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. 2024 Sep 3;24:2388. doi: 10.1186/s12889-024-19742-w

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