Accumulating evidence suggests that maternal exposure to per- and polyfluoroalkyl substances during pregnancy is associated with adverse outcomes in offspring. As a short-chain alternative to perfluorooctane sulfonate (PFOS), the impacts of perfluorobutane sulfonate (PFBS) on pulmonary development across the lifespan remain unclear. Herein, pregnant BALB/c mice were provided drinking water containing 10 μg/L PFBS, 500 μg/L PFBS, or 500 μg/L PFOS from gestation through lactation. Significant bioaccumulation of PFBS was identified in fetal organs. On postnatal day 1 (PND 1), offspring prenatally exposed to PFOS or PFBS exhibited simplified alveolar structures, decreased surfactant protein C levels, and impaired angiogenesis. The expression of Vegfα, an angiogenesis-related gene, was downregulated in the high-dose exposure groups, with a corresponding reduction in VEGFA protein levels. Meanwhile, Ocln, Cldn1, and Occludin were significantly decreased, indicating disrupted pulmonary barrier function. These alterations were reversed by PND 21. Furthermore, under ovalbumin challenge, all exposed adult offspring exhibited increased allergic susceptibility, characterized by enhanced pulmonary inflammatory infiltration, elevated bronchial mucin secretion, reduced Occludin protein levels, and upregulated Th2-type inflammatory cytokines (including IL-4, IL-5, and IL-13). RNA-seq analysis revealed that exposure to both PFBS and PFOS impaired the expression of genes critical for pulmonary development. Overall, our study indicates that perinatal exposure to PFOS or PFBS leads to both short- and long-term adverse effects on pulmonary development, suggesting that PFBS is not a safe alternative to PFOS.

Previous studies indicate pesticides may disrupt female reproductive hormone levels. However, the combined effects of multiclass pesticides on these hormones and whether different types exert distinct effects in women undergoing assisted reproductive technology (ART) remain unclear. Thus, we examined associations between combined multiclass pesticide exposure and reproductive hormone levels in ART women. The study included 462 women enrolled in the sub-cohort of the China National Birth Cohort between July 2017 and December 2018. Blood and urine samples were collected before ART treatment. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Mullerian hormone (AMH) were obtained from medical records. Urine was quantified for organophosphates (OPs), pyrethroids (PYRs), neonicotinoids (NEOs), and their metabolites. Using hierarchical bayesian kernel machine regression models we found combined exposure to multiclass pesticides was associated with increased FSH (-12.35%, 95% CI: -22.41%, -0.97% for 30th vs. 50th percentile) and decreased AMH (-15.74%, 95% CI: -28.83%, -0.25% for 75th vs. 50th percentile) levels. 4-fluoro-3-phenoxybenzoic acid (4F-3PBA, a PYR metabolite, condPIP = 0.79) and nitenpyram (NIT, a NEO metabolite, condPIP = 0.45) contributed most to elevated FSH and reduced AMH levels, respectively. Furthermore, OPs and PYRs were mainly associated with increased FSH, and NEOs with decreased AMH. Our study suggests that combined exposure to multiclass pesticides may adversely affect female reproductive function.

Atopic dermatitis (AD) is a common childhood allergic disease associated with substantial health and economic burdens. Although prenatal exposure to per- and polyfluoroalkyl substances (PFAS) has been linked to adverse child health outcomes, its association with AD and the potential modifying role of maternal adverse psychological status (MAPS) remain unclear. Based on the China National Birth Cohort, we quantified 759 maternal serum PFAS concentrations during the first trimester and evaluated MAPS (including stress, depression, and anxiety) across all three trimesters. AD in infants at 6 months of age was diagnosed according to the UK Working Party diagnostic criteria. The associations of individual PFAS exposure with AD were estimated using multivariable logistic regression, whereas the joint effects of PFAS mixtures were assessed using quantile g-computation. Interaction terms and stratified analyses were performed based on MAPS group (positive vs. negative). After adjusting for potential confounders, prenatal PFAS exposure was associated with an increased risk of AD in 6-month-old infants. Moreover, when MAPS was positive overall, or specifically for anxiety, depression, or stress, prenatal PFAS exposure was associated with a further elevated risk of infant AD at 6 months. These findings underscore the need for further research into childhood health determinants and for public health policies that reduce prenatal exposure to PFAS pollutants and maternal psychological distress, thereby potentially alleviating AD risk in future generations.

As perfluorooctanesulfonate (PFOS) is phased out, its alternative, 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), has been widely used in China. However, the health risks associated with F-53B exposure, particularly its potential effects on offspring respiratory outcomes, remain largely unclear. We therefore investigated whether gestational and lactational exposures to PFOS or F-53B alter early lung development and influence asthma susceptibility in offspring. Pregnant mice were exposed to PFOS or F-53B at a dose relevant to the human tolerable daily intake of PFOS during gestation and lactation, and maternal-fetal distribution was quantified by ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) at embryonic day 18.5. Both PFOS and F-53B efficiently crossed the placenta and accumulated in the fetal lungs. Following ovalbumin sensitization and challenge, offspring from exposed dams showed increased airway inflammatory pathology and goblet cell hyperplasia, along with higher bronchoalveolar lavage protein and elevated pulmonary Il5 and Il1b expression, with PFOS inducing more pronounced functional changes. Early life exposure downregulated pulmonary tight junction proteins ZO-1 and Occludin at postnatal day 1, while transcriptomics revealed persistent dysregulation of immune-related pathways. 16S rRNA gene sequencing further demonstrated alterations in gut microbiota diversity and composition. Together, these findings suggest that early life exposure to PFOS or F-53B is associated with changes in lung-barrier development, immune signaling, and gut microbial composition, which may contribute to an increased asthma susceptibility in the offspring. Notably, F-53B exhibits transplacental transfer efficiency comparable to that of PFOS, raising concerns regarding its safety as a PFOS alternative.

Intrauterine inflammation is associated with lung injury in offspring and long-term adverse pulmonary outcomes, but the underlying mechanism remains elusive. This study aimed to investigate the underlying molecular mechanism from the perspective of metabolites. Pregnant C57BL/6 mice received an intraperitoneal injection of LPS on gestational day 12.5 to establish an intrauterine inflammation model. The results showed that prenatal LPS exposure induced bronchopulmonary dysplasia (BPD)-like alveolar simplification. Then, by LC/MS untargeted metabolomics analysis, succinic acid was found to be elevated in murine placentas and preterm human umbilical cord blood with intrauterine inflammation. Besides, the expression of succinate dehydrogenase B subunit (Sdhb), a key catalytic enzyme of succinic acid, was downregulated in the murine placentas with intrauterine inflammation. Tail intravenous administration of Sdhb siRNA led to the accumulation of succinic acid in the placenta and aggravated LPS-induced lung injury in the offspring. In offspring mice, intrauterine inflammation decreased E-cadherin levels in lung tissue, which were further reduced by Sdhb siRNA injection. Conversely, overexpression of E-cadherin alleviated inflammation-induced lung injury. In vitro experiments revealed that succinic acid downregulated E-cadherin expression in alveolar epithelial cells through the PI3K/Akt/Hif-1α pathway. Succinic acid also indirectly downregulated the E-cadherin expression in alveolar epithelial cells by inducing macrophage M2 polarization and the production of Tgf-β1. In conclusion, this study demonstrates that succinic acid is a critical mediator of intrauterine inflammation-induced lung injury in offspring.NEW & NOTEWORTHY Intrauterine inflammation induces the accumulation of succinic acid in the placenta, which subsequently downregulated E-cadherin expression in the alveolar epithelial cells, thereby contributing to lung injury.

Intrauterine inflammation (IUI) is involved in the development of bronchopulmonary dysplasia (BPD). Previously, we observed BPD-like pathological changes in a mouse model of IUI. This study aimed to identify the key molecules involved in IUI-induced lung injury, focusing on NR4A1. Pregnant C57BL/6 mice were randomly divided into control and IUI groups. To verify the intervention effects, Nr4a1 siRNA was administered intranasally on postnatal day 3, while an NR4A1 overexpression plasmid was applied in MLE-12 cells to investigate downstream molecules. We found that the lungs of IUI-induced offspring exhibited a simplified structure on postnatal day 1 and excessive collagen fiber deposition by day 90. Postnatal NR4A1 intervention reversed IUI-induced neonatal lung injury. NR4A1 overexpression reduced cell proliferation and AKT and ERK1/2 phosphorylation levels, while also affecting the expression of the key epithelial–mesenchymal transition (EMT)-related gene TGF-β. EREG is a downstream target with potential NR4A1 binding sites in its promoter region. The expression of EMT-related genes can be recovered by blocking the receptor of EREG. Our findings imply that IUI induces BPD-like lung injury in neonates and fibrosis-like lung lesions in adult mice. The NR4A1-EREG-EGFR signaling pathway in pulmonary epithelial cells is crucial in IUI-induced lung injury, highlighting a key therapeutic target for mitigating BPD-like injury.

This retrospective cohort study aimed to investigate the correlation between vaginal infections and adverse pregnancy outcomes in a Chinese obstetric population. This study was conducted at the International Peace Maternity and Child Health Hospital in Shanghai from 2021 to 2023. The primary objective was to assess the incidence of various vaginal infections and their associations with preterm birth (PTB), low birth weight (LBW), and preterm premature rupture of membranes (PPROM). Data were collected from medical records, with vaginal infection diagnoses confirmed through standard laboratory procedures. This study included women who registered and delivered at our hospital between 2021 and 2023. Strict exclusion criteria were applied to control confounding factors, excluding women with a history of syphilis, human immunodeficiency virus infection, hepatitis virus infection, or non-live birth outcomes. Continuous variables were analyzed using the Mann–Whitney U test, whereas categorical variables were assessed using the Pearson chi-square test or Fisher exact test. Logistic regression analysis was employed for multivariate assessments to determine whether vaginal infections were independent risk factors for adverse pregnancy outcomes. Vaginal infections were significantly associated with adverse pregnancy outcomes. Women with vaginal infections had higher rates of PTB (15.65

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a large class of synthetic chemicals with ubiquitous human exposure. Maternal PFAS exposure has been linked with adverse birth outcomes, but their associations with preterm birth (PTB) remained ambiguous. METHODS: To assess the associations of individual and mixed PFAS exposure with preterm birth (PTB) and its subtypes (spontaneous and iatrogenic), a nested case-control study involving 177 PTB cases and 531 controls was conducted in Shanghai, China. Serum concentration of seven PFAS were measured in early pregnancy via ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). PTB, gestational weeks and birth weight were obtained from electronic medical record system. Conditional logistic regression and restricted cubic spline regression (RCS) were used for individual assessment. Weighted quantile sum (WQS) regression, quantile-based g-computation (QGC), and Bayesian kernel machine regression (BKMR) were conducted for PFAS mixture. Subtype analysis and sex stratified analysis were further examined. RESULTS: Both individually and in mixtures, significant associations were observed between elevated PFAS concentrations and increased PTB risk, along with reduced gestational weeks and lower birth weight. The WQS, QGC, and BKMR identified perfluorooctanoic acid (PFOA), per-fluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnDA) as the major contributors, with PFOA being particularly significant. Moreover, higher risks of PFAS-associated PTB were observed in the iatrogenic PTB subgroup and pregnant women with male infants. CONCLUSION: Maternal exposure to PFAS, whether individually or in mixtures, was significantly associated with increased risk of PTB. These associations might be subtype-specific and sex-specific. Further research is needed to validate our results and elucidate the underlying mechanisms.

Phenols and parabens, as endocrine-disrupting chemicals (EDCs), are prevalent in daily consumer products and industrial applications. Folate, a vital vitamin, plays a crucial role in numerous metabolic processes. The interaction between EDCs and folate is not well understood and warrants investigation. We utilized data from the National Health and Nutrition Examination Survey (NHANES) 2005-2016. Since many pollutants are co-exposed congeners, with interactive effects between pollutants, we employed multivariate linear regression model, weighted quantile sum regression, and Bayesian kernel machine regression (BKMR) to quantify the impact of folate levels in serum and red blood cell (RBC) and the overall effects of combined exposures. The study included 4395 children and adolescents. A negative correlation was observed between RBC folate concentrations and urinary concentrations of Bisphenol A (BPH), Triclosan (TRS), Methyl paraben (MPB), Propyl paraben (PPB), and Butyl paraben (BUP), in children and adolescents. Specifically, an increase in RBC folate levels was linked to a decrease in urinary BPH, TRS, MPB, PPB, and BUP concentrations. Similar associations were found with serum folate. The weighted quantile sum index showed a decrease in both RBC and serum folate levels with an increase in the mixture of phenols and parabens. BKMR further supported the overall negative impact of the chemical mixture on folate levels. This study provides evidence of an inverse relationship between exposure to phenols and parabens and folate concentrations in children and adolescents, which would be of significance in providing guidance for clinical interventions and calling for remediation actions to be prioritized during childhood.

BackgroundPer- and polyfuoroalkyl substances (PFAS) are categorized as persistent organic pollutants and commonly detected in humans, and their toxicity has attracted widespread attention. However, few studies have reported comparison of PFAS levels and potential factors between women pregnant using assisted reproduction technology (ART) and women pregnant naturally. ObjectiveTo analyze and compare serum concentrations and sociodemographic determinants of PFAS in pregnant women conceiving through ART and conceiving naturally from Shanghai. MethodsBased on the China National Birth Cohort (CNBC) in Shanghai from 2017 to 2019, 333 pregnant women conceiving through ART and 689 pregnant women conceiving naturally were recruited during the same period as study subjects. The concentrations of 32 PFAS were measured in early-pregnancy serum of all pregnant women, and four PFAS with the highest co-exposure levels in both groups were included in the subsequent analysis. Multiple linear regression models were performed to evaluate the associations of sociodemographic factors with serum PFAS concentrations in the two groups respectively. Beta coefficients and 95% confidence intervals (CI) were exponentiated to calculate the ratio of the geometric mean (GM) of PFAS concentrations after each unit change in the independent variable.ResultsPerfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), 6∶2 chlorinated polyfluoroethersulfonic acid (6∶2 Cl-PFESA), and perfluorohexanesulfonic acid (PFHxS) were four major PFAS in serum of pregnant women conceiving through ART and conceiving naturally, and the concentrations of PFOA, PFOS, and 6∶2 Cl-PFESA were higher in pregnant women conceiving through ART than in pregnant women conceiving naturally (P <0.05). The results of multiple linear regression analysis showed that age at pregnancy and household income were associated with serum PFAS levels in both groups. The serum concentrations of PFOS were higher in pregnant women aged ≥35 years old who conceiving through ART (GM ratio=1.26, 95%CI: 1.04, 1.54) and conceiving naturally (GM ratio=1.24, 95%CI: 1.08, 1.42) than pregnant women aged <30 years old respectively. Pregnant women conceiving through ART and conceiving naturally whose household annual income >300000 CNY had lower serum concentrations of PFOA [GM ratio (95%CI): 0.82 (0.72, 0.95) and 0.89 (0.81, 0.97), respectively] and PFHxS [GM ratio (95%CI): 0.66 (0.51, 0.86) and 0.77 (0.66, 0.90), respectively] than those women whose household annual income <200000 CNY. Additionally, pregnant women conceiving naturally with a graduate education or above had lower serum 6∶2 Cl-PFESA concentrations than women with an education below college (GM ratio: 0.81), and multiparous pregnant women conceiving naturally had higher serum concentrations of PFOS, 6∶2 Cl-PFESA, and PFHxS than primiparous pregnant women (GM ratio: 1.14, 1.25, and 1.27 respectively). ConclusionAlthough differences in serum PFAS levels are found between pregnant women conceiving through ART and women conceiving naturally in this study, maternal age and household income are common determinants of PFAS exposure levels in both populations. We find no special sociodemographic factors to affect PFAS concentrations of pregnant women conceiving through ART compared to pregnant women conceiving naturally. Further research is required to explore other potential factors.

BackgroundPesticide exposure may impact the reproductive health of women undergoing assisted reproductive technology (ART). However, data on pesticide exposure levels in women undergoing ART in China are scarce, and current research on influencing factors is limited. ObjectiveTo evaluate the preconceptional pesticide exposure levels and identify potential determinants among women undergoing ART. MethodsThis study was designed as a cross-sectional survey and recruited 508 women undergoing ART from July 2017 to December 2018 at the fertility clinic of the International Peace Maternity and Child Health Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. Gas chromatography/liquid chromatography-tandem mass spectrometry was used to determine the metabolite concentrations of organophosphate pesticides (OPs), pyrethroid pesticides (PYRs), and neonicotinoid pesticides (NEOs) in urine. The sum of molar concentrations of the three pesticide classes (∑2OPs, ∑2PYRs, and ∑2NEOs) were calculated. A questionnaire was used to collect demographic characteristics, dietary habits, and behavioral information. Multiple linear regression was employed to analyze the associations of demographic characteristics, dietary habits, and behavioral variables with the concentrations of pesticide metabolites in urine among the participants. ResultsThe median creatinine-adjusted concentrations of ∑2OPs, ∑2PYRs, and ∑2NEOs in this study were 419.77, 2.95, and 20.36 nmol·g−1, respectively. The multiple linear regression results showed that the urinary concentration of ∑2OPs was 42.88% higher in the participants with daily vegetable intake than in those who consumed vegetables ≤3 d per week (P<0.05), and the urinary concentration of ∑2PYRs was 37.24% higher in the participants with daily fruit intake than in those who consumed fruits ≤3 d per week (P<0.01). Similarly, the urinary concentrations of ∑2NEOs were 24.51% and 29.30% higher in the participants who consumed fruits daily and 4-6 d per week, respectively, than in those who consumed fruits ≤3 d per week (P<0.05). Besides, we also found that the urinary concentration of ∑2PYRs was negatively correlated with body mass index (BMI) in the participants (P<0.05). Furthermore, the urinary concentration of ∑2NEOs was not only positively correlated with age (P<0.05), but also significantly associated with pet ownership and infertility causes among the participants. Specifically, the participants who continued to own pets after conception had a 30.11% higher urinary concentration of ∑2NEOs than those who never owned pets (P<0.05), and the participants with infertility due to female factors had a 24.10% lower urinary concentration of ∑2NEOs than those who received ART treatment for infertility caused by male factors (P<0.05). ConclusionThe women undergoing ART in Shanghai are widely exposed to pesticides. Age, BMI, frequency of vegetable and fruit intake, pet ownership, and infertility causes may be related to the pesticide exposure levels in this population. However, more human data are needed to confirm these findings.

Objective: This study aimed to investigate the association of maternal first-trimester vitamin D levels and vitamin D supplementation during pregnancy with infant atopic dermatitis (AD) and to determine the effect of variables such as mode of conception on the association. Methods: This study was based on the Shanghai sub-cohort of the International Birth Cohort of China. A total of 4051 woman–infant pairs with singleton pregnancies were recruited. Vitamin D deficiency and insufficiency were defined as serum 25-hydroxyvitamin D concentrations of 25 and 50 nmol/L, respectively. AD in infants was assessed during the first six months using a standardized questionnaire based on the British Working Party criteria. Modified Poisson regression estimated the association between maternal vitamin D status and infant AD. Results: The risk of AD in infants was higher in women with deficient 25-hydroxyvitamin D levels in the first trimester (RR: 1.77, 95% CI: 1.41–2.23). This increased risk was seen in naturally conceived pregnancies, but not in those conceived using assisted reproductive technology (ART). The incidence of AD decreased in infants of mothers who took multi-vitamin (RR: 0.79, 95% CI: 0.67–1.98) and vitamin D supplements (RR: 0.51, 95% CI: 0.37–0.71) compared to those whose mothers did not take any supplements. Maternal vitamin D deficiency had varying effects on AD risk based on passive smoking exposure and breastfeeding patterns. Conclusions: Our findings highlight the importance of monitoring and supplementing vitamin D during pregnancy, especially in specific maternal populations, to reduce the risk of AD in offspring.

Prior research has reported that perfluoroalkyl and polyfluoroalkyl substances (PFAS) may be linked to impaired glucose homeostasis in pregnant women. However, few studies have investigated PFAS alternatives and isomers, and even less is known about the association among women conceiving through assisted reproductive technology (ART). The prospective cohort study aimed to explore associations of legacy PFAS, alternatives and isomers with gestational diabetes mellitus (GDM) and glucose homeostasis during pregnancy among 336 women conceiving through ART. Nineteen PFAS, including nine linear legacy PFAS, four short-chain alternatives, four branched isomers, and two emerging PFAS alternatives, were determined in first-trimester maternal serum. Fasting plasma glucose (FPG), 1-h and 2-h glucose concentrations following the oral glucose tolerance test (OGTT), and glycated hemoglobin (HbA1c) were measured during the second trimester. After adjusting for confounding variables, nearly half of individual PFAS (10/19) and PFAS mixtures were correlated with increased GDM risk or elevated 2-h glucose levels. Among PFAS congeners, emerging PFAS alternatives, chlorinated perfluoroalkyl ether sulfonic acids (Cl-PFESAs), showed a notable association with impaired glucose homeostasis. For example, 6:2 Cl-PFESA exhibited a correlation with GDM (OR = 1.31, 95

Assisted reproductive technology (ART) pregnancies present a higher risk of singleton preterm birth than natural pregnancies, but the underlying molecular mechanism remains largely unknown. RNA m6A modification is a key epigenetic mechanism regulating cellular function, but the role of m6A modification, especially its “reader” YTHDC1, in preterm delivery remains undefined. To delineate the role and epigenetic mechanism of m6A modification in ART preterm delivery, the effects of YTHDC1 on trophoblastic function were evaluated by CCK-8, EdU, Transwell, and flow cytometry analyses post its overexpression or knockdown. Downstream signaling pathways of YTHDC1 were investigated by RNA-seq, and targeted mRNAs were explored by RIP-seq and MeRIP-seq. Upstream transcriptional factors of YTHDC1 were determined by ChIP-seq and luciferase reporter assays. Elevated YTHDC1 was detected in human ART-conceived preterm placentas and in murine preterm placentas post estradiol (E2) exposure. In vitro experiments showed that YTHDC1 promoted trophoblastic cell proliferation and migration, but inhibited cell apoptosis. Mechanistically, E2 was proven to upregulate YTHDC1 expression via retinoid X receptor alpha (RXRA) in trophoblastic cells. Enhanced YTHDC1 expression augmented the translation of RPL37 in an m6A-dependent manner by binding to m6A-modified RPL37 mRNA and concomitantly promoted the overall translational output. Importantly, administration of siRNA targeting YTHDC1 effectively delayed the progression of preterm delivery. In conclusion, the identified E2/RXRA/YTHDC1/RPL37 axis provides new insights into the epigenetic mechanism underlying ART-associated preterm delivery. The findings offer a potential prognostic biomarker and therapeutic target for preterm delivery.

BACKGROUND AND AIM: Chronic or persistent anxiety (PA) over the course of pregnancy may lead to adverse maternal and infant outcomes. Several studies have investigated the potential contributing factors to transient anxiety (TA) at one point in pregnancy, but little is known about PA. This study aimed to identify the risk factors for TA and PA during pregnancy. METHOD: Pregnant women with no history of mental illness were recruited from 2016 to 2021 based on a Shanghai sub-cohort of the China National Birth Cohort study (CNBC). Structured survey interviews were conducted in early pregnancy to collect the socio-demographic information, obstetrical and physical health status, and lifestyle factors. The Zung Self-Rating Anxiety Scale (SAS) was used to assess the anxiety status of pregnant women and their partners during each trimester. Separate logistic regression models were performed to identify risk factors for TA (SAS scores ≥ 50 for only one trimester) and PA (SAS scores ≥ 50 for at least two trimesters). RESULTS: The prevalence of TA and PA among the total of 3456 pregnant women was 12% (n=421) and 4.2% (n=146), respectively. Logistic regression showed that younger age, poor physical health, low intake of vegetables, and poor sleep quality were the common factors strongly associated with TA and PA in pregnancy. Additionally, a low intake of milk (OR = 1.314, 95% CI: 1.034 – 1.677) was the exclusive predictor of TA. Self-pay medical insurance (OR = 1.757, 95% CI: 1.063 – 2.815) and partner anxiety (OR = 1.053, 95% CI: 1.029 – 1.076) were unique predictor of PA. CONCLUSIONS: Poor physical health, partner anxiety, and some socio-demographic (e.g. age and medical insurance) and lifestyle (e.g. diet and sleep) factors may play important roles in TA or PA during pregnancy. Identification of these risk factors may guide the development of early intervention strategies.

Epidemiological surveys indicate that intrauterine inflammation increases the risk of asthma in offspring. However, the underlying mechanisms remain largely unknown. Previous studies in BALB/c and C57BL/6 mice showed that prenatal exposure to endotoxins prevented allergic airway inflammation in offspring, which is inconsistent with most clinical observations. In this study, we found that prenatal LPS exposure increased airway resistance and total exfoliated cell counts, eosinophils, and IL-4 concentrations in BAL fluid of ovalbumin-sensitized Institute of Cancer Research (ICR) mice. Importantly, long noncoding RNA (lncRNA) NONMMUT033452.2 was upregulated in the lungs of LPS-exposed ICR offspring. Fluorescence in situ hybridization and cytoplasmic and nuclear fraction analyses revealed that this lncRNA was distributed in both the nuclei and cytoplasm of lung and airway epithelial cells, smooth muscle cells, and fibroblasts. Intranasal administration of NONMMUT033452.2 siRNA markedly alleviated allergic airway inflammation in ovalbumin-sensitized ICR mice. In vitro functional experiments demonstrated that overexpression of NONMMUT033452.2 inhibited the proliferation of lung and bronchiolar epithelial cells and promoted oxidative stress. RNA pull-down assays proved that NONMMUT033452.2 could directly bind Eef1D (eukaryotic translation elongation factor 1 delta). Overexpression of NONMMUT033452.2 induced the redistribution of Eef1D and substantially inhibited the expression of its downstream heat shock genes. NONMMUT033452.2 was also involved in the modulation of IL-1, IL-12, and some key molecules related to asthma, including Npr3 (natriuretic peptide receptor 3), Rac1 (Rac family small GTPase 1), and Nr4a3 (nuclear receptor subfamily 4, group A, member 3). Furthermore, the human lncRNA NONHSAT078603.2 was identified as a functional homolog of NONMMUT033452.2. These findings provide new insight into the pathogenic mechanism underlying asthma development.

Objective To assess the association between birth weight and childhood asthma risk using data from the 2019–2020 National Survey of Children’s Health database.Design Cross-sectional study.Setting The USA.Patients A representative cohort of American children.Exposure The exposure of this study was birth weight regardless of gestational age. Birth weight was divided into three groups: <1500 g, 1500–2500 g and >2500 g.Main outcome measures Primary outcomes were parent-reported diagnosis of asthma.Method The Rao-Scott χ2 test was used to compare the groups. The main analyses examined the association between birth weight and parent-report asthma in children using univariable and multivariable logistic models adjusting for preterm birth, age, sex, race, family poverty, health insurance, smoking, maternal age. Subgroup analysis was performed based on interaction test.Results A total of 60 172 children aged 3–17 years were enrolled in this study; of these, 5202 (~8.6%) had asthma. Children with asthma were more likely to be born preterm, with low birth weight (LBW) or very LBW (VLBW). The incidence of asthma was the highest in VLBW children at 20.9% and showed a downward trend with an increase in birth weight class, with rates of 10.7% and 8.1% in the LBW and normal birthweight groups, respectively. Children with VLBW (OR 1.97; 95% CI 1.29 to 3.01) had higher odds of developing asthma in the adjusted analysis model. However, VLBW was only shown to be a risk factor for asthma among Hispanics, black/African-Americans and children between the ages of 6 and 12 years, demonstrating racial and age disparities.Conclusions VLBW increases the risk of childhood asthma; however, racial and age disparities are evident.

Background Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition that is prevalent in children worldwide. We evaluated the potential relationship between birth weight and ADHD using newly released data from the National Survey of Children’s Health 2019–2020. Methods This population-based survey study used parent recollection data that were collected and submitted by 50 states and the District of Columbia to the National Survey of Children’s Health database from the National Survey of Children’s Health database. Those aged < 3 years and without birth weight or ADHD records were excluded. Children were stratified according to ADHD diagnosis and birth weight: very low birth weight (VLBW, < 1,500 g), low birth weight (LBW, 1,500–2,500 g), and normal birth weight (NBW, ≥ 2,500 g). Multivariable logistic regression was applied to examine the causal association between birth weight and ADHD while controlling for child and household characteristics. Results The final sample consisted of 60,358 children, of whom 6,314 (9.0%) were reported to have an ADHD diagnosis. The prevalence of ADHD was 8.7% in NBW children, 11.5% in LBW, and 14.4% in VLBW. Compared with NBW children, LBW children [adjusted odds ratio (aOR), 1.32 (95% CI, 1.03–1.68)], and VLBW children [aOR, 1.51 (95% CI, 1.06–2.15)] had a significantly higher risk of ADHD after adjusting all variables. These associations persisted in the male subgroups. Conclusion and relevance This study found that LBW and VLBW children were at a higher risk of ADHD.

RESEARCH QUESTION:Is ART associated with adverse neurodevelopmental outcome in 12-month-old offspring compared with those conceived through natural conception?DESIGN:In this prospective cohort study, 488 infertile women undergoing ART and 1397 women with natural conception were recruited and followed until their offspring were 12 months old. The primary outcome was the neurodevelopment in the offspring. The association between exposure to ART and Gesell developmental scale scores was investigated using multiple linear regression models after adjusting for confounders. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were used to verify the results.RESULTS:In total, 18 (3.7%) and 40 (2.9%) children in the ART and natural conception groups, respectively, had been diagnosed with neurodevelopmental delay at 12 months of age. It was found that gross motor, adaptive behaviour, language and total development quotient scores were comparable between the groups. Following multivariate linear regression and IPTW, social behaviour development quotient scores were found to be slightly higher in the ART group than the natural conception group. Higher social behaviour development quotient scores in the ART group were also observed in the male and the singleton subgroups.CONCLUSIONS:At 12 months, offspring born after ART appeared to have similar motor, language and adaptive behaviour skills, and total development quotient scores, to those born after natural conception. However, social behaviour development in 12-month-old infants was slightly higher in those conceived using ART than in naturally conceived offspring, especially in male or singleton infants. These findings may provide new information in evaluating the potential benefits and risks of ART.