Topiramate (Epilepsy)

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Alsfouk (Topiramate) (Controls exposed to Lamotrigine, sick), 2021	retrospective cohort	Patients’ electronic and paper-based medical records.	Patients’ electronic and paper-based medical records.	None.
Alsfouk (Topiramate) (Controls unexposed, sick), 2021	retrospective cohort	Patients’ electronic and paper-based medical records.	Patients’ electronic and paper-based medical records.	None.
AlSheikh (Topiramate) (Controls exposed to Lamotrigine, sick), 2020	prospective cohort	Information was collected through a structured questionnaire ‘Questionnaire for Investigation of Epilepsy in Tropical Countries'.	Information was collected through a structured questionnaire ‘Questionnaire for Investigation of Epilepsy in Tropical Countries'. From the history, and through QuadraMed® hospital database (ICD-9 coding system).	None.
AlSheikh (Topiramate) (Controls unexposed, sick), 2020	prospective cohort	Information was collected through a structured questionnaire ‘Questionnaire for Investigation of Epilepsy in Tropical Countries'.	Information was collected through a structured questionnaire ‘Questionnaire for Investigation of Epilepsy in Tropical Countries'. From the history, and through QuadraMed® hospital database (ICD-9 coding system).	None.
Arkilo (Topiramate), 2015	retrospective cohort	Questionnaires were sent to women.	Questionnaires were sent to women. The developmental outcomes were assessed at 2 years of age by developmental specialists assigned by the school districts.	None.
Babic (Topiramate), 2014	prospective cohort	Not specified.	The authors evaluated the pregnancy complications and perinatal outcomes in their patients.	None.
Battino, 2024	prospective cohort	Reporting physicians collected information on drug therapy after each trimester.	Abnormalities in the offspring were recorded descriptively by reporting physicians. A committee blinded to type of exposure assessed and categorized these abnormalities. When necessary, the committee solicited additional information from the reporting physicians.	Exclusion of pregnancies exposed to known teratogenic drugs, and those with comorbidities associated with teratogenic risks. No adjustment for this group of comparison.
Bjørk (Topiramate) (Controls exposed to Lamotrigine, sick), 2022	population based cohort retrospective	Prescriptions through national prescription registers according to Anatomical Therapeutic Chemical classification codes N03, N05BA09, and S01EC01.	Severe neurodevelopmental disorders are diagnosed by child psychiatrists and psychologists in specialist health care in the Nordic countries and recorded with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes.	No adjustment for this control group.
Bjørk (Topiramate) (Controls exposed to Lamotrigine, sick), 2018	population based cohort propective	Information on anti-epileptics use was obtained from the questionnaires completed by mothers during gestational weeks 17 to 19 (Q1) and 30 (Q2); and through the Medical Birth Registry of Norway.	The instruments are based on parent-reported measures. Autistic traits were evaluated using the Modified Checklist for Autism (M-CHAT) at 18 months (missed any 3 of 23 items or 2 of 6 critical items) and Social Communication Questionnaire (SCQ) at 36 months (score of 13 or more).	No adjustment for this group of exposure.
Bjørk (Topiramate) (Controls unexposed NOS), 2022	population based cohort retrospective	Prescriptions through national prescription registers according to Anatomical Therapeutic Chemical classification codes N03, N05BA09, and S01EC01.	Severe neurodevelopmental disorders are diagnosed by child psychiatrists and psychologists in specialist health care in the Nordic countries and recorded with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes.	No adjustment for this control group.
Bjørk (Topiramate) (Controls unexposed, disease free), 2018	population based cohort propective	Information on anti-epileptics use was obtained from the questionnaires completed by mothers during gestational weeks 17 to 19 (Q1) and 30 (Q2); and through the Medical Birth Registry of Norway.	The instruments are based on parent-reported measures. Autistic traits were evaluated using the Modified Checklist for Autism (M-CHAT) at 18 months (missed any 3 of 23 items or 2 of 6 critical items) and Social Communication Questionnaire (SCQ) at 36 months (score of 13 or more).	No adjustment for this group of exposure.
Bjørk (Topiramate) (Controls unexposed, sick), 2022	population based cohort retrospective	Prescriptions through national prescription registers according to Anatomical Therapeutic Chemical classification codes N03, N05BA09, and S01EC01.	Severe neurodevelopmental disorders are diagnosed by child psychiatrists and psychologists in specialist health care in the Nordic countries and recorded with International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes.	Adjusted for maternal age, education and marital status, parity, child’s birth year, sex, and country of birth. Plus maternal use of antidepressants or opioids, depression, anxiety, personality disorders, chronic somatic diseases, and hospitalizations the year before. Repeating primary analyses after adjusting for maternal neurodevelopmental disorders, BMI and smoking did not change the estimates.
Bjørk (Topiramate) (Controls unexposed, sick), 2018	population based cohort propective	Information on anti-epileptics use was obtained from the questionnaires completed by mothers during gestational weeks 17 to 19 (Q1) and 30 (Q2); and through the Medical Birth Registry of Norway.	The instruments are based on parent-reported measures. Autistic traits were evaluated using the Modified Checklist for Autism (M-CHAT) at 18 months (missed any 3 of 23 items or 2 of 6 critical items) and Social Communication Questionnaire (SCQ) at 36 months (score of 13 or more).	No adjustment for this group of exposure.
Bromley (Topiramate), 2016	retrospective cohort (registry)	Information was collected at registration and changes of antiepileptic drugs during pregnancy were detected during the follow-up duration by sending a standardised questionnaire to the patient's general practitioner. Other health care practitioners were contacted if identified.	Assessments were conducted blinded by authors with the WISC–Fourth Edition or the WPPSI–Third Edition. Specific cognitive domains were assessed utilizing subtests from the NEPSY and the Clinical Evaluation of Language Fundamentals–Fourth Edition and parental rating using the BASC.	None.
Christensen (Topiramate) (Epilepsy) (Controls exposed to LTG), 2024	population based cohort retrospective	Prenatal exposure was identified via national prescription registers. These registers contain the Anatomical Therapeutic Chemical (ATC) classification code (www.whocc.no) and the date of dispensing.	Information on birth weight, gestational age and head circumference at birth was obtained from the medical birth registers for all births occurring at 22 weeks’ gestation or later.	Singleton only. No adjustment for this group of comparison.
Christensen (Topiramate) (Epilepsy) (Controls unexposed, general population), 2024	population based cohort retrospective	Prenatal exposure was identified via national prescription registers. These registers contain the Anatomical Therapeutic Chemical (ATC) classification code (www.whocc.no) and the date of dispensing.	Information on birth weight, gestational age and head circumference at birth was obtained from the medical birth registers for all births occurring at 22 weeks’ gestation or later.	Singleton only. All models were adjusted for country of birth, year of birth, sex of child, maternal age, maternal parity, maternal marital or cohabitation status, pre-pregnancy hospital admittances, maternal education, smoking in early pregnancy, maternal psychiatric history (F00-F99), and use of psychotropic drugs in pregnancy (ATC N06A, N05A, N05B, excl. N05BA09).
Cohen (Topiramate) (Controls exposed to Lamotrigine, sick), 2019	retrospective cohort (claims database)	The Medicaid Analytic Extract data include prescriptions filled on an outpatient basis.	Claims in maternal or infant records after 20 weeks of gestation and were validated based on medical record review. The outcomes are assessed with ICD-9 diagnosis.	Adjustment for all potential confounding factors including demographic factors, risk factors for ischemic placental disease and preterm birth, potential indication for mood stabilizer use, other psychiatric and pain diagnoses, other psychiatric and pain medications (LMP-90 to LMP 140), and severity/health service utilization proxies by inclusion of propensity score stratification weights.
Cohen (Topiramate) (Controls unexposed NOS), 2019	retrospective cohort (claims database)	The Medicaid Analytic Extract data include prescriptions filled on an outpatient basis.	Claims in maternal or infant records after 20 weeks of gestation and were validated based on medical record review. The outcomes are assessed with ICD-9 diagnosis.	Adjustment for all potential confounding factors including demographic factors, risk factors for ischemic placental disease and preterm birth, potential indication for mood stabilizer use, other psychiatric and pain diagnoses, other psychiatric and pain medications (LMP-90 to LMP 140), and severity/health service utilization proxies by inclusion of propensity score stratification weights.
Dreier (Topiramate) (Epilepsy) (Controls exposed to LTG), 2023	population based cohort propective	Information on use of antiseizure medications was based on the national prescription registers, which contain information on all reimbursed prescription medications dispensed at pharmacies in each country, including date of dispensing and Anatomical Therapeutic Chemical (ATC) classification code.	Information on psychiatric disorders was retrieved from the patient registers, which contain diagnostic information from inpatient admissions and outpatient visits in specialist care.	Singletons only. No adjustment for this group of comparison.
Dreier (Topiramate) (Epilepsy) (Controls unexposed, sick), 2023	population based cohort propective	Information on use of antiseizure medications was based on the national prescription registers, which contain information on all reimbursed prescription medications dispensed at pharmacies in each country, including date of dispensing and Anatomical Therapeutic Chemical (ATC) classification code.	Information on psychiatric disorders was retrieved from the patient registers, which contain diagnostic information from inpatient admissions and outpatient visits in specialist care.	Singletons only. Adjusted for year of birth, country of birth, sex of the child, smoking in pregnancy, use of antidepressants (ATC code N06A) in pregnancy, and maternal characteristics assessed at the time of birth (age, parity, highest level of completed education, and psychiatric co-morbidity).
Hao (Controls exposed to LTG), 2025	prospective cohort	Treatment information was collected through case report forms mainly through face-to-face visits in the neurology clinic or remotely by video/telephone calls, at each trimester of pregnancy.	The study data came primarily from the neurology clinics, and additional data were abstracted from the electronic medical record system at the four centers. Potential malformations are reviewed by obstetric, neonatology, and pediatric specialists for confirmation.	None.
Hao (Controls unexposed, sick), 2025	prospective cohort	Treatment information was collected through case report forms mainly through face-to-face visits in the neurology clinic or remotely by video/telephone calls, at each trimester of pregnancy.	The study data came primarily from the neurology clinics, and additional data were abstracted from the electronic medical record system at the four centers. Potential malformations are reviewed by obstetric, neonatology, and pediatric specialists for confirmation.	None.
Hernandez-Diaz, 2024	retrospective cohort (claims database)	Medicaid beneficiaries nationwide, and the Merative MarketScan Commercial Claims and Encounters Database, two data sources that contain information on dispensed outpatient prescription medications.	Clinical diagnoses of autism spectrum disorder were ascertained with the use of a validated claims-based algorithm that requires at least two visits with codes for autism spectrum disorder at or after the age of 1 year.	Exclusion of children with chromosomal anomalies. Propensity score–adjusted for cohort source, maternal age, US region, year of delivery, mental health or developmental conditions, health care use, alcohol, tobacco or substance use disorder, other medications (antidepressants, antipsychotics, ...), comorbidities (diabetes, hypertension, ...), multiple gestation, prenatal vitamin dispensing...
Hernández-Díaz (Topiramate), 2012	prospective cohort	Women were questioned with a computer-assisted telephone interview 3 times.	Women were questioned with a computer-assisted telephone interview 3 times and medical records were obtained. The written descriptions in the pediatricians’ examinations were reviewed separately by the clinical teratologist.	None.
Hernández-Díaz (Topiramate), 2017	prospective cohort	Women were questioned with a computer-assisted telephone interview 3 times.	Women were questioned with a computer-assisted telephone interview 3 times and medical records were obtained.	Confunders included calendar year, maternal age, race, diabetes, cigarette smoking, alcohol use, periconceptional folic acid supplementation, illicit drug use, and education.
Husebye (Topiramate) (Controls exposed to Lamotrigine, sick), 2020	population based cohort propective	Information on the anti-epileptic (AED) use was obtained from the maternal questionnaires completed during gesta week 17–19 and week 30 and from Medical Birth Registry data. AEDs plasma concentrations were analysed in maternal and umbilical cord samples (73%) and were detected in 93% of children.	Parent-reported screening instruments: the Ages and Stages Questionnaires (at 5 years) the Speech and Language Assessment Scale (at 5 years) and the Norwegian instrument Twenty Statements about Language-related Difficulties (at 5 and 8 years).	No adjustment for this group of comparison.
Husebye (Topiramate) (Controls unexposed, disease free), 2020	population based cohort propective	Information on the anti-epileptic (AED) use was obtained from the maternal questionnaires completed during gesta week 17–19 and week 30 and from Medical Birth Registry data. AEDs plasma concentrations were analysed in maternal and umbilical cord samples (73%) and were detected in 93% of children.	Parent-reported screening instruments: the Ages and Stages Questionnaires (at 5 years) the Speech and Language Assessment Scale (at 5 years) and the Norwegian instrument Twenty Statements about Language-related Difficulties (at 5 and 8 years).	Maternal age, parental SES, low household income, parity, maternal prepregnancy BMI, maternal report of familial language delay (5y model), smoking and alcohol (8y model), maternal anxiety/depression, Apgar score at 5 min, gestational age, report of seldom/never helping child read letters and sounds during a typical week (5y model) or report of never reading to their child (8y model).
Husebye (Topiramate) (Controls unexposed, sick), 2020	population based cohort propective	Information on the anti-epileptic (AED) use was obtained from the maternal questionnaires completed during gesta week 17–19 and week 30 and from Medical Birth Registry data. AEDs plasma concentrations were analysed in maternal and umbilical cord samples (73%) and were detected in 93% of children.	Parent-reported screening instruments: the Ages and Stages Questionnaires (at 5 years) the Speech and Language Assessment Scale (at 5 years) and the Norwegian instrument Twenty Statements about Language-related Difficulties (at 5 and 8 years).	No adjustment for this group of comparison.
Li (Topiramate) (Controls exposed to LTG), 2023	prospective cohort	The use of antiseizure medications on the included patients was registered by doctors and trained researchers.	After delivery, the offspring of the Women with epilepsy (WWE) were followed up by pediatricians. Offspring health was assessed by a multidisciplinary team, composed mainly of pediatricians and pediatric neurologists.	No adjustment. The exclusion criteria were as follows: (1) intelligence quotient (IQ) <70, ... (4) a voluntary termination of pregnancy of the mother’s personal choice and unrelated to fetal health.
Li (Topiramate) (Controls unexposed, sick), 2023	prospective cohort	The use of antiseizure medications on the included patients was registered by doctors and trained researchers.	After delivery, the offspring of the Women with epilepsy (WWE) were followed up by pediatricians. Offspring health was assessed by a multidisciplinary team, composed mainly of pediatricians and pediatric neurologists.	No adjustment. The exclusion criteria were as follows: (1) intelligence quotient (IQ) <70, ... (4) a voluntary termination of pregnancy of the mother’s personal choice and unrelated to fetal health.
Madley-Dowd_SE (Topiramate) (Controls exposed to LTG), 2024	population based cohort retrospective	Self-reported maternal consumption of antiseizure medications were prospectively recorded at antenatal care visits (from a structured interview at the first visit at 8–10 weeks of gestation, supplemented from 2005 with drug all prescription dispensations in Sweden (tetrachoric correlation 0.98).	Inpatient and specialized outpatient diagnoses were obtained using ICD-8/9/10 codes from the National Patient Registry, and to further identify cases of ADHD, prescription information on licensed ADHD medications was also incorporated.	No adjustment for this group of comparison.
Madley-Dowd_SE (Topiramate) (Controls unexposed, sick), 2024	population based cohort retrospective	Self-reported maternal consumption of antiseizure medications were prospectively recorded at antenatal care visits (from a structured interview at the first visit at 8–10 weeks of gestation, supplemented from 2005 with drug all prescription dispensations in Sweden (tetrachoric correlation 0.98).	Inpatient and specialized outpatient diagnoses were obtained using ICD-8/9/10 codes from the National Patient Registry, and to further identify cases of ADHD, prescription information on licensed ADHD medications was also incorporated.	Adjusted for ASM presumed indication, any maternal neurodevelopmental diagnoses, maternal age, residential region, hazardous drinking or illicit drug use during pregnancy, gravidity, maternal health care use and seizure events (year before pregnancy), use of antipsychotics/ antidepressants (year before pregnancy), hyperemesis or antiemetic prescriptions, year of birth and socioeconomic position.
Madley-Dowd_UK (Topiramate) (Controls exposed to LTG) (Epilepsy), 2024	retrospective cohort (claims database)	Prescriptions were identified from primary care records.	Diagnoses were obtained from primary care records using Read codes for all patients and from inpatient and outpatient Hospital Episode Statistics (HES) using ICD-10 codes. For ADHD, prescription on ADHD medications (methylphenidate, dexamfetamine, lisdexamfetamine and atomoxetine) was incorporated.	No adjustment for this group of comparison.
Madley-Dowd_UK (Topiramate) (Controls unexposed, sick) (Epilepsy), 2024	retrospective cohort (claims database)	Prescriptions were identified from primary care records.	Diagnoses were obtained from primary care records using Read codes for all patients and from inpatient and outpatient Hospital Episode Statistics (HES) using ICD-10 codes. For ADHD, prescription on ADHD medications (methylphenidate, dexamfetamine, lisdexamfetamine and atomoxetine) was incorporated.	Adjusted for ASM presumed indication, any maternal neurodevelopmental diagnoses, maternal age, residential region, hazardous drinking or illicit drug use during pregnancy, gravidity, maternal health care use and seizure events (year before pregnancy), use of antipsychotics/ antidepressants (year before pregnancy), hyperemesis or antiemetic prescriptions, year of birth and socioeconomic position.
Mawer (Topiramate) (Controls exposed to Lamotrigine, sick), 2010	prospective cohort	The research nurse recorded personal and medical history with forms. An epilepsy specialist confirmed antiepileptic medication. Information from the patient was supplemented from clinical records.	Congenital abnormalities were identified from reports of fetal scans and paediatric medical examination of the baby before discharge. Major malformations were distinguished from minor anomalies using Eurocat instructions and those with chromosome abnormalities were not included.	No matching for this group of comparison. No adjustement.
Mawer (Topiramate) (Controls unexposed, disease free), 2010	prospective cohort	The research nurse recorded personal and medical history with forms. An epilepsy specialist confirmed antiepileptic medication. Information from the patient was supplemented from clinical records.	Congenital abnormalities were identified from reports of fetal scans and paediatric medical examination of the baby before discharge. Major malformations were distinguished from minor anomalies using Eurocat instructions and those with chromosome abnormalities were not included.	Matched for age (within a five-year band), for parity, for residential district (postal code) and employment. No adjustement.
Mawer (Topiramate) (Controls unexposed, sick), 2010	prospective cohort	The research nurse recorded personal and medical history with forms. An epilepsy specialist confirmed antiepileptic medication. Information from the patient was supplemented from clinical records.	Congenital abnormalities were identified from reports of fetal scans and paediatric medical examination of the baby before discharge. Major malformations were distinguished from minor anomalies using Eurocat instructions and those with chromosome abnormalities were not included.	No matching for this group of comparison. No adjustement.
Meador (Topiramate) (Controls exposed to Lamotrigine, sick), 2021	prospective cohort	Data were collected from participants using a daily electronic diary that was verified at study visits and with medical records.	Data were collected from participants using a daily electronic diary that was verified at study visits and with medical records.	Adjusted for mother's IQ, education level, and post-birth average Beck Anxiety Inventory (BAI) score, and child's sex, ethnicity, and birthweight.
Meador (Topiramate) (Controls exposed to Lamotrigine, sick), 2020	prospective cohort	Data were obtained from participants and their medical records.	Data were obtained from participants and their medical records.	No adjustment for this group of exposure.
Meador (Topiramate) (Controls unexposed, disease free), 2021	prospective cohort	Data were collected from participants using a daily electronic diary that was verified at study visits and with medical records.	Data were collected from participants using a daily electronic diary that was verified at study visits and with medical records.	Adjusted for mother's IQ, education level, and post-birth average Beck Anxiety Inventory (BAI) score, and child's sex, ethnicity, and birthweight.
Meador (Topiramate) (Controls unexposed, disease free), 2020	prospective cohort	Data were obtained from participants and their medical records.	Data were obtained from participants and their medical records.	No adjustment for this group of exposure.
Meador (Topiramate) (Controls unexposed, sick), 2020	prospective cohort	Data were obtained from participants and their medical records.	Data were obtained from participants and their medical records.	No adjustment for this group of exposure.
Morrow (Topiramate) (Controls exposed to Lamotrigine, sick), 2006	prospective cohort	Information was collected at registration and changes of antiepileptic drugs during pregnancy were detected during the follow-up duration by sending a standardised questionnaire to the patient's general practitioner. Other health care practitioners were contacted if identified.	Outcome data were collected by sending the patient’s general practitioner a standardised questionnaire for completion during the follow-up duration. Other health care practitioners were contacted if identified. Pregnancy losses with no major malformation are excluded.	No adjustment for this group of comparison.
Morrow (Topiramate) (Controls unexposed, sick), 2006	prospective cohort	Information was collected at registration and changes of antiepileptic drugs during pregnancy were detected during the follow-up duration by sending a standardised questionnaire to the patient's general practitioner. Other health care practitioners were contacted if identified.	Outcome data were collected by sending the patient’s general practitioner a standardised questionnaire for completion during the follow-up duration. Other health care practitioners were contacted if identified. Pregnancy losses with no major malformation are excluded.	No adjustment for this group of exposure.
Nadebaum (Topiramate), 2011	prospective cohort	Details are obtained by four in-depth telephone interviews with the women. Details provided by the participants are confirmed, as far as possible, by the treating medical practitioners.	Children participated in neuropsychological examination and all assessors were blinded to drug exposure: the Clinical Evaluation of Language Fundamentals, fourth edition and the Wechsler Intelligence Scale for Children, fourth edition were administered.	None.
Ornoy (Topiramate), 2008	prospective cohort	Details of exposure were collected during pregnancy at the initial contact before pregnancy outcome was known, using a structured questionnaire.	After the expected date of delivery, follow-up was conducted with the woman, her physician or midwife via a telephone interview and/or mailed questionnaire. When anomaly is reported, medical records were requested and a paediatrician contacted the mother for details and verification.	No adjustment for this group of exposure.
Razaz (Topiramate), 2024	population based cohort retrospective	Prescription for antiseizure medication (ASM) was ascertained using nationwide prescription registers and identified ASMs based on Anatomical Therapeutic Chemical Classification.	All maternal and neonatal conditions were ascertained from each country’s Medical Birth Register, Patient Register, and Cause of Death Register records, according to the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10).	Singleton only. Adjusted for maternal age, parity, birth year, child’s sex, mother’s education, marital status, country, maternal prepregnancy psychiatric comorbidity, number of somatic diagnoses, and hospitalizations in the year preceding pregnancy.
Razaz (Topiramate) (Controls exposed to Lamotrigine, sick), 2017	population based cohort retrospective	The Prescribed Drug Registry stores data on all drugs prescribed in ambulatory care and dispensed at a Swedish pharmacy. Prescription were coded using the Drug Identification Numbers and the ATC system.	The National Patient Register which has provided diagnostic codes on hospital inpatient care. Diagnoses in these databases were coded using the Swedish version of the ICD-9 and 10.	No adjustment for this group of exposure.
Razaz (Topiramate) (Controls unexposed, disease free), 2017	population based cohort retrospective	The Prescribed Drug Registry stores data on all drugs prescribed in ambulatory care and dispensed at a Swedish pharmacy. Prescription were coded using the Drug Identification Numbers and the ATC system.	The National Patient Register which has provided diagnostic codes on hospital inpatient care. Diagnoses in these databases were coded using the Swedish version of the ICD-9 and 10.	No adjustment for this group of exposure.
Razaz (Topiramate) (Controls unexposed, sick), 2017	population based cohort retrospective	The Prescribed Drug Registry stores data on all drugs prescribed in ambulatory care and dispensed at a Swedish pharmacy. Prescription were coded using the Drug Identification Numbers and the ATC system.	The National Patient Register which has provided diagnostic codes on hospital inpatient care. Diagnoses in these databases were coded using the Swedish version of the ICD-9 and 10.	No adjustment for this group of exposure.
Thomas (Topiramate) (Controls exposed to Lamotrigine, sick), 2021	prospective cohort	Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them.	Screening for major congenital malformation with antenatal screening by serum alpha fetoprotein estimation and detailed anomaly scan between 12 and 18 weeks of pregnancy; physical examination at birth, at 3 months of age (at least) and at 1 year of age if possible.	No adjustment for this group of comparison.
Thomas (Topiramate) (Controls unexposed, disease free), 2021	prospective cohort	Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them.	Screening for major congenital malformation with antenatal screening by serum alpha fetoprotein estimation and detailed anomaly scan between 12 and 18 weeks of pregnancy; physical examination at birth, at 3 months of age (at least) and at 1 year of age if possible.	None.
Thomas (Topiramate) (Controls unexposed, sick), 2021	prospective cohort	Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them.	Screening for major congenital malformation with antenatal screening by serum alpha fetoprotein estimation and detailed anomaly scan between 12 and 18 weeks of pregnancy; physical examination at birth, at 3 months of age (at least) and at 1 year of age if possible.	Adjusted for age and educational status of mother, and epilepsy class.
Thomas b (Controls exposed to LTG), 2022	prospective cohort	Each pregnant woman in the Kerala Registry of Epilepsy and Pregnancy (KREP) maintained a pregnancy diary to record the daily use of antiseizure medications (ASMs). Data were then transferred to the clinical records of the registry during their clinic visits.	Developmental paediatricians and developmental therapists, who were blinded to antenatal ASM exposure evaluated motor and mental development of infants (>12 months) using the Developmental Assessment Scale for Indian Infants (an Indian adaptation of the Bayley Scale of Infant Development).	None (the adjusted motor and mental development quotients (aMODQ and aMEDQ) not provided, only their difference from the reference group (unexposed infants)).
Thomas b (Controls unexposed, sick), 2022	prospective cohort	Each pregnant woman in the Kerala Registry of Epilepsy and Pregnancy (KREP) maintained a pregnancy diary to record the daily use of antiseizure medications (ASMs). Data were then transferred to the clinical records of the registry during their clinic visits.	Developmental paediatricians and developmental therapists, who were blinded to antenatal ASM exposure evaluated motor and mental development of infants (>12 months) using the Developmental Assessment Scale for Indian Infants (an Indian adaptation of the Bayley Scale of Infant Development).	None (the adjusted motor and mental development quotients (aMODQ and aMEDQ) not provided, only their difference from the reference group (unexposed infants)).
Tomson (Topiramate), 2018	prospective cohort	Information obtained during early pregnancy and follow-up by the treating physician who transferred it online to a EURAP national coordinator. He then, reviewed the reports for completeness and accuracy before transmission to the EURAP central database.	Abnormalities in the offspring were reported descriptively by enrolling physicians These reports were reviewed and classified (2005 EUROCAT criteria) by an outcome committee unaware of the type of exposure. Supplementary information from the reporting physician can be request.	None.
Trivedi (Topiramate) (Controls exposed to Lamotrigine, sick), 2018	prospective cohort	Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them.	Women were under regular antenatal follow up by the obstetricians.	No adjustment for this group of comparison.
Trivedi (Topiramate) (Controls unexposed, sick), 2018	prospective cohort	Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them.	Women were under regular antenatal follow up by the obstetricians.	Adjusted for enrollment status, age at conception, type of epilepsy, folic acid use in pregnancy, seizures in pregnancy, Generalised Tonic Clonic Seizures in pregnancy, prior spontaneous fetal loss, parental major congenital malformation.
Vajda (Topiramate) (Controls exposed to Lamotrigine, sick), 2013	prospective cohort	Details are obtained by four in-depth telephone interviews with the women. Details provided by the participants are confirmed, as far as possible, by the treating medical practitioners.	Details are obtained by four in-depth telephone interviews with the women. Details provided by the participants are confirmed, as far as possible, by the treating medical practitioners.	None.
Vajda (Topiramate) (Controls unexposed, sick), 2013	prospective cohort	Details are obtained by four in-depth telephone interviews with the women. Details provided by the participants are confirmed, as far as possible, by the treating medical practitioners.	Details are obtained by four in-depth telephone interviews with the women. Details provided by the participants are confirmed, as far as possible, by the treating medical practitioners.	None.
Vajda a (Topiramate) (Controls exposed to LTG), 2024	prospective cohort	Not specified. All contact between the pregnant women and the Melbourne-based register has been by telephone.	The register has collected data concerning each woman’s medical details at enrolment, at about 28 WG and around the end of the first post-partum month. The accuracy of the information provided by the pregnant women was checked with their treating medical practitioners, as far as feasible.	Exclusion of previous ‘lost’ pregnancies and pregnancies where either parent had a foetal malformation.
Vajda a (Topiramate) (Controls unexposed sick), 2024	prospective cohort	Not specified. All contact between the pregnant women and the Melbourne-based register has been by telephone.	The register has collected data concerning each woman’s medical details at enrolment, at about 28 WG and around the end of the first post-partum month. The accuracy of the information provided by the pregnant women was checked with their treating medical practitioners, as far as feasible.	Exclusion of previous ‘lost’ pregnancies and pregnancies where either parent had a foetal malformation.
Vajda b (Topiramate) (Epilepsy) (Controls exposed to Lamotrigine, sick), 2024	prospective cohort	Details are obtained by four in-depth telephone interviews with the women (at time of enrolment; at approximately 28 weeks of pregnancy; after the 1st post-partum (pp) month, and at one year pp). The accuracy of the information provided by the pregnant women is checked with their treating doctors.	Details are obtained by four in-depth telephone interviews with the women (at time of enrolment; at approximately 28 weeks of pregnancy; after the 1st post-partum (pp) month, and at one year pp). The accuracy of the information provided by the pregnant women is checked with their treating doctors.	None.
Vajda b (Topiramate) (Epilepsy) (Controls unexposed, sick), 2024	prospective cohort	Details are obtained by four in-depth telephone interviews with the women (at time of enrolment; at approximately 28 weeks of pregnancy; after the 1st post-partum (pp) month, and at one year pp). The accuracy of the information provided by the pregnant women is checked with their treating doctors.	Details are obtained by four in-depth telephone interviews with the women (at time of enrolment; at approximately 28 weeks of pregnancy; after the 1st post-partum (pp) month, and at one year pp). The accuracy of the information provided by the pregnant women is checked with their treating doctors.	None.
Veiby (Topiramate) (Controls exposed to Lamotrigine, sick), 2014	population based cohort retrospective	A standardised notification form is filled in from the first prenatal visit with the general practitioner until discharge and transferred to the database by practitioners attending the delivery. (According to ATC Classification System).	A standardised notification form is filled in from the first prenatal visit until discharge and transferred to the database by practitioners attending the delivery. (Coded according to ICD-10). Additional information on congenital malformations came from Norwegian pediatric wards.	No adjustment for this group of comparison.
Veiby (Topiramate) (Controls unexposed, disease free), 2014	population based cohort retrospective	A standardised notification form is filled in from the first prenatal visit with the general practitioner until discharge and transferred to the database by practitioners attending the delivery. (According to ATC Classification System).	A standardised notification form is filled in from the first prenatal visit until discharge and transferred to the database by practitioners attending the delivery. (Coded according to ICD-10). Additional information on congenital malformations came from Norwegian pediatric wards.	Adjusted for maternal age, parity, smoking, folate supplementation, and maternal chronic disease other than epilepsy
Veiby (Topiramate) (Controls unexposed, sick), 2014	population based cohort retrospective	A standardised notification form is filled in from the first prenatal visit with the general practitioner until discharge and transferred to the database by practitioners attending the delivery. (According to ATC Classification System).	A standardised notification form is filled in from the first prenatal visit until discharge and transferred to the database by practitioners attending the delivery. (Coded according to ICD-10). Additional information on congenital malformations came from Norwegian pediatric wards.	No adjustment for this group of comparison.
Wood (Topiramate), 2015	prospective cohort	Details are obtained by four in-depth telephone interviews with the women. And treating doctors are contacted to confirm medical details.	Assessments with the Childhood Autism Rating Scale (CARS) were conducted by two authors blinded to drug exposure status of the child and clinical diagnosis of the mother and a consensus meetings conducted to confirm scoring.	None.

master protocol