Neurotoxicology and teratology最新文献

{"title":"Prenatal methamphetamine exposure increased addiction vulnerability through neural circuit dysfunction and epigenetic modifications in offspring","authors":"Yuqi Wang ,&nbsp;Daiju Tao ,&nbsp;Rongji Sun ,&nbsp;Li Zhang ,&nbsp;Renhua Yang ,&nbsp;Ying Shen ,&nbsp;Haiyu Su ,&nbsp;Bingquan Chen ,&nbsp;Zhiqiang Shen ,&nbsp;Peng Chen ,&nbsp;Bo He","doi":"10.1016/j.ntt.2026.107604","DOIUrl":"10.1016/j.ntt.2026.107604","url":null,"abstract":"<div><div>Methamphetamine (METH), a type of synthetic drug with effects similar to amphetamines, remains a significant public health concern, particularly among women of childbearing age. Prenatal methamphetamine exposure (PME) has been demonstrated to negatively affect fetal neurodevelopment and increase addiction in exposed individuals. Although there is increasing evidence of transgenerational effects, the molecular mechanisms that mediate addiction vulnerability induced by PME are not yet fully understood. In this comprehensive review, we combine findings from epidemiology and mechanistic studies using animal models to create a more complete picture regarding the mechanisms by which PME changes the neural circuitry, through its effects on the ventral tegmental area (VTA), nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus. There is an increasing body of research on epigenetics that illustrates a relationship between epigenetic alterations to DNA via methylation, histone modifications, and the dysregulation of non-coding RNAs in neurodevelopmental programming and the eventual treatment outcomes for substance use disorders. Elucidating these neurobiological mechanisms provides critical insights for identifying vulnerable populations, developing targeted interventions, and establishing evidence-based strategies to mitigate addiction risk in PME-affected offspring.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"115 ","pages":"Article 107604"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postnatal environment differentially modulates neurodevelopmental outcomes following voluntary prenatal oxycodone exposure in rats","authors":"Kelsea R. Gildawie ,&nbsp;Kerri E. Budge ,&nbsp;Sara B. Isgate ,&nbsp;Jillian Celatka ,&nbsp;Megan Gulsby ,&nbsp;Cora C. Cunningham ,&nbsp;Fair M. Vassoler ,&nbsp;Elizabeth M. Byrnes","doi":"10.1016/j.ntt.2026.107603","DOIUrl":"10.1016/j.ntt.2026.107603","url":null,"abstract":"<div><div>As prenatal opioid exposure becomes increasingly prevalent, understanding which neurodevelopmental effects are amenable to postnatal intervention has become a critical question. Clinically, prenatal exposure and maternal factors that affect offspring development often co-occur, making it difficult to determine which developmental outcomes are directly attributable to drug effects versus postnatal environmental influences. Preclinical models can be useful in disentangling these interacting factors. Using a rat model of voluntary maternal Oxycodone (Oxy) self-administration, we examined whether postnatal rearing environment could ameliorate neonatal opioid withdrawal syndrome (NOWS)-like symptoms. Cross-fostering separated prenatal drug effects from postnatal rearing and revealed differential sensitivity to environmental modification. Altered ultrasonic vocalizations were rescued when Oxy-exposed offspring were reared by drug-naïve dams, while increased motor activity persisted regardless of rearing condition. Oxy-exposed offspring reared by Oxy-exposed dams showed a distinct developmental trajectory characterized by increased vocal power and reduced frequency variability. These early alterations persisted across the postnatal period. Unexpectedly, maternal opioid intake levels during pregnancy did not predict NOWS-like symptom severity. However, early vocalization patterns did show group-specific predictive relationships with adult markers (plasma corticosterone and nucleus accumbens MeCP2 expression), suggesting potential continuity between early behavioral alterations and later physiological changes. The functional significance of these relationships requires further investigation. Overall, some, but not all, developmental effects of prenatal opioid exposure could be ameliorated by the postnatal rearing environment. These findings suggest that early behavioral profiles may help identify offspring at greatest risk for persistent developmental alterations, highlighting the potential value of early assessment and postnatal intervention.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"115 ","pages":"Article 107603"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spermatogenic timing, dose, and route of administration as determinants of paternal transmission of developmental neurotoxicity","authors":"Issam Rimawi,&nbsp;Joseph Yanai","doi":"10.1016/j.ntt.2026.107605","DOIUrl":"10.1016/j.ntt.2026.107605","url":null,"abstract":"<div><div>Growing evidence challenges the long-standing assumption that the paternal germline is insulated from environmental perturbation and identifies preconception paternal exposure as an underrecognized pathway of developmental neurotoxicity. Across mammalian models, paternal exposure to substances of abuse, including cocaine, nicotine, ethanol, morphine, and cannabinoids, induces reproducible, often sex-specific alterations in offspring brain function and behavior, including changes in cognition, stress responsivity, reward processing, and affective behaviors, accompanied by transcriptional and epigenetic modifications. A critical but underappreciated determinant of these outcomes is exposure design, particularly exposure duration relative to the spermatogenic cycle, which emerges as a primary toxicodynamic relevant variable. Exposures spanning a full spermatogenic cycle frequently produce persistent neurobehavioral and molecular alterations, whereas shorter exposures targeting late spermatids or mature sperm can also generate robust offspring phenotypes, highlighting stage-specific germ cell vulnerability. Importantly, delaying mating beyond a complete spermatogenic cycle often attenuates offspring effects, suggesting that temporal separation between exposure and conception may mitigate neurodevelopmental risk. Mechanistically, paternal exposures disrupt sperm epigenetic regulation, including altered DNA methylation, histone modifications, and small RNA profiles, often linked to germline oxidative stress as a potential upstream mediator. Exposure dose and route further modulate transmission through pharmacokinetic effects on systemic and germline exposure. We propose a stage-specific framework in which paternal transmission magnitude and persistence are primarily determined by exposure duration relative to spermatogenesis, with dose and route acting as key modifiers. This framework integrates behavioral and molecular findings and provides a biologically grounded basis for developmental neurotoxicity risk assessment and male preconception health.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"115 ","pages":"Article 107605"},"PeriodicalIF":2.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147818248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bromelain mitigates monosodium glutamate-induced neurobehavioral impairment in mice by modulating AChE-MAO-GAD and oxido-inflammatory pathways: Experimental and computational insights","authors":"Joseph Chimezie ,&nbsp;Noah A. Omeiza ,&nbsp;Oludare M. Ogunyemi ,&nbsp;Abayomi M. Ajayi ,&nbsp;Jude I. Abeje ,&nbsp;Nafisat O. Abdullahi ,&nbsp;Grace O. Isehunwa ,&nbsp;Solomon Owumi ,&nbsp;Temitope G. Adedeji","doi":"10.1016/j.ntt.2026.107586","DOIUrl":"10.1016/j.ntt.2026.107586","url":null,"abstract":"<div><div>Excessive exposure to monosodium glutamate (MSG) induces glutamate-mediated excitotoxicity, oxidative stress, and neuroinflammation, culminating in neurobehavioral impairments. Bromelain, a cysteine protease derived from <em>Ananas comosus</em>, exhibits potent antioxidative and anti-inflammatory properties; however, its potential to attenuate excitotoxic neuronal injury remains insufficiently characterized. This study investigated the neuroprotective effects of bromelain against MSG-induced neurotoxicity through integrated behavioral, biochemical, histological, and computational analyses. Male Swiss mice (7–8 weeks) received MSG (4 g/kg, i.p.) to induce excitotoxicity and were subsequently treated orally with bromelain (50 or 100 mg/kg) or fluoxetine (1 mg/kg) for 21 days. Behavioral tests assessed locomotor, cognitive, and affective functions, while biochemical and histological analyses evaluated oxidative stress, neuroinflammatory markers, and neurotransmitter-modulating enzyme activities. In silico AlphaFold3 modeling and protein–protein docking were employed to elucidate bromelain's interactions with acetylcholinesterase (AChE), monoamine oxidase-B (MAO-B), and glutamate decarboxylase (GAD). Bromelain treatment significantly ameliorated MSG-induced behavioral deficits, restored cortical and hippocampal redox balance, suppressed pro-inflammatory cytokines, and preserved neuronal cytoarchitecture. It normalized neurotransmitter metabolism by inhibiting AChE and MAO-B activities while enhancing GAD function. AlphaFold3 modeling revealed a compact, high-confidence bromelain conformation (pLDDT &gt;90) with strong predicted binding affinities to catalytically active residues of AChE, MAO-B, and GAD, supporting its multi-target neuromodulatory role. Altogether, these findings provide the first integrated experimental and computational evidence that bromelain confers neuroprotection by regulating redox homeostasis, inflammation, and neurotransmitter signaling, highlighting its promise as a nutraceutical candidate for mitigating glutamate-mediated neurodegenerative disorders.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"114 ","pages":"Article 107586"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146172212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Profiles of polysubstance exposure in youth with fetal alcohol spectrum disorders and the association with neurodevelopmental outcomes","authors":"Madeline N. Delage ,&nbsp;Emily L. Speybroeck ,&nbsp;Alesia A. Richardson ,&nbsp;Lynn L. Cole ,&nbsp;Carson Kautz-Turnbull ,&nbsp;Christie L.M. Petrenko","doi":"10.1016/j.ntt.2026.107585","DOIUrl":"10.1016/j.ntt.2026.107585","url":null,"abstract":"<div><h3>Background</h3><div>Prenatal polysubstance exposure is highly prevalent among individuals with fetal alcohol spectrum disorders (FASD), yet little research has examined how specific patterns of co-exposure relate to neuropsychological outcomes. While alcohol is a known teratogen, other substances such as opioids, stimulants, cannabis, and nicotine also disrupt neurodevelopmental processes. Prior studies often assess single substances in isolation, failing to reflect real-world exposure patterns. Identifying meaningful patterns of co-occurring exposures and their associations with neuropsychological outcomes is critical for advancing targeted assessment and intervention.</div></div><div><h3>Methods</h3><div>Latent class analysis was conducted on data from 635 youth with FASD (mean age of diagnosis 7.4 years, range 0.24–21.61) to identify distinct profiles of prenatal exposure to six substances: alcohol, nicotine, marijuana, opioids, cocaine, and other drugs. Class differences in neuropsychological functioning, postnatal experiences, and demographics were examined using the Bolck, Croon, and Hagenaars method.</div></div><div><h3>Results</h3><div>A three-class solution demonstrated best model fit (AIC = 3945.216, saBIC = 3970.790, aLRT = 18.521, <em>p</em> = .006). Classes comprised of an all-exposure (Class 1, 47%), mainly alcohol exposed (Class 2, 46%), and mainly opioid exposed (Class 3, 7%). Significant between-class differences emerged across domains of memory, motor speed, sensory processing, and child-reported anxiety (χ² = 9.264–42.659, <em>p</em> = .046–0.001). Class 2 demonstrated significantly greater neuropsychological challenges, while Class 3 demonstrated high sensory sensitivity and anxiety. Results also reveal caregiver disruption was more prevalent in Class 2.</div></div><div><h3>Discussion</h3><div>Findings highlight heterogeneity in neuropsychological outcomes based on distinct patterns of prenatal polysubstance exposures. Neuropsychological assessment remains essential for capturing this variability and informing individualized, exposure-responsive care.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"114 ","pages":"Article 107585"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"S-adenosyl-L-methionine reverses ethanol-induced developmental toxicity in FASD model of Danio rerio embryos via dual-modulation of oxidative stress and glutathione homeostasis","authors":"Prasanth Babu Nandagopal,&nbsp;Anu Varghese Kaithamattathil,&nbsp;Gopika Jayakrishnan,&nbsp;Sampath Raghul Kannan,&nbsp;Ramasamy Tamizhselvi,&nbsp;Venkatraman Manickam","doi":"10.1016/j.ntt.2026.107589","DOIUrl":"10.1016/j.ntt.2026.107589","url":null,"abstract":"<div><div>Fetal Alcohol Spectrum Disorder (FASD) represents a major global public health concern, affecting approximately 7.7 per 1000 births worldwide and remains as the most common preventable cause of lifelong neurodevelopmental impairment. Despite its prevalence, current clinical interventions are largely symptom-supportive and fail to address the underlying developmental pathology, underscoring the need for targeted, mechanism-based therapeutic strategies. Given the central involvement of oxidative stress and inflammation in FASD pathogenesis, this study evaluated the protective efficacy of S-adenosyl-L-methionine (SAMe), a key metabolic intermediate and universal methyl donor, using a zebrafish embryo model because of its high translational relevance and optical transparency. Fertilized embryos were exposed to 1.25% ethanol and co-treated with SAMe (15 and 30 μM) until 96 h post-fertilization (hpf). Ethanol exposure resulted in reduced survival and hatching rates, cardiac rhythm abnormalities, pronounced morphological defects, and compromised tissue integrity. SAMe treatment, particularly at 30 μM, significantly ameliorated these developmental abnormalities and associated biochemical dysregulations. Mechanistically, SAMe exerted a dual protective effect by restoring glutathione biosynthesis and attenuating oxidative stress-driven inflammatory responses. This was evidenced by marked reductions in reactive oxygen species, apoptosis, lipid peroxidation, and nitric oxide levels, alongside significant downregulation of pro-inflammatory cytokines, including <em>TNF-α</em> and <em>IL-1β</em>. Importantly, these biochemical and molecular improvements were consistently translated into phenotypic rescue, with substantial normalization of tissue architecture and developmental morphology. Collectively, these findings establish SAMe as a promising anti-teratogenic intervention that directly targets core oxidative and inflammatory pathways underlying FASD, highlighting its potential translational relevance as a mechanism-driven therapeutic strategy.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"114 ","pages":"Article 107589"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene × environment interaction between latrophilin-3 (Lphn3 or Adgrl3) and developmental permethrin exposure in Sprague Dawley rats","authors":"Charles V. Vorhees,&nbsp;Adam L. Fritz,&nbsp;Brooke M. Gollaway,&nbsp;Michael T. Williams","doi":"10.1016/j.ntt.2026.107587","DOIUrl":"10.1016/j.ntt.2026.107587","url":null,"abstract":"<div><div>Attention deficit hyperactivity disorder (ADHD) occurs in 9.8% of U.S. children and has a large hereditary component arising from multiple gene variants. One of these is <em>Latrophiln-3</em> (<em>LPHN-3</em>). Using CRISPR/Cas9 we deleted exon 3 in Sprague Dawley rats to create a global <em>Lphn3</em> knockout (gKO). The gKO rats are hyperactive, startle hyper-reactive, impulsive, and have impaired working, spatial, and egocentric learning and memory. Permethrin (PRM) is a widely used pyrethroid insecticide. Acute exposure to PRM alters acoustic startle but its long-term effects from developmental exposure are unknown. The present experiment tested whether <em>Lphn3</em> heterozygosity interacts with PRM developmental exposure to affect post exposure neurobehavior in rats. We used Lphn3^+/− (Het) rats since they have an intermediate phenotype compared with gKO rats that are severely affected (<span><span>Regan et al., 2022</span></span>). There were 4 groups: Lphn3-Het + PRM (120 mg/kg daily by gavage from postnatal day (P) 6–20 in 5 mL/kg corn oil (CO)), Lphn3-Het + CO, wildtype (WT) + PRM, and WT + CO. From 25 litters, 20–22 males and 20–22 females of each combination were obtained with not more than one male and one female from any given litter. Adult offspring were tested in an automated open-field for 1 h, in home-cage activity for 72 h, startle (including prepulse inhibition), novel object recognition (NOR), working memory (radial water maze (RWM)), spatial learning (Morris water maze (MWM)), and egocentric learning in the Cincinnati water maze (CWM). On acquisition and reversal probe trials in the MWM and on learning trials in the CWM, Lphn3-Het-PRM rats performed worse than other groups. In open-field, home-cage, startle, NOR, and RWM there were no interactions between <em>Lphn3</em> and PRM but there were effects of Lphn3 heterozygosity. The results indicate that heterozygosity of the ADHD risk gene <em>Lphn3</em> when combined with developmental exposure to PRM increases the adverse effects of either one alone.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"114 ","pages":"Article 107587"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776511","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic links between cadmium and MAPK pathways leading to neurodegeneration","authors":"Sneha De ,&nbsp;Shinjini Kanrar ,&nbsp;Aluru Parithathvi ,&nbsp;P. Harshitha ,&nbsp;Herman Sunil Dsouza","doi":"10.1016/j.ntt.2026.107588","DOIUrl":"10.1016/j.ntt.2026.107588","url":null,"abstract":"<div><div>Cadmium, a Group 1 carcinogen, represents a significant public health concern due to its widespread environmental distribution and exposure through industrial processes, contaminated water, dietary intake, and tobacco use. Prolonged cadmium exposure is associated with systemic toxicity, including neurodegenerative outcomes mediated by oxidative stress, protein misfolding, neuroinflammation, and mitochondrial dysfunction. Disruption of autophagy and MAPK signalling pathways (ERK, JNK, and P38) further impairs neuronal function. Cadmium-induced misfolding of key proteins such as tau, amyloid-β, and α-synuclein is implicated in Alzheimer's and Parkinson's diseases. This systematic review aims to map the role of cadmium exposure in neurodegenerative disorders, with a focus on oxidative stress, protein misfolding, autophagy dysregulation, and MAPK signalling pathways. A thorough literature search was conducted across databases including PubMed, Scopus, and Science Direct using specific keywords. Elevated markers, including IL-6, IL-8, and cytochrome <em>c</em>, may serve as diagnostic indicators of cadmium-associated neurodegeneration.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"114 ","pages":"Article 107588"},"PeriodicalIF":2.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprogramming of prenatal phthalate exposures on fluid cognition: A latent variable modeling approach to quantify exposure burden and integrate neurobehavioral data","authors":"Jamil M. Lane ,&nbsp;Nathan Cohen ,&nbsp;Vishal Midya ,&nbsp;Cecilia S. Alcala ,&nbsp;Shoshannah Eggers ,&nbsp;Sandra Martinez-Medina ,&nbsp;Damaskini Valvi ,&nbsp;Martha M. Téllez-Rojo ,&nbsp;Deborah A. Cory-Slechta ,&nbsp;Robert O. Wright ,&nbsp;Shelley H. Liu","doi":"10.1016/j.ntt.2025.107575","DOIUrl":"10.1016/j.ntt.2025.107575","url":null,"abstract":"<div><h3>Background</h3><div>Phthalates are endocrine-disrupting chemicals with neuroactive properties linked to maladaptive neurodevelopment in children. However, few studies have utilized latent variable methodologies to estimate their cumulative impact and assess the complex integration of cognitive processes that characterize fluid cognition—the ability to efficiently process, manipulate, and integrate information to solve reasoning problems.</div></div><div><h3>Objective</h3><div>We investigated the prenatal trimester-specific neuroprogramming effects of the phthalate burden scores on fluid cognition in Mexican children.</div></div><div><h3>Methods</h3><div>Children (<em>n</em> = 626) aged 6–7 years from a prospective pregnancy cohort in Mexico City were administered subtests from the CANTAB, completing the between error, strategy, and mean latency measures intended to evaluate a broad spectrum of cognitive domains representative of fluid cognition. Phthalate metabolites were measured in maternal urine collected at 2nd and 3rd pregnancy trimesters. A CFA validated and quantified two correlated latent phthalate burden scores representing prenatal exposure to low molecular weight (LMW) and high molecular weight (HMW) phthalates. Trimester-specific models using a covariate-adjusted SEM estimated the associations of latent phthalate burden scores with a latent construct of fluid cognition, an integration of working memory, executive function, and attention tasks.</div></div><div><h3>Results</h3><div>In the 3rd trimester, higher LMW phthalate burden was associated with poorer fluid cognition (b = −1.860; [95 % CI = −3.505, −0.215]; <em>p</em> = 0.027), while HMW phthalate burden showed a positive association (b = 1.815; [95 % CI = 0.176, 3.453]; <em>p</em> = 0.030). Conversely, in the 2nd trimester, neither burden levels of LMW (b = −0.508; [95 % CI = −1.639, 0.623]; <em>p</em> = 0.378) nor HMW (b = 0.451; [95 % CI = −0.671, 1.573]; <em>p</em> = 0.431]; <em>p</em> = 0.44) phthalate demonstrated significant associations with fluid cognitive performance.</div></div><div><h3>Conclusion</h3><div>The temporal sensitivity of prenatal phthalate exposures on fluid cognition showed effects in later stages, with higher LMW burden linked to poorer performance and HMW burden showing a positive association. Our findings emphasize latent variable approaches and the need for more research on exposure-driven integrated cognitive programming.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"113 ","pages":"Article 107575"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145692907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gestational and early childhood air pollution exposure and neurodevelopmental outcomes in early childhood","authors":"Christina Berninger ,&nbsp;Yingying Xu ,&nbsp;Patrick Ryan ,&nbsp;Kim M. Cecil ,&nbsp;Bruce P. Lanphear ,&nbsp;Aimée Vester ,&nbsp;Kimberly Yolton","doi":"10.1016/j.ntt.2025.107576","DOIUrl":"10.1016/j.ntt.2025.107576","url":null,"abstract":"<div><h3>Background</h3><div>Exposure to ambient air pollution, including fine particulate matter (PM_2.5), nitrogen dioxide (NO₂), and elemental carbon, has been associated with worse neurodevelopmental outcomes in children, but research on early childhood outcomes is limited.</div></div><div><h3>Objective</h3><div>This study examined the associations between gestational and early childhood exposures to PM_2.5 and NO₂ and child developmental outcomes measured at ages 1, 2, and 3 years.</div></div><div><h3>Methods</h3><div>In the Health Outcomes and Measures of the Environment (HOME) Study, a longitudinal pregnancy and birth cohort, we used spatiotemporal models to estimate the concentration of each air pollutant at participants' home addresses during early brain development. Neurodevelopmental outcomes were measured using the Bayley Scales of Infant Development, Second Edition (BSID-II) at ages 1, 2, and 3 years. For 329 children, we examined the associations of air pollution with BSID-II scores using generalized linear models with generalized estimating equations (GEE).</div></div><div><h3>Results</h3><div>Gestational and early childhood NO₂ concentrations were positively associated with cognitive development at age 1 year but negatively associated with cognitive development at age 3 years. Similarly, PM_2.5 exposure through age 3 years was negatively associated with cognitive development at age 3 years. Gestational NO₂ concentration was positively associated with motor development at age 1 year but negatively associated with motor development at ages 2 and 3 years.</div></div><div><h3>Discussion</h3><div>These results suggest that exposure to traffic-related air pollution during gestation and after birth may impact neurodevelopment in early childhood.</div></div>","PeriodicalId":19144,"journal":{"name":"Neurotoxicology and teratology","volume":"113 ","pages":"Article 107576"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}