| Study | Country Study period |
Population source | Exposure definition | Non-exposure definition | Sample size | Rmk |
|---|---|---|---|---|---|---|
| Adab (Phenytoin), 2004 |
UK 1989 - 1999 |
Women (n=219) with epilepsy with children (n= 375) aged between 6 months to 16 years were identified and agreed to participate. | Children exposed to phenytoin 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. |
26 / 101 | The language delay of this sample is better assessed in Vinten et al., 2009 (in discrete values). |
| Adams (Phenytoin), 2022 |
Boston, USA 1983-1993 1996-2000 |
Pregnant women with seizure disorders without tonic-clonic seizures during pregnancy recruited through a surveillance study conducted during the first period. Then during the second study period, subjects were identified through referrals from local neurologists, pediatricians, and obstetrician/gynecologists and through a large health maintenance organization in the Boston area. | Children following gestational exposure to phenytoin 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. |
40 / 40 | 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. |
| Al Bunyan (Phenytoin), 1999 |
Saudi Arabia 1985 - 1994 |
Pregnant epileptic patients followed up in the neurology clinics during the study period. | Children whose epileptic mothers were exposed to phenytoin 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. |
9 / 10 | The control group with the data of historical controls in Saudi Arabia isn't an adequate control group. |
| Alsfouk (Phenytoin) (Controls exposed to Lamotrigine, sick), 2021 |
Riyadh and Jeddah, Saudi Arabia. 1993 - 2020 |
Pregnant women with epilepsy followed up prospectively between the study period. | Epileptic mothers with phenytoin 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. |
1 / 15 | |
| Alsfouk (Phenytoin) (Controls unexposed, sick), 2021 |
Riyadh and Jeddah, Saudi Arabia. 1993 - 2020 |
Pregnant women with epilepsy followed up prospectively between the study period. | Epileptic mothers with phenytoin 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. |
1 / 30 | |
| Arkilo (Phenytoin), 2015 |
USA 2006 - 2011 |
Women with epilepsy who were pregnant between the study period and exposed to monotherapy antiepileptic medication at any point during the pregnancy. | Singleton whose epileptic mothers were exposed to phenytoin 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. |
5 / 24 | |
| Artama (Phenytoin), 2005 |
Finland 1991 - 2000 |
Children born during the study period (n= 2350) to women who became eligible for full reimbursement for antiepileptic drugs with epilepsy as indication diagnosed before the birth. | Children whose epileptic mothers were exposed to phenytoin 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. |
38 / 939 | |
| Artama (Phenytoin) (Controls exposed to Lamotrigine, sick), 2013 |
Finland 1996 - 2008 |
All singleton births (n = 751,139) in Finland during the study period. | Births in pregnant women with epilepsy exposed to phenytoin 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. |
26 / 173 | |
| Artama (Phenytoin) (Controls unexposed, disease free), 2013 |
Finland 1996 - 2008 |
All singleton births (n = 751,139) in Finland during the study period. | Births in pregnant women with epilepsy exposed to phenytoin 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. |
26 / 721948 | |
| Artama (Phenytoin) (Controls unexposed, sick), 2013 |
Finland 1996 - 2008 |
All singleton births (n = 751,139) in Finland during the study period. | Births in pregnant women with epilepsy exposed to phenytoin 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. |
26 / 1800 | |
| Aydin (Phenytoin) (Controls exposed to Lamotrigine, sick), 2020 |
Turkey 2007 - 2017 |
Pregnant women with epilepsy who delivered and had follow ups at the division of perinatalogy between the study period. | Pregnant women with epilepsy who received phenytoin 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. |
1 / 7 | There were no patients who had drug changes or discontinued during pregnancy. |
| Aydin (Phenytoin) (Controls unexposed, sick), 2020 |
Turkey 2007 - 2017 |
Pregnant women with epilepsy who delivered and had follow ups at the division of perinatalogy between the study period. | Pregnant women with epilepsy who received phenytoin 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. |
1 / 22 | There were no patients who had drug changes or discontinued during pregnancy. |
| Bank (Phenytoin) (Mixed indications), 2017 |
USA 2002 - 2006 |
Only pregnant women who were treated with antiepileptic drugs for epilepsy or bipolar disorder who chose to continue antiepileptic drugs during pregnancy and whose infants had umbilical cord antiepileptic drugs levels drawn at the time of delivery were included. | Singleton pregnancies in mothers taking phenytoin monotherapy during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Singleton pregnancies in mothers taking lamotrigine monotherapy during pregnancy. |
3 / 36 | |
| Battino (Phenytoin), 1992 |
Milan 1977 - 1989 |
Epileptic patients were followed prospectively from the beginning of the pregnancy during the study period in the context of the Milan Collaborative Study on Epilepsy and Pregnancy. | Offspring of epileptic mothers treated with phenytoin 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. |
27 / 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. |
| Battino (Phenytoin), 1999 |
Japan, Italy and Canada 1978 - 1991 |
Female patient of childbearing age with epilepsy who visited clinics and who consented to be followed throughout their pregnancy. The data from three studies carried out in Canada, Japan and Italy were pooled. | Infants whose epileptic mothers were exposed to phenytoin 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. |
118 / 36 | Each country has its own reference standards, then the data from the different countries are pooled. Exposition period deducted from Kaneko 1999. |
| Bromley (Phenytoin) (Controls exposed to Lamotrigine, sick), 2008 |
UK 2000 - 2006 |
620 women (with or without epilepsy) were recruited from antenatal clinics and information has been collected on 632 live births. | Live births were to women with epilepsy exposed to phenytoin monotherapy at the beginning of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Live births were to women with epilepsy exposed to lamotrigine monotherapy at the beginning of gestation. |
9 / 44 | |
| Bromley (Phenytoin) (Controls unexposed, disease free), 2008 |
UK 2000 - 2006 |
620 women (with or without epilepsy) were recruited from antenatal clinics and information has been collected on 632 live births. | Live births were to women with epilepsy exposed to phenytoin monotherapy at the beginning of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Live births born to women without epilepsy who were not taking medication. |
9 / 336 | |
| Bromley (Phenytoin) (Controls unexposed, sick), 2008 |
UK 2000 - 2006 |
620 women (with or without epilepsy) were recruited from antenatal clinics and information has been collected on 632 live births. | Live births were to women with epilepsy exposed to phenytoin monotherapy at the beginning of gestation. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Children born to women with epilepsy who were not medicated during the time of the pregnancy. |
9 / 47 | |
| Canger (Phenytoin), 1999 |
Italy 1977 - 1996 |
517 women with epilepsy reffered to the study mainly from the Milan metropolitan and suburban areas or other Italian regions. They were followed up during the preconceptional period and/or from the beginning of pregnancy. | Infants of epileptic mothers exposed to phenytoin 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. |
31 / 25 | Only the first pregnancies of each of the 517 women were included in the analysis. |
| Cohen (Phenytoin), 2011 |
UK and USA 1999 - 2004 |
Pregnant women with epilepsy who were taking a single antiepileptic drug in one of the 25 centers across UK and USA. | Infants of women exposed to phenytoin 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. |
40 / 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. |
| Cohen (Phenytoin), 2013 |
USA and UK 1999 - 2004 |
Pregnant women (n=192) with epilepsy who were taking a single antiepileptic drug in one of the 25 epilepsy centers across UK and USA. | Infants of women exposed to phenytoin 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. |
31 / 63 | A nonexposed control group was not included. |
| D'Souza (Phenytoin) (Controls unexposed, disease free), 1991 |
UK 1980 - 1982 |
A group of pregnant mothers each of whom gave a history of grand mal epilepsy and who were referred to the antenatal clinic during the study period. | Infants born to epileptic mothers treated with phenytoin 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. |
22 / 62 | |
| D'Souza (Phenytoin) (Controls unexposed, sick), 1991 |
UK 1980 - 1982 |
A group of pregnant mothers each of whom gave a history of grand mal epilepsy and who were referred to the antenatal clinic during the study period. | Infants born to epileptic mothers treated with phenytoin 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. |
22 / 8 | |
| Dean (Phenytoin), 2002 |
Scotland 1976 - 2000 |
Children of mothers taking antiepileptic drugs in pregnancy during the study period were ascertained from hospital obstetric records. | Children whose mothers took phenytoin 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. |
25 / 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. |
| Dean (Phenytoin) (Controls exposed to Lamotrigine, sick), 2007 |
Scotland 1976 - 2002 |
Children of mothers who were prescribed antiepileptic drugs during a pregnancy between the study period were identified from hospital records. | Children whose epileptic mothers were exposed to phenytoin 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. |
24 / 4 | A previous publication (Dean 2002) gives a better review of the major malformations. |
| Dean (Phenytoin) (Controls unexposed, sick), 2007 |
Scotland 1976 - 2002 |
Children of mothers who were prescribed antiepileptic drugs during a pregnancy between the study period were identified from hospital records. | Children whose epileptic mothers were exposed to phenytoin 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. |
24 / 46 | A previous publication (Dean 2002) gives a better review of the major malformations. |
| Díaz-Romero (Phenytoin), 1999 |
Mexico 1993 - 1996 |
Full-term eutrophic newborns of epileptic mothers who attended the Epilepsy Clinic of the National Institute of Perinatology, a third-level gyneco-obstetric center in Mexico City during the study period. | Full-term eutrophic newborns of epileptic mothers exposed to only phenytoin 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. |
21 / 8 | All newborns in the intensive care unit, and those with congenital malformations with a different specific recognizable etiology were excluded. |
| Fedrick (Phenytoin), 1973 |
UK 1966 - 1970 |
All births (whether hospital or domiciliary) and all deaths of residents in Oxfordshire and most of Berkshire from all women coded as having epilepsy and who delivered in the study period. | Infants of epileptic mothers exposed to phenytoin alone in the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Infants of epileptic mothers not taking drugs. |
33 / 19 | The control series with three control pregnancies resulting in livebirths chosen for each pregnancy resulting in a livebirth to an epileptic mother cannot be used for defect control per antiepileptic drugs types. |
| Forsberg (Phenytoin) (Controls unexposed NOS), 2011 |
Sweden 1973 - 1986 |
Using the Swedish Medical Birth Register, deliveries among women with epilepsy were identified between the study period. | Children identified with maternal epilepsy who had been exposed to phenytoin 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. |
316 / 1307083 | These analyses were made after exclusion of children with a diagnosis of a congenital malformation. |
| Forsberg (Phenytoin) (Controls unexposed, sick), 2011 |
Sweden 1973 - 1986 |
Using the Swedish Medical Birth Register, deliveries among women with epilepsy were identified between the study period. | Children identified with maternal epilepsy who had been exposed to phenytoin 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. |
316 / -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. |
| He (Phenytoin) (Controls exposed to Lamotrigine, sick), 2017 |
China 2009 - 2015 |
Women with epilepsy who decided to settle on West China Second University Hospital of Sichuan University for antenatal examination and delivery. | Pregnancies in which phenytoin monotherapy was used during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Pregnancies in which lamotrigine monotherapy was used during pregnancy. |
4 / 8 | Patients who developed epilepsy during pregnancy or after delivery were not included. |
| He (Phenytoin) (Controls unexposed, sick), 2017 |
China 2009 - 2015 |
Women with epilepsy who decided to settle on West China Second University Hospital of Sichuan University for antenatal examination and delivery. | Pregnancies in which phenytoin monotherapy was used during pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Pregnancies in which antiepileptic drugs were never used before and during pregnancy. |
4 / 31 | Patients who developed epilepsy during pregnancy or after delivery were not included. |
| Hernández-Díaz (Phenytoin) (Controls exposed to Lamotrigine, sick), 2012 |
North America and Canada 1997 - 2011 |
Pregnant women who are taking an antiepileptic drug for any reason and had a liveborn infant, a stillborn infant, or a pregnancy terminated because of a fetal abnormality and enrolled as 'pure' or 'traditional' enrollees. | Infants of pregnant women who used phenytoin 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). |
416 / 1562 | Total congenital malformations results are completely overlapped by the update on the registry website. Less than 90% of women are taking Lamotrigine for epilepsy. |
| Hernández-Díaz (Phenytoin) (Controls unexposed, disease free), 2012 |
North America and Canada 1997 - 2011 |
Pregnant women who are taking an antiepileptic drug for any reason and had a liveborn infant, a stillborn infant, or a pregnancy terminated because of a fetal abnormality and enrolled as 'pure' or 'traditional' enrollees. | Infants of pregnant women who used phenytoin 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. |
416 / 442 | Total congenital malformations results are completely overlapped by the update on the registry website. |
| Holmes (Phenytoin) (Controls unexposed, disease free), 2001 |
United States 1986 - 1993 |
128,049 pregnant women at delivery who gave birth to singleton in the labor and delivery suites during the study period. | Infants exposed in utero to phenythoin 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. |
87 / 508 | 9% are exposed for other indications (no specified per type of AED). |
| Holmes (Phenytoin) (Controls unexposed, sick), 2001 |
United States 1986 - 1993 |
128,049 pregnant women at delivery who gave birth to singleton in the labor and delivery suites during the study period. | Infants exposed in utero to phenythoin 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. |
87 / 98 | 9% are exposed for other indications (no specified per type of AED). |
| Hvas (Phenytoin) (Controls unexposed, disease free), 2000 |
Denmark 1989 - 1997 |
Singleton pregnancies in Danish-speaking women who attended for antenatal care and delivered at Aarhus University Hospital during the study period. All women who reported chronic disease other than epilepsy were excluded. | Children of women with epilepsy exposed to phenytoin 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. |
1 / 24094 | |
| Hvas (Phenytoin) (Controls unexposed, sick), 2000 |
Denmark 1989 - 1997 |
Singleton pregnancies in Danish-speaking women who attended for antenatal care and delivered at Aarhus University Hospital during the study period. All women who reported chronic disease other than epilepsy were excluded. | Children of women with epilepsy exposed to phenytoin 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. |
1 / 106 | |
| Kaaja (Phenytoin), 2003 |
Finland 1980 - 1998 |
All women with epilepsy regardless of whether they used antiepileptic drugs during the index pregnancy. | Infants whose epileptic mothers took phenytoin as 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. |
124 / 239 | |
| Källén (Phenytoin) (Controls exposed to Lamotrigine, sick) (Indications NOS), 2013 |
Swedish 1996 - 2011 |
Nearly all births in Sweden during the study period (1,575,847) are registered in The Swedish Medical Birth Register. | Infants whose mothers used phenytoin in monotherapy in early pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants whose mothers used lamotrigine in monotherapy in early pregnancy. |
140 / 1084 | Indications for antiepileptic drugs are not specified. Wide 2004 outcomes' are already included in Källèn et al 2013 or are not compared to an adequate control group. Follow-up period known thanks to author's email reply. |
| Källén (Phenytoin) (Controls unexposed, NOS) (Indications NOS), 2013 |
Swedish 1996 - 2011 |
Nearly all births in Sweden during the study period (1,575,847) are registered in The Swedish Medical Birth Register. | Infants whose mothers used phenytoin in monotherapy in early pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Infants in population whose mothers used at least one of a central nervous system active drugs (less than 3%) or weren't exposed in early pregnancy. |
140 / 1575847 | Indications for antiepileptic drugs are not specified. Follow-up period known thanks to author's email reply. |
| Kaneko (Phenytoin), 1999 |
Japan, Italy and Canada. 1978 - 1991 |
Female patient of childbearing age with epilepsy who visited clinics and who consented to be followed throughout their pregnancy. The data from three studies carried out in Canada, Japan and Italy were pooled. | Offspring whose epileptic mothers were under phenytoin 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. |
132 / 98 | Details about the design were completed thanks to Battino et al., 1999 publication. Kaneko 1999 overlapped with Kaneko 1988, Oguni 1992, Dansky 1982, Canger 1999 and Battino 1992. |
| Katz (Phenytoin), 2001 |
USA 1990 - 2000 |
The clinical histories of women with epilepsy cared for at the center, contributing 103 newborns during the study period. | Newborn of women with epilepsy exposed to phenytoin 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. |
6 / 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. |
| Kelly (Phenytoin), 1984 |
USA 1977 - 1982 |
Women of childbearing age with epilepsy. | Children and older sibs born to study epileptic mothers receiving diphenylhydantoin alone at the time they were enrolled. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Children and older sibs born to study epileptic mothers not on anticonvulsant treatment at the time they were enrolled. |
41 / 21 | |
| Kilic (Phenytoin) (Controls exposed to Lamotrigine, sick) (Mixed indications), 2014 |
Denmark 1997 - 2008 |
All singleton live-born children in Denmark during the study period. | Children whose mothers have been exposed to phenytoin in monotherapy during the exposure window defined from 30 days before the estimated day of conception to the day prior to birth. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Children whose mothers have been exposed to lamotrigine in monotherapy during the exposure window defined from 30 days before the estimated day of conception to the day prior to birth. |
5 / 880 | Less than 90% of women are epileptic. |
| Kilic (Phenytoin) (Controls unexposed NOS) (Mixed indications), 2014 |
Denmark 1997 - 2008 |
All singleton live-born children in Denmark during the study period. | Children whose mothers have been exposed to phenytoin in monotherapy during the exposure window defined from 30 days before the estimated day of conception to the day prior to birth. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Children whose mothers haven't been exposed to antiepileptic drugs 30 days before the estimated day of conception to the day of birth. |
5 / 676834 | Less than 90% of women are epileptic. |
| Kilic (Phenytoin) (Controls unexposed, sick) (Mixed indications), 2014 |
Denmark 1997 - 2008 |
All singleton live-born children in Denmark during the study period. | Children whose mothers have been exposed to phenytoin in monotherapy during the exposure window defined from 30 days before the estimated day of conception to the day prior to birth. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Children whose mothers have an epilepsy diagnosis and haven't been exposed to antiepileptic drugs 30 days before the estimated day of conception to the day of birth. |
5 / 5296 | Less than 90% of women are epileptic. |
| Kini (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 |
UK 1989 - 1999 |
375 children aged between 6 months and 16 years from 219 mothers with epilepsy exposed and not exposed to antiepileptic drugs during pregnancy attending epilepsy clinics or antenatal care between the study period. | Children exposed to phenytoin 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. |
26 / 9 | Because we don't know the exact number of children exposed to lamotrigine and analyzed for malformations, this outcome cannot be reported here. |
| Kini (Phenytoin) (Controls unexposed, sick), 2006 |
UK 1989 - 1999 |
375 children aged between 6 months and 16 years from 219 mothers with epilepsy exposed and not exposed to antiepileptic drugs during pregnancy attending epilepsy clinics or antenatal care between the study period. | Children exposed to phenytoin 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. |
26 / 101 | A better review of the WISC score for children aged 6 and above are provided by Adab 2004 publication. |
| Koch (Phenytoin), 1996 |
Germany 1976 - 1983 |
Children born to epileptic women who had been treated during pregnancy with antiepileptic drug monotherapy of either primidone/phenobarbitone, phenytoin or valproic acid were studied in detail. The mothers were randomly recruited during their pregnancy from five obstetric departments within the city of Berlin. | Children born to epilepic mothers who had been exposed to phenytoin during fetal life. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Children born to mothers randomly recruited during their pregnancy from the same obstetric departments. |
13 / 65 | Study design partly completed with cited source [13]. |
| Lowe (Phenytoin) (Controls unexposed, disease free), 1973 |
UK (Wales) 1965 - 1971 |
All the infants (31,877) born to women domiciled in Cardiff during the study period. | Infants born to women who gave a history of having had an epileptic seizure at any time in their lives and exposed to phenytoin alone 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 women living in Cardiff who didn't gave a history of having had an epileptic seizure at any time in their lives. |
9 / 31632 | |
| Lowe (Phenytoin) (Controls unexposed, sick), 1973 |
UK (Wales) 1965 - 1971 |
All the infants (31,877) born to women domiciled in Cardiff during the study period. | Infants born to women who gave a history of having had an epileptic seizure at any time in their lives and exposed to phenytoin alone during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Infants of mothers with a history of epilepsy but not on anticonvulsants. |
9 / 111 | |
| Mawer (Phenytoin) (Controls exposed to Lamotrigine, sick), 2010 |
UK 2000 - 2006 |
Midwives in the antenatal clinics approached each woman, who gave a history of epilepsy (n=231), whatever her stage of gestation. | Children born to mothers with epilepsy exposed to phenytoin 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. |
7 / 40 | Kini's 2007 malformation results are overlapped. Specific major malformations' numerators are extracted from the review by Weston et al. 2016 because not classified per types in the original publication. Period of exposure confirm by author's email. |
| Mawer (Phenytoin) (Controls unexposed, disease free), 2010 |
UK 2000 - 2006 |
Women with epilepsy (WWE) and the healthy woman controls attending the same clinic. | Children born to mothers with epilepsy exposed to phenytoin 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. |
7 / 315 | Kini's 2007 malformation results are overlapped. Specific major malformations' numerators are extracted from the review by Weston et al. 2016 because not classified per types in the original publication. Period of exposure confirm by author's email. |
| Mawer (Phenytoin) (Controls unexposed, sick), 2010 |
UK 2000 - 2006 |
Midwives in the antenatal clinics approached each woman, who gave a history of epilepsy (n=231), whatever her stage of gestation. | Children born to mothers with epilepsy exposed to phenytoin 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. |
7 / 46 | Kini's 2007 malformation results are overlapped. Specific major malformations' numerators are extracted from the review by Weston et al. 2016 because not classified per types in the original publication. Period of exposure confirm by author's email. |
| Meador (Phenytoin), 2009 |
UK and USA 1999 - 2004 |
Livebirths (n=309) of pregnant women with epilepsy who were receiving antiepileptic drugs in monotherapy. | Infants of women exposed to phenytoin 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. |
52 / 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. |
| Meador (Phenytoin), 2011 |
UK and USA 1999 - 2004 |
Pregnant women (n=211) with epilepsy who were taking a single antiepileptic drug in one of the 25 centers across UK and USA. | Infants of women exposed to phenytoin 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. |
39 / 70 | A non-exposed control group was not included. |
| Meador (Phenytoin), 2013 |
UK and USA. 1999 - 2004 |
Livebirths (n=311) of pregnant women with epilepsy who were receiving a single antiepileptic drug in one of the 25 centers across UK and USA between the study period. | Infants of epileptic mothers exposed to phenytoin 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. |
55 / 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. |
| Meador (Phenytoin), 2006 |
USA and UK 1999 - 2004 |
Pregnant women with epilepsy treated with antiepileptic drugs in monotherapy. | Infants of women exposed to phenytoin 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. |
56 / 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. |
| Miškov (Phenytoin) (Controls exposed to Lamotrigine, sick), 2016 |
Croatia 2003 - 2013 |
Pregnant women with epilepsy during the study period at the the Sestre milosrdnice University Hospital Center. | Pregnancies in women with epilepsy on phenytoin 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. |
1 / 37 | Includes all Miskov's 2010 outcomes. |
| Miškov (Phenytoin) (Controls unexposed, disease free), 2016 |
Croatia 2003 - 2013 |
Pregnant women with epilepsy during the study period at the the Sestre milosrdnice University Hospital Center. | Pregnancies in women with epilepsy on phenytoin monotherapy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Pregnancies in healthy controls. |
1 / 147 | Includes all Miskov's 2010 outcomes. |
| Miškov (Phenytoin) (Controls unexposed, sick), 2016 |
Croatia 2003 - 2013 |
Pregnant women with epilepsy during the study period at the the Sestre milosrdnice University Hospital Center. | Pregnancies in women with epilepsy on phenytoin 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. |
1 / 4 | Includes all Miskov's 2010 outcomes. |
| Morrow (Phenytoin) (Controls exposed to Lamotrigine, sick), 2006 |
UK and Ireland 1996 - 2005 |
Pregnant women with epilepsy, whether or not they were taking an AED, either in monotherapy or polytherapy, and who were referred to the register before the outcome of the pregnancy was known. | Infants of women with epilepsy exposed to phenytoin 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. |
82 / 647 | Exposure period is completed thanks to Campbell 2014 which is also a UKEPR based study. |
| Morrow (Phenytoin) (Controls unexposed, sick), 2006 |
UK and Ireland 1996 - 2005 |
Pregnant women with epilepsy, whether or not they were taking an antiepileptic drug, either in monotherapy or polytherapy, and who were referred to the register before the outcome of the pregnancy was known. | Infants of women with epilepsy exposed to phenytoin in monotherapy during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Infants of women with epilepsy and who didn't take any antiepileptic drugs during pregnancy. |
82 / 227 | Exposure period is completed thanks to Campbell 2014 which is also a UKEPR based study. |
| Nulman (Phenytoin) (Controls unexposed, NOS) (Mixed indications), 1997 |
Canada 1987 - 1992 |
Pregnant women treated with either phenytoin or carbamazepine in monotherapy and an additional group of women with epilepsy who did not take medications during the index pregnancy and seen between the study period. | Mother-child pairs exposed to phenytoin in monotherapy at least during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed (general population or NOS)
Child from the next woman attending the Motherisk Clinic whose reason for attendance was counseling after gestational exposure to nonteratogens. |
34 / 34 | Less than 90% of women are taking Phenytoin for epilepsy. Gladstone 1992 malformations result's are partly included in this study due to overlapping of the study period with the same register. |
| Nulman (Phenytoin) (Controls unexposed, sick) (Mixed indications), 1997 |
Canada 1987 - 1992 |
Pregnant women treated with either phenytoin or carbamazepine in monotherapy and an additional group of women with epilepsy who did not take medications during the index pregnancy and seen between the study period. | Mother-child pairs exposed to phenytoin in monotherapy at least during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Child from epileptic women who did not receive drug therapy during the index pregnancy. |
34 / 9 | Less than 90% of women are taking Phenytoin for epilepsy. Gladstone 1992 malformations result's are partly included in this study due to overlapping of the study period with the same register. |
| Pennell (Phenytoin), 2012 |
USA and UK 1999 - 2004 |
Pregnant women with epilepsy (n=329) producing 311 live births, who were taking a single antiepileptic drug at time of conception to enrollment in one of the 25 centers across UK and USA. | Infants of women exposed to phenytoin 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. |
55 / 98 | |
| Samrén (Phenytoin), 1999 |
Netherlands 1972 - 1994 |
Offspring of women with epilepsy, with or without antiepileptic drug use during pregnancy, born during the study period. | Children born to mothers with epilepsy and using phenytoin monotherapy at least during the first trimester of pregnancy |
unexposed, disease free
Children born to nonepileptic nonexposed women. |
151 / 2000 | |
| Sonneveld (Phenytoin) (Controls unexposed NOS), 1990 |
Tasmania 1981- 1988 |
Pregnancies of all private and public patients in Tasmania during the study period. 56,557 deliveries during the study period of which 347 were in patients with epilepsy. | Epileptic pregnancies exposed to phenytoin 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. |
79 / 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. |
| Sonneveld (Phenytoin) (Controls unexposed, sick), 1990 |
Tasmania 1981- 1988 |
Pregnancies of all private and public patients in Tasmania during the study period. 56,557 deliveries during the study period of which 347 were in patients with epilepsy. | Epileptic pregnancies exposed to phenytoin 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. |
79 / 87 | |
| Steegers-Theunissen (Phenytoin), 1994 |
Netherlands Not specified |
Epileptic and healthy control women visiting the outpatient departments were recruited before conception and just one singleton pregnancy per woman is studied. | Singleton of epileptic women exposed to phenytoin 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. |
8 / 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 NAAED (Controls exposed to Lamotrigine, sick) (Indications NOS), 2022 |
North America and Canada 1997 - 2020 |
Pregnant women who are taking an antiepileptic drug for any reason and had a liveborn infant, a stillborn infant, or a pregnancy terminated because of a fetal abnormality and enrolled as 'pure' or 'traditional' enrollees. | Infants of pregnant women who used phenytoin as monotherapy, during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Infants of pregnant women who used lamotrigine as monotherapy, during the first trimester. |
423 / 2333 | Study design completed with the publication of Hernández-Díaz et al. 2012. Data extracted from the North American AED pregnancy registry website. Indications not specified. |
| The NAAED (Controls unexposed, disease free) (Indications NOS), 2022 |
North America and Canada 1997 - 2020 |
Pregnant women who are taking an antiepileptic drug for any reason and had a liveborn infant, a stillborn infant, or a pregnancy terminated because of a fetal abnormality and enrolled as 'pure' or 'traditional' enrollees. | Infants of pregnant women who used phenytoin as monotherapy, during the first trimester. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, disease free
Infants of pregnant women, not taking an antiepileptic drug and without epilepsy, who were recruited from among the friends and family members of the enrolled women taking an antiepileptic drug. |
423 / 1201 | Study design completed with the publication of Hernández-Díaz et al. 2012. Data extracted from the North American AED pregnancy registry website. Internal control group reported rather than the external (for relevance purpose). Indications not specified. |
| Thomas (Phenytoin), 2022 |
India 1998 - 2006 |
Children (13–21 years) of women with epilepsy (CWWE) who were 13 years old or older on 31 December 2019 and had undergone developmental assessment at one year. | Children of women with epilepsy (CWWE) exposed to Phenytoin monotherapy during pregnancy. |
unexposed, sick
Children of women with epilepsy (CWWE) not exposed to antiseizure medications during pregnancy. |
10 / 11 | Overlapping: Thomas 2022 included data on language and cognitive delay, also evaluated in Sreedharan et al., 2018; Thomas 2007 and Gopinath 2015, but with more exposed pregnancies, more relevant control group and older children => Use of Thomas 2022. |
| Thomas (Phenytoin) (Controls exposed to Lamotrigine, sick), 2021 |
India 1998 - 2019 |
All pregnancies with known outcomes in women with epilepsy enrolled in the registry during 1998 - 2013 and the diagnosis of epilepsy was confirmed before registration. | Children of women with epilepsy using phenytoin 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. |
119 / 50 | Study design completed with Thomas et al., 2017. Keni's 2018 malformations results are already reported in this publication. |
| Thomas (Phenytoin) (Controls unexposed, disease free), 2021 |
India 1998 - 2015 |
All pregnancies with known outcomes in women with epilepsy enrolled in the registry during 1998 - 2013 and the diagnosis of epilepsy was confirmed before registration. | Children of women with epilepsy using phenytoin 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. |
106 / 319 | This external control group is only available in the 2017 publication. |
| Thomas (Phenytoin) (Controls unexposed, sick), 2021 |
India 1998 - 2019 |
All pregnancies with known outcomes in women with epilepsy enrolled in the registry during 1998 - 2013 and the diagnosis of epilepsy was confirmed before registration. | Children of women with epilepsy using phenytoin 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. |
119 / 340 | Study design completed with Thomas et al., 2017. Thomas et al., 2008 completely overlapped with this publication. |
| Thomas b (Phenytoin), 2008 |
India 1998 - 2004 |
395 infants born to mothers with epilepsy enrolled in the preconception period or during early pregnancy before the fetal outcome is known. | Infants whose epileptic mothers were on phenytoin monotherapy anytime during the pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Infants not prenatally exposed to antiepileptic drugs anytime during the pregnancy. |
29 / 32 | The Developmental Assessment Scale for Indian Infants (DASII) is an adaptation of the Bayley Scale of Infant Development standardized for Indian infants. |
| Titze (Phenytoin) (Controls unexposed, disease free), 2008 |
Germany 1976 - 1984 |
Adolescents born during the study period from mothers randomly recruited during their pregnancy, were asked to participate if they had been followed up to 6 years of age. | Adolescents whose epileptic mothers were exposed to hydantoin 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. |
12 / 49 | 'The most common antiepileptic drugs were diphenylhydantoin' so the hydantoin group is assessed as predominantly phenytoin exposure. |
| Titze (Phenytoin) (Controls unexposed, sick), 2008 |
Germany 1976 - 1984 |
Adolescents born during the study period from mothers randomly recruited during their pregnancy, were asked to participate if they had been followed up to 6 years of age. | Adolescents whose epileptic mothers were exposed to hydantoin 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. |
12 / 13 | 'The most common antiepileptic drugs were diphenylhydantoin' so the hydantoin group is assessed as predominantly phenytoin exposure. |
| Tomson (Phenytoin), 2018 |
42 countries 1999 - 2016 |
Pregnancies registered in the database during the study period who had been exposed to antiepileptic drug monotherapy and had complete follow-up data up to 1 year. They were enrolled within gestation week 16 and before fetal outcome is known. | Offspring exposed in utero to phenytoin 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. |
125 / 2514 | This study is an update of Tomson's 2011 publication. They excluded from the current analysis pregnancies occurring in women without epilepsy. EURAP registry: potential overlap. |
| Trivedi (Phenytoin) (Controls exposed to Lamotrigine, sick), 2018 |
India 1998 - 2015 |
All women with epilepsy who had completed their pregnancies and enrolled in the registry between the study period. The diagnosis of epilepsy was confirmed before registration. | Pregnant women with epilepsy who used phenytoin 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. |
129 / 48 | Study design partly completed with cites source Thomas et al., 2017. |
| Trivedi (Phenytoin) (Controls unexposed, sick), 2018 |
India 1998 - 2015 |
All women with epilepsy who had completed their pregnancies and enrolled in the registry between the study period. The diagnosis of epilepsy was confirmed before registration. | Pregnant women with epilepsy who used phenytoin 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. |
129 / 178 | Study design partly completed with cites source Thomas et al., 2017. |
| Vajda (Phenytoin) (Controls exposed to Lamotrigine, sick), 2019 |
Australia 1999 - 2018 |
Pregnant women taking antiepileptic drugs for any indications or not treated with antiepileptic drugs in at least the first half of pregnancy. | Offsprings born from women nearly always with epilepsy exposed to phenytoin in monotherapy in at least the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Offsprings born from women nearly always with epilepsy exposed to lamotrigine in monotherapy in at least the first trimester of pregnancy. |
44 / 406 | Women with epilepsy accounted for 98.3%. Completely overlap Vajda 2007; 2010 (x2); 2012 (x2); 2013 and 2014. Study design partly completed with Vajda 2013. |
| Vajda (Phenytoin) (Controls exposed to Lamotrigine, sick), 2018 |
Australia 1999 - 2016 |
Pregnant women whether treated with antiepileptic drugs or left untreated in at least the first half of pregnancy. | Offsprings of pregnant women with epilepsy exposed to phenytoin in monotherapy throughout. (This is a subgroup of exposure among the whole exposed group considered in the study). |
exposed to other treatment, sick
Offsprings of pregnant women with epilepsy exposed to lamotrigine in monotherapy throughout. |
42 / 382 | |
| Vajda (Phenytoin) (Controls exposed to Lamotrigine, sick), 2013 |
Australia 1999 - 2013 |
Pregnant women with epilepsy whether treated with antiepileptic drugs or left untreated or pregnant women taking antiepileptic drugs for other purposes. | Offsprings from women with epilepsy exposed to phenytoin 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. |
44 / 315 | Women taking AED for epilepsy are in majority (more than 90%). Vajda 2019 provides the most recent update for major malformations results for this register. Specific malformations' results are extracted from the review by Weston et al. 2016. |
| Vajda (Phenytoin) (Controls unexposed, sick), 2019 |
Australia 1999 - 2018 |
Pregnant women taking antiepileptic drugs for any indications or not treated with antiepileptic drugs in at least the first half of pregnancy. | Offsprings born from women nearly always with epilepsy exposed to phenytoin in monotherapy in at least the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Offsprings born from women nearly always with epilepsy not treated with antiepileptic drugs in at least the first half of pregnancy. |
44 / 176 | Women with epilepsy accounted for 98.3%. Completely overlap Vajda 2007; 2010 (x2); 2012 (x2); 2013 and 2014. Study design partly completed with Vajda 2013. |
| Vajda (Phenytoin) (Controls unexposed, sick), 2018 |
Australia 1999 - 2016 |
Pregnant women whether treated with antiepileptic drugs or left untreated in at least the first half of pregnancy. | Offsprings of pregnant women with epilepsy exposed to phenytoin in monotherapy throughout. (This is a subgroup of exposure among the whole exposed group considered in the study). |
unexposed, sick
Offsprings of pregnant women with epilepsy that have been untreated in at least the first half of pregnancy. |
42 / 170 | |
| Vajda (Phenytoin) (Controls unexposed, sick), 2013 |
Australia 1999 - 2013 |
Pregnant women with epilepsy whether treated with antiepileptic drugs or left untreated or pregnant women taking antiepileptic drugs for other purposes. | Offsprings from women with epilepsy exposed to phenytoin 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. |
44 / 147 | Women taking AED for epilepsy are in majority (more than 90%). Vajda 2019 provides the most recent update for major malformations results for this register. Specific malformations' results are extracted from the review by Weston et al. 2016. |
| Viinikainen (Phenytoin) (Controls unexposed, disease free) a, 2006 |
Finland 1989 - 2000 |
24,778 singleton pregnancies in 16,598 women and 179 of these were pregnancies of women with epilepsy followed up during the pregnancy by the Department of Neurology and gave birth in the hospital. | Pregnancies of mothers who had active epilepsy and were using phenytoin 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. |
2 / 24778 | Multiple pregnancies and pregnancies with evident neonatal chromosomal abnormalities were excluded. |
| Viinikainen (Phenytoin) (Controls unexposed, sick) a, 2006 |
Finland 1989 - 2000 |
24,778 singleton pregnancies in 16,598 women and 179 of these were pregnancies of women with epilepsy followed up during the pregnancy by the Department of Neurology and gave birth in the hospital. | Pregnancies of mothers who had active epilepsy and were using phenytoin 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. |
2 / 52 | Multiple pregnancies and pregnancies with evident neonatal chromosomal abnormalities were excluded. |
| Vinten (Phenytoin), 2005 |
UK Not specified. |
Women with a diagnosis of epilepsy who had children aged between 6 and 16 years recruited from specialist epilepsy clinics and obstetric clinics from the Liverpool and Manchester region. | Children born to epileptic mothers on phenytoin 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. |
21 / 83 | Repeat population groups and the same data are already obtained in Adab 2004 for all the neurodevelopmental outcomes (with more exposed pregnancies and better scale) except the verbal IQ score <69. Vinten 2009 langage assessment is overlapped. |
| Waters (Phenytoin) (Controls unexposed, disease free), 1994 |
USA 1987 - 1990 |
Women with epilepsy in a high risk obstetric clinic. | Infants born to epileptic mothers exposed to phenytoin 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. |
28 / 355 | Mothers who abused alcohol and other drugs were excluded from both patient ad control groups. |
| Waters (Phenytoin) (Controls unexposed, sick), 1994 |
USA 1987 - 1990 |
Women with epilepsy in a high risk obstetric clinic. | Infants born to epileptic mothers exposed to phenytoin 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. |
28 / 15 | Mothers who abused alcohol and other drugs were excluded from both patient ad control groups. |
| Wide (Phenytoin), 2000 |
Sweden 1985 - 1995 |
Children born to mothers with epilepsy ascertain in early pregnancy who were treated with antiepileptic drugs from conception and monitor throughout pregnancy. | First-born infants whose epileptic mothers were continuously treated with phenytoin 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. |
22 / 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. |
| Yerby (Phenytoin), 1992 |
USA Not specified. |
Women with a diagnosis of epilepsy determined by a neurologist, antiepileptic drug use, and active planning for pregnancy or early (first trimester) pregnancy. | Infants of mothers with epilepsy treated by phenytoin 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. |
12 / 46 | Women were excluded if they had another chronic illness and were not compliant. |
| Study | Country Study period |
Case | Control | Sample size | Rmk |
|---|---|---|---|---|---|
| Arteaga-Vázquez (Phenytoin), 2012 |
Mexico 1978 - 2010 |
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. | 71 / 95 | |
| Bànhidy (Phenytoin), 2011 |
Hungary 1980 - 1996 |
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. | 95 / 90 | Congenital abnormalities syndromes caused by major mutant genes or chromosomal aberrations with preconceptional origin were excluded. Exposure period completed with Czeizel 1992. |
| Czeizel (Phenytoin), 1992 |
Hungary 1980 - 1987 |
Children affected with congenital abnormalities born from treated or untreated mothers. | Children without congenital abnormalities born from treated or untreated mothers. | 100 / 54 | The study design was partly completed thanks to the reference [6] cited in the publication. All congenital abnormalities except spina bifida are overlapped by the publication of Bànhidy 2011. |
| Thomas a (Phenytoin), 2008 |
India 1998 - 2004 |
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. | 36 / 426 | Completely overlapped with Thomas et al., 2021. |
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