| 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. | ||||||||
|
Battino (Topiramate) (Epilepsy) 2024 |
Worldwide (47 countries) 1999 - 2022 prospective cohort |
The International Registry of Antiepileptic Drugs and Pregnancy (EURAP). | Pregnant women with epilepsy exposed to Topiramate monotherapy at the time of conception. |
exposed to other treatment, sick
Pregnant women with epilepsy exposed to lamotrigine monotherapy at the time of conception. |
early pregnancy | 204 / 3584 | Overlapping/Update: (Major) malfo as a whole: Battino 2024 (1999-2022) updates and totally includes Tomson 2018 (1999-2016) and Tomson 2011=> Use of Battino 2024 for these outcomes. | |
| Reporting physicians collected information on drug therapy after each trimester. | ||||||||
|
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): Dreier 2023 and Bjork 2022, with more pregnancies in Bjork 2022 because all indications included => use of Bjork 2022 data. Not the same category of age for Intellectual disabilities. | |
| 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): Dreier 2023 and Bjork 2022, with more pregnancies in Bjork 2022 because all indications included => use of Bjork 2022 data. Not the same category of age for Intellectual disabilities. | |
| 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. | ||||||||
|
Christensen (Topiramate) (All indications) (Controls exposed to LTG) 2024 |
Denmark, Finland, Iceland, Norway, and Sweden 1996 - 2017 population based cohort retrospective |
Nordic population-based cohort study including register data from Denmark, Finland, Iceland, Norway, and Sweden–the SCAN-AED project. | Children of mothers who had redeemed at least one prescription of Topiramate monotherapy from 30 days before the first day of the last menstrual period to the date of birth (i.e., the exposure period). |
exposed to other treatment, sick
Children of mothers who had redeemed at least one prescription of Lamotrigine monotherapy from 30 days before the first day of the last menstrual period to the date of birth (i.e., the exposure period). |
during pregnancy (anytime or not specified) | 638 / 8756 | Overlapping: For LBW and SGA: Christensen 2024 totally included Kilic 2014 => use of Christensen 2024 for these outcomes (longer study period, 5 countries and more pregnancies). | |
| 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. | ||||||||
|
Christensen (Topiramate) (All indications) (Controls unexposed, general population) 2024 |
Denmark, Finland, Iceland, Norway, and Sweden 1996 - 2017 population based cohort retrospective |
Nordic population-based cohort study including register data from Denmark, Finland, Iceland, Norway, and Sweden–the SCAN-AED project. | Children of mothers who had redeemed at least one prescription of Topiramate monotherapy from 30 days before the first day of the last menstrual period to the date of birth (i.e., the exposure period). |
unexposed (general population or NOS)
Children of mothers who had not redeemed prescription of anti-seizure medication. |
during pregnancy (anytime or not specified) | 638 / 4467848 | Overlapping: For LBW and SGA: Christensen 2024 totally included Kilic 2014 => use of Christensen 2024 for these outcomes (longer study period, 5 countries and more pregnancies). | |
| 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. | ||||||||
|
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) (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): Dreier 2023 and Bjork 2022, with more pregnancies in Dreier 2023 => use of Dreier 2023 data. Not the same category of age for Intellectual disabilities. | |
| 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): Dreier 2023 and Bjork 2022, with more pregnancies in Dreier 2023 => use of Dreier 2023 data. Not the same category of age for Intellectual disabilities. | |
| 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. | ||||||||
|
Hao (Topiramate) (Epilepsy) (Controls exposed to LTG) 2025 |
China Not specified. prospective cohort |
The West China Registry of Pregnancy in Epilepsy (WCRP_ Epi), an ongoing prospective multicenter cohort study based in Sichuan Province, Southwest China. | Pregnant women with confirmed epilepsy that used topiramate monotherapy during the first trimester of pregnancy. |
exposed to other treatment, sick
Pregnant women with confirmed epilepsy that used lamotrigine monotherapy during the first trimester of pregnancy. |
1st trimester | 21 / 84 | Use of monotherapy data (table 2). | |
| 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. | ||||||||
|
Hao (Topiramate) (Epilepsy) (Controls unexposed, sick) 2025 |
China Not specified. prospective cohort |
The West China Registry of Pregnancy in Epilepsy (WCRP_ Epi), an ongoing prospective multicenter cohort study based in Sichuan Province, Southwest China. | Pregnant women with confirmed epilepsy that used topiramate monotherapy during the first trimester of pregnancy. |
unexposed, sick
Pregnant women with confirmed epilepsy and no anti-seizure medication use during the first trimester. |
1st trimester | 21 / 261 | Use of monotherapy data (table 2). | |
| 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. | ||||||||
|
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. | ||||||||
|
Hernandez-Diaz (Topiramate) (Epilepsy) 2024 |
USA 2000 - 2020 retrospective cohort (claims database) |
Medicaid beneficiaries nationwide, and the Merative MarketScan Commercial Claims and Encounters Database (referred as MarketScan). | Women with epilepsy with at least one dispensing for topiramate monotherapy during the second half of pregnancy (defined as week 19 of gestation to delivery), which is a period of substantial synaptogenesis. |
unexposed, sick
Women with epilepsy without any dispensing of antiseizure medication between 90 days before the last menstrual period and delivery. |
2nd and/or 3rd trimester | 623 / 8815 | In antiseizure medication meta-analysis : use of monotherapy data only => for this study, use of the secondary analyses, where exposure is defined as monotherapy (only provided for the Epilepsy-Restricted Cohort). => No use of the full-cohort data. | |
| Medicaid beneficiaries nationwide, and the Merative MarketScan Commercial Claims and Encounters Database, two data sources that contain information on dispensed outpatient prescription medications. | ||||||||
|
Hernández-Díaz (Topiramate) (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 | For (Major) Malformations as a whole: overlapping/update with NAAED updated website reports. => Outcomes not reported here (use of NAAED 2023 website data). Less than 90% of women are taking Lamotrigine and 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. Overlapping: For LBW and SGA: Kilic 2014 included in a larger study published by Christensen 2024 ((longer study period, 5 countries and more pregnancies) => use of Christensen 2024 for these outcomes. | |
| 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. Overlapping: For LBW and SGA: Kilic 2014 included in a larger study published by Christensen 2024 ((longer study period, 5 countries and more pregnancies) => use of Christensen 2024 for these outcomes. | |
| 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. Overlapping: For LBW and SGA: Kilic 2014 included in a larger study published by Christensen 2024 ((longer study period, 5 countries and more pregnancies) => use of Christensen 2024 for these outcomes. | |
| 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. | ||||||||
|
Madley-Dowd_SE (Topiramate) (Controls exposed to LTG) (Mixed indications) 2024 |
Sweden 1995 - 2020 population based cohort retrospective |
The Swedish Developmental Origins of Health and Disease (DOHaD) cohort, which is a registry study linking several national electronic data sources. | Fetal exposure to Topiramate monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with self-reported consumption during pregnancy or a prescription 30 days before pregnancy or during pregnancy. |
exposed to other treatment, sick
Fetal exposure to Lamotrigine monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with self-reported consumption during pregnancy or a prescription 30 days before pregnancy or during pregnancy. |
during pregnancy (anytime or not specified) | 264 / 5035 | Partial overlapping of swedish data with Bjork 2022 and Dreier 2023 (IQ, ASD, ADHD) => these studies were kept and tagged. => Data extracted from the e-Supp pdf (Table S1; S2; S9) and excel (Figure S9 – Active comparator Analysis). | |
| 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). | ||||||||
|
Madley-Dowd_SE (Topiramate) (Controls unexposed, general pop) (Mixed indications) 2024 |
Sweden 1995 - 2020 population based cohort retrospective |
The Swedish Developmental Origins of Health and Disease (DOHaD) cohort, which is a registry study linking several national electronic data sources. | Fetal exposure to Topiramate monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with self-reported consumption during pregnancy or a prescription 30 days before pregnancy or during pregnancy. |
unexposed (general population or NOS)
No fetal exposure to antiseizure medication at any time during the pregnancy period. |
during pregnancy (anytime or not specified) | 264 / 2651210 | Partial overlapping of swedish data with Bjork 2022 and Dreier 2023 (IQ, ASD, ADHD) => these studies were kept and tagged. => Data extracted from the e-Supp pdf (Table S1; S2 and S6). | |
| 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). | ||||||||
|
Madley-Dowd_SE (Topiramate) (Controls unexposed, sibling) (Mixed indications) 2024 |
Sweden 1995 - 2020 population based cohort retrospective |
The Swedish Developmental Origins of Health and Disease (DOHaD) cohort, which is a registry study linking several national electronic data sources. | Siblings with fetal exposure to Topiramate monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with self-reported consumption during pregnancy or a prescription 30 days before pregnancy or during pregnancy. |
sibling
Discordant siblings without fetal exposure to antiseizure medication at any time during the pregnancy period. |
during pregnancy (anytime or not specified) | -9 / -9 | Partial overlapping of swedish data with Bjork 2022 and Dreier 2023 (IQ, ASD, ADHD) => these studies were kept and tagged. => Data extracted from the e-Supp pdf (Table S8) and excel (Figure S8 – Discordant Sibling Analysis). | |
| 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). | ||||||||
|
Madley-Dowd_UK (Topiramate) (Controls exposed to LTG) (Mixed indications) 2024 |
United Kingdom 1995 - 2018 retrospective cohort (claims database) |
The UK primary care-based Clinical Practice Research Datalink (CPRD) GOLD, with linkage to the CPRD Pregnancy Register, the CPRD Mother-Baby link, the Hospital Episode Statistics (HES) database, ... | Fetal exposure to Topiramate monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with a prescription that started or ended during the pregnancy period. |
exposed to other treatment, sick
Fetal exposure to Lamotrigine monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with a prescription that started or ended during the pregnancy period. |
during pregnancy (anytime or not specified) | 154 / 939 | Partial overlapping of swedish data with Bjork 2022 and Dreier 2023 (IQ, ASD, ADHD) => these studies were kept and tagged. => Data extracted from the e-Supp pdf (Table S1, S2 and S9) and excel (Figure S9 – Active Comparator Analysis). | |
| Prescriptions were identified from primary care records. | ||||||||
|
Madley-Dowd_UK (Topiramate) (Controls unexposed, general pop) (Mixed indications) 2024 |
United Kingdom 1995 - 2018 retrospective cohort (claims database) |
The UK primary care-based Clinical Practice Research Datalink (CPRD) GOLD, with linkage to the CPRD Pregnancy Register, the CPRD Mother-Baby link, the Hospital Episode Statistics (HES) database, ... | Fetal exposure to Topiramate monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with a prescription that started or ended during the pregnancy period. |
unexposed (general population or NOS)
No fetal exposure to antiseizure medication at any time during the pregnancy period. |
during pregnancy (anytime or not specified) | 154 / 514066 | Partial overlapping of swedish data with Bjork 2022 and Dreier 2023 (IQ, ASD, ADHD) => these studies were kept and tagged. => Data extracted from the e-Supp pdf (Table S1, S2 and S6). | |
| Prescriptions were identified from primary care records. | ||||||||
|
Madley-Dowd_UK (Topiramate) (Controls unexposed, sibling) (Mixed indications) 2024 |
United Kingdom 1995 - 2018 retrospective cohort (claims database) |
The UK primary care-based Clinical Practice Research Datalink (CPRD) GOLD, with linkage to the CPRD Pregnancy Register, the CPRD Mother-Baby link, the Hospital Episode Statistics (HES) database, ... | Siblings with fetal exposure to Topiramate monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with a prescription that started or ended during the pregnancy period. |
sibling
Discordant siblings without fetal exposure to antiseizure medication at any time during the pregnancy period. |
during pregnancy (anytime or not specified) | -9 / -9 | Partial overlapping of swedish data with Bjork 2022 and Dreier 2023 (IQ, ASD, ADHD) => these studies were kept and tagged. => Data extracted from the e-Supp pdf (Table S8) and excel (Figure S8 – Discordant Sibling Analysis). | |
| Prescriptions were identified from primary care records. | ||||||||
|
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. | ||||||||
|
Razaz (Topiramate) (Epilepsy) 2024 |
Denmark, Finland, Iceland, Norway and Sweden. 1996 - 2017 population based cohort retrospective |
The SCAN-AED project, using the Nordic register infrastructures. | Mothers with epilepsy who filled a prescription for Topiramate monotherapy between the date of the last menstrual period (LMP) and the day of birth. |
unexposed, sick
Mothers with epilepsy who did not fill an antiseizure medication (ASM) prescription in the period between 90 days before the last menstrual period (LMP) and the day of birth. |
during pregnancy (anytime or not specified) | 249 / 19043 | ||
| Prescription for antiseizure medication (ASM) was ascertained using nationwide prescription registers and identified ASMs based on Anatomical Therapeutic Chemical Classification. | ||||||||
|
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 (Topiramate) (Controls exposed to LTG) (Indications NOS) 2023 |
North America and Canada 1997 - 2022 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 | 510 / 2461 | Study design completed with the publication of Hernández-Díaz et al. 2012. Data extracted from the North American AED pregnancy registry website. Overlapping/update with Hernández-Díaz et al. 2012 and previous website reports. | |
| Women are interviewed at enrollment, at 7 months’ gestation and at 8 –12 weeks after the expected date of delivery. The computer-assisted interviews include questions on start and stop dates of each antiepileptic drugs taken, dose, frequency and changes in medication. | ||||||||
|
The NAAED (Topiramate) (Controls unexposed, disease free) (Indications NOS) 2023 |
North America and Canada 1997 - 2022 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 | 510 / 1311 | Study design completed with the publication of Hernández-Díaz et al. 2012. Data extracted from the North American AED pregnancy registry website. Overlapping/update with Hernández-Díaz et al. 2012 and previous website reports. Use of internal control. | |
| Women are interviewed at enrollment, at 7 months’ gestation and at 8 –12 weeks after the expected date of delivery. The computer-assisted interviews include questions on start and stop dates of each antiepileptic drugs taken, dose, frequency and changes in medication. | ||||||||
|
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. | ||||||||
|
Thomas (Topiramate) (Epilepsy) (Controls exposed to LTG) 2022 |
India 1998 - 2019 prospective cohort |
The Kerala Registry of Epilepsy and Pregnancy (KREP), India. | Infants of women with epilepsy who were exposed to Topiramate monotherapy at anytime during the antenatal period. |
exposed to other treatment, sick
Infants of women with epilepsy who were exposed to Lamotrigine monotherapy at anytime during the antenatal period. |
during pregnancy (anytime or not specified) | 6 / 26 | No use of delayed mental development, because discrepancy in LTG data '1/26 (11.5%)'. | |
| 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. | ||||||||
|
Thomas (Topiramate) (Epilepsy) (Controls unexposed, sick) 2022 |
India 1998 - 2019 prospective cohort |
The Kerala Registry of Epilepsy and Pregnancy (KREP), India. | Infants of women with epilepsy who were exposed to Topiramate monotherapy at anytime during the antenatal period. |
unexposed, sick
Infants of women with epilepsy who were not exposed to any antiseizure medications (ASMs) during pregnancy. |
during pregnancy (anytime or not specified) | 6 / 110 | ||
| 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. | ||||||||
|
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 | Overlapping/Update: (Major) malfo as a whole: Battino 2024 (1999-2022) updates Tomson 2018 (1999-2016), Tomson 2011, Martinez 2009 => These outcomes are not reported here (use of Battino 2024). | |
| 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) 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 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 a (Topiramate) (Controls exposed to LTG) (Epilepsy) 2024 |
Australia 1999 - 2023 prospective cohort |
The Australian Pregnancy Register of Antiepileptic Drugs (APR). | Women with epilepsy exposed to Topiramate monotherapy during pregnancy. |
exposed to other treatment, sick
Women with epilepsy exposed to lamotrigine monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 58 / 442 | Overlapping between Vajda 2024a (1999 - 2023) and Vajda 2018 (1999 - 2016) based on the same register and for the almost same outcome (with or without elective termination) => Use of Vajda 2024a because accounting for more relevant confounders. | |
| Not specified. All contact between the pregnant women and the Melbourne-based register has been by telephone. | ||||||||
|
Vajda a (Topiramate) (Controls unexposed sick) (Epilepsy) 2024 |
Australia 1999 - 2023 prospective cohort |
The Australian Pregnancy Register of Antiepileptic Drugs (APR). | Women with epilepsy exposed to Topiramate monotherapy during pregnancy. |
unexposed, sick
Women with epilepsy unexposed to antiseizure medication during pregnancy. |
during pregnancy (anytime or not specified) | 58 / 184 | Overlapping between Vajda 2024a (1999 - 2023) and Vajda 2018 (1999 - 2016) based on the same register and for the almost same outcome (with or without elective termination) => Use of Vajda 2024a because accounting for more relevant confounders. | |
| Not specified. All contact between the pregnant women and the Melbourne-based register has been by telephone. | ||||||||
|
Vajda b (Topiramate) (Epilepsy) (Controls exposed to Lamotrigine, sick) 2024 |
Australia 1999 - 2022 prospective cohort |
The Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs (referred to as ‘Australian Pregnancy Register’ from this point forward). | Women with epilepsy exposed to topiramate in monotherapy in early pregnancy. |
exposed to other treatment, sick
Women with epilepsy exposed to lamotrigine in monotherapy in early pregnancy. |
early pregnancy | 65 / 473 | Overlapping: Vajda 2024 totally included other APR data (Vajda 2019; Vajda 2007; 2010 (x2); 2012 (x2); 2013; 2014). Study design partly completed with Vajda 2013. | |
| 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. | ||||||||
|
Vajda b (Topiramate) (Epilepsy) (Controls unexposed, sick) 2024 |
Australia 1999 - 2022 prospective cohort |
The Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs (referred to as ‘Australian Pregnancy Register’ from this point forward). | Women with epilepsy exposed to topiramate in monotherapy in early pregnancy. |
unexposed, sick
Women with epilepsy not treated with antiepileptic drugs in early pregnancy. |
at least 1st trimester | 65 / 201 | Overlapping: Vajda 2024 totally included other APR data (Vajda 2019; Vajda 2007; 2010 (x2); 2012 (x2); 2013; 2014). Study design partly completed with Vajda 2013. | |
| 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. | ||||||||
|
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. | ||||||||
| 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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