Topiramate (All indications)

Exposed non-exposed, cohort studies

Study Country
Study period
Study design		 Data source Exposure definition Non-exposure definition Exposition period Sample size
(exposed/unexposed) Or (case / control)		 Remarks Risk of bias
Alsfouk (Topiramate) (Controls exposed to Lamotrigine, sick)
2021 		Riyadh and Jeddah, Saudi Arabia.
1993 - 2020
retrospective cohort 		The King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh and Jeddah, Saudi Arabia. Epileptic mothers with topiramate monotherapy administered during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Epileptic mothers with lamotrigine monotherapy administered during pregnancy. 		during pregnancy (anytime or not specified) 2 / 15
Patients’ electronic and paper-based medical records.
Alsfouk (Topiramate) (Controls unexposed, sick)
2021 		Riyadh and Jeddah, Saudi Arabia.
1993 - 2020
retrospective cohort 		The King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh and Jeddah, Saudi Arabia. Epileptic mothers with topiramate monotherapy administered during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Epileptic mothers who did not take antiseizure medications during pregnancies. 		during pregnancy (anytime or not specified) 2 / 30
Patients’ electronic and paper-based medical records.
AlSheikh (Topiramate) (Controls exposed to Lamotrigine, sick)
2020 		Saudi Arabia
2018 - 2019
prospective cohort 		King Fahd University Hospital Fetuses/neonates of patients with active epilepsy who received topiramate monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Fetuses/neonates of patients with active epilepsy who received lamotrigine monotherapy during pregnancy. 		during pregnancy (anytime or not specified) 1 / 20
Information was collected through a structured questionnaire ‘Questionnaire for Investigation of Epilepsy in Tropical Countries'.
AlSheikh (Topiramate) (Controls unexposed, sick)
2020 		Saudi Arabia
2018 - 2019
prospective cohort 		King Fahd University Hospital Fetuses/neonates of patients with active epilepsy who received topiramate monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Fetuses/neonates of patients with active epilepsy who did not take antiepileptic drugs during pregnancy. 		during pregnancy (anytime or not specified) 1 / 8
Information was collected through a structured questionnaire ‘Questionnaire for Investigation of Epilepsy in Tropical Countries'.
Arkilo (Topiramate)
2015 		USA
2006 - 2011
retrospective cohort 		Minnesota Epilepsy Group, P.A. of United Hospital and Children's Hospitals and Clinics of Minnesota Singleton whose epileptic mothers were exposed to topiramate monotherapy at any point during the pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Singleton whose epileptic mothers were exposed to lamotrigine monotherapy at any point during the pregnancy. 		during pregnancy (anytime or not specified) 2 / 24
Questionnaires were sent to women.
Babic (Topiramate)
2014 		Serbia
1998 - 2008
prospective cohort 		Clinic of Neurology and Psychiatry for Children and Youth Children whose epileptic mothers were exposed to topiramate in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children whose epileptic mothers were exposed to lamotrigine in monotherapy during pregnancy. 		during pregnancy (anytime or not specified) 2 / 8
Not specified.
Bank (Topiramate) (Mixed indications)
2017 		USA
2002 - 2006
prospective cohort 		Emory Women’s Epilepsy and Mental Health Programs Singleton pregnancies in mothers taking topiramate monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Singleton pregnancies in mothers taking lamotrigine monotherapy during pregnancy. 		during pregnancy (anytime or not specified) 2 / 36
Medical records were obtained for review from the treating obstetrician, the delivery hospital, and the treating pediatrician. Umbilical cord and maternal venous blood were collected to measure total anti-epileptic levels by liquid chromatography/mass spectrometry.
Bech (Topiramate) (Mixed indications)
2018 		Denmark
2005 - 2008
population based cohort propective 		The Danish Prescription Register, the Danish Medical Birth Register, the Danish Psychiatric Central Research Register and Danish National Patient Registry. Singleton offspring of mothers exposed to topiramate monotherapy within 90 days prior to conception to birth. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Singleton offspring of mothers exposed to antiepileptic drugs at any time but not during pregnancy. 		during pregnancy (anytime or not specified) 27 / 434
The Danish National Prescription Register was used to obtain data on redeemed prescriptions using Anatomical Therapeutic Chemical (ATC) codes.
Bjørk (Topiramate) (Controls exposed to Lamotrigine, sick)
2018 		Norway
1999 - 2008
population based cohort propective 		The Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway. Children of women with reported epilepsy and topiramate monotherapy use during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children of women with reported epilepsy and lamotrigine monotherapy use during pregnancy. 		during pregnancy (anytime or not specified) 10 / 104
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.
Bjørk (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications)
2022 		Danemark, Finland, Iceland, Norway and Sweden.
1996 - 2017
population based cohort retrospective 		Social register data from Danemark, Finland, Iceland, Norway, Sweden for SCAN-AED: Nordic register-based study of antiepileptic drugs in pregnancy. Pregnacies in mothers filling at least one topiramate monotherapy prescription from her last menstrual period until birth. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Pregnacies in mothers filling at least one lamotrigine monotherapy prescription from her last menstrual period until birth. 		during pregnancy (anytime or not specified) 471 / 7950 Overlapping for ASD (2 outcomes) and Intellectual disabilities (2 outcomes): Dreier 2023 and Bjork 2022, with more pregnancies in Bjork 2022 because all indications included => use of Bjork 2022 data. Bjørk 2021 is an abstract of this publication.
Prescriptions through national prescription registers according to Anatomical Therapeutic Chemical classification codes N03, N05BA09, and S01EC01.
Bjørk (Topiramate) (Controls unexposed NOS) (Mixed indications)
2022 		Danemark, Finland, Iceland, Norway and Sweden.
1996 - 2017
population based cohort retrospective 		Social register data from Danemark, Finland, Iceland, Norway, Sweden for SCAN-AED: Nordic register-based study of antiepileptic drugs in pregnancy. Pregnacies in mothers filling at least one topiramate monotherapy prescription from her last menstrual period until birth. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed (general population or NOS)
Pregnacies in mothers without antiseizure medication prescription from her last menstrual period until birth. 		during pregnancy (anytime or not specified) 471 / 4463879 Overlapping for ASD (2 outcomes) and Intellectual disabilities (2 outcomes): Dreier 2023 and Bjork 2022, with more pregnancies in Bjork 2022 because all indications included => use of Bjork 2022 data. Bjørk 2021 is an abstract of this publication.
Prescriptions through national prescription registers according to Anatomical Therapeutic Chemical classification codes N03, N05BA09, and S01EC01.
Bjørk (Topiramate) (Controls unexposed, disease free)
2018 		Norway
1999 - 2008
population based cohort propective 		The Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway. Children of women with reported epilepsy and topiramate monotherapy use during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
All children of mothers without reported epilepsy unexposed to antiepileptic drugs during pregnancy. 		during pregnancy (anytime or not specified) 10 / 104222
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.
Bjørk (Topiramate) (Controls unexposed, sick)
2018 		Norway
1999 - 2008
population based cohort propective 		The Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway. Children of women with reported epilepsy and topiramate monotherapy use during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children of women with reported epilepsy but no antiepileptic drug intake during pregnancy. 		during pregnancy (anytime or not specified) 10 / 389 In this control group 127 (70.9%) reported inactive epilepsy defined as not using AEDs during the 2 years before conception or no seizures during the previous 5 years.
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.
Bjørk (Topiramate) (Controls unexposed, sick) (Mixed indications)
2022 		Danemark, Finland, Iceland, Norway and Sweden.
1996 - 2017
population based cohort retrospective 		Social register data from Danemark, Finland, Iceland, Norway, Sweden for SCAN-AED: Nordic register-based study of antiepileptic drugs in pregnancy. Pregnacies in mothers filling at least one topiramate monotherapy prescription from her last menstrual period until birth. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Pregnacies in epileptic mothers without antiseizure medication prescription from her last menstrual period until birth. 		during pregnancy (anytime or not specified) 471 / 21634 Overlapping for ASD (2 outcomes) and Intellectual disabilities (2 outcomes): Dreier 2023 and Bjork 2022, with more pregnancies in Bjork 2022 because all indications included => use of Bjork 2022 data. Bjørk 2021 is an abstract of this publication.
Prescriptions through national prescription registers according to Anatomical Therapeutic Chemical classification codes N03, N05BA09, and S01EC01.
Blotière (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications)
2019 		France
2011 - 2015
retrospective cohort (claims database) 		The French national health insurance database (DCIR) and the French hospital discharge database (PMSI). Pregnancies exposed to topiramate monotherapy between 1 month before and 2 months after the beginning of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Pregnancies exposed to lamotrigine monotherapy between 1 month before and 2 months after the beginning of pregnancy. 		1st trimester 517 / 2997 Authors excluded twin pregnancies and pregnancies with a chromosomal abnormality identified. Less than 90% of exposed pregnancies have a proxy for epilepsy. Publication's OR were not kept when lower limit of the confidence interval or OR equal to 0.
The French national health insurance database contains all health care claims reimbursed by French National Health Insurance. Include dispensed drugs coded according to the ATC classification. Monotherapy was defined as the absence of any other antiepileptic drug dispensed during the same period.
Blotière (Topiramate) (Controls unexposed NOS) (Mixed indications)
2019 		France
2011 - 2015
retrospective cohort (claims database) 		The French national health insurance database (DCIR) and the French hospital discharge database (PMSI). Pregnancies exposed to topiramate monotherapy between 1 month before and 2 months after the beginning of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed (general population or NOS)
Pregnancies with no reimbursement for antiepileptic drugs. 		1st trimester 517 / 1875733 Authors excluded twin pregnancies and pregnancies with a chromosomal abnormality identified. Less than 90% of exposed pregnancies have a proxy for epilepsy. Publication's OR were not kept when lower limit of the confidence interval or OR equal to 0.
The French national health insurance database contains all health care claims reimbursed by French National Health Insurance. Include dispensed drugs coded according to the ATC classification. Monotherapy was defined as the absence of any other antiepileptic drug dispensed during the same period.
Bromley (Topiramate)
2016 		UK
2004 - 2007
retrospective cohort (registry) 		The UK Epilepsy and Pregnancy Register. Children whose epileptic mothers were exposed to topiramate monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children whose epileptic mothers were untreated by antiepileptic drugs during their pregnancy. 		during pregnancy (anytime or not specified) 27 / 55 Design parts of this study were completed thanks to Morrow 2006. Families were not invited to participate if their child had a genetic condition associated with neurodevelopmental impairment.
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.
Cohen (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications)
2019 		USA
2000 - 2010
retrospective cohort (claims database) 		Medicaid Analytic eXtract (MAX) Pregnancies in women with at least one dispensed prescription for topiramate monotherapy (no other mood stabilizers or other anticonvulsants) in the first 20 weeks of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Pregnancies in women with at least one dispensed prescription for lamotrigine monotherapy (no other mood stabilizers or other anticonvulsants) in the first 20 weeks of pregnancy. 		early pregnancy 2280 / 2682 Authors excluded deliveries with a major congenital malformation (identified by ICD-9).
The Medicaid Analytic Extract data include prescriptions filled on an outpatient basis.
Cohen (Topiramate) (Controls unexposed NOS) (Mixed indications)
2019 		USA
2000 - 2010
retrospective cohort (claims database) 		Medicaid Analytic eXtract (MAX) Pregnancies in women with at least one dispensed prescription for topiramate monotherapy (no other mood stabilizers or other anticonvulsants) in the first 20 weeks of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed (general population or NOS)
Pregnancies in patients with no dispensing of lithium or any anticonvulsant (including those not used as mood stabilizers) from 3 months before pregnancy until 20 weeks of gestation. 		early pregnancy 2280 / 1440631 Authors excluded deliveries with a major congenital malformation (identified by ICD-9).
The Medicaid Analytic Extract data include prescriptions filled on an outpatient basis.
Cohen (Topiramate) (Mixed indications) (Controls exposed to LTG)
2023 		Denmark, Finland, Iceland, Norway, and Sweden
1996 - 2020
population based cohort retrospective 		Health national registers from the 5 Nordic countries. Pregnancies in which the mother had filled one or more prescriptions of topiramate ([ATC] code N03AX11) monotherapy during the first trimester. exposed to other treatment, sick
Pregnancies in which the mother had filled one or more prescriptions of lamotrigine monotherapy during the first trimester. 		1st trimester 509 / 8339 Overlapping: For Kallen 2013 and Veiby 2014 => less of 50% of overlapping => the 2 studies were kept. Main topiramate indications: 47% epilepsy; 27% unknown; 23% migraine.
Data on filled prescriptions were obtained from the medical birth registers linked with registers for prescribed drugs.
Cohen (Topiramate) (Mixed indications) (Controls unexposed, NOS)
2023 		Denmark, Finland, Iceland, Norway, and Sweden
1996 - 2020
population based cohort retrospective 		Health national registers from the 5 Nordic countries. Pregnancies in which the mother had filled one or more prescriptions of topiramate ([ATC] code N03AX11) monotherapy during the first trimester. unexposed (general population or NOS)
Pregnancies in which the mother had not filled a prescription for any Antiseizure medication (ATC code N03A) from 90 days before LMP to the end of the first trimester. 		1st trimester 509 / 4866362 Overlapping: For Kallen 2013 and Veiby 2014 => less of 50% of overlapping => the 2 studies were kept. Main topiramate indications: 47% epilepsy; 27% unknown; 23% migraine.
Data on filled prescriptions were obtained from the medical birth registers linked with registers for prescribed drugs.
Coste (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications)
2020 		France
2011 - 2014
retrospective cohort (claims database) 		The French national health data system (SNDS) Children born from mothers exposed to topiramate monotherapy indicated for the treatment of epilepsy and migraine with at least one dispensing between the month preceding onset of pregnancy and its end. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children born from mothers exposed to lamotrigine monotherapy for mixed indications during pregnancy. 		during pregnancy (anytime or not specified) 477 / 2916 Children with a diagnosis of brain malformation (ICD-10 codes Q00 to Q04 and Q05.0 to Q05.4) during their stay in the maternity unit are excluded. Results are extracted from Blotière et al. 2020 because they reported aOR for vs LTG.
Defned by at least one dispensing of the drug to the mother between the beginning of the month preceding onset of pregnancy and the end of pregnancy. Mother had used this drug as monotherapy, defined by the use of a single drug during pregnancy.
Coste (Topiramate) (Controls unexposed, NOS) (Mixed indications)
2020 		France
2011 - 2014
retrospective cohort (claims database) 		The French national health data system (SNDS) Children born from mothers exposed to topiramate monotherapy indicated for the treatment of epilepsy and migraine with at least one dispensing between the month preceding onset of pregnancy and its end. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed (general population or NOS)
Children born from mothers not exposed to any antiepileptic drug during pregnancy. 		during pregnancy (anytime or not specified) 477 / 1710441 Children with a diagnosis of brain malformation (ICD-10 codes Q00 to Q04 and Q05.0 to Q05.4) during their stay in the maternity unit are excluded.
Defned by at least one dispensing of the drug to the mother between the beginning of the month preceding onset of pregnancy and the end of pregnancy. Mother had used this drug as monotherapy, defined by the use of a single drug during pregnancy.
Dreier (Topiramate)
2021 		Danemark, Finland, Iceland, Norway, Sweden
1996 (depends)-2017
population based cohort retrospective 		Social register data from Danemark, Finland, Iceland, Norway, Sweden for SCAN-AED: Nordic register-based study of antiepileptic drugs in pregnancy. Offspring of women with prescription for topiramate monotherapy from 90 days before pregnancy to birth. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Offspring of women with epilepsy not using antiseizure medication in pregnancy. 		during pregnancy (anytime or not specified) 217 / -9 Unknown number in the exposed and unexposed group (abstract).
Reimbursement codes for prescriptions.
Dreier (Topiramate) (Epilepsy) (Controls exposed to LTG)
2023 		Denmark, Finland, Iceland, Norway, and Sweden.
1996 - 2017
population based cohort propective 		A prospective, population-based register study within the SCAN-AED project, based on children born in Denmark, Finland, Iceland, Norway, and Sweden. Children prenatally exposed to Topiramate monotherapy, i.e whose mother had redeemed 1 or more prescriptions during the exposure window, which was defined as 30 days before the first day of the last menstrual period (estimated using gestational age in days at birth) until the date of birth. exposed to other treatment, sick
Children prenatally exposed to Lamotrigine monotherapy, i.e whose mother had redeemed 1 or more prescriptions during the exposure window, which was defined as 30 days before the first day of the last menstrual period (estimated using gestational age in days at birth) until the date of birth. 		during pregnancy (anytime or not specified) 290 / 5288 Overlapping for ASD (2 outcomes) and Intellectual disabilities (2 outcomes): Dreier 2023 and Bjork 2022, with more pregnancies in Bjork 2022 because all indications included => use of Bjork 2022 data.
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.
Dreier (Topiramate) (Epilepsy) (Controls unexposed, sick)
2023 		Denmark, Finland, Iceland, Norway, and Sweden.
1996 - 2017
population based cohort propective 		A prospective, population-based register study within the SCAN-AED project, based on children born in Denmark, Finland, Iceland, Norway, and Sweden. Children prenatally exposed to topiramate monotherapy, i.e whose mother had redeemed 1 or more prescriptions during the exposure window, which was defined as 30 days before the first day of the last menstrual period (estimated using gestational age in days at birth) until the date of birth. unexposed, sick
Children not prenatally exposed to antiseizure medication. 		during pregnancy (anytime or not specified) 290 / 22203 Overlapping for ASD (2 outcomes) and Intellectual disabilities (2 outcomes): Dreier 2023 and Bjork 2022, with more pregnancies in Bjork 2022 because all indications included => use of Bjork 2022 data.
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.
Hernández-Díaz (Topiramate)
2017 		United States and Canada
1997 - 2017
prospective cohort 		The North American Antiepileptic Drug Pregnancy Registry Infants born to women who used topiramate in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Infants born to women who used lamotrigine in monotherapy during pregnancy. 		during pregnancy (anytime or not specified) 394 / 1799 'Most women used their AED throughout pregnancy. The exception was topiramate due to a larger proportion of women with intermittent use for migraine'. The main indications for AED were epilepsy (91%).
Women were questioned with a computer-assisted telephone interview 3 times.
Hernández-Díaz (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications)
2012 		North America and Canada
1997 - 2011
prospective cohort 		The North American Antiepileptic Drug Pregnancy Register and the Active Malformations Surveillance Program. Infants of pregnant women who used topiramate for mixed indications as monotherapy, during the first 4 lunar months after the last menstrual period (equal 16 weeks of gestation). (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Infants of pregnant women who used lamotrigine for mixed indications as monotherapy, during the first 4 lunar months after the last menstrual period (equal 16 weeks of gestation). 		1st trimester 359 / 1562 Total congenital malformations results are completely overlapped by the update on the registry website. Less than 90% of women are taking Lamotrigine and Topiramate for epilepsy.
Women were questioned with a computer-assisted telephone interview 3 times.
Hernández-Díaz (Topiramate) (Controls unexposed, disease free) (Mixed indications)
2012 		North America and Canada
1997 - 2011
prospective cohort 		The North American Antiepileptic Drug Pregnancy Register and the Active Malformations Surveillance Program. Infants of pregnant women who used topiramate for mixed indications as monotherapy, during the first 4 lunar months after the last menstrual period (equal 16 weeks of gestation). (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Infants of pregnant women, not taking an antiepileptic drug and without epilepsy, who were recruited from among the friends and family members of the enrolled women taking an antiepileptic drug. 		1st trimester 359 / 442 Total congenital malformations results are completely overlapped by the update on the registry website. Less than 90% of women are taking Topiramate for epilepsy.
Women were questioned with a computer-assisted telephone interview 3 times.
Hernandez-Diaz (Topiramate) (Mixed indications)
2018 		USA
2000 - 2010
prospective cohort 		Medicaid Analytic eXtract (MAX) Pregnancies exposed to topiramate in first trimester but without any dispensing for other anticonvulsant drugs during the 3 months before the start of pregnancy or during the first trimester. unexposed (general population or NOS)
Pregnancies unexposed to topiramate or other anticonvulsants during the 3 months prior to the start of pregnancy and during the first trimester. 		1st trimester 1790 / 1322955 Less than 90% of women are taking Topiramate for epilepsy. Pregnancies exposed to a known teratogenic medication during the first trimester other than an antiepileptic drug and pregnancies with a documented chromosomal abnormality were excluded.
In the Medicaid Analytic eXtract, use of medications is identified by drug-dispensing claims that include National Drug Codes. Exposure was defined as filling ≥1 prescriptions during the first trimester of pregnancy.
Hernández-Díaz (Topiramate) (Mixed indications) (Controls exposed to Lamotrigine, sick)
2014 		United States and Canada
1997 - 2012
prospective cohort 		The North American Antiepileptic Drug Pregnancy Register Infants of women exposed to topiramate for mixed indications as monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study.). exposed to other treatment, sick
Infants of women exposed to lamotrigine for mixed indications as monotherapy during pregnancy. 		during pregnancy (anytime or not specified) 347 / 1581 Less than 90% of women are taking Topiramate and Lamotrigine for epilepsy. A more recent publication Hernández-Díaz 2017 gives a better review of the outcome 'small for gestational age' (largest exposed population).
Women were questioned with a computer-assisted telephone interview 3 times.
Hernández-Díaz (Topiramate) (Mixed indications) (Controls unexposed, disease free)
2014 		United States and Canada
1997 - 2012
prospective cohort 		The North American Antiepileptic Drug Pregnancy Register Infants of women exposed to topiramate for mixed indications as monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study.). unexposed, disease free
Infants of pregnant women not taking an antiepileptic drugs and without epilepsy who had been recruited among the friends and relatives of antiepileptic drugs-exposed participants. 		during pregnancy (anytime or not specified) 347 / 457 Less than 90% of women are taking topiramate for epilepsy. A more recent publication (Hernández-Díaz 2017) gives a better review for the outcome 'small for gestational age'.
Women were questioned with a computer-assisted telephone interview 3 times.
Husebye (Topiramate) (Controls exposed to Lamotrigine, sick)
2020 		Norway
1999 - 2008
population based cohort propective 		Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway. Children of mothers with epilepsy exposed to topiramate monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children of mothers with epilepsy exposed to lamotrigine monotherapy during pregnancy. 		during pregnancy (anytime or not specified) 11 / 112
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 were detected in 93% of maternal blood and umbilical samples collected.
Husebye (Topiramate) (Controls unexposed, disease free)
2020 		Norway
1999 - 2008
population based cohort propective 		Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway. Children of mothers with epilepsy exposed to topiramate monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Children of mothers without epilepsy. 		during pregnancy (anytime or not specified) 11 / 113674
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.
Husebye (Topiramate) (Controls unexposed, sick)
2020 		Norway
1999 - 2008
population based cohort propective 		Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway. Children of mothers with epilepsy exposed to topiramate monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children of mothers with epilepsy unexposed to antiepileptic durgs during pregnancy. 		during pregnancy (anytime or not specified) 11 / 388 For this comparison group, results are only available according to folic acid intake.
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.
Källén (Topiramate) (Controls exposed to Lamotrigine, sick) (Indications NOS)
2013 		Swedish
1996 - 2011
population based cohort retrospective 		The Swedish Medical Birth Register, the Swedish Register of Prescribed Drugs the Register of Birth Defect and Hospital Discharge Register. Infants whose mothers used topiramate in monotherapy in early pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Infants whose mothers used lamotrigine in monotherapy in early pregnancy. 		early pregnancy 49 / 1084 Overlapping: Cohen 2023 and Kallen 2013 => less of 50% of overlapping => the 2 studies were kept. Razaz 2017 and Wide 2004 outcomes' already included in Källèn 2013 or not compared to an adequate control group. Follow-up period: author's email reply.
At the midwife interview at the first antenatal care visit, the woman was asked if she had used any drugs since she became pregnant. Or determined by the use of the Swedish Register of Prescribed Drugs (since 2006).
Källén (Topiramate) (Controls unexposed, NOS) (Indications NOS)
2013 		Swedish
1996 - 2011
population based cohort retrospective 		The Swedish Medical Birth Register, the Swedish Register of Prescribed Drugs, the Register of Birth Defect and Hospital Discharge Register. Infants whose mothers used topiramate in monotherapy in early pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed (general population or NOS)
Infants in population whose mothers used at least one of a central nervous system active drugs (less than 3%) or weren't exposed in early pregnancy. 		early pregnancy 49 / 1575847 Overlapping: Cohen 2023 and Kallen 2013 => less of 50% of overlapping => the 2 studies were kept. Indications for antiepileptic drugs are not specified. Follow-up period known thanks to author's email reply.
At the midwife interview at the first antenatal care visit, the woman was asked if she had used any drugs since she became pregnant. Or determined by the use of the Swedish Register of Prescribed Drugs (since 2006).
Kilic (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications)
2014 		Denmark
1997 - 2008
population based cohort retrospective 		The Danish Medical Birth Registry, the Danish Civil Registration System, the Danish National Hospital Registry, and the Danish Register of Medicinal Product Statistics. Children whose mothers have been exposed to topiramate in monotherapy during the exposure window defined from 30 days before the estimated day of conception to the day prior to birth. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children whose mothers have been exposed to lamotrigine in monotherapy during the exposure window defined from 30 days before the estimated day of conception to the day prior to birth. 		during pregnancy (anytime or not specified) 59 / 880 Less than 90% of women are epileptic.
The Danish Register of Medicinal Product Statistics holds information on all redeemed prescriptions. Monotherapy exposure was defined as redemption of prescription for one type of AED with the Anatomical Therapeutic Codes.
Kilic (Topiramate) (Controls unexposed NOS) (Mixed indications)
2014 		Denmark
1997 - 2008
population based cohort retrospective 		The Danish Medical Birth Registry, the Danish Civil Registration System, the Danish National Hospital Registry, and the Danish Register of Medicinal Product Statistics. Children whose mothers have been exposed to topiramate in monotherapy during the exposure window defined from 30 days before the estimated day of conception to the day prior to birth. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed (general population or NOS)
Children whose mothers haven't been exposed to antiepileptic drugs 30 days before the estimated day of conception to the day of birth. 		during pregnancy (anytime or not specified) 59 / 676834 Less than 90% of women are epileptic.
The Danish Register of Medicinal Product Statistics holds information on all redeemed prescriptions. Monotherapy exposure was defined as redemption of prescription for one type of AED with the Anatomical Therapeutic Codes.
Kilic (Topiramate) (Controls unexposed, sick) (Mixed indications)
2014 		Denmark
1997 - 2008
population based cohort retrospective 		The Danish Medical Birth Registry, the Danish Civil Registration System, the Danish National Hospital Registry, and the Danish Register of Medicinal Product Statistics. Children whose mothers have been exposed to topiamate in monotherapy during the exposure window defined from 30 days before the estimated day of conception to the day prior to birth. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children whose mothers have an epilepsy diagnosis and haven't been exposed to antiepileptic drugs 30 days before the estimated day of conception to the day of birth. 		during pregnancy (anytime or not specified) 59 / 5296 Less than 90% of women are epileptic.
The Danish Register of Medicinal Product Statistics holds information on all redeemed prescriptions. Monotherapy exposure was defined as redemption of prescription for one type of AED with the Anatomical Therapeutic Codes.
Li (Topiramate) (Controls exposed to LTG)
2023 		China
2009 - 2022
prospective cohort 		A prospective cohort study entitled 'Construction and Application of the Women with Epilepsy of Child-bearing Age Ontology (WWECA)', with West China Hospital of Sichuan University as the main center. Women with epilepsy (WWE) using Topiramate monotherapy during pregnancy. exposed to other treatment, sick
Women with epilepsy (WWE) using Lamotrigine monotherapy during pregnancy. 		during pregnancy (anytime or not specified) 7 / 38 Overlapping: He 2017 totally included in Li 2023. Authors did not provide analysis after monotherapy exposure but raw data of major congenital malformation provided in the e-Supp allowed to extract data for monotherapy => only this outcome reported here.
The use of antiseizure medications on the included patients was registered by doctors and trained researchers.
Li (Topiramate) (Controls unexposed, sick)
2023 		China
2009 - 2022
prospective cohort 		A prospective cohort study entitled 'Construction and Application of the Women with Epilepsy of Child-bearing Age Ontology (WWECA)', with West China Hospital of Sichuan University as the main center. Women with epilepsy (WWE) using Topiramate monotherapy during pregnancy. unexposed, sick
Women with epilepsy (WWE) not using antiseizure medications during pregnancy. 		during pregnancy (anytime or not specified) 7 / 253 Overlapping: He 2017 totally included in Li 2023. Authors did not provide analysis after monotherapy exposure but raw data of major congenital malformation provided in the e-Supp allowed to extract data for monotherapy => only this outcome reported here.
The use of antiseizure medications on the included patients was registered by doctors and trained researchers.
Lyons (Topiramate) (Indications NOS)
2023 		USA
2000 - 2015
retrospective cohort (claims database) 		The Mother-Infant Linkage (MIL) data within the Sentinel Common Data Model from six data partners contributing to the Sentinel Distributed Database, USA. Singleton live birth of mothers with at least one dispensing of topiramate during the first trimester of pregnancy (and no use of other anticonvulsants). unexposed (general population or NOS)
Singleton live birth of mothers unexposed to anticonvulsants (with no dispensing for topiramate or other anticonvulsants in the 90 days prior to estimated last menstrual period through the first trimester). 		1st trimester -9 / 1066086 Numbers of cases and exposures in topiramate monotherapy group not provided by authors (topiramate monotheray studied as a sensitivity analysis in the publication).
Exposure determined using outpatient dispensing data and National Drug Codes.
Mawer (Topiramate) (Controls exposed to Lamotrigine, sick)
2010 		UK
2000 - 2006
prospective cohort 		11 National Health Service (NHS) hospitals within Merseyside and Greater Manchester. Children born to mothers with epilepsy exposed to topiramate monotherapy in utero. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children born to mothers with epilepsy exposed to lamotrigine monotherapy in utero. 		1st trimester 3 / 40 Kini's 2007 malformation results are completely overlapped by this study (largest exposed population, longer study period). Period of exposure confirm by author's email.
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.
Mawer (Topiramate) (Controls unexposed, disease free)
2010 		UK
2000 - 2006
prospective cohort 		11 National Health Service (NHS) hospitals within Merseyside and Greater Manchester. Children born to mothers with epilepsy exposed to topiramate monotherapy in utero. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Children born to mothers without epilepsy who attended the same clinic on the same day or a few days later. 		1st trimester 3 / 315 Kini's 2007 malformation results are completely overlapped by this study (largest exposed population, longer study period). Period of exposure confirm by author's email.
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.
Mawer (Topiramate) (Controls unexposed, sick)
2010 		UK
2000 - 2006
prospective cohort 		11 National Health Service (NHS) hospitals within Merseyside and Greater Manchester. Children born to mothers with epilepsy exposed to topiramate monotherapy in utero. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children born to women with untreated epilepsy, who took no antiepileptic drugs before or during pregnancy. 		1st trimester 3 / 46 Kini's 2007 malformation results are completely overlapped by this study (largest exposed population, longer study period). Period of exposure confirm by author's email.
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.
Meador (Topiramate) (Controls exposed to Lamotrigine, sick)
2020 		US
2012 - 2016
prospective cohort 		The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study (20 US tertiary epilepsy centers). Children born to pregnant women with epilepsy exposed to topiramate monotherapy during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children born to pregnant women with epilepsy exposed to lamotrigine monotherapy during the first trimester. 		1st trimester 6 / 113
Data were obtained from participants and their medical records.
Meador (Topiramate) (Controls exposed to Lamotrigine, sick)
2021 		US
2012 - 2016
prospective cohort 		The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study (20 US tertiary epilepsy centers). Children with epileptic mothers using topiramate monotherapy in the third trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children with epileptic mothers using lamotrigine monotherapy in the third trimester. 		3rd trimester 5 / 93 Exclusion criteria included history of psychogenic nonepileptic spells, expected IQ of less than 70, other major medical illness, and switching of ASMs in pregnancy before enrollment.
Data were collected from participants using a daily electronic diary that was verified at study visits and with medical records.
Meador (Topiramate) (Controls unexposed, disease free)
2020 		US
2012 - 2016
prospective cohort 		The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study (20 US tertiary epilepsy centers). Children born to pregnant women with epilepsy exposed to topiramate monotherapy during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Children born to healthy pregnant women. 		1st trimester 6 / 106
Data were obtained from participants and their medical records.
Meador (Topiramate) (Controls unexposed, disease free)
2021 		US
2012 - 2016
prospective cohort 		The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study (20 US tertiary epilepsy centers). Children with epileptic mothers using topiramate monotherapy in the third trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Children of healthy women. 		3rd trimester 5 / 106 Exclusion criteria included history of psychogenic nonepileptic spells, expected IQ of less than 70, other major medical illness, and switching of ASMs in pregnancy before enrollment.
Data were collected from participants using a daily electronic diary that was verified at study visits and with medical records.
Meador (Topiramate) (Controls unexposed, sick)
2020 		US
2012 - 2016
prospective cohort 		The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study (20 US tertiary epilepsy centers). Children born to pregnant women with epilepsy exposed to topiramate monotherapy during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children born to pregnant women with epilepsy with no antiepileptic drug use. 		1st trimester 6 / 15
Data were obtained from participants and their medical records.
Mines (Topiramate) (Other indications)
2014 		USA
1997 - 2010
retrospective cohort (claims database) 		The HealthCore Integrated Research Database and OptumInsight's Normative Health Information database, the Truven Health MarketScan® Multi‐State Medicaid Database and Kaiser Permanente Northern California (KPNC). Infant born to women exposed to topiramate monotherapy during the first trimester of pregnancy. unexposed, sick
Infant born to women formerly exposed to topiramate or any other antiepileptic drugs but with no exposure to these agents in the first trimester or 4 months before the earliest estimated date of conception. 		1st trimester 1745 / 13512 There is 3.3% epilepsy indication in the topiramate cohorte and 2.5% epilepsy indication in the formerly exposed cohort. Potential cases of oral cleft identified with concurrent diagnoses of syndromic, genetic, or chromosomal defects were disqualified.
Exposure was ascertained from prescription claims data or pharmacy data of KPNC. Claims for drug dispensings include National Drug Codes. They considered a mother exposed if a drug was dispensed during first trimester or earlier, if calculated day’s supply extended into the first trimester.
Morrow (Topiramate) (Controls exposed to Lamotrigine, sick)
2006 		UK and Ireland
1996 - 2005
prospective cohort 		The UK Epilepsy and Pregnancy Register Infants of women with epilepsy exposed to topiramate in monotherapy during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Infants of women with epilepsy exposed to lamotrigine in monotherapy during the first trimester. 		1st trimester 28 / 647 There is a larger sample of women exposed to topiramate in this study than in Campbell's 2013 so its malformations results are preferred. Exposure period is completed thanks to Campbell 2014 which is also a UKEPR based study.
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.
Morrow (Topiramate) (Controls unexposed, sick)
2006 		UK and Ireland
1996 - 2005
prospective cohort 		The UK Epilepsy and Pregnancy Register Infants of women with epilepsy exposed to topiramate in monotherapy during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Infants of women with epilepsy and who didn't take any antiepileptic drugs during pregnancy. 		1st trimester 28 / 227 Exposure period is completed thanks to Campbell 2014 which is also a UKEPR based study.
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.
Nadebaum (Topiramate)
2011 		Australia
2007 - 2009
prospective cohort 		The Australian Pregnancy Register for Women with Epilepsy and Allied Disorders (APR). Children exposed to topiramate monotherapy in utero from epileptic mother. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children exposed to lamotrigine monotherapy in utero from epileptic mother. 		during pregnancy (anytime or not specified) 1 / 9 Children with major birth defects or a diagnosis of epilepsy were ineligible for the study to avoid possible confounding effects of these known risk factors for intellectual impairment.
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.
Ornoy (Topiramate)
2008 		Israel
1996 - 2006
prospective cohort 		Israeli Teratogens Information Service Pregnancies exposed to topiramate monotherapy at least during the first trimester of pregnancy. unexposed (general population or NOS)
Pregnancies of women who contacted the TIS at the same period of time and were exposed to non-teratogenic agents. 		at least 1st trimester 29 / 212 The design of the study isn't made explicit in the materials and methods so an other publication from the Israeli Teratogen Information Service is used to complete those informations (Diav-Citrin 2008).
Details of exposure were collected during pregnancy at the initial contact before pregnancy outcome was known, using a structured questionnaire.
Richards (Topiramate) (Controls exposed to Lamotrigine, sick) (Indications NOS)
2019 		New Zealand
2008 - 2012
population based cohort retrospective 		The Pharmaceutical Collection, the National Minimum Dataset (NMDS; hospital events), and the Before School Check (B4SC) database. Children exposed to topiramate monotherapy during pregnancy (the exposure window was defined as nine months before the day of birth). (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children exposed to lamotrigine monotherapy during pregnancy (the exposure window was defined as nine months before the day of birth). 		during pregnancy (anytime or not specified) 28 / 149 The National Minimum Dataset does not provide reliable diagnosis information. Indications not specified.
Obtained from the Pharmaceutical Collection database. Any redeemed prescription of an antiepileptic drug belonging to the Anatomical Therapeutic Chemical class N03A. Monotherapy is defined as if only one type of AED was prescribed during the exposure window.
Richards (Topiramate) (Controls unexposed, NOS) (Indications NOS)
2019 		New Zealand
2008 - 2012
population based cohort retrospective 		The Pharmaceutical Collection, the National Minimum Dataset (NMDS; hospital events), and the Before School Check (B4SC) database. Children exposed to topiramate monotherapy during pregnancy (the exposure window was defined as nine months before the day of birth). (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed (general population or NOS)
All other children unexposed to antiepileptic drug in utero who had a Before School Check (B4SC) in the study period. 		during pregnancy (anytime or not specified) 28 / 286966 The National Minimum Dataset does not provide reliable diagnosis information. Indications not specified.
Obtained from the Pharmaceutical Collection database. Any redeemed prescription of an antiepileptic drug belonging to the Anatomical Therapeutic Chemical class N03A. Monotherapy is defined as if only one type of AED was prescribed during the exposure window.
Rihtman (Topiramate) (Mixed indications)
2012 		Israel
2001 - 2006
prospective cohort 		The Israeli Teratogen Information Service Children exposed in utero at least during the first trimester to topiramate monotherapy from mothers with or without epilepsy. unexposed (general population or NOS)
Children recruited by means of a convenience sample from the general population. 		at least 1st trimester 9 / 18 The exclusion criteria for all groups stipulated that no children had genetic abnormalities nor had a full scale IQ of less than 70. Mixed indications because 'three took TX for reasons other than epilepsy' (33.3%).
Details of exposure were collected during pregnancy at the initial contact.
The NAAED (Controls exposed to Lamotrigine, sick) (Indications NOS)
2022 		North America and Canada
1997 - 2020
prospective cohort 		The North American Antiepileptic Drug Pregnancy Register Infants of pregnant women who used topiramate as monotherapy, during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Infants of pregnant women who used lamotrigine as monotherapy, during the first trimester. 		1st trimester 503 / 2333 Study design completed with the publication of Hernández-Díaz et al. 2012. Data extracted from the North American AED pregnancy registry website. Indications not specified.
Women were questioned with a computer-assisted telephone interview 3 times.
The NAAED (Controls unexposed, disease free) (Indications NOS)
2022 		North America and Canada
1997 - 2020
prospective cohort 		The North American Antiepileptic Drug Pregnancy Register Infants of pregnant women who used topiramate as monotherapy, during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Infants of pregnant women, not taking an antiepileptic drug and without epilepsy, who were recruited from among the friends and family members of the enrolled women taking an antiepileptic drug. 		1st trimester 503 / 1201 Study design completed with the publication of Hernández-Díaz et al. 2012. Data extracted from the North American AED pregnancy registry website. Internal control group reported rather than the external (for relevance purpose). Indications not specified.
Women were questioned with a computer-assisted telephone interview 3 times.
Thomas (Topiramate) (Controls exposed to Lamotrigine, sick)
2021 		India
1998 - 2019
prospective cohort 		The Kerala Registry of Epilepsy and Pregnancy (KREP) Children of women with epilepsy using topiramate monotherapy any time during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children of women with epilepsy using lamotrigine monotherapy any time during the first trimester of pregnancy. 		1st trimester 9 / 50 Study design completed with Thomas et al., 2017. Keni's 2018 malformations results are already reported in this publication.
Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them.
Thomas (Topiramate) (Controls unexposed, disease free)
2021 		India
1998 - 2015
prospective cohort 		The Kerala Registry of Epilepsy and Pregnancy (KREP) Children of women with epilepsy using topiramate monotherapy any time during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Children of women without epilepsy in the first trimester of pregnancy and not using antiepileptic drugs from the antenatal clinic of government hospital. 		1st trimester 6 / 319 This external control group is only available in the 2017 publication.
Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them.
Thomas (Topiramate) (Controls unexposed, sick)
2021 		India
1998 - 2019
prospective cohort 		The Kerala Registry of Epilepsy and Pregnancy (KREP) Children of women with epilepsy using topiramate monotherapy any time during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children of women with epilepsy not using any antiepileptic drugs during the first trimester. 		1st trimester 9 / 340 Study design completed with Thomas et al., 2017.
Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them.
Tomson (Topiramate)
2018 		42 countries
1999 - 2016
prospective cohort 		The EURAP epilepsy and pregnancy registry Offspring exposed in utero to topiramate monotherapy during the first trimester and born from epileptic mothers. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Offspring exposed in utero to lamotrigine monotherapy during the first trimester and born from epileptic mothers. 		at least 1st trimester 152 / 2514 This study is an update of Tomson's 2011 publication. They excluded from the current analysis pregnancies occurring in women without epilepsy. EURAP registry: potential overlap.
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.
Trivedi (Topiramate) (Controls exposed to Lamotrigine, sick)
2018 		India
1998 - 2015
prospective cohort 		The Kerala Registry of Epilepsy and Pregnancy (KREP) Pregnant women with epilepsy who used topiramate monotherapy any time during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Pregnant women with epilepsy who used lamotrigine monotherapy any time during the first trimester of pregnancy. 		1st trimester 11 / 48 Study design partly completed with cites source Thomas et al., 2017.
Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them.
Trivedi (Topiramate) (Controls unexposed, sick)
2018 		India
1998 - 2015
prospective cohort 		The Kerala Registry of Epilepsy and Pregnancy (KREP) Pregnant women with epilepsy who used topiramate monotherapy any time during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Pregnant women with epilepsy who were not on antiepileptic drug during their first trimester. 		1st trimester 11 / 178 Study design partly completed with cites source Thomas et al., 2017.
Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them.
Vajda (Topiramate) (Controls exposed to Lamotrigine, sick)
2019 		Australia
1999 - 2018
prospective cohort 		The Australian Register of Antiepileptic Drugs in Pregnancy. Offsprings born from women nearly always with epilepsy exposed to topiramate in monotherapy in at least the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Offsprings born from women nearly always with epilepsy exposed to lamotrigine in monotherapy in at least the first trimester of pregnancy. 		at least 1st trimester 53 / 406 Women with epilepsy accounted for 98.3%. Completely overlap Vajda 2007; 2010 (x2); 2012 (x2); 2013; 2014 and Jazayeri 2018. Study design partly completed with Vajda 2013.
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 and through hospital records.
Vajda (Topiramate) (Controls exposed to Lamotrigine, sick)
2013 		Australia
1999 - 2013
prospective cohort 		The Australian Register of Antiepileptic Drugs in Pregnancy. Offsprings from women with epilepsy exposed to topiramate in monotherapy in at least the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Offsprings from women with epilepsy exposed to lamotrigine in monotherapy in at least the first trimester of pregnancy. 		at least 1st trimester 44 / 315 Women taking AED for epilepsy are in majority (more than 90%). Vajda 2019 provides the most recent update for major malformations results for this register. Specific malformations' results are extracted from the review by Weston et al. 2016.
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.
Vajda (Topiramate) (Controls exposed to Lamotrigine, sick)
2018 		Australia
1999 - 2016
prospective cohort 		The Australian Register of Antiepileptic Drugs in Pregnancy. Offsprings of pregnant women with epilepsy exposed to topiramate in monotherapy throughout. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Offsprings of pregnant women with epilepsy exposed to lamotrigine in monotherapy throughout. 		throughout pregnancy 51 / 382
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.
Vajda (Topiramate) (Controls unexposed, sick)
2019 		Australia
1999 - 2018
prospective cohort 		The Australian Register of Antiepileptic Drugs in Pregnancy. Offsprings born from women nearly always with epilepsy exposed to topiramate in monotherapy in at least the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Offsprings born from women nearly always with epilepsy not treated with antiepileptic drugs in at least the first half of pregnancy. 		at least 1st trimester 53 / 176 Women with epilepsy accounted for 98.3%. Completely overlap Vajda 2007; 2010 (x2); 2012 (x2); 2013; 2014; 2016 and Jazayeri 2018. Study design partly completed with Vajda 2013.
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 and through hospital records.
Vajda (Topiramate) (Controls unexposed, sick)
2013 		Australia
1999 - 2013
prospective cohort 		The Australian Register of Antiepileptic Drugs in Pregnancy. Offsprings from women with epilepsy exposed to topiramate in monotherapy in at least the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Offsprings from women with epilepsy not exposed to antiepileptic drugs in at least the first trimester of pregnancy. 		at least 1st trimester 44 / 147 Women taking AED for epilepsy are in majority (more than 90%). Vajda 2019 provides the most recent update for major malformations results for this register. Specific malformations' results are extracted from the review by Weston et al. 2016.
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.
Vajda (Topiramate) (Controls unexposed, sick)
2018 		Australia
1999 - 2016
prospective cohort 		The Australian Register of Antiepileptic Drugs in Pregnancy. Offsprings of pregnant women with epilepsy exposed to topiramate in monotherapy throughout. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Offsprings of pregnant women with epilepsy that have been untreated in at least the first half of pregnancy. 		throughout pregnancy 51 / 170
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.
Veiby (Topiramate) (Controls exposed to Lamotrigine, sick) (Mixed indications)
2014 		Norway
1999 - 2011
population based cohort retrospective 		Medical Birth Registry of Norway Children exposed prenatally to topiramate as monotherapy indicated for their mothers' epilepsy or other indications. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children exposed prenatally to lamotrigine as monotherapy indicated for their mothers' epilepsy or other indications. 		throughout pregnancy 48 / 833 Overlapping: Cohen 2023 and Veiby 2014 => less of 50% of overlapping => the 2 studies were kept. Less than 90% of women are treated with Topiramate and Lamotrigine for epilepsy (Mixed indications).
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).
Veiby (Topiramate) (Controls unexposed, disease free) (Mixed indications)
2014 		Norway
1999 - 2011
population based cohort retrospective 		Medical Birth Registry of Norway Children exposed prenatally to topiramate as monotherapy indicated for their mothers' epilepsy or other indications. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
All unexposed children born to women without epilepsy. 		throughout pregnancy 48 / 771412 Overlapping: Cohen 2023 and Veiby 2014 => less of 50% of overlapping => the 2 studies were kept. Less than 90% of women are treated with Topiramate and Lamotrigine for epilepsy (Mixed indications).
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).
Veiby (Topiramate) (Controls unexposed, sick) (Mixed indications)
2014 		Norway
1999 - 2011
population based cohort retrospective 		Medical Birth Registry of Norway Children exposed prenatally to topiramate as monotherapy indicated for their mothers' epilepsy or other indications. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children born to women with a history of epilepsy but no antiepileptic drug treatment during pregnancy. 		throughout pregnancy 48 / 3773 Overlapping: Cohen 2023 and Veiby 2014 => less of 50% of overlapping => the 2 studies were kept. Less than 90% of women are treated with Topiramate and Lamotrigine for epilepsy (Mixed indications).
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).
Wood (Topiramate)
2015 		Australia
2007 - 2010
prospective cohort 		The Australian Pregnancy Register (APR) for Women on Antiepileptic Medication. Children of women with epilepsy exposed to topiramate in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children of women with epilepsy exposed to lamotrigine in monotherapy during pregnancy. 		during pregnancy (anytime or not specified) 1 / 9 Children with major birth defects or a diagnosis of epilepsy were excluded, as these conditions are known risk factors for autism spectrum disorders. Child IQ isn't specified for this monotherapy alone.
Details are obtained by four in-depth telephone interviews with the women. And treating doctors are contacted to confirm medical details.

Case-control studies

Study Country
Study period
Study design		 Data source Case Control Exposition Exposition period Sample size
(exposed/unexposed) Or (case / control)		 Remarks Risk of bias
Margulis (Topiramate) (Mixed indication)
2012 		USA
1997 - 2009
case control 		The Slone Epidemiology Center Birth Defects Study (BDS), the National Birth Defects Prevention Study (NBDPS) and the Centers for Disease Control and Prevention’s (CDC). Infants with major congenital malformations as a group (including oral clefts) and separately on CL/P with or without other major congenital malformations. Infants without congenital malformations randomly selected. Exposure information is collected after delivery by means of a detailed computer-assisted telephone interview. 1st trimester 33605 / 15367 To avoid duplication of participants, the BDS does not enroll women who are in the same catchments as NBDPS subjects. In this study, epilepsy was reported by less than half of topiramate users.
Information on the presence of congenital malformations is obtained from hospital discharges and medical records and experts review.

Risk of bias: : NA;   : low;   : moderate;   : serious;   : critical;   : unclear;  

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