| Study | Country Study period |
Population source | Exposure definition | Non-exposure definition | Sample size | Rmk |
|---|---|---|---|---|---|---|
| Alsfouk, 2021 |
Riyadh and Jeddah, Saudi Arabia. 1993 - 2020 |
Pregnant women with epilepsy followed up prospectively between the study period. | 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. |
15 / 30 | |
| AlSheikh, 2020 |
Saudi Arabia 2018 - 2019 |
Pregnant patients with active epilepsy admitted to the Obstetrics and Gynecology outpatient clinic and those seeking follow-up from our outpatient clinic. Patients on treatment and who had at least one seizure in the past one year. | 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. |
20 / 8 | |
| Artama (Controls unexposed, disease free), 2013 |
Finland 1996 - 2008 |
All singleton births (n = 751,139) in Finland during the study period. | 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. |
173 / 721948 | |
| Artama (Controls unexposed, sick), 2013 |
Finland 1996 - 2008 |
All singleton births (n = 751,139) in Finland during the study period. | 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. |
173 / 1800 | |
| Aydin, 2020 |
Turkey 2007 - 2017 |
Pregnant women with epilepsy who delivered and had follow ups at the division of perinatalogy between the study period. | 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. |
7 / 22 | There were no patients who had drug changes or discontinued during pregnancy. |
| Baker (Controls unexposed, disease free), 2015 |
UK 2000 - 2004 |
Women with and without epilepsy were recruited from antenatal clinics between the study period. | 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. |
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. |
| Baker (Controls unexposed, sick), 2015 |
UK 2000 - 2004 |
Women with and without epilepsy were recruited from antenatal clinics between the study period. | 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. |
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. |
| Bjørk (Controls unexposed, disease free), 2018 |
Norway 1999 - 2008 |
Pregnancies registered in the MoBa cohort when information concerning use of folic acid supplements and/or plasma folate concentration during pregnancy was available. | 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. |
104 / 104222 | |
| Bjørk (Controls unexposed, NOS), 2022 |
Danemark, Finland, Iceland, Norway and Sweden. 1996 - 2017 |
Singleton births born from mothers from five Nordic countries. | 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. |
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. |
| Bjørk (Controls unexposed, sick), 2022 |
Danemark, Finland, Iceland, Norway and Sweden. 1996 - 2017 |
Singleton births born from mothers from five Nordic countries. | 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. |
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. |
| Bjørk (Controls unexposed, sick), 2018 |
Norway 1999 - 2008 |
Pregnancies registered in the MoBa cohort when information concerning use of folic acid supplements and/or plasma folate concentration during pregnancy was available. | 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. |
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. |
| Borthen (Controls unexposed, disease free), 2011 |
Norway 1999 - 2006 |
During the study period, 38 483 deliveries took place at Haukeland University Hospital. | 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. |
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'. |
| Borthen (Controls unexposed, disease free), 2010 |
Norway 1999 - 2005 |
All singleton births and the first child in multiple pregnancies were included (n= 365107). Miscarriages and stillbirths below week 21 were also included. | 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. |
233 / 362302 | |
| Borthen (Controls unexposed, sick), 2010 |
Norway 1999 - 2005 |
All singleton births and the first child in multiple pregnancies were included (n= 365107). Miscarriages and stillbirths below week 21 were also included. | 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. |
233 / 1863 | |
| Borthen (Controls unexposed, sick), 2011 |
Norway 1999 - 2006 |
During the study period, 38 483 deliveries took place at Haukeland University Hospital. | 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. |
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'. |
| Bromley (Controls unexposed, disease free), 2010 |
UK 2000 - 2006 |
Midwives in the antenatal clinics approached each woman, who gave a history of epilepsy, whatever her stage of gestation. | 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. |
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). |
| Bromley (Controls unexposed, disease free), 2013 |
UK 2000 - 2004 |
Children born to pregnant women epileptic or not, recruited from antenatal clinics. | 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. |
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. |
| Bromley (Controls unexposed, sick), 2010 |
UK 2000 - 2006 |
Midwives in the antenatal clinics approached each woman, who gave a history of epilepsy, whatever her stage of gestation. | 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. |
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). |
| Bromley (Controls unexposed, sick), 2013 |
UK 2000 - 2004 |
Children born to pregnant women epileptic or not, recruited from antenatal clinics. | 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. |
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. |
| Bromley (Lamotrigine) (Epilepsy), 2023 |
United Kingdom 2014 - 2016 |
Pregnant women with epilepsy, of <21 weeks gestation, recruited from 21 hospitals in the UK (across the North West and North East of England and from Northern Ireland). | Pregnant women with epilepsy exposed to lamotrigine during pregnancy. |
unexposed, sick
Pregnant women with epilepsy and with no antiseizure medication. |
106 / 80 | |
| Campbell, 2014 |
UK and Ireland 1996 - 2012 |
Pregnant women with epilepsy, whether or not they were taking an antiepileptic drug, either in monotherapy or polytherapy, and who were referred to the register before the outcome of the pregnancy was known. | 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. |
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). |
| Cassina, 2013 |
Italy 2000 - 2008 |
695 pregnant epileptic or non-epileptic women exposed to antiepileptic drugs therapy had been registered during the study period. | 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. |
26 / 867 | Chromosomal anomalies and genetic syndromes were excluded. |
| Charlton, 2011 |
UK 1990 - 2006 |
Mother-baby pairs whose mothers are identified as having epilepsy and who were, or had been, permanently registered at a general practionner practice considered by the database. | 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. |
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. |
| Charlton (Controls unexposed, disease free), 2017 |
UK 2000 - 2006 |
All pregnancies to women with epilepsy were identified in the database, where the pregnancy ended in a live delivery between the study period. And subsequently matched mother–child pairs without epilepsy from the same database. | 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. |
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. |
| Charlton (Controls unexposed, sick), 2017 |
UK 2000 - 2006 |
All pregnancies to women with epilepsy were identified in the database, where the pregnancy ended in a live delivery between the study period. | 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. |
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. |
| Cohen, 2019 |
USA 2000 - 2010 |
Deliveries during the study period in mothers 12-55 years of age with continuous enrollment from 3 months before pregnancy until 1 month after delivery. They are linked to live born infants in the database. | 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. |
-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. |
| Cohen-Israel, 2018 |
Israel 2004 – 2014 |
Women identified by a search of the Teratology Information Service, who gave birth at Rabin Medical Center–Beilinson Hospital between the study period and who were treated with lamotrigine. | 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. |
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. |
| Cummings, 2011 |
Northern Ireland 2002 - 2005 |
Infants and children born to mothers with epilepsy taking one of three antiepileptic drugs (lamotrigine, sodium valproate or carbamazepine) as monotherapy throughout pregnancy and enrolled on the UK Epilepsy and Pregnancy Register. And control children are identified from 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. |
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. |
| Dean, 2007 |
Scotland 1976 - 2002 |
Children of mothers who were prescribed antiepileptic drugs during a pregnancy between the study period were identified from hospital records. | 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. |
4 / 46 | |
| Diav-Citrin, 2017 |
Israel 1997 - 2008 |
Pregnant women who contacted (directly or through their healthcare provider) the Teratology Information Service regarding gestational lamotrigine exposure or exposures known to be nonteratogenic during the study period. | 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. |
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. |
| Dreier, 2021 |
Danemark, Finland, Iceland, Norway, Sweden 1996 (depends)-2017 |
Live-born singleton children from women with epilepsy in five Nordic countries. | 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. |
4679 / -9 | Unknown number in the exposed and unexposed group (abstract). |
| Dreier, 2023 |
Denmark, Finland, Iceland, Norway, and Sweden. 1996 - 2017 |
Live-born singleton children of mothers with epilepsy in Denmark (1997-2017), Finland (1996- 2016), Iceland (2004-2017), Norway (2005-2017), and Sweden (2006-2017). | 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. |
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. |
| Gopinath, 2015 |
India 2010 - 2012 |
All children of women with epilepsy born in the registry between April 1998 and December 2001. | 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. |
1 / 16 | Study design partly completed with Thomas et al., 2007 from the same registry. |
| He, 2017 |
China 2009 - 2015 |
Women with epilepsy who decided to settle on West China Second University Hospital of Sichuan University for antenatal examination and delivery. | 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. |
8 / 31 | Patients who developed epilepsy during pregnancy or after delivery were not included. |
| Holmes, 2008 |
North America and Canada 1997 - 2006 |
Women who were enrolled ('pure' or 'traditional' prospective women) in the registry during the study period, monotherapy antiepileptic drug-exposed and who had a liveborn infant, a stillborn infant, or a pregnancy terminated because of a fetal abnormality. | 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. |
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'. |
| Hosny, 2021 |
Egypt 2018 - 2020 |
Pregnant women with epilepsy enrolled within the first trimester recruited from the epilepsy outpatient clinic and several private epilepsy centers during the study period. | Pregnant women with epilepsy on lamotrigine monotherapy during the first trimester. |
unexposed, sick
Pregnant women with epilepsy with no treatment during the first trimester. |
3 / 21 | Each woman had one pregnancy during the study period. |
| Husebye (Controls unexposed, disease free), 2020 |
Norway 1999 - 2008 |
Children of mothers with and without epilepsy included in the MoBa cohort. | 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. |
112 / 113674 | |
| Husebye (Controls unexposed, sick), 2020 |
Norway 1999 - 2008 |
Children of mothers with and without epilepsy included in the MoBa cohort. | 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. |
112 / 388 | For this comparison group, results are only available according to folic acid intake. |
| Kasradze, 2017 |
Georgia 2001 |
Women with epilepsy whose children had reached ages from 36 to 72 months at the time of the study and registered in the registry. | 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 |
3 / 50 | Children with major congenital malformations were excluded from the study. |
| Kini, 2006 |
UK 1989 - 1999 |
375 children aged between 6 months and 16 years from 219 mothers with epilepsy exposed and not exposed to antiepileptic drugs during pregnancy attending epilepsy clinics or antenatal care between the study period. | 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. |
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. |
| Li, 2023 |
China 2009 - 2022 |
All pregnant participants occurring between 2009 and 2022 in the cohort of women with epilepsy (WWE) of childbearing age (20–45 years old) enrolled from 31 medical institutions. | Women with epilepsy (WWE) using Lamotrigine monotherapy during pregnancy. |
unexposed, sick
Women with epilepsy (WWE) not using antiseizure medications during pregnancy. |
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. |
| Mawer (Controls unexposed, disease free), 2010 |
UK 2000 - 2006 |
Women with epilepsy (WWE) and the healthy woman controls attending the same clinic. | 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. |
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. |
| Mawer (Controls unexposed, sick), 2010 |
UK 2000 - 2006 |
Midwives in the antenatal clinics approached each woman, who gave a history of epilepsy (n=231), whatever her stage of gestation. | 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. |
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. |
| Meador, 2023 |
USA 2012 - 2016 |
Children of pregnant women (aged 14–45 years) with and without epilepsy who were enrolled during pregnancy (≤20 weeks’ gestational age). | Children born to women with epilepsy treated with Lamotrigine monotherapy. |
unexposed, disease free
Children born to women without epilepsy. |
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). |
| Meador (Controls unexposed, disease free), 2020 |
US 2012 - 2016 |
Pregenant women with epilepsy were recruited primarily from the clinical populations at the 20 MONEAD sites, but also via referral from physicians, as well as self-referral. They were ages 14–45 years and ≤20 weeks gestational age. | 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. |
113 / 106 | |
| Meador (Controls unexposed, sick), 2020 |
US 2012 - 2016 |
Pregnant women with epilepsy were recruited primarily from the clinical populations at the 20 MONEAD sites, but also via referral from physicians, as well as self-referral. They were ages 14–45 years and ≤20 weeks gestational age. | 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. |
113 / 15 | |
| Miškov (Controls unexposed, disease free), 2016 |
Croatia 2003 - 2013 |
Pregnant women with epilepsy during the study period at the the Sestre milosrdnice University Hospital Center. | 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. |
37 / 147 | Includes all Miskov's 2010 outcomes. |
| Miškov (Controls unexposed, sick), 2016 |
Croatia 2003 - 2013 |
Pregnant women with epilepsy during the study period at the the Sestre milosrdnice University Hospital Center. | 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. |
37 / 4 | Includes all Miskov's 2010 outcomes. |
| Pekoz (Lamotrigine) (Epilepsy), 2023 |
Turkey 2014 - 2019 |
Pregnant women with epilepsy (PWWE) followed up at the participating centers during the study period, with a live birth. | Pregnant women with epilepsy (PWWE) receiving Lamotrigine as monotherapy. |
unexposed, sick
Pregnant women with epilepsy (PWWE), antiseizure medication free. |
141 / 43 | |
| Petersen (Controls unexposed NOS), 2017 |
UK 1995 - 2014 |
Pregnant women who gave live birth within the database. They were subsequently linked their clinical records to those of the children with the same household identifier if they were registered with the same general practice within 6 months after the children were born. | 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). |
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) |
| Petersen (Controls unexposed, sick), 2017 |
UK 1995 - 2014 |
Pregnant women who gave live birth within the database. They were subsequently linked their clinical records to those of the children with the same household identifier if they were registered with the same general practice within 6 months after the children were born. | 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). |
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) |
| Razaz (Controls unexposed, disease free), 2017 |
Sweden 1997- 2011 |
All singleton births at 22 or more completed gestational weeks. | 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. |
503 / 1424279 | |
| Razaz (Controls unexposed, sick), 2017 |
Sweden 1997- 2011 |
All singleton births at 22 or more completed gestational weeks. | 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. |
503 / 1868 | |
| Ren (Lamotrigine) (Epilepsy), 2023 |
Denmark 1997 - 2002 |
All live-born singletons in Denmark between the study period. | 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. |
166 / 3167 | Overlapping: this publication totally included the data of Elkjaer, 2018, for an higher academic grade => use of Ren 2023. |
| Rihtman, 2013 |
Israel 2001 - 2006 |
Pregnant or pre-pregnant women who contacted the Teratogen Information Service during the study period with queries concerning valproate or lamotrigine. | 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. |
42 / 52 | Exclusion criteria (all groups) were genetic abnormalities and full scale IQ of less than 70. |
| Thomas (Controls unexposed, disease free), 2021 |
India 1998 - 2015 |
All pregnancies with known outcomes in women with epilepsy enrolled in the registry during 1998 - 2013 and the diagnosis of epilepsy was confirmed before registration. | 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. |
38 / 319 | This external control group is only available in the 2017 publication. |
| Thomas (Controls unexposed, sick), 2021 |
India 1998 - 2019 |
All pregnancies with known outcomes in women with epilepsy enrolled in the registry during 1998 - 2013 and the diagnosis of epilepsy was confirmed before registration. | 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. |
50 / 340 | Study design completed with Thomas et al., 2017. |
| Trivedi, 2018 |
India 1998 - 2015 |
All women with epilepsy who had completed their pregnancies and enrolled in the registry between the study period. The diagnosis of epilepsy was confirmed before registration. | 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. |
48 / 178 | Study design partly completed with cites source Thomas et al., 2017. |
| Vajda, 2018 |
Australia 1999 - 2016 |
Pregnant women whether treated with antiepileptic drugs or left untreated in at least the first half of 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. |
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). |
| Vajda, 2019 |
Australia 1999 - 2018 |
Pregnant women taking antiepileptic drugs for any indications or not treated with antiepileptic drugs in at least the first half of 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. |
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. |
| Vajda, 2013 |
Australia 1999 - 2013 |
Pregnant women with epilepsy whether treated with antiepileptic drugs or left untreated or pregnant women taking antiepileptic drugs for other purposes. | 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. |
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. |
| Van Marter (Controls unexposed, disease free), 2021 |
US 2012 - 2016 |
Pregnant (gestational age of 20 weeks or less) women with epilepsy and healthy women who gave birth while enrolled in the study and their children who were enrolled at birth were included in the analysis population. | 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. |
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. |
| Van Marter (Controls unexposed, sick), 2021 |
US 2012 - 2016 |
Pregnant (gestational age of 20 weeks or less) women with epilepsy and healthy women who gave birth while enrolled in the study and their children who were enrolled at birth were included in the analysis population. | 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. |
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. |
| Vanya (Controls unexposed, sick), 2015 |
Hungary 2000 - 2014 |
All pregnant women with epilepsy who contacted the department between the study period. | 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). |
6 / 20 | Chromosomal anomalies and genetic syndromes were excluded from the study. The only exploitable outcome with a control group concern major congenital malformation. |
| Veiby (Controls unexposed, disease free), 2014 |
Norway 1999 - 2011 |
777,785 deliveries recorded in the database during the study period. | 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. |
593 / 771412 | We will only consider the subgroup of women exposed to antiepileptic drugs for the strict indication of epilepsy. |
| Veiby (Controls unexposed, disease free) a, 2013 |
Norway 1999 - 2008 |
108,976 children were registered in the Norwegian Mother and Child Cohort Study cohort from pregnant women attending routine ultrasonographic scanning recruited from hospitals and maternity units. | 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. |
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. |
| Veiby (Controls unexposed, disease free) b, 2013 |
Western Norway, Hordaland County. 1999 - 2008 |
107,072 pregnancies were registered in the MoBa cohort with a total of 108,976 children, constituting approximately 18 % of all births in Norway during this period. | 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. |
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. |
| Veiby (Controls unexposed, sick), 2014 |
Norway 1999 - 2011 |
777,785 deliveries recorded in the database during the study period. | 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. |
593 / 3773 | We will only consider the subgroup of women exposed to antiepileptic drugs for the strict indication of epilepsy. |
| Veiby (Controls unexposed, sick) a, 2013 |
Norway 1999 - 2008 |
108,976 children were registered in the Norwegian Mother and Child Cohort Study cohort from pregnant women attending routine ultrasonographic scanning recruited from hospitals and maternity units. | 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. |
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. |
| Veiby (Controls unexposed, sick) b, 2013 |
Western Norway, Hordaland County. 1999 - 2008 |
107,072 pregnancies were registered in the MoBa cohort with a total of 108,976 children, constituting approximately 18 % of all births in Norway during this period. | 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. |
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. |
| Videman, 2016 |
Finland 2009 - 2013 |
All pregnant women with epilepsy (PWE) treated with antiepileptic drugs living in Helsinki between the study period. Pregnant women with no antiepileptic drug or other brain-acting medication was recruited by a nurse during regular pregnancy monitoring in an outpatient clinic or by a newspaper announcement. | 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. |
8 / 67 | Study design partly completed with a previous article of Videman 2016. |
| Wiggs, 2020 |
Sweden 1996 - 2011 |
Children born in Sweden during the study period and to women with epilepsy any time before childbirth. | 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. |
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. |
| Study | Country Study period |
Case | Control | Sample size | Rmk |
|---|
4 studies, not fulfilled eligibility criteria, were excluded. See excluded tab for the list of these studies and reason of exclusion.
-
About
-
Master protocol
-
Browse exposition
-
RSS
-
Made with in Lyon
-
Contact us
-
Privacy policy
-
