| 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 |
|---|---|---|---|---|---|---|---|---|
|
Adab (Carbamazepine) 2004 |
UK 1989 - 1999 retrospective cohort |
The Mersey Regional Epilepsy Clinic, the Epilepsy Clinic at the Manchester Royal Infirmary and the antenatal clinic at St Mary’s Hospital. | Children exposed to carbamazepine monotherapy in utero and born to mothers with epilepsy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Children unexposed to antiepileptic drugs in utero and born to mothers with epilepsy. |
during pregnancy (anytime or not specified) | 94 / 101 | Vinten et al., 2009 is completely overlapped for the language and cognitive delay assessment (with more exposed pregnancies and better scale in this publication). | |
| A clinician conducted semi-structured interviews of mothers and clinical records were used to confirm information. | ||||||||
|
Adams (Carbamazepine) 2022 |
Boston, USA 1983-1993 1996-2000 retrospective cohort |
First at five maternity hospitals in the Boston area then during the second recruitment phase from a large health maintenance organization in the Boston area. | Children following gestational exposure to carbamazepine monotherapy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Children born to antiseizure medication-unexposed women with seizure disorders. |
during pregnancy (anytime or not specified) | 41 / 41 | Pregnant women with any exposure to other agents known to be of teratogenic concern during pregnancy were excluded. Additionally, children who were born prematurely were excluded from the study. | |
| Women were interviewed during the peri- and post- partum periods regarding multiple pregnancy characteristics and risks. | ||||||||
|
Al Bunyan (Carbamazepine) 1999 |
Saudi Arabia 1985 - 1994 retrospective cohort |
King Khalid University Hospital, Riyadh (KKUH) | Children whose epileptic mothers were exposed to carbamazepine monotherapy during the pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Children whose epileptic mothers did not take antiepileptic drugs during the pregnancy because their seizures were in remission and as a personal preference. |
during pregnancy (anytime or not specified) | 31 / 10 | The control group with the data of historical controls in Saudi Arabia isn't an adequate control group. | |
| The antenatal and perinatal records of the pregnant epileptic patients were examined. | ||||||||
|
Alsaadi (Controls exposed to LTG) 2020 |
United Arab Emirates 2008 - 2015 retrospective cohort |
The Obstetric Medicine Neurology Clinic at Corniche Hospital in Abu Dhabi, United Arab Emirates (UAE). | Women with epilepsy who were taking Carbamazepine in monotherapy during the first trimester of pregnancy. |
exposed to other treatment, sick
Women with epilepsy who were taking Lamotrigine in monotherapy during the first trimester of pregnancy. |
1st trimester | 29 / 13 | ||
| Retrospective review: exposure pre-pregnancy and at conception until registered at the clinic was recorded. | ||||||||
|
Alsaadi (Controls unexposed sick) 2020 |
United Arab Emirates 2008 - 2015 retrospective cohort |
The Obstetric Medicine Neurology Clinic at Corniche Hospital in Abu Dhabi, United Arab Emirates (UAE). | Women with epilepsy who were taking carbamazepine in monotherapy during the first trimester of pregnancy. |
unexposed, sick
Women with epilepsy who were not taking antiseizure drugs (ASDs) during the first trimester of pregnancy. |
1st trimester | 29 / 40 | ||
| Retrospective review: exposure pre-pregnancy and at conception until registered at the clinic was recorded. | ||||||||
|
Alsfouk (Carbamazepine) 2022 |
Riyadh and Jeddah, Saudi Arabia. 2005 - 2020 retrospective cohort |
The King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh and Jeddah, Saudi Arabia. | Epileptic mothers with carbamazepine monotherapy administered during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Epileptic mothers with lamotrigine monotherapy administered during pregnancy. |
during pregnancy (anytime or not specified) | 31 / 15 | ||
| Patients records. | ||||||||
|
Alsfouk (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2021 |
Riyadh and Jeddah, Saudi Arabia. 1993 - 2020 retrospective cohort |
The King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh and Jeddah, Saudi Arabia. | Epileptic mothers with carbamazepine monotherapy administered during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Epileptic mothers with lamotrigine monotherapy administered during pregnancy. |
during pregnancy (anytime or not specified) | 31 / 15 | ||
| Patients’ electronic and paper-based medical records. | ||||||||
|
Alsfouk (Carbamazepine) (Controls unexposed, sick) 2021 |
Riyadh and Jeddah, Saudi Arabia. 1993 - 2020 retrospective cohort |
The King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh and Jeddah, Saudi Arabia. | Epileptic mothers with carbamazepine 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) | 31 / 30 | ||
| Patients’ electronic and paper-based medical records. | ||||||||
|
AlSheikh (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2020 |
Saudi Arabia 2018 - 2019 prospective cohort |
King Fahd University Hospital | Fetuses/neonates of patients with active epilepsy who received carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Fetuses/neonates of patients with active epilepsy who received lamotrigine monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 5 / 20 | ||
| Information was collected through a structured questionnaire ‘Questionnaire for Investigation of Epilepsy in Tropical Countries'. | ||||||||
|
AlSheikh (Carbamazepine) (Controls unexposed, sick) 2020 |
Saudi Arabia 2018 - 2019 prospective cohort |
King Fahd University Hospital | Fetuses/neonates of patients with active epilepsy who received carbamazepine 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) | 5 / 8 | ||
| Information was collected through a structured questionnaire ‘Questionnaire for Investigation of Epilepsy in Tropical Countries'. | ||||||||
|
Arkilo (Carbamazepine) 2015 |
USA 2006 - 2011 retrospective cohort |
Minnesota Epilepsy Group, P.A. of United Hospital and Children's Hospitals and Clinics of Minnesota | Singleton whose epileptic mothers were exposed to carbamazepine monotherapy at any point during the pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Singleton whose epileptic mothers were exposed to lamotrigine monotherapy at any point during the pregnancy. |
during pregnancy (anytime or not specified) | 17 / 24 | ||
| Questionnaires were sent to women. | ||||||||
|
Artama (Carbamazepine) 2005 |
Finland 1991 - 2000 retrospective cohort (registry) |
The Medical Birth Register and the Social Insurance Institution (SII) of Finland. | Children whose epileptic mothers were exposed to carbamazepine as monotherapy during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Children whose epileptic mothers were untreated during the first trimester of pregnancy. |
1st trimester | 805 / 939 | ||
| Information on the antiepileptic drugs received during pregnancy was abstracted from medical records of the mothers with epilepsy. | ||||||||
|
Artama (Carbamazepine) (Controls exposed to Lamotrigine, 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 carbamazepine 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). |
exposed to other treatment, sick
Births in pregnant women with epilepsy exposed to lamotrigine in monotherapy 1 month prior to pregnancy and/or any time during pregnancy. |
3rd trimester, during pregnancy (anytime or not specified) | 1084 / 173 | Overlapping: For LBW and SGA: Artama 2013 included in a larger study published by Christensen 2024 ((longer study period, 5 countries and more pregnancies) => use of Christensen 2024 for these outcomes. | |
| The Special Refund Entitlement Register and the Register on Reimbursement Drugs contained informations on maternal drug treatment under ATC category N03. | ||||||||
|
Artama (Carbamazepine) (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 carbamazepine 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) | 1084 / 721948 | Overlapping: For LBW and SGA: Artama 2013 included in a larger study published by Christensen 2024 ((longer study period, 5 countries and more pregnancies) => use of Christensen 2024 for these outcomes. | |
| The Special Refund Entitlement Register and the Register on Reimbursement Drugs contained informations on maternal drug treatment under ATC category N03. | ||||||||
|
Artama (Carbamazepine) (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 carbamazepine 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) | 1084 / 1800 | Overlapping: For LBW and SGA: Artama 2013 included in a larger study published by Christensen 2024 ((longer study period, 5 countries and more pregnancies) => use of Christensen 2024 for these outcomes. | |
| The Special Refund Entitlement Register and the Register on Reimbursement Drugs contained informations on maternal drug treatment under ATC category N03. | ||||||||
|
Aydin (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2020 |
Turkey 2007 - 2017 retrospective cohort |
The Division of Perinatology, Department of Obstetrics and Gynecology, Hacettepe University | Pregnant women with epilepsy who received carbamazepine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Pregnant women with epilepsy who received lamotrigine in monotherapy during pregnancy. |
throughout pregnancy | 15 / 7 | 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. | ||||||||
|
Aydin (Carbamazepine) (Controls unexposed, sick) 2020 |
Turkey 2007 - 2017 retrospective cohort |
The Division of Perinatology, Department of Obstetrics and Gynecology, Hacettepe University | Pregnant women with epilepsy who received carbamazepine 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 | 15 / 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 (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2015 |
UK 2000 - 2004 prospective cohort |
11 National Health Service hospitals. | Children born to women with epilepsy and exposed to carbamazepine monotherapy in utero. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children born to women with epilepsy and exposed to lamotrigine monotherapy in utero. |
during pregnancy (anytime or not specified) | 59 / 36 | 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 (Carbamazepine) (Controls unexposed, disease free) 2015 |
UK 2000 - 2004 prospective cohort |
11 National Health Service hospitals. | Children born to women with epilepsy and exposed to carbamazepine 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) | 59 / 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 (Carbamazepine) (Controls unexposed, sick) 2015 |
UK 2000 - 2004 prospective cohort |
11 National Health Service hospitals. | Children born to women with epilepsy and exposed to carbamazepine 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) | 59 / 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. | ||||||||
|
Barqawi (Carbamazepine) 2005 |
Jordan Not specified prospective cohort |
King Hussein Medical Centre antenatal clinic. | Pregnant women treated for epilepsy received monotherapy with carbamazepine. |
unexposed, sick
Pregnant epileptic women who received no drugs because they refused treatment for fear of harming the fetus. |
during pregnancy (anytime or not specified) | 16 / 18 | ||
| All patients were on treatment before pregnancy and the serum level of the drugs was taken at each visit. | ||||||||
|
Barroso (Carbamazepine) 2015 |
Brazil 2000 - 2010 retrospective cohort |
The register of the Sao Paulo Hospital’s obstetrics center. | Newborns of epileptic parturients receiving carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Newborns of nonepileptic parturients who had deliveries immediately before and after the delivery of epileptic parturients. |
during pregnancy (anytime or not specified) | 12 / 316 | ||
| The complete medical records of both the mother and her newborn were later analyzed. | ||||||||
|
Battino 2024 |
Worldwide (47 countries) 1999 - 2022 prospective cohort |
The International Registry of Antiepileptic Drugs and Pregnancy (EURAP). | Pregnant women with epilepsy exposed to Carbamazepine monotherapy at the time of conception. |
exposed to other treatment, sick
Pregnant women with epilepsy exposed to lamotrigine monotherapy at the time of conception. |
early pregnancy | 2255 / 3584 | Overlapping/Update: (Major) malfo as a whole: Battino 2024 (1999-2022) updates Tomson 2018 (1999-2016), Tomson 2011, Jimenez 2020, Huber-Mollema 2019, Martinez 2009 and 2018 => Use of Battino 2024 for the 8 (plus 16 in eSupp) monotherapies studied. | |
| Reporting physicians collected information on drug therapy after each trimester. | ||||||||
|
Battino (Carbamazepine) 1999 |
Japan, Italy and Canada 1978 - 1991 prospective cohort |
Centers in Japan, Italy and Canada | Infants whose epileptic mothers were exposed to carbamazepine in monotherapy until term. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Infants whose epileptic mothers were not treated with antiepileptic drugs during pregnancy. |
throughout pregnancy | 158 / 36 | Each country has its own reference standards, then the data from the different countries are pooled. Exposition period deducted from Kaneko 1999. | |
| Mothers were seen by an obstetrician and neurologist at least every 4 weeks throughout pregnancy, and blood samples were taken for the measurement of antiepileptic drugs concentrations. | ||||||||
|
Battino (Carbamazepine) 1992 |
Italy 1977 - 1989 prospective cohort |
The Milan Collaborative Study on Epilepsy and Pregnancy, Italy. | Offspring of epileptic mothers treated with carbamazepine monotherapy during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Offspring of epileptic mothers with no antiepileptic drugs administered. |
1st trimester | 61 / 9 | The results for the malformations are already available in Canger 1999 (a more recent publication with a larger exposed group) except for minor malformations. | |
| At least every 4 weeks throughout the pregnancy blood samples were taken for measurement of antiepileptic drugs concentrations. | ||||||||
|
Bjørk (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2018 |
Norway 1999 - 2008 population based cohort propective |
The Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway. | Children of women with reported epilepsy and carbamazepine monotherapy use during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children of women with reported epilepsy and lamotrigine monotherapy use during pregnancy. |
during pregnancy (anytime or not specified) | 70 / 104 | ||
| Information on anti-epileptics use was obtained from the questionnaires completed by mothers during gestational weeks 17 to 19 (Q1) and 30 (Q2); and through the Medical Birth Registry of Norway. | ||||||||
|
Bjørk (Carbamazepine) (Controls exposed to Lamotrigine, 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 carbamazepine monotherapy prescription from her last menstrual period until birth. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Pregnacies in epileptic mothers filling at least one lamotrigine monotherapy prescription from her last menstrual period until birth. |
during pregnancy (anytime or not specified) | 2609 / 5073 | 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 (Carbamazepine) (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 carbamazepine 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) | 70 / 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 (Carbamazepine) (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 carbamazepine 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) | 2609 / 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 (Carbamazepine) (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 carbamazepine 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) | 70 / 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 (Carbamazepine) (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 carbamazepine 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) | 2609 / 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. | ||||||||
|
Blotiere (Carbamazepine) 2020 |
France 2011 - 2014 retrospective cohort (claims database) |
The French national health data system (SNDS) | Children born from mothers considered to be treated for epilepsy exposed to carbamazepine monotherapy with at least one dispensing between the beginning of the month preceding onset of pregnancy and its end. (Subgroup of exposure among the whole exposed group in the study). |
exposed to other treatment, sick
Children born from mothers considered to be treated for epilepsy exposed to lamotrigine monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 176 / 2108 | Children with a diagnosis of brain malformation (ICD-10 codes Q00 to Q04 and Q05.0 to Q05.4) diagnosed at the maternity unit are excluded. Results are extracted from Blotière et al. 2020 rather than Coste 2020 because they specified epilespy indication. | |
| Defned by at least one dispensing of the drug to the mother between the beginning of the month preceding onset of pregnancy and the end of pregnancy. Mother had used this drug as monotherapy, defined by the use of a single drug during pregnancy. | ||||||||
|
Borthen (Carbamazepine) (Controls exposed to Lamotrigine, 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 carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Births in women who gave a past or present history of epilepsy and exposed to lamotrigine monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 388 / 233 | ||
| 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 (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2011 |
Norway 1999 - 2006 retrospective cohort |
The Medical Birth Registry of Norway and the National Population Registry. | Women with epilepsy using carbamazepine as monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Women with epilepsy using lamotrigine as monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 28 / 30 | 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 outcomes '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 (Carbamazepine) (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 carbamazepine 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) | 388 / 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 (Carbamazepine) (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 carbamazepine 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) | 28 / 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 outcomes '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 (Carbamazepine) (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 carbamazepine 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) | 388 / 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 (Carbamazepine) (Controls unexposed, sick) 2011 |
Norway 1999 - 2006 retrospective cohort |
The Medical Birth Registry of Norway and the National Population Registry | Women with epilepsy using carbamazepine 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) | 28 / 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 outcomes '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 (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2013 |
UK 2000 - 2004 prospective cohort |
The Liverpool and Manchester Neurodevelopment Group (LMNDG) | Children born to epileptic mothers exposed to carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children born to epileptic mothers exposed to lamotrigine monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 59 / 36 | 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 (Carbamazepine) (Controls exposed to Lamotrigine, 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 carbamazepine monotherapy in utero. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children born to mothers with epilepsy exposed to lamotrigine monotherapy in utero. |
during pregnancy (anytime or not specified) | 48 / 34 | 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 (Carbamazepine) (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 carbamazepine 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) | 48 / 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 (Carbamazepine) (Controls unexposed, disease free) 2013 |
UK 2000 - 2004 prospective cohort |
The Liverpool and Manchester Neurodevelopment Group (LMNDG) | Children born to epileptic mothers exposed to carbamazepine 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) | 59 / 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 (Carbamazepine) (Controls unexposed, sick) 2013 |
UK 2000 - 2004 prospective cohort |
The Liverpool and Manchester Neurodevelopment Group (LMNDG) | Children born to epileptic mothers exposed to carbamazepine 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) | 59 / 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 (Carbamazepine) (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 carbamazepine 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) | 48 / 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 (Carbamazepine) (Epilepsy) (Controls exposed to LTG) 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 Carbamazepine during pregnancy. |
exposed to other treatment, sick
Pregnant women with epilepsy exposed to Lamotrigine during pregnancy. |
during pregnancy (anytime or not specified) | 27 / 106 | ||
| 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). | ||||||||
|
Bromley (Carbamazepine) (Epilepsy) (Controls unexposed, sick) 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 Carbamazepine during pregnancy. |
unexposed, sick
Pregnant women with epilepsy and with no antiseizure medication. |
during pregnancy (anytime or not specified) | 27 / 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). | ||||||||
|
Burja (Carbamazepine) (Controls unexposed, disease free) 2006 |
Slovenia 1998 - 2002 retrospective cohort (registry) |
Hospital neonatal and obstetric records at the Maribor Teaching Hospital Department of Perinatology, the Regional Hospital Discharge Registry and the the Perinatal Statistical Database of Slovenia. | Newborn in women diagnosed as having epilepsy who had taken carbamazepine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Newborn in a randomized sample of pregnant women who had received no prescription at all (with the only diagnosis 'vaginal delivery') in the same period. |
during pregnancy (anytime or not specified) | 19 / 211 | ||
| Hospital neonatal and obstetric records at the MariborTeaching Hospital Department of Perinatology. | ||||||||
|
Burja (Carbamazepine) (Controls unexposed, sick) 2006 |
Slovenia 1998 - 2002 retrospective cohort (registry) |
Hospital neonatal and obstetric records at the Maribor Teaching Hospital Department of Perinatology, the Regional Hospital Discharge Registry and the the Perinatal Statistical Database of Slovenia. | Newborn in women diagnosed as having epilepsy who had taken carbamazepine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Newborn in women diagnosed as having epilepsy who didn't take antiepileptic drugs during pregnancy. |
during pregnancy (anytime or not specified) | 19 / 32 | ||
| Hospital neonatal and obstetric records at the MariborTeaching Hospital Department of Perinatology. | ||||||||
|
Campbell (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2014 |
UK and Ireland 1996 - 2012 prospective cohort |
The United Kingdom Epilepsy and Pregnancy Register | Infants of women with epilepsy exposed to carbamazepine in monotherapy during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants of women with epilepsy exposed to lamotrigine in monotherapy during the first trimester. |
1st trimester | 1718 / 2198 | Morrow et al., 2009 specific malformations results and major malformations results from Morrow et al., 2006 and Campbell et al., 2013 are completely overlapped by this publication. Study design was partly completed with Morrow 2006. | |
| 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. | ||||||||
|
Campbell (Carbamazepine) (Controls unexposed, sick) 2014 |
UK and Ireland 1996 - 2012 prospective cohort |
The United Kingdom Epilepsy and Pregnancy Register | Infants of women with epilepsy exposed to carbamazepine 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 | 1718 / 541 | Study design was partly completed with Morrow 2006. Morrow et al., 2006 major malformations results are completely overlapped by this publication with a larger exposed group. | |
| 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. | ||||||||
|
Canger (Carbamazepine) 1999 |
Italy 1977 - 1996 prospective cohort |
The Epilepsy Center of the San Paolo Hospital in Milan or other in the Lombardy region, Italy | Infants of epileptic mothers exposed to carbamazepine monotherapy during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Infants of epileptic mothers unexposed to antiepileptic drugs during pregnancy. |
1st trimester | 113 / 25 | Only the first pregnancies of each of the 517 women were included in the analysis. | |
| The patients received monthly obstetric and neurologic examinations, and antiepileptic drug blood levels were tested monthly. | ||||||||
|
Cassina (Carbamazepine) (Controls exposed to Lamotrigine, sick) 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 carbamazepine 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). |
exposed to other treatment, sick
Children whose epileptic mothers were treated with lamotrigine in monotherapy between the 5th and the 14th week after their last menstrual period. |
1st trimester | 102 / 26 | 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. | ||||||||
|
Cassina (Carbamazepine) (Controls unexposed, disease free) 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 carbamazepine 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 | 102 / 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 (Carbamazepine) (Controls exposed to Lamotrigine, 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 carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Mother–child pairs where the mother had epilepsy and received lamotrigine monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 148 / 122 | 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 (Carbamazepine) (Controls exposed to Lamotrigine, sick) 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 carbamazepine monotherapy exposure during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants of mother-baby pairs who had lamotrigine monotherapy exposure during the first trimester. |
1st trimester | 311 / 98 | 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 (Carbamazepine) (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 carbamazepine 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) | 148 / 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 (Carbamazepine) (Controls unexposed, sick) 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 carbamazepine 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 | 311 / 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 (Carbamazepine) (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 carbamazepine 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) | 148 / 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. | ||||||||
|
Christensen (Carbamazepine) (Epilepsy) (Controls exposed to LTG) 2024 |
Denmark, Finland, Iceland, Norway, and Sweden 1996 - 2017 population based cohort retrospective |
Nordic population-based cohort study including register data from Denmark, Finland, Iceland, Norway, and Sweden–the SCAN-AED project. | Children of mothers with epilepsy who had redeemed at least one prescription of Carbamazepine monotherapy from 30 days before the first day of the last menstrual period to the date of birth (i.e., the exposure period). |
exposed to other treatment, sick
Children of mothers who had redeemed at least one prescription of Lamotrigine monotherapy from 30 days before the first day of the last menstrual period to the date of birth (i.e., the exposure period). |
during pregnancy (anytime or not specified) | 2669 / 5299 | Overlapping: For LBW and SGA: Christensen 2024 totally included Artama 2013 => use of Christensen 2024 for these outcomes (longer study period, 5 countries and more pregnancies). | |
| Prenatal exposure was identified via national prescription registers. These registers contain the Anatomical Therapeutic Chemical (ATC) classification code (www.whocc.no) and the date of dispensing. | ||||||||
|
Christensen (Carbamazepine) (Epilepsy) (Controls unexposed, general population) 2024 |
Denmark, Finland, Iceland, Norway, and Sweden 1996 - 2017 population based cohort retrospective |
Nordic population-based cohort study including register data from Denmark, Finland, Iceland, Norway, and Sweden–the SCAN-AED project. | Children of mothers with epilepsy who had redeemed at least one prescription of Carbamazepine monotherapy from 30 days before the first day of the last menstrual period to the date of birth (i.e., the exposure period). |
unexposed, sick
Children of mothers with epilepsy who had not redeemed prescription of anti-seizure medication. |
during pregnancy (anytime or not specified) | 2669 / 22227 | Overlapping: For LBW and SGA: Christensen 2024 totally included Artama 2013 => use of Christensen 2024 for these outcomes (longer study period, 5 countries and more pregnancies). | |
| Prenatal exposure was identified via national prescription registers. These registers contain the Anatomical Therapeutic Chemical (ATC) classification code (www.whocc.no) and the date of dispensing. | ||||||||
|
Cohen (Carbamazepine) 2013 |
USA and UK 1999 - 2004 prospective cohort |
25 epilepsy centers in the USA and UK. | Infants of women exposed to carbamazepine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants of women exposed to lamotrigine in monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 53 / 61 | A nonexposed control group was not included. | |
| They obtained information from the patients, their seizure or medication diary, or review of their medical records. | ||||||||
|
Cohen (Carbamazepine) 2011 |
UK and USA 1999 - 2004 prospective cohort |
25 epilepsy centers in the USA and UK. | Infants of women exposed to carbamazepine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants of women exposed to lamotrigine in monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 61 / 76 | A nonexposed control group was not included. Total number of children exposed to each antiepileptic drugs is not specified, so the number of mothers is reported instead. | |
| They obtained information from the patients, their seizure or medication diary, or review of their medical records. | ||||||||
|
Cohen (Carbamazepine) (Controls exposed to Lamotrigine, sick) 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 carbamazepine monotherapy (no other mood stabilizers or other anticonvulsants) in the first 20 weeks of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
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. |
early pregnancy | -9 / -9 | 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 (Carbamazepine) (Controls unexposed NOS) 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 carbamazepine 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. | ||||||||
|
Cummings (Carbamazepine) (Controls exposed to Lamotrigine, sick) 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 carbamazepine as monotherapy throughout pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children born to epileptic mothers taking lamotrigine as monotherapy throughout pregnancy. |
throughout pregnancy | 49 / 35 | 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. | ||||||||
|
Cummings (Carbamazepine) (Controls unexposed, disease free) 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 carbamazepine 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 | 49 / 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. | ||||||||
|
D'Souza (Carbamazepine) (Controls unexposed, disease free) 1991 |
UK 1980 - 1982 prospective cohort |
Antenatal clinic of St Mary's Hospital. | Infants born to epileptic mothers treated with carbamazepine alone throughout pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Infants born to mothers without epilepsy not taking any drugs regularly. |
throughout pregnancy | 3 / 62 | ||
| Every two weeks, clinical assessment of seizure control, and adjustment of anticonvulsant dosage in accordance with serum drug concentration or clinical response. | ||||||||
|
D'Souza (Carbamazepine) (Controls unexposed, sick) 1991 |
UK 1980 - 1982 prospective cohort |
Antenatal clinic of St Mary's Hospital. | Infants born to epileptic mothers treated with carbamazepine alone throughout pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Infants whose mothers had a history of epilepsy but received no drugs during pregnancy. |
throughout pregnancy | 3 / 8 | ||
| Every two weeks, clinical assessment of seizure control, and adjustment of anticonvulsant dosage in accordance with serum drug concentration or clinical response. | ||||||||
|
Dean (Carbamazepine) 2002 |
Scotland 1976 - 2000 retrospective cohort |
Aberdeen Maternity Hospital, the antenatal clinic and postnatal wards. | Children whose mothers took carbamazepine monotherapy in pregnancy and continued beyond the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Sibs of exposed cases not exposed to antiepileptic drugs in utero. Either the mothers had epilepsy or the child was born before epilepsy developed. |
at least 1st trimester | 70 / 38 | The data for major congenital malformations include all pregnancies surviving into the second trimester. The vast majority of the mothers were treated for epilepsy. Developmental delay is already assessed in Dean et al. 2007. | |
| A structured interview was carried out by a trained research nurse using questionnaires. | ||||||||
|
Dean (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2007 |
Scotland 1976 - 2002 retrospective cohort |
Aberdeen Maternity Hospital. | Children whose epileptic mothers were exposed to carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children whose epileptic mothers were exposed to lamotrigine monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 77 / 4 | A previous publication (Dean 2002) gives a better review of the major malformations. | |
| A trained research nurse undertook interviews recording antiepileptic drugs use in each pregnancy. Maternal antiepileptic drugs dose was verified from case records where possible. | ||||||||
|
Dean (Carbamazepine) (Controls unexposed, sick) 2007 |
Scotland 1976 - 2002 retrospective cohort |
Aberdeen Maternity Hospital. | Children whose epileptic mothers were exposed to carbamazepine 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) | 77 / 46 | A previous publication (Dean 2002) gives a better review of the major malformations. | |
| A trained research nurse undertook interviews recording antiepileptic drugs use in each pregnancy. Maternal antiepileptic drugs dose was verified from case records where possible. | ||||||||
|
Deshmukh (Carbamazepine) 2016 |
North America and Canada 1997 - 2010 prospective cohort |
The North American Antiepileptic Drug Pregnancy Register. | Children of women who used carbamazepine as monotherapy throughout pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children of women who used lamotrigine as monotherapy throughout pregnancy. |
throughout pregnancy | 97 / 104 | Study design completed with cited source [28]. Major malformation rate of this sample is already assessed in Hernández-Díaz 2012. | |
| Women were questioned with a computer-assisted telephone interview 3 times. | ||||||||
|
Diav-Citrin (Carbamazepine) 2001 |
Israel 1989 - 1999 prospective cohort |
The Israeli Teratogen Information Service | Pregnant women with at least first trimester exposure to carbamazepine for an epileptic indication in monotherapy. |
unexposed (general population or NOS)
Callers women who had been counselled (over a similar timeframe) during pregnancy in regard to exposures known to be nonteratogenic or foetotoxic. |
at least 1st trimester | 108 / 210 | ||
| Details of exposure were collected during pregnancy at the initial contact before pregnancy outcome was known, using a structured questionnaire. | ||||||||
|
Díaz-Romero (Carbamazepine) 1999 |
Mexico 1993 - 1996 cohort |
The Epilepsy Clinic of the National Institute of Perinatology. | Full-term eutrophic newborns of epileptic mothers exposed to only carbamazepine during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Offspring of epileptic women without seizures during pregnancy and without exposure to any drug. |
during pregnancy (anytime or not specified) | 26 / 8 | All newborns in the intensive care unit, and those with congenital malformations with a different specific recognizable etiology were excluded. | |
| Not specified | ||||||||
|
Dreier (Carbamazepine) (Epilepsy) (Controls exposed to LTG) 2023 |
Denmark, Finland, Iceland, Norway, and Sweden. 1996 - 2017 population based cohort propective |
A prospective, population-based register study within the SCAN-AED project, based on children born in Denmark, Finland, Iceland, Norway, and Sweden. | Children prenatally exposed to Carbamazepine monotherapy, i.e whose mother had redeemed 1 or more prescriptions during the exposure window, which was defined as 30 days before the first day of the last menstrual period (estimated using gestational age in days at birth) until the date of birth. |
exposed to other treatment, sick
Children prenatally exposed to Lamotrigine monotherapy, i.e whose mother had redeemed 1 or more prescriptions during the exposure window, which was defined as 30 days before the first day of the last menstrual period (estimated using gestational age in days at birth) until the date of birth. |
during pregnancy (anytime or not specified) | 2665 / 5288 | 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 (Carbamazepine) (Epilepsy) (Controls unexposed, sick) 2023 |
Denmark, Finland, Iceland, Norway, and Sweden. 1996 - 2017 population based cohort propective |
A prospective, population-based register study within the SCAN-AED project, based on children born in Denmark, Finland, Iceland, Norway, and Sweden. | Children prenatally exposed to Carbamazepine 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) | 2665 / 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. | ||||||||
|
Endo (Carbamazepine) (Controls unexposed, disease free) 2004 |
Japan 1991 - 2000 retrospective cohort |
Yokohama City University Hospital. | Newborns of epileptic mothers who take carbamazepine monotherapy for epilepsy throughout pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Newborns of nonepileptic mothers. |
throughout pregnancy | 8 / 656 | 30 (83.3%) cases of 36 pregnancies continued taking drugs throughout pregnancy. Three (8.3%) patients discontinued after week 13 of pregnancy. Some results do not coincide between table 1 and table 2 and are therefore not reported. | |
| Medical records. | ||||||||
|
Endo (Carbamazepine) (Controls unexposed, sick) 2004 |
Japan 1991 - 2000 retrospective cohort |
Yokohama City University Hospital. | Newborns of epileptic mothers who take carbamazepine monotherapy for epilepsy throughout pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Newborns of epileptic mothers who had not taken any antiepileptic drugs. |
throughout pregnancy | 8 / 1 | 30 (83.3%) cases of 36 pregnancies continued taking drugs throughout pregnancy. Three (8.3%) patients discontinued after week 13 of pregnancy. Some results do not coincide between table 1 and table 2 and are therefore not reported. | |
| Medical records. | ||||||||
|
Eriksson (Carbamazepine) 2005 |
Finland 1989 - 2000 prospective cohort |
Community-based pregnancy registry at the Kuopio University Hospital. | Pregnancies in which the mother had used carbamazepine during conception and throughout pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnancies in which the mother reported having previous history of epilepsy but had not needed antiepileptic drugs during pregnancy. |
throughout pregnancy | 13 / 13 | The period of exposure is specified in Viinikainen 2006. The cognitive delay of this sample at the same age is already assessed in Viinikainen 2006, thus, not reported here. | |
| The medical records of the children and their mothers were reviewed separately by two of the other authors. | ||||||||
|
Ertürk Çetin (Epilepsy) (Carbamazepine) 2024 |
Turkey Not specified. prospective cohort |
Two university hospital epilepsy centers, Istanbul, Turkey. | Pregnant women with a diagnosis of epilepsy who were continuously treated with Carbamazepine monotherapy from conception throughout pregnancy. |
exposed to other treatment, sick
Pregnant women with a diagnosis of epilepsy who were continuously treated with Lamotrigine monotherapy from conception throughout pregnancy. |
throughout pregnancy | 4 / 9 | ||
| Patients with a diagnosis of epilepsy and who become pregnant were selected and followed prospectively. All patients were compliant with the treatment. The compliance was assessed through clinical interviews (no details). | ||||||||
|
Forsberg (Carbamazepine) (Controls unexposed NOS) 2011 |
Sweden 1973 - 1986 retrospective cohort (registry) |
Swedish Medical Birth Register, the Patient Register (formerly Hospital Discharge Register), a local study at South Hospital, Stockholm and The Swedish School Mark Registry. | Children identified with maternal epilepsy who had been exposed to carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
All other children born in Sweden between the study period. |
during pregnancy (anytime or not specified) | 243 / 1307083 | These analyses were made after exclusion of children with a diagnosis of a congenital malformation. | |
| The Medical Birth Register is built from data in standardized medical records. To identify the use of anticonvulsants, the original medical documents were retrieved and scrutinized and the information was added to the records of deliveries from women with epilepsy. | ||||||||
|
Forsberg (Carbamazepine) (Controls unexposed, sick) 2011 |
Sweden 1973 - 1986 retrospective cohort (registry) |
Swedish Medical Birth Register, the Patient Register (formerly Hospital Discharge Register), a local study at South Hospital, Stockholm and The Swedish School Mark Registry. | Children identified with maternal epilepsy who had been exposed to carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Children identified with maternal epilepsy but no use of antiepileptic drug. |
during pregnancy (anytime or not specified) | 243 / -9 | These analyses were made after exclusion of children with a diagnosis of a congenital malformation. Number of children identified with maternal epilepsy but no use of antiepileptic drug not specified. | |
| The Medical Birth Register is built from data in standardized medical records. To identify the use of anticonvulsants, the original medical documents were retrieved and scrutinized and the information was added to the records of deliveries from women with epilepsy. | ||||||||
|
Gaily (Carbamazepine) (Controls unexposed, disease free) 2004 |
Helsinki 1989 - 1994 prospective cohort |
The Department of Obstetrics and Gynecology of the Helsinki University Central Hospital (HUCS) | Children of mothers with epilepsy exposed to carbamazepine monotherapy during the second half of the pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
The next child born at the same hospital to a nonepileptic mother and unexposed to antiepileptic drugs. |
2nd and/or 3rd trimester | 86 / 141 | ||
| Data have been collected prospectively and entered to a database maintained by one of the authors. | ||||||||
|
Gaily (Carbamazepine) (Controls unexposed, sick) 2004 |
Helsinki 1989 - 1994 prospective cohort |
The Department of Obstetrics and Gynecology of the Helsinki University Central Hospital (HUCS) | Children of mothers with epilepsy exposed to carbamazepine monotherapy during the second half of the pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Children of mothers with epilepsy with no drug exposure. |
2nd and/or 3rd trimester | 86 / 45 | ||
| Data have been collected prospectively and entered to a database maintained by one of the authors. | ||||||||
|
Guveli (Epilepsy) 2017 |
Turkey 1990 - 2006 retrospective cohort |
Departments of Istanbul Faculty of Medicine, Istanbul University, Turkey. | Children born from mothers with epilepsy on Carbamazepine monotherapy during pregnancy. |
unexposed, sick
Children born from mothers were not exposed to Antiepileptic drugs (AED) during pregnancy. |
during pregnancy (anytime or not specified) | 24 / 26 | ||
| The clinical data of patients (dosages of AEDs used during pregnancy) were recorded retrospectively from patient files. | ||||||||
|
Hao (Controls exposed to LTG) 2025 |
China Not specified. prospective cohort |
The West China Registry of Pregnancy in Epilepsy (WCRP_ Epi), an ongoing prospective multicenter cohort study based in Sichuan Province, Southwest China. | Pregnant women with confirmed epilepsy that used carbamazepine monotherapy during the first trimester of pregnancy. |
exposed to other treatment, sick
Pregnant women with confirmed epilepsy that used lamotrigine monotherapy during the first trimester of pregnancy. |
1st trimester | 52 / 84 | Use of monotherapy data (table 2). | |
| Treatment information was collected through case report forms mainly through face-to-face visits in the neurology clinic or remotely by video/telephone calls, at each trimester of pregnancy. | ||||||||
|
Hao (Controls unexposed, sick) 2025 |
China Not specified. prospective cohort |
The West China Registry of Pregnancy in Epilepsy (WCRP_ Epi), an ongoing prospective multicenter cohort study based in Sichuan Province, Southwest China. | Pregnant women with confirmed epilepsy that used carbamazepine monotherapy during the first trimester of pregnancy. |
unexposed, sick
Pregnant women with confirmed epilepsy and no anti-seizure medication use during the first trimester. |
1st trimester | 52 / 261 | Use of monotherapy data (table 2). | |
| Treatment information was collected through case report forms mainly through face-to-face visits in the neurology clinic or remotely by video/telephone calls, at each trimester of pregnancy. | ||||||||
|
Hernández-Díaz (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2012 |
North America and Canada 1997 - 2011 prospective cohort |
The North American Antiepileptic Drug Pregnancy Register and the Active Malformations Surveillance Program. | Infants of pregnant women who used carbamazepine for epileptic indication as monotherapy, during the first 4 lunar months after the last menstrual period (equal 16 weeks of gestation). (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants of pregnant women who used lamotrigine for mixed indications as monotherapy, during the first 4 lunar months after the last menstrual period (equal 16 weeks of gestation). |
1st trimester | 1033 / 1562 | Less than 90% of women are taking Lamotrigine for epilepsy. | |
| Women were questioned with a computer-assisted telephone interview 3 times. | ||||||||
|
Hernández-Díaz (Carbamazepine) (Controls unexposed, disease free) 2012 |
North America and Canada 1997 - 2011 prospective cohort |
The North American Antiepileptic Drug Pregnancy Register and the Active Malformations Surveillance Program. | Infants of pregnant women who used carbamazepine for epileptic indication as monotherapy, during the first 4 lunar months after the last menstrual period (equal 16 weeks of gestation). (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Infants of pregnant women, not taking an antiepileptic drug and without epilepsy, who were recruited from among the friends and family members of the enrolled women taking an antiepileptic drug. |
1st trimester | 1033 / 442 | ||
| Women were questioned with a computer-assisted telephone interview 3 times. | ||||||||
|
Holmes (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2011 |
North America and Canada 1997 - 2011 prospective cohort |
The North American Antiepileptic Drug Pregnancy Register and the Active Malformations Surveillance Program. | Infants of pregnant women who used carbamazepine as monotherapy, during the first 4 lunar months after the last menstrual period (equal 16 weeks of gestation). (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants of pregnant women who used lamotrigine as monotherapy, during the first 4 lunar months after the last menstrual period (equal 16 weeks of gestation). |
1st trimester | 674 / 1118 | Less than 90% of women are taking Lamotrigine for epilepsy. Major malformations results are already assessed in Hernández-Díaz 2012 with more exposed pregnancies. | |
| Women were questioned with a computer-assisted telephone interview 3 times. | ||||||||
|
Holmes (Carbamazepine) (Controls unexposed, disease free) 2001 |
United States 1986 - 1993 retrospective cohort |
Brigham and Women’s Hospital, Beth Israel Hospital, St. Margaret’s Hospital, St. Elizabeth’s Hospital, and Newton–Wellesley Hospital. | Infants exposed in utero to carbamazepine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Infants unexposed in utero to any antiepileptic drugs born to women with no history of seizure and closest in time from the corresponding exposed children. |
during pregnancy (anytime or not specified) | 58 / 508 | 9% are exposed for other indications (not specified per type of AED). | |
| Women are interviewed and completed questionnaires administered by a research assistant. | ||||||||
|
Holmes (Carbamazepine) (Controls unexposed, disease free) 2011 |
North America and Canada 1997 - 2011 prospective cohort |
The North American Antiepileptic Drug Pregnancy Register and the Active Malformations Surveillance Program. | Infants of pregnant women who used carbamazepine as monotherapy, during the first 4 lunar months after the last menstrual period (equal 16 weeks of gestation). (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Infant of pregnant women not taking an antiepileptic drugs and without epilepsy who had been recruited among the friends and relatives of antiepileptic drugs-exposed participants. |
1st trimester | 674 / 209 | Major malformations results are already assessed in Hernández-Díaz 2012 with more exposed pregnancies. | |
| Women were questioned with a computer-assisted telephone interview 3 times. | ||||||||
|
Holmes (Carbamazepine) (Controls unexposed, sick) 2001 |
United States 1986 - 1993 retrospective cohort |
Brigham and Women’s Hospital, Beth Israel Hospital, St. Margaret’s Hospital, St. Elizabeth’s Hospital, and Newton–Wellesley Hospital. | Infants exposed in utero to carbamazepine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Infants unexposed in utero to any antiepileptic drugs born to women with a history of seizure. |
during pregnancy (anytime or not specified) | 58 / 98 | 9% are exposed for other indications (no specified per type of AED). | |
| Women are interviewed and completed questionnaires administered by a research assistant. | ||||||||
|
Hosny (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2021 |
Egypt 2018 - 2020 prospective cohort |
Kasr Al-Ainy Hospital, Cairo University, Egypt | Pregnant women with epilepsy on carbamazepine monotherapy during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Pregnant women with epilepsy on lamotrigine monotherapy during the first trimester. |
1st trimester | 31 / 1 | Each woman had one pregnancy during the study period. The correct figures were sent by the authors. | |
| The following data were evaluated: seizure control 6 months before pregnancy, seizure control during each trimester, type and dose of ASMs at conception. | ||||||||
|
Hosny (Carbamazepine) (Controls unexposed, sick) 2021 |
Egypt 2018 - 2020 prospective cohort |
Kasr Al-Ainy Hospital, Cairo University, Egypt | Pregnant women with epilepsy on carbamazepine monotherapy during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnant women with epilepsy with no treatment during the first trimester. |
1st trimester | 31 / 21 | Each woman had one pregnancy during the study period. The correct figures were sent by the authors. | |
| The following data were evaluated: seizure control 6 months before pregnancy, seizure control during each trimester, type and dose of ASMs at conception. | ||||||||
|
Huber-Mollema (Carbamazepine) 2019 |
The Netherlands 2015 - 2018 prospective cohort |
The Dutch European Registry of Antiepileptic Drugs and Pregnancy (EURAP) | Children age between 6 years and 7 years 11 months of mothers with epilepsy exposed to carbamazepine monotherapy starting before conception and continuing during the entire pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children age between 6 years and 7 years 11 months of mothers with epilepsy exposed to lamotrigine monotherapy starting before conception and continuing during the entire pregnancy. |
throughout pregnancy | 37 / 88 | The method for measuring exposure is not specified, although the EURAP registry method was thought to be used. Overlapping: For malformations: data totally included in Battino 2024 => not reported here. | |
| The data concerning treatment at the time of conception are obtained by the physicians responsible for the women’s care and transferred online. | ||||||||
|
Husebye (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2020 |
Norway 1999 - 2008 population based cohort propective |
Norwegian Mother and Child Cohort Study (MoBa) and The Medical Birth Registry of Norway. | Children of mothers with epilepsy exposed to carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children of mothers with epilepsy exposed to lamotrigine monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 72 / 112 | ||
| Information on the anti-epileptic (AED) use was obtained from the maternal questionnaires completed during gesta week 17–19 and week 30 and from Medical Birth Registry data. AEDs plasma concentrations were analysed in maternal and umbilical cord samples (73%) and were detected in 93% of children. | ||||||||
|
Husebye (Carbamazepine) (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 carbamazepine 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) | 72 / 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 (Carbamazepine) (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 carbamazepine 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) | 72 / 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. | ||||||||
|
Hvas (Carbamazepine) (Controls unexposed, disease free) 2000 |
Denmark 1989 - 1997 retrospective cohort |
Department of Obstetrics and Gynaecology at Aarhus University Hospital. | Children of women with epilepsy exposed to carbamazepine monotherapy 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 chronic disease. |
1st trimester | 37 / 24094 | ||
| Women completed a questionnaire. They were categorised as users or nonusers of anticonvulsant drugs, by self-reported daily intake of any anticonvulsant drug during the first trimester. | ||||||||
|
Hvas (Carbamazepine) (Controls unexposed, sick) 2000 |
Denmark 1989 - 1997 retrospective cohort |
Department of Obstetrics and Gynaecology at Aarhus University Hospital. | Children of women with epilepsy exposed to carbamazepine monotherapy 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 without treatment. |
1st trimester | 37 / 106 | ||
| Women completed a questionnaire. They were categorised as users or nonusers of anticonvulsant drugs, by self-reported daily intake of any anticonvulsant drug during the first trimester. | ||||||||
|
Kaaja (Carbamazepine) 2003 |
Finland 1980 - 1998 prospective cohort |
Department of Obstetrics and Gynecology from Helsinki University Central Hospital | Infants whose epileptic mothers took carbamazepine monotherapy during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Infants whose epileptic mothers didn't take any antiepileptic drugs during the first trimester. |
1st trimester | 363 / 239 | ||
| Follow-up of the pregnant women with epilepsy included assessment of serum concentration of antiepileptic drugs at the end of the first trimester. | ||||||||
|
Kaneko (Carbamazepine) 1999 |
Japan, Italy and Canada. 1978 - 1991 prospective cohort |
Centers from Japan (Hirosaki, Fukushima, Nagoya, and Nagasaki), Italy (Milan), and Canada (Montreal). | Offspring whose epileptic mothers were under carbamazepine monotherapy until term. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Offspring from epileptic mothers without antiepileptic drug exposure until term. |
throughout pregnancy | 158 / 98 | Details about the design were completed thanks to Battino et al., 1999 publication. Kaneko 1999 overlapped with Kaneko 1986, 1988, 1992, Oguni 1992, Dansky 1982, Canger 1999 and Battino 1992. | |
| Mothers were seen by an obstetrician and neurologist at least every 4 weeks throughout pregnancy, and blood samples were taken for the measurement of antiepileptic drugs concentrations. | ||||||||
|
Kasradze (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2017 |
Georgia 2001 prospective cohort |
The Georgian National Antiepileptic drugs-Pregnancy Registry (the Georgian registry of EURAP). | Children born to epileptic mothers exposed to carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children born to epileptic mothers exposed to lamotrigine monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 16 / 3 | 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. | ||||||||
|
Kasradze (Carbamazepine) (Controls unexposed, disease free) 2017 |
Georgia 2001 prospective cohort |
The Georgian National Antiepileptic drugs-Pregnancy Registry (the Georgian registry of EURAP). | Children born to epileptic mothers exposed to carbamazepine 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) | 16 / 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. | ||||||||
|
Katz (Carbamazepine) 2001 |
USA 1990 - 2000 retrospective cohort |
Department of Neurology, New York University School of Medicine. | Newborn of women with epilepsy exposed to carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Newborn of women with epilepsy exposed to lamotrigine monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 21 / 3 | The analysis of developmental delay excluded the 20 pregnancies occurring within 1 year of chart review because of insufficient time to evaluate developmental milestones. | |
| Telephone interviews were given to the patient as a supplement to the chart analysis. Spouses were interviewed only when additional information could not be provided by the patient. | ||||||||
|
Kini (Carbamazepine) (Controls exposed to Lamotrigine, sick) 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 carbamazepine monotherapy during pregnancy and with epileptic mothers. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children exposed to lamotrigine monotherapy during pregnancy and with epileptic mothers. |
during pregnancy (anytime or not specified) | 94 / 9 | 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. | ||||||||
|
Kini (Carbamazepine) (Controls unexposed, sick) 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 carbamazepine 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) | 94 / 101 | A better review of the WISC score for children aged 6 and above are provided by Adab 2004 publication. | |
| Structured interviews were conducted with the mothers and medical records were available to confirm details in about 80% of participants. | ||||||||
|
Leite 2024 |
Brazil 2008 - 2021 retrospective cohort |
Prenatal and prepartum clinics in Maceio, Arapiraca and Santana do Ipanema, which are the reference institutions for the care of pregnant women with epilepsy in the state of Alagoas, Brazil. | Pregnant women with epilepsy using Carbamazepine in monotherapy. |
unexposed, disease free
Pregnant women without epilepsy (PWNE). |
during pregnancy (anytime or not specified) | 29 / 492 | Outcomes occurring during pregnancy (preeclampsia, oligohydramnios, abortions...) not reported here because it is not possible to know if exposure was before the outcome occurred (xls table in e-Supp showed that exposure only considered as Yes or No). | |
| This was a retrospective cohort study with data collected from physical and electronic medical records. | ||||||||
|
Li (Carbamazepine) (Epilepsy) (Controls exposed to LTG) 2023 |
China 2009 - 2022 prospective cohort |
A prospective cohort study entitled 'Construction and Application of the Women with Epilepsy of Child-bearing Age Ontology (WWECA)', with West China Hospital of Sichuan University as the main center. | Women with epilepsy (WWE) using Carbamazepine monotherapy during pregnancy. |
exposed to other treatment, sick
Women with epilepsy (WWE) using Lamotrigine monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 31 / 38 | 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. | ||||||||
|
Li (Carbamazepine) (Epilepsy) (Controls unexposed, sick) 2023 |
China 2009 - 2022 prospective cohort |
A prospective cohort study entitled 'Construction and Application of the Women with Epilepsy of Child-bearing Age Ontology (WWECA)', with West China Hospital of Sichuan University as the main center. | Women with epilepsy (WWE) using Carbamazepine monotherapy during pregnancy. |
unexposed, sick
Women with epilepsy (WWE) not using antiseizure medications during pregnancy. |
during pregnancy (anytime or not specified) | 31 / 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. | ||||||||
|
Madley-Dowd_SE (Carbamazepine) (Controls exposed to LTG) 2024 |
Sweden 1995 - 2020 population based cohort retrospective |
The Swedish Developmental Origins of Health and Disease (DOHaD) cohort, which is a registry study linking several national electronic data sources. | Fetal exposure to Carbamazepine monotherapy for epilepsy indication at any time during the pregnancy period, i.e any pregnancy with self-reported consumption during pregnancy or a prescription 30 days before pregnancy or during pregnancy. |
exposed to other treatment, sick
Fetal exposure to Lamotrigine monotherapy for epilepsy indication at any time during the pregnancy period, i.e any pregnancy with self-reported consumption during pregnancy or a prescription 30 days before pregnancy or during pregnancy. |
during pregnancy (anytime or not specified) | 1842 / 2383 | Data extracted from the e-Supp pdf (Table S10). | |
| Self-reported maternal consumption of antiseizure medications were prospectively recorded at antenatal care visits (from a structured interview at the first visit at 8–10 weeks of gestation, supplemented from 2005 with drug all prescription dispensations in Sweden (tetrachoric correlation 0.98). | ||||||||
|
Madley-Dowd_SE (Carbamazepine) (Controls unexposed, sick) 2024 |
Sweden 1995 - 2020 population based cohort retrospective |
The Swedish Developmental Origins of Health and Disease (DOHaD) cohort, which is a registry study linking several national electronic data sources. | Fetal exposure to Carbamazepine monotherapy for epilepsy indication at any time during the pregnancy period, i.e any pregnancy with self-reported consumption during pregnancy or a prescription 30 days before pregnancy or during pregnancy. |
unexposed, sick
No fetal exposure to antiseizure medication at any time during the pregnancy period, restricted for epilepsy indication. |
during pregnancy (anytime or not specified) | 1842 / 10769 | Data extracted from the excel file (Tab Fig S12) and the e-Supp pdf (Table S10). | |
| Self-reported maternal consumption of antiseizure medications were prospectively recorded at antenatal care visits (from a structured interview at the first visit at 8–10 weeks of gestation, supplemented from 2005 with drug all prescription dispensations in Sweden (tetrachoric correlation 0.98). | ||||||||
|
Madley-Dowd_UK (Carbamazepine) (Controls exposed to LTG) 2024 |
United Kingdom 1995 - 2018 retrospective cohort (claims database) |
The UK primary care-based Clinical Practice Research Datalink (CPRD) GOLD, with linkage to the CPRD Pregnancy Register, the CPRD Mother-Baby link, the Hospital Episode Statistics (HES) database, ... | Fetal exposure to Carbamazepine monotherapy for epilepsy indication at any time during the pregnancy period, i.e any pregnancy with a prescription that started or ended during the pregnancy period. |
exposed to other treatment, sick
Fetal exposure to Lamotrigine monotherapy for epilepsy indication at any time during the pregnancy period, i.e any pregnancy with a prescription that started or ended during the pregnancy period. |
during pregnancy (anytime or not specified) | 460 / 791 | Partial overlapping of swedish data with Bjork 2022 and Dreier 2023 (IQ, ASD, ADHD) => these studies were kept and tagged. => Data extracted from the e-Supp pdf (Table S10). | |
| Prescriptions were identified from primary care records. | ||||||||
|
Madley-Dowd_UK (Carbamazepine) (Controls unexposed, sick) 2024 |
United Kingdom 1995 - 2018 retrospective cohort (claims database) |
The UK primary care-based Clinical Practice Research Datalink (CPRD) GOLD, with linkage to the CPRD Pregnancy Register, the CPRD Mother-Baby link, the Hospital Episode Statistics (HES) database, ... | Fetal exposure to Carbamazepine monotherapy for epilepsy indication at any time during the pregnancy period, i.e any pregnancy with a prescription that started or ended during the pregnancy period. |
unexposed, sick
No fetal exposure to antiseizure medication at any time during the pregnancy period, restricted for epilepsy indication. |
during pregnancy (anytime or not specified) | 460 / 4075 | Partial overlapping of swedish data with Bjork 2022 and Dreier 2023 (IQ, ASD, ADHD) => these studies were kept and tagged. => Data extracted from the excel file (Tab Fig S12) and the e-Supp pdf (Table S10). | |
| Prescriptions were identified from primary care records. | ||||||||
|
Mari (Carbamazepine) 2022 |
Rome, Italy 2009 - 2019 retrospective cohort |
The Epilepsy Center of Policlinico Tor Vergata and the Epilepsy Center of Policlinico Campus Bio-Medico | Women with focal epilepsy (FE) or generalized epilepsy (GE) undergoing Anti-seizure medications monotherapy with carbamazepine. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Women with focal epilepsy (FE) or generalized epilepsy (GE) undergoing Anti-seizure medications monotherapy with lamotrigine. |
throughout pregnancy | 29 / 11 | In 46 out of 57 pregnancies, ASMs therapy remained unchanged during gestation (only one switch from CBZ to LEV, others are dosage-related). | |
| Collected data at Epilepsy centers. | ||||||||
|
Mawer (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2010 |
UK 2000 - 2006 prospective cohort |
11 National Health Service (NHS) hospitals within Merseyside and Greater Manchester. | Children born to mothers with epilepsy exposed to carbamazepine monotherapy in utero. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children born to mothers with epilepsy exposed to lamotrigine monotherapy in utero. |
1st trimester | 74 / 40 | Kini's 2007 malformation results are overlapped. 39% WWE also actively participated in a NEAD study in Meador 2006. Specific major malformations' numerators are extracted from the review by Weston et al. 2016. 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 (Carbamazepine) (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 carbamazepine 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 | 74 / 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 (Carbamazepine) (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 carbamazepine 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 | 74 / 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. | ||||||||
|
McVearry (Carbamazepine) 2009 |
UK and USA 1999 - 2004 prospective cohort |
13 participating NEAD Study clinical centers. | Preschool children whose mothers were exposed to carbamazepine in monotherapy during pregnancy for a minimum period of 6 months. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Preschool children whose mothers were exposed to lamotrigine in monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 16 / 17 | In utero AED monotherapy exposure for a minimum period of six months. Gestational diabetes not reported because not possible to know if exposure was before outcome. | |
| Recorded during pregnancy using seizure journals, serious adverse event reports, and clinical evaluations reported by the investigator-neurologist managing the epilepsy of enrolled mother. | ||||||||
|
Meador (Carbamazepine) 2013 |
UK and USA. 1999 - 2004 prospective cohort |
25 centers in the USA and UK. | Infants of epileptic mothers exposed to carbamazepine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants of epileptic mothers exposed to lamotrigine in monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 94 / 100 | A nonexposed control group was not included. Meador 2020 and Cohen 2019 are re-examination or an assessment of subscales of data already assessed in this publication. Cognitif assessment in Meador 2009 and 2011 (x2) is better assessed in this publication. | |
| They obtained information from the patients, their seizure or medication diary, or review of their medical records and assessed antiepileptic drug levels for 229 (75%) mothers. | ||||||||
|
Meador (Carbamazepine) 2006 |
USA and UK 1999 - 2004 prospective cohort |
25 centers across UK and USA. | Infants of women exposed to carbamazepine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants of women exposed to lamotrigine in monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 110 / 98 | Malformations secondary to known genetic disorders and chromosomal abnormalities are not considered within the major malformation group. 108 women with epilepsy are also used in Mawer 2010 so there is a 33% overlap for malformations. | |
| They obtained information from the patients, their seizure or medication diary, or review of their medical records. | ||||||||
|
Meador (Carbamazepine) 2009 |
UK and USA 1999 - 2004 prospective cohort |
25 centers across UK and USA. | Infants of women exposed to carbamazepine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants of women exposed to lamotrigine in monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 92 / 99 | Meador 2011 is completely overlapped with this study which gives a better review of the IQ at age 3 years old (more exposed pregnancies). The cognitive delay at 3 years old is already evaluated in Meador et al., 2013. | |
| They obtained information from the patients, their seizure or medication diary, or review of their medical records. | ||||||||
|
Meador (Carbamazepine) 2011 |
UK and USA 1999 - 2004 prospective cohort |
25 epilepsy centers in the USA and UK. | Infants of women exposed to carbamazepine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants of women exposed to lamotrigine in monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 59 / 70 | A non-exposed control group was not included. | |
| They obtained information from the patients, their seizure or medication diary, or review of their medical records. | ||||||||
|
Meador (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2020 |
US 2012 - 2016 prospective cohort |
The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study (20 US tertiary epilepsy centers). | Children born to pregnant women with epilepsy exposed to carbamazepine monotherapy during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children born to pregnant women with epilepsy exposed to lamotrigine monotherapy during the first trimester. |
1st trimester | 14 / 113 | ||
| Data were obtained from participants and their medical records. | ||||||||
|
Meador (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2021 |
US 2012 - 2016 prospective cohort |
The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study (20 US tertiary epilepsy centers). | Children with epileptic mothers using carbamazepine monotherapy in the third trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children with epileptic mothers using lamotrigine monotherapy in the third trimester. |
3rd trimester | 12 / 93 | Exclusion criteria included history of psychogenic nonepileptic spells, expected IQ of less than 70, other major medical illness, and switching of ASMs in pregnancy before enrollment. | |
| Data were collected from participants using a daily electronic diary that was verified at study visits and with medical records. | ||||||||
|
Meador (Carbamazepine) (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 carbamazepine 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 | 14 / 106 | ||
| Data were obtained from participants and their medical records. | ||||||||
|
Meador (Carbamazepine) (Controls unexposed, disease free) 2021 |
US 2012 - 2016 prospective cohort |
The Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs (MONEAD) study (20 US tertiary epilepsy centers). | Children with epileptic mothers using carbamazepine monotherapy in the third trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Children of healthy women. |
3rd trimester | 12 / 106 | Exclusion criteria included history of psychogenic nonepileptic spells, expected IQ of less than 70, other major medical illness, and switching of ASMs in pregnancy before enrollment. | |
| Data were collected from participants using a daily electronic diary that was verified at study visits and with medical records. | ||||||||
|
Meador (Carbamazepine) (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 carbamazepine 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 | 14 / 15 | ||
| Data were obtained from participants and their medical records. | ||||||||
|
Miškov (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2016 |
Croatia 2003 - 2013 prospective cohort |
The Sestre milosrdnice University Hospital Center in Zagreb | Pregnancies in women with epilepsy on carbamazepine monotherapy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Pregnancies in women with epilepsy on lamotrigine monotherapy. |
during pregnancy (anytime or not specified) | 13 / 37 | Includes all Miskov's 2010 outcomes. | |
| Data collected on pregnant women during outpatient visits to the neurologist, gynecologist and pediatrician neurologist. | ||||||||
|
Miškov (Carbamazepine) (Controls unexposed, disease free) 2016 |
Croatia 2003 - 2013 prospective cohort |
The Sestre milosrdnice University Hospital Center in Zagreb | Pregnancies in women with epilepsy on carbamazepine 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) | 13 / 147 | Includes all Miskov's 2010 outcomes. | |
| Data collected on pregnant women during outpatient visits to the neurologist, gynecologist and pediatrician neurologist. | ||||||||
|
Miškov (Carbamazepine) (Controls unexposed, sick) 2016 |
Croatia 2003 - 2013 prospective cohort |
The Sestre milosrdnice University Hospital Center in Zagreb | Pregnancies in women with epilepsy on carbamazepine 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) | 13 / 4 | Includes all Miskov's 2010 outcomes. | |
| Data collected on pregnant women during outpatient visits to the neurologist, gynecologist and pediatrician neurologist. | ||||||||
|
Nadebaum (Carbamazepine) 2011 |
Australia 2007 - 2009 prospective cohort |
The Australian Pregnancy Register for Women with Epilepsy and Allied Disorders (APR). | Children exposed to carbamazepine monotherapy in utero from epileptic mother. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children exposed to lamotrigine monotherapy in utero from epileptic mother. |
during pregnancy (anytime or not specified) | 34 / 9 | Children with major birth defects or a diagnosis of epilepsy were ineligible for the study to avoid possible confounding effects of these known risk factors for intellectual impairment. | |
| Details are obtained by four in-depth telephone interviews with the women. Details provided by the participants are confirmed, as far as possible, by the treating medical practitioners. | ||||||||
|
Ornoy (Carbamazepine) 1996 |
Israel 1988 - 1994 prospective cohort |
The Israeli Teratogen Information Service | Children whose epileptic mothers used carbamazepine as their sole anticonvulsant throughout pregnancy. |
unexposed (general population or NOS)
Children whose mothers were unexposed to carbamazepine. |
throughout pregnancy | 47 / 47 | Ornoy 1996 major malformations results are already included in Diav-Citrin 2001 with more exposed pregnancies. Children were excluded from analysis because of prematurity (born before 32 weeks of gestation). | |
| Each woman was interviewed during pregnancy. | ||||||||
|
Pekoz (Carbamazepine) (Epilepsy) (Controls exposed to LTG) 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 Carbamazepine as monotherapy. |
exposed to other treatment, sick
Pregnant women with epilepsy (PWWE) receiving Lamotrigine as monotherapy. |
during pregnancy (anytime or not specified) | 141 / 141 | ||
| The patients were examined by a neurologist every 2 months during pregnancy, and the use of Anti-seizure medications (ASMs) was assessed. | ||||||||
|
Pekoz (Carbamazepine) (Epilepsy) (Controls unexposed, sick) 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 Carbamazepine 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. | ||||||||
|
Pennell (Carbamazepine) 2012 |
USA and UK 1999 - 2004 prospective cohort |
25 centers in the United States and United Kingdom | Infants of women exposed to carbamazepine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants of women exposed to lamotrigine in monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 93 / 98 | Gestational hypertension and diabetes not reported here because baseline characteristics and not possible to know if exposure was before outcome. | |
| They obtained information from the patients, their seizure or medication diary, or review of their medical records. | ||||||||
|
Razaz (Carbamazepine) 2024 |
Denmark, Finland, Iceland, Norway and Sweden. 1996 - 2017 population based cohort retrospective |
The SCAN-AED project, using the Nordic register infrastructures. | Mothers with epilepsy who filled a prescription for Carbamazepine monotherapy between the date of the last menstrual period (LMP) and the day of birth. |
unexposed, sick
Mothers with epilepsy who did not fill an antiseizure medication (ASM) prescription in the period between 90 days before the last menstrual period (LMP) and the day of birth. |
during pregnancy (anytime or not specified) | 2628 / 19043 | ||
| Prescription for antiseizure medication (ASM) was ascertained using nationwide prescription registers and identified ASMs based on Anatomical Therapeutic Chemical Classification. | ||||||||
|
Ren (Carbamazepine) (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 carbamazepine 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) | 226 / 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. | ||||||||
|
Robert (Carbamazepine) 1986 |
France 1976 - 1983 retrospective cohort |
Hospital of neurology and neurosurgery P. Wertheimer and three maternity wards in Lyon | Infants born from epileptic mothers exposed during the first trimester to carbamazepine in monotherapy. |
unexposed, sick
Infants born from epileptic mothers unexposed during the first trimester to any antiepileptic drugs. |
1st trimester | 3 / 35 | ||
| Questionnaires were sent to women identified in hospital records and the second collection of data was obtained from 3 maternity with computerized records. | ||||||||
|
Samrén (Carbamazepine) 1999 |
Netherlands 1972 - 1994 retrospective cohort |
28 hospitals in four provinces of the Netherlands and National Perinatal Data Base LVR. | Children born to mothers with epilepsy and using carbamazepine monotherapy at least during the first trimester of pregnancy |
unexposed, disease free
Children born to nonepileptic nonexposed women. |
at least 1st trimester | 376 / 2000 | ||
| Data were collected from medical records and include medication. The prescribed dose of thedrugs was also retrieved from obstetric files. | ||||||||
|
Sonneveld (Carbamazepine) (Controls unexposed NOS) 1990 |
Tasmania 1981- 1988 prospective cohort |
The Tasmanian Obstetric and Perinatal audit | Epileptic pregnancies exposed to carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Total number of deliveries during the study period. |
during pregnancy (anytime or not specified) | 74 / 56557 | The total population of this study serves as a control group, thus it includes the exposed group but accounting only for 0.6% of the sample. In the result authors used 55953 for the total number of deliveries when all perinatal deaths are excluded. | |
| Since 1981, drugs ingested during pregnancy have been included in the information collected. | ||||||||
|
Sonneveld (Carbamazepine) (Controls unexposed, sick) 1990 |
Tasmania 1981- 1988 prospective cohort |
The Tasmanian Obstetric and Perinatal audit | Epileptic pregnancies exposed to carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Epileptic pregnancies who used no anticonvulsant drug therapy. |
during pregnancy (anytime or not specified) | 74 / 87 | ||
| Since 1981, drugs ingested during pregnancy have been included in the information collected. | ||||||||
|
Steegers-Theunissen (Carbamazepine) 1994 |
Netherlands Not specified prospective cohort |
Five centres in the Netherlands: two university hospitals (of Amsterdam and of Nijmegen), and three general hospitals (Maria and Elisabeth hospital, Tilburg and Catharina hospital, Eindhoven). | Singleton of epileptic women exposed to carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Singleton of healthy women unexposed during pregnancy. |
during pregnancy (anytime or not specified) | 39 / 106 | Women could only participate if they or any first-degree relative had no genetic disorder known to cause major congenital malformations, and if they were not under treatment for infectious, metabolic, endocrine or malignant diseases. | |
| The use of antiepileptic drugs was checked in each woman by measurement of the blood concentration. Data such as antiepileptic drug treatment were collected. The consulting doctors were finally contacted to obtain additional information on treatment regimen. | ||||||||
|
Stjerna (Carbamazepine) (Epilepsy) 2024 |
Czech Republic, Finland, Germany, Italy, Spain, Sweden and the Netherlands. 2008 - 2020 retrospective cohort |
The neurocognitive extension study (NCEP), an extension of the prospective EURAP study, a registry-based multicenter study. | Children of mothers with epilepsy that used Carbamazepine monotherapy during the entire period from conception to birth. |
exposed to other treatment, sick
Children of mothers with epilepsy that used lamotrigine monotherapy during the entire period from conception to birth. |
throughout pregnancy | 41 / 82 | Use of adjusted continuous data (transformed in OR) rather than unadjusted dichotomised data. Indications: Epilepsy (Table 1). Overlapping: Huber-Mollema 2020 (n=99; NL only) totally included in Stjerna 2024 (n=162; 7 countries) => Use of Stjerna. | |
| Prospectively collected data on antiseizure medications (ASMs) and seizures during pregnancy were retrieved from the core EURAP registry. | ||||||||
|
Thomas (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2021 |
India 1998 - 2019 prospective cohort |
The Kerala Registry of Epilepsy and Pregnancy (KREP) | Children of women with epilepsy using carbamazepine monotherapy any time during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children of women with epilepsy using lamotrigine monotherapy any time during the first trimester of pregnancy. |
1st trimester | 490 / 50 | Study design completed with Thomas et al., 2017. Keni's 2018 malformations results are already reported in this publication. | |
| Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them. | ||||||||
|
Thomas (Carbamazepine) (Controls unexposed, disease free) 2021 |
India 1998 - 2015 prospective cohort |
The Kerala Registry of Epilepsy and Pregnancy (KREP) | Children of women with epilepsy using carbamazepine 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 | 389 / 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 (Carbamazepine) (Controls unexposed, sick) 2021 |
India 1998 - 2019 prospective cohort |
The Kerala Registry of Epilepsy and Pregnancy (KREP) | Children of women with epilepsy using carbamazepine 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 | 490 / 340 | Study design completed with Thomas et al., 2017. Thomas et al., 2008 completely overlapped with this publication. | |
| Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them. | ||||||||
|
Thomas a (Carbamazepine) 2022 |
India 1998 - 2006 prospective cohort |
The Kerala Registry of Epilepsy and Pregnancy (KREPS), India. | Children of women with epilepsy (CWWE) exposed to Carbamazepine monotherapy during pregnancy. |
unexposed, sick
Children of women with epilepsy (CWWE) not exposed to antiseizure medications during pregnancy. |
during pregnancy (anytime or not specified) | 38 / 11 | Overlapping/Update: Thomas 2022: data on language and cognitive delay, also assessed in Sreedharan 2018; Thomas 2007; Gopinath 2015; Bhaskaran 2025, but with more exposed pregnancies, more relevant control group and older children => Use of Thomas 2022. | |
| The details of Antiseizure medications exposure were extracted from the clinical records in the registry. | ||||||||
|
Thomas b (Carbamazepine) (Epilepsy) (Controls exposed to LTG) 2022 |
India 1998 - 2019 prospective cohort |
The Kerala Registry of Epilepsy and Pregnancy (KREP), India. | Infants of women with epilepsy who were exposed to Carbamazepine monotherapy at anytime during the antenatal period. |
exposed to other treatment, sick
Infants of women with epilepsy who were exposed to Lamotrigine monotherapy at anytime during the antenatal period. |
during pregnancy (anytime or not specified) | 317 / 26 | Overlapping/Update: Bhaskaran 2025 and Thomas 2008b (1998 - 2004) totally included in Thomas 2022b (1998 - 2019): Use of Thomas 2022b (more exposed pregnancies). No use of delayed mental development, because discrepancy in LTG data '1/26 (11.5%)'. | |
| Each pregnant woman in the Kerala Registry of Epilepsy and Pregnancy (KREP) maintained a pregnancy diary to record the daily use of antiseizure medications (ASMs). Data were then transferred to the clinical records of the registry during their clinic visits. | ||||||||
|
Thomas b (Carbamazepine) (Epilepsy) (Controls unexposed, sick) 2022 |
India 1998 - 2019 prospective cohort |
The Kerala Registry of Epilepsy and Pregnancy (KREP), India. | Infants of women with epilepsy who were exposed to Carbamazepine monotherapy at anytime during the antenatal period. |
unexposed, sick
Infants of women with epilepsy who were not exposed to any antiseizure medications (ASMs) during pregnancy. |
during pregnancy (anytime or not specified) | 317 / 110 | Overlapping/Update: Bhaskaran 2025 and Thomas 2008b (1998 - 2004) totally included in Thomas 2022b (1998 - 2019): Use of Thomas 2022b (more exposed pregnancies). | |
| Each pregnant woman in the Kerala Registry of Epilepsy and Pregnancy (KREP) maintained a pregnancy diary to record the daily use of antiseizure medications (ASMs). Data were then transferred to the clinical records of the registry during their clinic visits. | ||||||||
|
Titze (Carbamazepine) (Controls unexposed, disease free) 2008 |
Germany 1976 - 1984 prospective cohort |
Five antenatal clinics in the city of Berlin (West Germany). | Adolescents whose epileptic mothers were exposed to carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Adolescents from non-affected mothers. |
during pregnancy (anytime or not specified) | 4 / 49 | ||
| The pregnant women were asked to continuously monitor their treatment. | ||||||||
|
Titze (Carbamazepine) (Controls unexposed, sick) 2008 |
Germany 1976 - 1984 prospective cohort |
Five antenatal clinics in the city of Berlin (West Germany). | Adolescents whose epileptic mothers were exposed to carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Adolescents whose epileptic mothers weren't exposed to any antiepileptic drugs during pregnancy. |
during pregnancy (anytime or not specified) | 4 / 13 | ||
| The pregnant women were asked to continuously monitor their treatment. | ||||||||
|
Tomson (Carbamazepine) 2015 |
42 countries 1999 - 2013 prospective cohort |
The EURAP epilepsy and pregnancy registry | Pregnancies in women with epilepsy treated with carbamazepine monotherapy at least during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Pregnancies in women with epilepsy treated with lamotrigine monotherapy at least during the first trimester. |
at least 1st trimester | 1713 / 1910 | Pregnancies that occurred in women without epilepsy were excluded. EURAP registry: potential overlap. | |
| The data concerning treatment at the time of conception are obtained by the physicians responsible for the women’s care and transferred online. (Intention-to-treat principle). | ||||||||
|
Tomson (Carbamazepine) 2018 |
42 countries 1999 - 2016 prospective cohort |
The EURAP epilepsy and pregnancy registry | Offspring exposed in utero to carbamazepine monotherapy during the first trimester and born from epileptic mothers. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Offspring exposed in utero to lamotrigine monotherapy during the first trimester and born from epileptic mothers. |
at least 1st trimester | 1957 / 2514 | Overlapping/Update: (Major) malfo as a whole: Battino 2024 (1999-2022) updates Tomson 2018 (1999-2016), Tomson 2011, Jimenez 2020, Martinez 2009 and 2018 => Not reported here and use of Battino 2024 for the 8 (plus 16 in eSupp) monotherapies studied. | |
| Information obtained during early pregnancy and follow-up by the treating physician who transferred it online to a EURAP national coordinator. He then, reviewed the reports for completeness and accuracy before transmission to the EURAP central database. | ||||||||
|
Trivedi (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2018 |
India 1998 - 2015 prospective cohort |
The Kerala Registry of Epilepsy and Pregnancy (KREP) | Pregnant women with epilepsy who used carbamazepine monotherapy any time during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Pregnant women with epilepsy who used lamotrigine monotherapy any time during the first trimester of pregnancy. |
1st trimester | 465 / 48 | Study design partly completed with cites source Thomas et al., 2017. | |
| Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them. | ||||||||
|
Trivedi (Carbamazepine) (Controls unexposed, sick) 2018 |
India 1998 - 2015 prospective cohort |
The Kerala Registry of Epilepsy and Pregnancy (KREP) | Pregnant women with epilepsy who used carbamazepine 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 | 465 / 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 (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2013 |
Australia 1999 - 2013 prospective cohort |
The Australian Register of Antiepileptic Drugs in Pregnancy. | Offsprings from women with epilepsy exposed to carbamazepine in monotherapy in at least the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Offsprings from women with epilepsy exposed to lamotrigine in monotherapy in at least the first trimester of pregnancy. |
at least 1st trimester | 361 / 315 | Women taking AED for epilepsy are in majority (more than 90%). Vajda 2019 provides the most recent update for major malformations results for this register. Specific malformations' results are extracted from the review by Weston et al. 2016. | |
| Details are obtained by four in-depth telephone interviews with the women. Details provided by the participants are confirmed, as far as possible, by the treating medical practitioners. | ||||||||
|
Vajda (Carbamazepine) (Controls unexposed, sick) 2013 |
Australia 1999 - 2013 prospective cohort |
The Australian Register of Antiepileptic Drugs in Pregnancy. | Offsprings from women with epilepsy exposed to carbamazepine 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 | 361 / 147 | Women taking AED for epilepsy are in majority (more than 90%). Vajda 2019 provides the most recent update for major malformations results for this register. Specific malformations' results are extracted from the review by Weston et al. 2016. | |
| Details are obtained by four in-depth telephone interviews with the women. Details provided by the participants are confirmed, as far as possible, by the treating medical practitioners. | ||||||||
|
Vajda a (Carbamazepine) (Controls exposed to LTG) 2024 |
Australia 1999 - 2023 prospective cohort |
The Australian Pregnancy Register of Antiepileptic Drugs (APR). | Women with epilepsy exposed to carbamazepine monotherapy during pregnancy. |
exposed to other treatment, sick
Women with epilepsy exposed to lamotrigine monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 400 / 442 | Overlapping between Vajda 2024a (1999 - 2023) and Vajda 2018 (1999 - 2016) based on the same register and for the almost same outcome (with or without elective termination) => Use of Vajda 2024a because accounting for more relevant confounders. | |
| Not specified. All contact between the pregnant women and the Melbourne-based register has been by telephone. | ||||||||
|
Vajda a (Carbamazepine) (Controls unexposed sick) 2024 |
Australia 1999 - 2023 prospective cohort |
The Australian Pregnancy Register of Antiepileptic Drugs (APR). | Women with epilepsy exposed to carbamazepine monotherapy during pregnancy. |
unexposed, sick
Women with epilepsy unexposed to antiseizure medication during pregnancy. |
during pregnancy (anytime or not specified) | 400 / 184 | Overlapping between Vajda 2024a (1999 - 2023) and Vajda 2018 (1999 - 2016) based on the same register and for the almost same outcome (with or without elective termination) => Use of Vajda 2024a because accounting for more relevant confounders. | |
| Not specified. All contact between the pregnant women and the Melbourne-based register has been by telephone. | ||||||||
|
Vajda b (Carbamazepine) (Controls unexposed, sick) 2024 |
Australia 1999 - 2022 prospective cohort |
The Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs (referred to as ‘Australian Pregnancy Register’ from this point forward). | Women with epilepsy exposed to carbamazepine in monotherapy in early pregnancy. |
unexposed, sick
Women with epilepsy not treated with antiepileptic drugs in early pregnancy. |
at least 1st trimester | 446 / 201 | Overlapping: Vajda 2024 totally included other APR data (Vajda 2019; Vajda 2007; 2010 (x2); 2012 (x2); 2013; 2014). Study design partly completed with Vajda 2013. | |
| Details are obtained by four in-depth telephone interviews with the women (at time of enrolment; at approximately 28 weeks of pregnancy; after the 1st post-partum (pp) month, and at one year pp). The accuracy of the information provided by the pregnant women is checked with their treating doctors. | ||||||||
|
Vajda b (Carbamazepine) Controls exposed to Lamotrigine, sick) 2024 |
Australia 1999 - 2022 prospective cohort |
The Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs (referred to as ‘Australian Pregnancy Register’ from this point forward). | Women with epilepsy exposed to carbamazepine in monotherapy in early pregnancy. |
exposed to other treatment, sick
Women with epilepsy exposed to lamotrigine in monotherapy in early pregnancy. |
early pregnancy | 446 / 473 | Overlapping: Vajda 2024 totally included other APR data (Vajda 2019; Vajda 2007; 2010 (x2); 2012 (x2); 2013; 2014). Study design partly completed with Vajda 2013. | |
| Details are obtained by four in-depth telephone interviews with the women (at time of enrolment; at approximately 28 weeks of pregnancy; after the 1st post-partum (pp) month, and at one year pp). The accuracy of the information provided by the pregnant women is checked with their treating doctors. | ||||||||
|
Van der Pol (Carbamazepine) (Controls unexposed, disease free) 1991 |
The Netherlands 1973 - 1981 prospective cohort |
The Groningen University Hospital | Children born to epileptic mothers exposed to carbamazepine only throughout pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Children of nonepileptic mothers selected from singletons born in the same period. |
throughout pregnancy | 12 / 61 | ||
| The dosages of antiepileptic drugs were constant throughout pregnancy. | ||||||||
|
Van der Pol (Carbamazepine) (Controls unexposed, sick) 1991 |
The Netherlands 1973 - 1981 prospective cohort |
The Groningen University Hospital | Children born to epileptic mothers exposed to carbamazepine only throughout pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Children born to epileptic mothers not exposed to antiepileptic medication. |
throughout pregnancy | 12 / 24 | ||
| The dosages of antiepileptic drugs were constant throughout pregnancy. | ||||||||
|
Vanya (Carbamazepine) (Controls exposed to Lamotrigine, 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 carbamazepine monotherapy throughout the nine months of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Neonates of epileptic women treated with lamotrigine monotherapy throughout the nine months of pregnancy. |
throughout pregnancy | 10 / 6 | 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). | ||||||||
|
Vanya (Carbamazepine) (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 carbamazepine 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 | 10 / 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 (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2014 |
Norway 1999 - 2011 population based cohort retrospective |
Medical Birth Registry of Norway | Children exposed prenatally to carbamazepine as monotherapy indicated for their mothers' epilepsy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children exposed prenatally to lamotrigine as monotherapy indicated for their mothers' epilepsy. |
throughout pregnancy | 613 / 593 | 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 (Carbamazepine) (Controls exposed to Lamotrigine, 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 carbamazepine monotherapy during pregnancy born from epileptic mothers. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children exposed to lamotrigine monotherapy during pregnancy born from epileptic mothers. |
during pregnancy (anytime or not specified) | 48 / 71 | Overlap for the neuro-developmental outcomes at 18 and 36 months old and the 'weight less than 10th percentile' outcomes with Bjørk 2018. | |
| 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 (Carbamazepine) (Controls exposed to Lamotrigine, 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 carbamazepine monotherapy during pregnancy born from epileptic mothers. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children exposed to lamotrigine monotherapy during pregnancy born from epileptic mothers. |
during pregnancy (anytime or not specified) | 69 / 104 | 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 (Carbamazepine) (Controls unexposed, disease free) 2014 |
Norway 1999 - 2011 population based cohort retrospective |
Medical Birth Registry of Norway | Children exposed prenatally to carbamazepine 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 | 613 / 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 (Carbamazepine) (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 carbamazepine 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) | 48 / 77770 | Overlap for the neuro-developmental outcomes at 18 and 36 months old and the 'weight less than 10th percentile' outcomes with Bjørk 2018. | |
| 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 (Carbamazepine) (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 carbamazepine 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) | 69 / 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 (Carbamazepine) (Controls unexposed, sick) 2014 |
Norway 1999 - 2011 population based cohort retrospective |
Medical Birth Registry of Norway | Children exposed prenatally to carbamazepine 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 | 613 / 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 (Carbamazepine) (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 carbamazepine 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) | 48 / 276 | Overlap for the neuro-developmental outcomes at 18 and 36 months old and the 'weight less than 10th percentile' outcomes with Bjørk 2018. | |
| 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 (Carbamazepine) (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 carbamazepine 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) | 69 / 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 (Carbamazepine) (Controls exposed to Lamotrigine, sick) 2016 |
Finland 2009 - 2013 prospective cohort |
The Helsinki University Hospital | Newborns from epileptic women with fetal monotherapy carbamazepine exposure during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Newborns from epileptic women with fetal monotherapy lamotrigine exposure during pregnancy. |
during pregnancy (anytime or not specified) | 9 / 8 | 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. | ||||||||
|
Videman (Carbamazepine) (Controls unexposed, disease free) 2016 |
Finland 2009 - 2013 prospective cohort |
The Helsinki University Hospital | Newborns from epileptic women with fetal monotherapy carbamazepine 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) | 9 / 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. | ||||||||
|
Viinikainen (Carbamazepine) (Controls unexposed, disease free) a 2006 |
Finland 1989 - 2000 prospective cohort |
Community-based pregnancy registry at the Kuopio University Hospital. | Pregnancies of mothers who had active epilepsy and were using carbamazepine in monotherapy before conception and through the whole pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Pregnancies of mothers without epilepsy and unexposed to antiepileptic drugs. |
throughout pregnancy | 72 / 24778 | Multiple pregnancies and pregnancies with evident neonatal chromosomal abnormalities were excluded. | |
| Obstetric data derived from the pregnancy registry and supplemented with medical records. And plasma levels of the antiepileptic drugs were monitoring during pregnancy at each control visit. | ||||||||
|
Viinikainen (Carbamazepine) (Controls unexposed, sick) a 2006 |
Finland 1989 - 2000 prospective cohort |
Community-based pregnancy registry at the Kuopio University Hospital. | Pregnancies of mothers who had active epilepsy and were using carbamazepine in monotherapy before conception and through the whole pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnancies of mothers who reported having previous history of epilepsy but no need for antiepileptic drugs at the time of the pregnancy. |
throughout pregnancy | 72 / 52 | Multiple pregnancies and pregnancies with evident neonatal chromosomal abnormalities were excluded. | |
| Obstetric data derived from the pregnancy registry and supplemented with medical records. And plasma levels of the antiepileptic drugs were monitoring during pregnancy at each control visit. | ||||||||
|
Viinikainen (Carbamazepine) b 2006 |
Finland 1989 - 2000 prospective cohort |
Community-based pregnancy registry at the Kuopio University Hospital. | Pregnancies in which the mother had used carbamazepine during conception and throughout pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnancies in which the mother reported having previous history of epilepsy but had not needed antiepileptic drugs during pregnancy. |
throughout pregnancy | 13 / 13 | None evident malformations and any other causes for possible neurological dysfunctions, e.g. signs suggestive for chromosomal or metabolic diseases were found. The evaluators were blinded. Partly completed with Eriksson 2005. | |
| The medical records of the children and their mothers were reviewed separately by two of the authors. | ||||||||
|
Vinten (Carbamazepine) 2005 |
UK Not specified. retrospective cohort |
Specialist epilepsy clinics and obstetric clinics from the Liverpool and Manchester region (belong to the Liverpool and Manchester Neurodevelopment Study Group). | Children born to epileptic mothers on carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Children born to epileptic mothers not on antiepileptic medication during their pregnancy. |
during pregnancy (anytime or not specified) | 52 / 83 | Repeat population groups and the same data are already obtained in Adab 2004 for all the neurodevelopmental outcomes except the IQ score within the extremely low range (IQ<69). | |
| The women recruited were initially interviewed to ascertain information including the antiepileptic drug dose throughout the pregnancy. Clinical records were used to confirm the medical information. | ||||||||
|
Waters (Carbamazepine) (Controls unexposed, disease free) 1994 |
USA 1987 - 1990 prospective cohort |
The obstetrics service at Los Angeles County/University of Southern California Medical Center. | Infants born to epileptic mothers exposed to carbamazepine during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Infants born to nonepileptic mothers selected from a computer-generated list of all women who gave birth in the same facility during this period. |
1st trimester | 33 / 355 | Mothers who abused alcohol and other drugs were excluded from both patient ad control groups. | |
| An attending neurologist took a history, performed an examination, and monitored the administration of antiepileptic drugs throughout the pregnancy. Documented at each visit on a standard form. | ||||||||
|
Waters (Carbamazepine) (Controls unexposed, sick) 1994 |
USA 1987 - 1990 prospective cohort |
The obstetrics service at Los Angeles County/University of Southern California Medical Center. | Infants born to epileptic mothers exposed to carbamazepine during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnancies in women with epilepsy in which there was no exposure to antiepileptic drugs. |
1st trimester | 33 / 15 | Mothers who abused alcohol and other drugs were excluded from both patient ad control groups. | |
| An attending neurologist took a history, performed an examination, and monitored the administration of antiepileptic drugs throughout the pregnancy. Documented at each visit on a standard form. | ||||||||
|
Wide (Carbamazepine) 2000 |
Sweden 1985 - 1995 prospective cohort |
The Sodersjukhuset Hospital in the south-east region of Stockholm. | First-born infants whose epileptic mothers were continuously treated with carbamazepine monotherapy from conception throughout pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Children born in the same hospital within 2 days of the study subjects of mothers not treated with antiepileptic drugs. |
throughout pregnancy | 39 / 87 | Sex-matched control infants were found for 69 of 87 (87 of 100) subjects, but the other matching criteria were fulfilled for the total study group. | |
| Mothers attended the outpatient clinic for pregnant women with epilepsy at the department of neurology where drug plasma levels were determined at monthly intervals. | ||||||||
|
Wiggs 2024 |
Sweden 1996 - 2016 population based cohort retrospective |
Cohort of individuals obtained from the Medical Birth Register (MBR), the National Patient Register (NPR). | Children born to women with epilepsy who reported the use of carbamazepine monotherapy at their first antenatal visit (8th-12th week of pregnancy). |
unexposed, sick
Children whose mothers had a diagnosis of epilepsy but who did not report the use of any antiseizure medications (ASMs) at their first antenatal visit. |
early pregnancy | 1456 / 12666 | Overlapping: this study totally included Razaz 2017. Use of data in children born to women with any diagnosis of epilepsy prior to conception and with single antiseizure medication exposure. Total number of unexposed group based on eTable 2. | |
| Information recorded at the first antenatal visit (8th-12th week of pregnancy) includes prescription drug use. | ||||||||
|
Wood (Carbamazepine) 2015 |
Australia 2007 - 2010 prospective cohort |
The Australian Pregnancy Register (APR) for Women on Antiepileptic Medication. | Children of women with epilepsy exposed to carbamazepine in monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children of women with epilepsy exposed to lamotrigine in monotherapy during pregnancy. |
during pregnancy (anytime or not specified) | 34 / 9 | Children with major birth defects or a diagnosis of epilepsy were excluded, as these conditions are known risk factors for autism spectrum disorders. Child's IQ results are already reported by the publication of Nadebaum 2011. | |
| Details are obtained by four in-depth telephone interviews with the women. And treating doctors are contacted to confirm medical details. | ||||||||
|
Yerby (Carbamazepine) 1992 |
USA Not specified. prospective cohort |
The Child Development and Mental Retardation Center at the University of Washington. | Infants of mothers with epilepsy treated by carbamazepine monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Infants of women without a chronic illness or a personal or family history of epilepsy. |
during pregnancy (anytime or not specified) | 19 / 46 | Women were excluded if they had another chronic illness and were not compliant. | |
| Women with epilepsy had a determination of antiepileptic drug concentrations. They were scheduled for monthly visits and with their babies two times post partum | ||||||||
| Study | Country Study period Study design |
Data source | Case | Control | Exposition | Exposition period | Sample size (exposed/unexposed) Or (case / control) |
Remarks | Risk of bias |
|---|---|---|---|---|---|---|---|---|---|
|
Arteaga-Vázquez (Carbamazepine) 2012 |
Mexico 1978 - 2010 case control |
Registro y Vigilancia Epidemiológica de Malformaciones Congénitas (RYVEMCE): 36 hospitals participated from different states of the Mexican Republic. | Newborn with one or more congenital malformations. | Newborn control without congenital malformations which is the birth following the newborn with congenital malformations of the same sex born at the same hospital. | The intake of anticonvulsants was obtained by direct interview of the mother during the first 24 hours after delivery or by consulting the obstetric record. | 1st trimester | 71 / 95 | ||
| Clinical examination systematized of all consecutive births that occur in the hospitals that participate in the program. Uniform information is obtained through the filling of a specifically designed clinical form for the registry. | |||||||||
|
Bànhidy (Carbamazepine) 2011 |
Hungary 1980 - 1996 case control |
Hungarian Congenital Abnormality Registry (HCAR), the National Birth Registry of the Central Statistical Office and the Hungarian Case-Control Surveillance of Congenital Abnormalities (HCCSCA). | Children affected with congenital abnormalities and who had mothers with medically recorded epilepsy. | Newborn infants without congenital abnormality and who had mothers with medically recorded epilepsy. | Mothers were mailed a questionnaire (after the selection of cases and controls) requested information on medicinal products taken during pregnancy and to send their prenatal maternity logbook and other medical records. Regional nurses were asked to visit and question the non-respondent. | throughout pregnancy | 95 / 90 | Malformations caused by major mutant genes or chromosomal aberrations with preconceptional origin were excluded. Exposure period completed with Czeizel 1992. | |
| Notification of cases with congenital abnormality is mandatory for physicians to the HCAR. Pathologists sent a copy of autopsy report for stillbirths and infant deaths cases and defect diagnosed in prenatal diagnostic centers with or without termination of pregnancy were also included. | |||||||||
|
Jentink (Carbamazepine) 2010 |
Europe 1995 - 2005 case control |
The EUROCAT Antiepileptic Study Database (drawn from 19 population based registries) | All live births, fetal deaths from 20 weeks’ gestation, and terminations of pregnancy after prenatal diagnosis, non-chromosomal and non-monogenic, with at least one of the five major congenital malformations under study. | Live births, fetal deaths from 20 weeks’ gestation, and terminations of pregnancy after prenatal diagnosis that involved major malformations other than the five malformations under study. | The EUROCAT central database contains medications taken in the first trimester of pregnancy (Anatomical Therapeutic Chemical coded). | 1st trimester | 11790 / 69883 | ||
| EUROCAT major congenital malformation classification (based on ICD-10). | |||||||||
|
Källén (Carbamazepine) 1994 |
Sweden 1973 - 1991 nested case control |
The Sweden Medical Birth Registry, the Hospital Discharge Registry and the Maternal Health Centre records. | Infants with spina bifida. | Infants whose mothers had epilepsy and were matched. | Information on epilepsy during pregnancy and possible anticonvulsant drugs used were obtained from the Maternal Health Centre records (usually weeks 10 to 12 of pregnancy). | during pregnancy (anytime or not specified) | 9 / 18 | ||
| Diagnoses in the Medical Birth Registry. Authors retrieved the original hospital records. | |||||||||
|
Thomas a (Carbamazepine) 2008 |
India 1998 - 2004 nested case control |
The Kerala Registry of Epilepsy and Pregnancy | Infants with cardiac malformation defined as any major malformation of the heart or intrathoracic great vessels that is actually or potentially of functional significance. | Infants without cardiac malformation. | The maternal use of antiepileptic drugs is recorded in the protocol forms from the month prior to the last menstrual period through the entire pregnancy and postpartum period on a monthly basis. | 1st trimester | 36 / 426 | Completely overlapped with Thomas et al., 2021. | |
| A cardiologist blinded to antiepileptic drugs exposure of the infants carries out a clinical examination and echocardiogram on all infants. A second cardiologist confirmed malformation whenever required. | |||||||||
Risk of bias: : NA; : low; : moderate; : serious; : critical; : unclear;
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