Perinatal environmental enrichment changes anxiety-like behaviours in mice and produces similar intergenerational benefits in offspring.

Environmental enrichment implemented in early life is able to induce long-term changes in gene expression, synaptic function and behavioural responses. In this study, we evaluated the adult behavioural effects of perinatal environment enrichment in male and female mice (PEE), as well as the males and females of PEE male offspring (OPEE). For this purpose, animals were submitted to the following battery of behavioural analyses: elevated plus maze, open field test, light-dark box and novelty suppression feeding test. The frontal cortex and ventral hippocampus of PEE mice were collected for the evaluation of the expression of gamma-aminobutyric acid (GABA)-related genes. The PEE animals showed an increase in exploratory activity, associated with a reduction in anxiety-like behaviours on the elevated plus maze; this effect was mainly observed in males. Additionally, the male OPEE showed a reduction in anxiety-like behaviours on the elevated plus maze, mainly observed in a reduction of risk assessment-related behaviours. The PEE male mice also showed reduced expression of Gabra3 in the ventral hippocampus when compared to the control group. These results demonstrate that perinatal environmental enrichment promotes a reduction in anxiety-like behaviour that can be transferred intergenerationally.

Leptin decreases the transcription of BKCa channels and Gs to Gi protein-ratio in late pregnant rat uterus.

Obesity can have a significant impact on pregnancy outcomes by compromising the ability of the uterus to relax, which increases the likelihood of conditions such as preterm labor. One of the key pathways responsible for uterine relaxation is the ß-adrenergic signaling pathway, and it is well-documented that obesity, often linked to a high-fat diet, can disrupt this pathway within the uterine environment. Hyperleptinemia is a significant feature of pregnancy as well as obesity. However, the effect of leptin on ß-adrenergic signaling pathway has not been studied. In the present study, we studied the effects of leptin on transcriptions of the major proteins defining the ß-adrenergic signaling pathway in pregnant rat uterus. Leptin treatment at a supraphysiological concentration to pregnant rat uterine strips increased the mRNA and protein expressions of Gs protein but not the mRNA of ß2- and ß3-adrenoceptors. It also enhanced the expression of Gi-protein, but not the Gq protein. Nevertheless, the mRNA ratio of Gs to Gi protein experienced a significant decrease. Further, leptin reduced the transcription of BKCaα and BKCaß channel subunits. In leptin-stimulated tissues, there was also an increase in the expression of leptin receptor and JAK-2. In conclusion, leptin decreases the ratio of Gs to Gi proteins and BKCaα and BKCaß channel subunits suggesting hyperleptinemia is a likely factor inducing uterine relaxant dysfunction in obesity.

Oxidative stress in donor mares for ovum pick-up delays embryonic development.

The in vitro production of equine embryos via ovum pick-up (OPU) and intracytoplasmic sperm injection (ICSI) has increased rapidly. There is a marked effect of the individual mare on the outcome of OPU-ICSI, but little is known about the influence of the mare's health condition. This study aimed to investigate the potential associations between the concentrations of interleukin-6 (IL-6), reactive oxygen metabolites (d-ROMs), and biological antioxidant potential (BAP) in serum of oocytes' donor mares and the subsequent embryonic development. Just before OPU, a blood sample was collected from 28 Warmblood donor mares, that were subjected to a routine OPU-ICSI program. The serum concentrations of IL-6, d-ROMs, and BAP were assayed photometrically. The maturation, cleavage and blastocyst rate as well as the kinetics of blastocyst development were recorded. The average blastocyst rate was 24.68 ± 5.16% and the average concentrations of IL-6, d-ROMs, and BAP were 519.59 ± 157.08 pg/mL, 171.30 ± 4.55 carratelli units (UCARR), and 2711.30 ± 4.55 µmol/L, respectively. Serum concentrations of IL-6, d-ROMs, and BAP were not significantly different between mares yielding at least one blastocyst (552.68 ± 235.18 pg/mL, 168.36 ± 5.56 UCARR, and 2524.80 ± 159.55 µmol/L) and mares yielding no blastocysts (468.47 ± 179.99 pg/mL, 175.85 ± 7.89 UCARR, and 2999.50 ± 300.13 µmol/L, respectively). Serum concentrations of d-ROMs were significantly lower in mares with fast growing (at day 7-8 post ICSI; 148.10 ± 8.13 UCARR) compared to those with slow growing blastocysts (≥ day 9 post ICSI; 179.41 ± 4.89 UCARR; P = 0.003). Taken together, the serum concentration of IL-6, d-ROMs, and BAP do not determine the mare's ability to produce blastocysts in vitro. Although it may be questioned whether a single sample is representative of the mare's health status, changes in serum metabolites related to oxidative stress at the time of oocyte retrieval were linked to a delayed blastocyst development in a clinical OPU-ICSI outcome.

DOCK1 insufficiency disrupts trophoblast function and pregnancy outcomes via DUSP4-ERK pathway.

Abnormal trophoblast function is associated with diseases such as recurrent spontaneous abortion, pre-eclampsia, and preterm birth, and endangers maternal and fetal health. However, the underlying regulatory mechanisms remain unclear. In this study, we found DOCK1 expression is decreased in the placental villi of patients with recurrent spontaneous abortion, and that its expression determined the invasive properties of extravillous trophoblasts (EVTs), highlighting a previously unknown role of DOCK1 in regulating EVT function. Furthermore, DOCK1 deficiency disturbed the ubiquitinated degradation of DUSP4, leading to its accumulation. This caused inactivation of the ERK signaling pathway, resulting in inadequate EVT migration and invasion. DOCK1 was implicated in regulating the ubiquitin levels of DUSP4, possibly by modulating the E3 ligase enzyme HUWE1. The results of our in vivo experiments confirmed that the DOCK1 inhibitor TBOPP caused miscarriage in mice by inactivating the DUSP4/ERK pathway. Collectively, our results revealed the crucial role of DOCK1 in the regulation of EVT function via the DUSP4-ERK pathway and a basis for the development of novel treatments for adverse pregnancy outcomes caused by trophoblast dysfunction.

Cytochrome P4503A4 gene polymorphisms guide safe sufentanil analgesic doses in pregnant Chinese mothers: a multicenter, randomized, prospective study.

BACKGROUND: Sufentanil and ropivacaine when used as epidural anesthetics effectively reduce maternal pain during labor. From previous reports, rs2242480 single nucleotide polymorphisms (SNPs) can alter sufentanil metabolism, which affects analgesic efficacy. METHODS: We randomly divided 573 eligible mothers into groups A and B (in a 1 : 3 ratio). The control group (group A) was given sufentanil at the usual 0.5 mg/L-1 dose + 0.15% ropivacaine hydrochloride mixture in 10 ml. The sufentanil dose given to the intervention group (group B) was determined by genotype: the GA and AA genotype group (group B1) was given 87.6% (design based on previous study results) of the usual sufentanil clinical dose (0.438 mg/L-1 sufentanil + 0.15% ropivacaine hydrochloride mixture in 10 ml) and the GG genotype group (group B2) was given the same dose as group A. Efficacy indicators consisting of maternal vital signs, obstetric transfer, neonatal prognostic indicators, and adverse effects were recorded before and after analgesia across groups. RESULTS: Visual analog scale scores after analgesia across groups were significantly different from scores before analgesia, showing that analgesic effects across groups were effective. No significant differences were observed in efficacy, obstetric transfer, and neonatal prognosis indicators between groups. In comparison to groups B1 and B2, group A showed more markedly suppressed cardiovascular and respiratory effects, and also a higher incidence of negative side effects such as vomiting and urinary retention. CONCLUSION: We confirmed that individualizing sufentanil doses based on maternal genotypes increased safety and success rates for women during childbirth.

Maternal obstructive sleep apnea aggravates metabolic dysfunction-associated fatty liver disease via HMGB1-TLR4 signaling-mediated endoplasmic reticulum stress in male offspring rats.

AIMS/HYPOTHESIS: Maternal obstructive sleep apnea (MOSA) may inflict long-term metabolic effects on offspring. We hypothesize that MOSA increases the propensity for metabolic dysregulation in offspring and thus facilitates the development of metabolic dysfunction-associated fatty liver disease (MAFLD). This study aims to test the hypothesis and explore the underlying mechanism. METHODS: The MOSA rat model of upper airway obstruction was established and fecundated. The postweaning male offspring (n = 171) from both the control group and MOSA group were randomly fed the normal chow diet (NCD, n = 89) or high-fat diet (HFD, n = 82) for the next 5 months. Liver function, lipid profile, glucose, and insulin levels were measured. Expression levels of fibrosis-related proteins and endoplasmic reticulum (ER) stress-related proteins in liver tissues were assessed using immunohistochemistry and western blotting. RESULTS: MOSA increased body and liver weight in male offspring, along with augmented liver organ coefficient. Serum levels of aminotransferases, low-density lipoprotein, high-density lipoprotein, triglycerides, total cholesterol, total bile acid, fasting glucose, and insulin increased significantly. MOSA exacerbated HFD-induced hepatic steatosis and fibrosis. These effects were driven by the overactivated double-stranded RNA-activated protein kinase (PKR)-like eukaryotic initiation factor 2(PERK)-activating transcription factor (ATF)4-C/EBP homologous protein (CHOP) signaling pathway-induced ER stress, and hyperacetylation and release of high mobility group box-1(HMGB1) elicited above signaling in a TLR4-dependent manner. CONCLUSIONS: These findings indicate that MOSA can exert prolonged adverse effects manifested as metabolic dysfunction in male offspring. Therefore, surveillance and management of OSA during pregnancy may be necessary to prevent and alleviate MAFLD in offspring.

Maternal-placental axis and its impact on fetal outcomes, metabolism, and development.

Maternal obesity could impact offspring's health. During "critical period" such as pregnancy insults have a significant role in developing chronic diseases later in life. Literature has shown that diet can play a major role in essential metabolic and development processes on fetal outcomes. Moreover, the placenta, an essential organ developed in pregnancy, seems to have its functions impaired based on pre-gestational and gestational nutritional status. Specifically, a high-fat diet has been shown as a potential nutritional insult that also affects the maternal-placental axis, which is involved in offspring development and outcome. Moreover, some classes of nutrients are associated with pregnancy complications such as reduced intake of micronutrients and diabetes, preeclampsia, and preterm delivery. Thus, we will summarize the current literature on maternal environment factors that impacts the placental development and consequently the fetal an offspring health, or the maternal-placental axis, and this on fetal outcomes, metabolism, and development.

Global Prevalence and Mental Health Outcomes of Intimate Partner Violence Among Women: A Systematic Review and Meta-Analysis.

The aim of this systematic review was to assess the magnitude of the association between types of intimate partner violence (IPV) and mental health outcomes and shed light on the large variation in IPV prevalence rates between low- to middle-income countries and high-income countries. The study is a systematic review and meta-analysis. The following databases were searched for this study: Cochrane, MEDLINE, EMBASE, PsycINFO, Cumulative Index to Nursing and Allied Health Literature, and the Applied Social Sciences Index and Abstracts. The inclusion criteria for this study are as follows: quantitative studies published from 2012 to 2020 on IPV exposure in women aged 16+, using validated measures. Random effects meta-analyses and subgroup analysis exploring heterogeneity across population groups in different economic contexts are used in this study. In all, 201 studies were included with 250,599 women, primarily from high-income countries. Higher prevalence rates were reported for women's lifetime IPV than past year IPV. Lifetime psychological violence was the most prevalent form of IPV. Women in the community reported the highest prevalence for physical, psychological, and sexual violence in the past year compared to clinical groups. Perinatal women were most likely to have experienced lifetime physical IPV. Prevalence rates differed significantly (p = .037 to <.001) for "any IPV" and all subtypes by income country level. Meta-analysis suggested increased odds for all mental health outcomes associated with IPV including depression (odds ratio [OR] = 2.04-3.14), posttraumatic stress disorder (PTSD) (OR = 2.15-2.66), and suicidality (OR = 2.17-5.52). Clinical and community populations were exposed to high prevalence of IPV and increased likelihood of depression, PTSD, and suicidality. Future research should seek to understand women's perspectives on service/support responses to IPV to address their mental health needs. Work with IPV survivors should be carried out to develop bespoke services to reduce IPV in groups most at risk such as pregnant and/or help-seeking women.

Prenatal Measurements of Congenital Lung Malformations: Can They Predict Postnatal Size?

INTRODUCTION: Prenatally diagnosed congenital lung malformations (CLMs) are monitored via ultrasound and measured by congenital pulmonary airway malformation volume ratios (CVRs) which can predict postnatal respiratory symptoms. This study compared CVR to postnatal lesion size to help guide prenatal counseling. METHODS: A retrospective chart review evaluated the prenatal imaging and postnatal outcomes for patients who were prenatally diagnosed with CLMs and had a postnatal computed tomography (CT) scan at one institution. RESULTS: Fifty-seven patients were included. Four had symptoms requiring urgent resection. The remaining were discharged and had clinic follow-up with CT scan to determine next steps: five had no identified lesions, eight had lesions whose diagnosis did not warrant an operation, and 40 had lesions whose diagnosis rendered size a factor in operative decision-making. Of these 40, 26/40 patients (65%) underwent elective resection (median maximum CVR 0.97; median lesion size 4 cm) and 14/40 patients (35%) were observed without resection (median maximum CVR 0.5; median lesion size 3 cm). There was a positive correlation between prenatal CVR and postnatal lesion size, with R-squared = 0.46. Maximum CVRs were better than last CVRs when predicting whether postnatal CT size would fall above or below our institution's level of recommended resection, with an area under the curve of 0.85 and a CVR cut-point of 0.61. CONCLUSIONS: For newborns with asymptomatic CLMs, higher maximum CVRs correlated with larger size on postnatal CT. A maximum CVR ≤0.6 was correlated with a smaller postnatal CT size that may be eligible for nonoperative management. While these results are not intended to recommend surgery based on higher CVRs alone, this information could potentially be used to reassure expectant parents whose babies' prenatal imaging demonstrate lower maximum CVRs.

The predictive effect of mid-pregnancy sleep disorders on perinatal depression within women with or without depression in early pregnancy: A prospective cohort study.

BACKGROUND: To investigate the relationship between depression in early pregnancy and sleep quality in mid-pregnancy, and explore whether sleep disorders independently predicts depression across the perinatal period within women with or without depression in early pregnancy. METHODS: Data were collected at 7 time points from 12 weeks of pregnancy to 6 weeks postpartum. Multiple logistic regression and survival analysis were used to explore the relationship between sleep quality in mid-pregnancy and perinatal depression within women with or without depression in early pregnancy. RESULTS: 390 women were included. Women with depression in early pregnancy were more likely to have sleep disorders and perinatal depression. Women with sleep disorders had a higher risk of perinatal depression compared to women without sleep disorders in mid-pregnancy. Stratified analysis based on whether depressed at 12 weeks of pregnancy found that among women without depression, those with sleep disorders in mid-pregnancy were more likely to have subsequent perinatal depression and appeared earlier; whereas, among women with depression, mid-pregnancy sleep disorders was not a predictor of subsequent perinatal depression. LIMITATION: High rates of missed visits may lead to sample bias, with depression and sleep quality being assessed by self-report. CONCLUSIONS: Women with depression in early pregnancy are more likely to have sleep disorders in mid-pregnancy. There is a strong correlation between sleep quality in mid-pregnancy and perinatal depression among women without depression in early pregnancy. Routine screening and intervention for sleep disorders should be a priority in perinatal care to reduce the incidence of perinatal depression.

High glucose exposure of preimplantation embryos causes glucose intolerance and insulin resistance in F1 and F2 male offspring.

BACKGROUND: Although studies suggest that maternal high glucose (HG) increases offspring susceptibility to type 2 diabetes mellitus (T2DM), the underlying mechanisms are largely unclear. We studied whether glucose levels in oviducts are elevated when pregestational diabetic females get pregnant and whether the oviductal HG (OVHG) would act directly on embryos to increase offspring's T2DM susceptibility. METHODS: We established an in vivo model of OVHG by injecting female mice with streptozotocin (STZ) during the preimplantation period and an in vitro model of embryo culture with HG (ECHG) by culturing preimplantation embryos with HG, before examining glucose tolerance and insulin resistance (IR) in F1 and F2 offspring. FINDINGS: Injection of female mice with STZ induced a lasting significant glucose elevation in blood and oviduct fluid during the preimplantation period. The glucose tolerance test showed that both the STZ-induced OVHG and the ECHG caused glucose intolerance in F1 male and F1-sired F2 male offspring but had no effect on female offspring. Insulin tolerance test and the analysis for IR-related gene expression and glycogen contents in liver and muscle revealed significant IR in these male offspring. INTERPRETATION: This study provided evidence that HG can act directly on preimplantation embryos to increase offspring's T2DM susceptibility suggesting that the preimplantation period is a critical stage for transmission of mother's diabetes to offspring. FUND: This study was supported by grants from the China National Natural Science Foundation (Nos. 31772599, 32072738, 31702114, and 31902160), and the Natural Science Foundation of Shandong Province (Nos. ZR2022MC036, ZR2017BC025 and ZR2020QC102).

Sexual Coercion, Intimate Partner Violence, and Homicide: A Scoping Literature Review.

The specific relationship between sexual coercion, intimate partner violence (IPV) during pregnancy, and intimate partner homicide (IPH) is poorly understood. Through a scoping literature review, we identified 101 studies on sexual coercion, IPV during pregnancy, and IPH and created a conceptual model suggesting unintended pregnancies may serve as both a risk factor for and a product of IPV that may escalate to IPH. We illustrate a healthcare systems intervention implication of this model in the context of the Colorado Family Planning Initiative (CFPI). Descriptive statistics suggest an inverse association between contraception access and IPH, which declined by 62% during the first 4 years of the CFPI. Interventions aimed at improving reproductive agency, including improving contraception access and reducing unintended pregnancy, may be a useful opportunity for clinician and health systems to contribute to reducing both lethal and nonlethal IPV.

Determinants of organophosphate esters exposure in pregnant women from East China.

Organophosphate esters (OPEs) have been broadly used in various industrial and consumer products, resulting in global distribution and human exposure. Gestational exposure to OPEs may adversely affect the health of both pregnant women and their offspring. To better understand OPE exposure in pregnant women, our study determined eight urinary metabolites of major OPEs in pregnant women (n = 733) recruited at 12-16 weeks of gestation from Shanghai, China, and explored the determinants of OPE exposure among various sociodemographic characteristics, lifestyles, and dietary factors. Urinary metabolites of OPEs, including bis (1,3-dichloro-2-propyl) phosphate (BDCPP), bis (2-chloroethyl) phosphate (BCEP), bis (1-chloro-2-propyl) phosphate (BCIPP), dicresyl phosphate (DCP), diphenyl phosphate (DPP), dibutyl phosphate (DBP), bis (2-ethylhexyl) phosphate (BEHP), and bis (2-butoxyethyl) phosphate (BBOEP), exhibited a detection rate ranging from 69.30% to 99.32%. Multivariate linear regression models indicated that pregnant women who were multiparous, had a higher family income per capita, worked in white-collar jobs, and took nutritional supplements such as milk powder and fish oil tended to have higher urinary OPE metabolite concentrations. Besides, independent of sociodemographic characteristics and lifestyle factors, consumption of more aquatic products, soy products, pork, and puffed food, as well as drinking of purified tap water versus tap water, were associated with increased urinary OPEs metabolite concentrations. Our study demonstrated that OPE exposure was ubiquitous in pregnant women from Shanghai, and provided new insights into the potential factors influencing OPE exposure during pregnancy.

Prenatal exposure to replacement flame retardants and organophosphate esters and childhood adverse respiratory outcomes.

BACKGROUND: The association of prenatal exposure to organophosphate esters (OPEs) and replacement brominated flame retardants (RBFRs) with respiratory outcomes has not been previously investigated in humans, despite reports that these chemicals can cross the placenta and alter lung development as well as immune functions. METHODS: In a cohort of 342 pregnant women recruited between 2003 and 2006 in the greater Cincinnati, Ohio Metropolitan area, we measured indoor dust OPEs and RBFRs at 20 weeks of gestation and urinary OPEs at 16 and 26 weeks of gestation and at delivery. We performed generalized estimating equations and linear mixed models adjusting for covariates to determine the associations of prenatal OPEs and RBFRs exposures with adverse respiratory outcomes in childhood, reported every six months until age 5 years and with lung function at age 5 years. We used multiple informant modeling to examine time-specific associations between maternal urinary OPEs and the outcomes. RESULTS: Dust concentrations of triphenyl phosphate (TPHP) (RR: 1.40, 95% CI: 1.18-1.66), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (RR: 1.51, 95% CI: 1.23-1.85), and bis(2-ethylhexyl) tetrabromophthalate (RR: 1.57, 95% CI: 1.28-1.94) were associated with higher risk of wheezing during childhood. Dust TPHP concentrations were associated with higher risk of respiratory infections (RR: 1.43, 95% CI: 1.08-1.94), and dust tris-(2-chloroethyl) phosphate concentrations were associated with hay fever/allergies (RR: 1.11, 95% CI: 1.01-1.21). We also found that dust tris-(2-chloroethyl) phosphate loadings were associated with lower lung function. Urinary OPEs mainly at week 16 of gestation tended to be associated with adverse respiratory outcome, while bis(1-chloro-2-propyl) phosphate and diphenyl phosphate at delivery were associated with lower risk of hay fever/allergies. CONCLUSIONS: In-utero exposure to OPEs and RBFRs may be a risk factor for adverse respiratory outcomes in childhood, depending on the timing of exposure.

Gestational GenX and PFOA exposures induce hepatotoxicity, metabolic pathway, and microbiome shifts in weanling mice.

Ammonium perfluoro (2-methyl-3-oxahexanoate) (GenX), a replacement for perfluorooctanoic acid (PFOA), has been detected in multiple environmental media and biological samples worldwide. Accumulated evidence implies that GenX exposure might exert adverse health effects, although the underlying mechanisms have not been fully revealed. In this study, pregnant BALB/c mice were exposed to GenX (2 mg/kg/day), PFOA (1 mg/kg/day), or Milli-Q water by gavage from the first day of gestation (GD0) until GD21. Necropsy and tissue collection were conducted in pups at 4 weeks of age. PFOA and GenX induced similar histopathological changes in both the liver and the intestinal mucosa, accompanied by higher serum levels of alanine and aspartate aminotransferase. Moreover, the capacity of hepatic glycogen storage and intestinal mucus secretion were significantly decreased, suggesting dysfunction of liver metabolism and the intestinal mucosal barrier. A total of 637 and 352 differentially expressed genes (DEGs) were identified in the liver tissues of GenX and PFOA group, respectively. Most of the enriched pathways from the DEGs by KEGG enrichment analysis were metabolism-associated. Moreover, overexpression of CYP4A14, Sult2a1, Cpt1b, Acaa1b, Igfbp1, Irs-2 and decreased expression of Gys2 were observed in livers of GenX exposed pups, supporting the hypothesis that there was metabolic disruption. Furthermore, DNA damage and cell cycle arrest proteins (Gadd45ß, p21, Ppard) were significantly increased, while cell proliferation-related proteins (Cyclin E, Myc, EGFR) were decreased by gestational GenX exposure in the pups' liver. In addition, imbalance of gut microbiota and dysfunction of the intestinal mucosa barrier might contribute to hepatotoxicity at least in part. Taken together, our results suggested that gestational GenX exposure triggered metabolic disorder, which might be responsible for the hepatotoxicity in the pups in addition to dysfunction of the intestinal mucosa barrier. This study enriches the mechanisms of GenX-induced developmental hepatotoxicity by associating metabolic disorder with intestinal homeostasis.

Prenatal exposure to per- and polyfluoroalkyl substances and DNA methylation in the placenta: A prospective cohort study.

Epidemiological studies regarding the relationship between per- and polyfluoroalkyl substances (PFAS) and DNA methylation were limited. We investigated the associations of maternal PFAS concentrations with placental DNA methylation and examined the mediating role of methylation changes between PFAS and infant development. We measured the concentrations of 11 PFAS in maternal plasma during early pregnancy and infant development at six months of age. We analyzed genome-wide DNA methylation in 16 placental samples using reduced representation bisulfite sequencing. Additionally, we measured DNA methylation levels using bisulfite amplicon sequencing in 345 mother-infant pairs for five candidate genes, including carbohydrate sulfotransferase 7 (CHST7), fibroblast growth factor 13 (FGF13), insulin receptor substrate 4 (IRS4), paired like homeobox 2Ap (PHOX2A), and plexin domain containing 1 (PLXDC1). We found that placental DNA methylation profiles related to PFOA mainly enriched in angiogenesis and neuronal signaling pathways. PFOA was associated with hypomethylation of IRS4 and PLXDC1, and PFNA was associated with PLXDC1 hypomethylation. There were positive associations of CHST7 methylation with PFTrDA and IRS4 methylation with PFDoA and PFTrDA. PLXDC1 hypomethylation mediated the association between PFOA and suspected developmental delay in infants. Future studies with larger sample sizes are warranted to confirm these findings.

Fluorescence lifetime imaging microscopy for early diagnosis and severity prediction of preeclampsia with Nile Blue probe.

Preeclampsia (PE) is a common pregnancy complication and the leading cause of maternal and perinatal mortality. Unfortunately, the early diagnostic methods for PE are still rare. Fluorescence lifetime imaging (FLIM) technology has proven to be applicable for diagnosis of various diseases. Here, we explore the possibility of the FLIM technique for PE early diagnosis and severity prediction with Nile Blue probe as biosensor. 23 placental slices and 162 third-trimester-collected maternal peripheral blood serum samples were stained with Nile blue and imaged by FLIM system. Fluorescence lifetimes of the probe increased significantly as the disease worsened (p < 0.0001). Characterization of the probe showed an increasing tendency in lifetimes under lower polarity conditions and revealed that the reason for the lifetime differences in serum sample was polarity changes caused by abnormal lipid metabolism in serum. For early diagnosis, we investigated 42 12th-week-collected chronic hypertension (CH) serum samples and successfully distinguished PE patients from pregnant women. With the functions of measuring fluorescence lifetime and detecting polarity changes caused by an abnormal lipid microenvironment in maternal peripheral blood, FLIM technology, together with Nile Blue probe, presents a feasible and advantageous approach for PE early noninvasive diagnosis and severity prediction.

A Chinese longitudinal maternity cohort study (2013-2021) on intrahepatic cholestasis phenotypes: Risk associations from environmental exposure to adverse pregnancy outcomes.

Intrahepatic cholestasis of pregnancy (ICP) is an idiopathic disease that occurs during mid-to-late pregnancy and is associated with various adverse pregnancy outcomes, including intrauterine fetal demise. However, since the underlying cause of ICP remains unclear, there is an ongoing debate on the phenotyping criteria used in the diagnostic process. Here, we identified single- and multi-symptomatic ICP (ICP-S and ICP-M) in 104,221 Chinese females from the ZEBRA maternity cohort, with the objective of exploring the risk implications of the two phenotypes on pregnancy outcomes and from environmental exposures. We employed multivariate binary logistic regression to estimate confounder-adjusted odds ratios and found that ICP-M was more strongly associated with preterm birth and low birth weight compared to ICP-S. Throughout pregnancy, incremental exposure to PM2.5, O3, and greenness could alter ICP risks by 17.3%, 12.5%, and -2.3%, respectively, with more substantial associations observed with ICP-M than with ICP-S. The major scientific advancements lie in the elucidation of synergistic risk interactions between pollutants and the protective antagonistic effects of greenness, as well as highlighting the risk impact of preconceptional environmental exposures. Our study, conducted in the context of the "three-child policy" in China, provides epidemiological evidence for policy-making to safeguard maternal and neonatal health.

Exposure to greenness during pregnancy and the first three years after birth and autism spectrum disorder: A matched case-control study in shanghai, China.

Causes of autism spectrum disorder (ASD) have not been fully understood. Previous studies have linked environmental factors with ASD. However, evidence for the greenness-ASD association is limited, especially in China. To fill this gap, we conducted a matched case-control study to examine the association between greenness and ASD in China. Participants in this study were 84,934 children aged 3-12 years in Shanghai, China, selected using a multi-stage cluster sampling method. ASD cases were firstly screened by questionnaires completed by both children's parents and teachers, and were then confirmed by clinical examinations. Further, 10 healthy controls were randomly selected to match each ASD case by age and sex. The final analyses included 146 ASD cases and 1460 healthy controls. Participants' exposure to greenness before and after birth was assessed by normalized difference vegetation index (NDVI) and enhanced vegetation index (EVI) from NASA's Earth Observing System according to their residential locations. We used conditional logistic regression to examine the ASD-greenness association. Per interquartile range (IQR) increase in EVI500m and NDVI500m during the year before birth were associated with lower risks of ASD with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of 0.96 (95%CI: 0.946, 0.975, IQR = 0.074) and 0.937 (95%CI: 0.915, 0.959, IQR = 0.101). Exposure to greenness during the first 3 years after birth was also significantly associated with lower risk of ASD [IQR ORs for EVI500m and NDVI500m were 0.935 (95%CI: 0.91, 0.962, IQR = 0.06) and 0.897 (95%CI: 0.861, 0.935, IQR = 0.09), respectively]. Air pollution showed mediation effects on thegreenness-ASD association. Greenness was observed to have stronger beneficial effects on children without historical diseases and term birth. More greenness exposure before and after birth were significantly associated with lower risks of ASD in children. Our results highlight the importance of greenness in urban planning.