the dynamic changes of CpG and CH methylation induced by e-cig exposure, underscoring the susceptibility of the developing brain to maternal e-cig exposure and its potential implications for developmental disorders and neurodegenerative diseases later in life.

BackgroundFluoride exposure during pregnancy has been associated with various effects on offspring, including changes in behavior and IQ. To provide clues to possible mechanisms by which fluoride may affect human fetal development, we completed proteomic analyses of cord blood serum collected from second-trimester pregnant women residing in northern California, USA.ObjectiveTo identify changes in cord blood proteins associated with maternal serum fluoride concentration in pregnant women.MethodsThe proteomes of 19 archived second-trimester cord blood samples from women living in northern California, USA, and having varied serum fluoride concentrations, were analyzed by quantitative mass spectrometry. The 327 proteins that were quantified were characterized by their abundance relative to maternal serum fluoride concentration, and subjected to pathway analyses using PANTHER and Ingenuity Pathway Analysis processes.ResultsPathway analyses showed significant increases in process related to reactive oxygen species and cellular oxidant detoxification, associated with increasing maternal serum fluoride concentrations. Pathways showing significant decreases included complement cascade, suggesting alterations in alterations in process associated with inflammation.ConclusionMaternal fluoride exposure, as measured by serum fluoride concentrations in a small, but representative sample of women from northern California, USA, showed significant changes in the second trimester cord blood proteome relative to maternal serum fluoride concentration.

OBJECTIVE: Prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) is associated with adverse birth and developmental outcomes in children. We aimed to describe prenatal PAH exposures in a large, multisite U.S. consortium. METHODS: We measured 12 mono-hydroxylated metabolites (OH-PAHs) of 7 PAHs (naphthalene, fluorene, phenanthrene, pyrene, benzo(c)phenanthrene, chrysene, benz(a)anthracene) in mid-pregnancy urine of 1,892 pregnant individuals from the ECHO PATHWAYS consortium cohorts: CANDLE (n = 988; Memphis), TIDES (n = 664; Minneapolis, Rochester, San Francisco, Seattle) and GAPPS (n = 240; Seattle and Yakima, WA). We described concentrations of 8 OH-PAHs of non-smoking participants (n = 1,695) by site, socioeconomic characteristics, and pregnancy stage (we report intraclass correlation coefficients (ICC) for n = 677 TIDES participants). RESULTS: Exposure to the selected PAHs was ubiquitous at all sites. 2-hydroxynaphthalene had the highest average concentrations at all sites. CANDLE had the highest average concentrations of most metabolites. Among non-smoking participants, we observed some patterns by income, education, and race but these were not consistent and varied by site and metabolite. ICCs of repeated OH-PAH measures from TIDES participants were ≤ 0.51. CONCLUSION: In this geographically-diverse descriptive analysis of U.S. pregnancies, we observed ubiquitous exposure to low molecular weight PAHs, highlighting the importance of better understanding PAH sources and their pediatric health outcomes attributed to early life PAH exposure.

BackgroundAutism spectrum disorder (ASD) is a prevalent and heterogeneous neurodevelopmental disorder. Risk is attributed to genetic and prenatal environmental factors, though the environmental agents are incompletely characterized.MethodsIn Early Autism Risk Longitudinal Investigation (EARLI) and Markers of Autism Risk in Babies Learning Early Signs (MARBLES), two pregnancy cohorts of siblings of children with ASD, urinary metals concentrations during two pregnancy time periods (

The human immunodeficiency virus (HIV) heavily affects women from resource-limited settings who are vulnerable to potentially harmful mycotoxins including aflatoxin B1 (AFB1), fumonisin B1 (FB1) and ochratoxin A (OTA). We aimed to conduct biomonitoring and ascertain the determinants of maternal mycotoxin exposure in pregnancy, lactation and post-lactation periods. We conducted a retrospective longitudinal study in HIV-infected and HIV-uninfected women from Harare, Zimbabwe. 175 and 125 random urine samples in pregnancy and 24 months after delivery (post-lactation) respectively were analysed for aflatoxin M1 (AFM1) and FB1 by ELISA. 6 weeks after delivery (lactation), 226 and 262 breast milk (BM) samples were analysed for AFM1 and OTA respectively by ELISA. The association of demographics and food consumption with mycotoxins was evaluated using multivariable logistic regression. In HIV-infected, urinary AFM1 was detected in 46/94 (Median: 0.05; Range: 0.04–0.46 ng mL−1) in pregnancy and 47/66 (Median: 0.05; Range: 0.04–1.01 ng mL−1) post-lactation. Urinary FB1 was detected in 86/94 (Median: 1.39; Range: 0.17–6.02 ng mL−1) in pregnancy and 56/66 (Median: 0.72; Range: 0.20–3.81 ng mL−1) post-lactation. BM AFM1 was detected in 28/110 (Median: 7.24; Range: 5.96–29.80 pg mL−1) and OTA in 11/129 (Median: 0.20; Range: 0.14–0.65 ng mL−1). In HIV-uninfected, urinary AFM1 was detected in 48/81 (Median: 0.05; Range: 0.04–1.06 ng mL−1) in pregnancy and 41/59 (Median: 0.05; Range: 0.04–0.52 ng mL−1) post-lactation. Urinary FB1 was detected in 74/81 (Median: 1.15; Range: 0.17–6.16 ng mL−1) in pregnancy and 55/59 (Median: 0.96; Range: 0.20–2.82 ng mL−1) post-lactation. BM AFM1 was detected in 38/116 (Median: 7.70; Range: 6.07–31.75 pg mL−1) and OTA in 4/133 (Median: 0.24; Range: 0.18–0.83 ng mL−1). Location, wealth, and peanut butter consumption were determinants of AFB1 exposure. HIV infection, BMI, location, rainy season, unemployment, and age were determinants of FB1 exposure. Women especially those pregnant and/or HIV-infected are at risk of adverse effects of mycotoxins. [ABSTRACT FROM AUTHOR]

Adverse childhood experiences (ACEs) increase risk for mental illness in women and their children, and dysregulation of the hypothalamic-pituitary-adrenal axis may play a role. The impact of ACEs on the hypothalamic-pituitary-adrenal axis may be strongest when ACEs occur prepubertally and in people who are exposed to abuse ACEs. To test this, we measured salivary cortisol in 96 mother-infant dyads while mothers were separated from their infants, who were experiencing a laboratory stressor. Mothers completed the Adverse Childhood Experiences Questionnaire; ACEs that occurred prepubertally (pACEs) were measured, and mother-infant dyads were grouped based on maternal pACE history as follows: no pACEs, ≥1 pACEs with abuse, or ≥1 pACEs but no abuse. Mothers with ≥1 pACEs exhibited decreases in cortisol (relative to preinfant stressor), which differed significantly from the cortisol increase experienced by mothers with no pACEs, regardless of abuse presence (p =.001) or absence (p =.002). These pACE groups did not differ from one another (p =.929). Significant sex differences in infant cortisol were observed in infants of mothers with ≥1 pACEs (regardless of abuse) but not in infants of mothers with no pACEs. When mothers had experienced ≥1 pACEs, males showed decreases in cortisol in response to a stressor whereas females demonstrated increases, and males and females differed significantly when their mothers had ≥1 pACEs with (p =.025) and without (p =.032) abuse. Regardless of maternal exposure to childhood abuse, in response to a stressor, pACEs were associated with lower cortisol response in mothers and sex differences in 6-month-old infants, with males showing a lower cortisol response than females. [ABSTRACT FROM AUTHOR]

The prevalence of constant light exposure and high-fat diet in modern society raises concerns regarding their impact on maternal and offspring health outcomes. In rodents, exposure to maternal high-fat diet or continuous light negatively program metabolic and stress response outcomes of offspring. A 2x3 factorial study was conducted to investigate the impact of diet (control–CON, 10% fat, or high fat–HF, 60% fat) and exposure to different lighting conditions: regular 12-hour light-dark cycles (LD), continuous dim light (L5), or continuous bright light (L100) on female ICR mice daily patterns of time in and out of the nest, feed intake, and fecal corticosterone levels during gestation and lactation. Our previous analysis of these mice found HF diet decreased number of pups born, but increased litter growth rate to postnatal (PN) d12. Whereas continuous light increased gestation length and tended to increase PN litter growth. Here we report that patterns of grams of feed intake, an indicator of feeding activity, were affected by light, diet, period of the day (day versus night) and physiological state (gestation and lactation), with significant interactions among all these variables (P<0.05). HF diet and light treatment increased fecal corticosterone output (P<0.05) during lactation. Dams exhibited significant 12 h and 24 h rhythms of activity out of the nest in the first 48 h postnatal, with time outside of the nest greater in the second 24 h period. L100 treatment and HF diet attenuated rhythms and shifted phase of rhythms relative to LD and CON, respectively (P<0.05). Alterations in behavior affect maternal physiology, including level and timing of release of corticosteroids. Elevated fecal corticosterone levels due to high-fat diet and continuous light may have potential implications on maternal-offspring health, and potentially underlie some of the adverse effects of modern lifestyle factors on maternal and offspring health. [ABSTRACT FROM AUTHOR]

We investigated associations between prenatal genocidal trauma, including maternal rape, and postnatal adverse childhood experiences (ACEs) on DNA methylation of genes associated with the stress response. In a comparative cross-sectional study of 91 Rwandan young adults, categorized by prenatal exposure to genocide and maternal rape, genocide without rape, and unexposed controls, we analyzed DNA methylation from dried blood spots and assessed ACEs and depression and anxiety symptoms at age 24. Prenatal exposure to maternal rape was associated with DNA methylation changes in BDNF and SLC6A4, with the association in BDNF attenuated after including ACE exposure in the model. Genocide exposure without rape was associated with methylation changes in PRDM8 after adjusting for early adversity. Methylation in BDNF and SLC6A4 correlated with depression and anxiety symptoms. These findings underscore the impact of prenatal and postnatal trauma on DNA methylation and mental wellbeing, emphasizing the need for continued support for survivors in the decades after conflict. [ABSTRACT FROM AUTHOR]

AbstractMaternal exposure to zearalenone (ZEA), a mycotoxin, can impact fetal liver development. This study investigated the protective effects of carvacrol (CRV) against ZEA-induced fetal liver damage. Thirty-two pregnant rats were allocated to four groups (eight rats/group); control, CRV (75 mg/kg), ZEA (5 mg/kg), and co-treated group (ZEA + CRV). The animals were given their doses during the gestation period. Maternal exposure to ZEA revealed a significant increase in the malondialdehyde (MDA) level in the fetal liver. In contrast, glutathione S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT) activities, besides glutathione (GSH) levels, were decreased in ZEA-intoxicated rats. Additionally, ZEA increased the expression of pro-apoptotic genes (P53, Bax, and caspase-9), elevated the immunoreactivity of caspase-3, decreased anti-apoptotic Bcl-2, and induced severe fatty degeneration, congestion, and necrosis in the fetal liver. The comet assays revealed significant DNA damage, as evidenced by reduced head DNA content and increased tail DNA content and tail moment in the ZEA-exposed rats. Surprisingly, co-treatment with CRV significantly mitigated fetal hepatic lipid peroxidation, antioxidant disturbance, apoptosis, and DNA damage after maternal exposure to ZEA. These findings highlight the potential of CRV as a promising approach to mitigate ZEA-associated developmental hepatotoxicity. [ABSTRACT FROM AUTHOR]

Opioid use disorders (OUD) are a major issue in the U.S. Current treatments for pregnant women, like methadone and buprenorphine require daily dosing and have adverse effects. Monthly injectable naltrexone (XR‐NTX) mitigates these adverse effects but is not recommended during pregnancy due to limited pharmacokinetic and safety data. This study developed a physiologically based pharmacokinetic (PBPK) model to describe XR‐NTX pharmacokinetics during pregnancy, and to predict dosing recommendations. Model predictions were successfully validated with observed data. Maternal plasma XR‐NTX profiles were simulated for 400 non‐pregnant virtual females at the approved dose of 380 mg, then randomized to continue with either 380, 285, 190, or 95 mg during pregnancy. The non‐pregnant virtual females had a mean predicted Cmax, AUC0‐7days, and AUC0‐28days of 23.3 ng/mL, 142 ng·d/mL, and 148 ng·d/mL, respectively. Maternal XR‐NTX exposure (AUC0‐28days) were predicted to increase by 1.37, 1.43, and 1.72 times during the first, second, and third trimester of pregnancy. However, the fetal‐to‐maternal exposure (AUC0‐28days) was lower in the first (15%), second (7%), and third (9%) trimesters. A dose of 285 mg of XR‐NTX in pregnancy during the first/second trimester and dose of 190 mg in the third trimester were predicted to provide maternal exposures that were comparable to non‐pregnant levels at the standard dose. This study provides crucial insights into XR‐NTX pharmacokinetics and proposes a dosing strategy during pregnancy, potentially aiding further clinical investigations and decision making regarding XR‐NTX use during pregnancy. [ABSTRACT FROM AUTHOR]

Optimal dosing in pregnant and lactating women requires an understanding of the pharmacokinetics in the mother, fetus, and breastfed infant. Physiologically‐based pharmacokinetic (PBPK) modeling can be used to simulate untested scenarios and hence supplement clinical data to support dosing decisions. A PBPK model for the antiretroviral dolutegravir (mainly metabolized by UGT1A1) was verified using reported exposures in non‐pregnant healthy volunteers, pregnant women, and the umbilical cord, lactating mothers, and breastfed neonates. The model was then applied to predict the impact of UGT1A1 phenotypes in extensive (EM), poor (PM), and ultra‐rapid metabolizers (UM). The predicted dolutegravir maternal plasma and umbilical cord AUC in UGT1A1 PMs was 1.6‐fold higher than in EMs. The predicted dolutegravir maternal plasma and umbilical cord AUC in UGT1A1 UMs mothers was 1.3‐fold lower than in EMs. The predicted mean systemic and umbilical vein concentrations were in excess of the dolutegravir IC90 at 17, 28, and 40 gestational weeks, regardless of UGT1A1 phenotype, indicating that the standard dose of dolutegravir (50 mg q.d., fed state) is generally appropriate in late pregnancy, across UGT1A1 phenotypes. Applying the model in breastfed infants, a 1.5‐, 1.7‐, and 2.2‐fold higher exposure in 2‐day‐old neonates, 10‐day‐old neonates, and infants who were UGT1A1 PMs, respectively, compared with EMs of the same age. However, it should be noted that the exposure in breastfed infants who were UGT1A1 PMs was still an order of magnitude lower than maternal exposure with a relative infant daily dose of <2%, suggesting safe use of dolutegravir in breastfeeding women. [ABSTRACT FROM AUTHOR]

(1) The evidence is mounting that polycyclic aromatic hydrocarbons (PAHs) are a class of hazardous organic compounds with established carcinogenic and toxic properties. Humans may be exposed to PAHs through several different routes, including diet, inhalation, and dermal contact. There is also a possibility that they could transfer into breast milk following maternal exposure, which could potentially endanger breastfeeding infants. (2) The objective of this study was to ascertain the concentration of polycyclic aromatic hydrocarbons (PAHs) in breast milk samples from 50 Hungarian mothers, employing high-performance liquid chromatography with fluorescence detection (HPLC–FLD). An Incremental Life Risk Calculation (IRCL) model estimated the carcinogenic risk to infants. (3) Total PAH concentrations ranged from 0 to 78 ng/mL, with fluorene (5.3 ng/mL), phenanthrene (3.2 ng/mL), and pyrene (2.5 ng/mL) being the most abundant. PAHs were detected in 48 of the 50 samples, with phenanthrene present in 92% of samples. Dibenzo (a,h)anthracene was not detected. (4) According to the model measurements, most of the samples were within acceptable risk levels; however, 2 samples out of 50 posed a higher risk. Statistical analysis of questionnaires completed by the mothers indicated that factors such as diet, residence, and education may influence PAH levels in breast milk. [ABSTRACT FROM AUTHOR]

The massive use of herbicides, particularly glyphosate‐based herbicides (GBHs), raises several worries, notably their neurotoxic effects. Several studies have explored the consequences of developmental exposure. Our work aims to determine the impact of maternal exposure to GBH on behavioral disorders and memory deficits, as well as the involvement of oxidative stress in the hippocampus and prefrontal cortex. In addition, our study explores the neuroprotective properties of melatonin in male and female offspring. Pregnant Wistar rats were injected with GBH 75 mg/kg during gestation and lactation. After weaning, the offspring were treated with melatonin (4 mg/kg) from postnatal days 30–58. Our results show that GBH increases anxiety‐like behavior levels in offspring, as well as depression‐like behavior. GBH also impairs working memory in progeny. While markers of oxidative stress show a disturbance in lipid peroxidation and catalase activity, with a more pronounced effect in females, on the other hand, melatonin considerably attenuated the neurotoxic impact observed in the offspring, with higher efficacy in females. The oxidative stress results confirm the antioxidant power of melatonin to counteract the damaging effects of exposure to environmental contaminants such as glyphosate‐based pesticides. It will then be interesting to further our work to fully understand the sex‐dependent effect of melatonin. [ABSTRACT FROM AUTHOR]

There is increasing evidence that thirdhand exposure to e-cigarette vapor (e-vapor) can have detrimental effects on the lungs. However, whether maternal exposure during pregnancy results in harmful changes to the offspring is unknown. Using two different e-cigarette settings (low vs. high power), BALB/c mice were subjected to thirdhand e-vapor (e-vapor deposited onto towels, towels changed daily) in the absence or presence of nicotine, before, during, and after pregnancy. Male adult offspring were then infected with mouse-adapted influenza A virus (A/PR/8/34 H1N1; Flu) and lung and bone marrow immune cell responses were assessed 7 days postinfection. Maternal thirdhand exposure to low-power (MLP) or high-power (MHP) e-vapor with nicotine (MLP + NIC and MHP + NIC, respectively) increased the percentage of lung immune cells and neutrophils in the bone marrow. Interestingly, Flu-infected offspring from MLP + NIC and MHP + NIC groups had lower percentages of lung alveolar macrophages and more pronounced increases in neutrophils in the bone marrow, when compared with offspring from MSham Flu controls. Flu infection also decreased the percentage of lung CD4+ T cells and increased the percentage of lung CD8+ T cells, irrespective of maternal exposure (MLP −/+ NIC and MHP −/+ NIC). Significantly, both MLP + NIC and MHP + NIC resulted in blunted activation of lung CD4+ T cells, but only MLP + NIC caused blunted activation of lung CD8+ T cells. Together, we show for the first time that maternal thirdhand exposure to e-vapor results in significant, long-lived effects on lung and bone marrow immune cell responses in offspring at baseline and response to Flu infection. NEW & NOTEWORTHY: Maternal exposure to environmental residues of e-cigarette use has significant effects on immune cell responses in the lungs and bone marrow of offspring at both baseline and in response to influenza A virus (Flu) infection. [ABSTRACT FROM AUTHOR]

Background: The bed nucleus of the stria terminalis (BNST) is a structure with a peculiar neurochemical composition involved in modulating anxietylike behavior and fear. Aim: The present study investigated the effects on the BNST neurochemical composition and neuronal structure in critical moments of the postnatal period in gestational protein-restricted male rats' offspring. Methods: Dams were maintained during the pregnancy on isocaloric rodent laboratory chow with standard protein content [NP, 17%] or low protein content [LP, 6%]. BNST from male NP and age-matched LP offspring was studied using the isotropic fractionator method, Neuronal 3D reconstruction, dendritic-tree analysis, blotting analysis, and high-performance liquid chromatography. Results: Serum corticosterone levels were higher in male LP offspring than NP rats in 14-day-old offspring, without any difference in 7-day-old progeny. The BNST total cell number and anterodorsal BNST division volume in LP progeny were significantly reduced on the 14th postnatal day compared with NP offspring. The BNST HPLC analysis from 7 days-old LP revealed increased norepinephrine levels compared to NP progeny. The BNST blot analysis from 7-day-old LP revealed reduced levels of GR and BDNF associated with enhanced CRF1 expression compared to NP offspring. 14-day-old LP offspring showed reduced expression of MR and 5HT1A associated with decreased DOPAC and DOPA turnover levels relative to NP rats. In Conclusion, the BNST cellular and neurochemical changes may represent adaptation during development in response to elevated fetal exposure to maternal corticosteroid levels. In this way, gestational malnutrition alters the BNST content and structure and contributes to already-known behavioral changes. [ABSTRACT FROM AUTHOR]

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

Objective: We review the prevalence of allergic diseases in children across prenatal exposures to heavy metals. Methods: This systematic review and meta-analysis is registered in the PROSPERO database (CRD42023478471). A comprehensive search of PubMed, Web of Science, Medline and Cochrane library was conducted from the database inception until 31 October 2023. The Newcastle-Ottawa Quality Assessment Scale (NOS) was used to assess the quality of included studies. We used a random-effects model to summarize the effects from the studies. Results: A total of 16 studies were included, 120,065 mother-child pairs enrolled. The NOS scores indicated that the quality of the literature included in the study was of a high standard. Conclusion: The final results indicate that prenatal exposure to Pb increased the incidence of wheeze and Eczema in infants, and exposure to Ni and CD increased the incidence of AD in infants. [ABSTRACT FROM AUTHOR]

There are increasing concerns regarding the rapid expansion of polystyrene nanoplastics (PS-NPs), which could impact human health. Previous studies have shown that nanoplastics can be transferred from mothers to offspring through the placenta and breast milk, resulting in cognitive deficits in offspring. However, the neurotoxic effects of maternal exposure on offspring and its mechanisms remain unclear. In this study, PS-NPs (50 nm) were gavaged to female rats throughout gestation and lactation to establish an offspring exposure model to study the neurotoxicity and behavioral changes caused by PS-NPs on offspring. Neonatal rat hippocampal neuronal cells were used to investigate the pathways through which NPs induce neurodevelopmental toxicity in offspring rats, using iron inhibitors, autophagy inhibitors, reactive oxygen species (ROS) scroungers, P53 inhibitors, and NCOA4 inhibitors. We found that low PS-NPs dosages can cause ferroptosis in the hippocampus of the offspring, resulting in a decline in the cognitive, learning, and memory abilities of the offspring. PS-NPs induced NOCA4-mediated ferritinophagy and promoted ferroptosis by inciting ROS production to activate P53-mediated ferritinophagy. Furthermore, the levels of the antioxidant factors glutathione peroxidase 4 (GPX4) and glutathione (GSH), responsible for ferroptosis, were reduced. In summary, this study revealed that consumption of PS-NPs during gestation and lactation can cause ferroptosis and damage the hippocampus of offspring. Our results can serve as a basis for further research into the neurodevelopmental effects of nanoplastics in offspring. [ABSTRACT FROM AUTHOR]

Preeclampsia, a hypertensive disorder during pregnancy, frequently correlates with adverse neurological outcomes in offspring, including cognitive impairments, autism spectrum disorder, depressive disorder, attention deficit hyperactivity disorder, and cerebral palsy. Despite these known consequences, the understanding of neuronal damage in the offspring of preeclamptic mothers remains insufficient. Here, we review the neuronal abnormalities resulting from maternal preeclampsia exposure, which include disrupted neurogenesis, loss of neuronal cell integrity, accumulation of cellular debris, decreased synaptogenesis and myelination, and increased neurite growth stimulated by maternal preeclampsia serum. The underlying mechanisms potentially driving these effects involve microglial activation, inflammatory responses, and reduced angiogenesis. Intervention strategies aimed at improving fetal neuronal outcomes are also discussed, encompassing pharmacological treatments such as pravastatin, tadalafil, and melatonin, as well as non-pharmacological approaches like dietary modifications, maternal exercise, and standard care for children. These interventions hold promise for clinical application, offering avenues to address early neuronal abnormalities and prevent the onset of long-term neurological disorders. [ABSTRACT FROM AUTHOR]

Maternal cadmium exposure during pregnancy has been demonstrated to have detrimental effects on offspring development. However, the impact of maternal cadmium exposure on offspring oocytes remains largely unknown, and the underlying mechanisms are not fully understood. In this study, we found that maternal cadmium exposure during pregnancy resulted in selective alteration in epigenetic modifications of mouse oocytes in offspring, including a decrease in H3K4me2 and H4K12ac, as well as an increase in DNA methylation of H19. Although ROS levels and mitochondrial activity remain at normal levels, the DNA damage marker γH2AX was significantly increased and the DNA repair marker DNA-PKcs was remarkably decreased in offspring oocytes from maternal cadmium exposure. These alterations are responsible for the decrease in the quality of mouse oocytes in offspring induced by maternal cadmium exposure. As a result, the meiotic maturation of oocytes and subsequent early embryonic development are influenced by maternal cadmium exposure. RNA-seq results showed that maternal cadmium exposure elicits modifications in the expression of genes associated with metabolism, signal transduction, and endocrine regulation in offspring ovaries, which also contribute to the disorders of oocyte maturation and failures in early embryonic development. Our research provides direct evidence of transgenerational epigenetic inheritance of cadmium reproductive toxicity in mouse germ cells. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusions Maternal preeclampsia is associated with both congenital heart defects and changes in left ventricular structure and function in the offspring. Whether preeclampsia and gestational hypertension also affect the offspring's cardiac conduction system is unknown.This study assesses whether infants exposed to maternal hypertensive disorders of pregnancy (HDPs) exhibit changes in their electrocardiogram (ECG) compared with infants unexposed to HDPs.This population‐based cohort study included newborns from the Copenhagen Baby Heart Study who had an ECG performed within 30 days of birth and had available obstetric information. ECG parameters of newborns exposed to maternal HDPs were compared with those of unexposed newborns using linear regression.Our study cohort included 11,826 newborns, including 441 exposed to maternal preeclampsia and 320 exposed to gestational hypertension. Infants exposed to preeclampsia had prolonged QRS durations (adjusted mean difference 0.6 ms, 95% confidence interval [CI] 0.04, 1.16) and lower maximum amplitudes of the R‐wave in V1 (adjusted mean difference, linear scale 0.95, 95% CI 0.90, 1.00), compared with unexposed infants. Exposure to maternal preeclampsia was not associated with changes in other ECG parameters. Exposure to gestational hypertension was associated with increased QT interval durations (QTc Bazett, adjusted mean difference 2.48 ms, 95% CI −0.23, 5.20; QTc Fridericia, adjusted mean difference 2.32 ms, 95% CI −0.19, 4.83).Our findings suggest that the newborn cardiac conduction system is affected by exposure to maternal preeclampsia. This could reflect the previously described thickening of the left ventricular myocardium in infants exposed to preeclampsia. [ABSTRACT FROM AUTHOR]

Background/Objectives: Childhood obesity, particularly in girls, is linked to early puberty onset, heightening risks for adult-onset diseases. Addressing childhood obesity and precocious puberty is vital to mitigate societal burdens. Despite existing costly and invasive medical interventions, introducing lifestyle-based alternatives is essential. Our study investigates alternate-day fasting's (ADF) impact on pubertal development in normal-weight and high-fat diet (HFD)-induced obese female mice. Methods: Four groups of female mice were utilized, with dams initially fed control chow during and before pregnancy. Post-parturition, two groups continued on control chow, while two switched to an HFD. Offspring diets mirrored maternal exposure. One control and one HFD group were subjected to ADF. Morphometry and hormone analyses at various time points were performed. Results: Our findings demonstrate that ADF in normal-weight mice led to reduced body length, weight, uterine, and ovarian weights, accompanied by delayed puberty and lower levels of sex hormones and growth hormone (GH). Remarkably, GH treatment effectively prevented ADF-induced growth reduction but did not prevent delayed puberty. Conversely, an HFD increased body length, induced obesity and precocious puberty, and altered sex hormones and leptin levels, which were counteracted by ADF regimen. Our data indicate ADF's potential in managing childhood obesity and precocious puberty. Conclusions: ADF reduced GH and sex hormone levels, contributing to reduced growth and delayed puberty, respectively. Therefore, parents of normal-weight children should be cautious about prolonged overnight fasting. ADF prevented HFD-induced obesity and precocious puberty, offering an alternative to medical approaches; nevertheless, further studies are needed for translation into clinical practice. [ABSTRACT FROM AUTHOR]

The article comments on E.M. Poole and M.R. Boland's study which examined the association between hormonal modulators in hydraulic fracturing fluid chemicals and birth outcomes in the U.S. Topics discussed include the endocrine-disrupting properties of chemicals used during hydraulic fracturing to release trapped oil and gas reserves in rock formation, the linking of chemical exposure assessment to county-level birth outcome measures, and potential mismatch in the use of county-level measures.

We examined the association between serum aflatoxin B1‐lysine adduct (AFB1‐lys) levels in pregnant women and adverse pregnancy outcomes (low birthweight, miscarriage and stillbirth) through a nested matched case–control study of pregnant women enroled at ≤28 weeks' gestation in Mombasa, Kenya, from 2017 to 2019. Cases comprised women with an adverse birth outcome, defined as either delivery of a singleton infant weighing <2500 g, or a miscarriage, or a stillbirth, while controls were women who delivered a singleton live infant with a birthweight of ≥2500 g. Cases were matched to controls at a ratio of 1:2 based on maternal age at enrolment, gestational age at enrolment and study site. The primary exposure was serum AFB1‐lys. The study included 125 cases and 250 controls. The median gestation age when serum samples were collected was 23.0 weeks (interquartile range [IQR]: 18.1–26.0) and 23.5 (IQR: 18.1–26.5) among cases and controls, respectively. Of the 375 tested sera, 145 (38.7%) had detectable serum AFB1‐lys: 36.0% in cases and 40.0% in controls. AFB1‐lys adduct levels were not associated with adverse birth outcomes on multivariable analysis. Mid‐upper arm circumference was associated with a 6% lower odds of adverse birth outcome for every unit increase (p = 0.023). Two‐fifths of pregnant women had detectable levels of aflatoxin midway through pregnancy. However, we did not detect an association with adverse pregnancy outcomes, likely because of low serum AFB1‐lys levels and low power, restricting meaningful comparison. More research is needed to understand the public health risk of aflatoxin in pregnant women to unborn children. Key messages: Aflatoxin B1 (AFB1), a commonly ingested toxin, can cross the placental barrier and cause adverse pregnancy outcomes.Two‐fifths of participants had detectable serum AFB1‐lys levels, a marker of aflatoxin exposure, but the low levels recorded were not associated with adverse pregnancy outcomes.Every unit increase in mid‐upper arm circumference (MUAC) during pregnancy was associated with a 6% reduced likelihood of adverse pregnancy outcomes, highlighting the potential protective role of adequate maternal nutrition.There is need for additional studies in different settings on the determinants and mechanisms of the relationship between aflatoxin exposure and adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Prenatal indoor air pollution and maternal psychosocial factors have been associated with adverse psychopathology. We used environmental-exposure mixture methodology to investigate joint effects of both exposure classes on child behavior trajectories. For 360 children from the South African Drakenstein Child Health Study, we created trajectories of Child Behavior Checklist scores (at 24, 42, and 60 months) using latent-class linear mixed effects models. Indoor air pollutants and psychosocial factors were measured during pregnancy (second trimester). After adjusting for confounding, single-exposure effects (per natural log-1 unit increase) were assessed using polytomous logistic regression models, joint effects using self-organizing maps, and principal component analysis. Three trajectories were chosen for both internalizing and externalizing problems, with "high" (externalizing) or "increasing" (internalizing) being the most adverse trajectories. High externalizing trajectory was associated with increased exposure to particulate matter of ≤ 10 microns in diameter (PM10) (odds ratio [OR] = 1.25; 95% CI, 1.01-1.55) and self-organizing maps exposure profile most associated with smoking (OR = 2.67; 95% CI, 1.14-6.27). Medium internalizing trajectory was associated with increased emotional intimate partner violence (OR = 2.66; 95% CI, 1.17-5.57), increasing trajectory with increased benzene (OR = 1.24; 95% CI, 1.02-1.51) and toluene (1.21; 95% CI, 1.02-1.44) and the principal component most correlated with benzene and toluene (OR = 1.25; 95% CI, 1.02-1.54). Prenatal exposure to environmental pollutants and psychosocial factors was associated with internalizing and externalizing child behavior trajectories. Understanding joint effects of adverse exposure mixtures will facilitate targeted interventions to prevent childhood psychopathology. This article is part of a Special Collection on Mental Health. [ABSTRACT FROM AUTHOR]

To determine a possible correlation between SARS-CoV-2 infection during pregnancy and altered fetal behavior. Kurjak's antenatal neurodevelopmental test (KANET) was applied from 28 to 40 weeks in 38 gestations (group A) diagnosed with COVID-19 infection during the first week and 43 non-COVID pregnant women (group B). No statistically significant differences considering maternal age (33±3.9 years for group A vs. 31±4.1 years for group B) and gestational age (33±1.6 weeks for group A compared to 33±2.1 weeks for group B) were observed. KANET scores were not different between the two groups. Fetal behavior differences are not altered in women diagnosed with SARS-CoV-2 infection during the third trimester of pregnancy. [ABSTRACT FROM AUTHOR]

Previous studies evaluating the risk of spontaneous abortions following exposure to macrolides reported controversial results. The goal of the current study was to examine the risk for spontaneous abortions following exposure to macrolides during pregnancy. We conducted a population‐based retrospective cohort study by linking three computerized databases: Clalit Health Services drug dispensation database, Soroka Medical Center (SMC) birth database, and SMC hospitalizations database. Multivariate time‐varying Cox regressions were performed and adjusted for suspected confounders and known risk factors for spontaneous abortions. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated. A secondary analysis was performed to assess the association between exposure to macrolides in terms of the defined daily dose dispensed and spontaneous abortions. The study cohort included 65,457 pregnancies that ended at Soroka Medical Center between 2004 and 2009, of which 6508 (9.9%) resulted in a spontaneous abortion. A total of 825 (1.26%) pregnancies were exposed to macrolides during the exposure period. Exposure to macrolides was not associated with spontaneous abortions as a group (adjusted HR 1.00 95% CI 0.77‐1.31) or as specific medications. There was no evidence of a dose‐response relationship between exposure to macrolides and spontaneous abortions. In conclusion, this population‐based retrospective cohort study did not detect an increased risk for spontaneous abortion following exposure to macrolides during the first trimester of pregnancy. [ABSTRACT FROM AUTHOR]

This study aims to explore the acute effects of short-term exposure to PM2.5 components and their mixture on PROM. Counts of hospital admissions due to PROM were collected at the Fourth Hospital of Shijiazhuang. The associations between the PROM and PM2.5 components was examined using a time-stratified case-crossover approach. The overall effects of components on TPROM were examined using the BKMR. During the study period 30,709 cases of PROMwere identified. The relative risks and the 95% CI of TPROM were 1.013 (1.002, 1.028) and 1.015 (1.003, 1.028) associated with per interquartile range increase in nitrate and ammonium ion on the current day and they were 1.007 (1.001, 1.013) and 1.003 (1.000, 1.005) on the previous day. The results from the BKMR models showed a higher risk of TPROM was associated with exposure to mixtures, in which, nitrate and organic matter were the main contributors to the overall effect. [ABSTRACT FROM AUTHOR]

Background: Studies have demonstrated that Sertoli cells are the direct target of Dibutyl phthalate (DBP). However, the role of neurotransmitter receptors is not elucidated. Methods: Based on our previous studies, maternal Sprague–Dawley (SD) rats in Gestation Day (GD) 14–18 and TM4 cells exposure to 750 mg/kg/day and 100 μM DBP were regarded as treated groups. Firstly, qRT-PCR array was used to determine the different expression of neurotransmitter receptors. We examined the OX1R expression on Rats in Control and DBP groups by immunohistochemistry. Real-time PCR and Western Blot were used to detect the protein and mRNA expression levels of OX1R in vivo and in vitro. The potential downstream signaling pathways were explored by analyzing the GSE99690 cohort. In addition, we extracted Primary Sertoli Cells (PSCs) from the testis of control group. The apoptosis-related proteins, AKT signaling pathway-related proteins and mRNA expressions were detected by Western Blot and Real-time PCR in PSCs. The validity of PSCs was measured by CCK-8 assay and flow cytometric analysis was used to demonstrate the apoptotic rates of PSCs after DBP exposure. Results: The Orexin receptor 1 (OX1R) was screened out by qRT-PCR array. Our results showed that DBP could significantly suppress the OX1R expression of Sertoli cells in vivo and in vitro. Functional analysis showed the AKT signaling pathway was mediated by OX1R. The highly expressed apoptosis level and impaired cell activity were observed in PSCs, which can be reversed by Orexin A. Meanwhile, the p-AKT signaling pathway were hindered after DBP exposure while rescued in DBP + Orexin-A group. Conclusions: DBP can induce Sertoli cell apoptosis through its toxicological effect by suppressing OX1R and p-AKT expression, which provide a novel insight on the role of neurotransmitter receptors. [ABSTRACT FROM AUTHOR]

Phenols, parabens, and phthalates (PPPs) are suspected or known endocrine disruptors. They are used in consumer products that pregnant women and their progeny are exposed to daily through the placenta, which could affect offspring health. This review aims to compile data from cohort studies and in vitro and in vivo models to provide a summary regarding placental transfer, fetoplacental development, and the predisposition to adult diseases resulting from maternal exposure to PPPs during the gestational period. In humans, using the concentration of pollutants in maternal urine, and taking the offspring sex into account, positive or negative associations have been observed concerning placental or newborn weight, children's BMI, blood pressure, gonadal function, or age at puberty. In animal models, without taking sex into account, alterations of placental structure and gene expression linked to hormones or DNA methylation were related to phenol exposure. At the postnatal stage, pollutants affect the bodyweight, the carbohydrate metabolism, the cardiovascular system, gonadal development, the age of puberty, sex/thyroid hormones, and gamete quality, but these effects depend on the age and sex. Future challenges will be to explore the effects of pollutants in mixtures using models and to identify the early signatures of in utero exposure capable of predicting the health trajectory of the offspring. [ABSTRACT FROM AUTHOR]

Psoriasis is an immune cell-mediated chronic relapsing inflammatory skin disease that often develops during the reproductive years of women. The treatment of psoriasis during pregnancy is challenging as remarkable changes occur in the maternal body, and it requires the selection of therapy which is safe for both mother and fetus. The use of interleukin-23 (IL-23)/IL-17 inhibitors has been growing in psoriasis disease management and so the risk of their exposure during pregnancy is increasing too. However, human safety data in pregnancy are limited. This article aims to review pregnancy outcomes associated with IL-23/IL-17 inhibitor exposure in psoriasis patients and to see possible therapeutic options for psoriasis treatment during pregnancy. A search of the PubMed database up to June 2023 for articles was performed. The search strategy included a combination of terms as (pregnancy) AND (psoriasis) AND (Ustekinumab)/(Secukinumab)/(ixekizumab)/(brodalumab)/(guselkumab)/(tildrakizumab)/(risankizumab)/IL-23 inhibitors/IL-17 inhibitors. Resulted articles were reviewed manually for case reports, exposures from registries, and clinical trials. Most of the exposures to IL-23/IL-17 inhibitors were inadvertent, and therapy was suspended upon the detection of pregnancy. No signals on miscarriages, spontaneous abortions, and adverse developmental outcomes have been reported with first-trimester exposures to IL-23/IL-17 inhibitors. However, benefit–risk profile cannot be extrapolated based on first-trimester exposure as the transfer of these biologics across the placenta occurs in the later stage of pregnancy. More safety data from large cohorts of full-term exposure are required for IL-23/IL-17 inhibitors to consider them safe therapeutic options during pregnancy.

Abstract There are increasing concerns regarding the rapid expansion of polystyrene nanoplastics (PS-NPs), which could impact human health. Previous studies have shown that nanoplastics can be transferred from mothers to offspring through the placenta and breast milk, resulting in cognitive deficits in offspring. However, the neurotoxic effects of maternal exposure on offspring and its mechanisms remain unclear. In this study, PS-NPs (50 nm) were gavaged to female rats throughout gestation and lactation to establish an offspring exposure model to study the neurotoxicity and behavioral changes caused by PS-NPs on offspring. Neonatal rat hippocampal neuronal cells were used to investigate the pathways through which NPs induce neurodevelopmental toxicity in offspring rats, using iron inhibitors, autophagy inhibitors, reactive oxygen species (ROS) scroungers, P53 inhibitors, and NCOA4 inhibitors. We found that low PS-NPs dosages can cause ferroptosis in the hippocampus of the offspring, resulting in a decline in the cognitive, learning, and memory abilities of the offspring. PS-NPs induced NOCA4-mediated ferritinophagy and promoted ferroptosis by inciting ROS production to activate P53-mediated ferritinophagy. Furthermore, the levels of the antioxidant factors glutathione peroxidase 4 (GPX4) and glutathione (GSH), responsible for ferroptosis, were reduced. In summary, this study revealed that consumption of PS-NPs during gestation and lactation can cause ferroptosis and damage the hippocampus of offspring. Our results can serve as a basis for further research into the neurodevelopmental effects of nanoplastics in offspring. Graphical Abstract

BackgroundPhthalate exposures are ubiquitous during pregnancy and may contribute to racial and ethnic disparities in preterm birth.ObjectivesWe investigated race and ethnicity in the relationship between biomarkers of phthalate exposure and preterm birth by examining: a) how hypothetical reductions in racial and ethnic disparities in phthalate metabolites might reduce the probability of preterm birth; and b) exposure-response models stratified by race and ethnicity.MethodsWe pooled individual-level data on 6,045 pregnancies from 16 U.S. cohorts. We investigated covariate-adjusted differences in nine urinary phthalate metabolite concentrations by race and ethnicity [non-Hispanic White (White, 43%), non-Hispanic Black (Black, 13%), Hispanic/Latina (38%), and Asian/Pacific Islander (3%)]. Using g-computation, we estimated changes in the probability of preterm birth under hypothetical interventions to eliminate disparities in levels of urinary phthalate metabolites by proportionally lowering average concentrations in Black and Hispanic/Latina participants to be approximately equal to the averages in White participants. We also used race and ethnicity-stratified logistic regression to characterize associations between phthalate metabolites and preterm birth.ResultsIn comparison with concentrations among White participants, adjusted mean phthalate metabolite concentrations were consistently higher among Black and Hispanic/Latina participants by 23%-148% and 4%-94%, respectively. Asian/Pacific Islander participants had metabolite levels that were similar to those of White participants. Hypothetical interventions to reduce disparities in metabolite mixtures were associated with lower probabilities of preterm birth for Black [13% relative reduction; 95% confidence interval (CI): -34%, 8.6%] and Hispanic/Latina (9% relative reduction; 95% CI: -19%, 0.8%) participants. Odds ratios for preterm birth in association with phthalate metabolites demonstrated heterogeneity by race and ethnicity for two individual metabolites (mono-n-butyl and monoisobutyl phthalate), with positive associations that were larger in magnitude observed among Black or Hispanic/Latina participants.ConclusionsPhthalate metabolite concentrations differed substantially by race and ethnicity. Our results show hypothetical interventions to reduce population-level racial and ethnic disparities in biomarkers of phthalate exposure could potentially reduce the probability of preterm birth. https://doi.org/10.1289/EHP12831.

BackgroundAssociations between maternal tobacco exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL) have yielded mixed results. This may be due to biases in self-reported smoking or other differences in individual-level risk factors. We utilized a biological marker of maternal tobacco exposure to evaluate the association between maternal tobacco exposure during pregnancy, genetics, and subsequent childhood ALL risk in two large population-based studies of childhood ALL in California.MethodsMaternal exposure to tobacco smoke was assessed with a validated methylation marker (cg05575921) of the aryl hydrocarbon receptor repressor (AHRR) gene in newborn dried blood spots. We adjusted for sex, birthweight, gestational age, mode of delivery, year of birth, AHRR quantitative trait locus (mQTL) rs77111113, and a polygenetic risk score for childhood ALL. We additionally adjusted for principal components in a gene-environment interaction testing method that incorporates gene-only and environment-only effects along with interactions.ResultsAHRR hypomethylation overall was not associated with childhood ALL. In gene-environment interaction testing, several genetic variants displayed significant interaction with AHRR hypomethylation and childhood ALL.ConclusionsOur results suggest that novel candidates in PTPRK and DPP6 may play a role in tobacco-related leukemogenesis. Further research is necessary to better understand the effects of tobacco and these variants on childhood ALL risk.ImpactDespite the lack of an overall "main effect," tobacco exposure during pregnancy affects childhood ALL risk depending on specific genetic variants.

BackgroundDrinking water is a common source of exposure to inorganic arsenic. In the US, the Safe Drinking Water Act (SDWA) was enacted to protect consumers from exposure to contaminants, including arsenic, in public water systems (PWS). The reproductive effects of preconception and prenatal arsenic exposure in regions with low to moderate arsenic concentrations are not well understood.ObjectivesThis study examined associations between preconception and prenatal exposure to arsenic violations in water, measured via residence in a county with an arsenic violation in a regulated PWS during pregnancy, and five birth outcomes: birth weight, gestational age at birth, preterm birth, small for gestational age (SGA), and large for gestational age (LGA).MethodsData for arsenic violations in PWS, defined as concentrations exceeding 10 parts per billion, were obtained from the Safe Drinking Water Information System. Participants of the Environmental influences on Child Health Outcomes Cohort Study were matched to arsenic violations by time and location based on residential history data. Multivariable, mixed effects regression models were used to assess the relationship between preconception and prenatal exposure to arsenic violations in drinking water and birth outcomes.ResultsCompared to unexposed infants, continuous exposure to arsenic from three months prior to conception through birth was associated with 88.8 g higher mean birth weight (95% CI: 8.2, 169.5), after adjusting for individual-level confounders. No statistically significant associations were observed between any preconception or prenatal violations exposure and gestational age at birth, preterm birth, SGA, or LGA.ConclusionsOur study did not identify associations between preconception and prenatal arsenic exposure, defined by drinking water exceedances, and adverse birth outcomes. Exposure to arsenic violations in drinking water was associated with higher birth weight. Future studies would benefit from more precise geodata of water system service areas, direct household drinking water measurements, and exposure biomarkers.

BACKGROUND: During gestation, stressors to the fetus, including viral exposure or maternal psychological distress, can fundamentally alter the neonatal epigenome, and may be associated with long-term impaired developmental outcomes. The impact of in utero exposure to the COVID-19 pandemic on the newborn epigenome has yet to be described. METHODS: This study aimed to determine whether there are unique epigenetic signatures in newborns who experienced otherwise healthy pregnancies that occurred during the COVID-19 pandemic (Project RESCUE). The pre-pandemic control and pandemic cohorts (Project RESCUE) included in this study are part of a prospective observational and longitudinal cohort study that evaluates the impact of elevated prenatal maternal stress during the COVID-19 pandemic on early childhood neurodevelopment. Using buccal swabs collected at birth, differential DNA methylation analysis was performed using the Infinium MethylationEPIC arrays and linear regression analysis. Pathway analysis and gene ontology enrichment were performed on resultant gene lists. RESULTS: Widespread differential methylation was found between neonates exposed in utero to the pandemic and pre-pandemic neonates. In contrast, there were no apparent epigenetic differences associated with maternal COVID-19 infection during pregnancy. Differential methylation was observed among genomic sites that underpin important neurological pathways that have been previously reported in the literature to be differentially methylated because of prenatal stress, such as NR3C1. CONCLUSIONS: The present study reveals potential associations between exposure to the COVID-19 pandemic during pregnancy and subsequent changes in the newborn epigenome. While this finding warrants further investigation, it is a point that should be considered in any study assessing newborn DNA methylation studies obtained during this period, even in otherwise healthy pregnancies.

BACKGROUND: Season of birth has been associated with age at menarche. Maternal vitamin D levels in pregnancy may explain this effect. We investigated whether the season of first trimester or maternal 25-hydroxyvitamin D3 [25(OH)D3] levels were associated with pubertal timing in children. METHODS: We conducted a follow-up study of 15 819 children born in 2000-03 from the Puberty Cohort, nested in the Danish National Birth Cohort (DNBC). Mean differences in attaining numerous pubertal markers, including a combined estimate for the average age at attaining all pubertal markers, were estimated for low (November-April) relative to high (May-October) sunshine exposure season in the first trimester using multivariable interval-censored regression models. Moreover, we conducted a two-sample instrumental variable analysis using season as an instrument for maternal first-trimester 25(OH)D3 plasma levels obtained from a non-overlapping subset (n = 827) in the DNBC. RESULTS: For the combined estimate, girls and boys of mothers who had their first trimester during November-April had earlier pubertal timing than girls and boys of mothers whose first trimester occurred during May-October: -1.0 months (95% CI: -1.7 to -0.3) and -0.7 months (95% CI: -1.4 to -0.1), respectively. In the instrumental variable analysis, girls and boys also had earlier pubertal timing: respectively, -1.3 months (95% CI: -2.1 to -0.4) and -1.0 months (95% CI: -1.8 to -0.2) per SD (22 nmol/L) decrease in 25(OH)D3. CONCLUSIONS: Both first pregnancy trimester during November-April and lower 25(OH)D3 were associated with earlier pubertal timing in girls and boys.

BackgroundAlthough maternal stressor exposure has been associated with shorter telomere length (TL) in offspring, this literature is based largely on White samples. Furthermore, timing of maternal stressors has rarely been examined. Here, we examined how maternal stressors occurring during adolescence, pregnancy, and across the lifespan related to child TL in Black and White mothers.MethodMothers (112 Black; 110 White; Mage = 39) and their youngest offspring (n = 222; Mage = 8) were part of a larger prospective cohort study, wherein mothers reported their stressors during adolescence (assessed twice during adolescence for the past year), pregnancy (assessed in midlife for most recent pregnancy), and across their lifespan (assessed in midlife). Mother and child provided saliva for TL measurement. Multiple linear regression models examined the interaction of maternal stressor exposure and race in relation to child TL, controlling for maternal TL and child gender and age. Race-stratified analyses were also conducted.ResultsNeither maternal adolescence nor lifespan stressors interacted with race in relation to child TL. In contrast, greater maternal pregnancy stressors were associated with shorter child TL, but this effect was present for children of White but not Black mothers. Moreover, this effect was significant for financial but not social pregnancy stressors. Race-stratified models revealed that greater financial pregnancy stressors predicted shorter telomeres in offspring of White, but not Black mothers.ConclusionsRace and maternal stressors interact and are related to biological aging across generations, but these effects are specific to certain races, stressors, and exposure time periods.

Abstract Background Previous studies indicated that excessive engagement in digital devices could lead to negative psychological impacts in general population. We aimed to determine the association of electronic screen exposure with depression among women in early pregnancy. Methods A cross-sectional study was conducted from June 2021 to June 2022. A total of 665 women in early pregnancy were recruited and the information included socio-demographic characteristics, screen exposure and Patient Health Questionnaire − 9 depression scale. Results Among the women in early pregnancy, the total daily smartphone viewing time was the longest (median [P25-P75], 5 [3–6] hours/day) in the three types of electronic screen exposure. The total daily smartphone viewing time (P = 0.015, OR[95%CI] = 1.09[1.11–1.18]), smartphone (P = 0.016, OR[95%CI] = 1.24[1.04–1.47]) and television viewing time (P = 0.006, OR[95%CI] = 1.35[1.09–1.67]) before nocturnal sleep were significantly associated with depression among women in early pregnancy. The thresholds calculated by receiver operator characteristic curves were 7.5 h/day, 1.5 h/day and 1.5 h/day, respectively. In addition, women with higher scores of smartphone addiction were more susceptible to depression (P