Skip to main content
NCBI home page
Biomolecules & Therapeutics logoLink to Biomolecules & Therapeutics
. 2025 Jun 11;33(4):557–571. doi: 10.4062/biomolther.2025.031

Association between Prenatal Particulate Matter Exposure and Neuropsychiatric Disorders Development

Ho Jung Bae 1,†, Tamanna Jahan Mony 2,†, Se Jin Park 3,4,*
PMCID: PMC12215041  PMID: 40494647

Abstract

This comprehensive review explores the relationship between prenatal exposure to particulate matter (PM) air pollution and the development of various neuropsychiatric disorders in offspring. Air pollution, specifically by PM, is a global health concern, with PM2.5 and PM10 being the most detrimental to health. This review delves into the impact of prenatal PM exposure on neurodevelopment and the onset of disorders such as cognitive impairment, Autism Spectrum Disorder (ASD), Attention Deficit Hyperactivity Disorder (ADHD), anxiety, depression, and schizophrenia. Utilizing data from international databases and focusing on full-text research papers from 2013 to 2023, we identified 18 relevant studies that explore the association between prenatal PM exposure and subsequent neuropsychiatric outcomes. The review discusses the potential mechanisms underlying these associations, including systemic inflammation, oxidative stress, and disruptions in the gut-brain axis. Key findings include the detrimental effects of PM exposure on fetal brain development, leading to cognitive deficits, heightened risk of ASD, ADHD, and altered mental health outcomes. Moreover, the review highlights the need for further research to unravel the complex interplay of genetic, environmental, and individual factors in the development of these disorders. The implications of these findings underscore the importance of reducing air pollution exposure, particularly during pregnancy, to safeguard fetal brain development and prevent neuropsychiatric disorders in offspring.

Keywords: Prenatal exposure, Particulate matter, Neuropsychiatric disorders, Neurotoxicity

INTRODUCTION

Air pollution comprises a diverse mixture of tiny solid and liquid particles that are present in the environment, and is now recognized as a significant global health concern (Block and Calderón-Garcidueñas, 2009; Hoang et al., 2021; Fernando et al., 2025). Among various air pollutants, particulate matter (PM) is notably detrimental to health, and is associated with diseases, including cardiovascular and pulmonary diseases as well as cancer (Jang et al., 2019; Costa et al., 2020; Manisalidis et al., 2020; Cho et al., 2024). PM classifications, based on aerodynamic diameters, include PM10 (coarse particles, median particle diameter ≤10 μm), PM2.5 (fine particles, median particle diameter ≤2.5 μm), and PM0.1 (ultrafine particles, median particle diameter ≤0.1 μm) (O’Piela et al., 2022). Growing evidence indicates that chronic exposure to PM2.5 or PM10 has been linked to cardiovascular disease (Guo et al., 2023), pulmonary dysfunction (Lim et al., 2020), metabolic dysfunction (Wei et al., 2016), and mental illness (Kanner et al., 2021). Notably, the impact of PM exposure spans from pregnancy to childhood and/or adolescence, and can contribute to postpartum depression and suicide (Lindahl et al., 2005). Furthermore, fetuses exposed to PM during gestation may be born preterm, and have low birth weight, and developmental delays (Li et al., 2017).

Neurodevelopment in mammals commences with the formation of a neural tube, which precedes a sophisticated and dynamic cascade of cellular activity throughout gestation and early developmental phases (Greene and Copp, 2014). This progression is not only genetically encoded but also influenced by epigenetic mechanisms and crucially, external environmental factors (Tau and Peterson, 2010). Consequently, specific brain regions may exhibit heightened vulnerability to environmental contaminants during distinct gestational stages. Even minor deviations in these critical neurodevelopmental periods can disrupt subsequent processes, leading to aberrant or delayed maturation of the fetal brain (Costa et al., 2019; Cserbik et al., 2020). Moreover, various toxicological and epidemiological studies have identified a possible correlation between prenatal PM exposure and compromised neurodevelopment (Guxens et al., 2014; Kim et al., 2014; Chiu et al., 2016; Clifford et al., 2016; Lertxundi et al., 2019; Lin et al., 2021; Cristaldi et al., 2022; Wang et al., 2022). In addition, some studies suggest that maternal air pollution exposure during gestation can cause oxidative stress and inflammation in the placenta either directly and/or indirectly, with the potential to cross the blood-placental barrier (Saenen et al., 2019; Johnson et al., 2021; Bongaerts et al., 2022). Thus, in humans, the prenatal period and early neonatal stages are known to constitute a key window of neurodevelopment and are highly vulnerable to fine PM exposure.

In this review, we delve into the updated literature that elucidates the possible association between air pollution exposure, especially PM exposure during pregnancy, and neuropsychiatric disorders.

METHODOLOGY

To locate published studies, we conducted searches across various international databases including PubMed, Google Scholar, Science Direct, Web of Science, Wiley Online Library, Cochrane Library, Reference Manager, ProQuest Full Text Library, and Embase. Our data collection was limited to articles published in English, encompassing in vivo, ecological, and epidemiological human studies. We employed a specific set of keywords: particulate matter, neurodegenerative diseases, neurological disorder, pregnancy, gestation, and air pollution. The search timeframe spanned from January 2013 to January 2024, focusing exclusively on full-text research papers. We excluded letters, opinions, commentaries, reviews, and non-relevant articles.

The preliminary search yielded 2281 potentially relevant records (Fig. 1). We identified and removed 1062 duplicate full research articles. After thoroughly reviewing the abstracts and titles of the remaining 1219 records, we identified 37 full research articles as suitable for final quality evaluation. Of these, 19 were excluded due to poor quality and/or insufficient data. Ultimately, 22 full research articles were included in our study (Table 1).

Fig. 1.

Fig. 1

Open in a new tab

PRISMA flow diagram.

Table 1.

Summary of human and animal studies of the effects of prenatal particulate matter exposure on neuropsychiatric disorders

Study Site Type and period of study Annual pollutant(s) mean (μg/m3) Statistical analysis Major Findings
Cognitive impairment
Lei et al., 2022 China (Shanghai) Retrospective pregnancy cohort study (2013-2016) PM2.5: 50.23 Multivariable linear regression model For every 10 μg/m3 increase in PM2.5 noticeably reduced cognitive function in offspring
Lertxundi et al., 2019 Spain (Gipuzkoa, Sabadell, Valencia) Retrospective pregnancy cohort study (2004-2008) PM2.5: 17.7
NO2: 32.2		 Multivariable linear regression model Prenatal exposure of PM2.5 negatively influenced the cognitive function in children, specifically at the age of 4 to 6 in male
Chiu et al., 2016 USA (Boston) Retrospective pregnancy cohort study (2012-2014) PM2.5: 11.3 Linear distributed lag model Female showed significant associations in cognitive impairment with increased PM2.5 exposure during gestation weeks 18-26
Ha et al., 2019 USA (New York) Retrospective pregnancy cohort study (2008-2010) PM2.5: 9.7
O3: 36.2 ppb		 Generalized mixed models Living near major roads and prenatal or early life exposures to PM2.5 and O3 can contribute to developmental delays in children
Xu et al., 2022 China Nationwide cohort (2010-2018) PM2.5: 64.9 Ordinary least squares and instrumental variable+two-stage least square models A detrimental effect of prenatal PM2.5 exposure on adolescent cognitive ability
Guxens et al., 2018 The Netherlands (Rotterdam) Retrospective pregnancy cohort study (2002-2006) PM2.5: 16.8-28.1
NO2: 25.3-73.3		 Monte Carlo null-Z simulations Reduced cortical thickness plated a mediating role in the link between prenatal PM2.5 exposure and cognitive impairment in children
Autism Spectrum disorder (ASD)
Rahman et al., 2022 USA (California) Retrospective pregnancy cohort study (2001-2014) PM2.5: 9.6-16.9 Cox proportional hazard models PM2.5 exposures increased ASD risk, especially among boys
Higher levels of PM2.5 in the first two trimesters increased ASD risk
Rahman et al., 2023 USA (California) Retrospective pregnancy cohort study (2001-2014) PM2.5: 9.6-16.9 Cox proportional hazard models Tailpipes pollution (carbon, organic carbon) increased ASD risk
Frye et al., 2021 USA (Arkansas) Clinical investigation Mixed-model analysis Prenatal exposure to PM2.5 disrupts children’s mitochondrial metabolism
Emam et al., 2020 - In vivo (Wistar rat) PM2.5: 43.8 ± 21.1 ANOVA analysis Exposure to ambient air pollution contributed to ASD by alteration of OXTR protein
Morgan et al., 2023 USA (California) Retrospective pregnancy cohort study (2020-2022) Cox proportional hazard models Prenatal exposure to ambient air pollution is associated with neurodevelopmental outcomes at 2 years of age
Attention-Deficient Hyperactivity (ADHD)
Chang et al., 2022 Taiwan Nationwide birth cohort (2004-2011) PM2.5: Prenatal, 37.21 ± 14.65; Postnatal, 35.34 ± 14.86 Cox proportional hazard models The risk of ADHD increased in pregnant women exposed to PM2.5 levels greater than 16 μg/m3 from conception through early childhood
Min and Min, 2017 Republic of Korea Nationwide birth cohort (2002-2012) PM10: 60.39-70.87
NO2: 43.99-56.27		 Cox proportional hazard models ADHD prevalence in children was correlated with exposure to PM10 and NO2
Liu et al., 2022 China (Shenzhen City) Retrospective pregnancy cohort study (2014-2017) PM10: 54.57
PM2.5: 36.16		 T-test or chi-squared test Early life exposure to PM10, PM2.5 and NO2 is associated with an increased risk of child ADHD-like behaviors at the age of approximately 3 years old. The late-prenatal and early postnatal periods might be the susceptible exposure windows
Mortamais et al., 2019 Spain (Catalonia) Retrospective pregnancy cohort study (2008-2015) PM2.5: 11.8-39.5 Linear regression model Prenatal PM2.5 exposure observed to be linked to a reduction in corpus callosum (CC) volume in children which could lead to an increase in the prevalence of behavioral problems in children that resemble ADHD
Kim et al., 2014 Republic of Korea Retrospective pregnancy cohort study (2010-2013) PM10: 64.9 Binary logistic regression model Prenatal exposure to PM10 and NO2 and children's neurodevelopment from birth to 24 months of age: mothers and Children's Environmental Health (MOCEH) study
Wang et al., 2022 China (Wuhan) Retrospective pregnancy cohort study (2013-2014) PM2.5, PM10, NO Binary logistic regression model Prenatal and early postnatal exposure to ambient particulate matter and early childhood neurodevelopment: A birth cohort study
Anxiety and Depression
Li et al., 2021 China (Nanjing) Retrospective pregnancy cohort study (2018) PM2.5: 7.87-10.55 (μg/kg/day) Binary logistic regression model Among pregnant women, the average daily dose of PM2.5 in the mentally stressed (case) group was significantly higher than that in the control group
Lin et al., 2017 China (Shanghai) Clinical investigation (2010) PM10: 73.9 Binary logistic regression model The study findings supported a dose-dependent association between PM10 and emotional stress during pregnancy
Fonken et al., 2011 - In vivo (C57BL/6 mouse) PM2.5: 94.38 ANOVA analysis Prolonged (10 months) exposure to PM2.5 in mice led to cognitive impairment and affective disturbances, under pinned by changes in hippocampal physiology and cytokine profiles
Schizophrenia (SCZ)
Nephew et al., 2020 - In vivo (Sprague-Dawley rat) PM2.5: 200 ANOVA analysis Traffic-related PM exposure reduced social and grooming behaviors in rodents
Broseus et al., 2024 France (Nancy) Retrospective pregnancy cohort study (2003-2006) PM10: 65.9 Binary logistic regression model Placental DNA methylation signatures of prenatal air pollution exposure and potential effects on birth outcomes: an analysis of three prospective cohorts
Open in a new tab

RESULTS

Association between prenatal PM exposure and neuropsychiatric disorders

Cognitive impairment: Cognitive function encompasses the mental processes responsible for perception, memory, intelligence and action. Any impairment in cognitive function not only reduces quality of life but is often linked to neuropsychiatric disorders, such as Alzheimer’s disease, depression, and schizophrenia. A growing body of research has established a link between air pollution exposure and cognitive impairment (Chiu et al., 2016; Tzivian et al., 2017; Rivas et al., 2019; Xu et al., 2022). There is significant concern over findings that suggest environmental nanoparticles can transfer from a mother to her fetus via the placenta (Bove et al., 2019), and might even penetrate the blood brain barrier (Yamashita et al., 2011), possibly leading to long-lasting neurological damage in the fetus. Moreover, living in areas with high air pollution levels is increasingly linked to neuroinflammatory induction and neuropathological manifestations that induce cognitive impairment (Tzivian et al., 2017; Lertxundi et al., 2019; Lei et al., 2022; Xu et al., 2022; Park et al., 2024b). These changes are thought to be induced by prenatal PM exposure, potentially leading to cognitive impairment in newborns.

Lei and colleagues (2022) explored the impact of prenatal PM2.5 exposure on infant cognitive abilities in Shanghai, China. Analyzing a cohort of 2,435 mother-infant pairs, the authors found that increased exposure to PM2.5 and its components (black carbon, mineral dust and sea salts, NH4+, NO3–, SO42- and organic matter) during the third trimester of pregnancy negatively impacted the infants’ cognitive abilities (Lei et al., 2022). These data were retrieved from the China Regional Estimates developed using a combined geoscience-statistical method. Infant cognitive ability in five domains was evaluated at the 12 month follow-up using the Ages and Stages Questionnaire (ASQ). In this investigation, multivariable linear regressions stratified by sex and breastfeeding duration were used to evaluate the effects of exposure to PM2.5 and its components on the ASQ scores. Specifically, an increase in PM2.5 exposure was associated with declines in gross motor function, problem-solving, and personal-social domain scores. For every 10 μg/m3 increase in the levels of PM2.5 and its components during the third trimester, there was a noticeable reduction in problem-solving scores (10.79, 95% CI 17.40, 4.18 to 4.68, 95% CI 7.84, 1.53). Notably, infants who breastfed for less than six months and male infants were particularly affected.

Similarly, Lertxundi and colleagues (2019) examined the relationship between prenatal exposure to PM2.5 and NO2 and cognitive development in infants (Lertxundi et al., 2019). Drawing from a Spanish birth cohort spanning three regions (Gipuzkoa, Sabadell and Valencia), the study enrolled 2,150 pregnant women from February 2004 to February 2008. They were recruited during their initial specialized antenatal care visits (10-13 weeks of gestation) at regional health centers. The findings highlighted that most cognitive domain coefficients were negatively influenced by both PM2.5 and NO2 exposure. Of particular concern was the pronounced vulnerability observed in male children, specifically between the ages of 4 and 6 years, affecting their memory and general cognitive functions.

On the other hand, Chiu and colleagues (2016) presented findings that, while in line with the aforementioned studies, showed certain inconsistencies (Chiu et al., 2016). The authors delved into the differential effects of prenatal PM2.5 exposure on neurodevelopment across fetal sex. The study of 267 urban children in Boston revealed that increased PM2.5 exposure during specific stages of pregnancy might be linked to decreased cognitive function in areas of memory and attention. Notably, distinctions were apparent between males and females. The children were assessed at approximately 6.5 years of age (± 0.98), and the outcomes encompassed IQ, attention metrics omission errors (OEs), commission errors (CEs), hit reaction time (HRT), and HRT standard error (HRT-SE) on the Conners’ CPT-II), and memory measures (general memory (GM) index, verbal and visual memory (VVM), and attention-concentration (AC)-indices on the WRAML-2). For males, increased PM2.5 exposure levels during gestational weeks 31-38 was linked to reduced IQ, higher exposure during weeks 20-26 was linked to increased OEs, higher exposure during weeks 32-36 was linked to a slower HRT, and higher exposure during weeks 22-40 was linked to increased HRT-SE. In contrast, females showed significant associations of memory domain scores with increased PM2.5 exposure during gestational weeks 18-26, resulting in decreased VVM, and increased exposure during weeks 12-20 led to decreased GM. Although the cohort size in this study was smaller than that in the studies by (Lertxundi et al., 2019; Lei et al., 2022), a distinguishing feature was the authors’ thorough methodology. They provided weekly, location-specific PM2.5 exposure for each pregnant participant that led to more accurate data regarding the associations between prenatal PM exposure and infant cognitive abilities. In addition, the authors found that the impact of PM exposure by sex was different in the above two reports. While the sex-specific impacts of prenatal PM exposure on offspring neurodevelopment are recognized, they remain controversial. Various in vivo studies have reported conflicting results on prenatal PM exposure induced disruption of neurodevelopment in offspring by sex (Bolton et al., 2012; Allen et al., 2014; Bolton et al., 2014). Given these variances, there is a pressing need for more exhaustive research on the influence of prenatal PM exposure on neurodevelopment, considering factors such as race, sex, and geographical region.

Ha and colleagues (2019) investigated how living close to major roadways and prenatal exposure to PM2.5 and O3 may affect child development (Ha et al., 2019). Drawing from a New York state-based birth cohort, the study involved 4,089 singletons and 1,016 twins born between 2008 and 2010. The NY Department of Transportation’s road network data were used to determine how close participants lived to major roads. Moreover, the Environmental Protection Agency’s Downscaler models were used to estimated PM2.5 and O3 concentrations. These estimations were then related to each child’s prenatal and early-life residential history, including addresses, maternal workplaces, and daycare locations. Parents gauged their children’s developmental milestones at various age intervals (8, 12, 18, 24, 30 and 36 months) using the Ages and Stages Questionnaire. The study utilized generalized mixed models to assess the risk associated with developmental delays per increased unit of PM2.5 and O3 concentrations and living proximity to major roads. The findings showed that children living 50-500 m away from a major road had approximately twice the risk of communication delays compared to those living more than 1000 m away. Additionally, increased prenatal exposure to both PM2.5 and O3 during various pregnancy windows had weak but significant associations with a failing score in any developmental domain, with effects ranging from 1.6 to 2.7% for a 10 μg/m3 increase in the PM2.5 concentration and 0.7 to 1.7% for a 10 ppb increase in the O3 concentration. In summary, this study suggested that living near major roads and prenatal/early-life exposures to PM2.5 and O3 can contribute to developmental delays in children.

Xu and colleagues (2022) investigated the effects of prenatal PM2.5 exposure on the cognitive function of adolescents (Xu et al., 2022). Using a Chinese nationwide cohort study consisting of 1,555 adolescents with an average age of 13.3 years (of which 45.4% were female), the authors employed both ordinary least squares (OLS) and instrumental variable+two-stage least square (IV+2SLS) methodologies to study the causal effects of PM2.5 exposure during pregnancy on adolescent cognitive function. The average maternal PM2.5 exposed concentration was noted at 64.9 μg/m3, and the average cognitive function score was 38.1 among the participants. Interestingly, there was a divergence in the findings between the OLS and IV+2SL methods. While the OLS results suggested that maternal air pollution exposure might enhance cognitive function in adolescent offspring, pointing to potential endogeneity issues, the IV+2SLS results indicated a detrimental effect of prenatal PM2.5 exposure on adolescent cognitive ability (β=-0.040, p<0.05). This discrepancy might stem from biases in the scale of data collection, whether at the country or district level, which may skew the real exposure levels of pregnant women. Moreover, factors such as postnatal PM2.5 exposure, which often correlates with prenatal levels and can influence cognitive development, were not fully considered. Furthermore, the study exclusively focused on PM2.5, excluding other air pollutants, such as O3 and NO. Despite these insights, the study had limitations. Many studies have not looked at how air pollution affects people in the long term. This makes the study by Xu et al. (2022) especially important.

Last, Guxens and colleagues (2018) provided compelling evidence that fetal exposure to air pollution can lead to structural changes in a child’s brain (Guxens et al., 2018). This study aimed to determine whether air pollution exposure during fetal development affects brain morphology and whether such alterations play a role in the relationship between fetal air pollution exposure and cognitive function in school-aged children. Data were sourced from a population-based birth cohort in Rotterdam, The Netherlands, which included 1,932 children born between April 2002 and January 2006. Of these children, 783 between 6 and 10 years of age underwent an MRI substudy for structural neuroimaging and participated in a cognitive function substudy. To gauge the extent of air pollution exposure during fetal life, the authors utilized land-use regression models. The average PM2.5 exposure level was found to be 20.2 μg/m3, with a range from 16.8 to 28.1 μg/m3. The findings were notable in that children with higher exposure to PM2.5 in the womb had a thinner cortex in several regions across both brain hemispheres. Particularly, for every 5 μg/m3 increase in the PM2.5 exposure level, the thickness of the cerebral cortex of the precuneus region reduced by 0.045 mm. Moreover, a similar increase in PM2.5 exposure was linked with a higher number of inhibition errors during cognitive tasks. The study also established that reduced cortical thickness in the precuneus and rostral middle frontal regions played a mediating role in the link between PM2.5 exposure and compromised inhibitory control in children. While the research did not find a correlation between air pollution exposure and global brain volumes, it was the first to demonstrate the relationship among fetal exposure to PM2.5, structural changes in the cerebral cortex in childhood, and associated cognitive impairments. To gain deeper insights into the interplay between air pollution exposure and brain development, future studies should replicate the robust methodology of Guxens et al. (2016), including a large number of participants, detailed individual-level air pollution data throughout the entire fetal period, and comprehensive adjustments for socioeconomic and lifestyle factors in imaging analyses.

While there are some inconsistencies across studies (Harris et al., 2015; Guxens et al., 2016), the prevailing evidence suggests that prenatal PM2.5 exposure is adversely associated with infant cognitive abilities. As our understanding deepens, there is a pressing need to conduct more research to understand the mechanisms behind these findings and to develop strategies to minimize air pollution and protect fetal brain development.

Autism Spectrum Disorder (ASD): ASD is a prevalent neurodevelopmental disorder marked by challenges in social interaction and repetitive behavioral patterns (Hodges et al., 2020). The exact cause of ASD is still unknown. But new research shows that prenatal complications, including drug or toxin exposure, may increase autism risk (Stoner et al., 2014; Adil et al., 2022). In addition, several epidemical studies have suggested a possible association between prenatal exposure to PM2.5 and the disruption of neurodevelopment that leads to ASD risk (Frye et al., 2021; Rahman et al., 2022, 2023). Furthermore, prenatal and early life exposure to PM2.5 caused behavioral deficits, including increased repetitive behavior, poor social interaction and an inability to differentiate social novelty due to increased oxidative stress in the brains of Wistar rats (Emam et al., 2020). However, little is known about the mechanisms of prenatal air pollutant exposure, especially PM exposure, in the onset of ASD.

Recently, Rahman and colleagues (2022) examined the impact of PM2.5 exposure during the first two trimesters of pregnancy on the risk of ASD in children in California, USA (Rahman et al., 2022). The study drew from a population-based retrospective cohort from Kaiser Permanente Southern California (KPSC) hospitals, comprising 294,937 mother-child pairs. The authors investigated the correlations between weekly PM2.5 exposure and ASD risk using spatiotemporal prediction models to estimate weekly average exposure to PM2.5, NO2, and O3. Applying Cox proportional hazard models with distributed lags, the authors assessed the association between weekly air pollutant exposure and ASD risk for the entire group and performed separate assessments for boys and girls. The study identified sensitive windows during gestation, specifically from weeks 1-27, where PM2.5 exposure was associated with ASD onset (hazard ratio (HR), 1.14, 95% CI 1.06, 1.23). Conversely, O3 exposure during gestational weeks 34-37 was linked to an elevated ASD risk (HR, 1.06, 95% CI 1.01, 1.11) but appeared to be a protective factor during gestational weeks 20-28 (HR, 0.93, 95% CI 0.89, 0.98). Furthermore, the study found that male children exhibited heightened vulnerability to PM2.5 exposure early in gestation (males, HR, 1.16, 95% CI 1.08, 1.26; females, HR, 1.06, 95% CI 0.89, 1.26). In summary, the authors concluded that increased PM2.5 exposure during the first two trimesters and O3 exposure late in the third trimester were correlated with an increased risk of ASD in offspring.

Supporting this evidence, Rahman et al. (2023) reported that maternal exposure to traffic-derived PM2.5 during pregnancy was significantly associated with elevated ASD risk in offspring (Rahman et al., 2023). A retrospective cohort of 318,750 children born at KPSC hospital in the USA between 2001 and 2014 was examined, and they were followed up until they reached the age of 5 years. The study highlighted the specific risks associated with exposure to carbonaceous material from two different sources: tailpipe and non-tailpipe sources. In the single pollutant model, ASD was primarily associated with tailpipe emissions, including elemental carbon, organic carbon, and metals (Cu, Fe, and Mn). The authors suggested that reducing tailpipe emissions through the widespread use of electric vehicles has noteworthy implications for reducing the potential ASD risk caused by exposure to traffic-related air pollution.

Frye et al. (2021) highlighted the possible pathophysiological mechanism by which prenatal PM2.5 exposure influences neurodevelopment and behavior in children with ASD (Frye et al., 2021). This study investigated the potential for abnormalities in children’s mitochondrial metabolism as a result of increased exposure to air pollution during gestation (second to third trimester). In addition, the authors speculated that disruption in mitochondrial respiration could play a pivotal role in ASD development, emphasizing the importance of understanding the impact of air pollution exposure on fetal development. However, this study preliminarily demonstrated a link between early life exposure to air pollution and long-term anomalies in mitochondrial physiology. Therefore, it is uncertain whether the alteration in behaviors may increase a person’s susceptibility to disease or ASD symptoms that persist as a result of later life events.

Providing a complementary perspective, Emam and colleagues (2020) explored the possible mechanisms by which prenatal air pollution exposure might impact neuronal development and lead to ASD using a valproic acid-induced ASD-like rodent model (Emam et al., 2020). They used behavioral and molecular studies to examine the impact of exposure to PM2.5 and gaseous pollutants on ASD risk. The authors revealed that exposure to ambient air pollution aggravated ASD-like behavioral changes in a valproic acid-induced ASD-like rodent model, and suggesting a potential role for OXTR protein in mediating this relationship. In addition, Rahman et al. (2022) reported that a greater association between prenatal exposure to PM2.5 and an increased risk of ASD in male children, and they observed significantly more affective behavior in male rats (Rahman et al., 2022). These results are in line with investigations into the molecular and epidemiological aspects of human and experimental animal neuropathology. Additional studies are needed to understand the impact of fine particulate exposure and its mechanisms on ASD development. Furthermore, Morgan and colleagues (2023) linked ambient PM10 exposure during gestation with altered gene expression in neural tissue, correlating with increased ASD susceptibility (Morgan et al., 2023). These results align with prior hypotheses regarding inflammation-driven disruptions in neurodevelopment.

On the other hand, Pagalan and colleagues (2019) found that while NO exposure correlates with ASD incidence, PM2.5 and NO2 exposure did not show a correlation in children from Vancouver, Canada (Pagalan et al., 2019). Although their findings were consistent with those reported in European cohort studies (Guxens et al., 2016; Gong et al., 2017), the authors acknowledged statistical limitations and the need to explore multipollutant exposure. The authors suggested that these results were not tested for multiple comparisons and that residual confounding may remain, likely biasing the effect estimates toward the null. Additionally, trimester-specific analyses were limited by the high correlation between trimester exposures. Furthermore, the most notable difference from other studies is that this study only tested associations for single pollutants. Therefore, further studies for investigating pollutant mixtures are needed. However, epidemiological studies have indicated a possible association between prenatal air pollutant exposure and ASD risk.

Overall, emerging research underscores the significance of understanding the potential links between prenatal exposure to PM and ASD risk. Although the evidence is compelling, it is crucial to appreciate the multifaceted nature of ASD and recognize that a combination of genetic, environmental, and individual factors likely contribute to ASD onset. Therefore, further studies that are more comprehensive, including genetic and other factors, are needed.

Attention Deficit Hyperactivity Disorder (ADHD): ADHD is characterized as a neurobehavioral disorder exhibiting developmental and neuropsychiatric symptoms, such as impulsivity, hyperactivity, and inattention (Mahone and Denckla, 2017). Among children, ADHD is the most common neurobehavioral disorder with a reported global incidence of 8 to 12% (Faraone and Mick, 2010; Cserbik et al., 2020). While the causes of ADHD are largely believed to be genetic, numerous studies underscore the correlation between ADHD in children and PM exposures during pregnancy and early life stages (Mortamais et al., 2019; McGuinn et al., 2020; Shih et al., 2020; Chang et al., 2022; Liu et al., 2022). Moreover, crucial periods such as fetal life and early childhood emerge as high-risk phases due to the pivotal cellular differentiation and growth that is essential for brain maturation and the formation of neural networks (Thygesen et al., 2020; Saadeh et al., 2022). Therefore, air pollution is considered an important environmental risk factor for ADHD.

An insightful study found that higher exposure to PM2.5 during early pregnancy and the first few years of life was associated with an increased risk of ADHD in children, in a near-linear dose-response manner (Chang et al., 2022). Intriguingly, vulnerability peaked during the first trimester of pregnancy, with PM2.5 concentrations exceeding 16 μg/m3 having a notable association with the hazard ratio (HR) for ADHD incidence (HR, 1.27, 95% CI 1.14, 1.43). This aligns with the result from McGuinn et al. (2020), indicating diminished Adaptive Skills scores, which indicate poorer functioning, in relation to heightened PM2.5 exposure during the first trimester. These effects may be linked to fetal growth limitations induced by first-trimester exposure to PM2.5 and directly impact the developing brain (Michikawa et al., 2022). However, the exact pathophysiological mechanisms remain elusive.

Consistently, Min and colleagues (2017) suggested the possible association between PM10 and NO2 exposure and the incidence of ADHD in children in Korea (Min and Min, 2017). A total of 8,936 infants born between January 2002 and December 2002 were followed up for ten years. During the study period, ADHD was diagnosed in 314 participants (3.5%). Using a population-wide dataset of health insurance claims from the National Health Insurance Service in Korea (2002-2012), the study reported an association wherein a 1 μg/m3 increase in PM10 (HR, 1.18, 95% CI 1.15, 1.21) and NO2 exposure levels (HR, 1.03, 95% CI 1.02, 1.04). Interestingly, the study indicated that newborns in the greatest tertile of PM10 or NO2 exposure (PM10≥70.87 μg/m3, NO2≥56.27 μg/m3) or infants in the lowest tertile of exposure (PM10≤60.39 μg/m3, NO2≤43.99 μg/m3) had a 2- to 3-fold greater risk for ADHD (greatest tertile, HR, 3.88, 95% CI 2.87, 5.23; lowest tertile, HR, 2.10, 95% CI 1.54, 2.85). This study is largely consistent with other previous studies on the air pollution-related risk of ADHD or ADHD-related behaviors, and its strength is based on the large sample size drawn from the nationally representative database.

Moreover, Lie and colleagues (2022) elucidated correlations between late gestational exposure to various air pollutants, including PM10, PM2.5, NO2, CO, O3 and SO2, and heightened ADHD behavioral risks during early childhood in China (Liu et al., 2022). The study suggested that early exposure to PM10, PM2.5, and NO2 is positively related to the likelihood of child hyperactivity. The risk of child hyperactivity increased significantly from the seventh month of pregnancy to the fourth month after birth for every 10 μg/m3 increase in PM10, PM2.5, and NO2 exposure concentrations during early life, with the strongest association in the ninth month of pregnancy (PM10, HR, 1.043, 95% CI 1.016, 1.071; PM2.5, HR, 1.062, 95% CI 1.024, 1.102; NO2, HR, 1.043, 95% CI 1.014, 1.051). However, connections between carbon monoxide (CO), O3 and sulfur dioxide (SO2) exposure and hyperactive tendencies were notably absent. Echoing these findings, Mortamais and colleagues (2019) observed that prenatal PM2.5 exposure (ranging from 11.8 to 39.5 μg/m3) during the third trimester of pregnancy was tied to reduced corpus callosum (CC) volume in Spanish children (Mortamais et al., 2019). The authors suggest that this volume decrease potentially leads to ADHD-like behavioral alternations.

In addition, a contrasting birth cohort study from Taiwan illuminated a robust association between prenatal NO exposure and childhood hyperactivity (Shih et al., 2020). The authors observed that increases in NO levels during pregnancy (3.14 ppb, interquartile range) were associated with a 26% increased likelihood of hyperactivity in the fetus. However, PM10 exposure showed no significant associations. Conversely, Kim and colleagues (2014) reported a significant association between prenatal PM10 and NO2 exposure and delayed cognitive development in Korean children, particularly in boys (Kim et al., 2014). Similarly, Wang and colleagues (2022) reported deficits in attention and memory associated with exposure to air pollution during late pregnancy and the early postnatal period, underscoring these stages as particularly sensitive windows for neurodevelopmental impact (Wang et al., 2022).

The plethora of evidence connecting prenatal PM exposure to ADHD in children is incontrovertible. However, the risk intricacies encompass diverse factors, such as pregnancy stage, pollutant type, concentrations, child sex, and socioeconomic status. Despite the overwhelming evidence, a complete understanding of the underlying mechanisms has not yet been achieved. The compelling association between air pollution exposure and childhood ADHD necessitates meticulous and synergistic evaluations of air particulates in future research endeavors.

Anxiety and Depression: Globally, anxiety and depressive disorders are prevalent, with current rates of approximately 6.5% and 2.6%, respectively (Collaborators, 2021; Park et al., 2024a). Furthermore, mental health disorders that emerge during childhood, which are often chronic, have profound implications for children’s holistic development, academic progression, and subsequent social growth (Fusar-Poli, 2019). Therefore, mental health care is more important during childhood than at other ages. Several studies have highlighted that children exposed to high levels of air pollutants during embryonic development have an increased likelihood of developing depression and anxiety disorders (Genkinger et al., 2015; Margolis et al., 2016; Jorcano et al., 2019). Moreover, growing evidence suggests that prenatal or postnatal exposure to air pollution, particularly PM, is associated with a range of childhood mental health disturbances, including emotional and aggression challenges (Lin et al., 2017; Anokye et al., 2018; Sheffield et al., 2018; Niedzwiecki et al., 2020; Li et al., 2021). While several epidemiological studies support the toxicant effect of prenatal PM exposure on mental health, the mechanisms remain unclear.

In a case-control study by Li et al. (2021), the effects of PM2.5 exposure on the mental stress of pregnant women in Nanjing, China, were explored. From January 2018 to December 2018, a total of 313 high-symptom cases and 144 matched controls were used in the analysis. The study unveiled a significant correlation between heightened PM2.5 exposure and increased mental distress in expectant mothers, with perceptions about PM2.5 effects acting as a mediator. According to binary logistic regression, the likelihood that pregnant women would experience high levels of mental stress increased by 13.76% for every additional unit of PM2.5 exposure. Women who were pregnant tended to be more anxious if they had higher exposure to PM2.5 and a higher risk perception. The association between PM2.5 exposure and psychological stress was mediated by perceived indoor attribution.

Similarly, Lin and colleagues (2017) demonstrated a link between maternal exposure to PM10 or NO2 during mid- to late pregnancy and heightened depression, suggesting increased emotional distress (Lin et al., 2017). The authors collected data for 1,931 pregnant women from February to October 2010 in Shanghai, China. In the logistic regression models, SO2 and PM10 concentrations on the recruitment day and the 5-day moving average concentrations of NO2 were associated with higher SCL-90-R Global Severity Index (P75-P100) scores. These associations were stronger among women with high levels (P25-P100) of air pollutant exposure than among women with low levels (P1-P25) of pollutant exposure. Stronger associations and higher levels of pollutants were observed in the cool season compared to the warm season. An increased SO2 concentration on the recruitment day was also associated with an increased risk of having a high depression score (P75-P100). These findings supported a dose-dependent association between air pollution exposure and emotional stress during pregnancy.

Delving deeper, in vivo studies provide intriguing insights into the relationship between PM exposure and mental health. Fonken and colleagues (2011) suggested that prolonged (10 months) exposure to PM2.5 in mice led to cognitive impairment and affective disturbances, underpinned by changes in hippocampal physiology and cytokine profiles (Fonken et al., 2011). The authors elucidated that PM2.5 exposure led to decreased apical dendritic spine density and dendritic branching in the hippocampal CA1 and CA3 regions through increased levels of cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)1-β, HMGB1 and HO1. Similarly, Yokota et al. (2009) associated prenatal exposure to diesel exhaust particles with altered neurochemical dynamics, suggesting potential dep-ressive propensities and disruptions in the central dopaminergic system (Yokota et al., 2009).

Postpartum depression (PPD) is another critical concern impacting maternal and infant health (Anokye et al., 2018). Distinctively characterized by depressed mood, anxiety, and anhedonia, PPD can manifest variably post-childbirth (Putnam et al., 2017). Interestingly, two notable studies (Sheffield et al., 2018; Niedzwiecki et al., 2020) identified connections between gestational exposure to PM and PPD symptoms. Sheffield et al. (2018) suggested that an increase in postpartum anhedonia was associated with PM exposure during mid-pregnancy (Sheffield et al., 2018). In addition, Niedzwiecki et al. (2020) highlighted that PM exposure during pregnancy caused sudden increases in heart rate, maternal blood volume, cardiac output, and pulmonary circulation to maintain the proper blood supply for the developing fetus in Mexico City, Mexico (Niedzwiecki et al., 2020). These findings suggest the enduring effects of PM exposure during pregnancy on maternal mental health. However, the precise mechanisms connecting prenatal pollution exposure and postpartum psychological well-being remain unexplored.

In summary, the burgeoning prevalence of anxiety and depression, especially in children, profoundly affects their subsequent well-being and social developmental trajectories. Identifying potential risk factors, such as pollution exposure, is crucial for prevention. The intricate relationship between air pollutant exposure and maternal mental health during and after pregnancy warrants further, in-depth exploration.

Schizophrenia (SCZ): SCZ is largely recognized as a neuropsychiatric disease that is characterized by positive symptoms, such as delusions and hallucinations, negative symptoms, such as diminished motivation, decreased spontaneous speech, and social disengagement, and cognitive impairment (Müller et al., 2015). Globally, this disease is a severe and enduring mental disorder that affects more than 21 million people (Jaeschke et al., 2021). Although the development of schizophrenia is highly linked with genetic factors, growing evidences indicate that environmental factors, such as air pollution may be a developmental risk factors (Eguchi et al., 2018). Urban residents are known to experience mental illness more frequently than rural residents (Alegria et al., 2018). Thus, prenatal or postnatal individuals who are exposed to environmental toxins, such as fine air pollution particles, are more likely to experience from psychological conditions such as schizophrenia. In addition, a few studies have found a link between prenatal exposure to traffic-related particulate matter (TRP) and a higher incidence of schizophrenia (Pedersen and Mortensen, 2006; Nephew et al., 2020). However, the epidemiological evidence to support this hypothesis is still limited.

Nephew and colleagues (2020) investigated subclinical cognitive effects of TRP exposure throughout development, including reduced mental development, elevated anxiety and depressed symptoms, and attentional issues in rodent model pups of Sprague-Dawley rats (Nephew et al., 2020). For 6 weeks, pregnant and lactating rats were exposed to PM from a Boston (MA, USA) traffic tunnel for 5 hours per day, 5 days per week (3 weeks of pregnancy, 3 weeks of lactation). The target exposure concentration for the fine fraction of nebulized PM, measured as PM2.5, was 200 μg/m3. The TRP exposure group chowed reduced social play and grooming behaviors, which are related to schizophrenia symptoms, such as social and cognitive deficits and/or increased anxiety. In addition, MRI analysis of ex vivo brains revealed 14% lower fractional anisotropy in the anterior cingulate and hippocampus of the PM-exposed group.

Moreover, Broséus and colleagues (2024) revealed that prenatal PM10 exposure leads to methylation changes in placental genes implicated in neurodevelopmental pathways (Broseus et al., 2024). Such alterations may influence fetal programming and vulnerability to later-life psychiatric disorders. However, there was no correlation between schizophrenia-like behaviors and cytokine levels. Research on the effects of prenatal exposure to fine particulate matter on behavior as well as assessments of neuronal dispersion in the neonatal and adult brain is urgently needed.

The potential mechanisms

The gestational period is characterized by heightened sensitivity for the fetus. During this time, PM exposure poses potential threats to the integrity of the placental barrier and the health of the developing fetus. This section delves into the adverse effects of PM exposure, their mechanisms, and the implications, as illustrated in Fig. 2.

Fig. 2.

Fig. 2

Open in a new tab

The potential mechanisms by which PM exposure affects the health of the developing fetus.

Systemic inflammation from maternal PM exposure: The placenta acts as a shield between the mother and fetus. Nonetheless, airborne pollutants can impair its protective functions, leading to potential prenatal and postnatal health concerns, such as reduced oxygen and nutrient transfer (Gernand et al., 2016; Saenen et al., 2019; Jukarainen et al., 2022). Some studies have found that environmental particles can be transferred from the mother to the fetus through the placenta, thus exposing the fetus directly during the most vulnerable period of life and affecting fetal brain development. Other studies reported that air pollutants could cross the blood brain barrier in pregnant mice and be detected in the fetal brain, possibly leading to permanent fetal neurological damage or death through oxidative stress and inflammatory mechanisms, and the disruption of synaptogenesis (Olvera Alvarez et al., 2018).

Gangwar and colleagues (2020) emphasized the role of PM in activating oxidative stress and inflammatory cytokines, which can compromise CNS development and homeostasis (Gangwar et al., 2020). Ransohoff and Brown (2012) indicated that the peripheral immune system communicates with the CNS through circulating cytokines, such as IL-1, IL-6, and granulocyte-macrophage colony-stimulating factor (GMCF), which impact peripheral immune cells and stimulate peripheral neuronal afferents (Ransohoff and Brown, 2012). This can potentially disrupt the CNS by diffusing into the brain. In addition, an upsurge in systemic inflammation, influenced by PM, can subsequently lead to changes in the brain’s reactive oxygen species (ROS) and cytokine balance and even modify innate immune cell morphology, including macrophages, neutrophils, monocytes or dendritic cells (Sankowski et al., 2015). Activated astrocytes and microglia exacerbate local inflammation by releasing pro-inflammatory cytokines through c-Jun N-terminal kinase (JNK) and nuclear factor-κB related signaling pathways (Kulas et al., 2018; Gómez-Budia et al., 2020). These inflammatory responses can obstruct normal brain development by influencing processes, such as myelination in white matter, leading to the induction of apoptosis, decreased neuronal density, and impairment in synaptic plasticity (Szepesi et al., 2018; Garcia Rivera et al., 2022).

Oxidative stress induced by maternal PM exposure and its consequences: The complex chemical composition of PM endows it with pronounced oxidative potential, manifesting in ROS production not only in maternal pulmonary tissues but also in distal organs, including fetal cells (Daellenbach et al., 2020). The fetus, with its immature immune system and lack of a robust endogenous antioxidant defense mechanism, is susceptible to oxidative stress, leading to potential developmental abnormalities in brain regions such as the hippocampus (Perrone et al., 2018). Increased ROS levels have been observed in multiple brain cell types after air pollution exposure, both in vivo and in vitro. The high energy requirements of the developing fetal brain make it vulnerable to damage from abundant free radicals or an underdeveloped redox signaling system (Cobley et al., 2018). Additionally, oxidative stress can further exacerbate neuroinflammation by producing proinflammatory cytokines and activating inflammatory pathways in microglia and/or astrocytes (Gómez-Budia et al., 2020; Kulas et al., 2018; Morris et al., 2021).

On the other hand, a compelling area of concern is the potential insufficiency of maternal antioxidants to adequately shield the fetus from PM-induced oxidative harm (Catarino et al., 2012; Daellenbach et al., 2020). Studies have revealed differences in antioxidant capacity between maternal blood and cord blood, suggesting that maternal exposure to PM could deplete antioxidants, making the fetus more susceptible. Moreover, endogenous antioxidant overconsumption may occur in mother as a result of PM-induced systemic oxidative stress (Wang et al., 1997; Wang et al., 2019; Lee et al., 2020). Thus, maternal circulating antioxidants that are produced naturally during pregnancy might not be sufficient to protect the fetus.

Endoplasmic reticulum (ER) stress, instigated by the accumulation of misfolded proteins that are not effectively cleared by autophagy, has been proposed as a mechanism for PM-induced brain damage. Often occurring during neuroinflammation, the improper clearance of these misfolded proteins intensifies inflammation and oxidative stress (Onoda et al., 2020; Yi et al., 2022). Evidence from in vivo studies suggests that prolonged exposure to even low levels of PM can exacerbate neurological brain damage (Zhang et al., 2018; Peters et al., 2019; Lee et al., 2020). These studies indicated that PM-induced ER stress could activate the caspase12/DR5/caspase8 pathway, leading to apoptosis and neuronal death in the brain.

Placental dysfunction and epigenetic regulatory mechanisms: In fetuses, the underdeveloped or improperly formed blood-brain barrier permits the entry of peripheral pro-inflammatory signals into the brain, facilitating the activation of astrocytes and microglia (Shang et al., 2023). Supporting this, Sram and colleagues (2017) demonstrated the pro-inflammatory potential of PM10 within both placental and fetal brain tissues, where it induced oxidative stress and endothelial dysfunction factors known to impair neuronal differentiation and synaptogenesis (Sram et al., 2017). Moreover, Recent transcriptomic analyses, have identified significant dysregulation in genes critical for synaptic development, including SHANK3 and NRXN1, which are crucial for synapse formation and synaptic stability (Morgan et al., 2023). Additionally, neuronal migration pathways involving Reelin and Doublecortin were notably altered in response to PM10 exposure, potentially impairing neuronal positioning and cortical layering. Furthermore, the recent studies demonstrated the changes in placental gene expression linked to neuroinflammation (e.g., IL-6, TNF-α, IL-1β) and neurogenesis (e.g., BDNF, NGF) (Morgan et al., 2023; Broseus et al., 2024). These detailed molecular insights highlight the complexity and direct impact of PM10 on neurodevelopmental processes.

Further aspects: Epidemiological and animal-based studies have provided insights into various factors that contribute to prenatal neurodevelopmental brain damage and the heightened risk of subsequent neuropsychiatric disorders. These factors include inflammation-induced maternal immune activation, prenatal exposure to immune challenges, and maternal obesity, stress, and gastrointestinal symptoms during pregnancy (Buffington et al., 2016; Kim et al., 2017; Shin Yim et al., 2017). Furthermore, certain compounds found in PM, such as alkylphenols, bisphenol A and phthalates, are recognized as endocrine-disrupting compounds that can disrupt the regulation of steroid hormones (Biemann et al., 2021). Such hormonal dysregulation has been linked not only endocrine system-related disorder, but also to neuropsychiatric disorders, including ASD, depression, ADHD and SCZ (Franca and Lotti, 2017).

Interestingly, a recent study has suggested that PM-induced dysbiosis of the gut microbiome can lead to schizophrenia-like behaviors and disrupt endocrine functions in mice (Yi et al., 2023). Additionally, several animal studies have indicated that the maternal gut microbiome plays a crucial role in the neurodevelopment of offspring during gestation, with sustained correlations and long-term pathological consequences during development (Hsiao et al., 2013; Kang et al., 2017). These findings collectively suggest that the gut-brain axis may be established through bidirectional communication among the nervous, endocrine, and immune systems. Consequently, disruption in the gut microbiome could offer valuable research insights into the mechanisms underlying neuropsychiatric disorders induced by prenatal exposure to PM.

DISCUSSION

Overall, numerous epidemiological studies on the negative effects of PM have focused on neuropsychiatric disorders. However, in recent years, the attention of stakeholders and the public, has turned to the potential neurodegenerative effects of PM particularly to the long-term effects of prenatal exposure to PM. From the present review it is possible to deduce how exposure to PM during pregnancy is associated with the onset of various neuropsychiatric disorders in offspring.

This review has some major limitations. Our study only included studies reporting the systemic and neuropathological changes in mother and fetuses. In future investigations, additional potential pathologies that might be present should be considered. In addition, new or disease-specific processes, as well as recognized detrimental mechanisms, such as oxidative stress and inflammation, were not thoroughly discussed. Further research on each neuropsychiatric disease is necessary to determine the precise consequences of fine particle air pollution exposure. There are, of course, a wide range of additional factors at play in addition to the effects of fine particulate air pollution exposure. Nonetheless, a number of epidemiological, clinical, and preclinical studies have found a link between particular neuropsychiatric and neurodevelopmental disorders and fine particle air pollution exposure. Hence, major interventional research will be needed in the future to investigate potential causal links.

ACKNOWLEDGMENTS

This study was supported by the research grant of Kangwon National University in 2024, the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (RS-2023-00242836) and the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (RS-2021-NR060130).

Footnotes

CONFLICT OF INTEREST

The authors declare no conflicts of interest.

AUTHOR CONTRIBUTIONS

Ho Jung Bae: Data Curation, Writing and Reviewing – Original Draft. Tamanna Jahan Mony: Conceptualization, Methodology, Investigation, Data Curation, Writing - Original Draft. Se Jin Park: Conceptualization, Writing - Original Draft and Overall Supervision.

REFERENCES

  1. Adil K. J., Gonzales E. L., Remonde C. G., Boo K. J., Jeon S. J., Shin C. Y. Autism-like behavioral phenotypes in mice treated with systemic N-methyl-D-aspartate. Biomol. Ther. (Seoul) 2022;30:232–237. doi: 10.4062/biomolther.2021.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alegria M., NeMoyer A., Falgas Bague I., Wang Y., Alvarez K. Social determinants of mental health: where we are and where we need to go. Curr. Psychiatry Rep. 2018;20:95. doi: 10.1007/s11920-018-0969-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Allen J. L., Liu X., Pelkowski S., Palmer B., Conrad K., Oberdorster G., Weston D., Mayer-Proschel M., Cory-Slechta D. A. Early postnatal exposure to ultrafine particulate matter air pollution: persistent ventriculomegaly, neurochemical disruption, and glial activation preferentially in male mice. Environ. Health Perspect. 2014;122:939–945. doi: 10.1289/ehp.1307984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Anokye R., Acheampong E., Budu-Ainooson A., Obeng E. I., Akwasi A. G. Prevalence of postpartum depression and interventions utilized for its management. Ann. Gen. Psychiatry. 2018;17:18. doi: 10.1186/s12991-018-0188-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Biemann R., Bluher M., Isermann B. Exposure to endocrine-disrupting compounds such as phthalates and bisphenol A is associated with an increased risk for obesity. Best Pract. Res. Clin. Endocrinol. Metab. 2021;35:101546. doi: 10.1016/j.beem.2021.101546. [DOI] [PubMed] [Google Scholar]
  6. Block M. L., Calderón-Garcidueñas L. Air pollution: mechanisms of neuroinflammation and CNS disease. Trends Neurosci. 2009;32:506–516. doi: 10.1016/j.tins.2009.05.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bolton J. L., Auten R. L., Bilbo S. D. Prenatal air pollution exposure induces sexually dimorphic fetal programming of metabolic and neuroinflammatory outcomes in adult offspring. Brain Behav. Immun. 2014;37:30–44. doi: 10.1016/j.bbi.2013.10.029. [DOI] [PubMed] [Google Scholar]
  8. Bolton J. L., Smith S. H., Huff N. C., Gilmour M. I., Foster W. M., Auten R. L., Bilbo S. D. Prenatal air pollution exposure induces neuroinflammation and predisposes offspring to weight gain in adulthood in a sex-specific manner. FASEB J. 2012;26:4743–4754. doi: 10.1096/fj.12-210989. [DOI] [PubMed] [Google Scholar]
  9. Bongaerts E., Lecante L. L., Bove H., Roeffaers M. B. J., Ameloot M., Fowler P. A., Nawrot T. S. Maternal exposure to ambient black carbon particles and their presence in maternal and fetal circulation and organs: an analysis of two independent population-based observational studies. Lancet Planet. Health. 2022;6:e804–e811. doi: 10.1016/S2542-5196(22)00200-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bove H., Bongaerts E., Slenders E., Bijnens E. M., Saenen N. D., Gyselaers W., Van Eyken P., Plusquin M., Roeffaers M. B. J., Ameloot M., Nawrot T. S. Ambient black carbon particles reach the fetal side of human placenta. Nat. Commun. 2019;10:3866. doi: 10.1038/s41467-019-11654-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Broseus L., Guilbert A., Hough I., Kloog I., Chauvaud A., Seyve E., Vaiman D., Heude B., Chevrier C., Tost J., Slama R., Lepeule J. Placental DNA methylation signatures of prenatal air pollution exposure and potential effects on birth outcomes: an analysis of three prospective cohorts. Lancet Planet. Health. 2024;8:e297–e308. doi: 10.1016/S2542-5196(24)00045-7. [DOI] [PubMed] [Google Scholar]
  12. Buffington S. A., Di Prisco G. V., Auchtung T. A., Ajami N. J., Petrosino J. F., Costa-Mattioli M. Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring. Cell. 2016;165:1762–1775. doi: 10.1016/j.cell.2016.06.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Catarino C., Santos-Silva A., Belo L., Rocha-Pereira P., Rocha S., Patrício B., Quintanilha A., Rebelo I. Inflammatory disturbances in preeclampsia: relationship between maternal and umbilical cord blood. J. Pregnancy. 2012;2012:684384. doi: 10.1155/2012/684384. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Chang Y. C., Chen W. T., Su S. H., Jung C. R., Hwang B. F. PM(2.5) exposure and incident attention-deficit/hyperactivity disorder during the prenatal and postnatal periods: a birth cohort study. Environ. Res. 2022;214:113769. doi: 10.1016/j.envres.2022.113769. [DOI] [PubMed] [Google Scholar]
  15. Chiu Y. H., Hsu H. H., Coull B. A., Bellinger D. C., Kloog I., Schwartz J., Wright R. O., Wright R. J. Prenatal particulate air pollution and neurodevelopment in urban children: examining sensitive windows and sex-specific associations. Environ. Int. 2016;87:56–65. doi: 10.1016/j.envint.2015.11.010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Cho S., Park Y. J., Bae J. S. Therapeutic effects of (+)-afzelechin on particulate matter-induced pulmonary injury. Biomol. Ther. (Seoul) 2024;32:162–169. doi: 10.4062/biomolther.2023.187. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Clifford A., Lang L., Chen R., Anstey K. J., Seaton A. Exposure to air pollution and cognitive functioning across the life course--a systematic literature review. Environ. Res. 2016;147:383–398. doi: 10.1016/j.envres.2016.01.018. [DOI] [PubMed] [Google Scholar]
  18. Cobley J. N., Fiorello M. L., Bailey D. M. 13 Reasons why the brain is susceptible to oxidative stress. Redox Biol. 2018;15:490–503. doi: 10.1016/j.redox.2018.01.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Collaborators C.-M. D. Global prevalence and burden of depressive and anxiety disorders in 204 countries and territories in 2020 due to the COVID-19 pandemic. Lancet. 2021;398:1700–1712. doi: 10.1016/S0140-6736(21)02143-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Costa L. G., Cole T. B., Dao K., Chang Y. C., Coburn J., Garrick J. M. Effects of air pollution on the nervous system and its possible role in neurodevelopmental and neurodegenerative disorders. Pharmacol. Ther. 2020;210:107523. doi: 10.1016/j.pharmthera.2020.107523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Costa L. G., Cole T. B., Dao K., Chang Y. C., Garrick J. M. Developmental impact of air pollution on brain function. Neurochem. Int. 2019;131:104580. doi: 10.1016/j.neuint.2019.104580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Cristaldi A., Fiore M., Oliveri Conti G., Pulvirenti E., Favara C., Grasso A., Copat C., Ferrante M. Possible association between PM(2.5) and neurodegenerative diseases: a systematic review. Environ. Res. 2022;208:112581. doi: 10.1016/j.envres.2021.112581. [DOI] [PubMed] [Google Scholar]
  23. Cserbik D., Chen J. C., McConnell R., Berhane K., Sowell E. R., Schwartz J., Hackman D. A., Kan E., Fan C. C., Herting M. M. Fine particulate matter exposure during childhood relates to hemispheric-specific differences in brain structure. Environ. Int. 2020;143:105933. doi: 10.1016/j.envint.2020.105933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Daellenbach K. R., Uzu G., Jiang J., Cassagnes L.-E., Leni Z., Vlachou A., Stefenelli G., Canonaco F., Weber S., Segers A., Kuenen J. J. P., Schaap M., Favez O., Albinet A., Aksoyoglu S., Dommen J., Baltensperger U., Geiser M., El Haddad I., Jaffrezo J.-L., Prévôt A. S. H. Sources of particulate-matter air pollution and its oxidative potential in Europe. Nature. 2020;587:414–419. doi: 10.1038/s41586-020-2902-8. [DOI] [PubMed] [Google Scholar]
  25. Eguchi R., Onozuka D., Ikeda K., Kuroda K., Ieiri I., Hagihara A. Psychological assessment of acute schizophrenia patients who experienced seclusion either alone or in combination with restraint. Int. J. Psychiatry Med. 2018;53:171–188. doi: 10.1177/0091217417749788. [DOI] [PubMed] [Google Scholar]
  26. Emam B., Shahsavani A., Khodagholi F., Zarandi S. M., Hopke P. K., Hadei M., Behbahani H., Yarahmadi M. Effects of PM2.5 and gases exposure during prenatal and early-life on autism-like phenotypes in male rat offspring. Part. Fibre Toxicol. 2020;17:8. doi: 10.1186/s12989-020-0336-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Faraone S. V., Mick E. Molecular genetics of attention deficit hyperactivity disorder. Psychiatr. Clin. North Am. 2010;33:159–180. doi: 10.1016/j.psc.2009.12.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Fernando P., Piao M. J., Herath H., Kang K. A., Ha K. S., Chae S., Hyun J. W. C-peptide ameliorates particulate matter 2.5-induced skin cell apoptosis by inhibiting NADPH oxidation. Biomol. Ther. (Seoul) 2025;33:221–230. doi: 10.4062/biomolther.2024.053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Fonken L. K., Xu X., Weil Z. M., Chen G., Sun Q., Rajagopalan S., Nelson R. J. Air pollution impairs cognition, provokes depressive-like behaviors and alters hippocampal cytokine expression and morphology. Mol. Psychiatry. 2011;16:987–995. 973. doi: 10.1038/mp.2011.76. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Franca K., Lotti T. M. Psycho-neuro-endocrine-immunology: a psychobiological concept. Adv. Exp. Med. Biol. 2017;996:123–134. doi: 10.1007/978-3-319-56017-5_11. [DOI] [PubMed] [Google Scholar]
  31. Frye R. E., Cakir J., Rose S., Delhey L., Bennuri S. C., Tippett M., Melnyk S., James S. J., Palmer R. F., Austin C., Curtin P., Arora M. Prenatal air pollution influences neurodevelopment and behavior in autism spectrum disorder by modulating mitochondrial physiology. Mol. Psychiatry. 2021;26:1561–1577. doi: 10.1038/s41380-020-00885-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Fusar-Poli P. Integrated mental health services for the developmental period (0 to 25 years): a critical review of the evidence. Front. Psychiatry. 2019;10:355. doi: 10.3389/fpsyt.2019.00355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Gangwar R. S., Bevan G. H., Palanivel R., Das L., Rajagopalan S. Oxidative stress pathways of air pollution mediated toxicity: recent insights. Redox Biol. 2020;34:101545. doi: 10.1016/j.redox.2020.101545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Garcia Rivera P., Dinkelacker B. T., Kioutsioukis I., Adams P. J., Pandis S. N. Source-resolved variability of fine particulate matter and human exposure in an urban area. Atmos. Chem. Phys. 2022;22:2011–2027. doi: 10.5194/acp-22-2011-2022. [DOI] [Google Scholar]
  35. Genkinger J. M., Stigter L., Jedrychowski W., Huang T. J., Wang S., Roen E. L., Majewska R., Kieltyka A., Mroz E., Perera F. P. Prenatal polycyclic aromatic hydrocarbon (PAH) exposure, antioxidant levels and behavioral development of children ages 6-9. Environ. Res. 2015;140:136–144. doi: 10.1016/j.envres.2015.03.017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Gernand A. D., Schulze K. J., Stewart C. P., West K. P., Jr, Christian P. Micronutrient deficiencies in pregnancy worldwide: health effects and prevention. Nat. Rev. Endocrinol. 2016;12:274–289. doi: 10.1038/nrendo.2016.37. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Gómez-Budia M., Konttinen H., Saveleva L., Korhonen P., Jalava P. I., Kanninen K. M., Malm T. Glial smog: interplay between air pollution and astrocyte-microglia interactions. Neurochem. Int. 2020;136:104715. doi: 10.1016/j.neuint.2020.104715. [DOI] [PubMed] [Google Scholar]
  38. Gong T., Dalman C., Wicks S., Dal H., Magnusson C., Lundholm C., Almqvist C., Pershagen G. Perinatal exposure to traffic-related air pollution and autism spectrum disorders. Environ. Health Perspect. 2017;125:119–126. doi: 10.1289/EHP118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Greene N. D., Copp A. J. Neural tube defects. Ann. Rev. Neurosci. 2014;37:221–242. doi: 10.1146/annurev-neuro-062012-170354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Guo J., Chai G., Song X., Hui X., Li Z., Feng X., Yang K. Long-term exposure to particulate matter on cardiovascular and respiratory diseases in low- and middle-income countries: a systematic review and meta-analysis. Front. Public Health. 2023;11:1134341. doi: 10.3389/fpubh.2023.1134341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Guxens M., Garcia-Esteban R., Giorgis-Allemand L., Forns J., Badaloni C., Ballester F., Beelen R., Cesaroni G., Chatzi L., de Agostini M., de Nazelle A., Eeftens M., Fernandez M. F., Fernández-Somoano A., Forastiere F., Gehring U., Ghassabian A., Heude B., Jaddoe V. W., Klümper C., Kogevinas M., Krämer U., Larroque B., Lertxundi A., Lertxuni N., Murcia M., Navel V., Nieuwenhuijsen M., Porta D., Ramos R., Roumeliotaki T., Slama R., Sørensen M., Stephanou E. G., Sugiri D., Tardón A., Tiemeier H., Tiesler C. M., Verhulst F. C., Vrijkotte T., Wilhelm M., Brunekreef B., Pershagen G., Sunyer J. Air pollution during pregnancy and childhood cognitive and psychomotor development: six European birth cohorts. Epidemiology. 2014;25:636–647. doi: 10.1097/EDE.0000000000000133. [DOI] [PubMed] [Google Scholar]
  42. Guxens M., Ghassabian A., Gong T., Garcia-Esteban R., Porta D., Giorgis-Allemand L., Almqvist C., Aranbarri A., Beelen R., Badaloni C., Cesaroni G., de Nazelle A., Estarlich M., Forastiere F., Forns J., Gehring U., Ibarluzea J., Jaddoe V. W., Korek M., Lichtenstein P., Nieuwenhuijsen M. J., Rebagliato M., Slama R., Tiemeier H., Verhulst F. C., Volk H. E., Pershagen G., Brunekreef B., Sunyer J. Air pollution exposure during pregnancy and childhood autistic traits in four european population-based cohort studies: the ESCAPE project. Environ. Health Perspect. 2016;124:133–140. doi: 10.1289/ehp.1408483. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Guxens M., Lubczynska M. J., Muetzel R. L., Dalmau-Bueno A., Jaddoe V. W. V., Hoek G., van der Lugt A., Verhulst F. C., White T., Brunekreef B., Tiemeier H., El Marroun H. Air pollution exposure during fetal life, brain morphology, and cognitive function in school-age children. Biol. Psychiatry. 2018;84:295–303. doi: 10.1016/j.biopsych.2018.01.016. [DOI] [PubMed] [Google Scholar]
  44. Ha S., Yeung E., Bell E., Insaf T., Ghassabian A., Bell G., Muscatiello N., Mendola P. Prenatal and early life exposures to ambient air pollution and development. Environ. Res. 2019;174:170–175. doi: 10.1016/j.envres.2019.03.064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Harris M. H., Gold D. R., Rifas-Shiman S. L., Melly S. J., Zanobetti A., Coull B. A., Schwartz J. D., Gryparis A., Kloog I., Koutrakis P., Bellinger D. C., White R. F., Sagiv S. K., Oken E. Prenatal and childhood traffic-related pollution exposure and childhood cognition in the Project Viva Cohort (Massachusetts, USA) Environ. Health Perspect. 2015;123:1072–1078. doi: 10.1289/ehp.1408803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Hoang N. M. H., Kim S., Nguyen H. D., Kim M., Kim J., Kim B. C., Park D., Lee S., Yu B. P., Chung H. Y., Kim M. S. Age-dependent sensitivity to the neurotoxic environmental metabolite, 1,2-diacetylbenzene. Biomol. Ther. (Seoul) 2021;29:399–409. doi: 10.4062/biomolther.2020.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Hodges H., Fealko C., Soares N. Autism spectrum disorder: definition, epidemiology, causes, and clinical evaluation. Transl. Pediatr. 2020;9:S55–S65. doi: 10.21037/tp.2019.09.09. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Hsiao E. Y., McBride S. W., Hsien S., Sharon G., Hyde E. R., McCue T., Codelli J. A., Chow J., Reisman S. E., Petrosino J. F., Patterson P. H., Mazmanian S. K. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155:1451–1463. doi: 10.1016/j.cell.2013.11.024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Jaeschke K., Hanna F., Ali S., Chowdhary N., Dua T., Charlson F. Global estimates of service coverage for severe mental disorders: findings from the WHO Mental Health Atlas 2017. Glob. Ment. Health (Camb.) 2021;8:e27. doi: 10.1017/gmh.2021.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Jang H. S., Lee J. E., Myung C. H., Park J. I., Jo C. S., Hwang J. S. Particulate matter-induced Aryl Hydrocarbon Receptor regulates autophagy in keratinocytes. Biomol. Ther. (Seoul) 2019;27:570–576. doi: 10.4062/biomolther.2019.025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Johnson N. M., Hoffmann A. R., Behlen J. C., Lau C., Pendleton D., Harvey N., Shore R., Li Y., Chen J., Tian Y., Zhang R. Air pollution and children's health-a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter. Environ. Health Prev. Med. 2021;26:72. doi: 10.1186/s12199-021-00995-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Jorcano A., Lubczyńska M. J., Pierotti L., Altug H., Ballester F., Cesaroni G., El Marroun H., Fernández-Somoano A., Freire C., Hanke W., Hoek G., Ibarluzea J., Iñiguez C., Jansen P. W., Lepeule J., Markevych I., Polańska K., Porta D., Schikowski T., Slama R., Standl M., Tardon A., Vrijkotte T. G. M., von Berg A., Tiemeier H., Sunyer J., Guxens M. Prenatal and postnatal exposure to air pollution and emotional and aggressive symptoms in children from 8 European birth cohorts. Environ. Int. 2019;131:104927. doi: 10.1016/j.envint.2019.104927. [DOI] [PubMed] [Google Scholar]
  53. Jukarainen S., Kiiskinen T., Kuitunen S., Havulinna A. S., Karjalainen J., Cordioli M., Rämö J. T., Mars N., Samocha K. E., Ollila H. M., Pirinen M., Ganna A. Genetic risk factors have a substantial impact on healthy life years. Nat. Med. 2022;28:1893–1901. doi: 10.1038/s41591-022-01957-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Kang D. W., Adams J. B., Gregory A. C., Borody T., Chittick L., Fasano A., Khoruts A., Geis E., Maldonado J., McDonough-Means S., Pollard E. L., Roux S., Sadowsky M. J., Lipson K. S., Sullivan M. B., Caporaso J. G., Krajmalnik-Brown R. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome. 2017;5:10. doi: 10.1186/s40168-016-0225-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Kanner J., Pollack A. Z., Ranasinghe S., Stevens D. R., Nobles C., Rohn M. C. H., Sherman S., Mendola P. Chronic exposure to air pollution and risk of mental health disorders complicating pregnancy. Environ. Res. 2021;196:110937. doi: 10.1016/j.envres.2021.110937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Kim E., Park H., Hong Y. C., Ha M., Kim Y., Kim B. N., Kim Y., Roh Y. M., Lee B. E., Ryu J. M., Kim B. M., Ha E. H. Prenatal exposure to PM(1)(0) and NO(2) and children's neurodevelopment from birth to 24 months of age: mothers and Children's Environmental Health (MOCEH) study. Sci. Total Environ. 2014;481:439–445. doi: 10.1016/j.scitotenv.2014.01.107. [DOI] [PubMed] [Google Scholar]
  57. Kim S., Kim H., Yim Y. S., Ha S., Atarashi K., Tan T. G., Longman R. S., Honda K., Littman D. R., Choi G. B., Huh J. R. Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring. Nature. 2017;549:528–532. doi: 10.1038/nature23910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Kulas J. A., Hettwer J. V., Sohrabi M., Melvin J. E., Manocha G. D., Puig K. L., Gorr M. W., Tanwar V., McDonald M. P., Wold L. E., Combs C. K. In utero exposure to fine particulate matter results in an altered neuroimmune phenotype in adult mice. Environ. Pollut. 2018;241:279–288. doi: 10.1016/j.envpol.2018.05.047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Lee A. G., Cowell W., Kannan S., Ganguri H. B., Nentin F., Wilson A., Coull B. A., Wright R. O., Baccarelli A., Bollati V., Wright R. J. Prenatal particulate air pollution and newborn telomere length: effect modification by maternal antioxidant intakes and infant sex. Environ. Res. 2020;187:109707. doi: 10.1016/j.envres.2020.109707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Lei X., Zhang Y., Wang Z., Lu Z., Pan C., Zhang S., Chen Q., Yuan T., Zhang J., Gao Y., Tian Y. Effects of prenatal exposure to PM2.5 and its composition on cognitive and motor functions in children at 12 months of age: The Shanghai Birth Cohort Study. Environ. Int. 2022;170:107597. doi: 10.1016/j.envint.2022.107597. [DOI] [PubMed] [Google Scholar]
  61. Lertxundi A., Andiarena A., Martínez M. D., Ayerdi M., Murcia M., Estarlich M., Guxens M., Sunyer J., Julvez J., Ibarluzea J. Prenatal exposure to PM(2.5) and NO(2) and sex-dependent infant cognitive and motor development. Environ. Res. 2019;174:114–121. doi: 10.1016/j.envres.2019.04.001. [DOI] [PubMed] [Google Scholar]
  62. Li J., Huang L., Han B., van der Kuijp T. J., Xia Y., Chen K. Exposure and perception of PM2.5 pollution on the mental stress of pregnant women. Environ. Int. 2021;156:106686. doi: 10.1016/j.envint.2021.106686. [DOI] [PubMed] [Google Scholar]
  63. Li X., Huang S., Jiao A., Yang X., Yun J., Wang Y., Xue X., Chu Y., Liu F., Liu Y., Ren M., Chen X., Li N., Lu Y., Mao Z., Tian L., Xiang H. Association between ambient fine particulate matter and preterm birth or term low birth weight: an updated systematic review and meta-analysis. Environ. Pollut. 2017;227:596–605. doi: 10.1016/j.envpol.2017.03.055. [DOI] [PubMed] [Google Scholar]
  64. Lim Y. H., Kim W., Choi Y., Kim H. C., Na G., Kim H. R., Hong Y. C. Effects of particulate respirator use on cardiopulmonary function in elderly women: a quasi-experimental study. J. Korean Med. Sci. 2020;35:e64. doi: 10.3346/jkms.2020.35.e64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Lin H.-C., Guo J.-M., Ge P., Ou P. Association between prenatal exposure to ambient particulate matter and risk of hypospadias in offspring: a systematic review and meta-analysis. Environ. Res. 2021;192:110190. doi: 10.1016/j.envres.2020.110190. [DOI] [PubMed] [Google Scholar]
  66. Lin Y., Zhou L., Xu J., Luo Z., Kan H., Zhang J., Yan C., Zhang J. The impacts of air pollution on maternal stress during pregnancy. Sci. Rep. 2017;7:40956. doi: 10.1038/srep40956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Lindahl V., Pearson J. L., Colpe L. Prevalence of suicidality during pregnancy and the postpartum. Arch. Womens Ment. Health. 2005;8:77–87. doi: 10.1007/s00737-005-0080-1. [DOI] [PubMed] [Google Scholar]
  68. Liu B., Fang X., Strodl E., He G., Ruan Z., Wang X., Liu L., Chen W. Fetal exposure to air pollution in late pregnancy significantly increases ADHD-risk behavior in early childhood. Int. J. Environ. Res. Public Health. 2022;19:10482. doi: 10.3390/ijerph191710482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Mahone E. M., Denckla M. B. Attention-deficit/hyperactivity disorder: a historical neuropsychological perspective. J. Int. Neuropsychol. Soc. 2017;23:916–929. doi: 10.1017/S1355617717000807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Manisalidis I., Stavropoulou E., Stavropoulos A., Bezirtzoglou E. Environmental and health impacts of air pollution: a review. Front Public Health. 2020;8:14. doi: 10.3389/fpubh.2020.00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Margolis A. E., Herbstman J. B., Davis K. S., Thomas V. K., Tang D., Wang Y., Wang S., Perera F. P., Peterson B. S., Rauh V. A. Longitudinal effects of prenatal exposure to air pollutants on self-regulatory capacities and social competence. J. Child Psychol. Psychiatry. 2016;57:851–860. doi: 10.1111/jcpp.12548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. McGuinn L. A., Bellinger D. C., Colicino E., Coull B. A., Just A. C., Kloog I., Osorio-Valencia E., Schnaas L., Wright R. J., Téllez-Rojo M. M., Wright R. O., Horton M. K. Prenatal PM(2.5) exposure and behavioral development in children from Mexico City. Neurotoxicology. 2020;81:109–115. doi: 10.1016/j.neuro.2020.09.036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Michikawa T., Morokuma S., Yamazaki S., Takami A., Sugata S., Yoshino A., Takeda Y., Nakahara K., Saito S., Hoshi J., Kato K., Nitta H., Nishiwaki Y. Exposure to chemical components of fine particulate matter and ozone, and placenta-mediated pregnancy complications in Tokyo: a register-based study. J. Exp. Sci. Environ. Epidemiol. 2022;32:135–145. doi: 10.1038/s41370-021-00299-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Min J. Y., Min K. B. Exposure to ambient PM(10) and NO(2) and the incidence of attention-deficit hyperactivity disorder in childhood. Environ. Int. 2017;99:221–227. doi: 10.1016/j.envint.2016.11.022. [DOI] [PubMed] [Google Scholar]
  75. Morgan Z. E. M., Bailey M. J., Trifonova D. I., Naik N. C., Patterson W. B., Lurmann F. W., Chang H. H., Peterson B. S., Goran M. I., Alderete T. L. Prenatal exposure to ambient air pollution is associated with neurodevelopmental outcomes at 2 years of age. Environ Health. 2023;22:11. doi: 10.1186/s12940-022-00951-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Morris R. H., Counsell S. J., McGonnell I. M., Thornton C. Early life exposure to air pollution impacts neuronal and glial cell function leading to impaired neurodevelopment. BioEssays. 2021;43:e2000288. doi: 10.1002/bies.202000288. [DOI] [PubMed] [Google Scholar]
  77. Mortamais M., Pujol J., Martínez-Vilavella G., Fenoll R., Reynes C., Sabatier R., Rivas I., Forns J., Vilor-Tejedor N., Alemany S., Cirach M., Alvarez-Pedrerol M., Nieuwenhuijsen M., Sunyer J. Effects of prenatal exposure to particulate matter air pollution on corpus callosum and behavioral problems in children. Environ Res. 2019;178:108734. doi: 10.1016/j.envres.2019.108734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Müller N., Weidinger E., Leitner B., Schwarz M. J. The role of inflammation in schizophrenia. Front. Neurosci. 2015;9:372. doi: 10.3389/fnins.2015.00372. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Nephew B. C., Nemeth A., Hudda N., Beamer G., Mann P., Petitto J., Cali R., Febo M., Kulkarni P., Poirier G., King J., Durant J. L., Brugge D. Traffic-related particulate matter affects behavior, inflammation, and neural integrity in a developmental rodent model. Environ. Res. 2020;183:109242. doi: 10.1016/j.envres.2020.109242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Niedzwiecki M. M., Rosa M. J., Solano-González M., Kloog I., Just A. C., Martínez-Medina S., Schnaas L., Tamayo-Ortiz M., Wright R. O., Téllez-Rojo M. M., Wright R. J. Particulate air pollution exposure during pregnancy and postpartum depression symptoms in women in Mexico City. Environ. Int. 2020;134:105325. doi: 10.1016/j.envint.2019.105325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. O'Piela D. R., Durisek G. R., Escobar Y. H., Mackos A. R., Wold L. E. Particulate matter and Alzheimer's disease: an intimate connection. Trends Mol. Med. 2022;28:770–780. doi: 10.1016/j.molmed.2022.06.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Olvera Alvarez H. A., Kubzansky L. D., Campen M. J., Slavich G. M. Early life stress, air pollution, inflammation, and disease: an integrative review and immunologic model of social-environmental adversity and lifespan health. Neurosci. Biobehav. Rev. 2018;92:226–242. doi: 10.1016/j.neubiorev.2018.06.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Onoda A., Kawasaki T., Tsukiyama K., Takeda K., Umezawa M. Carbon nanoparticles induce endoplasmic reticulum stress around blood vessels with accumulation of misfolded proteins in the developing brain of offspring. Sci. Rep. 2020;10:10028. doi: 10.1038/s41598-020-66744-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Pagalan L., Bickford C., Weikum W., Lanphear B., Brauer M., Lanphear N., Hanley G. E., Oberlander T. F., Winters M. Association of prenatal exposure to air pollution with autism spectrum disorder. JAMA Pediatr. 2019;173:86–92. doi: 10.1001/jamapediatrics.2018.3101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Park E. S., Shin C. Y., Jeon S. J., Ham B. J. Is there such a thing as post-viral depression?: implications for precision medicine. Biomol. Ther. (Seoul) 2024a;32:659–684. doi: 10.4062/biomolther.2024.170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Park Y., Paing Y. M. M., Cho N., Kim C., Yoo J., Choi J. W., Lee S. H. Quinic acid alleviates behavior impairment by reducing neuroinflammation and MAPK activation in LPS-treated mice. Biomol. Ther. (Seoul) 2024b;32:309–318. doi: 10.4062/biomolther.2023.184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Pedersen C. B., Mortensen P. B. Urbanization and traffic related exposures as risk factors for Schizophrenia. BMC Psychiatry. 2006;6:2. doi: 10.1186/1471-244X-6-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Perrone S., Santacroce A., Longini M., Proietti F., Bazzini F., Buonocore G. The free radical diseases of prematurity: from cellular mechanisms to bedside. Oxid. Med. Cell. Longev. 2018;2018:7483062. doi: 10.1155/2018/7483062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Peters R., Ee N., Peters J., Booth A., Mudway I., Anstey K. J. Air pollution and dementia: a systematic review. J. Alzheimers Dis. 2019;70:S145–S163. doi: 10.3233/JAD-180631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  90. Putnam K. T., Wilcox M., Robertson-Blackmore E., Sharkey K., Bergink V., Munk-Olsen T., Deligiannidis K. M., Payne J., Altemus M., Newport J., Apter G., Devouche E., Viktorin A., Magnusson P., Penninx B., Buist A., Bilszta J., O'Hara M., Stuart S., Brock R., Roza S., Tiemeier H., Guille C., Epperson C. N., Kim D., Schmidt P., Martinez P., Di Florio A., Wisner K. L., Stowe Z., Jones I., Sullivan P. F., Rubinow D., Wildenhaus K., Meltzer-Brody S. Clinical phenotypes of perinatal depression and time of symptom onset: analysis of data from an international consortium. Lancet Psychiatry. 2017;4:477–485. doi: 10.1016/S2215-0366(17)30136-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. Rahman M. M., Carter S. A., Lin J. C., Chow T., Yu X., Martinez M. P., Levitt P., Chen Z., Chen J. C., Rud D., Lewinger J. P., Eckel S. P., Schwartz J., Lurmann F. W., Kleeman M. J., McConnell R., Xiang A. H. Prenatal exposure to tailpipe and non-tailpipe tracers of particulate matter pollution and autism spectrum disorders. Environ. Int. 2023;171:107736. doi: 10.1016/j.envint.2023.107736. [DOI] [PMC free article] [PubMed] [Google Scholar]
  92. Rahman M. M., Shu Y. H., Chow T., Lurmann F. W., Yu X., Martinez M. P., Carter S. A., Eckel S. P., Chen J. C., Chen Z., Levitt P., Schwartz J., McConnell R., Xiang A. H. Prenatal exposure to air pollution and autism spectrum disorder: sensitive windows of exposure and sex differences. Environ. Health Perspect. 2022;130:17008. doi: 10.1289/EHP9509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. Ransohoff R. M., Brown M. A. Innate immunity in the central nervous system. J. Clin. Invest. 2012;122:1164–1171. doi: 10.1172/JCI58644. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Rivas I., Basagana X., Cirach M., Lopez-Vicente M., Suades-Gonzalez E., Garcia-Esteban R., Alvarez-Pedrerol M., Dadvand P., Sunyer J. Association between early life exposure to air pollution and working memory and attention. Environ. Health Perspect. 2019;127:57002. doi: 10.1289/EHP3169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. Saadeh R. A., Jayawardene W. P., Lohrmann D. K., Youssefagha A. H., Allouh M. Z. Air pollutants and attention deficit hyperactivity disorder medication administration in elementary schools. Biomed. Rep. 2022;17:85. doi: 10.3892/br.2022.1568. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. Saenen N. D., Martens D. S., Neven K. Y., Alfano R., Bove H., Janssen B. G., Roels H. A., Plusquin M., Vrijens K., Nawrot T. S. Air pollution-induced placental alterations: an interplay of oxidative stress, epigenetics, and the aging phenotype? Clin. Epigenetics. 2019;11:124. doi: 10.1186/s13148-019-0688-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Sankowski R., Mader S., Valdés-Ferrer S. I. Systemic inflammation and the brain: novel roles of genetic, molecular, and environmental cues as drivers of neurodegeneration. Front. Cell. Neurosci. 2015;9:28. doi: 10.3389/fncel.2015.00028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  98. Shang M., Tang M., Xue Y. Neurodevelopmental toxicity induced by airborne particulate matter. J. Appl. Toxicol. 2023;43:167–185. doi: 10.1002/jat.4382. [DOI] [PubMed] [Google Scholar]
  99. Sheffield P. E., Speranza R., Chiu Y. M., Hsu H. L., Curtin P. C., Renzetti S., Pajak A., Coull B., Schwartz J., Kloog I., Wright R. J. Association between particulate air pollution exposure during pregnancy and postpartum maternal psychological functioning. PLoS One. 2018;13:e0195267. doi: 10.1371/journal.pone.0195267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  100. Shih P., Huang C. C., Pan S. C., Chiang T. L., Guo Y. L. Hyperactivity disorder in children related to traffic-based air pollution during pregnancy. Environ. Res. 2020;188:109588. doi: 10.1016/j.envres.2020.109588. [DOI] [PubMed] [Google Scholar]
  101. Shin Yim Y., Park A., Berrios J., Lafourcade M., Pascual L. M., Soares N., Yeon Kim J., Kim S., Kim H., Waisman A., Littman D. R., Wickersham I. R., Harnett M. T., Huh J. R., Choi G. B. Reversing behavioural abnormalities in mice exposed to maternal inflammation. Nature. 2017;549:482–487. doi: 10.1038/nature23909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  102. Sram R. J., Veleminsky M., Jr, Veleminsky M., Sr, Stejskalova J. The impact of air pollution to central nervous system in children and adults. Neuro Endocrinol. Lett. 2017;38:389–396. [PubMed] [Google Scholar]
  103. Stoner R., Chow M. L., Boyle M. P., Sunkin S. M., Mouton P. R., Roy S., Wynshaw-Boris A., Colamarino S. A., Lein E. S., Courchesne E. Patches of disorganization in the neocortex of children with autism. N. Engl. J. Med. 2014;370:1209–1219. doi: 10.1056/NEJMoa1307491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Szepesi Z., Manouchehrian O., Bachiller S., Deierborg T. Bidirectional Microglia-Neuron Communication in Health and Disease. Front. Cell. Neurosci. 2018;12:323. doi: 10.3389/fncel.2018.00323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  105. Tau G. Z., Peterson B. S. Normal development of brain circuits. Neuropsychopharmacology. 2010;35:147–168. doi: 10.1038/npp.2009.115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  106. Thygesen M., Holst G. J., Hansen B., Geels C., Kalkbrenner A., Schendel D., Brandt J., Pedersen C. B., Dalsgaard S. Exposure to air pollution in early childhood and the association with Attention-Deficit Hyperactivity Disorder. Environ Res. 2020;183:108930. doi: 10.1016/j.envres.2019.108930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  107. Tzivian L., Jokisch M., Winkler A., Weimar C., Hennig F., Sugiri D., Soppa V. J., Dragano N., Erbel R., Jockel K. H., Moebus S., Hoffmann B., Heinz Nixdorf Recall Study G. Associations of long-term exposure to air pollution and road traffic noise with cognitive function-An analysis of effect measure modification. Environ. Int. 2017;103:30–38. doi: 10.1016/j.envint.2017.03.018. [DOI] [PubMed] [Google Scholar]
  108. Wang H., Zhang H., Li J., Liao J., Liu J., Hu C., Sun X., Zheng T., Xia W., Xu S., Wang S., Li Y. Prenatal and early postnatal exposure to ambient particulate matter and early childhood neurodevelopment: a birth cohort study. Environ. Res. 2022;210:112946. doi: 10.1016/j.envres.2022.112946. [DOI] [PubMed] [Google Scholar]
  109. Wang K., Tian Y., Zheng H., Shan S., Zhao X., Liu C. Maternal exposure to ambient fine particulate matter and risk of premature rupture of membranes in Wuhan, Central China: a cohort study. Environ. Health. 2019;18:96. doi: 10.1186/s12940-019-0534-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  110. Wang X., Ding H., Ryan L., Xu X. Association between air pollution and low birth weight: a community-based study. Environ. Health Perspect. 1997;105:514–520. doi: 10.1289/ehp.97105514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  111. Wei Y., Zhang J. J., Li Z., Gow A., Chung K. F., Hu M., Sun Z., Zeng L., Zhu T., Jia G., Li X., Duarte M., Tang X. Chronic exposure to air pollution particles increases the risk of obesity and metabolic syndrome: findings from a natural experiment in Beijing. FASEB J. 2016;30:2115–2122. doi: 10.1096/fj.201500142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Xu Z., Liu Z., Lu L., Liao W., Yang C., Duan Z., Zhou Q., He W., Zhang E., Li N., Ju K. Assessing the causal effects of long-term exposure to PM(2.5) during pregnancy on cognitive function in the adolescence: evidence from a nationwide cohort in China. Environ. Poll. 2022;293:118560. doi: 10.1016/j.envpol.2021.118560. [DOI] [PubMed] [Google Scholar]
  113. Yamashita K., Yoshioka Y., Higashisaka K., Mimura K., Morishita Y., Nozaki M., Yoshida T., Ogura T., Nabeshi H., Nagano K., Abe Y., Kamada H., Monobe Y., Imazawa T., Aoshima H., Shishido K., Kawai Y., Mayumi T., Tsunoda S., Itoh N., Yoshikawa T., Yanagihara I., Saito S., Tsutsumi Y. Silica and titanium dioxide nanoparticles cause pregnancy complications in mice. Nat. Nanotechnol. 2011;6:321–328. doi: 10.1038/nnano.2011.41. [DOI] [PubMed] [Google Scholar]
  114. Yi C., Wang Q., Qu Y., Niu J., Oliver B. G., Chen H. In-utero exposure to air pollution and early-life neural development and cognition. Ecotoxicol. Environ. Saf. 2022;238:113589. doi: 10.1016/j.ecoenv.2022.113589. [DOI] [PubMed] [Google Scholar]
  115. Yi W., Ji Y., Gao H., Luo S., Pan R., Song J., He Y., Li Y., Wu Y., Yan S., Liang Y., Sun X., Jin X., Mei L., Cheng J., Su H. Effects of urban particulate matter on gut microbiome and partial schizophrenia-like symptoms in mice: Evidence from shotgun metagenomic and metabolomic profiling. Sci. Total Environ. 2023;857:159305. doi: 10.1016/j.scitotenv.2022.159305. [DOI] [PubMed] [Google Scholar]
  116. Yokota S., Mizuo K., Moriya N., Oshio S., Sugawara I., Takeda K. Effect of prenatal exposure to diesel exhaust on dopaminergic system in mice. Neurosci. Lett. 2009;449:38–41. doi: 10.1016/j.neulet.2008.09.085. [DOI] [PubMed] [Google Scholar]
  117. Zhang J., Liu J., Ren L., Wei J., Duan J., Zhang L., Zhou X., Sun Z. PM(2.5) induces male reproductive toxicity via mitochondrial dysfunction, DNA damage and RIPK1 mediated apoptotic signaling pathway. Sci. Total Environ. 2018;634:1435–1444. doi: 10.1016/j.scitotenv.2018.03.383. [DOI] [PubMed] [Google Scholar]

Articles from Biomolecules & Therapeutics are provided here courtesy of Korean Society of Applied Pharmacology

RESOURCES