'Joining the Dots: Linking Prenatal Drug Exposure to Childhood and Adolescence' - research protocol of a population cohort study.

INTRODUCTION: Prenatal drug exposure (PDE) is one of the most important causes of child harm, but comprehensive information about the long-term outcomes of the families is difficult to ascertain. The Joining the Dots cohort study uses linked population data to understand the relationship between services, therapeutic interventions and outcomes of children with PDE. METHODS AND ANALYSIS: Information from routinely collected administrative databases was linked for all births registered in New South Wales (NSW), Australia between 1 July 2001 and 31 December 2020 (n=1 834 550). Outcomes for seven mutually exclusive groups of children with varying prenatal exposure to maternal substances of addiction, including smoking, alcohol, prescription/illicit drugs and neonatal abstinence syndrome will be assessed. Key exposure measures include maternal drug use type, maternal social demographics or social determinants of health, and maternal physical and mental health comorbidities. Key outcome measures will include child mortality, academic standardised testing results, rehospitalisation and maternal survival. Data analysis will be conducted using Stata V.18.0. ETHICS AND DISSEMINATION: Approvals were obtained from the NSW Population and Health Services Research Ethics Committee (29 June 2020; 2019/ETH12716) and the Australian Capital Territory Health Human Research Ethics Committee (11 October 2021; 2021-1231, 2021-1232, 2021-1233); and the Aboriginal Health and Medical Research Council (5 July 2022; 1824/21), and all Australian educational sectors: Board of Studies (government schools), Australian Independent Schools and Catholic Education Commission (D2014/120797). Data were released to researchers in September 2022. Results will be presented in peer-reviewed academic journals and at international conferences. Collaborative efforts from similar datasets in other countries are welcome.

Social Behavior in Animal Models of Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social deficits and stereotyped, repetitive patterns of behaviors, limited interests, and cognitive impairment. Especially, social deficit has been considered a core feature of ASD. Because of the limitations of the experimental approach in humans, valid animal models are essential in an effort to identify novel therapeutics for social deficits in ASD. The genetic and environmental factors are clinically relevant to the pathophysiology of ASD. Epidemiological studies demonstrate environmental interventions such as prenatal exposure to valproic acid (VPA). Prenatal exposure to VPA represents a robust model of ASD exhibiting face, construct, and predictive validity. Here, we introduce protocols of the social interaction test and the three-chamber test for evaluating social deficits in mice prenatally exposed to VPA.

Association Between Maternal Prenatal Exposure to Household Air Pollution and Child Respiratory Health: A Systematic Review and Meta-analysis.

Maternal prenatal exposure to household air pollution (HAP) is a critical public health concern with potential long-term implications for child respiratory health. The objective of this study is to assess the level of association between prenatal household air pollution and child respiratory health, and to identify which HAP pollutants are associated with specific respiratory illnesses or symptoms and to what degree. Relevant studies were retrieved from PubMed databases up to April 27, 2010, and their reference lists were reviewed. Random effects models were applied to estimate summarized relative risks (RRs) and 95% confidence intervals (CIs). The analysis involved 11 studies comprising 387 767 mother-child pairs in total, assessing various respiratory health outcomes in children exposed to maternal prenatal HAP. Children with prenatal exposure to HAP pollutants exhibited a summary RR of 1.26 (95% CI=1.08-1.33) with moderate between-study heterogeneity (I²=49.22%) for developing respiratory illnesses. Specific associations were found between prenatal exposure to carbon monoxide (CO) (RR=1.11, 95% CI: 1.09-1.13), Nitrogen Oxides (NOx) (RR=1.46, 95% CI: 1.09-1.60), and particulate matter (PM) (RR=1.26, 95% CI: 1.2186-1.3152) and child respiratory illnesses (all had I² close to 0%, indicating no heterogeneity). Positive associations with child respiratory illnesses were also found with ultrafine particles (UFP), polycyclic aromatic hydrocarbons (PAH), and ozone (O3). However, no significant association was observed for prenatal exposure to sulfur dioxide (SO2). In summary, maternal prenatal exposure to HAP may contribute to a higher risk of child respiratory health issues, emphasizing the need for interventions to reduce this exposure during pregnancy. Targeted public health strategies such as improved ventilation, cleaner cooking technologies, and awareness campaigns should be implemented to minimize adverse respiratory effects on children.

Phthalate Exposure and Neurotoxicity in Children: A Systematic Review and Meta-analysis.

Objectives: This systematic review aims to assess the relationship between prenatal and childhood exposure to phthalates and neurodevelopmental outcomes, identifying periods of heightened susceptibility. Data sources considered studies examining repeated phthalate exposure during pregnancy and childhood on neurodevelopment. Methods: Evaluation included bias risk and study quality criteria. Evidence was synthesized by groups of low and high phthalate molecular weight and exposure measured prenatally and postnatally and outcome measured in childhood. Beta coefficients and their standard errors were extracted, leading to meta-analyses of various neurodevelopmental outcomes: cognition, motor skills, language, behavior, and temperament. Results: Eleven pregnancy and birth cohort studies were identified as relevant. For each phthalate group and outcome combination, there was low or very low evidence of an association, except for prenatal and postnatal phthalate exposure and behavioral development and postnatal exposure and cognition. Conclusion: The estimated effects sizes were relatively small and strong evidence for periods of heightened susceptibility could not be elucidated. No distinction between phthalates of low molecular weight and those of high molecular weight with regards to the outcomes was found.

Acetaminophen Use During Pregnancy and Children's Risk of Autism, ADHD, and Intellectual Disability.

Importance: Several studies suggest that acetaminophen (paracetamol) use during pregnancy may increase risk of neurodevelopmental disorders in children. If true, this would have substantial implications for management of pain and fever during pregnancy. Objective: To examine the associations of acetaminophen use during pregnancy with children's risk of autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. Design, Setting, and Participants: This nationwide cohort study with sibling control analysis included a population-based sample of 2 480 797 children born in 1995 to 2019 in Sweden, with follow-up through December 31, 2021. Exposure: Use of acetaminophen during pregnancy prospectively recorded from antenatal and prescription records. Main Outcomes and Measures: Autism, ADHD, and intellectual disability based on International Classification of Diseases, Ninth Revision and International Classification of Diseases, Tenth Revision codes in health registers. Results: In total, 185 909 children (7.49%) were exposed to acetaminophen during pregnancy. Crude absolute risks at 10 years of age for those not exposed vs those exposed to acetaminophen were 1.33% vs 1.53% for autism, 2.46% vs 2.87% for ADHD, and 0.70% vs 0.82% for intellectual disability. In models without sibling control, ever-use vs no use of acetaminophen during pregnancy was associated with marginally increased risk of autism (hazard ratio [HR], 1.05 [95% CI, 1.02-1.08]; risk difference [RD] at 10 years of age, 0.09% [95% CI, -0.01% to 0.20%]), ADHD (HR, 1.07 [95% CI, 1.05-1.10]; RD, 0.21% [95% CI, 0.08%-0.34%]), and intellectual disability (HR, 1.05 [95% CI, 1.00-1.10]; RD, 0.04% [95% CI, -0.04% to 0.12%]). To address unobserved confounding, matched full sibling pairs were also analyzed. Sibling control analyses found no evidence that acetaminophen use during pregnancy was associated with autism (HR, 0.98 [95% CI, 0.93-1.04]; RD, 0.02% [95% CI, -0.14% to 0.18%]), ADHD (HR, 0.98 [95% CI, 0.94-1.02]; RD, -0.02% [95% CI, -0.21% to 0.15%]), or intellectual disability (HR, 1.01 [95% CI, 0.92-1.10]; RD, 0% [95% CI, -0.10% to 0.13%]). Similarly, there was no evidence of a dose-response pattern in sibling control analyses. For example, for autism, compared with no use of acetaminophen, persons with low (<25th percentile), medium (25th-75th percentile), and high (>75th percentile) mean daily acetaminophen use had HRs of 0.85, 0.96, and 0.88, respectively. Conclusions and Relevance: Acetaminophen use during pregnancy was not associated with children's risk of autism, ADHD, or intellectual disability in sibling control analysis. This suggests that associations observed in other models may have been attributable to familial confounding.

Unmet need for alcohol use disorder treatment in reproductive-age females, with emphasis on pregnant and parenting populations in the United States: Findings from NSDUH 2015-2021.

The negative effects of alcohol use can transmit intergenerational harm if alcohol use disorder (AUD) occurs during pregnancy and/or while parenting a child. Prenatal alcohol exposure is the leading preventable cause of congenital anomalies in the USA, and heavy drinking in women has been on the rise, further accelerated by the COVID-19 pandemic. This study describes the most recent patterns in the past year AUD prevalence and treatment among reproductive-aged women, with a specific focus on pregnant and parenting women, and barriers to treatment among those affected. We analyzed data on reproductive-age women from the National Survey on Drug Use and Health (2015-2021). We used generalized linear models to estimate prevalence ratios (PR) for past 12-month AUD and its treatment based on DSM-V criteria. We considered sociodemographic characteristics, including age, race/ethnicity, income, health insurance type, and arrest history. Pregnant and parenting women displayed lower risk for AUD (PR = 0.48, 95% CI:0.41-0.57; PR = 0.5 95% CI:0.48-0.54, respectively) relative to non-pregnant/non-parenting women. Excess risk for AUD was associated with education (some college vs. college graduates, PR = 1.07, 95% CI:1.01-1.13) and history of arrests (PR = 2.93, 95% CI:2.67-3.21). There were no clear differences in AUD treatment use based on parenting or pregnancy status. Among those with AUD, the prevalence of treatment was higher among individuals aged 35-49 years compared to those 18-25 years (PR = 1.6, 95% CI: 1.19-2.14) and in those enrolled in Medicaid vs. private insurance (PR = 2.62, 95%CI:1.97-3.47). Financial barriers and treatment not being a priority were the most frequently reported barriers to treatment. To promote well-being among parents and their children, healthcare providers should prioritize reproductive-age women at higher AUD risk. Decreasing the stigma attached to AUD and intensifying efforts to educate women about the dangers of AUD may improve treatment use among pregnant and parenting women.

An overview of current advances in perinatal alcohol exposure and pathogenesis of fetal alcohol spectrum disorders.

The adverse use of alcohol is a serious global public health problem. Maternal alcohol consumption during pregnancy usually causes prenatal alcohol exposure (PAE) in the developing fetus, leading to a spectrum of disorders known as fetal alcohol spectrum disorders (FASD) and even fetal alcohol syndrome (FAS) throughout the lifelong sufferers. The prevalence of FASD is approximately 7.7 per 1,000 worldwide, and is even higher in developed regions. Generally, Ethanol in alcoholic beverages can impair embryonic neurological development through multiple pathways leading to FASD. Among them, the leading mechanism of FASDs is attributed to ethanol-induced neuroinflammatory damage to the central nervous system (CNS). Although the underlying molecular mechanisms remain unclear, the remaining multiple pathological mechanisms is likely due to the neurotoxic damage of ethanol and the resultant neuronal loss. Regardless of the molecular pathway, the ultimate outcome of the developing CNS exposed to ethanol is almost always the destruction and apoptosis of neurons, which leads to the reduction of neurons and further the development of FASD. In this review, we systematically summarize the current research progress on the pathogenesis of FASD, which hopefully provides new insights into differential early diagnosis, treatment and prevention for patents with FASD.

Developmental anaesthesia neurotoxicity in humans: finding the sweet spot?

A recent human epidemiological study in this issue of British Journal of Anaesthesia examined the association between anaesthesia exposure in pregnant women undergoing appendicectomy or cholecystectomy and the subsequent diagnosis of behavioural disorders in their offspring. When compared with unexposed children, prenatally exposed children had ∼30% greater likelihood of a diagnosis of disruptive or internalising behavioural disorders. Although these data are new and interesting, they should be interpreted with caution. Indeed, appendicitis and cholecystitis can produce acute and chronic systemic inflammation, and maternal immune activation can affect fetal neurodevelopment through inflammatory and epigenetic mechanisms. It is, therefore, possible that the findings are related to maternal and fetal inflammation than to anaesthesia exposure. As there is no causal evidence for the implication that anaesthesia and surgery induce such pathologies, it is unwise to consider alternative treatments when surgery is indicated in pregnant patients.

The Associations of Prenatal Exposure to Fine Particulate Matter and Its Chemical Components with Allergic Rhinitis in Children and the Modification Effect of Polyunsaturated Fatty Acids: A Birth Cohort Study.

BACKGROUND: Polyunsaturated fatty acids (PUFAs) have been shown to protect against fine particulate matter <2.5µm in aerodynamic diameter (PM2.5)-induced hazards. However, limited evidence is available for respiratory health, particularly in pregnant women and their offspring. OBJECTIVES: We aimed to investigate the association of prenatal exposure to PM2.5 and its chemical components with allergic rhinitis (AR) in children and explore effect modification by maternal erythrocyte PUFAs. METHODS: This prospective birth cohort study involved 657 mother-child pairs from Guangzhou, China. Prenatal exposure to residential PM2.5 mass and its components [black carbon (BC), organic matter (OM), sulfate (SO42-), nitrate (NO3-), and ammonium (NH4+)] were estimated by an established spatiotemporal model. Maternal erythrocyte PUFAs during pregnancy were measured using gas chromatography. The diagnosis of AR and report of AR symptoms in children were assessed up to 2 years of age. We used Cox regression with the quantile-based g-computation approach to assess the individual and joint effects of PM2.5 components and examine the modification effects of maternal PUFA levels. RESULTS: Approximately 5.33% and 8.07% of children had AR and related symptoms, respectively. The average concentration of prenatal PM2.5 was 35.50±5.31 µg/m3. PM2.5 was positively associated with the risk of developing AR [hazard ratio (HR)=1.85; 95% confidence interval (CI): 1.16, 2.96 per 5 µg/m3] and its symptoms (HR=1.79; 95% CI: 1.22, 2.62 per 5 µg/m3) after adjustment for confounders. Similar associations were observed between individual PM2.5 components and AR outcomes. Each quintile change in a mixture of components was associated with an adjusted HR of 3.73 (95% CI: 1.80, 7.73) and 2.69 (95% CI: 1.55, 4.67) for AR and AR symptoms, with BC accounting for the largest contribution. Higher levels of n-3 docosapentaenoic acid and lower levels of n-6 linoleic acid showed alleviating effects on AR symptoms risk associated with exposure to PM2.5 and its components. CONCLUSION: Prenatal exposure to PM2.5 and its chemical components, particularly BC, was associated with AR/symptoms in early childhood. We highlight that PUFA biomarkers could modify the adverse effects of PM2.5 on respiratory allergy. https://doi.org/10.1289/EHP13524.

Prevention of alcohol exposed pregnancies in Europe: the FAR SEAS guidelines.

INTRODUCTION: Drinking during pregnancy is the leading cause of birth defects and child developmental disorders in Europe. The adverse effects of drinking during pregnancy may include physical, behavioural and cognitive problems, known collectively as fetal alcohol spectrum disorders (FASD). Evidence-based comprehensive recommendations at the European level on how to implement preventive and treatment policies to reduce alcohol-exposed pregnancies are needed. FAR SEAS, a tendered service contract (number 20,187,106) awarded by the European Commission, aimed at developing guidelines to respond to this knowledge gap. METHODS: FAR SEAS recommendations were built on (1) a two-phase review of interventions, (2) an international expert consultation, and (3) a pilot study on prevention of FASD conducted in the Mazovia region of Poland. The review of interventions included nineteen electronic open access databases, several repositories of grey literature and a key informant consultation covering most European Union (EU) countries and an additional guidelines search. After triangulating sources, 94 records were collected. Experts contributed in the design of the research questions, addressing the gaps in the literature and reviewing the recommendations formulated. The Polish pilot added nuances from real world practice to the formulated recommendations, resulting in the final set of guidelines for dissemination. RESULTS: The FAR SEAS Guidelines comprise 23 recommendations grouped into different topics areas of policies, communication strategies, screening, brief intervention and referral to treatment, treatment and social services. The recommendations highlight the need to respect women's autonomy and avoid discrimination and stigmatization; using universal screening for women of childbearing age, including detection of other psychosocial risks (such as domestic violence); and individualized, comprehensive and multidisciplinary supportive interventions for those who require it, such as those with alcohol use disorders, including women's partners. Policies to prevent FASD should be multicomponent, and public health communication should combine information about the risks together with self-efficacy messages to promote changes. CONCLUSIONS: The FAR SEAS guidelines are a tool to support policy-makers and service managers in implementing effective programmes to reduce prenatal alcohol exposure among general and at-risk population groups. FASD prevention has to involve comprehensive and multi-level evidence-based policies and practice, with services and activities tailored to the needs of women at differing levels of risk, and with due attention to reducing stigma.

Reversing valproic acid-induced autism-like behaviors through a combination of low-frequency repeated transcranial magnetic stimulation and superparamagnetic iron oxide nanoparticles.

Transcranial magnetic stimulation (TMS) is a neurostimulation device used to modulate brain cortex activity. Our objective was to enhance the therapeutic effectiveness of low-frequency repeated TMS (LF-rTMS) in a rat model of autism spectrum disorder (ASD) induced by prenatal valproic acid (VPA) exposure through the injection of superparamagnetic iron oxide nanoparticles (SPIONs). For the induction of ASD, we administered prenatal VPA (600 mg/kg, I.P.) on the 12.5th day of pregnancy. At postnatal day 30, SPIONs were injected directly into the lateral ventricle of the brain. Subsequently, LF-rTMS treatment was applied for 14 consecutive days. Following the treatment period, behavioral analyses were conducted. At postnatal day 60, brain tissue was extracted, and both biochemical and histological analyses were performed. Our data revealed that prenatal VPA exposure led to behavioral alterations, including changes in social interactions, increased anxiety, and repetitive behavior, along with dysfunction in stress coping strategies. Additionally, we observed reduced levels of SYN, MAP2, and BDNF. These changes were accompanied by a decrease in dendritic spine density in the hippocampal CA1 area. However, LF-rTMS treatment combined with SPIONs successfully reversed these dysfunctions at the behavioral, biochemical, and histological levels, introducing a successful approach for the treatment of ASD.

Associations between maternal serum neonicotinoid pesticide exposure during pregnancy and newborn telomere length: Effect modification by sampling season.

BACKGROUND: An increasing amount of evidence suggests that telomere length (TL) at birth can predict lifespan and is associated with chronic diseases later in life, but newborn TL may be affected by environmental pollutants. Neonicotinoids (NEOs) are widely used worldwide, and despite an increasing number of studies showing that they may have adverse effects on birth in mammals and even humans, few studies have examined the effect of NEO exposure on newborn TLs. OBJECTIVE: To investigate the effects of prenatal exposure to NEOs and the interactions between NEOs and sampling season on newborn TL. METHODS: We conducted a prospective cohort study of 500 mother-newborn pairs from the Guangxi Zhuang Birth Cohort. Ultraperformance liquid chromatographymass spectrometry was used to detect ten NEOs in maternal serum, and fluorescence quantitative PCR was used to estimate the newborn TL. A generalized linear model (GLM) was used to evaluate the relationships between individual NEO exposures and TLs , and quantile g-computation (Qgcomp) model and Bayesian kernel machine regression (BKMR) model were used to evaluate the combined effect of mixtures of components. RESULTS: The results of the GLM showed that compared with maternal TMX levels < LOD, maternal TMX levels < median were negatively correlated with newborn TL (-6.93%, 95% CI%: -11.92%, -1.66%), and the decrease in newborn TL was more pronounced in girls (-9.60%, 95% CI: -16.84%, -1.72%). Moreover, different kinds of maternal NEO exposure had different effects on newborn TL in different sampling seasons, and the effect was statistically significant in all seasons except in autumn. Mixed exposure analysis revealed a potential positive trend between NEOs and newborn TL, but the association was not statistically significant. CONCLUSION: Prenatal exposure to TMX may shorten newborn TL, and this effect is more pronounced among female newborns. Furthermore, the relationship between NEO exposure and TL may be modified by the sampling season.

Evaluating offspring Genomic and Epigenomic alterations after prenatal exposure to Cancer treatment In Pregnancy (GE-CIP): a multicentric observational study.

INTRODUCTION: Around 1 in 1000-2000 pregnancies are affected by a cancer diagnosis. Previous studies have shown that chemotherapy during pregnancy has reassuring cognitive and cardiac neonatal outcomes, and hence has been proposed as standard of care. However, although these children perform within normal ranges for their age, subtle differences have been identified. Given that chemotherapeutic compounds can cross the placenta, the possibility that prenatal chemotherapy exposure mutates the offspring's genome and/or epigenome, with potential deleterious effects later in life, urges to be investigated. METHODS AND ANALYSES: This multicentric observational study aims to collect cord blood, meconium and neonatal buccal cells at birth, as well as peripheral blood, buccal cells and urine from infants when 6, 18 and/or 36 months of age. Using bulk and single-cell approaches, we will compare samples from chemotherapy-treated pregnant patients with cancer, pregnant patients with cancer not treated with chemotherapy and healthy pregnant women. Potential chemotherapy-related newborn genomic and/or epigenomic alterations, such as single nucleotide variants, copy number variants and DNA-methylation alterations, will be identified in mononuclear and epithelial cells, isolated from blood, buccal swabs and urine. DNA from maternal peripheral blood and paternal buccal cells will be used to determine de novo somatic mutations in the neonatal blood and epithelial cells. Additionally, the accumulated exposure of the fetus, and biological effective dose of alkylating agents, will be assessed in meconium and cord blood via mass spectrometry approaches. ETHICS AND DISSEMINATION: The Ethics Committee Research of UZ/KU Leuven (EC Research) and the Medical Ethical Review Committee of University Medical Center Amsterdam have approved the study. Results of this study will be disseminated via presentations at (inter)national conferences, through peer-reviewed, open-access publications, via social media platforms aimed to inform patients and healthcare workers, and through the website of the International Network on Cancer, Infertility and Pregnancy (www.cancerinpregnancy.org).

Environmental Exposure to Pesticides and the Risk of Child Neurodevelopmental Disorders.

Background and Objectives: Neurodevelopment is a fragile brain process necessary for learning from the beginning of childhood to adulthood. During the procedure, several risks could affect it, including environmental factors such as neurotoxic chemicals or environmental pollutants and, within them, exposure to pesticides. Materials and Methods: This ecological descriptive study attempted to assess the association between environmental exposure to pesticides and neurodevelopmental disorders. This study was conducted on 4830 children diagnosed for 11 years in a total population of 119,897 children in three areas: high, medium, and low greenhouse concentrations. Results: Chromosomal abnormalities were the most common prenatal disorder (28.6%), while intrauterine physical factors were the least common (0.5%). Among perinatal diagnoses, gestational age less than 32 weeks was the most common (25%), while hyperbilirubinemia requiring exchange transfusion and birth complications was the least common (0.4%). Brain damage was the most common problem detected in postnatal diagnosis (36.7%), while unspecified postnatal abnormalities were the least common (3.1%). Conclusions: The areas with the highest greenhouse concentration had higher incidences of neurodevelopmental disorders, particularly in boys, and lower age of referral. Chromosomal abnormalities were prevalent for prenatal diagnoses, gestational age below thirty-two weeks for perinatal diagnoses, and brain damage for postnatal diagnoses. Future studies should analyze the connection between pesticide exposure and neurodevelopmental disorders using spatial point pattern analysis.

Prenatal Fluoxetine Exposure Influences Glucocorticoid Receptor-Mediated Activity in the Prefrontal Cortex of Adolescent Rats Exposed to Acute Stress.

Any deviation from the programmed processes of brain development may modify its formation and functions, thereby precipitating pathological conditions, which often become manifest in adulthood. Exposure to a challenge during crucial periods of vulnerability, such as adolescence, may reveal molecular changes preceding behavioral outcomes. Based on a previous study showing that prenatal fluoxetine (FLX) leads to the development of an anhedonic-like behavior in adult rats, we aimed to assess whether the same treatment regimen (i.e., fluoxetine during gestation; 15 mg/kg/day) influences the ability to respond to acute restraint stress (ARS) during adolescence. We subjected the rats to a battery of behavioral tests evaluating the development of various phenotypes (cognitive deficit, anhedonia, and anxiety). Furthermore, we carried out molecular analyses in the plasma and prefrontal cortex, a brain region involved in stress response, and whose functions are commonly altered in neuropsychiatric conditions. Our findings confirm that prenatal manipulation did not affect behavior in adolescent rats but impaired the capability to respond properly to ARS. Indeed, we observed changes in several molecular key players of the hypothalamic pituitary adrenal axis, particularly influencing genomic effects mediated by the glucocorticoid receptor. This study highlights that prenatal FLX exposure influences the ability of adolescent male rats to respond to an acute challenge, thereby altering the functionality of the hypothalamic-pituitary-adrenal axis, and indicates that the prenatal manipulation may prime the response to challenging events during this critical period of life.

Outdoor fine particulate matter exposure and telomere length in humans: A systematic review and meta-analysis.

Although the association between changes in human telomere length (TL) and ambient fine particulate matter (PM2.5) has been documented, there remains disagreement among the related literature. Our study conducted a systematic review and meta-analysis of epidemiological studies to investigate the health effects of outdoor PM2.5 exposure on human TL after a thorough database search. To quantify the overall effect estimates of TL changes associated with every 10 µg/m3 increase in PM2.5 exposure, we focused on two main topics, which were outdoor long-term exposure and prenatal exposure of PM2.5. Additionally, we included a summary of short-term PM2.5 exposure and its impact on TL due to limited data availability. Our qualitative analysis included 20 studies with 483,600 participants. The meta-analysis showed a statistically significant association between outdoor PM2.5 exposure and shorter human TL, with pooled impact estimates (ß) of -0.12 (95% CI: -0.20, -0.03, I2= 95.4%) for general long-term exposure and -0.07 (95% CI: -0.15, 0.00, I2= 74.3%) for prenatal exposure. In conclusion, our findings suggest that outdoor PM2.5 exposure may contribute to TL shortening, and noteworthy associations were observed in specific subgroups, suggesting the impact of various research variables. Larger, high-quality studies using standardized methodologies are necessary to strengthen these conclusions further.

Association between prenatal antipsychotic exposure and the risk of attention-deficit/hyperactivity disorder and autism spectrum disorder: a systematic review and meta-analysis.

The paucity of evidence regarding the safety of gestational antipsychotic exposure has led to treatment discontinuation in pregnant women with severe mental health conditions. This systematic review and meta-analysis aimed to summarise the current evidence on the association between gestational antipsychotic exposure and attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children (Study protocol registered in PROSPERO:CRD42022311354). Five studies included in our meta-analysis with around 8.6 million pregnancy episodes in nine different countries/regions. Results from our meta-analysis indicate that the heightened risks of ASD and ADHD in children gestationally exposed to antipsychotics appear to be attributable to maternal characteristics, rather than having a causal relationship with the antipsychotic exposure during pregnancy. The results underscore the importance of meticulously monitoring the neurodevelopment of children born to mothers with mental illnesses, which can facilitate early interventions and provide requisite support.

Independent and Combined Effects of Prenatal Alcohol Exposure and Prenatal Stress on Fetal HPA Axis Development.

Prenatal alcohol exposure (PAE) and prenatal stress (PS) are highly prevalent conditions known to affect fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis. The objectives of this study were to assess the effect of light PAE, PS, and PAE-PS interaction on fetal HPA axis activity assessed via placental and umbilical cord blood biomarkers. Participants of the ENRICH-2 cohort were recruited during the second trimester and classified into the PAE and unexposed control groups. PS was assessed by the Perceived Stress Scale. Placental tissue was collected promptly after delivery; gene and protein analysis for 11ß-HSD1, 11ß-HSD2, and pCRH were conducted by qPCR and ELISA, respectively. Umbilical cord blood was analyzed for cortisone and cortisol. Pearson correlation and multivariable linear regression examined the association of PAE and PS with HPA axis biomarkers. Mean alcohol consumption in the PAE group was ~2 drinks/week. Higher PS was observed in the PAE group (p < 0.01). In multivariable modeling, PS was associated with pCRH gene expression (ß = 0.006, p < 0.01), while PAE was associated with 11ß-HSD2 protein expression (ß = 0.56, p < 0.01). A significant alcohol-by-stress interaction was observed with respect to 11ß-HSD2 protein expression (p < 0.01). Results indicate that PAE and PS may independently and in combination affect fetal programming of the HPA axis.