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Background and Objectives: 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. Methods: 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. Results: 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). Discussion and Conclusions: 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. Scientific Significance: 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]

ABSTRACT Background Objective Methods Results Conclusions Empirically evaluating the potential impact of recall bias on observed associations of prenatal medication exposure is crucial.We sought to assess the effects of exposure misclassification on previous studies of the use of nonsteroidal anti‐inflammatory drugs (NSAIDs) in early pregnancy and increased risk of amniotic band syndrome (ABS).Using data from the National Birth Defects Prevention Study (NBDPS) on births from 1997 to 2011, we included 189 mothers of infants with ABS and 11,829 mothers of infants without congenital anomalies. We identified external studies of medication use during pregnancy to obtain validity parameters for a probabilistic bias analysis to adjust for exposure misclassification. Due to uncertainty about the transportability of these parameters, we conducted multidimensional bias analyses to explore combinations of values on the results.When we assumed higher specificity in cases or higher sensitivity in controls, misclassification‐adjusted estimates suggested confounding‐adjusted estimates were attenuated. However, in a few instances, when we assumed greater sensitivity in the cases than the controls (and Sp ≥ 0.9), the misclassification‐adjusted estimates suggested upward bias in the confounding‐adjusted estimates.Results from our bias analysis highlighted that the magnitude of bias depended on the mechanism and the extent of misclassification. However, the parameters available from the validation studies were not directly applicable to our study. In the absence of reliable validation studies, considering mechanisms of bias and simulation studies to outline combinations of plausible scenarios to better inform conclusions on the effects of these medications on pregnancy outcomes remains important. [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]

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]

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]

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]

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]

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]

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]

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 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]

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]

Phthalates are ubiquitous in diverse environments and have been linked to a myriad of detrimental health outcomes. However, the association between phthalate exposure and allergic rhinitis (AR) remains unclear. To address this knowledge gap, we conducted a systematic review and meta‐analysis to comprehensively evaluate the relationship between phthalate exposure and childhood AR risk. We searched the Cumulative Index to Nursing and Allied Health Literature, Excerpta Medica Database, and PubMed to collect relevant studies and estimated pooled odds ratios (OR) and 95% confidence intervals (CI) for risk estimation. Ultimately, 18 articles, including seven cross‐sectional, seven case–control, and four prospective cohort studies, were selected for our systematic review and meta‐analysis. Our pooled data revealed a significant association between di‐2‐ethylhexyl phthalate (DEHP) exposure in children's urine and AR risk (OR = 1.188; 95% CI = 1.016–1.389). Additionally, prenatal exposure to combined phthalates and their metabolites in maternal urine was significantly associated with the risk of childhood AR (OR = 1.041; 95% CI = 1.003–1.081), although specific types of phthalates and their metabolites were not significant. Furthermore, we examined environmental phthalate exposure in household dust and found no significant association with AR risk (OR = 1.021; 95% CI = 0.980–1.065). Our findings underscore the potential hazardous effects of phthalates on childhood AR and offer valuable insights into its pathogenesis and prevention. [ABSTRACT FROM AUTHOR]

Background: The digit ratio (2D:4D), the ratio of the lengths of second (2D) to the fourth (4D) fingers, is a proxy indicator of prenatal androgen exposure. On average, males display lower 2D:4D than females. Previous studies have shown that lower 2D:4D ratios were associated with better sports and physical abilities. Aim: To assess whether a challenge condition, imposed by intense exercise, could increase handgrip strength (HGS) associated with 2D:4D. Methods: This cross‐sectional experimental study included 90 healthy young Polish adults (40 males, 50 females). They underwent intense physical exercise, before (7 days) and after which they were measured for HGS and 2D:4D. Height and weight were also measured. Analyses of Covariance were employed to delineate associations. Results: 2D:4D had significant predictive effects on the differences in HGS (DHGS) measured in two occasions, without and after, physical exercises. The lower was the 2D:4D, the higher the DHGS, particularly, for the left hand. Conclusion: The results reconfirmed that the link between prenatal testosterone exposure (indicated by 2D:4D) and physical strength depends on the context, such as a challenged condition. [ABSTRACT FROM AUTHOR]

Alcohol exposure affects brain structure, but the extent to which its effects differ across development remains unclear. Several countries are considering changes to recommended guidelines for alcohol consumption, so high‐quality evidence is needed. Many studies have been conducted among small samples, but recent efforts have been made to acquire large samples to characterize alcohol's effects on the brain on a population level. Several large‐scale consortia have acquired such samples, but this evidence has not been synthesized across the lifespan. We conducted a systematic review of large‐scale neuroimaging studies examining effects of alcohol exposure on brain structure at multiple developmental stages. We included studies with an alcohol‐exposed sample of at least N = 100 from the following consortia: ABCD, ENIGMA, NCANDA, IMAGEN, Framingham Offspring Study, HCP and UK BioBank. Twenty‐seven studies were included, examining prenatal (N = 1), adolescent (N = 9), low‐to‐moderate‐level adult (N = 11) and heavy adult (N = 7) exposure. Prenatal exposure was associated with greater brain volume at ages 9–10, but contemporaneous alcohol consumption during adolescence and adulthood was associated with smaller volume/thickness. Both low‐to‐moderate consumption and heavy consumption were characterized by smaller volume and thickness in frontal, temporal and parietal regions, and reductions in insula, cingulate and subcortical structures. Adolescent consumption had similar effects, with less consistent evidence for smaller cingulate, insula and subcortical volume. In sum, prenatal exposure was associated with larger volume, while adolescent and adult alcohol exposure was associated with smaller volume and thickness, suggesting that regional patterns of effects of alcohol are similar in adolescence and adulthood. This systematic review of large‐scale neuroimaging studies examining the effects of alcohol exposure on brain structure across multiple developmental stages showed that adult alcohol consumption was characterized by smaller volume and thickness in frontal, temporal, and parietal regions, and reductions in insula, cingulate, and subcortical structures. Adolescent alcohol consumption had similar effects, but with less consistent evidence for smaller cingulate, insula, and subcortical volume. This suggests that regional patterns of effects of alcohol are similar in adolescence and adulthood. [ABSTRACT FROM AUTHOR]

Aim: To assess inpatient growth parameter trajectories and to identify the type of opioid exposure and treatment characteristics influencing growth parameters of infants admitted to the newborn intensive care unit (NICU) for pharmacological treatment of neonatal opioid withdrawal syndrome (NOWS). Methods: Charts of term infants with NOWS admitted to NICU from 2012 to 2019, who received pharmacologic treatment, were reviewed. Intake (volume: mL/kg/day; calorie: kcal/kg/day) and growth parameter trajectories (weight, head circumference, and length) were analyzed based on the type of prenatal opioid exposure (short‐acting opioids (SAOs), long‐acting opioids (LAOs), and polysubstance), pharmacologic treatment, and sex. Growth measurement patterns over time were compared between groups using longitudinal mixed‐effects models. Results: One hundred nineteen infants were included in the study with median birth weight Z‐score of −0.19 at birth and decreased to a median of −0.72 at discharge. Exposure to SAO was associated with an increase in Z‐scores nearing discharge across all growth parameters (Z‐score for weight p = 0.03). Polysubstance exposure was associated with a decrease in Z‐scores for length and head circumference throughout hospitalization. Infants with adjunct clonidine treatment had an increase in Z‐score for weight trends. Male infants had a decrease in Z‐scores for weight (male −0.96, female −0.59, interaction p = 0.06) and length (male −1.17, female −0.57, interaction p = 0.003) at Day 28. Despite the difference in growth trajectories, intake in terms of amount (mL/kg/day) and calorie intake (kcal/kg/day) was similar based on prenatal exposure, treatment, and sex. Conclusion: Infants with NOWS requiring pharmacologic treatment have a decrease in Z‐scores for weight, length, and head circumference at birth and at hospital discharge. Infants with prenatal polysubstance exposure were at particular risk for poorer inpatient growth relative to infants exposed to SAO and LAO, indicated by lower Z‐scores for length and occipital frontal circumference (OFC). [ABSTRACT FROM AUTHOR]

Introduction: Prenatal exposure to supraphysiological glucocorticoid (GC) levels may lead to long‐lasting developmental changes in numerous biological systems. Our prior study identified an association between prenatal GC prophylaxis and reduced cognitive performance, electrocortical changes, and altered autonomic nervous system (ANS) activity in children aged 8–9 years. This follow‐up study aimed to examine whether these findings persisted into adolescence. Material and Methods: Prospective observational follow‐up study involving twenty‐one 14‐ to 15‐year‐old adolescents born to mothers who received betamethasone for induction of fetal lung maturation in threatened preterm birth, but who were born with a normal weight appropriate for their gestational age (median 37+4 gestational weeks). Thirty‐five children not exposed to betamethasone served as the reference group (median 37+6 gestational weeks). The primary endpoint was cognitive performance, measured by intelligence quotient (IQ). Key secondary endpoints included symptoms of attention‐deficit/hyperactivity disorder (ADHD) and metabolic markers. Additionally, we determined electrocortical (electroencephalogram), hypothalamus–pituitary–adrenal axis (HPAA), and ANS activity in response to a standardized stress paradigm. Results: No statistically significant group difference was observed in global IQ (adjusted mean: betamethasone 103.9 vs references 105.9, mean difference −2.0, 95% confidence interval [CI]: −7.12 to 3.12, p = 0.44). Similarly, ADHD symptoms, metabolic markers, the overall and stress‐induced activity of the HPAA and the ANS did not differ significantly between groups. However, the betamethasone group exhibited reduced electrocortical activity in the frontal brain region (spectral edge frequency–adjusted means: 16.0 Hz vs 17.8 Hz, mean difference −1.83 Hz, 95% CI: −3.21 to −0.45, p = 0.01). Conclusions: In 14‐ to 15‐year‐old adolescents, prenatal GC exposure was not associated with differences in IQ scores or ANS activity compared to unexposed controls. However, decelerated electrocortical activity in the frontal region potentially reflects disturbances in the maturation of cortical and/or subcortical brain structures. The clinical significance of these changes remains unknown. Given the small sample size, selective participation/loss of follow‐up and potential residual confounding, these findings should be interpreted cautiously. Further research is required to replicate these results in larger cohorts before drawing firm clinical conclusions. [ABSTRACT FROM AUTHOR]

Background: Past research on the safety of prenatal exposure to medications has focused on maternal use during gestation, with limited research into the potential effects of paternal use during the spermatogenic period preceding conception. Knowing the most common medications used by fathers around the time of conception can inform research priorities in this field. Objectives: To identify the most common medications dispensed to fathers in the preconception period. Methods: Within the MarketScan research database of commercially insured individuals in the United States from 2011 to 2020, we identified pregnancies, estimated the date of conception, linked each pregnancy to the father using family enrolment information and required minimum enrolment period and prescription benefits. Then, we described the use of prescription medications by the father during the 90 days before conception based on pharmacy dispensation claims. Results: Of 4,437,550 pregnancies, 51.6% were linked with a father. Among the 1,413,762 pregnancies connected with a father that also met the inclusion criteria, the most common classes of medications dispensed were psychotropics (8.66%), antibiotics (7.21%), and analgesics (6.82%). The most frequently dispensed medications were amoxicillin (3.75%), azithromycin (3.15%), fluticasone (2.70%) and acetaminophen/hydrocodone (2.70%). Some fathers filled prescriptions for medications associated with foetal embryopathy when used by the mother, including mycophenolate (0.04%), methotrexate (0.03%) and isotretinoin (0.02%). Conclusions: More than a third of fathers filled at least one prescription medication in the preconception period, and several of them are known to be embryotoxic, emphasizing the necessity for further investigation into the potential teratogenicity of paternal exposure. [ABSTRACT FROM AUTHOR]

Per‐ and poly‐fluoroalkyl substances (PFAS), which are long‐lasting environmental contaminants that are released into the environment during the e‐waste disassembly process, pose a threat to human health. Human milk is a complex and dynamic mixture of endogenous and exogenous substances, including steroid hormones and PFAS. Therefore, in this study, we aimed to investigate the association between PFAS and steroid hormones in human milk from women living close to an e‐waste disassembly area. In 2021, we collected milk samples from 150 mothers within 4 weeks of delivery and analyzed them via liquid chromatography‐tandem mass spectrometry to determine the levels of 21 perfluorinated compounds and five steroid hormones (estrone, estriol, testosterone, progesterone, and androstenedione [A‐dione]). We also performed multiple linear regression analysis to clarify the association between maternal PFAS exposure and steroid hormone concentrations. Our results indicated that PFOA and PFOS were positively associated with estrone (β, 0.23; 95% CI, 0.08–0.39) and A‐dione (β, 0.186; 95% CI, 0.016–0.357) concentrations in human milk, respectively. Further, the average estimated daily intake of PFOA and PFOS were 36.5 ng/kg bw/day (range, 0.52–291.7 ng/kg bw/day) and 5.21 ng/kg bw/day (range, 0.26–32.3 ng/kg bw/day), respectively. Of concern, the PFAS intake of breastfeeding infants in the study area was higher than the recommended threshold. These findings suggested that prenatal exposure to PFAS from the e‐waste disassembly process can influence steroid hormones levels in human milk. Increased efforts to mitigate mother and infant exposure to environmental pollutants are also required. Plain Language Summary: We recruited 150 mothers who provided human milk samples within 4 weeks of delivery. Using liquid chromatography‐tandem mass spectrometry, we measured concentrations of 21 perfluorinated compounds and five steroid hormones (estrone, estriol, testosterone, progesterone, and androstenedione [A‐dione]) in the human milk samples. Multiple linear regression analysis was performed to examine the association between maternal PFAS exposure and steroid hormone concentrations. Our findings revealed significant positive associations between specific PFAS compounds (PFOA and PFOS) and certain steroid hormone concentrations in human milk. Notably, PFOA showed positive associations with estrone concentrations, PFOS was associated with A‐dione levels. These results suggest that prenatal exposure to PFAS from e‐waste disassembly areas can impact the levels of steroid hormones in human milk. Key Points: Per‐ and poly‐fluoroalkyl substances and steroid hormones concentrations in human milk measured in an e‐waste disassembly areaPFOA was positively associated with DHEA and estrone concentrations in human milkPFOS was positively associated with A‐dione in human milk [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social communication disability and stereotypic behavior. This study aims to investigate the impact of prenatal exposure to 1‐nitropyrene (1‐NP), a key component of motor vehicle exhaust, on autism‐like behaviors in a mouse model. Three‐chamber test finds that prenatal 1‐NP exposure causes autism‐like behaviors during the weaning period. Patch clamp shows that inhibitory synaptic transmission is reduced in medial prefrontal cortex of 1‐NP‐exposed weaning pups. Immunofluorescence finds that prenatal 1‐NP exposure reduces the number of prefrontal glutamate decarboxylase 67 (GAD67) positive interneurons in fetuses and weaning pups. Moreover, prenatal 1‐NP exposure retards tangential migration of GAD67‐positive interneurons and downregulates interneuron migration‐related genes, such as Nrg1, Erbb4, and Sema3F, in fetal forebrain. Mechanistically, prenatal 1‐NP exposure reduces hydroxymethylation of interneuron migration‐related genes through inhibiting ten‐eleven translocation (TET) activity in fetal forebrain. Supplement with alpha‐ketoglutarate (α‐KG), a cofactor of TET enzyme, reverses 1‐NP‐induced hypohydroxymethylation at specific sites of interneuron migration‐related genes. Moreover, α‐KG supplement alleviates 1‐NP‐induced migration retardation of interneurons in fetal forebrain. Finally, maternal α‐KG supplement improves 1‐NP‐induced autism‐like behaviors in weaning offspring. In conclusion, prenatal 1‐NP exposure causes autism‐like behavior partially by altering DNA hydroxymethylation of interneuron migration‐related genes in developing brain. [ABSTRACT FROM AUTHOR]

Previous studies have reported sex differences in cortical gyrification. Since most cortical folding is principally defined in utero, sex chromosomes as well as gonadal hormones are likely to influence sex‐specific aspects of local gyrification. Classic congenital adrenal hyperplasia (CAH) causes high levels of androgens during gestation in females, whereas levels in males are largely within the typical male range. Therefore, CAH provides an opportunity to study the possible effects of prenatal androgens on cortical gyrification. Here, we examined the vertex‐wise absolute mean curvature—a common estimate for cortical gyrification—in individuals with CAH (33 women and 20 men) and pair‐wise matched controls (33 women and 20 men). There was no significant main effect of CAH and no significant CAH‐by‐sex interaction. However, there was a significant main effect of sex in five cortical regions, where gyrification was increased in women compared to men. These regions were located on the lateral surface of the brain, specifically left middle frontal (rostral and caudal), right inferior frontal, left inferior parietal, and right occipital. There was no cortical region where gyrification was increased in men compared to women. Our findings do not only confirm prior reports of increased cortical gyrification in female brains but also suggest that cortical gyrification is not significantly affected by prenatal androgen exposure. Instead, cortical gyrification might be determined by sex chromosomes either directly or indirectly—the latter potentially by affecting the underlying architecture of the cortex or the size of the intracranial cavity, which is smaller in women. [ABSTRACT FROM AUTHOR]

We estimate the effect of county‐level e‐cigarette indoor vaping restrictions (IVRs) on infant mortality using United States birth certificates from 2010 to 2015. We estimate difference‐in‐differences models and find that e‐cigarette IVRs increased infant mortality by 0.39 infants per 1000 live births (12.9%). These effects were disproportionately higher for infants born to younger mothers and in locations with higher baseline levels of prenatal smoking. Infant mortality increased by 34.1% between 100 days to 1 year after IVRs. Infant mortality due to infections and neoplasms were particularly elevated. [ABSTRACT FROM AUTHOR]

Purpose: To assess various aspects of visual function in school children prenatally exposed to opioid maintenance therapy (OMT) and to explore possible outcome differences between prenatal methadone and buprenorphine exposure. Methods: In a cross‐sectional case–control study, 63 children aged 5–13 years with prenatal OMT exposure were compared with 63 age‐ and gender‐matched, non‐exposed controls regarding important visual parameters, such as visual acuity, orthoptic status, refractive state, colour vision, and visual field. Results: The OMT‐exposed children had significantly poorer visual acuity, both for the best eye, the worst eye and binocularly. Two children had mild visual impairment. Manifest strabismus was more frequent in the OMT group, 30%, vs. 4.8% in the control group. The most frequent types of strabismus were accommodative esotropia and intermittent exotropia. Manifest nystagmus was present in 10 (16%) of the exposed children compared to one among the non‐exposed children. The accommodative amplitude was decreased in the OMT group compared to the controls. After adjusting for polydrug exposure and SGA (small‐for‐gestational‐age), the between‐group differences in visual acuity, strabismus, and nystagmus remained. The methadone‐exposed children had poorer visual acuity, increased frequency of strabismus and a higher percentage of nystagmus, hypermetropia and astigmatism compared to the buprenorphine‐exposed children. Conclusions: School‐age children exposed to methadone or buprenorphine in utero had a higher prevalence of strabismus and nystagmus, and a lower visual acuity and accommodation amplitude. Buprenorphine exposure was associated with more favourable results than methadone exposure on most visual outcome measures and should be the preferred substance in OMT. [ABSTRACT FROM AUTHOR]

Aim: Preschool children prenatally exposed to opioid maintenance therapy (OMT) have an increased risk of neurodevelopmental impairments. We aimed to investigate long-term motor and visual-motor integration outcome in children aged 5-13 Years, born to mothers in OMT. Methods: From January 2018 to June 2021, 63 children prenatally exposed to OMT and 63 comparison children matched for age and gender, were examined at two Norwegian hospitals. Motor skills were assessed by the Movement- ABC test and visual-motor integration by the Beery VMI test. A motor function neurological assessment test was used to examine neuromotor soft signs. Results: In the OMT-exposed group, 16% had motor impairment, 35% had motor problems and 19% had visual-motor integration problems. Forty-three percent of the exposed children had neuromotor soft signs. Strabismus had some influence on motor and visual- motor outcomes but could not explain the group differences. Conclusion: Children prenatally exposed to opioid maintenance therapy have an increased risk of long-term motor impairment and visual-motor problems. In addition, they exhibit significantly more neuromotor soft signs, which may affect general wellbeing, leisure activities and school performance. [ABSTRACT FROM AUTHOR]

Chondrodysplasia is closely associated with low birth weight and increased susceptibility to osteoarthritis in adulthood. Prenatal prednisone exposure (PPE) can cause low birth weight; however, its effect on offspring cartilage development remains unexplored. Herein, rats are administered clinical doses of prednisone intragastrically on gestational days (GDs) 0–20 and underwent long‐distance running during postnatal weeks (PWs) 24–28. Knee cartilage is assayed for quality and related index changes on GD20, PW12, and PW28. In vitro experiments are performed to elucidate the mechanism. PPE decreased cartilage proliferation and matrix synthesis, causing offspring chondrodysplasia. Following long‐distance running, the PPE group exhibited more typical osteoarthritis‐like changes. Molecular analysis revealed that PPE caused cartilage circRNomics imbalance in which circGtdc1 decreased most significantly and persisted postnatally. Mechanistically, prednisolone reduced circGtdc1 expression and binding with Srsf1 to promote degradation of Srsf1 via K48‐linked polyubiquitination. This further inhibited the formation of EDA/B+Fn1 and activation of PI3K/AKT and TGFβ pathways, reducing chondrocyte proliferation and matrix synthesis. Finally, intra‐articular injection of offspring with AAV‐circGtdc1 ameliorated PPE‐induced chondrodysplasia, but this effect is reversed by Srsf1 knockout. Altogether, this study confirms that PPE causes chondrodysplasia and susceptibility to osteoarthritis by altering the circGtdc1‐Srsf1‐Fn1 axis; in vivo, overexpression of circGtdc1 can represent an effective intervention target for ameliorating PPE‐induced chondrodysplasia. [ABSTRACT FROM AUTHOR]

Fetal programming may arise from prenatal exposure and increase the risk of diseases later in life, potentially mediated by the placenta. The objective of this systematic review was to summarize and critically evaluate publications describing associations between human placental changes and risk of atopic disorders during childhood. The review adhered to the Preferred Reporting Items for Systematic Reviews and Meta‐analysis guidelines. The inclusion criteria were original research articles or case reports written in English describing a human placental change in relation to disease occurring in offspring during childhood. The MEDLINE and EMBASE databases were searched for eligible studies. Risk of bias (RoB) was assessed using the ROBINS‐I tool. The results were pooled both in a narrative way and by a meta‐analysis. Nineteen studies were included (n = 12,997 participants). All studies had an overall serious RoB, and publication bias could not be completely ruled out. However, five studies showed that histological chorioamnionitis in preterm‐born children was associated with asthma‐related problems (pooled odds ratio = 3.25 (95% confidence interval = 2.22–4.75)). In term‐born children, a large placenta (≥750 g) increased the risk of being prescribed anti‐asthma medications during the first year of life. Placental histone acetylation, DNA methylation, and gene expression differences were found to be associated with different atopic disorders in term‐born children. There is some evidence supporting the idea that the placenta can mediate an increased risk of atopic disorders in children. However, further studies are needed to validate the findings, properly control for confounders, and examine potential mechanisms. [ABSTRACT FROM AUTHOR]

Background: Development of the gonads during fetal life is complex and vital for adult reproductive health. Cell and animal studies have shown an alarming effect of mild analgesics on germ cells in both males and females. More than 50% of pregnant women use mild analgesics during pregnancy, which potentially could compromise the reproductive health of the next generation. Objectives: We present a research protocol designed to evaluate the effect of prenatal exposure to mild analgesics and endocrine‐disrupting chemicals on gonadal function in the offspring. Population: Healthy, singleton pregnant women and their partners. Design: The COPANA cohort is a prospective, observational pregnancy and birth cohort. Methods: Participants were enrolled during the first trimester of pregnancy. Information on the use of mild analgesics was collected retrospectively 3 months prior to pregnancy and prospectively every 2 weeks throughout the study. We collected extensive data on lifestyle and reproductive health. Biospecimens were collected in the first trimester (maternal and paternal urine‐ and blood samples), in the third trimester in conjunction with a study‐specific ultrasound scan (maternal urine sample), and approximately 3 months post‐partum during the infant minipuberty period (maternal and infant urine‐ and blood samples). A comprehensive evaluation of reproductive function in the infants during the minipuberty phase was performed, including an ultrasound scan of the testis or ovaries and uterus. Preliminary Results: In total, 685 pregnant women and their partners were included between March 2020 and January 2022. A total of 589 infants (287 males) and their parents completed the follow‐up during the minipuberty phase (December 2020—November 2022). Conclusions: The Copenhagen Analgesic Study holds the potential to provide novel and comprehensive insights into the impact of early and late prenatal exposure to mild analgesics and other endocrine‐disrupting chemicals on future reproductive function in the offspring. [ABSTRACT FROM AUTHOR]

Purpose: To explore whether MR fingerprinting (MRF) scans provide motion‐robust and quantitative brain tissue measurements for non‐sedated infants with prenatal opioid exposure (POE). Study Type: Prospective. Population: 13 infants with POE (3 male; 12 newborns (age 7–65 days) and 1 infant aged 9‐months). Field Strength/Sequence: 3T, 3D T1‐weighted MPRAGE, 3D T2‐weighted TSE and MRF sequences. Assessment: The image quality of MRF and MRI was assessed in a fully crossed, multiple‐reader, multiple‐case study. Sixteen image quality features in three types—image artifacts, structure and myelination visualization—were ranked by four neuroradiologists (8, 7, 5, and 8 years of experience respectively), using a 3‐point scale. MRF T1 and T2 values in 8 white matter brain regions were compared between babies younger than 1 month and babies between 1 and 2 months. Statistical Tests: Generalized estimating equations model to test the significance of differences of regional T1 and T2 values of babies under 1 month and those older. MRI and MRF image quality was assessed using Gwet's second order auto‐correlation coefficient (AC2) with confidence levels. The Cochran–Mantel–Haenszel test was used to assess the difference in proportions between MRF and MRI for all features and stratified by the type of features. A P value <0.05 was considered statistically significant. Results: The MRF of two infants were excluded in T1 and T2 value analysis due to severe motion artifact but were included in the image quality assessment. In infants under 1 month of age (N = 6), the T1 and T2 values were significantly higher compared to those between 1 and 2 months of age (N = 4). MRF images showed significantly higher image quality ratings in all three feature types compared to MRI images. Conclusions: MR Fingerprinting scans have potential to be a motion‐robust and efficient method for nonsedated infants. Level of Evidence: 2 Technical Efficacy Stage: 1 [ABSTRACT FROM AUTHOR]

During pregnancy, the maternal environment is critical for normal ontogeny and central nervous system development. Occasionally, prenatal exposure to environmental factors affects tissue architecture and functional development of the brain, which causes developmental disorders, including disorders of the autism spectrum. One of these environmental factors is the exposure to infectious diseases during pregnancy. In this study, we generated mice with infectious disease‐induced inflammation by prenatal exposure to 200 μg/kg polyinosinic–polycytidylic acid sodium salt [Poly(I:C)] at embryonic day 12.5 and analyzed their phenotypes on 30‐weeks‐old. We attempted to detect abnormalities in spontaneous activity and social interaction, which may be indicators of developmental disorder‐like behavioral abnormalities, in free‐ranging behaviors in multiple rearing environments using multiple animal positioning systems and UMATracker in mice with fetal inflammation. Increased spontaneous activity and abnormal social interactions were observed in mice in the Poly(I:C)‐treated group compared with those in the control group. Prenatal exposure to Poly(I:C) increased motor activity and decreased social interaction, and social behavior in prenatally treated mice in a multiple‐individual rearing environment. Poly(I:C) exposure during the fetal period resulted in developmental disorder‐like behavioral abnormalities, such as increased activity and abnormal social interactions, even after maturation in a multiple‐individual rearing environment. This experimental method may provide a new way to analyze the behavior of mouse models of developmental disorders in a multiple‐individual rearing environment, in which free‐ranging behavior is possible. [ABSTRACT FROM AUTHOR]

The incidence of antenatal cancer is increasing, prompting a medical‐ethical evaluation. The International Network on Cancer, Infertility, and Pregnancy (INCIP) was established to study cancer treatment safety during pregnancy and its impact on maternal and child health. Pivotal research has led to a paradigm shift in clinical management, demonstrating the feasibility and safety of most antenatal oncological treatments. Short‐term outcomes reveal normal growth and cardiac function in the exposed offspring, but caution is advised against first‐trimester chemotherapy. Psychological impact studies highlight the elevated levels of distress in pregnant cancer patients, underscoring the need for personalized information and ongoing psychological support. Long‐term follow‐up studies address gaps in postnatal impacts, while research into specific chemotherapeutic agents continues. Despite generally reassuring outcomes, continued monitoring is crucial, especially in families, such as those where the child was born premature after cancer (treatment) during pregnancy or where mothers are frequently absent due to continued illness or have died from. The ongoing INCIP child follow‐up initiative aims to further elucidate knowledge gaps, emphasizing the importance of large‐scale studies and personalized patient care. [ABSTRACT FROM AUTHOR]

Prenatal opioid exposure has been associated with developmental problems, including autonomic nervous system dysregulation. However, little is known about the effects of prenatal opioid exposure on the autonomic nervous system beyond the first days of life, particularly across both the parasympathetic and sympathetic branches, and when accounting for exposure to other substances. The present study examined the effects of prenatal exposure to opioid agonist therapy (OAT, e.g., methadone) and other opioids on infant autonomic nervous system activity at rest and in response to a social stressor (the Still‐Face Paradigm) at six months among 86 infants varying in prenatal opioid and other substance exposure. Results indicated that OAT and other opioids have unique effects on the developing autonomic nervous system that may further depend on subtype (i.e., methadone versus buprenorphine) and timing in gestation. Results are discussed in the context of theoretical models of the developing stress response system. Prenatal opioid exposure (POE) is a major public health concern and impacts the fetal and neonatal autonomic nervous system (ANS). However, little is known about POE effects on the ANS beyond the neonatal period and accounting for other substance exposure. The present study describes the effects of POE on infant respiratory sinus arrhythmia and pre‐ejection period at six months of age and the differential effects of type and timing of exposure in the context of polysubstance exposure. [ABSTRACT FROM AUTHOR]

Objective: To explore the associations between prenatal temperature exposures and low birthweight (LBW) and modification by cash transfer (CT) receipt. Design: Retrospective cohort study. Setting: Five rural districts in Northern Ghana. Population or sample: A total of 3016 infants born to women interviewed as part of the Livelihood Empowerment Against Poverty (LEAP 1000) impact evaluation between 2015 and 2017. Methods: Birthweight was collected using household surveys administered to LEAP 1000 eligible women. We used a UNICEF‐developed multiple imputation approach to address missingness of birthweight and applied an empirical heaping correction to the multiply imputed birthweight data. Survey data were linked to the European Centre for Medium‐Range Weather Forecasts Reanalysis 5‐hourly temperature averaged to weeks for 2011–2017 using community centroids. Using distributed‐lag nonlinear models, we explored the lag‐specific associations between weekly average temperatures greater than 30°C and LBW, and stratified by LEAP 1000 treatment. Main outcome measures: Low birthweight (<2.5 kg). Results: Twelve percent (n = 365) of infants were LBW; the mean ± SD birthweight was 3.02 ± 0.37 kg. Overall, increasing temperatures were associated with increased odds of LBW, with the greatest odds observed in the 3 weeks before birth (odds ratio 1.005–1.025). These positive associations were even larger among comparison infants and null among treatment infants. Conclusions: Our study found increased odds of LBW with high weekly average temperatures throughout pregnancy and the preconception period and demonstrate mitigated effects by the LEAP 1000 CT program. More evidence on the potential of CTs to serve as adaptation interventions in low‐ and middle‐income countries is needed to protect pregnant persons and their infants from the impacts of climate change. [ABSTRACT FROM AUTHOR]

Background: Many clinical evidences have reported the higher risk of seizure in young children and infants after exposure to hyperthermia, which more likely can cause brain damage and affect cognitive function, so, many researches were focused on prevention or treatment of febrile seizure (FS) with minimal adverse effects. Considering the potential effects of oxidative stress as a prominent trigger in FS, and demonstrating the anti‐oxidant effects of metformin, the present study aimed to investigate the protective effect of metformin administration in prenatal and lactation periods in rat pups exposed to hyperthermia by which induced seizure. Method and materials: Pregnant rats were divided into six groups: (1) vehicle: pregnant rats received normal saline during pregnancy and lactation; (2) FS: pregnant rats received normal saline during pregnancy and lactation; (3–5) FS‐Met50/100/150 mg/kg: pregnant rats received different doses of metformin including 50, 100 and 150 mg/kg during pregnancy and lactation; (6) Met150 mg/kg: pregnant rats received Met150 mg/kg during pregnancy and lactation. The male pups born to mothers received in all FS groups exposed to hyperthermia. All experimental groups were allowed to grow up, and after the lactation period, they were subjected for behavioural tests and biochemical analysis. Results: According to the present findings, the prenatal and lactation exposure to the highest dose of metformin demonstrated significant difference with FS group in both behavioural and biochemical test analyses. Although the remaining doses of metformin were also effective, the much better results were reported with the highest dose of metformin (150 mg/kg). Interestingly, the highest dose of metformin administered alone demonstrated better result than vehicle in probe trial test. Conclusion: Considering the present research and related study in relation to metformin in ameliorating the epilepsy symptoms, there are numerous evidences on positive effect of metformin on seizure. Although the exact mechanism is unclear, the anti‐oxidant effect of metformin is strongly supported. [ABSTRACT FROM AUTHOR]

The endocrine disruptor hexavalent chromium [Cr(VI)] is a proven reproductive toxicant. We recently demonstrated that prenatal Cr(VI) exposure causes testicular resistance to gonadotropins, resulting in hypergonadotropic hypoandrogenism in F1 rats. However, the mechanism driving hypergonadotropism in F1 rats exposed to Cr (VI) prenatally remains an enigma. Therefore, we hypothesized that 'Prenatal Cr(VI) exposure may disrupt steroid hormones-mediated negative feedback regulation of the hypothalamic GnRH, and its receptor in the pituitary of F1 rats, leading to hypergonadotropism.' We administered potassium dichromate (50, 100, or 200 mg/L) to pregnant rats through drinking water between days 9 and 14, and their male F1 offspring were euthanized at 60 days of age. Prenatal Cr(VI) exposure in F1 rats resulted in the accumulation of Cr in the hypothalamus and pituitary. Western blot detected decreased hypothalamic GnRH, Kisspeptin1, and its receptor GPR54, along with diminished ERα, AR, aromatase, and 5α reductase, and GnRH regulatory transcription factors Pit-1 and GATA-4 proteins. Immunohistochemical studies revealed increased immunopositivity of GnRH receptor, AR, 5α reductase, ERα, ERβ, and aromatase proteins in the pituitary, whereas decreased Kisspeptin1, GPR54, and inhibin β. Our findings imply that Cr(VI) exposure during the prenatal period disrupts the hypothalamic Kisspeptin-GPR54-Pit-1/GATA4-GnRH network, boosting the pituitary GnRH receptor. We conclude that prenatal exposure to Cr(VI) alters GnRH expression in the hypothalamus and its receptor in the pituitary of F1 progeny through interfering with the negative feedback effect of androgens and estrogens. [ABSTRACT FROM AUTHOR]

Background: There are only preliminary studies examining the associations of postnatal antibiotic exposure with food allergy in childhood, and the effect of antibiotic exposure in utero has not been resolved. Thus, we aimed to investigate the effect of prenatal and postnatal antibiotic exposure on the risk of food allergy in childhood. Methods: Using the nationwide birth cohort in South Korea, all 3,163,206 infants (pairing mother; n = 2,322,735) born in South Korea between 2010 and 2017 were included in the analysis. The primary outcome was the diagnosis of food allergy, and the observation period was between January 1, 2009, and December 31, 2020. We implemented four different designs for the study, which consisted of a full unmatched cohort, 1:1 propensity‐matched cohort, sibling comparison cohort, and health screening cohort along with multiple subgroup analyses. Results: During the follow‐up period (median 6.92 years [IQR, 4.72–9.00]) of the 3,161,858 infants (52.6% male) in the birth cohort, 29,973 (1.9%) were diagnosed with food allergies. After a 1:1 propensity score matching, the use of antibiotics increased the risk of overall food allergy (prenatal [HR, 1.05; 95% CI, 1.04–1.09] and postnatal [HR, 1.05; 95% CI, 1.01–1.10] periods). The association was more significantly accentuated when antibiotic exposure was used in the short term, and the children were born preterm or with low birthweight; however, a trimester‐specific effect was not observed. We observed more pronounced risks of food allergy in the health screening cohort (prenatal, 17%; postnatal, 15%), thus addressing the adverse effects of critical factors including maternal BMI, smoking status, and type of infant feeding. Similar trends were observed across all four differnt cohorts. Conclusion: This study reported a moderate association between early‐life antibiotic use and subsequent food allergy during childhood throughout four different designs of analyses. This study suggests that clinicians need to consider the risks and benefits of antibiotics when administering antibiotics to individuals in the prenatal and postnatal periods. [ABSTRACT FROM AUTHOR]

Pulsatile gonadotropin‐releasing hormone (GnRH) release is critical for reproduction. Disruptions to GnRH secretion patterns may contribute to polycystic ovary syndrome (PCOS). Prenatally androgenized (PNA) female mice recapitulate many neuroendocrine abnormalities observed in PCOS patients. PNA and development induce changes in spontaneous GnRH neuron firing rate, response to synaptic input, and the afterhyperpolarization potential of the action potential. We hypothesized potassium currents are altered by PNA treatment and/or development. Whole‐cell patch‐clamp recordings were made of transient and residual potassium currents of GnRH neurons in brain slices from 3‐week‐old and adult control and PNA females. At 3 weeks of age, PNA treatment increased transient current density versus controls. Development and PNA altered voltage‐dependent activation and inactivation of the transient current. In controls, transient current activation and inactivation were depolarized at 3 weeks of age versus in adulthood. In GnRH neurons from 3‐week‐old mice, transient current activation and inactivation were more depolarized in control than PNA mice. Development and PNA treatment interacted to shift the time‐dependence of inactivation and recovery from inactivation. Notably, in cells from adult PNA females, recovery was prolonged compared to all other groups. Activation of the residual current occurred at more depolarized membrane potentials in 3‐week‐old than adult controls. PNA depolarized activation of the residual current in adults. These findings demonstrate the properties of GnRH neuron potassium currents change during typical development, potentially contributing to puberty, and further suggest PNA treatment may both alter some typical developmental changes and induce additional modifications, which together may underlie aspects of the PNA phenotype. There was not any clinical trial involved in this work. [ABSTRACT FROM AUTHOR]

Di‐methoxyethyl phthalate (DMEP) is a well‐known environmentally prevalent endocrine disruptor and may be associated with neurodevelopmental disorders including attention deficit/hyperactivity disorder and intellectual disability. However, the regulatory mechanisms leading to these neurodevelopmental disorders are still poorly understood. Here, we demonstrate that prenatal DMEP exposure causes abnormal brain morphology and function in the mice. DMEP (50 mg/kg) was chronically administered to pregnant mice orally once a day starting on embryonic day 0 (E0) to breast‐feeding cessation for the fetus. We found that prenatal DMEP exposure significantly reduced the number of neurons in the parietal cortex by impairing neurogenesis and gliogenesis during the developing cortex. Moreover, we found that prenatal DMEP exposure impaired dendritic spine architectures and synaptic activity in the parietal cortex. Finally, prenatal DMEP exposure in mice induces hyperactivity and reduces anxiety behaviors. Altogether, our study demonstrates that prenatal DMEP exposure leads to abnormal behaviors via impairment of neurogenesis and synaptic activity. [ABSTRACT FROM AUTHOR]

This paper examines the impact of foetal exposure to air pollution from agricultural fires on Brazilian students' cognitive performance later in life. We rely on comparisons across children who were upwind and downwind of the fires while in utero to address concerns around sorting and temporary income shocks. Our findings show that agricultural fires increase PM2.5$$ {\mathrm{PM}}_{2.5} $$, resulting in significant negative effects on pupils' scores in Portuguese and Maths in the 5th$$ 5\mathrm{th} $$ grade through prenatal exposure. Back‐of‐the‐envelope calculations suggest that a 1% reduction in PM2.5$$ {\mathrm{PM}}_{2.5} $$ from agricultural burning has the potential to increase later life wages by 2.6%. [ABSTRACT FROM AUTHOR]

Introduction: Fetal growth may be affected by both maternal polycystic ovary syndrome (PCOS) and metformin therapy. Here, we explore the effect of intrauterine metformin exposure on birth anthropometrics of infants born to women with PCOS. We also investigated whether the effect of metformin on birth anthropometrics is modified by maternal pre‐pregnancy body mass index, PCOS hyperandrogenic phenotype, serum androgen levels, preconception use of metformin and offspring sex. Additionally, we assessed newborn anthropometrics in relation to a national reference population. Material and methods: Individual data from three randomized controlled triasl were pooled. The randomized controlled trials investigated the effects of metformin in pregnant women with PCOS. In all, 397 and 403 were randomized to the metformin and placebo groups, respectively. A Scandinavian growth reference was used to calculate sex and gestational age adjusted z‐scores. Linear regression models were used to estimate the effect of metformin on offspring z‐scores of head circumference, birth length, birthweight, placental weight, body mass index, ponderal index and birthweight:placental weight ratio. S‐testosterone, s‐androstenedione, and s‐sex‐hormone binding globulin from four timepoints in pregnancy were analyzed. Results: Compared with the PCOS‐placebo group, newborns in the PCOS‐metformin group had larger head circumference (head circumference z‐score: mean difference = 0.25, 95% CI = 0.11– 0.40). This effect of metformin on head circumference z‐score was particularly observed among offspring of overweight/obese mothers and mothers with hyperandrogenic PCOS‐phenotype. We observed no difference in other anthropometric measures between the metformin and placebo groups or any clear interaction between maternal androgen levels and metformin. Newborns in the PCOS‐placebo group were shorter than in the reference population (birth length z‐score: mean = −0.04, 95% CI = –0.05 to −0.03), but head circumference and birthweight were similar. Conclusions: Larger head circumference was observed at birth in metformin‐exposed offspring of mothers with PCOS. PCOS‐offspring were also shorter, with a similar birthweight to the reference population, indirectly indicating higher weight‐to‐height ratio at birth. [ABSTRACT FROM AUTHOR]

In‐utero exposures interact in complex ways that influence neurodevelopment. Animal research demonstrates that fetal sex moderates the impact of joint exposure to metals and prenatal stress measures, including cortisol, on offspring socioemotional outcomes. Further research is needed in humans. We evaluated the joint association of prenatal exposures to a metal mixture and cortisol with infant negative affectivity, considering sex differences. Analyses included 226 (29% White, Non‐Hispanic) mother‐infant pairs with data on exposures and negative affectivity assessed using the Infant Behavior Questionnaire‐Revised in 6‐month‐olds. Results showed that girls whose mothers had higher cortisol had significantly higher scores of Fear and Sadness with greater exposure to the mixture. Examining higher‐order interactions may better elucidate the effects of prenatal exposure to metals and cortisol on socioemotional functioning. [ABSTRACT FROM AUTHOR]

The article discusses research which explored the correlation of consumption of gutka, a smokeless tobacco, during pregnancy with healthcare risks on maternal and child health in Karachi, Pakistan. Study findings revealed higher rates of premature birth, still birth, low birth weight and birth defects linked to gutka consumption, as well as anemia in pregnant women addicted to gutka, and potential transfer of harmful chemicals in tobacco to the infant during breastfeeding.

Recent evidence shows that a lower second‐to‐fourth digit ratio (2D:4D), which is a sexually dimorphic trait and the indicator of prenatal testosterone exposure, may be associated with aggressive behaviors. In this cross‐sectional, case‐control study, we investigated: (1) Are the aggression and impulsivity levels and emotional problems higher? (2) Is the 2D:4D ratio lower in adolescents and young adults who presented with a fifth metacarpal neck fracture (boxer's fracture) compared to controls? (3) Is the digit ratio correlated with aggressive measures in individuals with a fifth metacarpal neck fracture? Seventy‐one consecutive patients presented with a fifth metacarpal neck fracture within the age range of 11–25 years old comprised the study group. The control group consisted of 71 age and sex‐matched subjects without a history of aggression‐related injury. The aggression, impulsiveness, and psychosocial well‐being were measured by self‐reported questionnaires. 2D:4D was measured by conventional radiography. The 2D:4D ratio was similar between groups, however, when the analyses were conducted separately for sex, females in the study group showed lower 2D:4D than females in the control group (p = 0.001). The aggression level of the study group, measured by the Buss–Perry Aggression Questionnaire was higher than the control group (p = 0.014). The impulsiveness scores on the Barratt Impulsiveness Scale‐11 were similar (p = 0.60) and the total difficulty score on the Strengths and Difficulties Questionnaire was higher in the study group (p = 0.009). A lower 2D:4D ratio significantly predicted verbal and total aggression scores (p = 0.036, p = 0.032, respectively). Our findings suggest that females with a history of aggression‐related injury have lower 2D:4D, and a lower 2D:4D is correlated with higher aggression levels in both sexes. Understanding and addressing aggression in these patients may help prevent further self‐inflicted injuries. [ABSTRACT FROM AUTHOR]

Background: Use of acid‐suppressive medications (ASMs), for example, proton pump inhibitors (PPIs) and histamine‐2 receptor antagonists (H2RAs), has been rising along with the incidence of pediatric immune‐mediated diseases (IMDs). We conducted a scoping review to characterize the literature about prenatal or pediatric exposure to ASMs in relation to incident pediatric IMDs. Methods: Electronic searches were conducted to identify studies from 2001 to 2023 on (a) prenatal or pediatric exposure to PPIs and/or H2RAs and (b) the risk of developing chronic IMDs during childhood. Eligible studies after title/abstract and full‐text screening underwent data abstraction. Results: Of 26 eligible studies, 11 focused on prenatal ASM exposure and 16 on pediatric exposure. Asthma was the most commonly investigated outcome (16 studies), followed by other allergic diseases (8), eosinophilic esophagitis (3), inflammatory bowel disease (2), and other autoimmune diseases (2). Positive associations between ASM exposure and pediatric IMD outcomes emerged in all but two recent studies, which reported null or negative associations with allergic diseases. The strength of associations was similar across exposure times (prenatal/pediatric), medications (PPIs/H2RAs), and outcomes. Dose–response relationships were often present (7/11 studies). Reported effects by trimester and age of exposure varied. Commonly reported limitations were residual confounding, exposure misclassification, and outcome misclassification. Conclusion: In summary, prenatal or pediatric exposure to PPIs and/or H2RAs has frequently, but not exclusively, been associated with the development of asthma, other allergic diseases, and chronic gastrointestinal IMDs. However, concerns remain about confounding and other sources of bias. Prescribers and families should be aware of these possible risks of ASMs. [ABSTRACT FROM AUTHOR]

Background: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women. Objectives: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood. Population: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits. Preliminary Results: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). Conclusions: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development. [ABSTRACT FROM AUTHOR]

Background: Childhood overweight and obesity is a global public health problem. Rapid infant weight gain is predictive of childhood overweight. Studies found that exposure to ambient air pollution is associated with childhood overweight, and have linked prenatal exposure to air pollution with rapid infant weight gain. Objectives: To examine the association between prenatal and postnatal ambient NO2 exposure, a traffic-related marker, with rapid weight gain in infants. Methods: We carried out a population-based historical cohort study using data from the Israeli national network of maternal and child health clinics. The study included 474,136 infants born at term with birthweight ≥2500 g in 2011-2019 in central Israel. Weekly averages of NO2 concentration throughout pregnancy (prenatal) and the first 4 weeks of life (postnatal) were assessed using an optimized dispersion model and were linked to geocoded home addresses. We modelled weight gain velocity throughout infancy using the SuperImposition by Translation and Rotation (SITAR) method, a mixed-effects nonlinear model specialized for modelling growth curves, and defined rapid weight gain as the highest velocity tertile. Distributed-lag models were used to assess critical periods of risk and to measure relative risks for rapid weight gain. Adjustments were made for socioeconomic status, population group, subdistrict, month and year of birth, and the alternate exposure period -prenatal or postnatal. Results: The cumulative adjusted relative risk for rapid weight gain of NO2 exposure was 1.02 (95% confidence intereval [CI] 1.00, 1.04) for exposure throughout pregnancy and 1.02 (95% CI 1.01, 1.04) for exposure during the first four postnatal weeks per NO2 interquartile range increase (7.3 ppb). An examination of weekly associations revealed that the critical period of risk for the prenatal exposure was from mid-pregnancy to birth. Conclusions: Prenatal and postnatal exposures to higher concentrations of traffic-related air pollution are each independently associated with rapid infant weight gain, a risk factor for childhood overweight and obesity. [ABSTRACT FROM AUTHOR]

Introduction: The present study aimed to analyse both neurobehavioural and biochemical results of neonates born of mothers exposed to different doses of lithium along with the groups that received lithium at the highest dose with folic acid as a preventive treatment. Materials and methods: Male and female rats were mated in separate cages, and pregnant rats were divided into eight first group as (1) vehicle; (2) propylthiouracil (PTU)‐induced hypothyroidism; (3–4) received two different doses of lithium carbonate (15 and 30 mg/kg); (5–7) the highest doses of lithium (30 mg/kg) plus three different doses of folic acid (5, 10 and 15 mg/kg); and (8) received just folic acid (15 mg/kg). All treatments were dissolved in drinking water and continued until delivery, followed by returning to a regular diet without treatment. Results: Lithium (30 mg/kg) disrupts both behavioural and biochemical markers, including TSH, T3 and T4 as measuring indicators to assess thyroid function, IL‐10 and TNF‐α as anti‐inflammatory and inflammatory agents, respectively, malondialdehyde as an oxidative stress marker, alongside SOD, and catalase activity as antioxidant indicators. Besides, folic acid, almost at the highest dose (15 mg/kg), attenuated memory impairement and anxiety‐like behaviour caused by lithium. Moreover, the groups treated with folic acid alone in comparison with vehicles demonstrated higher levels of antioxidant and anti‐inflammatory indicators. Conclusion: According to the results, prenatal exposure to a high dose of lithium (30 mg/kg) leads to foetal neurodevelopmental disorder and growth restriction through various mechanisms more likely attributed to hypothyroidism, which means it should be either prohibited or prescribed cautiously during pregnancy. [ABSTRACT FROM AUTHOR]

Electronic waste that has not been properly treated can lead to environmental contamination including of heavy metals, which can pose risks to human health. Infants, a sensitive group, are highly susceptible to heavy metals exposure. The aim of this study was to investigate the association between prenatal heavy metal exposure and infant birth outcomes in an e‐waste recycling area in China. We analyzed cadmium (Cd), chromium (Cr), manganese (Mn), lead (Pb), copper (Cu), and arsenic (As) concentrations in 102 human milk samples collected 4 weeks after delivery. The results showed that 34.3% of participants for Cr, which exceeds the World Health Organization (WHO) guidelines, as well as the mean exposure of Cr exceeded the WHO guidelines. We collected data on the birth weight (BW) and length of infants and analyzed the association between metal concentration in human milk and birth outcomes using multivariable linear regression. We observed a significant negative association between the Cd concentration in maternal milk and BW in female infants (β = −162.72, 95% CI = −303.16, −22.25). In contrast, heavy metals did not associate with birth outcomes in male infants. In this study, we found that 34.3% of participants in an e‐waste recycling area had a Cr concentration that exceeded WHO guidelines, and there was a significant negative association between prenatal exposure to the Cd and infant BW in females. These results suggest that prenatal exposure to heavy metals in e‐waste recycling areas may lead to adverse birth outcomes, especially for female infants. Plain Language Summary: In this study, the concentrations of six heavy metals in human milk samples collected 4 weeks after delivery in one of the two largest e‐waste recycling areas in China, that is, Taizhou, Zhejiang Province, were measured. The effects of prenatal heavy metal exposure on infant birth outcomes were analyzed. The results reveal gender differences in infant birth outcomes. For example, prenatal cadmium exposure decreases the birth weight of female infants but has no effect on male infants. We believe that our study makes a significant contribution to the literature because we provide guidance for future analyses. We suggest that the effects of metal exposure in the e‐waste area on the growth and development of infants must be studied over the long term, particularly for female infants. Key Points: 34.3% of participants in an e‐waste recycling area had a Cr concentration that exceeded World Health Organization guidelinesExamined associations between prenatal exposure to heavy metals and birth outcomes in an area in China with e‐wastePrenatal Cd exposure decreases the birth weight of female infants [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the mediating role of child brain structure in the relationship between prenatal gestational diabetes mellitus (GDM) exposure and child adiposity. Methods: This was a cross‐sectional study of 9– to 10‐year‐old participants and siblings across the US. Data were obtained from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study®. Brain structure was evaluated by magnetic resonance imaging. GDM exposure was self‐reported, and discordance for GDM exposure within biological siblings was identified. Mixed effects and mediation models were used to examine associations among prenatal GDM exposure, brain structure, and adiposity markers with sociodemographic covariates. Results: The sample included 8521 children (7% GDM‐exposed), among whom there were 28 sibling pairs discordant for GDM exposure. Across the entire study sample, prenatal exposure to GDM was associated with lower global and regional cortical gray matter volume (GMV) in the bilateral rostral middle frontal gyrus and superior temporal gyrus. GDM‐exposed siblings also demonstrated lower global cortical GMV than unexposed siblings. Global cortical GMV partially mediated the associations between prenatal GDM exposure and child adiposity markers. Conclusions: The results identify brain markers of prenatal GDM exposure and suggest that low cortical GMV may explain increased obesity risk for offspring prenatally exposed to GDM. [ABSTRACT FROM AUTHOR]