Table 1. A summary of the characteristics of prospective cohorts studies.

ASD - autism spectrum disorders; AP - acetaminophen; IQ - intelligence quotient; EAS - Emotionality, Activity and Shyness Temperament Questionnaire; BSID - Bayley Scales of Infant Development; MCSA - McCarthy Scales of Children's Abilities; CPSCS - California Preschool Social Competence Scale; CAST - Childhood Autism Spectrum Test; ADHD-DSM-IV - Attention-Deficit/Hyperactivity Disorder Criteria of the Diagnostics and Statistical Manual of Mental Disorders, Fourth Edition Form List; K-CPT - Conner's Kiddie Continuous Performance Test; WPPSI-R - Wechsler Primary and Preschool Scales of Intelligence-Revised; WAIS - Wechsler Adult Intelligence Scale; NPR - Norwegian Patient Registry; ICD-10 - International Classification of Disease; NCE - negative control exposure

Author and year of publication	Study population and sample size	Acetaminophen exposure measurement	Outcome measurement	Statistical analysis
Ji et al. 2020 [17]	Boston Birth Cohort, 996 mother-child pairs were enrolled in the study at birth and were part of this study for the next 10 years in the Boston medical center.	Cord blood samples were collected at birth, and three acetaminophen metabolites were measured in the plasma sample, which is as follows: 1. unchanged acetaminophen, 2. acetaminophen glucuronide, 3. 3-[N-acetyl-l-cysteine-S-yl]-acetaminophen	Data of ASD, ADHD, combined ASD/ADHD, and other developmental disorders (DDs - other behavioral, mental, and neurodevelopmental disorders not related to ASD and ADHD) diagnosed by physicians were collected from the child's medical record.	Odds ratio with 95% confidence intervals.
Tovo-Rodrigues et al. 2018 [18]	2004 Pelotas Birth Cohort (Brazilian population). It included 4231 live births and 3722 children were assessed at age six and 3566 at age 11.	1. Questionnaires investigating perinatal factors were completed at the birth of the children. 2. Interviews during a) perinatal evaluations, and b) follow-up at ages six and 11 years.	Trained psychologists used the Strengths and Difficulties Questionnaires (SDQ) to assess the behavioral symptoms, and standardized scores were assigned to behavioral outcomes.	Crude and adjusted odds ratio. Cutoff values were used for the outcomes.
Bornehag et al. 2018 [19]	SELMA - the Swedish environmental, longitudinal, mother and child, asthma and allergy. It enrolled 754 mother-child pairs at eight to 13 weeks of pregnancy.	1. Maternal interviews 2. Urinary acetaminophen measurement at enrollment, adjusted for creatinine level. 3. AP use was assessed from conception to study entry and the number of tablets taken.	Language development of children at 30 months of age by: a) a nurse (advanced practitioner if required), b) questionnaire on a language scale filled by the parents.	Crude and adjusted odds ratio.
Vlenterie et al. 2016 [20]	Norwegian Mother and Child Cohort Study (MoBa), 51200 mother-child pairs	1. Maternal paper-based questionnaires at gestational weeks 17, 30, and six, 18, 36 months postpartum. 2. AP use is categorized as short-term (1-27 days) and long-term (28 days and more).	1. Maternal interview at child's 18 months of age: psychomotor development was measured by a) Ages and Stages Questionnaire (ASQ), b) objective measurement of child's starting age of unassisted walking, c) The Child Behavior Checklist (CBCL/11/2-5-LDS), d) temperament measurement with EAS.	Odds ratio and numbers needed to harm (NNH) for each outcome.
Avella-Garcia et al. 2016 [21]	Spanish Birth Cohort, 2644 mother-child pairs	1. Maternal interviews by trained evaluators at weeks 12 and 32 of pregnancy. 2. Timing of use was assessed as one month before and during pregnancy 3. Frequency was assessed as never, sporadic and persistent.	At one year: BSID at five years: 1. MCSA 2. CPSCS 3. CAST 4. ADHD(DSM-IV) 5. K-CPT completed by trained psychologists, teachers, and parents.	Relative risk (incidence rate ratios).
Liew et al. 2016 [22]	Danish National Birth Cohort (DNBC, 1996-2002), 1491 mothers and children enrolled in DNBC.	Lifestyle During Pregnancy Study (LDPS) (part of DNBC) provided data about lifestyle factors. Three computer-assisted telephonic interviews at gestational weeks 12, 30, and six months after pregnancy. AP use was categorized as a) ever use, b) never use. AP use in every trimester, every week, total weeks of use and in combination with other medicines were also assessed.	At five years of age: 1. attention function was measured by the Test of Everyday Attention for Children at Five (TEACH-5). 2. Executive function was evaluated by the Behavior Rating Inventory of Executive Function (BRIEF), which was completed by both the parents and the preschool teachers. These tools provided standard test scores for outcomes. The attention and executive function were completed by trained psychologists, who were blinded to exposure status.	Odds ratio.
Parker et al. 2020 [23]	It included 560 mother-child pairs.	Maternal interviews were conducted approximately one year after the delivery. AP use was categorized as short-term (<28 days) and long-term (>28 days). It was measured as any use or no use. AP use before pregnancy was also assessed.	At 6-12 years of age, the child's behavior was evaluated using Child Behavior Checklist (CBC) and Teacher Report Form (TRF). These checklists were completed by mothers and teachers independently.	Unadjusted and adjusted mean differences (MD) and risk ratios (RR).
Arneja et al. 2019 [24]	Ontario Birth Study (OBS), 1200 women enrolled in the study at 11-14 weeks of pregnancy.	Three questionnaires were completed at 12-16, 24-28 weeks of gestation, and 6-10 weeks after the pregnancy (medical and lifestyle data). AP use was assessed three months before pregnancy, at 12-16 weeks and 28-32 weeks. It was categorized as never, early, late, continuous, and never, one per week and more than once per week.	Data about a) child's sex, b) birth weight, c) gestational age at birth was collected from hospital medical charts. It helped evaluate outcomes including preterm birth, low birth weight, and small for gestation age.	Risk ratios.
Ystorm et al. 2017 [25]	Norwegian Mother and Child Cohort Study (MoBa), 112973 children and their parents.	MoBa questionnaires at gestational weeks 18, 30, and six months postpartum. Maternal and paternal assessment of AP use in six months before pregnancy. The use of other medicines was also evaluated.	1. ADHD diagnoses from the Norwegian patient registry (NRP) between 2008 and 2014. 2. Maternal questionnaires when children were six months, one and half years, and three years old.	Hazard's ratio.
liew et al. 2016 [26]	Danish Cohort Study/Danish National Birth Cohort (1996-2002), 1491 mother-child pairs enrolled at six to 12 weeks gestation	Three telephonic interviews at gestational weeks 12, 30, and six months postpartum. AP use is categorized as ever use, trimester-specific use, total weeks of use, never users.	1. Child IQ was assessed at the age of five years by using WPPSI-R by trained psychologists. 2. Maternal IQ was assessed with WAIS and the nonverbal Raven's Standard progression metrics.	Mean differences in child’s IQ using multiple linear regression and scores were calculated.
Leppert et al. 2019 [27]	Avon Longitudinal Study of Parents and Children (ALSPAC). Data collection in ALSPAC started in 1990 and is ongoing. It recruited 7921 mothers. Their genotype data were collected from ALSPAC.	Genotype data were used to estimate the association with 32 maternal early-life exposures (including acetaminophen), and maternal polygenic risk scores were calculated for ADHD, ASD, and schizophrenia. These scores were used to estimate effect sizes.	Questionnaires were used to assess the following factors: 1. maternal lifestyle and behavior (smoking, alcohol, BMI, and maternal age); 2. maternal use of nutritional supplements and medications in the pregnancy (acetaminophen, antidepressants, iron, vitamins, zinc and folic acid); 3. illnesses in the mother (hypertension, diabetes, depression, psoriasis, rheumatism, preeclampsia, infections, or bleeding during pregnancy); 4. factors related to preterm birth, birth weight and cesarean delivery; 5. maternal blood levels of vitamin D, selenium, mercury, cadmium, and lead during the pregnancy.	Odds ratios.
Gervin et al. 2017 [28]	Norwegian Mother and Child Cohort Study (MoBa) A total of 90,000 participants' samples, including a) parental blood samples during pregnancy, b) maternal blood sample and a cord blood sample collected at birth were included.	Three questionnaires. 1. conception to 18 weeks of gestation, 2. 18-30 weeks of gestation, 3. 30 weeks to delivery. Long-term use of AP is categorized as more than 20 days. Trimester of AP use was also recorded. Samples with co-medication history were excluded.	ADHD diagnoses from 2008-2014 were collected from NPR. Specialists made the diagnoses according to ICD-10 guidelines.	DNA methylation analyses were measured with a) microarray preprocessing and quality control, b) differential DNA methylation analysis.
Liew et al. 2019 [29]	Nurses' Health Study II Cohort. The data collected from 1993 to 2005 (1993, 1995, 1997, 1999, 2001, 2003, 2005). This period included two NCE periods, four years before and after the pregnancies and 8856 children were part of the study.	Maternal questionnaires about AP use 1) during the pregnancy: a) regular use (more than two times/week), b) pregnancy status was also recorded at the time of AP intake; 2. before and after the pregnancy: two questionnaires were completed for NCE periods, four years before and after the pregnancy.	Nurse mothers completed a questionnaire in 2013. This included ADHD diagnosis in their biological children and the year they were born. This questionnaire was completed in 2013 when children were around eight years to have a clear diagnosis of ADHD.	Odds ratio with 95% confidence interval.