Study | Country Study period |
Population source | Exposure definition | Non-exposure definition | Sample size | Rmk |
---|---|---|---|---|---|---|
Battino (Primidone), 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 primidone 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. |
37 / 36 | Each country has its own reference standards, then the data from the different countries are pooled. Exposition period deducted from Kaneko 1999. |
Battino (Primidone), 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 primidone 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. |
31 / 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. |
Burja (Primidone) (Controls unexposed, disease free), 2006 |
Slovenia 1998 - 2002 |
Newborns and their mothers who gave birth at the Maribor Department of Obstetric and Perinatology during the study period. | Newborn in women diagnosed as having epilepsy who had taken primidone 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. |
1 / 211 | |
Burja (Primidone) (Controls unexposed, sick), 2006 |
Slovenia 1998 - 2002 |
Newborns and their mothers who gave birth at the Maribor Department of Obstetric and Perinatology during the study period. | Newborn in women diagnosed as having epilepsy who had taken primidone 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. |
1 / 32 | |
Canger (Primidone), 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 primidone 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. |
35 / 25 | Only the first pregnancies of each of the 517 women were included in the analysis. |
Dean (Primidone), 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 primidone 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. |
2 / 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. |
Kaaja (Primidone), 2003 |
Finland 1980 - 1998 |
All women with epilepsy regardless of whether they used antiepileptic drugs during the index pregnancy. | Infants whose epileptic mothers took primidone 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. |
6 / 239 | |
Kaneko (Primidone), 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 primidone 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. |
35 / 98 | Details about the design were completed thanks to Battino et al., 1999 publication. Kaneko 1999 overlapped with Kaneko 1988, Canger 1999 and Battino 1992. |
Katz (Primidone), 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 primidone 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. |
2 / 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. |
Kini (Primidone) (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 primidone 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. |
2 / 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 (Primidone) (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 primidone 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. |
2 / 101 | Because we don't know the exact number of children exposed to primidone and analyzed for malformations, this outcome cannot be reported here. |
Koch (Primidone), 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 primidone 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. |
14 / 65 | Primidone and phenobarbitone are regarded as the same drug for the authors. Study design partly completed with cited source [13]. |
Lowe (Primidone) (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 primidone 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. |
4 / 31632 | |
Lowe (Primidone) (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 primidone 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. |
4 / 111 | |
Samrén (Primidone), 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 primidone monotherapy at least during the first trimester of pregnancy |
unexposed, disease free
Children born to nonepileptic nonexposed women. |
18 / 2000 | |
Steegers-Theunissen (Primidone), 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 primidone 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. |
1 / 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. |
Titze (Primidone) (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 primidone 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. |
9 / 49 | |
Titze (Primidone) (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 primidone 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. |
9 / 13 | |
Tomson (Primidone), 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 primidone 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. |
40 / 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. |
Vajda (Primidone) (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 primidone 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. |
2 / 406 | Women with epilepsy accounted for 98.3%. Completely overlap Vajda 2013 and 2014. Study design partly completed with Vajda 2013. |
Vajda (Primidone) (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 primidone 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. |
2 / 176 | Women with epilepsy accounted for 98.3%. Completely overlap Vajda 2013 and 2014. Study design partly completed with Vajda 2013. |
Study | Country Study period |
Case | Control | Sample size | Rmk |
---|---|---|---|---|---|
Bànhidy (Primidone), 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 (Primidone), 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 | Only one women was treated with primidone for eclampsia. 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. |