Table 1.

Epidemiological studies’ descriptions on prenatal/pregnancy air pollutants and ADHD/hyperactivity disorder.

Author/Year/Location/Design	Participants	Exposure Time	Exposure Measurement and Method	Pollutants	ADHD Symptoms and Diagnosis	Covariates	Results
Perera et al. (2012) USA Cohort [51]	253 children aged 6–7 years	Pregnancy	PAH measured by personal air monitoring of the mothers during pregnancy and DNA adducts specific to benzo[a]pyrene (BaP), a representative PAH, in maternal and cord blood.	PAH	Tool: CBCL/6–18. Method: The questionnaire was completed by mothers under the guidance of research workers trained in neurodevelopmental testing.	Child: sex, prenatal ETS. Mother: gestational age, maternal IQ, maternal education, ethnicity, prenatal demoralization, and age at assessment Family/environment: heating season and home caretaking environment (HOME inventory).	High prenatal PAH exposure was positively associated with symptoms in the CBCL syndromic scales of anxious/depressed and attention problems.
Gong et al. (2014) Sweden Cohort [52]	3426 twins’ parents. Children aged 9 or 12 years	Pregnancy, child’s first year	Air pollution concentrations at residential address during pregnancy of the mother and child‘s first year of life by dispersion model to obtain historical emission database on NOx and PM (PM10).	NOx and PM (PM10)	Tool: children neurodevelopment outcomes measures with A-TAC. Method: a telephone interview was conducted with parents.	Child: gender. Mother: gestational age, birth weight, maternal age at birth and maternal smoking during pregnancy. Family/environment: parity, neighbourhood deprivation index at child’s birth, and socio-economic data (maternal marital status, parental education, family income, and family size).	No clear association was found between air pollutants (NOx and PM10) and during pregnancy and in the first of child’s life and ADHD.
Perera et al. (2014) USA Cohort [53]	233, children aged 9 years	Pregnancy	Prenatal PAH exposure estimated by levels of PAH-DNA adducts in maternal and cord blood collected at delivery.	PAH	Tool: CBCL/6–18 and CPRS–Revised: long version. Method: questionnaires were answered by mothers under the guidance of trained research worker.	Child: gender, child ethnicity, and prenatal ETS. Mother: gestational age, maternal intelligence, maternal education, maternal demoralization score, and maternal ADHD. Family/environment: heating season and home caretaking environment (HOME inventory).	High maternal adducts were positivity associated with the DSM-oriented attention deficit/hyperactivity problems scale on the CBCL, albeit not significant.
Fuertes et al. (2016) Germany Cohort [54]	4745 children aged 10 and 15 years	At birth/pregnancy	NO2, PM10 mass and absorbance assigned at child’s birth, 10- and 15 years home address using land-use regression model.	NO2 and PM (PM10, PM2.5 mass and absorbance	Tool: SDQ parent and self-reported versions. Method: the questionnaire was parent-informed at age of 10 years and self-informed at age of 15 years.	Child: sex. Mother: exact age at follow-up, parental education, maternal age at birth, smoking during pregnancy, second-hand smoke exposure, time spent in front of the screen, time spent outside, and single parent status. Family/environment: parental psychopathology.	Hyperactivity/inattention symptoms at 10 and 15 years were associated with PM2.5 mass and absorbance estimated.
Yorifuji et al. (2016) Japan Cohort [55]	33,911 children at 2.5 and 5.5 age	Pregnancy	Air pollutants measuring throughout stations in Japan database managed by the National Institute for Environmental Studies in Japan during pregnancy of mothers.	SPM, NO2 and SO2	Tool: national survey including three ADHD questions related to attention, self-regulation, and socially appropriate behaviours at the age of 5.5 years. Methods: items were completed by parents using “yes” or “no” categories.	Child: sex, birth month. Mother: maternal age, maternal education, and maternal smoking habit. Family/environment: parental income at the birth year of the child, type of residential area, per capita taxable income, population density of each municipality, and parity.	Air pollution exposure, in particular SPM, NO2 and SO2, during gestation were positively associated with risk for behavioural problems related to attention and delinquent or aggressive behaviour.
Yorifuji et al. (2017) Japan Cohort [56]	33,911 children at 8 years	Pregnancy	Measured at all general monitoring stations throughout Japan database managed by the National Institute for Environmental Studies in Japan during pregnancy of mothers.	SPM, NO2 and SO2	Tool: CBCL/4–18, Japanese edition and three questions related to attention problems: (1) Does your child interrupt people? (2) Can your child wait his/her turn during play? (3) Can your child pay attention to the surrounding area when crossing the street? Method: parent-informed questionnaire at child’s 8 years of age.	Child: sex, birth month. Mother: maternal age, maternal education, and maternal smoking habit. Family/environment: parental income at the birth year of the child, type of residential area, per capita taxable income, population density of each municipality, and parity.	Positive association between prenatal traffic-related air pollution exposure, in particular suspended PM, and behavioural developmental delays related to attention, self-regulation and socially appropriate behaviour was found at age 5.5 years. Additionally, observed decreased in self-inhibitory control and poor impulsive control; behaviours associated with ADHD.
Forns et al. (2018) European countries (Denmark, Netherlands, Germany, Italy, Spain, Sweden, and France) Cohort [57]	29,127 children aged 3-10 years	Pregnancy	Air pollutant concentrations measured at participants’ home addresses at birth and during pregnancy, using land-use regression model.	NO2 and PM (PM10, PM2.5, PMcoarse and absorbance	Tool: A-TAC, CBCL/1 ½–5, SDQ parent version and ADHD-DSM-IV list. Method: the questionnaires were completed by parents (A-TAC, CBCL 1 ½–5, SDQ) and by teachers (ADHD-DSM-IV scale).	Child: age, sex, and season of birth. Mother: level of education, age at delivery, country of birth, prenatal smoking, mother’s height, pre-pregnancy weight, body mass index. Family/environment: type of living area.	No association was found with air pollution during pregnancy and ADHD symptoms in children.
Perera et al. (2018) USA Cohort [58]	351 children aged 9 years	Pregnancy	PAH exposure, PAH-DNA adducts were measured in maternal blood at delivery.	PAH	Tool: CBCL/6–18, CPRS—Revised: long version. Method: reported by mothers and under the guidance of trained research worker.	Child: sex, child anxiety and depression symptoms at 9 years old, ethnicity, and nonverbal intelligence (TONI-2). Mother: ethnicity, prenatal ETS, maternal education, gestational age, age at assessment, and maternal ADHD. Family/environment: heating season and home caretaking environment (HOME inventory).	Children with high prenatal PAH exposure (adducts) developed more ADHD symptoms than those with low prenatal PAH exposure.
Oudin et al. (2019) Sweden Cohort [59]	>48,000 children	Pregnancy born between 1998–2006	Concentration of NOx obtained from local sources, such as traffic using Gaussian dispersion model for NOx (AERMOD).	NOx	Tool: None Method: Information about children with ADHD was extracted from public databases. ADHD diagnosis criteria: ICD-10.	Child: sex Mother: parental birth country, potential perinatal and maternal risk factors (maternal smoking, maternal age) Family/environment: socio-economic status (maternal education, family income), distance from psychiatric unit.	No associations were found between prenatal NOx exposure and the risk of developing ADHD.
Pagliaccio et al. (2020) USA Cohort [60]	319 children	3rd trimester of Pregnancy born between 1998–2006	Personal air monitoring collected an external measure of exposure to PAH and maternal PAH-DNA adducts were also collected from a smaller subset.	PAH	Tool: CBCL/1½–5 and CBCL/6–18 years, CPRS-Revised, ADHD rating scale IV Method: Questionnaires were completed by parents under guidance of a trained research staff.	Child: sex Mother: gestational age, ethnicity, maternal IQ, maternal years of education. Family/environment: presence of a smoker in the home, quality of the proximal caretaking environment at age 3, and change of residence by age 5.	Children with higher prenatal PAH exposure showed significant association between postnatal ELS and CBCL attention and thought problems T-scores.
McGuinn et al. (2020) Mexico Cohort [61]	539 mother–child pairs	Pregnancy (2nd trimester)	1 km based satellite-based estimation model.	PM2.5	Tool: BASC-2 Method: questionnaires were completed by parents.	Child: sex, age. Mother: maternal age at enrolment, years of education, depressive symptoms during pregnancy, and maternal IQ. Family/environment: SES, home caretaking environment (HOME inventory), and season of conception.	An association between prenatal first trimester PM2.5 exposure and increases in the scores of several behavioural subscales, including attention problems and hyperactivity, was observed.
Shih et al. (2020) Taiwan Cohort [62]	16,376 mother–infant pairs. Children aged 8 years	Pregnancy	Air pollution data retrieved from fixed-site stations using nondispersive infrared spectroscopy for NO, NO2, NOx, CO, SO2; beta-ray attenuation for PM.	NO, NO2, NOx, SO2, PM (PM10 or less)	Tool: none Method: data extracted from Taiwan National Birth Registry from 2005. ADHD diagnosis criteria: not specified. Parents were asked for previous clinical diagnosis.	Child: sex, birth in summer (June–August). Mother: maternal age, delivery method. Family/environment: urban or rural residence, annual household income.	The occurrence of hyperactivity was significantly related to prenatal nitrogen oxide (NOx), but not to particulate matter 10 μm or less in diameter or SO2. Further analysis to separate effects by nitrogen dioxide (NO2) and/or nitric oxide (NO) showed that only NO was significantly related to hyperactivity.
Peterson et al. (2022) USA Cohort [63]	332 children aged 6–14 years	third trimester of pregnancy.	PM2.5 exposure measured for each day of pregnancy using spatiotemporal exposure models at home addresses; PAH exposure measured using personal air monitoring of the mothers over a 48 h period in the third trimester of pregnancy that collected vapours and particles ≥2.5 μg in diameter on a quartz microfiber filter.	PM2.5, PAH	Tool: ADHD severity Rating Scale. Method: children completed a detailed neuropsychological assessment at the time of MRI scanning, and mothers reported child’s social and emotional functioning.	Child: sex, child handedness. Mother: maternal ethnicity and maternal education. Family/environment: material hardship and quality of home environment.	Prenatal exposure to PAH and PM2.5 were found not significantly associated with any of the behavioural outcomes, ADHD severity or anxiety severity.
Chang et al. (2022) China Cohort [64]	425,736 children aged 5 years	Pregnancy	1 km based satellite-based estimation model.	PM2.5	Tool: none Method: data extracted from Taiwan National Birth Registry from 2004–2011. ADHD diagnosis criteria: ICD-9-CM.	Child: sex, birth weight, preterm birth, iron deficiency anaemia, asthma, atopic eczema, allergic rhinitis. Mother: maternal age at delivery, anaemia, heart disease, chronic diabetes, gestational diabetes mellitus, polyhydramnios and oligohydramnios, chronic hypertension, gestational hypertension, preeclampsia, maternal smoke, and drug use. Family/environment: SES.	The hazard ratio (HR) of ADHD was significantly associated with a 10 μg/m3 increase in PM2.5 during the first trimester and increased at PM2.5 over 16 μg/m3.
Liu et al. (2022) China Cohort [65]	26,052 children aged 3 years	Pregnancy	Air pollutants measured using land-use random forest (LURF) model collected from 57 monitoring stations.	SO2, NO2, CO, O3, PM2.5, PM10	Tool: CPRS-48 Method: questionnaires were completed by parents.	Child: sex, age, average daily sleep duration, feeding pattern, and birth weight. Mother: maternal age at birth, delivery way, parity, maternal passive smoking or alcohol consumption during pregnancy, multivitamins, folic acid or calcium supplementation during pregnancy, and gestational diseases. Family/environment: paternal education and age at birth, family income, parent–child interactive activities, number of persons in house, prenatal household air pollution conditions (fumes from cooking, ETS, home renovation, mosquito coils, and burning of incense indoors), ETS, and monthly mean ambient temperature during first three years of age.	An association was found between air pollutants NO2, PM10, PM2.5 and hyperactivity. Moreover, the risk of hyperactivity significantly increased with 10 μg/m3 exposure from 7th month of pregnancy to 4th month after birth and peak was noticed at 9th month of pregnancy. However, no significant relation observed for air pollutants CO, O3, and SO2 and child hyperactivity.

Abbreviations: SPM (suspended particulate matter), PM (particulate matter), NO (nitric oxide), NO_x (nitrogen oxide), NO₂ (nitrogen dioxide), SO₂ (sulphur dioxide), O₃ (ozone), PAH (polycyclic aromatic hydrocarbons), A-TAC (The Autism–Tics, ADHD and other Comorbidities inventory), CBCL (Child Behaviour Checklist) for 1 ½–5 years of age; 6–18 years of age; and 4–18 years of age, SDQ (Strengths and Difficulties Questionnaire), DSM (Diagnostic and Statistical Manual of Mental Disorders), ADHD-DSM-IV (ADHD Criteria of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), CPRS (Conners Parent Report Scale), ICD-9 or 10 (International Classification of Mental and Behavioural Disorders Version 9 or 10); BASC-2 (Behavioural Assessment System for Children, second edition); TONI (Test of Non-Verbal Intelligence), HOME (Home Observation for Measurement of the Environment), ELS (early life stress); SES (socio economic status).