Gabapentin (Epilepsy)

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Arkilo (Gabapentin), 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.
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.
Bromley (Gabapentin), 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 (Gabapentin) (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 (Gabapentin) (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).
Dean (Gabapentin), 2002	retrospective cohort	A structured interview was carried out by a trained research nurse using questionnaires.	Standardised assessment was carried out by a trained research nurse using examination schedules. Clinical photographs were assessed for facial features. Behavior disorders, developmental delay and later childhood medical problems were recorded and/or diagnosed by specialists.	None.
Dreier (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 (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).
Madley-Dowd_SE (Gabapentin) (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 (Gabapentin) (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 (Gabapentin) (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_SE (Gabapentin) (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 (Gabapentin) (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 (Gabapentin) (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 (Gabapentin) (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 (Gabapentin) (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 (Gabapentin) (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.
Miškov (Gabapentin) (Controls exposed to Lamotrigine, sick), 2016	prospective cohort	Data collected on pregnant women during outpatient visits to the neurologist, gynecologist and pediatrician neurologist.	Newborns were examined by pediatrician neurologist/geneticist at Clinical Department of Pediatrics and followed up yearly. Data on the control group were obtained from Clinical Department of Gynecology and Obstetrics and Clinical Department of Pediatrics.	None.
Miškov (Gabapentin) (Controls unexposed, disease free), 2016	prospective cohort	Data collected on pregnant women during outpatient visits to the neurologist, gynecologist and pediatrician neurologist.	Newborns were examined by pediatrician neurologist/geneticist at Clinical Department of Pediatrics and followed up yearly. Data on the control group were obtained from Clinical Department of Gynecology and Obstetrics and Clinical Department of Pediatrics.	None.
Miškov (Gabapentin) (Controls unexposed, sick), 2016	prospective cohort	Data collected on pregnant women during outpatient visits to the neurologist, gynecologist and pediatrician neurologist.	Newborns were examined by pediatrician neurologist/geneticist at Clinical Department of Pediatrics and followed up yearly. Data on the control group were obtained from Clinical Department of Gynecology and Obstetrics and Clinical Department of Pediatrics.	None.
Morrow (Gabapentin) (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 (Gabapentin) (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.
Razaz (Gabapentin), 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.
Vajda (Gabapentin) (Controls exposed to Lamotrigine, sick), 2018	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 (Gabapentin) (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 (Gabapentin) (Controls unexposed, sick), 2018	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 (Gabapentin) (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.
Wood (Gabapentin), 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.

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