Search

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]

This report is the first comprehensive update on the activities of existing epilepsy‐pregnancy registries since 2010. The primary aim of these registries, which were initiated by independent international research groups some 25 years ago, has been to assess the risk of major congenital malformations (MCMs) in offspring exposed in utero to different antiseizure medications (ASMs). Progress reports are provided here from the five original registries (the International Registry of Antiepileptic Drugs and Pregnancy EURAP, the North American Antiepileptic Drug Pregnancy Registry, the UK and Ireland Epilepsy and Pregnancy Register, the Kerala Registry of Epilepsy and Pregnancy, and the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs) plus the more recently initiated West China Registry. Since their inception, the registries have published a wealth of data revealing important differences in risks across the most frequently used ASM treatments, thereby facilitating rational management of women with epilepsy who are of childbearing potential. Although the number of pregnancies enrolled in the different registries has more than doubled since the 2010 report, many questions remain. These include outcomes following prenatal exposure to most of the newer ASMs or different ASM combinations, as well as associations with specific MCMs rather than MCMs as a collective. All the registries, therefore, remain active and continue to enroll pregnancies. Administrative health care databases have been utilized more recently for the assessment of MCM risks and other adverse pregnancy outcomes associated with in utero exposure to ASMs. Although these can provide population‐based complementary information, they cannot replace the specific epilepsy‐pregnancy registries with their more detailed validated individual information. Given the multiple newer ASMs that are increasingly used and the continuing multiple knowledge gaps for the older ASMs, epilepsy‐pregnancy registries will continue to play an important role in the future. [ABSTRACT FROM AUTHOR]

Fetal exposures to many drugs of abuse, e.g., opioids and alcohol (EtOH), are associated with adverse neurodevelopmental problems in early childhood, including abnormalities in activity of the serotonin (5HT) transporter (SERT), which transports 5HT across the placenta. Little is known about the effects of these drugs on SERT expression. Pregnant women who used EtOH or opioids were compared to gestational age-matched controls using a structured questionnaire to determine prenatal substance exposure. Following elective pregnancy termination, placental membranous vesicles and exosomes were prepared from first and second trimester human placentas. Changes in EtOH- or opioid-exposed placental SERT expression and modifications were assessed by quantitative western blot. Novel SERT isoforms were sequenced and analyzed. Opioid-exposed but not EtOH-exposed maternal placentas showed SERT cleavage and formation of new SERT fragments (isoforms). Alcohol-exposed cases showed reduced SERT levels. Antibodies to the N-terminal SERT region did not recognize either of the two cleavage products, while antibodies to the central and C-terminal regions recognized both bands. The secondary band seen in the opioid group may represent a hypophosphorylated SERT fragment. These changes in SERT modifications and expression may result in altered fetal brain serotonergic neurotransmission, which could have neurodevelopmental implications. [ABSTRACT FROM AUTHOR]

Objectives: The digit ratio (2D:4D) is a possible marker of prenatal hormone exposure. The purpose of this study was to explore the relationships between digit ratio (2D:4D) and anthropometric indexes in Chinese children and adolescents. Methods: This study is a cross‐sectional study. A school‐based survey among 685 children and adolescents aged 8–15 years were conducted by stratified cluster sampling. The length of index finger (2D) and ring finger (4D) of the left hand, height, sitting height (ST), weight, chest circumference (CC), waist circumference (WC), hip circumference (HC), and abdominal skinfold thickness (AST) were measured. Pearson correlation and multivariate linear regression were used to analyze associations between 2D:4D and above indexes. Results: In girls, 2D:4D was positively related to WC, AST, waist‐to‐height (WHtR), waist‐to‐hip ratio (WHR) after adjusting for ages (p < 0.05). The WC, AST, WHtR, and WHR among girls with 2D:4D ≥ 1 were significantly higher than those among girls with 2D:4D < 1, respectively (p < 0.05). However, there was no correlations between digit ratio (2D:4D) and above anthropometric indexes in boys (p > 0.05). Conclusions: The 2D:4D was related to anthropometric indexes in girls, which suggests that the maternal prenatal hormone exposure might be related to the anthropometric indexes of their female offspring. [ABSTRACT FROM AUTHOR]

Objective: Human sexual dimorphism in physical strength manifests itself in men having a greater muscle mass than women, reflecting ancestral roles in competition, protection, and provisioning. Prenatal testosterone exposure, approximated via the second‐to‐fourth digit ratio (2D:4D), is linked to increased muscular strength in both sexes, indicating a developmental influence. Previous research has shown that both physical strength and 2D:4D have facial shape correlates, especially in men, but most studies have focused on Western populations and one trait. We therefore hypothesized a broader relationship between facial shape and both physical strength and 2D:4D. Materials and Methods: In this study, we quantified the association between facial shape, handgrip strength (HGS), and 2D:4D in a non‐Western Turkish sample (72 men, 55 women; Md = 22 y, SIR = 1.8 y) using two dimensional geometric morphometrics. Thirty‐eight somatometric and 32 semi‐landmarks were digitized on facial photographs taken in frontal view. Physical strength was assessed via handgrip strength (HGS), and the second digit length was divided by the fourth digit length to calculate 2D:4D. Results: Both HGS and 2D:4D were significantly associated with shape in both sexes, but only in men did they explain a significant amount of facial variation. Thin‐plates spline deformation grids and geometric morphometric morphs visualized the facial shape changes related to variations in handgrip strength, 2D:4D, and sexual dimorphism, enabling trait comparisons. Conclusion: This study contributes a comparative sample from the Middle East, which is indispensable to discern universalities from Western peculiarities. It provides evidence to better understand the biological basis of facial traits, which can potentially serve as increasingly relevant social cues in today's online and digital environments. [ABSTRACT FROM AUTHOR]

Objectives: Second to fourth digit ratio is widely known indicator of prenatal sex hormones proportion. Higher prenatal androgenization results in longer fourth finger and lower 2D:4D index. The aim of this study was to determine whether the 2D:4D digit ratio is associated with DNA methylation (DNAm) age dependently on sex. Material and Methods: The study included 182 adults (106 females and 76 males) with a mean age of 51.5 ± 13 years. The investigation consisted of three main parts: a survey, anthropometric dimensions measurements (fingers length) and methylome analysis using collected blood samples. Genome‐wide methylation was analyzed using EPIC microarray technology. Epigenetic age and epigenetic age acceleration were calculated using several widely applied algorithms. Results: Males with the female left hand pattern had more accelerated epigenetic age than those with the male pattern as calculated with PhenoAge and DNAmTL clocks. Conclusions: Finger female pattern 2D:4D above or equal to 1 in males is associated with epigenetic age acceleration, indicating that prenatal exposure to estrogens in males may be related to aging process in the later ontogenesis. [ABSTRACT FROM AUTHOR]

Objective The ductus arteriosus normally closes after birth. Histamine 2 receptor antagonist (H 2 RA) has been associated with patent ductus arteriosus (PDA). We aimed to study the characteristics of term infants with PDA and their possible association with prenatal exposure to antacids—proton pump inhibitors (PPIs) and H 2 RA. Study Design This was a population-based matched case–control study of mothers registered at "Clalit" Health Maintenance Organization (HMO) and their infants born at "Soroka" University Medical Center (SUMC) between 2001 and 2018. Cases are defined as term infants born with PDA diagnosed by echocardiography and registered in the postdelivery discharge form. Each case was matched with four term newborns without PDA diagnosis. Exposure window was defined by the timing of first purchase of H 2 RA or PPI during pregnancy and based on information from a computerized medication database (Clalit HMO, SUMC). Results PDA was diagnosed in 1,884 term infants (4.9%). Characteristics included a significantly higher percentage of lack of prenatal care, cesarean section, in vitro fertilization, polyhydramnios, oligohydramnios, Apgar 1 minute <5, and prenatal exposure to H 2 RA (odds ratio [OR] 4.18) and PPIs (OR 3.50; all p < 0.001). PDA association with exposure window was similar in each trimester (1.5–2%) for both H 2 RA and PPI. Conclusion PDA incidence in term infants in our population was greater than previously reported. PPI and H 2 RA are both antiacids with different mechanisms of action. The similar OR for exposure to one as well as the other, and the lack of influence of the initial exposure period, are compatible with bias. Key Points Term newborns with PDA have different characteristics than newborns without PDA. Prenatal exposure to PPIs or H 2 RA is associated with greater risk of PDA in term newborns. The possible effect mechanism of PPIs on the ductus is unclear and understudied. [ABSTRACT FROM AUTHOR]

Introduction Health agencies have called for research evaluating e-cigarette (EC) use in supporting prenatal smoking cessation. This study aimed to describe (1) the characteristics of smokers who begin using electronic cigarettes (ECs) during pregnancy, (2) how frequently smokers reduce or eliminate pre- and post-natal combustible cigarette (CC) use, and (3) the risk for neonatal health complications among smokers who initiate ECs during pregnancy. Aims and Methods Pregnant women using CCs exclusively during prepregnancy, who participated in a U.S. surveillance study, were classified by their reported late-pregnancy smoking behavior as CC-exclusive users, EC initiators, or quitters. EC initiators were further subclassified as dual users (used both ECs and CCs) or EC replacers (used ECs exclusively). Results Of 29 505 pregnant smokers, 1.5% reported using ECs during the last three pregnancy months. Among them, 29.7% became EC-exclusive users. EC initiators were disproportionately non-Hispanic White. Relative to quitters, EC initiators had lower income, were less likely to be married, have intended pregnancies, receive first-trimester prenatal care, and participate in a federal assistance program. Compared to CC-exclusive users, EC initiators overall, and dual users specifically, were more likely to reduce pre- and post-natal CC usage relative to prepregnancy levels. EC initiators' risk for neonatal health complications fell between quitters and CC-exclusive users, though the differences were not statistically significant. Conclusions Although EC initiators reduced CC use more than CC-exclusive users, only 29.7% reported complete CC cessation, and there was insufficient evidence of reduction in neonatal health complications relative to CC-exclusive users. Currently, ECs should not be considered a viable gestational smoking cessation strategy. Implications Health agencies have identified a critical need for research evaluating the use of e-cigarettes in supporting prenatal smoking cessation. Using the U.S. Pregnancy Risk Assessment Monitoring System surveillance study data, we provide real-world evidence that prenatal e-cigarette initiation as a smoking cessation tool is used infrequently among pregnant CCs smokers. Most using e-cigarettes in the last 3 months of pregnancy also used CCs. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is known as a group of neurodevelopmental conditions including stereotyped and repetitive behaviors, besides social and sensorimotor deficits. Anatomical and functional evidence indicates atypical maturation of the striatum. Astrocytes regulate the maturation and plasticity of synaptic circuits, and impaired calcium signaling is associated with repetitive behaviors and atypical social interaction. Spontaneous calcium transients (SCT) recorded in the striatal astrocytes of the rat were investigated in the preclinical model of ASD by prenatal exposure to valproic acid (VPA). Our results showed sensorimotor delay, augmented glial fibrillary acidic protein -a typical intermediate filament protein expressed by astrocytes- and diminished expression of GABAA-ρ3 through development, and increased frequency of SCT with a reduced latency that resulted in a diminished amplitude in the VPA model. The convulsant picrotoxin, a GABAA (γ-aminobutyric acid type A) receptor antagonist, reduced the frequency of SCT in both experimental groups but rescued this parameter to control levels in the preclinical ASD model. The amplitude and latency of SCT were decreased by picrotoxin in both experimental groups. Nipecotic acid, a GABA uptake inhibitor, reduced the mean amplitude only for the control group. Nevertheless, nipecotic acid increased the frequency but diminished the latency in both experimental groups. Thus, we conclude that striatal astrocytes exhibit SCT modulated by GABAA-mediated signaling, and prenatal exposure to VPA disturbs this tuning. [ABSTRACT FROM AUTHOR]

Introduction: Prenatal antidepressant exposure has been associated with lower gestational age and birthweight. Yet, unmeasured residual confounding may inflate this association. We explored if maternal genetic liability for major depression explains part of the association of antidepressant use in pregnancy with lower gestational age and birthweight. Material and Methods: We employed the maternal polygenic score (PGS) for major depression as a measure of genetic liability. We used generalised linear models to estimate the differences in gestational age and birthweight at each PGS quintile between children whose mothers continued antidepressant use during pregnancy (continuation group), children whose mothers discontinued antidepressant use during pregnancy (discontinuation group) and unexposed children. Results: After adjusting for confounders, we found significant differences in birthweight between PGS quintiles in the continuation and unexposed group. Yet, this relationship was not linear. Furthermore, at the lowest and highest PGS quintiles, the continuation group had significantly reduced mean gestational ages (adjusted β ranges: 1.7–4.5 days, p < 0.001–0.008) and lower mean birthweights (adjusted β ranges: 58.6–165.4 g, p = 0.001–0.008) than the discontinuation and unexposed groups. Conclusion: We confirmed that antidepressant use in pregnancy was associated with small reductions in gestational age and birthweight but found that genetic liability for depression was not linearly associated with this risk. The causality of the observed associations could not be established due to the observational nature of the study. Residual confounding linked to the underlying disease was likely still present. [ABSTRACT FROM AUTHOR]

• Human iPSC neural progenitor cells (NPC) only respond to IL-6 by trans -signalling. • Microglia-secreted sIL6Ra levels insufficient to induce NPC IL-6 trans -signalling. • NPC display marginal transcriptional responses to IL-6 in co-culture with microglia. • There are clear and replicable effects of IL-6 on the microglial transcriptome. • Future work should explore the role of IL-6 cis- and trans -signalling in microglia. Elevated interleukin (IL-)6 levels during prenatal development have been linked to increased risk for neurodevelopmental disorders (NDD) in the offspring, but the mechanism remains unclear. Human-induced pluripotent stem cell (hiPSC) models offer a valuable tool to study the effects of IL-6 on features relevant for human neurodevelopment in vitro. We previously reported that hiPSC-derived microglia-like cells (MGLs) respond to IL-6, but neural progenitor cells (NPCs) in monoculture do not. Therefore, we investigated whether co-culturing hiPSC-derived MGLs with NPCs would trigger a cellular response to IL-6 stimulation via secreted factors from the MGLs. Using N=4 donor lines without psychiatric diagnosis, we first confirmed that NPCs can respond to IL-6 through trans -signalling when recombinant IL-6Ra is present, and that this response is dose-dependent. MGLs secreted soluble IL-6R, but at lower levels than found in vivo and below that needed to activate trans -signalling in NPCs. Whilst transcriptomic and secretome analysis confirmed that MGLs undergo substantial transcriptomic changes after IL-6 exposure and subsequently secrete a cytokine milieu, NPCs in co-culture with MGLs exhibited a minimal transcriptional response. Furthermore, there were no significant cell fate-acquisition changes when differentiated into post-mitotic cultures, nor alterations in synaptic densities in mature neurons. These findings highlight the need to investigate if trans -IL-6 signalling to NPCs is a relevant disease mechanism linking prenatal IL-6 exposure to increased risk for psychiatric disorders. Moreover, our findings underscore the importance of establishing more complex in vitro human models with diverse cell types, which may show cell-specific responses to microglia-released cytokines to fully understand how IL-6 exposure may influence human neurodevelopment. [ABSTRACT FROM AUTHOR]

• PPE inhibited the development of glomeruli and promoted compensatory growth of renal tubules. • PPE at clinical dose disturbed fetal kidney development with a time-effect difference, manifested as full-term pregnancy exposure > early pregnancy exposure > mid-late pregnancy exposure. • The developmental toxicity of PPE on fetal kidney was more serious to the female fetuses than the males. Prednisone is a synthetic glucocorticoid that is commonly used in both human and veterinary medication. Now, it is also recognized as an emerging environmental contaminant. Pregnant women may be exposed to prednisone actively or passively through multiple pathways and cause developmental toxicity to the fetus. However, the impact of prenatal prednisone exposure (PPE) on fetal kidney development remains unclear. In this study, pregnant mice were administered prednisone intragastrically during full-term pregnancy with different doses (0.25, 0.5, or 1 mg/(kg·day)), or at the dose of 1 mg/(kg·day) in different gestational days (GD) (GD0-9, GD10-18, or GD0-18). The pregnant mice were euthanized on GD18. HE staining revealed fetal kidney dysplasia, with an enlarged glomerular Bowman's capsule space and a reduced capillary network in the PPE groups. The expression of the podocyte and the mesangial cell marker genes was significantly reduced in the PPE groups. However, overall gene expression in renal tubules and collecting ducts were markedly increased. All of the above effects were more pronounced in high-dose, full-term pregnancy, and female fetuses. Studies on the mechanism of the female fetal kidney have revealed that PPE reduced the expression of Six2, increased the expression of Hnf1β, Hnf4α, and Wnt9b, and inhibited the expression of glial cell line-derived neurotrophic factor (GDNF) and Notch signaling pathways. In conclusion, this study demonstrated that there is a sex difference in the developmental toxicity of PPE to the fetal kidney, and the time effect is manifested as full-term pregnancy > early pregnancy > mid-late pregnancy. [Display omitted] [ABSTRACT FROM AUTHOR]

Nicotine exposure is a common adverse environment during pregnancy and causes developmental toxicity of long bones in offspring. However, the effect of prenatal nicotine exposure (PNE) on bone mass accumulation in female offspring and its mechanism remained to be further investigated. In this study, we constructed a PNE rat model and collected the long bone and the bone marrow mesenchymal stem cells (BMSCs) from female offspring rats for the detection of bone mass, cell apoptosis, and the expressions of osteogenesis‐ and apoptosis‐related genes. The results revealed that PNE induced low bone mass in female offspring rats and was associated with the suppression of osteogenic function. Moreover, the apoptosis of BMSCs derived from the PNE female offspring rats was raised, and the expression ratio of apoptosis marker genes BAX/BCL‐2 was significantly increased. Further, PNE inhibited the expression and function of insulin‐like growth factor l (IGF1) signaling pathway in BMSCs. However, the exogenous IGF1 treatment partially ameliorated the increased apoptosis of BMSCs derived from the PNE female offspring rats. In conclusion, PNE induced low bone mass in female offspring rats, which was attributed to the increased apoptosis of BMSCs due to functional inhibition of IGF1 signaling pathway. [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]

Introduction: Mammalian reproductive and somatic development is regulated by steroid hormones, growth hormone (GH), and insulin-like growth factor-1 (IGF-1). Based largely on information from humans, model organisms, and domesticated animals, testosterone (T) and the GH/IGF-1 system activate sexually differentiated development, promoting male-biased growth, often at a cost to health and survivorship. To test if augmented prenatal androgen exposure in females produces similar developmental patterns and trade-offs, we examine maternal effects in wild meerkats (Suricata suricatta), a non-model species in which adult females naturally, albeit differentially by status, express exceptionally high androgen concentrations, particularly during pregnancy. In this cooperative breeder, the early growth of daughters predicts future breeding status and reproductive success. Methods: We examine effects of normative and experimentally induced variation in maternal androgens on the ontogenetic patterns in offspring reproductive hormones (androstenedione, A4; T; estradiol, E2), IGF-1, growth from pup emergence at 1 month to puberty at 1 year, and survivorship. Specifically, we compare the male and female offspring of dominant control (DC or high-T), subordinate control (SC or lower-T), and dominant treated (DT or blocked-T) dams, the latter having experienced antiandrogen treatment in late gestation. Results: Meerkat offspring showed sex differences in absolute T and IGF-1 concentrations, developmental rates of A4 and E2 expression, and survivorship -- effects that were sometimes socially or environmentally modulated. Atypical for mammals were the early male bias in T that disappeared by puberty, the absence of sex differences in A4 and E2, and the female bias in IGF-1. Food availability was linked to steroid concentrations in females and to IGF-1, potentially growth, and survival in both sexes. Maternal treatment significantly affected rates of T, E2, and IGF-1 expression, and weight, with marginal effects on survivorship; offspring of DT dams showed peak IGF-1 concentrations and the best survivorship. Discussion: Maternal effects thus impact offspring development in meerkats, with associated trade-offs: Whereas prenatal androgens modify postnatal reproductive and somatic physiology, benefits associated with enhanced competitiveness in DC lineages may have initial costs of reduced IGF-1, delay in weight gain, and decreased survivorship. These novel data further confirm the different evolutionary and mechanistic pathways to cooperative breeding and call for greater consideration of natural endocrine variation in both sexes. [ABSTRACT FROM AUTHOR]

Background: The developing kidney is vulnerable to prenatal environmental factors such as metal exposure, potentially altering the risk of later-life kidney dysfunction. This study examines the relationship between prenatal metal exposures, individually and as mixtures, and adolescent kidney function in Project Viva, a prospective longitudinal birth cohort in Massachusetts, USA. Methods: We used data on metals measured in blood during pregnancy including 15 in the first trimester and four in the second trimester. We calculated estimated glomerular filtration rate (eGFR) in adolescents (mean: 17.7 years) using cystatin C- (eGFRcys) and creatinine-based (eGFRcreat) equations for children. We used linear regression for single metal analyses, and Bayesian kernel machine regression and quantile-based g-computation for mixture analyses, adjusting for relevant covariates. To account for multiple comparisons in the single metal analyses, we applied the Holm-Bonferroni procedure to control the false discovery rate. Results: This study included 371 participants with first trimester metals and adolescent eGFR, and 256 with second trimester metals. Each doubling in first trimester cadmium concentration was associated with lower adolescent eGFRcys (β:-1.51; 95% CI:-2.83, -0.18). Each doubling in first trimester chromium (β:-1.45; 95% CI:-2.71, -0.19), nickel (β:-1.91; 95% CI:-3.65, -0.16), and vanadium (β:-1.69; 95% CI:-3.21, -0.17) was associated with lower adolescent eGFRcreat. After adjusting for multiple comparisons, p-values for associations between adolescent eGFR and chromium, nickel, vanadium and cadmium did not meet the criteria for significance. Metal mixture analyses did not identify statistically significant associations with adolescent eGFR. Conclusions: These findings have important implications for future studies investigating the potential mechanisms through which prenatal metal exposures affect long-term kidney health in children. [ABSTRACT FROM AUTHOR]

Background: A large body of data shows that fetal brain development is vulnerable to disruption by air pollution experienced by the mother during pregnancy, adversely affecting cognitive and psychomotor capabilities during childhood (De Asis-Cruz et al., Biol Psychiatry 7:480–90, 2022; Morgan ZEM et al., Environ Health 22:11, 2023). This study has sought to identify gestational windows of susceptibility to prenatal exposure to air pollution. Methods: 470 African American and Latina mother/child pairs participated in a prospective cohort study based in the low-income communities of Northern Manhattan and the South Bronx, New York City. Gestational exposure to respirable particulate matter (PM2.5) and nitrogen dioxide (NO2) was assessed through validated models in relation to cognitive and motor development assessed at ages 1, 2, and 3 years using the Bayley-II Scales. Multiple linear regression models and distributed lag models (DLM) were used to identify critical windows of exposure by trimester and week of pregnancy. Results: By linear regression, average exposures to NO2 during the first and second trimesters and the entire pregnancy were significantly and negatively associated with the mental developmental index (MDI) at age 1. Average exposures to PM2.5 during the second trimester and the entire pregnancy were also significantly, inversely associated with age 1 MDI. No significant associations were found between these exposures and MDI at age 2. NO2 exposure during the first trimester was significantly negatively associated with MDI at age 3. Using DLM, exposures to NO2 at lags 29–30 weeks (within the first trimester) and PM2.5 at lags 17–18 weeks (second trimester) were significantly and inversely associated with MDI at age 1. Significant, inverse associations were found between exposures to NO2 at lag 29 weeks and PM2.5 at lags 27–29 weeks and children's MDI at age 3. No significant associations were found between psychomotor index (PDI) and prenatal exposures to NO2 or PM2.5 at ages 1, 2 or 3. Conclusions: Our finding that prenatal exposure to air pollution in the first and second trimesters was associated with lower scores for cognitive development at ages 1 and 3 is of concern because of the potential consequences of these outcomes for long-term functioning. They underscore the need for stronger policies to protect pregnant individuals and offspring, particularly during vulnerable, early life-stage of development. [ABSTRACT FROM AUTHOR]

Background: A growing body of literature links prenatal mood and substance use to children's cognitive and behavioral development. The relative contribution of these risk factors on children's executive function (EF) in the context of socioeconomic adversities needs further evaluation. To address this gap, we investigated the role of prenatal maternal anxiety and depression on childhood EF, specifically inhibitory control and working memory, within the context of socioeconomic adversities and prenatal substance use. We hypothesized that higher maternal mood symptoms, higher persistent prenatal drinking and smoking, and lower socioeconomic status would be associated with lower EF skills during early childhood. Methods: We used data from 334 mother–child dyads followed prospectively through pregnancy and the offspring's childhood. Prenatal maternal depression and anxiety were assessed via standardized questionnaires. Prenatal alcohol and tobacco consumption were assessed via a timeline follow-back interview. The EF touch battery assessed child inhibitory control and working memory at 3–5 years of age (4.76 ± 0.58 years, 171 females). Separate linear regression models were used to estimate the association of prenatal tobacco, alcohol, anxiety, and depression exposure with our two components of child EF, inhibitory control and working memory, while adjusting for gestational age, sex, and age at assessment. The following variables were also included as covariates: maternal educational achievement, employment status, parity, and household crowding index. Results: Children of mothers with high trait anxiety scores had reduced inhibitory control compared to children of mothers without trait anxiety or depression (β = -0.12, 95% CI:-0.22,-0.01). Children of mothers in the moderate to high continuous smoking group showed lower inhibitory control (β = − 0.19, 95% CI:-0.38,-0.01) compared to children of mothers in the none smoking group. Additionally, lower maternal education and higher household crowding were each associated with reduced inhibitory control. We found no significant association between prenatal maternal depression, anxiety, or socioeconomic factors with working memory. Conclusions: These results underscore the need for comprehensive context-specific intervention packages, including mental health support for women to promote healthy inhibitory control development in children. [ABSTRACT FROM AUTHOR]

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) may cause adverse birth outcomes. Thyroid hormones may play a key role in mediating the effects of PFAS. We enrolled 374 mother-infant pairs from the Ezhou birth cohort study between 2019 and 2020. Eight PFASs and six thyroid hormones were measured in maternal serum during the first trimester of pregnancy. Neonatal growth metrics, including birth weight, length, head circumference, and gestational age, were acquired. Multivariate linear regression was performed to determine the associations between maternal serum PFAS and thyroid hormone levels and birth outcomes and a mediation analysis was also conducted. Except for perfluoroheptanoic acid (41.2%), the other seven PFAS detection rates were more than 85%, and the highest median concentration was observed for PFOSA with levels of 5.21 ng/mL. After controlling for typical confounders, we observed a decrease in birth length (cm) with increasing serum concentrations of perfluorononanoic acid (PFNA) (β = -0.54; 95% CI = -1.0, -0.08) and perfluorohexane sulfonate (PFHxS) (β = -0.64; 95% CI = -0.86, -0.42). Additionally, a decrease in birth head circumference was observed with increasing concentrations of perfluorooctanote (PFOA) (β = -0.73, 95% CI = -1.19, -0.27) and PFHxS (β = -0.30; 95% CI = -0.53, -0.07). Maternal free triiodothyronine (FT3) mediated 36.7% of the negative association between PFNA and birth length, and free thyroxine (FT4) mediated 30.8% of the effect of PFOA on head circumference. When performing stratified analysis by infant sex, the associations might differ between boys and girls. Our study suggested prenatal exposure to some PFASs was negatively associated with birth length and circumference, and FT3 and FT4 may partly mediate the association. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Several recent studies reported the potential adverse effects of titanium exposure on glucose homeostasis among the non-pregnant population, but the association of titanium exposure with gestational diabetes mellitus (GDM) is scarce. Methods: The present study of 1,449 pregnant women was conducted within the Jiangsu Birth Cohort (JBC) study in China. Urine samples were collected in the early pregnancy, and urinary titanium concentration and non-targeted metabolomics were measured. Poisson regression estimated the association of titanium exposure in the early pregnancy with subsequent risk of GDM. Multiple linear regression screened for titanium-related urine metabolites. Mediation analyses assessed the mediating effects of candidate metabolites and pathways. Results: As parameterized in tertiles, titanium showed positive dose–response relationship with GDM risk (P for trend = 0.008), with women at the highest tertile of titanium exposure having 30% increased risk of GDM [relative risk (RR) = 1.30 (95% CI: 1.06, 1.61)] when compared to those exposure at the first tertile level. Meanwhile, we identified the titanium-related metabolites involved in four amino acid metabolic pathways. Notably, the perturbation of the aminoacyl-tRNA biosynthesis and alanine, aspartate and glutamate metabolism mediated 27.1% and 31.0%, respectively, of the relative effect of titanium exposure on GDM. Specifically, three titanium-related metabolites, choline, creatine and L-alanine, demonstrated predominant mediation effects on the association between titanium exposure and GDM risk. Conclusions: In this prospective study, we uniquely identified a correlation between early pregnancy titanium exposure and increased GDM risk. We unveiled novel insights into how perturbations in amino acid metabolism may mediate the link between titanium exposure and GDM. Notably, choline, creatine, and L-alanine emerged as key mediators influencing this association. Our findings imply that elevated titanium exposure in early pregnancy can lead to amino acid dysmetabolism, thereby elevating GDM risk. [ABSTRACT FROM AUTHOR]

This article presents information on how the child welfare (CW) system informs caregivers about prenatal substance exposure (PSE) and related concerns, and how those caregivers communicate back to CW about PSE issues. Focus group and interview data for this qualitative study were collected in Fall 2019 and Spring 2020 from two states, each including four local (regional/county) CW agency sites. Caregivers were eligible for inclusion if they had cared for a child served by one of the sites, with priority for those who had cared for a child with known PSE or related special needs, resulting in a total of 44 caregivers. Of these, 41 had served as non-relative caregivers, while 10 had served as informal or formal kinship caregivers. Caregivers emphasized the need for more information-sharing from CW professionals related to the histories and needs of the children in their care. Thematic findings underscore that having more information about the general impact of PSE and exposure status of individual children could better prepare caregivers. CW agencies can use these findings to inform training, information sharing, and caregiver support.When caregivers have relevant information about the children in their care, outcomes for development, family preservation, and support can be improved. [ABSTRACT FROM AUTHOR]

Malnutrition early in life increases the later-life risk of noncommunicable diseases, and previous epidemiologic studies have found a link between famine and renal impairment, but no consensus has been reached. This meta-analysis and systematic review were conducted to assess the correlation between early-life famine exposure and the risk of developing renal impairment. Search in Embase, Scopus, Web of Science, PubMed, and Cochrane using keywords that report the correlation between early famine exposure and renal function indicators. RevMan and Stata software were used for data analysis. This meta-analysis contained twelve observational studies. The findings demonstrated a link between prenatal famine exposure and a higher risk of developing chronic kidney disease (CKD) (odds ratio (OR) = 1.73, 95% confidence interval (CI): 1.25, 2.39), a decreased estimated glomerular filtration rate (eGFR) (mean difference (MD) = −10.05, 95% CI: −11.64, −8.46), and increased serum creatinine (Scr) (MD = 0.02, 95% CI: 0.01, 0.03) compared to unexposed individuals. Famine exposure in childhood was associated with decreased eGFR (MD = −9.43, 95% CI: −12.01, −6.84) and increased Scr (MD = 0.03, 95% CI: 0.01, 0.04), but not with CKD (OR = 0.980, 95% CI: 0.53, 1.81). Famine exposure in adolescence and adulthood was associated with decreased eGFR (MD = −20.73, 95% CI: −22.40, −19.06). Evidence certainty was deemed to be of low or extremely low quality. Famine exposure early in life could pose a greater risk of developing renal impairment in adulthood, but this outcome may be driven by uncontrolled age differences between famine-births and post-famine-births (unexposed). [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion The studies have shown that infants with prenatal OMT exposure had smaller brain volumes than non‐exposed controls, but long‐term outcome data are lacking. We examined 5–13‐year‐old OMT‐exposed children with brain MRI and tested motor and visual‐motor functions and possible associations between brain morphology and outcome.To this retrospective cohort study, we recruited 55 children with prenatal OMT exposure and 59 age‐ and gender‐matched controls. They were examined with brain MRI, Movement‐ABC and Beery‐VMI. MRI images were processed with the Free Surfer® software to obtain volumetrics and estimates of cortical surface area and thickness. We used a general linear regression model (GLM) to calculate group differences.The children in the OMT group had smaller mean total intracranial volume (ICV), 1407 cm3 (CI 95% 1379–1434) versus 1450 cm3 (CI 95% 1423–1476) in the control group (p = 0.026). After adjusting for ICV, significant group differences persisted for volumes of amygdala, basal ganglia and mid‐posterior part of corpus callosum. Cortical surface area was smaller in the left caudal middle frontal gyrus and the right inferior parietal lobule in the OMT‐group. Visual‐motor function was significantly correlated with ICV.Prenatal OMT exposure may alter early brain development with possible negative long‐term functional consequences. [ABSTRACT FROM AUTHOR]

Background: Organic solvents are used in formulating an extensive range of products for professional use. Animal and human studies suggest that in utero solvent exposure may affect neurodevelopment. Our objective was to assess the association between occupational exposure to solvents during pregnancy and child behavior aged 2–12 years. Methods: The French mother-child cohort PELAGIE (2002–2006) included 3,421 women recruited in early pregnancy. Occupational exposure to solvents was self-reported. For 459 children, parents used a questionnaire derived from the Child Behavior Checklist and the Preschool Social Behavior Questionnaire to assess their child's behavior, at age 2, and the Strengths and Difficulties Questionnaire at ages 6 and 12. A cross-lagged structural equation modeling approach was used to assess direct and indirect associations between exposure and child behavior. Results: At age 2, an increased externalizing behavior score was suggested with prenatal exposure to solvents (mean change in standardized score (95%CI): 0.28 (-0.01, 0.57) for occasional exposure and 0.23 (-0.05, 0.51) for regular exposure). At ages 6 and 12, distinct sex-specific patterns were observed: among boys, no association with externalizing behavior was observed, while among girls, an association was seen for both occasional and regular exposure (total effect at age 12: 0.45 (0.06,0.83) and 0.40 (0.03, 0.76), respectively). For both sexes, occasional exposure may be associated with internalizing behavior at ages 6 and 12 (total effect at age 6: 0.37 (0.06, 0.68) and at age 12: 0.27 (-0.08, 0.62)). Conclusions: Occupational exposure to solvents during pregnancy may impact child behavior through either direct or cumulative effects during childhood; these associations may persist until early adolescence, especially among girls. [ABSTRACT FROM AUTHOR]

The Saimaa ringed seal (Pusa hispida saimensis) is a subspecies of ringed seal, landlocked in Lake Saimaa, Finland. The small population of less than 500 seals is facing many human-induced threats, including chemical contaminants. Mercury, in particular, has previously been suggested to be one of the chemicals affecting the viability of this endangered population. We analysed mercury concentrations from placentas and lanugo pup tissues (blubber, brain, kidney, liver, and muscle) to determine current prenatal exposure levels. These pups were found dead in or near birth lairs and were less than 3 months old. Additionally, we used threshold values available in the literature to estimate the potential mercury toxicity to the Saimaa ringed seal. We also determined selenium concentrations for its potential to alleviate the adverse effects of mercury. We further supplemented our study with brain samples collected from various seal age classes. These seals were found dead by either natural causes or by being caught in gillnets. The analysed chemicals were present in all tissues. For lanugo pups, mercury concentrations were the highest in the kidney and liver, whereas the highest selenium to mercury molar ratio was observed in placentas. The toxicity evaluation suggested that, in severe cases, mercury may cause adverse effects in lanugo and older pups. In these cases, the selenium concentrations were low and selenium to mercury ratio was below 1:1 threshold ratio and thus unlikely to provide adequate protection from the adverse effects of mercury. Furthermore, adverse effects are more likely to occur in adult seals, as mercury bioaccumulates, leading to higher concentrations in older individuals. Placental mercury concentrations correlated to those in the livers and muscle tissues of lanugo pups. This, together with the fact that placentas can be collected non-invasively and in good condition, provides a potential novel method for biomonitoring mercury exposure in Saimaa ringed seals. [ABSTRACT FROM AUTHOR]

Background and Objectives: Opioid maintenance treatment (OMT), with methadone or buprenorphine, is a key approach for managing opioid use disorder (OUD) during pregnancy. Despite buprenorphine's superior short‐term outcomes, its long‐term effects remain understudied. This study aims to evaluate the effects of prenatal OMT exposure on the incidence of childhood neurodevelopmental disorders (NDDs) considering timing effect. Methods: A retrospective cohort study using Rhode Island Medicaid data linked to vital statistics from 2008 to 2018 was conducted. The study included pregnancies having live birth from 2008 to 2016 with continuous Medicaid insurance and OUD diagnosis within 3 months preceding conception until delivery. At least one buprenorphine dispensing or a claim of methadone was required for exposure definition. Exposure was evaluated during early (0–90 days) or late (>90 days) gestation, or at any pregnancy phase. NDDs, including autism, attention‐deficit/hyperactivity disorder (ADHD), learning disabilities, speech/language disorders, developmental coordination disorder, intellectual disability, and behavioral disorders, were identified using validated algorithms. Applying Cox proportional‐hazard models with propensity score overlap weighting, adjusted hazard ratios (aHR) were calculated, mitigating potential confounders. Children were followed up from birth until NDD diagnosis, disenrollment, or study end. Results: Of 416 mother–child dyads with OUD, 40% used methadone and 20% had buprenorphine exposure during pregnancy. NDDs were observed in 36% of children with early methadone exposure compared to 17% in the early buprenorphine exposed group (aHR: 2.75; 95% confidence interval [CI]: 1.42–5.35). Further comparison to late buprenorphine exposure, late methadone exposure was associated with higher NDD risk (aHR: 2.05; 95% CI: 1.09–3.86). Compared to unexposed group, children exposed to methadone during early and late periods showed higher NDD incidences (aHR: 2.33; 95% CI: 1.51–3.60 and aHR: 2.42; 95% CI: 1.54–3.80, respectively). Discussion: The study suggests that buprenorphine is a good treatment option for OUD during pregnancy due to minimal long‐term neurodevelopmental impacts on children. However, further extensive research is necessary to rule‐out potential confounding. [ABSTRACT FROM AUTHOR]

Background: Pregnancy represents a window of vulnerability to fetal development. Disruptions in the prenatal environment during this crucial period can increase the risk of the offspring developing diseases over the course of their lifetime. The central nervous system (CNS) has been shown to be particularly susceptible to changes during crucial developmental windows. To date, research focused on disruptions in the development of the CNS has predominantly centred on the brain, revealing a correlation between exposure to prenatal risk factors and the onset of neuropsychiatric disorders. Nevertheless, some studies indicate that the retina, which is part of the CNS, is also vulnerable to in utero alterations during pregnancy. Such changes may affect neuronal, glial and vascular components of the retina, compromising retinal structure and function and possibly impairing visual function. Methods: A search in the PubMed database was performed, and any literature concerning prenatal risk factors (drugs, diabetes, unbalanced diet, infection, glucocorticoids) affecting the offspring retina were included. Results: This review collects evidence on the cellular, structural and functional changes occurring in the retina triggered by maternal risk factors during pregnancy. We highlight the adverse impact on retinal development and its long‐lasting effects, providing a critical analysis of the current knowledge while underlining areas for future research. Conclusions: Appropriate recognition of the prenatal risk factors that negatively impact the developing retina may provide critical clues for the design of preventive strategies and for early therapeutic intervention that could change retinal pathology in the progeny. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Aim Method Outcome There is increasing evidence that maternal factors such as nutritional status (both under and over‐nutrition) and diabetes, alongside prenatal exposure to endocrine disrupting chemicals (EDCs), are associated with early pubertal onset in offspring. Such children are also at increased risk of the metabolic syndrome during adolescence and young adulthood.This literature review focuses on the role of the prenatal environment in programming pubertal onset, and the impact of prenatal metabolic stressors on the declining average age of puberty.A review of all relevant literature was conducted in PubMed by the authors.The mechanism for this appears to be mediated through metabolic signals, such as leptin and insulin, on the kisspeptin‐neuronal nitric oxide‐gonadotropin releasing hormone (KiNG) axis. Exposed children have an elevated risk of childhood obesity and display a phenotype of hyperinsunlinaemia and hyperleptinaemia. These metabolic changes permit an earlier attainment of the nutritional “threshold” for puberty. Unfortunately, this cycle may be amplified across subsequent generations, however early intervention may help “rescue” progression of this programming. [ABSTRACT FROM AUTHOR]

To investigate whether maternal stress in pregnancy is associated with pubertal timing in girls and boys and to explore potential mediation by childhood body mass index (BMI) and childhood psychosocial stress. Cohort study. Not applicable. In total, 14,702 girls and boys from the Puberty Cohort, nested within the Danish National Birth Cohort. Maternal stress was obtained from a computer-assisted telephone interview in gestational weeks 30–32 as maternal life stress and emotional distress in pregnancy using questions on the basis of validated screening tools. Maternal life stress and emotional distress in pregnancy were analyzed separately and in an interaction analysis. Pubertal timing was measured half-yearly from age 11 years and throughout pubertal development and assessed as Tanner stages 1–5 (breast and pubic hair development in girls and genital and pubic hair development in boys), menarche in girls, voice break and first ejaculation in boys, and occurrence of acne and axillary hair in both girls and boys. A combined estimate for overall pubertal timing was derived using Huber-White robust variance estimation. Mean differences in age at attaining the pubertal milestones according to prenatal exposure to no (reference), low-, moderate-, or high-maternal stress in pregnancy were estimated using a multivariable censored regression model. Potential mediation by childhood BMI and childhood psychosocial stress was investigated in separate models. After adjustment for potential confounding factors, prenatal exposure to high-maternal life stress (combined estimate: −1.8 months [95% CI, −2.7 to −0.8] and −0.9 months [95% CI, −1.8 to 0.0]), high maternal emotional distress (combined estimate: −1.5 months [95% CI, −2.5 to −0.5] and −1.7 months [95% CI, −2.8 to −0.7]), and both high-maternal life stress and emotional distress (combined estimate: −2.8 months [95% CI, −4.2, to −1.4] and −1.7 months [95% CI, −3.1 to −0.2]) were associated with earlier pubertal timing in girls and boys, respectively. The associations were not mediated by childhood BMI or childhood psychosocial stress. Prenatal exposure to maternal stress in pregnancy was associated with earlier pubertal timing in girls and boys in a dose-dependent manner. The associations were not mediated by childhood BMI or childhood psychosocial stress. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion We have previously shown that exposure to famine in early gestation was associated with poorer adult health and, in women, with reduced survival up to age 64.Here, we explore the association between prenatal famine exposure and mortality up to age 76 for men and women separately.We studied adult mortality (>18 years) in men (n = 989) and women (n = 1002) born as term singletons around the time of the 1944–1945 Dutch famine. We compared overall and cause‐specific mortality among men and women exposed to famine in late, mid, or early gestation to that among unexposed persons (born before or conceived after the famine) using Cox regression.In total, 500 persons (25.1%) had died after age 18. Women exposed to famine in early gestation had higher overall (HR 1.49, 95% CI 1.00, 2.23), cancer (HR 2.17, 95% CI 1.32,3.58) and cardiovascular mortality (HR 2.33, 95% CI 0.91, 5.95) compared to unexposed women. Mortality rates among men were not different between exposure groups.This study showed that women, but not men, exposed to famine in early gestation had increased overall, cardiovascular and cancer mortality up to age 76. Although prenatal famine exposure affects adult health of both men and women, it seems to only lead to increased mortality among women. [ABSTRACT FROM AUTHOR]

Evidence on serological responses to vaccination in children exposed to ustekinumab (UST) or vedolizumab (VDZ) in utero is lacking. This multicentre prospective study aimed to assess the impact of prenatal exposure to UST or VDZ due to maternal inflammatory bowel disease (IBD) on serological responses to vaccination and other immunological parameters in exposed children. Children aged ≥ 1 year who were exposed in utero to UST or VDZ and completed at least 1-year of mandatory vaccination were included. We assessed the serological response to vaccination (non-live: tetanus, diphtheria, and Haemophilus influenzae B; live: mumps, rubella, and measles), whole blood count, and immunoglobulin levels. The control group comprised unexposed children born to mothers without IBD. A total of 23 children (median age, 25 months) exposed to UST (n = 13) or VDZ (n = 10) and 10 controls (median age, 37 months) were included. The serological response to vaccination was comparable between the UST and VDZ groups and controls, with an adequate serological response rate of ≥ 80%. Only children exposed to UST showed a slightly reduced serological response to mumps (67% vs. 86% in controls), whereas all children exposed to VDZ showed an adequate response. The majority of the exposed children had normal levels of individual immunoglobulin classes, similar to the controls. No severe pathology was observed in any of the children. Conclusion: Despite the limited sample size, our findings suggest that in utero exposure to VDZ or UST does not significantly impair the vaccine response or broader immunological parameters in exposed children. What is known: • Treatment with anti-TNF inhibitors during pregnancy does not appear to affect serologic response to vaccination in exposed children. • Evidence on the efficacy of vaccination in children exposed to ustekinumab or vedolizumab in utero is almost lacking. What is new: • Our findings suggest that in utero exposure to ustekinumab or vedolizumab does not significantly affect the serological responses to common childhood non-live (tetanus, Haemophilus influenzae B, diphtheria) and live vaccines (measles, mumps, rubella). • No major adverse effects on overall immunological health were observed in children exposed in utero to ustekinumab or vedolizumab. [ABSTRACT FROM AUTHOR]

In mechanistic and preliminary human studies, prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is associated with oxidative stress, a potential contributor to maternal liver disease. Bilirubin is an endogenous antioxidant abundant in the liver that may serve as a physiological modulator of oxidative stress in pregnant people. Hence, our objective was to estimate the association between repeated measures of PFAS and bilirubin during pregnancy. The study population included 332 participants in the Atlanta African American Maternal-Child Cohort between 2014 and 2020. Serum samples were collected up to two times (early pregnancy: 6–18 gestational weeks; late pregnancy: 21–36 gestational weeks) for the measurement of perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and total bilirubin. We analyzed single PFAS with linear mixed effect regression and a mixture of the four PFAS with quantile g-computation. Models were repeated with a multiplicative interaction term to explore effect modification by study visit. Overall, PFHxS was positively associated with bilirubin (β = 0.08, 95 % CI = 0.01, 0.15). We also found during late pregnancy, there was a positive association of PFHxS and the PFAS mixture with bilirubin (β = 0.12, 95 % CI = 0.02, 0.22; ψ = 0.19, 95 % CI = 0.03, 0.34, respectively). Finally, study visit modified the PFOA-bilirubin association (interaction p-value = 0.09), which was greater during early pregnancy (β = 0.08, 95 % CI = 0.01, 0.15). In a prospective cohort of pregnant African Americans, an increase in PFOA, PFHxS, and the PFAS mixture was associated with an increase in bilirubin. Our results suggest that, depending on pregnancy stage, prenatal PFAS exposure disrupts the maternal liver antioxidant capacity. [Display omitted] • PFHxS was positively associated with bilirubin in an Atlanta African American birth cohort (n=332; 2014-2020). • We found a positive association of PFHxS and the PFAS mixture with bilirubin in late pregnancy. • Study visit modified the PFOA-bilirubin association which was greater during early pregnancy. [ABSTRACT FROM AUTHOR]

• Largest EWAS study on self-reported clinically evident prenatal infections with 2,338 mother–child dyads. • Weak associations between exposure to common infections (based on cumulative score) and newborn DNA methylation. • Suggestive sites implicate genes related to neurodevelopment and immune function. • Epigenetic proxy of infections not predictive of child mental or physical outcomes. • No link between prenatal infections and offspring epigenetic age acceleration. Infections during pregnancy have been robustly associated with adverse mental and physical health outcomes in offspring, yet the underlying molecular pathways remain largely unknown. Here, we examined whether exposure to common infections in utero associates with DNA methylation (DNAm) patterns at birth and whether this in turn relates to offspring health outcomes in the general population. Using data from 2,367 children from the Dutch population-based Generation R Study, we first performed an epigenome-wide association study to identify differentially methylated sites and regions at birth associated with prenatal infection exposure. We also examined the influence of infection timing by using self-reported cumulative infection scores for each trimester. Second, we sought to develop an aggregate methylation profile score (MPS) based on cord blood DNAm as an epigenetic proxy of prenatal infection exposure and tested whether this MPS prospectively associates with offspring health outcomes, including psychiatric symptoms, BMI, and asthma at ages 13–16 years. Third, we investigated whether prenatal infection exposure associates with offspring epigenetic age acceleration – a marker of biological aging. Across all analysis steps, we tested whether our findings replicate in 864 participants from an independent population-based cohort (ALSPAC, UK). We observed no differentially methylated sites or regions in cord blood in relation to prenatal infection exposure, after multiple testing correction. 33 DNAm sites showed suggestive associations (p < 5e10 − 5; of which one was also nominally associated in ALSPAC), indicating potential links to genes associated with immune, neurodevelopmental, and cardiovascular pathways. While the MPS of prenatal infections associated with maternal reports of infections in the internal hold out sample in the Generation R Study (R2 incremental = 0.049), it did not replicate in ALSPAC (R2 incremental = 0.001), and it did not prospectively associate with offspring health outcomes in either cohort. Moreover, we observed no association between prenatal exposure to infections and epigenetic age acceleration across cohorts and clocks. In contrast to prior studies, which reported DNAm differences in offspring exposed to severe infections in utero , we do not find evidence for associations between self-reported clinically evident common infections during pregnancy and DNAm or epigenetic aging in cord blood within the general pediatric population. Future studies are needed to establish whether associations exist but are too subtle to be statistically meaningful with present sample sizes, whether they replicate in a cohort with a more similar infection score as our discovery cohort, whether they occur in different tissues than cord blood, and whether other biological pathways may be more relevant for mediating the effect of prenatal common infection exposure on downstream offspring health outcomes. [ABSTRACT FROM AUTHOR]

Perinatal risk factors are implicated in the development of psychopathology, but their role in bipolar disorder (BD) and hypomania is unclear. Using data from a prospective community cohort, this is the first study to investigate the association between a range of perinatal risk factors, hypomanic symptoms, and 'high-risk' for BD in the general population. Parent report of perinatal events were available for 26,040 eighteen-month-olds from the Twins Early Development Study. Subsequent self-report hypomania was measured at ages 16 (Hypomania Checklist-16; N = 2943) and 26 (Mood Disorders Questionnaire; N = 7748). Participants were categorised as 'high-risk' for BD using established classifications. Linear and logistic regressions were conducted within a generalised estimating equations framework to account for relatedness in the sample. Prenatal alcohol exposure (β = 0.08, SE = 0.04, p =.0002) and number of alcohol units consumed (β = 0.09, SE = 0.02, p <.0001) were associated with hypomanic symptoms at age 16, and number of alcohol units (OR = 1.13, 95 % CI:1.06–1.21, p =.0003) and maternal stress (OR = 1.68, 95 % CI:1.21–2.34, p =.002) were associated with 'high-risk' for BD age 16. Prenatal tobacco exposure (β = 0.10, SE = 0.04, p <.0001) and number of cigarettes smoked (β = 0.10, SE = 0.01, p <.0001) were associated with hypomanic symptoms and 'high-risk' for BD at age 26, although these result were attenuated controlling for parental psychiatric history. Familial confounding could not be fully adjusted for. Rater reports include some biases. These findings show perinatal risk factors to be associated with subclinical hypomania and 'high-risk' for BD. Future work should explore the mechanisms underlying these longitudinal associations, which could shed light on prevention and intervention efforts. • Prenatal alcohol and tobacco exposure were associated with hypomanic symptoms. • Prenatal alcohol exposure was linked to 'high-risk' for bipolar disorder at age 16. • Maternal stress during pregnancy was linked to 'high-risk' at age 16. • Prenatal tobacco exposure was linked to 'high-risk' for bipolar disorder at age 26. • Prenatal tobacco exposure's association with 'high-risk' may be due to confounders. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that prenatal maternal smoking and maternal secondhand smoke exposure during pregnancy were associated with an increased risk of wheezing and asthma development. However, few studies have examined the influence of different sources of tobacco exposure in different perinatal timeframes (preconception, prenatal, and postnatal) on wheezing phenotypes in children. Using national survey data from Japan, we investigated the effects of exposure to tobacco smoke during pregnancy on wheezing phenotypes in children before the age of 3 years. Methods: Pregnant women who lived in the 15 regional centers in the Japan Environment and Children's Study were recruited. We obtained information on prenatal and postnatal exposure to active and secondhand smoke (SHS) and wheeze development up to 3 years of age. Multiple logistic regression analysis was performed to determine the association between tobacco smoke exposure and wheezing phenotypes in children. Results: We analyzed 73,057 singleton births and identified four longitudinal wheezing phenotypes: never wheezing; early transient wheezing (wheezing by age 1 year but not thereafter); late-onset wheezing (wheezing by age 2–3 years but not beforehand); and persistent wheezing. Maternal smoking during pregnancy was significantly associated with early transient and persistent wheezing in children compared with no maternal smoking [early transient wheezing: 1–10 cigarettes per day, adjusted odds ratio (aOR) 1.43, 95% confidence interval (CI) 1.23–1.66; ≥ 11 cigarettes per day, aOR 1.67, 95% CI 1.27–2.20; persistent wheezing: 1–10 cigarettes per day, aOR 1.64, 95% CI 1.37–1.97; ≥ 11 cigarettes per day, aOR 2.32, 95% CI 1.70–3.19]. Smoking cessation even before pregnancy was also significantly associated with increased risk of early transient wheezing, late-onset wheezing, and persistent wheezing in children. Moreover, maternal exposure to SHS during pregnancy was significantly associated with increased risk of early transient and persistent wheezing compared with no such exposure. Conclusions: Maternal smoking before and throughout pregnancy was associated with wheeze development in children up to 3 years of age. It appears that smoking is detrimental compared to never smoking, regardless of whether individuals quit smoking before or after becoming aware of the pregnancy. [ABSTRACT FROM AUTHOR]

Background/aim: Acetaminophen is frequently used as an analgesic during pregnancy. The purpose of the present study was to evaluate the effects of acetaminophen administered to pregnant mice on the fetal brain, attention, memory, and learning functions in the postnatal period, and genetic mechanisms in these mice. Materials and methods: The study was designed with two different groups. The first group consisted of pregnant mice that were injected with acetaminophen, while the second group was comprised of pregnant mice that were injected with saline. 1st, 2nd, and 3rd days of pregnancy, one of the mice was injected subcutaneously with 100 mg/kg acetaminophen, and the other mouse was injected subcutaneously with 0.9% saline. On the 21st day after birth, five female and five male mice were randomly selected for the experimental and control groups. Behavioral tests were performed on mice at 2 months of age. In addition, changes in the transcript levels of 93 genes were evaluated by Real-Time PCR in the hippocampus. Results: The control group showed more interest in the new object than the acetaminophen group (p=0.002). In the marble burying test, greater burying activity was observed in the control group than in the acetaminophen group (p=0.0345). No significant difference was observed between the control and acetaminophen groups in the social interaction and tail suspension tests. GABRG3, GRM3, PICK1, CEBPB, and EGR4 mRNA expression levels increased in the acetaminophen group (0.0317, 0.0159, 0.0069, 0.0457, 0.015, p value respectively). Conclusions: Prenatal acetaminophen exposure affected both behavioral tests and transcript levels. Therefore, the potential effects of prenatal acetaminophen exposure should be carefully investigated. [ABSTRACT FROM AUTHOR]

Simple Summary: The profitability of dairy farms primarily depends on the productive and reproductive performance of cows. However, the progressive decrease in reproductive performance in dairy cattle has led to the search for new potential phenotypes to keep the most profitable animals. Consequently, this study aimed to assess whether anogenital distance or anti-Müllerian hormone plasmatic concentrations could be used as predictors of future reproductive performance in dairy cattle. The anogenital distance was measured in 566 heifers from 9 dairy farms in Galicia (Spain), and blood samples were collected. Our results showed that animals with short anogenital distance were inseminated, became pregnant, and calved earlier than animals with long anogenital distance. Additionally, it was verified that this measure showed little variation with age. However, no association was found between anti-Müllerian hormone plasmatic concentration and anogenital distance or reproductive performance, underlining the need for further studies with larger sample sizes. Anogenital distance (AGD) is a marker of the degree of prenatal exposure to androgens in multiple species, and it has been suggested that there is an inverse association between AGD and fertility. Therefore, the aim of this study was to determine the usefulness of AGD and anti-Müllerian hormone (AMH) concentrations, an indirect marker of the follicular population, as predictors of future reproductive potential in Holstein cattle. The AGD was measured in 566 females from 9 dairy farms in Galicia (Spain). A group of 172 females underwent a second measurement 9 months after. Additionally, data on the age at first insemination (1stAI age), number of AI (AI-PREG), age at first pregnancy (1stPREG age), age at first calving (1stCAL age), and calving–pregnancy (CAL-PREG) and calving–calving (CAL-CAL) intervals were collected. Blood samples were collected from 80 heifers to determine AMH concentrations. Our results showed that AGD varied minimally with age, and that cows with short AGD had earlier 1stAI age, 1stPREG age, and 1stCAL age (p < 0.05) than cows with long AGD. No significant differences were observed for the CAL-PREG and CAL-CAL intervals. Additionally, no significant association was found between AMH concentration and AGD or reproductive parameters. Consequently, the results suggest the possibility of using AGD as a marker of future reproductive performance in Holstein heifers. However, there was insufficient evidence to associate AMH concentrations and reproductive performance, underlining the need for further studies with larger sample sizes. [ABSTRACT FROM AUTHOR]

The use of cannabis during pregnancy has emerged as a mounting cause for concern due to its potential adverse consequences on both the mother and her offspring. This review will focus on the dangers associated with prenatal exposure to cannabis, particularly those related to neurodevelopment. It will also discuss the features of maternal and placental functioning that are likely to have long-term effects on the offspring's development. The most pertinent and up-to-date materials can be found through a literature search. The literature emphasizes the substantial hazards associated with prenatal exposure to cannabis. These include impairments in cognitive function and difficulties in behavior in this particular instance. Structural and functional alterations in the brain can be noticed in offspring. The use of cannabis has been associated with an increased likelihood of experiencing pregnancy-related complications, such as giving birth prematurely and having a baby with a low birth weight. Additionally, it has been connected to potential negative effects on mental and emotional well-being. Studies have shown that when a pregnant woman is exposed to cannabis, it can negatively impact the functioning of the placenta and the growth of the fetus. This might potentially contribute to the development of placental insufficiency and restricted growth in the womb. Longitudinal studies reveal that children who were exposed to cannabis in the womb experience additional long-term developmental challenges, such as decreased cognitive abilities, reduced academic performance, and behavioral issues. In order to address the problem of cannabis usage during pregnancy, it is essential to adopt a comprehensive and coordinated strategy. This method should integrate and synchronize public health policy, education, and research initiatives. By implementing these targeted strategies, it is possible to mitigate potential health and welfare concerns for both present and future generations. [ABSTRACT FROM AUTHOR]

Background: Exposure to ambient air pollution is a top risk factor contributing to the global burden of disease. Pregnant persons and their developing fetuses are particularly susceptible to adverse health outcomes associated with air pollution exposures. During pregnancy, the thyroid plays a critical role in fetal development, producing thyroid hormones that are associated with brain development. Our objective is to systematically review recent literature that investigates how prenatal exposure to air pollution affects maternal and fetal thyroid function. Methods: Following the Navigation Guide Framework, we systematically reviewed peer-reviewed journal articles that examined prenatal exposures to air pollution and outcomes related to maternal and fetal thyroid function, evaluated the risk of bias for individual studies, and synthesized the overall quality and strength of the evidence. Results: We found 19 studies that collected data on pregnancy exposure windows spanning preconception to full term from 1999 to 2020 across nine countries. Exposure to fine particulate matter (PM2.5) was most frequently and significantly positively associated with fetal/neonatal thyroid hormone concentrations, and inversely associated with maternal thyroid hormone concentrations. To a lesser extent, traffic-related air pollutants, such as nitrogen dioxide (NO2) had significant effects on fetal/neonatal thyroid function but no significant effects on maternal thyroid function. However, the body of literature is challenged by risk of bias in exposure assessment methods and in the evaluation of confounding variables, and there is an inconsistency amongst effect estimates. Thus, using the definitions provided by the objective Navigation Guide Framework, we have concluded that there is limited, low quality evidence pertaining to the effects of prenatal air pollution exposure on maternal and fetal thyroid function. Conclusion: To improve the quality of the body of evidence, future research should seek to enhance exposure assessment methods by integrating personal monitoring and high-quality exposure data (e.g., using spatiotemporally resolved satellite observations and statistical modeling) and outcome assessment methods by measuring a range of thyroid hormones throughout the course of pregnancy. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are steroid hormones fundamental to the body's normal physiological functions and are pivotal in fetal growth and development. During gestation, the mother's cortisol concentration (active GCs) escalates to accommodate the requirements of fetal organ development and maturation. A natural placental GCs barrier, primarily facilitated by 11b hydroxysteroid dehydrogenase 2, exists between the mother and fetus. This enzyme transforms biologically active cortisol into biologically inactive corticosterone, thereby mitigating fetal GCs exposure. However, during pregnancy, the mother may be vulnerable to adverse factor exposures such as stress, hypoxia, caffeine, and synthetic GCs use. In these instances, maternal serum GCs levels may surge beyond the protective capacity of the placental GCs barrier. Moreover, these adverse factors could directly compromise the placental GCs barrier, resulting in excessive fetal exposure to GCs. It is well-documented that prenatal GCs exposure can detrimentally impact the offspring's cardiovascular system, particularly in relation to blood pressure, vascular function, and heart function. In this review, we succinctly delineate the alterations in GCs levels during pregnancy and the potential mechanisms driving these changes, and also analyze the possible causes of prenatal GCs exposure. Furthermore, we summarize the current advancements in understanding the adverse effects and mechanisms of prenatal GCs exposure on the offspring's cardiovascular system. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is globally increasing in prevalence. The rise of ASD can be partially attributed to diagnostic expansion and advocacy efforts; however, the interplay between genetic predisposition and modern environmental exposures is likely driving a true increase in incidence. A range of evidence indicates that prenatal exposures are critical. Infection during pregnancy, gestational diabetes, and maternal obesity are established risk factors for ASD. Emerging areas of research include the effects of maternal use of selective serotonin reuptake inhibitors, antibiotics, and exposure to toxicants during pregnancy on brain development and subsequent ASD. The underlying pathways of these risk factors remain uncertain, with varying levels of evidence implicating immune dysregulation, mitochondrial dysfunction, oxidative stress, gut microbiome alterations, and hormonal disruptions. This narrative review assesses the evidence of contributing prenatal environmental factors for ASD and associated mechanisms as potential targets for novel prevention strategies. [ABSTRACT FROM AUTHOR]

Introduction: Tobacco and alcohol are the two most common substances used during pregnancy, and both can disrupt neurodevelopment, resulting in cognitive and behavioral deficits including language difficulties. Previous studies show that children with prenatal substance exposure exhibit microstructural alterations in major white matter pathways, though few studies have investigated the impact of prenatal substance exposure on white matter microstructure and language skills during the toddler years. Methods: In this study, 93 children (34 exposed to alcohol and/or tobacco) aged 23 years from the Drakenstein Child Health Study, South Africa, completed Expressive and Receptive Communication assessments from the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and underwent diffusion MRI scans. Diffusion images were preprocessed, and 11 major white matter tracts were isolated. Fractional anisotropy (FA) and mean diffusivity (MD) were extracted for each white matter tract. Linear regression was used to examine differences between the tobacco/alcohol exposed group and unexposed controls for FA, MD, and language scores, as well as relationships between brain metrics and language. There were no significant group differences in language scores or FA. Results: Children with alcohol or tobacco exposure had lower average MD in the splenium of the corpus callosum compared to unexposed controls. Significant interactions between prenatal substance exposure and language scores were seen in 7 tracts but did not survive multiple comparisons correction. Discussion: Our findings show that prenatal alcohol and/or tobacco exposure appear to alter the relationship between white matter microstructure and early language skills in this population of toddlers, potentially laying the basis of language deficits observed later in older children with prenatal substance exposure, which may have implications for learning and interventions. [ABSTRACT FROM AUTHOR]

Every 15 minutes in the US, an infant exposed to opioids is born. Approximately 50% of these newborns will develop Neonatal Opioid Withdrawal Syndrome (NOWS) within 5 days of birth. It is not known which infants will develop NOWS, therefore, the current hospital standard-of-care dictates a 96-hour observational hold. Understanding which infants will develop NOWS soon after birth could reduce hospital stays for infants who do not develop NOWS and decrease burdens on hospitals and clinicians. We propose noninvasive clinical indicators of NOWS, including newborn neurobehavior, autonomic biomarkers, prenatal substance exposures, and socioeconomic environments. The goals of this protocol are to use these indicators shortly after birth to differentiate newborns who will be diagnosed with NOWS from those who will have mild/no withdrawal, to determine if the indicators predict development at 6 and 18 months of age, and to increase NOWS diagnostic sensitivity for earlier, more accurate diagnoses. [ABSTRACT FROM AUTHOR]

Environmental influences on brain structure and function during early development have been well-characterized, but whether early environments are associated with the pace of brain development is not clear. In pre-registered analyses, we use flexible non-linear models to test the theory that prenatal disadvantage is associated with differences in trajectories of intrinsic brain network development from birth to three years (n = 261). Prenatal disadvantage was assessed using a latent factor of socioeconomic disadvantage that included measures of mother's income-to-needs ratio, educational attainment, area deprivation index, insurance status, and nutrition. We find that prenatal disadvantage is associated with developmental increases in cortical network segregation, with neonates and toddlers with greater exposure to prenatal disadvantage showing a steeper increase in cortical network segregation with age, consistent with accelerated network development. Associations between prenatal disadvantage and cortical network segregation occur at the local scale and conform to a sensorimotor-association hierarchy of cortical organization. Disadvantage-associated differences in cortical network segregation are associated with language abilities at two years, such that lower segregation is associated with improved language abilities. These results shed light on associations between the early environment and trajectories of cortical development. Early environmental factors, like disadvantage, are associated with neurocognitive development. Here, the authors find that neonates and toddlers from economically disadvantaged backgrounds show accelerated brain development, with implications for language abilities in toddlerhood. [ABSTRACT FROM AUTHOR]

Background: A rodent autism spectrum disorder (ASD) model based on prenatal exposure to valproic acid (VPA) is widely recognized as a prominent model. Social behavior in rodent ASD models has primarily been evaluated through a three-chamber approach test. However, in this study, we focused on social attention in the VPA model of ASD. Methods: In male C57BL/6 J mice, attentional behaviors toward conspecifics were examined through reaching tasks around 9–11 weeks of age. On embryonic day 12.5, pregnant mice underwent a subcutaneous injection of 600 mg/kg VPA sodium salt dissolved in 0.9% saline solution (VPA group) or saline solution alone (Sal group) into their neck fat. Thirty-six mice—nine each in the VPA and saline groups, and 18 partners—underwent training in reaching behavior. Subsequently, we examined whether the VPA or Sal group demonstrated focused attention toward their partners during reaching tasks. A two-way analysis of variance (ANOVA) (condition [VPA/Sal] × situation [face-to-face (attention)/not paying attention (not attention)]) was conducted on the average success rate of the situation. Additionally, we measured the duration of sniffing behavior between pairs of mice in an open field twice in total at 4 and 8 weeks of age before reaching task. The pairs were constructed by pairing a VPA or Sal group mouse with its partner, with the objective of facilitating initial encounters between the mice. A one-way ANOVA was conducted on the average duration of sniffing behavior data from 4 weeks and a second one-way ANOVA on data from 8 weeks. Results: The analysis revealed a significant interaction between condition and situation in the reaching task [F (1, 28) = 6.75, p = 0.015, ηp² = 0.19]. The simple main effect test exhibited that the “not paying attention” rate was significantly higher than that of the “face-to-face” in the VPA group (p < 0.01). The results revealed a not significant difference in the average duration of sniffing behavior at 4 weeks [F (3, 32) = 2.71, p = 0.06, n.s., ηp² = 0.20], but significant difference at 8 weeks [F (3, 32) = 4.12, p < 0.05, ηp² = 0.28]. Multiple comparisons using the Bonferroni method revealed significant differences in the sniffing duration at 8 weeks between from the partner toward the VPA mouse and from the partner toward the Sal mouse (p < 0.05). Conclusion: The VPA rodent model of ASD exhibited differences in social attention compared to the saline group. By focusing on social attention and exploring various ASD models, insights can be gained from the neural mechanisms underlying gaze abnormalities during social interaction in individuals with ASD. [ABSTRACT FROM AUTHOR]

Children born small for gestational age (SGA) may be at risk for earlier puberty and adverse long-term health sequelae. This study investigates associations between SGA and age at menarche using secondary data on 1,027 female children in a population-based U.S. birth cohort that over-sampled non-marital births, which in the U.S. is a policy-relevant population. SGA was defined as <10th percentile of weight for gestational age compared to the national U.S. distribution. We estimated unadjusted and adjusted Ordinary Least Squares (OLS) models of associations between SGA and age at menarche in years, as well as unadjusted and adjusted logistic regression models of associations between SGA and early menarche (before age 11). SGA was not significantly associated with earlier age at menarche, even when adjusting for maternal sociodemographic characteristics, prenatal smoking, and maternal pre-pregnancy overweight and obesity. Similarly, SGA was not significantly associated with the odds of menarche occurring before age 11. However, maternal non-Hispanic Black race-ethnicity, Hispanic ethnicity, and pre-pregnancy obesity all had independent associations with average earlier age at menarche and menarche before age 11. Thus, maternal risk factors appear to play more influential roles in determining pubertal development. [ABSTRACT FROM AUTHOR]

Background and Objectives Methods Results Discussion and Conclusions Scientific Significance Prenatal cannabis use prevalence in the United States has increased. Relaxation of state‐level cannabis policy may be contributing to the diminished risk perception of using cannabis. The main psychoactive constituent of cannabis, delta‐9‐tetrahydrocannabinol, crosses the placenta, interacting with functional cannabinoid receptors in the fetus. Here, we assess the association between prenatal cannabis exposure (PCE) and a set of birth outcomes.Using the Michigan Archive for Research on Child Health, a prospective pregnancy cohort, we linked prenatal survey data with neonatal data from state‐archived birth records. Recruitment occurred in 23 clinics across Michigan. Pregnant participants with live birth records between October 2017 and January 2022, after exclusion for missing data on cannabis use, birth outcomes, and covariates, were included in the final analytic sample (n = 584). Analyses involved generalized linear models.An estimated 15% (95% confidence interval [CI]: 12%, 18%) of participants reported using cannabis during pregnancy. Covariate‐adjusted models revealed an association between PCE and birth size (ß = −0.3; 95% CI: −0.5, −0.003).Findings suggest a relationship between PCE and smaller birth size. Clinicians should follow guidelines outlined by the American College of Obstetricians and Gynecologists when counseling pregnant patients on cannabis use.We detected a significant association between PCE and birth size. Most studies focus only on the extremes of birth size, however, use of z‐scores allow for assessment of the sex‐specific birth weight‐for‐gestational age distribution, increasing the accuracy of detecting an effect of cannabis exposure on birth size. [ABSTRACT FROM AUTHOR]

This study investigates the association between maternal exposure to particulate matter (PM 10) and nitric dioxide (NO 2) during the first, second and third trimester and placental weight and birth weight/placental weight (BW/PW) ratio in twins at birth. Cross-sectional data of 3340 twins from the East Flanders Prospective Twin Survey was used. Air pollutant exposure was estimated via spatial temporal interpolation. Univariable and multivariable mixed model analyses with a random intercept to account for the relatedness of newborns were conducted for twins with separate placentas. Twin pairs with one placental mass were studied with linear and logistic regression. In the third trimester, for each 10 μm/m3 increase in PM 10 or NO 2 placental weight decreased −19.7 g (95%-C.I. −35.1; −4.3) and −17.7 g (95%-C.I. −30.4; −0.5) respectively, in moderate to late preterm twins with separate placentas. Consequently, BW/PW ratio increased with higher air pollution exposure. PM 10 exposure in the last week of pregnancy was associated with a higher odds ratio (OR) of 1.20 (95%-C.I. 1.00; 1.44) for a "small for gestational age placenta" (placental weight <10th percentile). Conversely, first trimester air pollutant exposure was associated with lower ORs of 0.55 (95%-C.I. 0.35; 0.88) and 0.60 (95%-C.I. 0.42; 0.84). The association of PM 10 and NO 2 on placental weight is trimester-specific, differs for twins with one versus two placentas and is most pronounced in moderate to late preterm twins. Longitudinal studies are needed to better understand the relationship between air pollutant exposure and placental weight evolution across different trimesters. • Effects of NO 2 /PM 10 on placental weight differ for twins with one or two placentas. • The effects of air pollutants are most pronounced in twins born between 32 and 36 weeks. • Higher NO 2 /PM 10 exposure in the last trimester is linked to lower placental weight. • NO 2 /PM 10 exposure in early pregnancy is linked to a lower odds for "SGA-placenta". • NO 2 /PM 10 exposure in late pregnancy is linked to a higher odds for "SGA-placenta". [ABSTRACT FROM AUTHOR]

Summary: Often, causal mediation analysis is of interest when both the mediator and the final outcome are repeatedly measured, but limited work has been done for this situation (as opposed to where only the mediator is repeatedly measured). Available methods are primarily based on parametric models and tend to be sensitive to model assumptions. This article presents semiparametric, continuous‐time models to provide a flexible and robust approach to causal mediation analysis for longitudinal data, which allows these data to be unbalanced or irregular. Specifically, the method uses spline linear mixed‐effects models for the mediator and for the final outcome, with a two‐step approach to model‐fitting in which a predicted mediator is used as a covariate in the final outcome model. The models allow flexible functions for both the mean and individual response functions for each outcome. We derive estimated natural direct and indirect effects as a function of time using an extended mediation formula and sequential ignorability assumption. In simulation studies, we compare properties of estimated direct and indirect effects, and a delta method estimate of the standard error of the latter, under alternative approaches for predicting the mediator. The approach is illustrated using harmonised data from two cohort studies to examine attention as a mediator of the effect of prenatal tobacco exposure on externalising behaviour in children. [ABSTRACT FROM AUTHOR]