Acetaminophen (Paracetamol)

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Ahlqvist (Population-Based), 2024	population based cohort retrospective	1995-2019: Prospective collection during the first antenatal visit (typically at 8-10 weeks’ gestation), during which midwives conducted structured interviews (including OTC), and later in pregnancy by the midwife and physician. From 2005: supplemented with Prescribed Drug Register.	Autism, ADHD, and intellectual disability diagnoses were identified using International Classification of Diseases (ICD) codes from the National Patient Register. ADHD diagnoses were also identified based on the dispensation of the ADHD medications (methylphenidate or atomoxetine).	Singleton. Adjusted for child sex; all other analgesics; parent’s diagnoses of migraine, chronic pain, infections, fever, rheumatoid arthritis, and headaches; parity; age; cohabitation at delivery; BMI; smoking; use of psycholeptics, antidepressants, and antiseizure medication; ...; household education and disposable income.
Ahlqvist (Sibling), 2024	population based cohort retrospective	1995-2019: Prospective collection during the first antenatal visit (typically at 8-10 weeks’ gestation), during which midwives conducted structured interviews (including OTC), and later in pregnancy by the midwife and physician. From 2005: supplemented with Prescribed Drug Register.	Autism, ADHD, and intellectual disability diagnoses were identified using International Classification of Diseases (ICD) codes from the National Patient Register. ADHD diagnoses were also identified based on the dispensation of the ADHD medications (methylphenidate or atomoxetine).	Singleton. Sibling (genetic, environment, history of neurodev disorders). Adjusted for child sex; all other analgesics; parent’s diagnoses of migraine, chronic pain, infections, fever, rheumatoid arthritis, and headaches; parity; age; cohabitation at delivery; BMI; smoking; use of psycholeptics, antidepressants, and antiseizure medication; ...; household education and disposable income.
Alemany_DNBC, 2021	prospective cohort	Paracetamol use was collected in three computer-assisted telephone interviews conducted at gestational weeks 12 and 30 and 6 months postpartum. At each interview, mothers were asked if they had taken acetaminophen as a singular or combination drug available over the counter or via prescription.	The autistic traits were assessed using the Strengths and Difficulties Questionnaire (SDQ - 25 items), completed by mothers. Abnormal scores in emotional problems and in peer problems or prosocial behaviour SDQ subscales were recommended to capture ASC symptoms.	Adjusted for maternal age, education, pre-pregnancy Body Mass Index, alcohol, prenatal smoking, mental health problems during pregnancy, parity, maternal fever and infections during pregnancy, parity, child sex and age at assessment.
Andersen, 2012	population based cohort retrospective	Maternal by-prescription paracetamol was extracted from the Aarhus University Prescription Database (AUPD), which includes data on all reimbursed medicines dispensed at community pharmacies in northern Denmark.	Asthma among children was defined using an algorithm that combines use of anti-asthma medications (dispensations ascertained from the Aarhus University Prescription Database) and a hospital diagnosis of asthma ascertained from the Danish National Patient Registry (DNPR).	Singletons only. Adjustment was made for year of birth, county, sex of child, gestational age, birth order, mode of delivery, mother’s age, maternal use of antibiotics during pregnancy, maternal smoking during pregnancy, and maternal asthma. Ad hoc analysis adding maternal prepregnancy body mass index (children born from 2004).
Andreasen, 2025	prospective cohort	Paracetamol exposure during pregnancy was evaluated by self-reported questionnaires on medication use during pregnancy and by measuring maternal paracetamol concentrations in urine samples. All pregnant women were asked to complete two questionnaires (Q1–2) during pregnancy and one after (Q3).	Anogenital distance was measured according to the standardized methods by technicians blinded maternal paracetamol use. The children were positioned on a flat surface with their legs held back in a frog-leg posture, forming an angle of 45–60 at the hips relative to the torso.	Singletons only. Preterm: No adjustment/weighting. Anogenital distance: Propensity score (PS) weighting to adjust for maternal education, maternal age, pre-pregnancy body mass index, a history of polycystic ovary syndrome (PCOS), preterm birth, fertility treatment, parity, cigarette smoking and alcohol use during pregnancy.
Arneja, 2020	prospective cohort	Participants completed three self-administered comprehensive questionnaires at 12–16 weeks of gestation, 24–28 weeks of gestation, and 6–10 weeks postpartum to capture exposures, including acetaminophen.	Information on the baby’s sex, birthweight, and gestational age was derived from clinical data collected from hospital medical charts.	Singleton. Multivariable adjusted models included: age (continuous), smoking in the 3 months before pregnancy, body mass index at baseline (continuous), maternal ethnicity, education, fever during pregnancy, and paternal smoking in the 3 months before pregnancy, comorbidities (such as diabetes, hypertension, ... none/one/two), and the use of other pain medications.
Aselton, 1985	retrospective cohort (claims database)	Automated pharmacy records from Seattle, giving outpatient drug and hospitalization information.	Identification from all automated hospital discharge files maintained, recorded and put on computer files by the Cooperative. For each infant, the clinical record was abstracted and reviewed for validation.	None.
Bertoldi_Pelotas, 2020	prospective cohort	Women were asked about any medications use during pregnancy at prenatal (before 16 weeks of gestation and at 16-24 weeks of gestation) and perinatal interviews (hours after delivery). Then, all drugs used were classified by trimester of use and number of days of use in each trimester.	Children cognitive development was evaluated using the INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) administered mainly at the research clinic and sometimes in the child's home by interviewers trained by neurodevelopment professionals. INTER-NDA: good agreement with the Bayley Scale.	Only raw data can be extracted (adjusted β (95% CI) of linear regression cannot be reported here)).
Broe (Controls unexposed, general pop), 2025	population based cohort retrospective	Exposure was determined using the Prescription register that contains individual-level prescription data from all Danish outpatient pharmacies.	Malformations were identified using infant records from three Danish health registries: The Birth register, the Patient register, and the Cause of Death Register during the first year of life.	Singleton only. Multivariable model including calendar year, maternal age at delivery, body mass index (BMI), smoking status, parity, and concurrent exposure to known teratogenic drugs during the first trimester.
Broe (Controls unexposed, sick), 2025	population based cohort retrospective	Exposure was determined using the Prescription register that contains individual-level prescription data from all Danish outpatient pharmacies.	Malformations were identified using infant records from three Danish health registries: The Birth register, the Patient register, and the Cause of Death Register during the first year of life.	Singleton only. Multivariable model including calendar year, maternal age at delivery, body mass index (BMI), smoking status, parity, and concurrent exposure to known teratogenic drugs during the first trimester.
Chen, 2019	nested case control	The Taiwan Longitudinal Health Insurance Database that contains comprehensive data on insured individuals, including prescriptions.	The Taiwan Longitudinal Health Insurance Database that contains comprehensive data on insured individuals, including clinical visit dates and disease diagnoses (ICD-9-CM are used for disease diagnosis).	Adjusted/matched for demographic data (age, sex, income, level of urbanization), gestational infections, comorbid perinatal conditions (including preterm or low birth weight, birth trauma, and intrauterine hypoxia/birth asphyxia) and for maternal mental health disorders. Sensitivity analysis excluding Gestational Infections and Maternal Mental Health Disorders => same significant associations.
Cifuentes, 2025	case control	Information on maternal medication exposure was primarily obtained from maternity records. Additional data sources for some registries included: infant medical records, general practitioner records, pregnancy passports, and maternal interviews conducted before or after birth. EFEMERIS: dispensing.	Cases and controls were obtained in registries from EUROCAT, the European network for surveillance of congenital anomalies.	Exclusions of mothers who reported with the use of known major teratogens and infectious diseases during pregnancy that could had have an impact on eye development. No adjustment for this exposure.
Couto, 2015	case control	Information the use of drugs and the time window of exposure to analgesics was obtained through a specifically designed and standardized survey. Face-to- face interviews were performed with the mothers of cases and controls to obtain information.	The patients were recruited from oncologic hospitals in the following cities in 11 states: Belo Horizonte, Brasília, Campinas, Campo Grande, Curitiba, Florianópolis, Goiânia, João Pessoa, Recife, Rio de Janeiro, Salvador, Santa Maria, and São Paulo.	Adjusted for selected variables, such as birth weight, maternal education, maternal age, child skin color, hormone use, and pesticide exposure during pregnancy.
Czeizel, 2005	retrospective cohort	Exposure data collected from 3 sources: a post-paid structured questionnaire sent to the parents requesting drugs taken during pregnancy, according to gestational months; maternal prenatal care logbook (in which obstetricians must record all prescribed drugs); nurses visited non-responding families.	Not specified. Controls of the Hungarian Case-Control Surveillance of Congenital Abnormalities.	Maternal age, birth order, marital and employment status, acute and chronic maternal diseases and other medicines used were evaluated as confounders (no other details).
Dathe, 2019	prospective cohort	Relevant data on drug exposure (duration of treatment, dosage, and anatomical therapeutic chemical [ATC] codes), including co-medication as a potential confounding factor) are recorded in addition to the counselling process, then 8 weeks after the expected date of delivery.	Details on complications during pregnancy, delivery, neonatal outcome parameters, and the results of the third paediatric examination (U3) at the age of 4–5 weeks are collected at the follow up, via a standardised and detailed questionnaire sent to the person who initially contacted our institute.	Exclusion criteria were exposure to nonsteroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid (ASA) >300 mg/day, or metamizole in the second or third trimester. No adjustment/matching.
De Castro, 2022	prospective cohort	Data were collected by trained interviewers during prenatal visits. The pregnant women were interviewed using a standardized questionnaire with 116 questions divided into 7 parts, including medication information (before and during pregnancy).	Anthropometric measurements of the newborn (weight, length, and circumferences) were obtained after birth in the Maternity Hospital by the nursing team previously trained for this purpose. The newborn was weighed and measured.	Models were adjusted for age, race/skin color, education, marital status, employment status, family income, pre-gestational weight, birth order, and baby’s sex. Smoking during pregnancy, alcohol use during pregnancy, chronic diseases (no details), acute diseases (no details), pre-gestational body mass index, history of preterm did not differ significantly between exposed and unexposed.
Feldkamp, 2010	case control	Trained interviewers administered a computer-assisted telephone interview to mothers of children in the case and control groups (acetaminophen consumption was specifically queried). Every woman was queried about medication use from 3 months before conception through the entire pregnancy.	Major birth defects ascertained from 10 centers in the United States collected by birth-defects surveillance programs at each center.	Adjusted for maternal age, education, preconception body mass index, gestational diabetes, fever, smoking in the first trimester, folic acid use from 3 months before conception through the first trimester, race/ethnicity and parity.
Fisher, 2016	prospective cohort	A printed questionnaire was given to women at the time of recruitment with instructions that it should be completed in time for collection ‘after your baby is born’, notably asking: ‘Have you taken any medicine during this pregnancy?’. If yes, gestational period and frequency were completed.	Infant anogenital distance (AGD) (measured from 2006 onwards), penile length and testicular descent were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated.	Cryptorchidism adjusted for body weight and gestation-corrected age. AGD, penile length or testicular descent distance: adjusted for time point and body weight Z score at time of measurement. Additionally, adjusted for exposure during other gestational periods where applicable; e.g. models for exposure to paracetamol during 8–14 weeks: adjusted for exposure at <8 weeks and >14 weeks.
Garcia-Marcos, 2009	retrospective cohort	Questionnaires were given to the parents by their children’s teachers and returned within 1 week. The questionnaires included a specific question on paracetamol consumption during pregnancy (never, at least once during pregnancy or at least once per month during pregnancy).	Questionnaires were given to the parents by their children’s teachers and returned within 1 week. Current wheezing was defined as a positive answer to the question: ‘Has your child had wheezing or whistling in the chest during the last 12 months?’.	Adjusted for smoking or non-smoking mother, duration of breast-feeding, older and younger siblings, cat ownership during the 1st year of the child’s life and premature birth.
Given, 2017	case control	First trimester maternal medication exposures were mostly obtained by registries from prospectively recorded maternity records. Additional data sources included the medical records of the infant, general practitioner records, maternity passports, and maternal interviews before or after birth.	EUROCAT registries that record all cases of major congenital anomalies among live births, foetal deaths ≥20 weeks’ gestation and termination of pregnancy for foetal anomaly (TOPFA), in their populations using International Classification of Diseases (ICD)-9/10.	Adjustment for maternal age group, registry and time period. Excluding diabetes and anti-epileptic medication exposed.
Goksor, 2011	prospective cohort	The parents answered questionnaires at 6 and 12 months and at 4.5 years of age. Information regarding pregnancy and maternal intake of medical drugs during pregnancy were obtained from the 6-month questionnaire.	The parents answered questionnaires at 6 and 12 months and at 4.5 years of age. At 12 months and at 4.5 years of age, questions were asked regarding current health and disease. Medical Birth Register for: gender, gestational age, caesarean, Apgar score, small or large for gestational age.	Adjusted for having a parent with asthma, eczema or rhinoconjunctivitis, maternal antibiotic use during pregnancy, maternal smoking during pregnancy, preterm, caesarean, asphyxia, antibiotics during the 1st week of life, breast-feeding > 4 months, early fish introduction (< 9 months), gender, own eczema or doctor-diagnosed food allergy during the first year of life and parental level of education.
Goodman, 2019	case control	Patients reported any use of over the counter or prescribed medications in the month prior to or during pregnancy, data obtained by interview at enrollment (mid-pregnancy ultrasound).	Diagnostic ultrasounds in the obstetric clinic system of the University of Oklahoma Health Sciences Center (OUHSC).	Singleton only. Controls matched to each case by maternal age and race/ethnicity. Adjusted for insurance, education, low body mass index and nulliparity.
Inoue, 2021	prospective cohort	Maternal acetaminophen use during pregnancy was ascertained from the study enrollment form and 3 computer-assisted telephone interviews (scheduled at approximately the 12th and 30th gestational weeks and at 6 months after birth), including acetaminophen as a single or combination drug.	Children’s behaviors were assessed based on the standardized Strengths and Difficulties Questionnaire (SDQ), completed by both parents and children.	Adjusted for maternal age, child’s birth year, parity, socio-occupational status, prepregnancy BMI, maternal smoking, alcohol drinking during pregnancy, mental health problems, maternal NSAIDs intake and diseases in muscles/joints, fever or infection/inflammation during pregnancy. Sensitivity for additional control for parental childhood behavioral problem scores (familial and genetic risks).
Jedrychowski, 2011	prospective cohort	Paracetamol use in pregnancy was collected by interviews during and probably after pregnancy ('The information about medication taken in each of the post natal periods was gathered as well').	After delivery, every three months in the first 24 months of the newborn’s life and every 6 months later, a detailed standardized face-to-face interview on the infant’s health was administered to each mother by a trained interviewer.	Only non-smoking women with singleton pregnancies ages 18–35 years, who were free from chronic diseases such as diabetes and hypertension and who had term babies. Adjusted for maternal age, education and atopy; gender of child; older siblings; damp/ mold house, and exposure to prenatal particulate matter. Adjusting for indication of prenatal and postnatal paracetamol => did not modify.
Jensen, 2010	prospective cohort	Data on exposure were collected both prospectively (before cryptorchidism could be recognized), by using the enrollment questionnaire and the 2 telephone interviews during pregnancy, and retrospectively during the telephone interview that took place 6 months postpartum.	Information on cryptorchidism, other congenital mal- formations, and surgical procedures undergone by boys in the cohort was obtained from the Danish National Patient Registry. This registry contains information on all inpatient and outpatient clinic diagnoses and surgeries.	Singleton only. Adjusted for maternal age at childbirth, household occupational status, parity before the index boy, time to pregnancy, treatment of infertility and smoking during pregnancy. 2nd analyses: adjusted for birth weight, gestational age, and other malformations; adjusted for diseases in muscles or joints, fever, or infections during pregnancy; exclusion of diabetes mellitus.
Källén, 2003	population based cohort retrospective	At the ﬁrst antenatal visit (usually week 10–12), a midwife interviewed the woman on the use of drugs during the pregnancy before the antenatal care visit. Throughout the subsequent antenatal care, additional prescriptions for drugs are recorded and also computerized.	Infants with cardiovascular defects were identiﬁed from three sources: The Swedish Medical Birth Registry, the Swedish Registry of Congenital Malformations and the Swedish Child Cardiology Registry. Pregnancy outcome information was obtained from the delivery and pediatric records.	Stratiﬁcation for year of birth and possible confounders: maternal age, parity, smoking habits in early pregnancy, and years of involuntary childlessness.
Kerr, 2019	case control	Within 6 months of delivery, trained Birth Defects Study (BDS) nurse- interviewers contacted mothers to complete a roughly 1-hr computer-assisted telephone interview, including medications during pregnancy.	Cases and controls were ascertained at participating hospitals or birth defect registries in the same areas.	Adjusted models included maternal age, race/ethnicity, education, study center, and study year (aORs were calculated when there were five or more exposed cases).
Killion, 2022	prospective cohort	Women completed up to four telephone surveys assessing exposures. An outcome interview updated late gestation information. All medications, including non-prescription medications, were self-reported at each phone interview, including start and stop dates, frequency, dosage and reason for use.	Women completed an outcome interview that captured gestational age at delivery, birthweight of the baby and preeclampsia/pregnancy-induced hypertension. Medical records from obstetricians and specialty providers were requested and used to validate maternal report when possible (~75% of pregnancies).	Adjusted for maternal age, tobacco use, race/ethnicity, pre-pregnancy body mass index, depression, anxiety, other mental health disorders, arthritis, Inflammatory Bowel Disease (IBD), Systemic lupus erythematosus (SLE) other autoimmune diseases, oral corticosteroids, and disease modifying antirheumatic.
Koniman, 2007	case control	Paracetamol intakes of the mother during pregnancy were assessed using questionnaire interviewer-administered to the mother. If the response was positive for paracetamol intake, details regarding period of intake, the frequency, duration of intake, daily dose and indications were asked.	Cases were recruited from the paediatric outpatient clinics and the Children’s Asthma and Allergy Network programme at the National University Hospital, Singapore. The health status of the sibling was determined by questioning to the parent. All patients were subjected to skin prick testing.	Sibling pairs (control for hereditary, socio-economic, familial and social environmental factors) => considered as matched. No adjustment.
Kristensen, 2011	prospective cohort	Pregnant women in the third trimester were questioned concerning disease and medicine use during the pregnancy (self-administered written questionnaire, or computer assisted telephone interview).	The testis was defined as cryptorchid if it was found high scrotal, supra-scrotal, inguinal or non-palpable after clinical examination by trained paediatricians. The examination technique and the definition of cryptorchidism developed by Scorer (1964) were applied.	Adjusted for disease reported during pregnancy (indication to treat), use of other medications during pregnancy, gestational age and twins (only written questionnaires), whereas no confounding effects was observed with birthweight, twins (only the telephone interview), mother’s age, smoking, chronic disease and infectious disease.
Li, 2003	retrospective cohort (claims database)	Information on use of non-steroidal anti-inflammatory drugs, aspirin, and paracetamol during pregnancy was obtained in an interview conducted soon after each woman’s pregnancy was confirmed (names of any drugs; conditions that they were to treat; timing, duration and frequency of their use).	Pregnancy outcomes were ascertained for all participants by searching the Kaiser Permanente care programme inpatient and outpatient databases, reviewing medical records, and contacting those participants whose outcomes could not be determined through the previous two methods.	Adjusted for previous miscarriage, education, maternal age, gravidity, race, use of Jacuzzi or hot tub, multivitamin use, and smoked since last menstruation. Further adjustment for coffee intake, alcohol use, fever, number of previous pregnancy, diabetes or hypertension did not change the results.
Li, 2021	nested case control	The Taiwan's Longitudinal Health Insurance Database that contains comprehensive data on insured individuals, including prescriptions.	The Taiwan's Longitudinal Health Insurance Database that contains comprehensive data on insured individuals, including clinical visit dates, disease diagnoses. The codes of the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) are used for disease diagnosis.	Controls matched for the mothers’ age, children's sex and age, pregnant age of mothers, income, and urbanization level. Adjusted for demographic data (age, sex, income, level of urbanization), gestational infections, maternal atopic disorders, comorbid perinatal conditions (LBW, preterm, hypoxia/asphyxia, birth trauma), maternal smoking, and maternal mental disorder during the pregnancy.
Li (Controls exposed to NSAIDS), 2018	retrospective cohort (claims database)	Participants were interviewed in person by experienced interviewers. The interview collected detailed information on exposure to NSAIDs and acetaminophen during pregnancy. In addition, medications obtained from KPNC’s pharmacy database were verified with the participant.	Miscarriage and other pregnancy outcomes were ascertained through Kaiser Permanente Northern California (KPNC) clinical Electronic Medical Record (EMR) data. Miscarriage status during both the initial interview and a follow-up interview at 20 weeks of gestation were verified.	Adjusted for previous miscarriage, maternal age, multivitamin use, caffeine drinking, and smoking during pregnancy; further adjustment for race/ethnicity, education level, number of previous pregnancies, fever during pregnancy, history of diabetes mellitus, and history of fertility problems did not change the results.
Li (Controls unexposed, NOS), 2018	retrospective cohort (claims database)	Participants were interviewed in person by experienced interviewers. The interview collected detailed information on exposure to NSAIDs and acetaminophen during pregnancy. In addition, medications obtained from KPNC’s pharmacy database were verified with the participant.	Miscarriage and other pregnancy outcomes were ascertained through Kaiser Permanente Northern California (KPNC) clinical Electronic Medical Record (EMR) data. Miscarriage status during both the initial interview and a follow-up interview at 20 weeks of gestation were verified.	Adjusted for previous miscarriage, maternal age, multivitamin use, caffeine drinking, and smoking during pregnancy; further adjustment for race/ethnicity, education level, number of previous pregnancies, fever during pregnancy, history of diabetes mellitus, and history of fertility problems did not change the results.
Liew, 2014	prospective cohort	Paracetamol use was collected in three computer-assisted telephone interviews conducted at gestational weeks 12 and 30 and 6 months postpartum. At each interview, mothers were asked if they had taken acetaminophen as a singular or combination drug available over the counter or via prescription.	Hyperkinetic disorders diagnosis identified from the National Hospital Registry, the Psychiatric Central Registry or 2 or more ADHD medication prescriptions (methylphenidate, atomoxetine or modafinil). ADHD-like behaviors based on the Strengths and Difficulties Questionnaire (parental report).	Adjusted for maternal age at birth, sex of child, child’s birth year, gestational age, birth weight, parity, socioeconomic status of mother, maternal smoking and alcohol drinking during pregnancy, maternal prepregnancy BMI, mother’s ever having had mental health problems, and maternal diseases in muscles/joints, fever, or infection/inflammation during pregnancy. Additional sensitivity analyses.
Liew, 2021	retrospective cohort	Mothers were interviewed by phone or replied to a mailed survey in English or Spanish three to six months post-partum. Mothers provided detailed information on pregnancy exposures (medication, trimester and frequency) including over-the-counter medication use.	In 2006–2007, a follow-up study was conducted to assess the offspring’s respiratory health, assessed via maternal report according to the International Study of Asthma and Allergies in Childhood (ISAAC) core questionnaire. Women responded to the survey by phone or mail.	Singletons only. Adjusted for maternal age, parity, household income, smoking before or during pregnancy, high fever during pregnancy, and maternal intake of aspirin or ibuprofen during pregnancy, pre-pregnancy body mass indew, use of antibiotics, maternal alcohol intake during pregnancy and air pollution (exposures to carbon monoxide (CO), nitrogen dioxide (NO2), PM10 and PM2.5 during pregnancy).
Liew a, 2016	prospective cohort	Paracetamol use was collected in three computer-assisted telephone interviews conducted at gestational weeks 12 and 30 and 6 months postpartum. At each interview, mothers were asked if they had taken acetaminophen as a singular or combination drug available over the counter or via prescription.	Child IQ was assessed with the Wechsler Primary and Preschool Scales of intelligence-revised (WPPSi-r) administered by trained psychologists.	Singleton only. Adjusted for parental education, maternal IQ, maternal smoking and drinking during pregnancy, parity, maternal age at child birth, child’s sex, maternal diseases in muscles/joints, fever, or infection/inflammation during pregnancy, and prenatal use of ibuprofen or aspirin. Sensitivity analysis excluding high alcohol drinkers or extreme child IQ values.
Liew b, 2016	prospective cohort	Paracetamol use was collected in three computer-assisted telephone interviews conducted at gestational weeks 12 and 30 and 6 months postpartum. At each interview, mothers were asked if they had taken acetaminophen as a singular or combination drug available over the counter or via prescription.	Autism Spectrum Disorder diagnosis (ICD-10) was ascertained by linking Danish National Birth Cohort to the Danish National Hospital Registry, which contains nationwide records for all somatic admissions, and the Danish Psychiatric Central Registry for admissions to psychiatric hospitals.	Singleton only. Adjusted for child’s sex, birth year, maternal age, parity, socio-economic status, maternal smoking and alcohol drinking during pregnancy, maternal prepregnancy body mass index, folic acid during pregnancy, mother’s psychiatric illnesses, maternal diseases in muscles/joints, fever, or infection/inflammation during pregnancy, maternal use of ibuprofen and aspirin during pregnancy.
Liew c, 2016	prospective cohort	Paracetamol use was collected in three computer-assisted telephone interviews conducted at gestational weeks 12 and 30 and 6 months postpartum. At each interview, mothers were asked if they had taken acetaminophen as a singular or combination drug available over the counter or via prescription.	Trained psychologists blinded to exposure status conducted a 3-hours neuropsychological assessment, using the Test of Everyday Attention for Children at Five (TEACh-5, for child attention). Parents and preschool teachers completed Behaviour Rating Inventory of Executive Function (BRIEF).	Singleton only. Adjusted for parental education, maternal IQ, maternal mental health status, prenatal smoking, prenatal drinking, parity, maternal age at child birth, child’s sex, maternal pre-pregnancy body mass index, maternal musculoskeletal diseases, fever or infection/inflammation during pregnancy, and maternal use of ibuprofen or aspirin. TEACh-5 additionally adjusted for tester.
Liew_Boys, 2019	prospective cohort	Mothers completed the enrollment form and the three telephone interviews (approximately at gestational weeks 12 and 30 and 6 months after birth), during which information on acetaminophen intake during pregnancy was collected.	Children’s body mass index and waist circumference were reported by the mother or father (100% at age 11 years old; 67% at 7 years old). At 7 years old, the remaining 33% of the measures were taken by the school doctor, public health nurse, or general practitioner.	Adjusted for maternal age, parity, birth year, parental socio-occupational status, maternal prepregnancy body mass index, maternal alcohol drinking during pregnancy, maternal smoking during pregnancy, maternal musculoskeletal diseases and pain, fever, or infection/inflammation during pregnancy, and maternal use of ibuprofen and aspirin during pregnancy.
Liew_Girls, 2019	prospective cohort	Mothers completed the enrollment form and the three telephone interviews (approximately at gestational weeks 12 and 30 and 6 months after birth), during which information on acetaminophen intake during pregnancy was collected.	Children’s body mass index and waist circumference were reported by the mother or father (100% at age 11 years old; 67% at 7 years old). At 7 years old, the remaining 33% of the measures were taken by the school doctor, public health nurse, or general practitioner.	Adjusted for maternal age, parity, birth year, parental socio-occupational status, maternal prepregnancy body mass index, maternal alcohol drinking during pregnancy, maternal smoking during pregnancy, maternal musculoskeletal diseases and pain, fever, or infection/inflammation during pregnancy, and maternal use of ibuprofen and aspirin during pregnancy.
Lind, 2013	case control	The National Birth Defects Prevention Study uses computer-assisted telephone interviews to collect information from women 6 weeks to 24 months after their estimated date of delivery.	Cases are identified through population-based birth defects surveillance from each states. A clinical geneticist classifies eligible cases of hypospadias as isolated.	Adjusted for maternal age, race/ethnicity, education, pre-pregnancy body mass index, previous live births, study site, and year of due date. Exclusion of infants with a positive first degree family history of hypospadias (father, full sibling, or previous pregnancy).
Magnus (Controls exposed to ibuprofen), 2016	prospective cohort	Participating mothers reported the use of medications for different indications during pregnancy through questionnaires completed at 18 gestational weeks, 30 gestational weeks and when the child was 6 months old.	Two asthma outcomes were examined based on the MoBa questionnaires and one outcome based on dispensed asthma medication.	Singletons only. No adjustment for this group of comparison.
Magnus (Controls unexposed, NOS), 2016	prospective cohort	Participating mothers reported the use of medications for different indications during pregnancy through questionnaires completed at 18 gestational weeks, 30 gestational weeks and when the child was 6 months old.	Two asthma outcomes were examined based on the MoBa questionnaires and one outcome based on dispensed asthma medication.	Singletons only. Adjusted for maternal age, parity, education, pre-pregnancy body-mass index, smoking during pregnancy, asthma, illness during pregnancy (respiratory tract infections/influenza, fever, pain and antibiotic use), child’s gender, birth weight, breastfeeding the first 6 months, respiratory tract infections by 6 months, body mass index at 6 months and use of antibiotics by 6 months.
Malaeb, 2021	case control	The questionnaire used was self-administered, anonymous, in Arabic and assessing behaviors during pregnancy like OTC medication use (questionnaires were distributed when students were grades 1 and 9).	A standardized questionnaire fill out by parents to document asthma status and evaluate respiratory symptoms using validated International Study of Asthma and Allergies in Childhood (ISAAC) items. Students were asked to take it home, fill it out by their parents, and return it to school.	Students with chronic respiratory condition were excluded. Variables entered in the model: paracetamol, ibuprofen, propranolol, acetylsalicylic acid, amoxicillin/clavulanic acid, vitamin C, fish oil, gender, school type, method of baby delivery, breastfeeding, mother’s and father’s level of education, and positive family history.
Marild, 2017	prospective cohort	Data on exposures were collected from questionnaires administered at weeks 18 and 30 of pregnancy (covering the period of the first 17 weeks of pregnancy and weeks 18 to 30 of pregnancy, respectively) and when the child is 6 months old (exposures after pregnancy week 30 and up until delivery).	Celiac Disease Diagnosis was defined as minimum 2 registrations of the International Classification of Diseases-10 code K90.0 in the Norwegian Patient Register (NPR) by December 31, 2013 or Celiac Disease reported by parental questionnaires administered when the child is 7 to 8 years.	Adjusted for child’s attained age at end of study, sex, maternal celiac disease, type 1 diabetes, smoking in pregnancy, education level, parity, birth weight, prematurity, parent-reported infection frequency in the child up to the age of 6 months and maternal infection frequency in pregnancy. In the analyses on the maternal use of paracetamol, it was also adjusted for her use of antibiotics.
Nelson, 1971	case control	All mothers were interviewed before discharge from maternity units to complete a questionnaire on drugs consumed during pregnancy. Finally, an attempt was made to recover the prescriptions issued to the mothers as proof that they had been taken for dispensing and as a record of the drugs supplied.	In the hospitals the antenatal and other outpatient records and inpatient records were studied. For general practitioners of mothers included in the survey: 53% were seen personally and 37% provided information by telephone and/or questionnaire (10 % non responders).	Some controls (about 50%) matched in respect of maternal age and parity and babies' sex with a similar number in the study group.
Ognjanovic, 2011	case control	Information was collected through computer-assisted telephone interviews with the biological mother. Analgesic questions included maternal use of aspirin, acetaminophen and non-aspirin NSAIDs, including the frequency of use during these two time periods.	Detailed reports on leukaemia cell cytogenetics and molecular abnormalities were obtained for cases and included leukaemia subtype (lymphoblastic or myeloid) and MLL gene translocation status.	Controls matched to cases on year of birth (and region of residence for phase II). Adjusted for maternal age, race, alcohol consumption during pregnancy, household income. Cases and controls were similar with respect to previous fetal loss, smoking during pregnancy, pre-pregnancy body mass index, and infant gender and birth weight.
Okubo (Controls unexposed, general population), 2025	retrospective cohort (claims database)	Acetaminophen use during pregnancy was identified from all prescription dispensation records using the Anatomical Therapeutic Chemical (ATC) codes. The exposure metric was the ever-use of acetaminophen during pregnancy.	The outcomes were identified in the Japan Medical Data Center (JMDC) database, that contains diagnoses and procedures (only confirmed diagnoses were used). For ADHD: the prescription data of ADHD medications, such as methylphenidate and atomoxetine was also used.	Propensity score matching for prescriptions before pregnancy (acetaminophen, NSAIDs, antipsychotics, antibiotics, ...), diagnoses (migraine, infection, headache, pain, asthma, ...) before and during pregnancy, prescriptions during pregnancy (NSAIDs, aspirin, antiepileptics, antidiabetics, H2 blocker, PPI, antibiotics, beta-blockers, antihistamine, drugs for asthma...), mother's age at birth.
Okubo (Controls unexposed, sibling), 2025	retrospective cohort (claims database)	Acetaminophen use during pregnancy was identified from all prescription dispensation records using the Anatomical Therapeutic Chemical (ATC) codes. The exposure metric was the ever-use of acetaminophen during pregnancy.	The outcomes were identified in the Japan Medical Data Center (JMDC) database, that contains diagnoses and procedures (only confirmed diagnoses were used). For ADHD: the prescription data of ADHD medications, such as methylphenidate and atomoxetine was also used.	Sibling design (partially control for genetic and familial confounding). To adjust for potential within-family imbalance, the covariates with absolute SMDs > 10% between the groups were included (e.g., age, birth order, clinical diagnoses (e.g., infections, headache), and prescriptions (e.g., NSAIDs, antimicrobials)).
Pastore, 1999	case control	Month-by-month exposure information was asked for most, but not all, variables of interest. The time between delivery and completion of the questionnaire varied between 2 and 4 years.	Data sources included birth certificates, fetal death certificates and a postal questionnaire.	Matched by maternal age and county. Controlled for maternal race/ethnicity, maternal age, county of residence, prior fetal loss, season of conception, twin gestation and occupational pesticide exposure.
Pérez-Molina, 2002	case control	Exposure data were obtained through a direct interview with the mothers of the study subjects, using structured questionnaires with closed-ended questions designed to document prior exposure to the studied variables.	Records corresponding to the cases and controls were extracted from the general congenital malformation database, and the original questionnaires were reviewed in detail to verify the clinical descriptions of each neural tube defect.	No adjustment. No significant differences in maternal age and maternal occupation.
Persky, 2008	retrospective cohort	Acetaminophen use was determined from 4 different questionnaires: (1) at enrollment (first trimester); (2) at the second visit (4-5 months of gestation); (3) at the third visit (7-8 months of gestation); and (4) at the first postpartum visit (visit 4).	Development of respiratory end points was determined by any positive response to the following questions at visit 4 (child 4 to 6 weeks old), at visit 5 (child 6 months old), at visit 6 (child 12 months old), or during telephone calls at 3 and 9 months.	Adjusted for maternal age, child's sex, home environment intervention group, ethnicity, child breastfed for 4 or more weeks, active smoking in middle to late pregnancy, passive smoke during pregnancy, low birth weight, antibiotic use in late pregnancy, age at which formula introduced, and family history of asthma. Additional analysis with infections and low intake of antioxidants in pregnancy.
Perzanowski, 2010	prospective cohort	Use of acetaminophen, ibuprofen and aspirin during pregnancy was ascertained in the third trimester. Mothers complete prenatal questionnaire items on analgesic use.	Questionnaires on the child’s environmental exposures and health status were administered to the mother during study visits at ages 1, 2, 3 and 5 years. Less detailed health follow-up questionnaires were administered by telephone at 3, 6, 9, 15, 18, 21 and 30 months.	Exclusion criteria: diabetes or HIV infection, self-report of illicit drug use, active smoking during pregnancy and age <18 years. Adjusted for sex, ethnicity, birth order, maternal asthma, maternal hardship, exposure to environmental tobacco smoke and postnatal acetaminophen use. Additional adjustment for antibiotic and ibuprofen use during pregnancy did not appreciably alter this association.
Petersen, 2018	prospective cohort	Exposure was collected in DNBC in the enrolment form and with computer-assisted telephone interviews at gw 16 and 31. In MoBa, these data were collected by self-administered questionnaires at gw 17 and 30. Later exposures were covered by data collections 6 months after delivery, in both sub-cohorts.	The Danish National Cerebral Palsy Registry includes all children with a diagnosis of pre- and perinatal acquired CP verified by a neuro-paediatrician. In Norway there is similar Cerebral Palsy Registry with a coverage rate of 76%. Also identified through linkage with the Patient Registry of Norway.	Singletons. Stabilized inverse probability weights: from birth year, maternal occupational status, body mass-index, IVF treatment, smoking, use of other mild analgesics, respiratory infection, fever and urinary tract infection in pregnancy. Trimester-specific: information on use of other analgesics, respiratory infection and fever in previous or same trimesters as index exposures were used.
Pleau, 2025	retrospective cohort (claims database)	Prescriptions from the Quebec prescription medication insurance.	Diagnosis or prescriptions available in the Quebec Pregnancy Cohort (RAMQ = Régie de l’assurance maladie du Québec).	Singletons. Exclusion: prenatal use of fetotoxic medications, malformations/genetic conditions. Adjusted for mothers’ age, type of drug plan coverage, acetaminophen in 1st trimester, NSAIDs, opioids, and nb of other medications in pregnancy, diagnoses of tobacco/alcohol/drug abuse, of of pain and fever, obesity, ADHD, hypertensions, diabetes, epilepsy, mental health disorders in pregnancy, SGA…
Poletta, 2012	case control	Data regarding medication use and illnesses during pregnancy were obtained by qualified physicians using standard interviews of the mothers before their discharge from the hospital at which they had given birth.	Live-birth cases were those that were registered by the Latin American Collaborative Study of Congenital Anomalies (ECLAMC) network (no other details).	No adjustment/matching. Controls show no difference to total births with respect to maternal age, gravidity, and birth weight.
Puho, 2007	case control	Mothers were asked to send their prenatal maternity logbook and other medical records and they were mailed a questionnaire. Regional nurses were asked to visit and question the non-respondent.	Notification by physicians to the Hungarian Congenital Abnormality Registry. Pathologists sent a copy of each autopsy report to the registry for stillborn fetuses or infant deaths and defect diagnosed in prenatal diagnostic centers with or without termination of pregnancy were included.	Adjusted for maternal age and employment status, parity and acute maternal diseases in the 2nd and/or 3rd months of pregnancy. Controls were matched according to sex, week of birth in the year when the case was born, and district of parent’s residence.
Rebordosa, 2009	prospective cohort	Exposures were identified from responses in the enrolment questionnaire and from the first, second or third telephone interviews (at 12th and 30th gestational weeks and when the child was 6 months old).	Outcomes coded using the International Classification of Diseases, 10th version (ICD-10) were based on the National Hospital Registry (NHR) covering all Danish inpatients and outpatients and to the Medical Birth Registry (MBR).	Singletons. Adjusted for mother’s age, socio-economic status, pre-pregnancy body mass index, cigarettes per day, birth order, coffee intake and sex of the child. For miscarriage risk: also adjusted for previous abortions. Gestational age, alcohol, pre-eclampsia, preterm, diabetes, fever, muscle/joint diseases, common cold/influenza, inflammation, infection or antibiotic use... => <1% change.
Rebordosa, 2010	prospective cohort	Exposure information was collected several times during pregnancy in order to facilitate recall, with the help of computer-assisted telephone interviews with the women twice during pregnancy (around the 12th and 30th week) and when the children were 6 and 18 months and 7 years of age.	Outcomes of interest were identified from the National Hospital Discharge Registry (NHDR) where all Danish in and out-patient hospital records of clinical diagnoses (ICD-10 codes) and/or based on maternal information collected in the second or third interview.	Singletons only. Adjusted for mother age, socio-occupational status, parity, history of preeclampsia, diabetes, body mass index, gestational weight gain and smoking. Preeclampsia probable and definitive is also adjusted by history of chronic hypertension.
Rebordosa a, 2008	prospective cohort	Data were mainly through 4 computer-assisted follow-up telephone interviews and a self-administered questionnaire at enrollment. Telephone interviewing took place at scheduled times and participants were asked to have prescriptions or medication packets available at the time of interviewing.	The National Hospital Registry (NHR) was used to identify children with congenital abnormality codes Q00.0-99.9 of the International Classification of Diseases, 10th version (ICD-10).	Singletons only. Adjusted by mother’s age, birth year, birth order, child’s gender, and history of chronic diseases (diabetes, epilepsy, obesity, or low fecundity).
Rebordosa b, 2008	prospective cohort	Women were asked to complete a self-administered enrolment questionnaire and participate in four telephone interviews (two during pregnancy and two more when the child was 6 months and 18 months of age). Information about paracetamol, aspirin and ibuprofen use was obtained from the interviews.	At 18-months-old, the mothers were asked if their children had ever had wheezing or whistling and if a physician had diagnosed them with asthma or bronchitis. At the 7-year interview, a questionnaire was used to obtain data about their children’s asthma symptoms, diagnosis, wheezing or whistling.	Singletons only. Adjusted for mother’s asthma, gestational age at birth, gender of the child, socio-economic status, duration of breastfeeding, smoking during pregnancy and antibiotic use during pregnancy. Mother age, birth order, fever or muscle/joint disease or inflammation/infection during pregnancy, mother allergy or eczema, pets during the first 18 months of live, ... => no impact.
Rifas-Shiman, 2020	prospective cohort	Intake of acetaminophen and ibuprofen were asked to pregnant women during interviews conducted during early (median 9.9 weeks of gestation) and mid-pregnancy (median 27.9 weeks of gestation), categorize as never, 1–9 times, or ≥10 times.	In mid-childhood, one parent (almost always the mother) and one classroom teacher per child completed the Behaviour Rating Inventory of Executive Function (BRIEF) and the Strengths and Difficulties Questionnaire (SDQ), with higher scores indicating worse functioning for both.	Singletons only. No adjustment for the raw values (mean and standard deviation) (Beta adjusted available in publication).
Robledo-Aceves, 2015	case control	The record used by the Centro de Registro y Investigación sobre Anomalías Congénitas (CRIAC) contained standardized questions concerning notably maternal exposures during the periconceptional period and prescription drugs. No other details.	The delivery and birth data were obtained directly from the hospital records.	Controls were matched for gender. Adjusted for maternal age, first-trimester alcohol consumption, anemia during pregnancy, pre-pregnancy Body Mass Index <18.5 kg/m2, first-trimester tobacco smoking, and passive tobacco smoking.
Ross, 2003	case control	Exposure information was collected from mothers using a structured telephone questionnaire. All prescription drugs recorded in the medical record were abstracted, including data for the trimester of pregnancy the drug was prescribed based upon gestational ages recorded in medical records.	Signed medical record release forms were obtained and complete copies of medical records were requested. Data were abstracted from medical records by two registered nurses using a structured protocol.	Controls matched to cases by birth date (within one year) and telephone area and exchange. Adjusted for maternal age, education, and income.
Rumack, 1981	prospective cohort	A complete drug history was obtained from the mother on day 2 post partum to determine whether any medication containing either aspirin or acetaminophen was ingested during the last week of pregnancy.	Diagnosis of intracranial hemorrhage in the infants was made with CT scan between days 3 and 7 after birth. Intracranial hemorrhage was diagnosed if intracerebral, intraventricular or subarachnoid hemorrhages were demonstrated in any combination.	No adjustment.
Shaheen (Controls unexposed, general pop), 2019	population based cohort retrospective	Information on prescribed analgesics dispensed during pregnancy was collected from the Swedish Prescribed Drug Register (SPDR) that contains information on prescription and dispense dates, number of packages, and dosage of all prescribed medications dispensed in Swedish pharmacies.	Information on childhood asthma was collected from the National Patient Register for all inpatient and specialist outpatient diagnoses (International Classification of Diseases (ICD)-10: J45 and J46), and from the SPDR for all asthma prescribed medications from both primary and specialist care.	Adjusted for maternal birth country, education, asthma, body mass index in early pregnancy, parity, smoking during pregnancy and age at delivery.
Shaheen (Controls unexposed, sibling), 2019	population based cohort retrospective	Information on prescribed analgesics dispensed during pregnancy was collected from the Swedish Prescribed Drug Register (SPDR) that contains information on prescription and dispense dates, number of packages, and dosage of all prescribed medications dispensed in Swedish pharmacies.	Information on childhood asthma was collected from the National Patient Register for all inpatient and specialist outpatient diagnoses (International Classification of Diseases (ICD)-10: J45 and J46), and from the SPDR for all asthma prescribed medications from both primary and specialist care.	Sibling design. Adjusted for maternal body mass index in early pregnancy, parity, smoking during pregnancy and age at delivery.
Smith-Webb, 2023	retrospective cohort	Information on acetaminophen use during pregnancy was collected via standardized telephone interview after delivery and prior to conduct of any neurodevelopmental assessments of the child. Maternal exposures collected on average 12 months after delivery (IQR: 3–18 months).	Adolescent behavior was assessed at childhood (5–10) and adolescence (11–17) using the school-age Achenbach System of Empirically Based Assessments, the parent-completed Child Behavior Checklist (CBCL), the teacher-completed Teacher Report Form (TRF), and the self-completed Youth Self Report (YSR).	Singletons only. Adjusted and SIPW (stabilized inverse probability weights) for confounders identified a priori based on prior literature, which included maternal age, education, marital status, parity, drinking, and smoking.
Snijder, 2012	prospective cohort	The three self-administered questionnaires assessed medication use during pregnancy and were sent out by post at gestational weeks 12, 20 and 30 with an average lag period to response of about 2 weeks.	The presence of cryptorchidism and hypospadias was ascertained during 10 visits of children to the child health care centres (0–48 months). All visits included physical examinations, performed by trained physicians, including manipulation of the testes and inspection of the genitalia.	Adjusted for maternal age, maternal educational level, maternal body mass index, maternal general health, maternal use of co-medication (yes/no), maternal underlying diseases (not other details) and maternal fever during pregnancy.
Sznajder, 2022	prospective cohort	Data on medication use during pregnancy was collected during the first interview of participants, conducted by telephone during their third trimester of pregnancy (mean gestational age of 35.2 weeks). They were asked if it was prescription or non-prescription, the dose, frequency taken, and reason.	Child behavioral problems were measured using the 7 syndrome scale scores from the 99-item Child Behavior Checklist (CBCL) for ages 1 1⁄2 to 5, completed by parents. Pregnancy and neonatal complications were based on the ICD-9 codes in the hospital discharge data and from the birth certificates.	Exclusion of pregnancies delivered before 34 weeks gestation. Neurodevelopmental outcomes: adjusted for infection during pregnancy and/or maternal age and/or maternal race and/or alcohol consumption and/or diagnosis of anxiety or depression and/or stress and/or insurance coverage and/or cold/allergies and/or trouble sleeping and/or thyroid conditions and/or muscle pain and/or mode of delivery.
Tapia, 2018	prospective cohort	Maternal pregnancy exposures were assessed by questionnaires that are available at [www.fhi.no/moba], administered at pregnancy weeks 17 and 30, and at child’s age 6 months (covering pregnancy weeks 0–17, 18–30 and 30 until delivery, respectively).	Children with type 1 diabetes were identified through the Norwegian Childhood Diabetes Registry (data capture until 31 May 2017), and the Norwegian Patient Register (NPR).	Adjusted for child’s sex, maternal age and parity, maternal type 1 diabetes, smoking in pregnancy, education level, pre-pregnancy body mass index, prematurity, birthweight, infections and antibiotic use.
Thulstrup, 1999	retrospective cohort (claims database)	The North Jutland Prescription Database of the Denmark was used to examined the exposure. The county is served by 33 pharmacies equipped with a computerized accounting system from which data are sent to the health insurance administration of the Danish National Health Service.	The Danish Birth Registry, which contains information on all births in Denmark, obtained from notifications of birth which are recorded by midwives or doctors for all deliveries. Also linked to the Danish Hospital Registry (for malformations).	Single child. Adjusted for birth order, smoking and maternal age. No important differences for marital status.
Torfs, 1996	case control	Specially trained interviewers administered a 2-hour structured questionnaire to case and control mothers in their homes. Mothers were asked about the medications, either prescribed or bought over the counter, that were used to treat their illnesses.	All birthing and tertiary referral hospitals in the counties surveyed, as well as genetic laboratories, are visited periodically, and all obstetric, nursery, and pathology logs are reviewed to identify infants with possible birth defects. Review of hospital charts of all cases.	Singletons only. Control mothers came from the same ethnic background as case mothers and were matched on age to within a year.
Tovo-Rodrigues, 2020	prospective cohort	Maternal use of medication during pregnancy was retrospectively assessed using a standardised questionnaire applied at the perinatal evaluation (within 24 hours after delivery).	At birth, the newborn was measured and had its gestational age assessed. At 24 and 48 months, the assessments were performed at the child's home (screening BDI and CBCL), in the presence of the mother or caregiver, by interviewers trained by a paediatrician or psychologist, respectively.	Adjusted for family wealth index; mother's skin colour; mother's age; mother's schooling; single mothers; parity; pre-pregnancy BMI; tobacco and alcohol use; and prenatal care (number of antenatal care appointments) during pregnancy, mood symptoms; infectious diseases; high blood pressure, gestational diabetes; use of other analgesics during pregnancy; and child sex.
Tovo-Rodrigues, 2018	prospective cohort	A standardized questionnaire was used during the perinatal evaluation conducted after the birth of the children. The mothers were asked to report all medicines used during pregnancy, and the beginning and end of use.	Standardized scores from the Strengths and Difficulties Questionnaire (SDQ) adapted and previously validated for the Brazilian population 4-16 years. Trained psychologists administered the SDQ in a standardized manner to the parents or caregivers during each follow-up.	Exclusion of children who presented severe mental deficit due to problems such as cerebral palsy and Down syndrome. Adjusted for sex, maternal age, parity, national economic index, maternal educational level, maternal skin color, smoking, alcohol consumption during pregnancy, infection during pregnancy, pre-gestational BMI, maternal mood issue and use of other analgesics during pregnancy.
Tronnes, 2020	prospective cohort	Information about medication use was obtained from two prenatal and one postnatal questionnaire completed by mothers (at gestational ages 17 and 30 weeks and at 6 months postpartum). Duration of paracetamol use was defined according to the number of trimesters it was used.	All outcomes were parent‐reported with: the Ages and Stages Questionnaire (ASQ) for communication skills; selected items from The Child Behaviour Checklist (CBCL) for children's behaviour and the Emotionality, Activity and Shyness Temperament Questionnaire (EAS) for temperament.	Exclusion of multiple pregnancies. Adjusted estimates are weighted with combined weights (IPTW × IPCW), including maternal age, martial status, education level, parity, pre‐pregnancy body mass index (BMI), folic acid supplement, smoking habits, alcohol use, symptoms of anxiety and depression, maternal health conditions during pregnancy, concomitant medication use, and child sex.
Vlenterie, 2016	prospective cohort	Women reported information about illnesses they experienced throughout pregnancy and the medication used for these illnesses, in the two prenatal and first post-partum questionnaire (at gestational week (GW) 17, GW30, and 6 months post-partum).	Outcomes were assessed by maternal assessment: psychomotor development by the Ages and Stages Questionnaire (ASQ); behaviour by the Child Behaviour Checklist (CBCL/11/2-5/LDS) and temperament with the short-form Emotionality, Activity and Shyness Temperament Questionnaire (EAS).	Singletons only. Exclusion of infants with major congenital malformations. Propensity score (PS) including maternal age, pre-pregnancy body mass index, parity, married/cohabiting, education, smoking, alcohol use, folate use, specific health conditions (pain, fever, infections, headache), psychotropic co-medication (opioids, antiepileptics, NSAIDs, ...) and depressive symptoms.
Walker, 2024	prospective cohort	Prenatally, mothers provided potential teratogens (e.g., drug use). Mothers were asked whether or not (yes or no) they have taken certain types of medications in the first three months and after the first three months of pregnancy.	Children self-completed the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Item Bank v2.0 – Anxiety Short Form 8a.	No adjustment (use of raw data).
Werler, 1992	case control	Mothers of infants with any of a range of birth defects were interviewed within 6 months after delivery about events and exposures during pregnancy, including medication use (from the 6 months prior to pregnancy through delivery). The median interval between delivery and interview was 4 months.	Cases and controls were drawn from the Boston University Slone Epidemiology Unit Birth Defects Study, an on-going case-control surveillance program. Medical records were available to review for 46 potential cases and the diagnosis of gastroschisis was confirmed for 45 of them.	Adjusted for maternal age, years of education, alcohol consumption, influenza in the first trimester, each of the study medications (salicylates, ibuprofen, pseudoephedrine, phenylpropanolamine, other decongestants, antihistamines (excluding antiemetics which contain antihistamines), antibiotics (excluding antifungals), oral conteraceptives, and spermicides), interview year; and study center.
Werler, 2002	case control	A nurse-interviewer administered the standardized questionnaire by telephone within 6 months after delivery. Information was collected notably on medication histories The interviewer was not blinded to case/control status.	Study subjects were ascertained from 29 pediatric tertiary care hospitals within 5 months of birth (no other details).	Adjusted for maternal age (SIA only; matched for gastroschisis), education, income, medication use (pseudoephedrine, phenylpropanolamine, aspirin, ibuprofen, antihistamines, guaifenesin, dextromethorphan), illness (fever, upper respiratory infection, and allergy), illicit drug use, and cigarette smoking.
Werler, 2014	case control	Mothers were interviewed by telephone within 12 months after delivery about medication use, including indication, product, timing, and frequency.	Study subjects were ascertained from birth defect registries in Massachusetts, New York, and North Carolina. Mothers were then interviewed and an orthopedist reviewed the children’s pediatric and orthopedic records (77% agreed). Controls identified from birth certificates or hospital records.	Odds ratios were adjusted for study site, first born, sex, body mass index, and maternal smoking through Lunar Months 4. Confounding by the use of multiple medications was assessed. Analysis with exclusion of first-degree history of clubfoot.
Werler, 2003	case control	Mothers of study subjects are interviewed by a study nurse within 6 months of delivery about events and exposures during pregnancy.	Liveborn and stillborn infants with major malformations are identified at birth and tertiary hospitals in the greater metropolitan areas of Boston, Philadelphia, and Toronto.	Multivariate-adjusted for maternal age, education, race/ethnicity, planned pregnancy, cigarette smoking during pregnancy, and year of interview.
Winship, 1984	case control	Information of the drugs prescribed was obtained from the family doctors' records only and is therefore, not necessarily a complete record of drugs taken (it excluded hospital prescriptions and over the counter medicines).	Information on each study and control child and their mothers was obtained from the records of the family doctors, who were interviewed by part time medical officers of the Committee on Safety of Medicines (CSM). Data were notably collected on outcome of pregnancy and congenital abnormality.	The control child was the nearest normal birth in the practice within three months after the birth of the study child.
Woodbury a, 2024	prospective cohort	At approximately 10–14, 16–18, 22–24, 28–30, and 34–36 weeks of gestation, and within 24hours of the child’s birth, participants were interviewed by telephone about their medication use (between last and current interview), including acetaminophen as an active ingredient.	Caregivers were asked to participate in follow-ups of the study child. Those who agreed were mailed a packet of questionnaires which included the MacArthur-Bates Communicative Development Inventories (CDI) at 26.5–28.5 months, and the Speech and Language Assessment Scale (SLAS) at 36–38 months.	Singletons only; Not advanced maternal age. All models were adjusted for maternal parity, maternal education, mean perceived stress during pregnancy, and mean depression during pregnancy. Child sex was included as a potential modifier. Sensitivity analyses for: maternal alcohol use, smoking, mother’s native language, marital status, postnatal depression scores and the other parent’s education.
Xu, 2024	retrospective cohort	Data were extracted from the electronic medical record (EMR) system, where the patient has a unique code to support the inquiry and tracking of patient medical records and medication information.	Diagnostic information, medication data, and perinatal outcomes were extracted from the electronic medical record (EMR) system, where the patient has a unique code to support the inquiry and tracking of patient medical records.	Adjusted for maternal age, pre-pregnancy BMI, previous live births, history of adverse perinatal outcomes, COVID-19, fever, common cold, upper respiratory tract infection, immuno-associated diseases, hypertension, preexisting and gestational diabetes, co-medication (NSAIDs, antibiotics, antiviral, ...), ... Exclusion: teratogens in pregnancy, chromosomal/genetic disease, multiple pregnancies.
Ystrom or Gustavson (Gustavson 2021 - Sibling), 2017	prospective cohort	Mothers reported on medication use and the total number of days the medication was taken in questionnaires at gestational weeks 17 and 30, and 6 months after birth. The sum of number of days' acetaminophen exposure across all indications and all questionnaires was calculated for each child.	Information about Attention deficit hyperactivity disorder (ADHD) diagnoses came from the Norwegian Patient Registry (including all government-funded clinics from 2008 - Hyperkinetic disorder (F90) according to ICD10).	Children from multiple births were excluded. Sibling. Propensity scores were used to adjust for type and numbers of indication groups for acetaminophen use, child's birth year, maternal age, alcohol use during pregnancy, smoking during pregnancy, symptoms of anxiety and depression, use of acetaminophen before and after pregnancy, number of co‐medications used during pregnancy, and child's sex.
Ystrom or Gustavson (Ystrom - Population-Based), 2017	prospective cohort	Information on acetaminophen use was obtained through MoBa questionnaires, at week 18, week 30, and 6 months postpartum. The mother could name the medication taken in an open textbox and specify the exposure windows (total calculated across all exposure windows).	Information about children’s ADHD diagnosis was obtained from the Norwegian Patient Registry (NPR, coded with International Classification of Diseases, 10th Revision diagnoses of hyperkinetic disorder (F90.0, F90.1, F90.8, or F90.9)) between 2008 and 2014.	Adjusted for maternal and paternal use before pregnancy, birth year, parental ADHD symptoms, alcohol use during pregnancy, smoking during pregnancy, symptoms of anxiety and depression during pregnancy, maternal education, marital status, BMI at 17th week of gestation, maternal age, and parity.
Zafeiri, 2022	retrospective cohort	Data were collected from medical notes of women retrospectively after delivery. Women were specifically asked about their use of over-the-counter (non-prescription) analgesics at their first antenatal clinic. Constant data cleaning and validation against case notes reported quarterly.	Data were collected from medical notes of women retrospectively after delivery.	Singleton only. Adjusted for year, maternal age at delivery, SIMD and maternal first antenatal visit. Gestation at delivery and pregnancy outcome were both additionally adjusted for maternal hypertensive disorders and antepartum haemorrhage. Weight and neonatal unit admission and malformations also adjusted for gestation at delivery. APGAR score adjusted for type of delivery.
Zarante, 2009	case control	Information collected in 10 Colombian hospitals (NOS).	Information collected in 10 Colombian hospitals (NOS).	No match/adjustment for this group of exposure.
Zierler, 1985	case control	Exposure data was obtained from detailed telephone questionnaires administered by one interviewer with questions designed to prompt recall of drug use and reasons for such use. The second source of exposure information was obstetric records of mothers of controls and affected children.	Cases mainly identifier from the New England Infant Cardiac Registry according to diagnoses of the cardiac defect recorded in medical records. Controls were randomly selected from available birth certificates filed with the Massachusetts Division of Health Statistics.	None.

master protocol