Table 1.
Characteristics of included studies
| Study, Year | Country | Population | Total cohort | Number of eligible participants | Age of ASD diagnosis (Years), mean ± SD | Follow-up period | Time of exposure | Pollution Detection Method | Subgroup of pollutant | Diagnostic or screening method | Inclusion criteria | Exclusion criteria | Exposure group | Control Group |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Alampi JD, 2021 [33] | Canada | Children | 8.716 | 478 | 3–4 (median, 40 months old) | 4 years | The first trimester of pregnancy | Cord blood |
Inorganic substances Metals Pesticides Phthalates Hydrocarbons Plastics Dioxins, Furans, PCBs Phenols/phenoxy acids |
Social Responsiveness Scale- 2 (SRS-2) questionnaire. Preschool-aged version | Pregnant being at least 18 years old, being able to communicate in French or English, and consenting to cord blood collection | Women who carried a fetus with a known abnormality had a primary chronic disease, used illicit drugs, or threatened abortion | Not described | Not described |
| Barkoski JM, 2021 [34] | USA | Children | Not described | 201 | Not described | 3 years | Second and third trimester of pregnancy | Urine | Pesticides |
Autism Diagnostic Observation Scale (ADOS) |
Mother or father had one or more children with ASD and or the gestating younger child had an older half-sibling or an equivalent or closer blood relative with ASD; Mother was at least 18 years of age or older; Mother was already pregnant or planning a pregnancy and biologically able to become pregnant; and Mother lived within 2 h of the Davis/Sacramento region at time of enrollment | Not described |
> LOD (> 0,1 ng/mL) Unit: natural log-transformed |
< LOD (< 0,1 ng/mL) Unit: natural log-transformed |
| Bernardo BA, 2019 [35] | Canada | Children | Not described | 546 | 3.4 ± 0.16 | 4 years | The first trimester of pregnancy | Plasma | Dioxins, Furans, PCBs | Social Responsiveness Scale-2 (SRS-2) | Mothers who had sociodemographic and child neurodevelopment information, plasma PCB concentrations, and total lipid concentrations measured during the first trimester of the pregnancy | Breastfeeding and pregnancy outcomes from our models and biomarkers of other prenatal contaminant exposures, including lead |
Fourth quartile exposure (> 3.6 ng/g) Unit: log 2 transformed |
First quartile exposure (< 1.4 ng/g) Unit: log 2 transformed |
| Braun JM, 2014 [36] | USA | Children | 389 | 175 | 4–5 (mean ± SD Not described) | 5 years | Second trimester of pregnancy and after childbirth | Serum or urine |
Phthalates Dioxins, Furans, PCBs Polyfluoroalkyl substances Pesticides Hydrocarbons |
Social Responsiveness Scale (SRS) |
a) 16 ± 3 weeks of pregnancy, b) age ≥ 18 years, c) residence in a home built before 1978, d) no history of HIV infection, and e) no medications taken for seizures or thyroid disorders |
Not described |
Pollutant unit Unit: log10-transformed |
Pollutant unit Unit: log10-transformed |
| Carter SA, 2022 [37] | USA | Children | Not described | 314.391 | Not described | 1 year | Throughout pregnancy | Freeway traffic load with California line-source dispersion model (CALINE4) | Particular matter | International Classification of Diseases (ICD)-9 codes and, after October 1, 2015, from ICD-10 codes |
Mother–child pairs of singleton deliveries at Kaiser Permanente Southern California (KPSC) hospitals between January 1, 2001, and December 31, 2014. Only geocodes with accuracy scores ≥ 98 and point or street address types were considered sufficiently accurate for traffic exposure assignments |
Missing or errors in birth weight, gender, maternal race/ethnicity and age at delivery, maternal age at delivery < 15 or > 55 years, and incomplete maternal residential address history in pregnancy, or due to geocodes not suitable for exposure assignment |
Five quintile exposure (> 3.80 ppb) |
First quintile exposure (≤ 0.89 ppb) |
| Gong T, 2014 [38] | Sweden | Children | 17.22 | 3.426 | 10.3 ± 1.5 | 9 years | Throughout pregnancy and the postnatal period | Air pollution concentrations at residential addresses during the mother's pregnancy, the child's first year of life, and the a year before the neurodevelopmental assessment was established mated by dispersion models, |
Nitrogen oxides Particular matter |
Autism-Tics, ADHD, and other Comorbidities inventory (A-TAC) | Twins born during 1992–2000 | Not described | High exposure (95th percentile) | Low exposure (5th percentile) |
| Granillo L, 2019 [39] | USA | Children | Not described | 104 | Not described | 3 years | Throughout pregnancy | Plasma | Dioxins, Furans, PCBs |
Autism Diagnostic Observation Schedule (ADOS) and Mullen Scales of Early Learning (MSEL) |
Families must reside within 2.5 h driving distance from the MIND Institute. Confirmed diagnosis of ASD in an older sibling of the child and active status in the MARBLES cohort, meaning participants had no loss to follow-up. They had not declined further participation in the study | The child of interest was a twin or had no final diagnosis | 50% highest concentration of PCB | 50% lowest concentration of PCB |
| Guxens M, 2016 [40] | Italy; the Netherlands; Sweden; Spain | Children | Not described | 8.079 | 4–10 (mean ± SD Not described) | 10 years | Throughout pregnancy | Were estimated for birth addresses by land-use regression models based on monitoring campaigns performed between 2008 and 2011 |
Nitrogen oxides Particular matter |
Swedish cohort: Autism-Tics, Attention deficit and hyperactivity disorders, and other Comorbidities (A-TAC) inventory; Dutch and Italian cohorts: Pervasive Developmental Problems (PDP) subscale of the Child Behavior Checklist for Toddlers (CBCL11⁄2–5); Dutch cohorts: Adapted 18-item version of the Social Responsiveness Scale (SRS); Spanish cohort: Childhood Autism Spectrum Test (CAST); | Mother–child pairs were recruited from 1992 through 2008 | Not described | > cutoff limit | < cutoff limit |
| Haggerty DK, 2021 [41] | USA | Children | Not described | 77 | 3–6 (mean ± SD Not described) | 6 years | The first trimester of pregnancy | Urine | Phthalates | Social Responsiveness Scale (SRS) | Women had to be 18 years of age or older and be able to communicate in English | Not described |
Pollutant unit (ng/mL) Unit: ln-transformed |
Pollutant unit (ng/mL) Unit: ln-transformed |
| Hansen J, 2021 [42] | Denmark | Children | 2.874 | 427 | 2 – 5 (mean ± SD Not described) | 5 years | End of the second trimester or beginning of the third trimester of pregnancy | Urine | Plastics | Child Behavior Checklist; 11⁄2–5 (CBCL/11⁄2–5) | 2010 to 2012, women residing in the municipality of Odense with a newly diagnosed pregnancy before 16 weeks of gestation | Twins and mothers of nonwestern origin |
Third tertile exposure (≥ 1.97 ng/mL) |
First tertile exposure (< 0.87 ng/mL) |
| Jo H, 2019 [43] | USA | Children | 246.42 | 2.471 | 0—5 (mean ± SD Not described) | 5 years | Preconception, each trimester, the entire pregnancy, and the first year of life |
Birth certificate residential addresses were geocoded using MapMarker USA Version 28.0.0.11. Exposure metrics at each geocoded address included regional O3, PM2.5, PM ≤ 10 μm in diameter (PM10), and nitrogen dioxide (NO2) |
Ozone Particular matter Nitrogen oxides |
Autism in Toddlers (CHAT) |
Mother–child pairs with singleton deliveries in KPSC hospitals between January 1, 1999, and December 31, 2009, in 14 service areas located across Southern California |
Children with birth certificate addresses outside Southern California or addresses that could not be accurately geocoded because of an address missing or not matchable to a U.S. postal service address |
> to the scaled average (PM 2.5 > 6.5 µg/m3; PM 10 > 16.1 µg/m3; NO2 > 10.4 ppb and O3 > 15.7 ppb) |
< to scaled average (PM 2.5 < 6.5 µg/m3; PM 10 < 16.1 µg/m3; NO2 < 10.4 ppb and O3 < 15.7 ppb) |
| Joyce EE, 2022 [44] | USA | Children | 256 | 154 | Not described | 3 years | First and second trimester of pregnancy | Dietary information was collected through a modified version of the National Cancer Institute's Dietary History Questionnaire (DHQ), which included additional questions from the validated version to capture contaminant exposure | Pesticides | Social Responsiveness Scale (SRS) | Women had to be 18 years or older, less than 29 weeks pregnant, English or Spanish-speaking, and living no farther than 2 h from recruitment sites | Not have outcome information available (either Social Responsiveness Scale (SRS) or diagnostic evaluation, both conducted at the 36-month visit and if they did not have information on prenatal diet. Twins were excluded due to the small number and correlation in exposures, following these exclusions | Fourth quartile exposure | First quartile exposure |
| Jung CR, 2013 [45] | China | Children | 49.833 | 535 | 6.26 ± 2.91 | 4 years | Early childhood ( up to 6 years) | Taiwan Environmental Protection Agency (EPA) monitoring station on Taiwan's main island. These air pollutants are measured hourly—CO by nondispersive infrared absorption, NO2 by chemiluminescence, O3 by ultraviolet absorption, SO2 by ultraviolet fluorescence, and PM10 by beta-gauge—and continuously |
Carbon monoxide Nitrogen oxides Sulfur oxides Ozone Particular matter |
International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) |
Individual's first date of enrollment until the first diagnosis of ASD | Children who had experienced ASD at the baseline and those who had missing information on air pollution | > 75th percentile | < 25th percentile |
| Kim JI, 2021 [46]* | South Korea | Children | 13.484 | 547 | 95.1 ± 1.4 months | 8 years | The second trimester of pregnancy and the postnatal period | Urine | Phthalates | Social Communication Questionnaire (SCQ) | Pregnant women in the second trimester (between 14 and 27 weeks of gestation) were enrolled in the Congenital Anomaly Study from 2008 to 2010 | Children who did not visit at least once between the ages of 4 and 8 years and children who did not see due to missing information on the social communication questionnaire (SCQ) scores | > LOD | < LOD |
| Lizé M, 2022 [47]* | France | Children | 3.421 | 185 | 4–11 (mean ± SD Not described) | 11 years | First and second trimester of pregnancy | Urine samples |
Organophosphates and carbamates Pesticides |
The Childhood Autism Spectrum Test (CAST) | Women with less than 19 weeks of gestation | Not described | Third tertile, > LOD or detectable exposure | First tertile, < LOD or not detectable exposure |
| Nowack N, 2015 [48] | Germany | Children | 234 | 116 | 10.23 ± 0.59 | 12 years | The third trimester of pregnancy and the postnatal period | Blood samples | Dioxins, Furans, PCBs | Social Responsiveness Scale (SRS) |
Babies from German- or Turkish-speaking families are born at term (weeks 38–42 of pregnancy) with an APGAR score of at least 8 Parity 1–3 |
Serious complications or illness during pregnancy or at parturition, and without congenital anomalies | Pollutant unit (pg/g lipid base) | Pollutant unit (pg/g lipid base) |
| Oudin A, 2019 [49] | Sweden | Adolescents | 48.571 | 768 | 8 ± 1.9 | 17 years | Throughout pregnancy | Geocoding | Nitrogen oxides | International Statistical Classification of Diseases and Related Health Problems (ICD-10) | Being born between 1999 and 2009 | Not described | Fourth quartile exposure | First quartile exposure |
| Oulhote Y, 2020 [50] | Canada | Children | 2.001 | 556 | 3.4 ± 0.74 | 4 years | The first trimester of pregnancy | Urine samples | Phthalates | Social Responsiveness Scale (SRS-2) | Pregnant woman older than 18 years |
Have a chronic disease Threatened abortion Consumption of psychoactive substances |
Pollutant unit (µg/L) Unit: Log 2-transformed |
Pollutant unit (µg/L) Unit: Log 2-transformed |
| Pagalan L, 2019 [51] | Canada | Children | 132.256 | 129.439 | 4.2 ± 1.4 | 5 years | Throughout pregnancy and the postnatal period | Land use regression model |
Particular matter Nitrogen oxides |
Autism Diagnostic Observation Schedule (ADOS) Autism Diagnostic Interview–Revised (ADI-R) |
Be registered in the provincial health insurance plan for 275 days or more Reside in the Vancouver metropolitan area during the calendar year of your pregnancy |
Unknown gestational age |
Per interquartile range (PM 2.5 > 1.5 µg/m3; NOX > 10.5 ppb and NO2 > 4.8 ppb) |
Per interquartile range (PM 2.5 < 1.5 µg/m3; NOX < 10.5 ppb and NO2 < 4.8 ppb) |
| Pham C, 2022 [52] | Australia | Children | 1.047 | 676 | 2–4 (mean ± SD Not described) | 4 years | Throughout pregnancy and the postnatal period | Geocoding |
Particular matter Nitrogen oxides |
Child Behavior Checklist for ages 1½–5 (CBCL 1½–5) | Not described |
Pregnant women under 18 years of age Require an interpreter to answer the questionnaires Baby with severe disease before 32 weeks |
Pollutant unit PM 2.5 (µg/m3) NO2 (ppb) |
Pollutant unit PM 2.5 (µg/m3) NO2 (ppb) |
| Philippat C, 2018 [53] | United States | Children | 203 | 101 | Not described | 3 years | Throughout pregnancy | Urine samples | Phthalates | Autism Diagnostic Observation Schedule (ADOS) |
Be at least 18 years of age Be the biological mother of a child with autism spectrum disorder Live within a 2-h drive of Davis/Sacramento |
Not taking the follow-up questionnaire | Not described | Not described |
| Rahman MM, 2022 [54] | United States | Children | 343.813 | 294.937 | 3.5(IQR 2.6 ± 5.3) | 9 years | Throughout pregnancy |
Air Quality System (AQS) Moderate Resolution Imaging Spectroradiometer |
Particular matter Nitrogen oxides Ozone |
International Statistical Classification of Diseases and Related Health Problems (ICD-10) | Mothers with singleton deliveries at Kaiser Permanente Southern California |
Maternal age at delivery < 15 or > 55 years of age Maternal residential address history in pregnancy |
Per interquartile range (PM2.5 > 7.4 μg/m3 NO2 > 17.4 ppb O3 > 19.3 ppb) |
Per interquartile range (PM2.5 < 7.4 μg/m3 NO2 < 17.4 ppb O3 < 19.3 ppb) |
| Rahman MM, 2023 [55] | United States | Children | 370.723 | 318.750 | 3.0 (IQR 2.3 ± 3.7) | 5 years | Throughout pregnancy | Geocoding |
Elemental carbon Organic carbon Metals Inorganic substances |
International Statistical Classification of Diseases and Related Health Problems (ICD-9) | Mothers with singleton deliveries at Kaiser Permanente Southern California |
Maternal age at delivery < 15 or > 55 years of age Maternal residential address history in pregnancy |
Per interquartile range (ng/m3) EC > 329.10 OC > 1249.74 Cu > 11.06 Fe > 169.56 Mn > 2.75 |
Per interquartile range (ng/m3) EC < 329.10 OC < 1249.74 Cu < 11.06 Fe < 169.56 Mn < 2.75 |
| Sagiv SK, 2018 [56] | United States | Adolescents | 601 | 534 | 14.06 ± 0.23 | 14 years | First and third trimester of pregnancy |
Urine samples Geocoding |
Dialkyl phosphates Diethyl phosphates Dimethyl phosphates Chlorpyrifos Diazinon Malathion Oxydemeton-methyl |
Social Responsiveness Scale (SRS-2) |
≥ 18 years old < 20 weeks gestation Spanish or English-speaking Qualifying for low-income health insurance Planning to deliver at the public hospital |
Not described |
Pollutant unit (nmol/L) Unit: Log-normal distribution |
Pollutant unit (nmol/L) Unit: Log-normal distribution |
| Van den Dries MA, 2019 [57] | Netherlands | Children | 9.778 | 622 | Not described | 6 years | Throughout pregnancy and postnatal period | Urine samples | Organophosphates and carbamates | Social Responsiveness Scale (SRS) | Resided in the study area in Rotterdam, the Netherlands | Not described |
Pollutant unit (nmol/g) Unit: log10 transformed |
Pollutant unit (nmol/g) Unit: log10 transformed |
| Von Ehrenstein OS, 2014 [58] | United States | Children | 1′745.754 | 148.722 | Not described | 5 years | Throughout pregnancy | Geocoding |
Volatile organic compounds Inorganic substances Hydrocarbons |
Diagnostic and Statistical Manual of Mental Disorders (DSM IV-R) (code 299.00) | Not described | Not described | > Interquartile range and km Buffers | < Interquartile range and km Buffers |
| Wang SY, 2021 [59]* | China | Adolescents | 1′000.000 | 62.919 | 15.30 ± 2.20 | 17 years | Throughout pregnancy | Automatic monitoring stations |
Particular matter 10 Carbon monoxide Nitrogen Dioxide Sulfur dioxide Ozone |
Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) | Not described |
Those who had missing data on the insurance enrollment date Lived outside the Taiwan main island |
Higher than the average exposure level in each trimester | Less than the average exposure level in each trimester |
LOD Lower Detection Limit, PM Particular matter, NO2 Nitrogen dioxide, NOX Nitrogen oxides, O3 Ozone, EC Elemental carbon, OC Organic carbon, Cu Copper/ Fe Iron, Mn Manganese
* Only studies included in the systematic review