Even moderate exposures to pesticides and plasticizers have been associated with neurotoxicity and autism characteristics; however, most studies of urine and blood provide a short-term exposure window compared to teeth, which capture long-term exposures from 13-14 weeks in-utero through early childhood. We investigated cumulative pesticide and plasticizer exposures in shed baby teeth from children with and without autism using a comprehensive targeted and non-targeted analysis with two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GCxGC-TOFMS). Compound identification was confirmed with standards and high-fidelity spectral library matches. Sixty compounds were detected in more than 50% of participants (n = 38). Of these, 95% (57/60) were higher in cases compared to controls, and 19/60 were statistically significantly elevated. Thirty-nine of the 60 compounds detected are known developmental toxicants or endocrine-disrupting compounds. To date, 21/60 compounds lack Environmental Protection Agency (EPA) developmental toxicity data. Compounds exhibiting higher levels in cases than in controls include benzyl benzoate (fragrance and food preservative) and organophosphate esters, which are frequently found in flame retardants and other baby products, PEX tubing, food contact materials, and products applied to the skin. Interestingly, five of the top nine compounds that differentiated cases from controls migrate from baby bottles. Elevated levels of toxicants in autism cases in our pilot study highlight a need for larger case-control studies to understand the effects of long-term exposure on autism.
OBJECTIVE:This exploratory pilot study evaluated whether subchronic late-gestational oral nicotine exposure alters postpartum maternal behavior in Wistar rats. METHODS:Twelve pregnant Wistar rats were obtained in three successive intake batches and randomly assigned to experimental or control groups. Control animals received a 2% saccharin solution; experimental animals received nicotine (nominal 200 μg/mL) in 2% saccharin solution ad libitum from gestational day 7 through parturition. The initial concentration of 200 μg/mL produced two maternal deaths and one embryonic reabsorption in the first experimental batch; the solution was diluted approximately 1:3 to ∼50 μg/mL for the third experimental batch. Postpartum maternal behavior was scored from 15-min light-phase video samples (three 5-min blocks at 5-s instantaneous sampling) on each of the 14 postpartum days. Dependent variables were daily frequency counts of 19 ethogram behaviors organized into proximal, nest-related, motor, and self-maintenance categories. Primary analyses were 2 × 14 mixed repeated-measures ANOVAs. Fluid consumption, litter parameters, and cohort attrition are also reported. RESULTS:Experimental dams reduced solution consumption by approximately 81% relative to their pre-nicotine water baseline, indicating that actual nicotine exposure was substantially below the nominal concentration. Among the three surviving dams per group, proximal maternal behaviors showed no reliable group differences on either parametric or non-parametric tests. The clearest between-group difference was in eating frequency (controls > experimentals; F(1, 4) = 48.96, p = .002, ηp2 = 0.92). A significant Day × Group interaction was observed for locomotion, concentrated on postpartum days 11-12. CONCLUSIONS:In this small pilot, subchronic late-gestational nicotine exposure did not produce consistent alterations in core proximal maternal behaviors among surviving dams, but was associated with substantial gestational losses, reduced maternal fluid intake, a qualitative low-pup-birth-weight observation, and a postpartum eating-frequency difference that cannot be unambiguously attributed to nicotine pharmacology. The findings are hypothesis-generating and motivate adequately powered replication with cotinine verification and gravimetric pup-weight measurement.
Periconceptional and prenatal tobacco exposure (PPTE) has been associated with early externalizing behaviors, yet the developmental pathways underlying this association remain poorly understood. The purpose of this study was to examine potential mechanisms through which PPTE may relate to child behavior. Data were drawn from a prospective, longitudinal cohort of mother-child dyads recruited at birth. The final sample included 203 mothers, predominantly White, with lower income, education, and partnership rates observed among heavier smoking groups. The study collected socio-demographic information and measures of maternal psychological distress, child language ability and behavior. PPTE, defined in this study as a continuous variable representing the average number of cigarettes smoked per day three months prior and during pregnancy, was the primary exposure variable. Maternal psychological distress and child language development were evaluated as potential intervening pathways. A path model was used to evaluate the relative contribution of direct and indirect effects of PPTE on externalizing behavior at 24-months. PPTE significantly predicted both greater maternal psychological distress and poorer child language ability. Both variables were associated with higher externalizing behaviors. In the indirect effects model, the direct effect of PPTE on externalizing behaviors was nonsignificant, while multiple indirect pathways were significant, including via child language development and maternal psychological distress. Findings suggest that the association between PPTE and externalizing behaviors may operate indirectly through maternal psychological distress and child language development.
Fluid reasoning (Gf), the ability to solve novel problems without prior knowledge, is a highly integrative skill with far-reaching impacts on multiple domains of functioning including attention and working memory. Gf abilities like abstract reasoning rapidly develop throughout childhood and adolescence in tandem with the maturation of underlying functional brain networks. With such dynamic plasticity, these networks are also critically vulnerable to the neurotoxic effects of environmental exposures. Herein, we characterized the links between chronic exposure to indoor radon, a ubiquitous toxin that commonly remains unmitigated, and the neural dynamics supporting Gf. A total of 101 neurotypical youth ages 8-to-15 years-old (M = 12.34 ± 2.23 years; 51 males) completed an abstract reasoning task during magnetoencephalography and completed a long-term home radon test to quantify home radon concentrations. We found that as a function of greater home radon exposure, youth were significantly slower to respond during the abstract reasoning task (b = 45.88, p = .047). Further, youth exhibited stronger theta responses in the right superior temporal gyrus (β = 0.33, p = .002), and stronger alpha/beta responses in the right medial prefrontal cortex (β = -0.36, p < .001) with greater radon exposure. The data suggested an overall pattern of radon-related neural inefficiency when engaging in Gf processing, which could have long-term impacts on extended neurocognitive outcomes. These findings highlight the importance of continued study of the potential neurotoxic effects of chronic home radon exposure on youth, and reiterate the need for greater public awareness regarding indoor radon safety.
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.
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.
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.
Electroacupuncture (EA) effectively enhances postoperative cognitive function in the elderly, though its underlying mechanism remains largely unexplored. This study aimed to explore the role of the p38 MAPK signaling pathway in how EA alleviates anesthesia/surgery-induced cognitive impairment in aged rats. We developed a POCD model using sevoflurane anesthesia and exploratory laparotomy in aged rats to evaluate whether EA at the Neiguan, Hegu and Zusanli points influences synaptic plasticity in the POCD pathological process. The Novel object recognition test assessed postoperative cognitive function. Nissl staining is used to evaluate the pathological changes of neurons. Changes in synaptic function and its potential mechanism were assessed using RNA-seq, Golgi-cox staining, Western blot and Immunofluorescence assay. The study found that anesthesia and surgery notably impaired cognitive performance and synaptic function in the hippocampal CA1 region of aged rats. EA improved cognitive function, restored hippocampal synaptic function, decreased the phosphorylated p38 and increase the PSD-95 and synaptophysin expression level in POCD rats. In conclusion, EA ameliorated POCD in aged rats, potentially by enhancing synaptic function via inhibition of the p38 MAPK signaling pathway.
BACKGROUND AND OBJECTIVES:Pediatric neurotoxicity remains a major cause of morbidity and mortality in low- and middle-income countries. In Morocco, the burden of toxic exposures leading to neurological disorders is still underexplored. This study aimed to describe the epidemiology, clinical profile, toxicological features, and outcomes of pediatric neurotoxic poisonings in a tertiary care hospital in Fez, Morocco. METHODS:A prospective cross-sectional study was conducted from January 2021 to January 2023 at the Pediatric Emergency Units of Hassan II University Hospital. Pediatric patients under 18 years presenting with neurological symptoms secondary to confirmed or suspected toxic exposures were included. Demographic, clinical, and toxicological data were collected using standardized forms, complemented by biological sampling and advanced toxicological analyses. RESULTS:Among 4183 pediatric emergency admissions, 743 (17.8%) presented with neurological disorders, of which 384 (51.7%) were attributed to toxic exposures. Of these 384 cases, major agents included pharmaceuticals, traditional herbal remedies, pesticides, venoms, and illicit substances. Multiple exposures were observed in 55% of cases, and 70% resulted from repeated exposure. Intensive care was required in 29.1% of patients, and overall mortality reached 11.9%, with phytotherapy, illicit drugs, and pesticides being the leading causes of death. Delayed consultation and limited antidote availability were major challenges. CONCLUSIONS:Pediatric neurotoxicity is highly prevalent in Morocco, shaped by a unique combination of cultural and environmental risk factors. These findings underscore the urgent need for strengthened toxicovigilance, regulation of hazardous substances, public education, and improved diagnostic and therapeutic resources.
Recently, it has been reported that 20% of pregnant women in the U.S. and Canada use cannabidiol (CBD) during pregnancy (Bhatia et al., 2024). The common perception is that CBD exposure is harmless to the fetus. However, the effects of CBD on the developing fetus are not well known, hampered by potential polydrug use, limited information on CBD levels in products, and varying drug administrative routes. Animal models may increase our understanding of the safety of CBD use during pregnancy. The current study exposed pregnant Sprague-Dawley rats to 50 mg/kg CBD or control vehicle once daily from gestational days 5-20. CBD was dissolved in honey and delivered via a cookie dough edible; controls received a cookie dough edible with no CBD. Exposure to CBD during gestation reduced the number of pups born and tended to increase the ratio of male-female pups by reducing the number of female pups, indicative of possible hormonal changes. Open field activity was examined in the offspring on postnatal days 30-34 (early adolescence) during the dark cycle. Prenatal CBD exposure significantly increased activity levels, impaired habituation, and increased risk-taking behavior in females, but not males. These data illustrate that prenatal CBD exposure may adversely impact behavioral development in a sex-dependent manner. Elucidation of the risks associated with CBD use during pregnancy is critical to inform pregnant women and promote healthy pregnancies.
Minamata disease, officially recognized in 1956, is a well-known food poisoning event that was caused by the consumption of fish and seafood contaminated with methylmercury. Although patients with congenital Minamata disease (CMD) with severe neurological impairments after birth are widely recognized, few studies have examined the effects of prenatal methylmercury exposure among residents, which is likely at lower levels than in CMD patients. We aimed to investigate the relationship between prenatal methylmercury exposure and subsequent neurological and neurocognitive outcomes. We conducted a cross-sectional study during 2024-2025 among 51 individuals aged approximately 70 years, 27 residents from an existing cohort established in 1970 in Minamata and 24 age-matched individuals who had lived in less-exposed regions. We performed a battery of neurological and neurocognitive tests in both groups and compared the results using multiple linear regression analyses. We also examined the association between intelligence scores obtained in 1970, and intelligence scores obtained in the present investigation, only among exposed participants. We found that exposed individuals had unfavorable neurological and neurocognitive test scores, in comparison with less-exposed controls. Scores on the Montreal Cognitive Assessment, Japanese Edition were 5.91 points lower (95% confidence interval: 3.09 to 8.73) for exposed residents than for the less-exposed group. Moreover, intelligence scores evaluated during exposed participants' adolescence were correlated with their neurocognitive scores in adulthood. Our findings showed that prenatal methylmercury exposure affected subsequent neurological and neurocognitive functions, including among individuals with lower exposure than in CMD patients, and even approximately 70 years after the initial exposure.
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 TNF-α and IL-1β. 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.
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 c, may serve as diagnostic indicators of cadmium-associated neurodegeneration.
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 Latrophiln-3 (LPHN-3). Using CRISPR/Cas9 we deleted exon 3 in Sprague Dawley rats to create a global Lphn3 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 Lphn3 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 (Regan et al., 2022). 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 Lphn3 and PRM but there were effects of Lphn3 heterozygosity. The results indicate that heterozygosity of the ADHD risk gene Lphn3 when combined with developmental exposure to PRM increases the adverse effects of either one alone.
Excessive exposure to monosodium glutamate (MSG) induces glutamate-mediated excitotoxicity, oxidative stress, and neuroinflammation, culminating in neurobehavioral impairments. Bromelain, a cysteine protease derived from Ananas comosus, 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 >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.
BACKGROUND: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. METHODS: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. RESULTS:A three-class solution demonstrated best model fit (AIC = 3945.216, saBIC = 3970.790, aLRT = 18.521, p = .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, p = .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. DISCUSSION: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.
INTRODUCTION:Microcephaly, a condition characterized by a head circumference below the mean for age and sex, is a significant indicator of impaired fetal brain development. While some environmental factors have been associated with the development of microcephaly in Africa, the available information remains disjointed, making it difficult for healthcare providers and policy makers to translate the information to preventive measures in maternal and child health. This systematic review aims to synthesize primary studies on environmental determinants of microcephaly, focusing on African populations. METHOD:A systematic literature search was conducted using PubMed, Scopus, AJOL, and Wiley Online Library to identify studies published between 2000 and 2025, focusing on environmental exposures and microcephaly in neonates and infants. Observational and interventional studies in English were included, following PRISMA 2020 guidelines. Data were extracted and tabulated by country, exposure type, study design, and reported outcomes. RESULTS:Sixteen African studies found a multifactorial relationship between environmental exposures and microcephaly. Zika virus infection was a consistent contributor, with maternal febrile illnesses, inadequate antenatal care, HIV exposure, and heavy metal toxicity also linked. Pesticide exposure, particularly to organophosphates and DDT, was associated with neurodevelopmental delays and restricted cranial growth. Ambient air pollution was negatively correlated with neonatal head circumference. Socioeconomic vulnerabilities intensified these environmental risks, especially during epidemic crises like Zika virus outbreaks. CONCLUSION:Microcephaly in African populations is a multifactorial issue, influenced by emerging infections like ZIKV, chronic environmental exposures, and healthcare gaps. It calls for integrated public health strategies, including surveillance, early prenatal screening, environmental regulation, and region-specific diagnostic standards. Global evidence supports shared biological vulnerability in low-resource settings.
BACKGROUND:Exposure to ambient air pollution, including fine particulate matter (PM2.5), nitrogen dioxide (NO2), and elemental carbon, has been associated with worse neurodevelopmental outcomes in children, but research on early childhood outcomes is limited. OBJECTIVE:This study examined the associations between gestational and early childhood exposures to PM2.5 and NO2 and child developmental outcomes measured at ages 1, 2, and 3 years. METHODS: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). RESULTS: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, PM2.5 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. DISCUSSION:These results suggest that exposure to traffic-related air pollution during gestation and after birth may impact neurodevelopment in early childhood.
BACKGROUND: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. OBJECTIVE:We investigated the prenatal trimester-specific neuroprogramming effects of the phthalate burden scores on fluid cognition in Mexican children. METHODS:Children (n = 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. RESULTS:In the 3rd trimester, higher LMW phthalate burden was associated with poorer fluid cognition (b = -1.860; [95 % CI = -3.505, -0.215]; p = 0.027), while HMW phthalate burden showed a positive association (b = 1.815; [95 % CI = 0.176, 3.453]; p = 0.030). Conversely, in the 2nd trimester, neither burden levels of LMW (b = -0.508; [95 % CI = -1.639, 0.623]; p = 0.378) nor HMW (b = 0.451; [95 % CI = -0.671, 1.573]; p = 0.431]; p = 0.44) phthalate demonstrated significant associations with fluid cognitive performance. CONCLUSION: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.
