Lamotrigine (Epilepsy)

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
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 lamotrigine 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) 15 / 30
Patients’ electronic and paper-based medical records.
AlSheikh
2020 		Saudi Arabia
2018 - 2019
prospective cohort 		King Fahd University Hospital Fetuses/neonates of patients with active epilepsy who received lamotrigine 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) 20 / 8
Information was collected through a structured questionnaire ‘Questionnaire for Investigation of Epilepsy in Tropical Countries'.
Artama (Controls unexposed, disease free)
2013 		Finland
1996 - 2008
population based cohort retrospective 		The Medical Birth Register (MBR), the Finnish Malformation Register, the Special Refund Entitlement Register, the Register on Reimbursement Drugs and Cause-of-Death Register. Births in pregnant women with epilepsy exposed to lamotrigine in monotherapy 1 month prior to pregnancy and/or any time during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Births in pregnant women without epilepsy and unexposed to any antiepileptic drugs 1 month prior to pregnancy and/or any time during pregnancy. 		3rd trimester, during pregnancy (anytime or not specified) 173 / 721948
The Special Refund Entitlement Register and the Register on Reimbursement Drugs contained informations on maternal drug treatment under ATC category N03.
Artama (Controls unexposed, sick)
2013 		Finland
1996 - 2008
population based cohort retrospective 		The Medical Birth Register (MBR), the Finnish Malformation Register, the Special Refund Entitlement Register, the Register on Reimbursement Drugs and Cause-of-Death Register. Births in pregnant women with epilepsy exposed to lamotrigine in monotherapy 1 month prior to pregnancy and/or any time during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Births in pregnant women with epilepsy and unexposed to any antiepileptic drugs 1 month prior to pregnancy and/or any time during pregnancy. 		3rd trimester, during pregnancy (anytime or not specified) 173 / 1800
The Special Refund Entitlement Register and the Register on Reimbursement Drugs contained informations on maternal drug treatment under ATC category N03.
Aydin
2020 		Turkey
2007 - 2017
retrospective cohort 		The Division of Perinatology, Department of Obstetrics and Gynecology, Hacettepe University, Turkey. Pregnant women with epilepsy who received lamotrigine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Pregnant women with epilepsy with no antiepileptic drugs during pregnancy. 		throughout pregnancy 7 / 22 There were no patients who had drug changes or discontinued during pregnancy.
Data were obtained from Perinatology Division’s computerized system. Antiepileptic drug use were reported.
Baker (Controls unexposed, disease free)
2015 		UK
2000 - 2004
prospective cohort 		11 National Health Service hospitals. Children born to women with epilepsy and exposed to lamotrigine monotherapy in utero. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Children born to women without epilepsy recruited from the same antenatal clinics of similar age, parity, and employment and residing within the same postal area. 		during pregnancy (anytime or not specified) 36 / 287 Women were excluded from recruitment if they had a severe learning disability or other chronic health condition requiring medication. Neuro-developmental disorders (as a whole) better assess in Bromley et al. 2013.
An epilepsy specialist confirmed antiepileptic drugs.
Baker (Controls unexposed, sick)
2015 		UK
2000 - 2004
prospective cohort 		11 National Health Service hospitals. Children born to women with epilepsy and exposed to lamotrigine 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 epilepsy and unexposed to antiepileptic drugs in utero. 		during pregnancy (anytime or not specified) 36 / 34 Women were excluded from recruitment if they had a severe learning disability or other chronic health condition requiring medication. Neuro-developmental disorders (as a whole) better assess in Bromley et al. 2013.
An epilepsy specialist confirmed antiepileptic drugs.
Bjørk (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 lamotrigine 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) 104 / 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 (Controls unexposed, NOS)
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 epileptic mothers filling at least one lamotrigine 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) 5073 / 4463879 Overlapping for ASD (2 outcomes) and Intellectual disabilities (2 outcomes): Dreier 2023 and Bjork 2022, with more pregnancies in Dreier 2023 => use of Dreier 2023 data.
Prescriptions through national prescription registers according to Anatomical Therapeutic Chemical classification codes N03, N05BA09, and S01EC01.
Bjørk (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 lamotrigine 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) 104 / 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 (Controls unexposed, sick)
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 epileptic mothers filling at least one lamotrigine 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) 5073 / 21634 Overlapping for ASD (2 outcomes) and Intellectual disabilities (2 outcomes): Dreier 2023 and Bjork 2022, with more pregnancies in Dreier 2023 => use of Dreier 2023 data.
Prescriptions through national prescription registers according to Anatomical Therapeutic Chemical classification codes N03, N05BA09, and S01EC01.
Borthen (Controls unexposed, disease free)
2011 		Norway
1999 - 2006
retrospective cohort 		The Medical Birth Registry of Norway and the National Population Registry Women with epilepsy using lamotrigine as monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Women without epilepsy recruited and identified from the database randomly selected among the deliveries in the same week at the same hospital as the case with epilepsy. 		during pregnancy (anytime or not specified) 30 / 205 A previous publication (Borthen 2010) gives a better review of the outcomes 'caesarean', 'postpartum haemorrhage' and 'induction of labour' (adjusted OR and largest exposed population). As Veiby 2014 for the outcome 'major malformations'.
Informations were extracted from a standardised antenatal form filled in by doctors and transferred to the database by practitioners attending the delivery and also from the neurological case records (according to ATC Classification System).
Borthen (Controls unexposed, disease free)
2010 		Norway
1999 - 2005
population based cohort retrospective 		The Medical Birth Registry of Norway, the National Population Registry Births in women who gave a past or present history of epilepsy and exposed to lamotrigine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Births in women without a past or present history of epilepsy and unexposed to any antiepileptic drugs during pregnancy. 		during pregnancy (anytime or not specified) 233 / 362302
A standardised antenatal form is filled in by doctors and transferred to the database by practitioners attending the delivery. Pregnancies registered with an anticonvulsant drug (according to ATC Classification System) were categorised as exposed.
Borthen (Controls unexposed, sick)
2010 		Norway
1999 - 2005
population based cohort retrospective 		The Medical Birth Registry of Norway, the National Population Registry Births in women who gave a past or present history of epilepsy and exposed to lamotrigine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Births in women who gave a past or present history of epilepsy and unexposed to any antiepileptic drugs during pregnancy. 		during pregnancy (anytime or not specified) 233 / 1863
A standardised antenatal form is filled in by doctors and transferred to the database by practitioners attending the delivery. Pregnancies registered with an anticonvulsant drug (according to ATC Classification System) were categorised as exposed.
Borthen (Controls unexposed, sick)
2011 		Norway
1999 - 2006
retrospective cohort 		The Medical Birth Registry of Norway and the National Population Registry Women with epilepsy using lamotrigine as monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Women with epilepsy not using any antiepileptic drugs during pregnancy. 		during pregnancy (anytime or not specified) 30 / 89 A previous publication (Borthen 2010) gives a better review of the outcomes 'caesarean', 'postpartum haemorrhage' and 'induction of labour' (adjusted OR and largest exposed population). As Veiby 2014 for the outcome 'major malformations'.
Informations were extracted from a standardised antenatal form filled in by doctors and transferred to the database by practitioners attending the delivery and also from the neurological case records (according to ATC Classification System).
Bromley (Controls unexposed, disease free)
2013 		UK
2000 - 2004
prospective cohort 		The Liverpool and Manchester Neurodevelopment Group (LMNDG) Children born to epileptic mothers exposed to lamotrigine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Children born to women without epilepsy. 		during pregnancy (anytime or not specified) 36 / 285 The children or mothers who had conditions likely to influence neurodevelopmental outcome were excluded. The result for autism spectrum disorders is an update compares to the preliminary findings presented in Bromley 2008.
Information was recorded from maternal interview and checked against medical records. An epilepsy specialist confirmed antiepileptic durg type and dose.
Bromley (Controls unexposed, disease free)
2010 		UK
2000 - 2006
prospective cohort 		11 different National Health Service hospitals within Merseyside and Greater Manchester (LMNDG: the Liverpool and Manchester Neurodevelopment Group) Children born to mothers with epilepsy exposed to lamotrigine 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 were recruited from the same antenatal clinics. 		during pregnancy (anytime or not specified) 34 / 230 Study design partly completed with Mawer et al., 2010. The locomotor dimension is already evaluated in Bromley et al., 2013 and language disorders/delay in Baker et al., 2015 (older children and better scales).
The research nurse took a personal and medical history in accordance with the prospectively designed Patient Basic and Control Basic Record Forms. An epilepsy specialist confirmed antiepileptic medication. Information from the patient was supplemented from clinical records.
Bromley (Controls unexposed, sick)
2013 		UK
2000 - 2004
prospective cohort 		The Liverpool and Manchester Neurodevelopment Group (LMNDG) Children born to epileptic mothers exposed to lamotrigine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children were born to women with epilepsy who were not taking medication during their pregnancy. 		during pregnancy (anytime or not specified) 36 / 34 The children or mothers who had conditions likely to influence neurodevelopmental outcome were excluded. The result for autism spectrum disorders is an update compares to the preliminary findings presented in Bromley 2008.
Information was recorded from maternal interview and checked against medical records. An epilepsy specialist confirmed antiepileptic durg type and dose.
Bromley (Controls unexposed, sick)
2010 		UK
2000 - 2006
prospective cohort 		11 different National Health Service hospitals within Merseyside and Greater Manchester (LMNDG: the Liverpool and Manchester Neurodevelopment Group) Children born to mothers with epilepsy exposed to lamotrigine monotherapy in utero. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children born to mothers with epilepsy not exposed to antiepileptic drugs in utero. 		during pregnancy (anytime or not specified) 34 / 27 Study design partly completed with Mawer et al., 2010. The locomotor dimension is already evaluated in Bromley et al., 2013 and language disorders/delay in Baker et al., 2015 (older children and better scales).
The research nurse took a personal and medical history in accordance with the prospectively designed Patient Basic and Control Basic Record Forms. An epilepsy specialist confirmed antiepileptic medication. Information from the patient was supplemented from clinical records.
Bromley (Lamotrigine) (Epilepsy)
2023 		United Kingdom
2014 - 2016
prospective cohort 		The NaME (Neurodevelopment of Babies Born to Mothers With Epilepsy) Study, recruiting across the North West and North East of England and from Northern Ireland, UK. Pregnant women with epilepsy exposed to lamotrigine during pregnancy. unexposed, sick
Pregnant women with epilepsy and with no antiseizure medication. 		during pregnancy (anytime or not specified) 106 / 80
The prescribed dose of the antiseizure medications was recorded prospectively from both medical records and maternal interviews at recruitment, and then again at ≥32 weeks gestation (by telephone interviews).
Campbell
2014 		UK and Ireland
1996 - 2012
prospective cohort 		The United Kingdom Epilepsy and Pregnancy Register Infants of women with epilepsy exposed to lamotrigine 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 on no antiepileptic drugs during pregnancy. 		1st trimester 2198 / 541 Study design was partly completed with Morrow 2006. Major malformation results in Morrow et al., 2006 are completely overlapped by this publication (with more exposed pregnancies).
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.
Cassina
2013 		Italy
2000 - 2008
prospective cohort 		Italian Teratology Information Services: Servizio di Informazione Teratologica, Telefono Rosso, Centro di Riferimento Regionale di Tossicologia Perinatale. Children whose epileptic mothers were treated with lamotrigine in monotherapy between the 5th and the 14th week after their last menstrual period. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Healthy pregnant women randomly selected among patients who contacted the Teratology Information Services during their pregnancy with regard to exposure to agents known not to be teratogenic (i.e. paracetamol, hair dying, etc.) during a similar time frame. 		1st trimester 26 / 867 Chromosomal anomalies and genetic syndromes were excluded.
At the first contact with the service, pregnant women answered to a formulated questionnaire. In addition, details regarding the treatment with antiepileptic drugs taken after the first contact to the Teratology Information Service were ascertained by a follow-up telephone interview.
Charlton
2011 		UK
1990 - 2006
retrospective cohort (claims database) 		The UK General Practice Research Database (GPRD) and the UK Epilepsy and Pregnancy Register. Infants of mother-baby pairs who had lamotrigine monotherapy exposure during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Infants of mother-baby pairs who had no antiepleptic drug exposure during the first trimester. 		1st trimester 98 / 902 The results obtained by the UK Epilepsy and Pregnancy Register are already obtained in the publication of Morrow 2006, thus, only those extracted from the UK General Practice Research Database are implemented here.
Data generated during routine clinical practice in the UK General Practice Research Database (GPRD). All prescriptions issued by general practitioners are recorded in the database.
Charlton (Controls unexposed, disease free)
2017 		UK
2000 - 2006
retrospective cohort (claims database) 		The UK Clinical Practice Research Datalink (CPRD) Mother–child pairs where the mother had epilepsy and received lamotrigine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Mother–child pairs where the mother did not meet the epilepsy criteria and had not been prescribed an antiepileptic drug at any time prior to her child turning age 6 years. 		during pregnancy (anytime or not specified) 122 / 6048 The results obtained by the Liverpool and Manchester Neurodevelopment Group are already obtained by the publication of Bromley 2013, thus, only those extracted from the UK Clinical Practice Research Datalink are implemented here.
Determined from issued prescription records. The UK Clinical Practice Research Datalink contains anonymised, patient medical and prescribing records routinely collected within general practice.
Charlton (Controls unexposed, sick)
2017 		UK
2000 - 2006
retrospective cohort (claims database) 		The UK Clinical Practice Research Datalink (CPRD) Mother–child pairs where the mother had epilepsy and received lamotrigine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Mother–child pairs where the mother had epilepsy and no antiepileptic drug exposure during pregnancy. 		during pregnancy (anytime or not specified) 122 / 472 The results obtained by the Liverpool and Manchester Neurodevelopment Group are already obtained by the publication of Bromley 2013, thus, only those extracted from the UK Clinical Practice Research Datalink are implemented here.
Determined from issued prescription records. The UK Clinical Practice Research Datalink contains anonymised, patient medical and prescribing records routinely collected within general practice.
Cohen
2019 		USA
2000 - 2010
retrospective cohort (claims database) 		Medicaid Analytic eXtract (MAX) Restricted to pregnancies in women with epilepsy with at least one dispensed prescription for lamotrigine 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 -9 / 1440631 Authors excluded deliveries with a major congenital malformation (identified by ICD-9). No crude data are available for the epilepsy subgroup with monotherapy exposure.
The Medicaid Analytic Extract data include prescriptions filled on an outpatient basis.
Cohen-Israel
2018 		Israel
2004 – 2014
retrospective cohort 		The Beilinson Teratology Information Service Children of epileptic women treated with lamotrigine (in monotherapy for 91.6%) during the first trimester of pregnancy. unexposed, disease free
Children born at the same hospital to healthy women. 		1st trimester 83 / 83 Statistical analysis performed separately for the monotherapy and combined therapy subgroups yielded no significant differences for any of the variables; therefore, all lamotrigine-treated patients were considered as a single group.
The women were identified by a search of the Beilinson Teratology Information Service which contains complete records.
Cummings
2011 		Northern Ireland
2002 - 2005
retrospective cohort (registry) 		The UK Epilepsy and Pregnancy Register and the Child Health System database. Children born to epileptic mothers taking lamotrigine as monotherapy throughout pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Children born to healthy women not taking prescribed medication other than folic acid or iron supplements during pregnancy. 		throughout pregnancy 35 / 44 Women who were taking any other prescribed medication other than folic acid or iron supplements are excluded. The method for exposition measure isn't recalled here but it's always the same for this register.
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.
Dean
2007 		Scotland
1976 - 2002
retrospective cohort 		Aberdeen Maternity Hospital. Children whose epileptic mothers were exposed to lamotrigine 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 not exposed during pregnancy. 		during pregnancy (anytime or not specified) 4 / 46
A trained research nurse undertook interviews recording antiepileptic drugs use in each pregnancy. Maternal antiepileptic drugs dose was verified from case records where possible.
Diav-Citrin
2017 		Israel
1997 - 2008
prospective cohort 		The Israeli Teratology Information Service Pregnancies with at least first trimester exposure to lamotrigine for epilepsy in monotherapy. unexposed, disease free
Pregnancies from a randomly selected group of women counseled (over a similar timeframe) during pregnancy in regard to exposures known to be nonteratogenic and without chronic diseases. 		at least 1st trimester 114 / 865 After one of the authors double-checked the raw data, the result on congenital malformations is 6/114 and not 7/114 'there were indeed 6 malformations in the epilepsy group'. All congenital malformations results is overlapped by Rihtman et al. 2013.
Details of exposure were collected during pregnancy at the initial contact before pregnancy outcome was known, using a structured questionnaire.
Dreier
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 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. unexposed, sick
Children not prenatally exposed to antiseizure medication. 		during pregnancy (anytime or not specified) 5288 / 22203 Overlapping for ASD (2 outcomes) and Intellectual disabilities (2 outcomes): Dreier 2023 and Bjork 2022, with more pregnancies in Dreier 2023 => use of Dreier 2023 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
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 lamotrigine 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) 4679 / -9 Unknown number in the exposed and unexposed group (abstract).
Reimbursement codes for prescriptions.
Gopinath
2015 		India
2010 - 2012
retrospective cohort (registry) 		The Kerala Registry of Epilepsy and Pregnancy (KREP) Children from epileptic mothers exposed to lamotrigine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children from epileptic mothers without any antiepileptic drugs exposure during pregnancy. 		during pregnancy (anytime or not specified) 1 / 16 Study design partly completed with Thomas et al., 2007 from the same registry.
The details of antiepileptic drugs exposure per month were recorded on a monthly basis in the protocol from the month prior to pregnancy through the entire period of pregnancy and three-month post partum. The drug compliance and seizure frequency were ascertained with a detailed diary.
He
2017 		China
2009 - 2015
prospective cohort 		The epilepsy center of West China Second University Hospital of Sichuan University Pregnancies in which lamotrigine monotherapy was used during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Pregnancies in which antiepileptic drugs were never used before and during pregnancy. 		during pregnancy (anytime or not specified) 8 / 31 Patients who developed epilepsy during pregnancy or after delivery were not included.
Data collected included antiepileptic drug use.
Holmes
2008 		North America and Canada
1997 - 2006
prospective cohort 		The North American Antiepileptic Drug Pregnancy Register and the Active Malformations Surveillance Program. Infants of women who had taken lamotrigine as monotherapy during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed (general population or NOS)
Unexposed newborn infants in the Active Malformations Surveillance Program at Brigham and Women’s Hospital surveyed between 1972 and 1974 and between 1979 and 2000. 		1st trimester 684 / 206224 The 'pure' prospective group isn't prefered because 'The findings in both the pure and traditional prospective groups were combined, as cleft palate is not very likely to be identified by prenatal screening by ultrasound'.
Women were questioned with a computer-assisted telephone interview 3 times.
Hosny
2021 		Egypt
2018 - 2020
prospective cohort 		Kasr Al-Ainy Hospital, Cairo University, Egypt Pregnant women with epilepsy on lamotrigine monotherapy during the first trimester. unexposed, sick
Pregnant women with epilepsy with no treatment during the first trimester. 		1st trimester 3 / 21 Each woman had one pregnancy during the study period.
The following data were evaluated: seizure control 6 months before pregnancy, seizure control during each trimester, type and dose of ASMs at conception.
Husebye (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 lamotrigine 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) 112 / 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 (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 lamotrigine 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) 112 / 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.
Kasradze
2017 		Georgia
2001
prospective cohort 		The Georgian National Antiepileptic drugs-Pregnancy Registry (the Georgian registry of EURAP). Children born to epileptic mothers exposed to lamotrigine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Children born to mothers without epilepsy, with no antiepileptic drug or other drug treatment during pregnancy 		during pregnancy (anytime or not specified) 3 / 50 Children with major congenital malformations were excluded from the study.
Antiepileptic drugs and total daily dosage before pregnancy/at 1st trimester/at 2nd trimester/at 3rd trimester were assessed retrospectively during the mother's structured interview.
Kini
2006 		UK
1989 - 1999
retrospective cohort 		Epilepsy clinics in Manchester and Liverpool, and at a Central Manchester Maternity Hospital on behalf of the Liverpool and Manchester Neurodevelopmental Study Group (LMNDG). Children exposed to lamotrigine monotherapy during pregnancy and with epileptic mothers. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children not exposed to antiepileptic drugs during pregnancy and with epileptic mothers. 		during pregnancy (anytime or not specified) 9 / 101 Because we don't know the exact number of children exposed to lamotrigine and analyzed for malformations, this outcome cannot be reported here.
Structured interviews were conducted with the mothers and medical records were available to confirm details in about 80% of participants.
Li
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 Lamotrigine monotherapy during pregnancy. unexposed, sick
Women with epilepsy (WWE) not using antiseizure medications during pregnancy. 		during pregnancy (anytime or not specified) 38 / 253 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. Overlapping: He 2017 totally included in Li 2023.
The use of antiseizure medications on the included patients was registered by doctors and trained researchers.
Mawer (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 lamotrigine 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 40 / 315 Kini's 2007 malformation results are overlapped. Specific major malformations' numerators are extracted from the review by Weston et al. 2016 because not classified per types in the original publication. 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 (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 lamotrigine 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 40 / 46 Kini's 2007 malformation results are overlapped. Specific major malformations' numerators are extracted from the review by Weston et al. 2016 because not classified per types in the original publication. 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
2023 		USA
2012 - 2016
prospective cohort 		The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study is a prospective, observational, multicentre cohort study at 20 specialty epilepsy centres in the USA. Children born to women with epilepsy treated with Lamotrigine monotherapy. unexposed, disease free
Children born to women without epilepsy. 		during pregnancy (anytime or not specified) 90 / 106 Imputations analysis reported here. Overlapping: Meador 2021 and 2023 used the same cohort in order to study the same outcome, at 2 different ages (=> use of the data on the older children, i.e Meador 2023).
Data for antiseizure medications were collected using a daily electronic diary and verified at study visits and with medical records.
Meador (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 lamotrigine 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 113 / 106
Data were obtained from participants and their medical records.
Meador (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 lamotrigine 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 113 / 15
Data were obtained from participants and their medical records.
Miškov (Controls unexposed, disease free)
2016 		Croatia
2003 - 2013
prospective cohort 		The Sestre milosrdnice University Hospital Center in Zagreb Pregnancies in women with epilepsy on lamotrigine monotherapy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Pregnancies in healthy controls. 		during pregnancy (anytime or not specified) 37 / 147 Includes all Miskov's 2010 outcomes.
Data collected on pregnant women during outpatient visits to the neurologist, gynecologist and pediatrician neurologist.
Miškov (Controls unexposed, sick)
2016 		Croatia
2003 - 2013
prospective cohort 		The Sestre milosrdnice University Hospital Center in Zagreb Pregnancies in women with epilepsy on lamotrigine monotherapy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Pregnancies in women with epilepsy without antiepileptic drugs. 		during pregnancy (anytime or not specified) 37 / 4 Includes all Miskov's 2010 outcomes.
Data collected on pregnant women during outpatient visits to the neurologist, gynecologist and pediatrician neurologist.
Pekoz (Lamotrigine) (Epilepsy)
2023 		Turkey
2014 - 2019
prospective cohort 		A Nationwide multicenter study, based on the neurology outpatient clinics of 21 centers in Turkey. Pregnant women with epilepsy (PWWE) receiving Lamotrigine as monotherapy. unexposed, sick
Pregnant women with epilepsy (PWWE), antiseizure medication free. 		during pregnancy (anytime or not specified) 141 / 43
The patients were examined by a neurologist every 2 months during pregnancy, and the use of Anti-seizure medications (ASMs) was assessed.
Petersen (Controls unexposed NOS)
2017 		UK
1995 - 2014
retrospective cohort (claims database) 		The Health Improvement Network (THIN) Women prescribed lamotrigine 31–105 days after the start of the pregnancy without valproate or carbamazepine polytherapy. 96% of the women prescribed lamotrigine had a record of epilepsy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed (general population or NOS)
Women with no records of antiepileptic drug treatment in the pregnancy or 28 days prior to the first day of last menstrual period (LMP). 		1st trimester 357 / 239151 'It is possible that individuals who were prescribed lamotrigine could also be prescribed other antiepileptics, however less than 0.01% were prescribed other AEDs (i.e. other than valproate and carbamazepine) during pregnancy.' (author's email)
The Health Improvement Network (THIN) provides data on patients’ clinical and prescribing records. Prescriptions are issued electronically via the general practice computer systems.
Petersen (Controls unexposed, sick)
2017 		UK
1995 - 2014
retrospective cohort (claims database) 		The Health Improvement Network (THIN) Women with a record of epilepsy prescribed lamotrigine 31–105 days after the start of the pregnancy without valproate or carbamazepine polytherapy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Women with a record of epilepsy but with no records of antiepileptic drug treatment in the pregnancy or 28 days prior to the first day of last menstrual period (LMP). 		1st trimester 344 / 2844 'It is possible that individuals who were prescribed lamotrigine could also be prescribed other antiepileptics, however less than 0.01% were prescribed other AEDs (i.e. other than valproate and carbamazepine) during pregnancy.' (author's email)
The Health Improvement Network (THIN) provides data on patients’ clinical and prescribing records. Prescriptions are issued electronically via the general practice computer systems.
Razaz (Controls unexposed, disease free)
2017 		Sweden
1997- 2011
population based cohort retrospective 		The Swedish Medical Birth Register, the Swedish National Patient Register and the Prescribed Drug Registry. Infants of mothers with epilepsy who had reimbursement for lamotrigine monotherapy between 30 days before the estimated day of conception to the day of birth. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Infants of mothers without epilepsy. 		during pregnancy (anytime or not specified) 503 / 1424279
The Prescribed Drug Registry stores data on all drugs prescribed in ambulatory care and dispensed at a Swedish pharmacy. Prescription were coded using the Drug Identification Numbers and the ATC system.
Razaz (Controls unexposed, sick)
2017 		Sweden
1997- 2011
population based cohort retrospective 		The Swedish Medical Birth Register, the Swedish National Patient Register and the Prescribed Drug Registry. Infants of mothers with epilepsy who had reimbursement for lamotrigine monotherapy between 30 days before the estimated day of conception to the day of birth. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Infants of mothers with epilepsy not receiving antiepileptic drug between 30 days before the estimated day of conception to the day of birth. 		during pregnancy (anytime or not specified) 503 / 1868
The Prescribed Drug Registry stores data on all drugs prescribed in ambulatory care and dispensed at a Swedish pharmacy. Prescription were coded using the Drug Identification Numbers and the ATC system.
Ren (Lamotrigine) (Epilepsy)
2023 		Denmark
1997 - 2002
population based cohort propective 		The Danish Civil Registration System, the Danish Medical Birth Registry, the Danish Agency for Information Technology and Learning, the Danish Register of Medicinal Product Statistics. Children born of mother with epilepsy, exposed in utero to Lamotrigine monotherapy, prescribed and redeemed within the exposure window defined from 30 days before the first day of the last menstrual period to 1 day before birth. unexposed, sick
Children born of mother with epilepsy, unexposed in utero to any antiepileptic drugs within the exposure time window during pregnancy. 		during pregnancy (anytime or not specified) 166 / 3167 Overlapping: this publication totally included the data of Elkjaer, 2018, for an higher academic grade => use of Ren 2023.
Information on medical exposure was retrieved from the Danish Register of Medicinal Product Statistics.
Rihtman
2013 		Israel
2001 - 2006
prospective cohort 		The Israeli Teratogen Information Service Children exposed to lamotrigine monotherapy for a minimum of the first trimester of pregnancy born from mothers with or without epilepsy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed (general population or NOS)
Children within the specified age-range and identified via word-of-mouth. 		at least 1st trimester 42 / 52 Exclusion criteria (all groups) were genetic abnormalities and full scale IQ of less than 70.
Details of exposure were collected during pregnancy at the initial contact before pregnancy outcome was known.
Thomas (Controls unexposed, disease free)
2021 		India
1998 - 2015
prospective cohort 		The Kerala Registry of Epilepsy and Pregnancy (KREP) Children of women with epilepsy using lamotrigine 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 38 / 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 (Controls unexposed, sick)
2021 		India
1998 - 2019
prospective cohort 		The Kerala Registry of Epilepsy and Pregnancy (KREP) Children of women with epilepsy using lamotrigine 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 50 / 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.
Trivedi
2018 		India
1998 - 2015
prospective cohort 		The Kerala Registry of Epilepsy and Pregnancy (KREP) Pregnant women with epilepsy who used lamotrigine 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 48 / 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
2018 		Australia
1999 - 2016
prospective cohort 		The Australian Register of Antiepileptic Drugs in Pregnancy. Offsprings of pregnant women with epilepsy exposed to lamotrigine 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 382 / 170 Regarding the calculated RR for intrauterine foetal death 'It should have been 6.23, not 8.23 from the CIA program that we used ' (author's email).
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
2019 		Australia
1999 - 2018
prospective cohort 		The Australian Register of Antiepileptic Drugs in Pregnancy. Offsprings born from women nearly always with epilepsy exposed to lamotrigine 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 406 / 176 Women with epilepsy accounted for 98.3%. Completely overlap Vajda 2004; 2007 (x2); 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. Details provided by the participants are confirmed, as far as possible, by the treating medical practitioners and through hospital records.
Vajda
2013 		Australia
1999 - 2013
prospective cohort 		The Australian Register of Antiepileptic Drugs in Pregnancy. Offsprings from women with epilepsy exposed to lamotrigine 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 315 / 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.
Van Marter (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 of pregnant women with epilepsy with exposure to lamotrigine monotherapy based on the mother’s prescribed antiepileptic drug at the time of enrollment. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Children of healthy pregnant women. 		at least 1st trimester 110 / 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.
Prescribed antiepileptic drug at the time of enrollment. Data were collected from subjects and their medical records.
Van Marter (Controls unexposed, sick)
2021 		US
2012 - 2016
prospective cohort 		The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study (20 US tertiary epilepsy centers). Children of pregnant women with epilepsy with exposure to lamotrigine monotherapy based on the mother’s prescribed antiepileptic drug at the time of enrollment. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children of pregnant women with epilepsy without prescribed antiepileptic drug at the time of enrollment. 		at least 1st trimester 110 / 15 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.
Prescribed antiepileptic drug at the time of enrollment. Data were collected from subjects and their medical records.
Vanya (Controls unexposed, sick)
2015 		Hungary
2000 - 2014
retrospective cohort 		Department of Obstetrics and Gynaecology Albert Szent-Györgyi Medical Health Center University of Szeged Neonates of epileptic women treated with lamotrigine monotherapy throughout the nine months of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Neonates of epileptic women treatment-naive for antiepileptic drugs during pregnancy (not exposed to antiepileptic drugs). 		throughout pregnancy 6 / 20 Chromosomal anomalies and genetic syndromes were excluded from the study. The only exploitable outcome with a control group concern major congenital malformation.
The epilepsy-related data evaluated included antiepileptic drugs therapy (NOS).
Veiby (Controls unexposed, disease free)
2014 		Norway
1999 - 2011
population based cohort retrospective 		Medical Birth Registry of Norway Children exposed prenatally to lamotrigine as monotherapy indicated for their mothers' epilepsy. (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 593 / 771412 We will only consider the subgroup of women exposed to antiepileptic drugs for the strict indication of epilepsy.
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 (Controls unexposed, disease free) a
2013 		Norway
1999 - 2008
prospective cohort 		Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway. Children exposed to lamotrigine monotherapy during pregnancy born from epileptic mothers. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Children of parents without epilepsy unexposed to antiepileptic drugs during pregnancy. 		during pregnancy (anytime or not specified) 71 / 77770 Overlap for the neuro-developmental outcomes at 18 and 36 months old and the 'weight less than 10th percentile' outcomes with Bjørk 2018 and Veiby 2013 b.
Reported by the mother in the first MoBa questionnaire (weeks 13-17) as well as recorded in the compulsory Medical Birth Registry by the attending physician and midwife at delivery.
Veiby (Controls unexposed, disease free) b
2013 		Western Norway, Hordaland County.
1999 - 2008
prospective cohort 		Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway. Children exposed to lamotrigine monotherapy during pregnancy born from epileptic mothers. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Children of parents without epilepsy unexposed to antiepileptic drugs during pregnancy. 		during pregnancy (anytime or not specified) 104 / 107597 Veiby 2013 major malformations results are already included in Veiby 2014 and risk of ASD better studied in Bjørk 2018 (with more exposed pregnancies). Small for gestationnal age results of Farmen 2015 are completely overlapped by this study.
Questionnaires were filled out by the mothers (at gestational week 13–17) and medical hospital-records were examined to validate the self-reported use of antiepileptic drugs during pregnancy.
Veiby (Controls unexposed, sick)
2014 		Norway
1999 - 2011
population based cohort retrospective 		Medical Birth Registry of Norway Children exposed prenatally to lamotrigine as monotherapy indicated for their mothers' epilepsy. (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 593 / 3773 We will only consider the subgroup of women exposed to antiepileptic drugs for the strict indication of epilepsy.
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 (Controls unexposed, sick) a
2013 		Norway
1999 - 2008
prospective cohort 		Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway. Children exposed to lamotrigine monotherapy during pregnancy born from epileptic mothers. (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 drugs during pregnancy. 		during pregnancy (anytime or not specified) 71 / 276 Overlap for the neuro-developmental outcomes at 18 and 36 months old and the 'weight less than 10th percentile' outcomes with Bjørk 2018 and Veiby 2013 b.
Reported by the mother in the first MoBa questionnaire (weeks 13-17) as well as recorded in the compulsory Medical Birth Registry by the attending physician and midwife at delivery.
Veiby (Controls unexposed, sick) b
2013 		Western Norway, Hordaland County.
1999 - 2008
prospective cohort 		Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway. Children exposed to lamotrigine monotherapy during pregnancy born from epileptic mothers. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children of mothers with epilepsy not treated with antiepileptic drugs during pregnancy. 		during pregnancy (anytime or not specified) 104 / 393 Veiby 2013 major malformations results are already included in Veiby 2014 and risk of ASD better studied in Bjørk 2018 (with more exposed pregnancies). Small for gestationnal age results of Farmen 2015 are completely overlapped by this study.
Questionnaires were filled out by the mothers (at gestational week 13–17) and medical hospital-records were examined to validate the self-reported use of antiepileptic drugs during pregnancy.
Videman
2016 		Finland
2009 - 2013
prospective cohort 		The Helsinki University Hospital, Finland. Newborns from epileptic women with fetal monotherapy lamotrigine exposure during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
Newborns from women with no antiepileptic drug or other brain-acting medication. 		during pregnancy (anytime or not specified) 8 / 67 Study design partly completed with a previous article of Videman 2016.
Exposure data (including daily doses and serum levels for oxcarbazepine, carbamazepine, valproic acid, lamotrigine, and levetiracetam) were obtained prospectively at outpatient visits taking place every trimester and postnatally.
Wiggs
2020 		Sweden
1996 - 2011
population based cohort retrospective 		Swedish Medical Birth Register, the National Patient Register, the Prescribed Drug Register, the Integrated Database for Labor Market Research and the Education Register. Children whose epileptic mothers reported use of lamotrigine monotherapy in the first trimester (77% were found to have filled prescriptions later in pregnancy: second or third trimester). (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children whose epileptic mothers reported no use of antiseizure medications. 		at least 1st trimester 996 / 11298 Children who were multiples were dropped. Crude data are not specified for monotherapy exposure. HR's results choose thanks to author's email.
Authors defined exposure using Anatomical Therapeutic Chemical codes for maternal-reported atiseizure medication use. They cross-referenced maternal self-reports against official records of filled prescriptions in The Prescribed Drug Register to verified previous findings of high agreement.

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

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

Empty. There are no case-control studies available for this drug.

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