Primidone (Epilepsy)

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Bànhidy (Primidone), 2011	case control	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.	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.	Matched according to sex, birth week in the year when cases were born, and district of parents’ residence.
Battino, 2024	prospective cohort	Reporting physicians collected information on drug therapy after each trimester.	Abnormalities in the offspring were recorded descriptively by reporting physicians. A committee blinded to type of exposure assessed and categorized these abnormalities. When necessary, the committee solicited additional information from the reporting physicians.	Exclusion of pregnancies exposed to known teratogenic drugs, and those with comorbidities associated with teratogenic risks. No adjustment for this group of comparison.
Battino (Primidone), 1999	prospective cohort	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.	The vital data of newborns at birth were recorded according to a standardized protocol; a more detailed clinical examination was performed on the fifth day. The infants were weighed within 1 hour of life, and their head circumference measured.	No adjustment for this group of exposure.
Battino (Primidone), 1992	prospective cohort	At least every 4 weeks throughout the pregnancy blood samples were taken for measurement of antiepileptic drugs concentrations.	Vital data of newborns at birth were recorded according to a standardized protocol; a more detailed clinical examination was performed on Day 5.	None.
Burja (Primidone) (Controls unexposed, disease free), 2006	retrospective cohort (registry)	Hospital neonatal and obstetric records at the MariborTeaching Hospital Department of Perinatology.	Data on the main outcome measures were recorded by health practitioners and extracted from the Regional Hospital Discharge Registry. The data are transferred from the registry to the Perinatal Statistical Database of Slovenia. Diagnoses were classified according to ICD10.	None.
Burja (Primidone) (Controls unexposed, sick), 2006	retrospective cohort (registry)	Hospital neonatal and obstetric records at the MariborTeaching Hospital Department of Perinatology.	Data on the main outcome measures were recorded by health practitioners and extracted from the Regional Hospital Discharge Registry. The data are transferred from the registry to the Perinatal Statistical Database of Slovenia. Diagnoses were classified according to ICD10.	None.
Canger (Primidone), 1999	prospective cohort	The patients received monthly obstetric and neurologic examinations, and antiepileptic drug blood levels were tested monthly.	At the time of delivery the infants underwent a standardized examination by a pediatrician, and a more detailed clinical examination on day 5 in San Paolo Hospital only and during the first months in other hospitals (if so medical records were also acquired).	None.
Christensen (Primidone) (Epilepsy) (Controls exposed to LTG), 2024	population based cohort retrospective	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.	Information on birth weight, gestational age and head circumference at birth was obtained from the medical birth registers for all births occurring at 22 weeks’ gestation or later.	Singleton only. No adjustment for this group of comparison.
Christensen (Primidone) (Epilepsy) (Controls unexposed, general population), 2024	population based cohort retrospective	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.	Information on birth weight, gestational age and head circumference at birth was obtained from the medical birth registers for all births occurring at 22 weeks’ gestation or later.	Singleton only. No adjustment for LBW. All models were adjusted for country of birth, year of birth, sex of child, maternal age, maternal parity, maternal marital or cohabitation status, pre-pregnancy hospital admittances, maternal education, smoking in early pregnancy, maternal psychiatric history (F00-F99), and use of psychotropic drugs in pregnancy (ATC N06A, N05A, N05B, excl. N05BA09).
Czeizel (Primidone), 1992	case control	Mothers were mailed a questionnaire requested information on medicinal products taken during pregnancy and to send their prenatal maternity logbook which related drug prescriptions. Regional nurses were asked to visit and question the non-respondent.	Notification of cases with congenital abnormality is mandatory for physicians to the HCAR. Pathologists sent autopsy report for stillbirths and infant deaths cases. Prenatally diagnosed and electively terminated malformed fetuses have also been registered.	None.
Dean (Primidone), 2002	retrospective cohort	A structured interview was carried out by a trained research nurse using questionnaires.	Standardised assessment was carried out by a trained research nurse using examination schedules. Clinical photographs were assessed for facial features. Behavior disorders, developmental delay and later childhood medical problems were recorded and/or diagnosed by specialists.	None.
Kaaja (Primidone), 2003	prospective cohort	Follow-up of the pregnant women with epilepsy included assessment of serum concentration of antiepileptic drugs at the end of the first trimester.	Infants were examined by a neonatologist at birth and at discharge from the hospital and charts for the infants admitted to the pediatric clinic or in case of termination of pregnancy were reviewed. Autopsy was performed on stillbirth.	No adjustment for this group of exposure.
Kaneko (Primidone), 1999	prospective cohort	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.	Congenital malformations were examined at each center at birth, at 5 days, and at the 1-month visit by a team of obstetricians and neurologists, according to a standardized check-list based on the report of the Japanese Association of Obstetricians for Maternal Welfare.	None.
Katz (Primidone), 2001	retrospective cohort	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.	Data collected in chart review about the newborn included the presence of developmental delay. Including pervasive developmental delay (based on the DSM-IV-TR criteria), combined or isolated speech and gross motor delay and attention deficit disorder with speech and auditory processing delay.	None.
Kini (Primidone) (Controls exposed to Lamotrigine, sick), 2006	retrospective cohort	Structured interviews were conducted with the mothers and medical records were available to confirm details in about 80% of participants.	A clinical examination was carried out to check the growth parameters and detect dysmorphic features and malformations. Clinical photographs were reviewed based on whether the gestalt was suggestive of fetal anticonvulsant syndrome by a panel of blind dysmorphologists.	None.
Kini (Primidone) (Controls unexposed, sick), 2006	retrospective cohort	Structured interviews were conducted with the mothers and medical records were available to confirm details in about 80% of participants.	A clinical examination was carried out to check the growth parameters and detect dysmorphic features and malformations. Clinical photographs were reviewed based on whether the gestalt was suggestive of fetal anticonvulsant syndrome by a panel of blind dysmorphologists.	None.
Koch (Primidone), 1996	prospective cohort	The pregnant women were asked to continuously monitor their seizures, treatment and additional illnesses.	Authors developed their own neonatal score consisted of symptoms of apathy and hyperexcitability. Then six-year-old children were examined for major and minor neurological dysfunction with the examination of Touwen. The examiners were not blinded for this part of the study.	Matched for five variables, namely socioeconomic status (lower and middle class), age of the mother at delivery, parity, amount of smoking during pregnancy and number of abortions previous to the subject’s birth.
Lowe (Primidone) (Controls unexposed, disease free), 1973	population based cohort retrospective	Detailed information has been collected, coded, and computer stored. The hospital and general practitioner records of women with a history of epilepsy were traced and inspected.	Detailed information has been collected, coded, and computer stored whether the infant is observed to be congenitally malformed.	None.
Lowe (Primidone) (Controls unexposed, sick), 1973	population based cohort retrospective	Detailed information has been collected, coded, and computer stored. The hospital and general practitioner records of women with a history of epilepsy were traced and inspected.	Detailed information has been collected, coded, and computer stored whether the infant is observed to be congenitally malformed.	None.
Samrén (Primidone), 1999	retrospective cohort	Data were collected from medical records and include medication. The prescribed dose of thedrugs was also retrieved from obstetric files.	Data were collected from medical records and include information on pregnancy and child. Information on major congenital abnormalities was completed with information from the pediatrician whenever necessary.	Matched for age (±2 years) and parity of the mother, and sex, birth year, and hospital of delivery of the child.
Steegers-Theunissen (Primidone), 1994	prospective cohort	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.	The infants were examined systematically for major malformations according to the ICD9 British Paediatric Association System and for minor malformations according to Mehes and Stalder by a trained research fellow.	None.
Titze (Primidone) (Controls unexposed, disease free), 2008	prospective cohort	The pregnant women were asked to continuously monitor their treatment.	In adolescents, the German versions of the revised Wechsler Intelligence Scales for children and for adults were applied.	Matched for socioeconomic status (SES), nicotine consumption in the last trimester, maternal age at birth, parity, and number of previous abortions. No adjustment for this group of exposure.
Titze (Primidone) (Controls unexposed, sick), 2008	prospective cohort	The pregnant women were asked to continuously monitor their treatment.	In adolescents, the German versions of the revised Wechsler Intelligence Scales for children and for adults were applied.	No matching for this group of comparison. No adjustment for this group of exposure.
Vajda (Primidone) (Controls exposed to Lamotrigine, sick), 2019	prospective cohort	Details are obtained by four in-depth telephone interviews with the women. Details provided by the participants are confirmed, as far as possible, by the treating medical practitioners and through hospital records.	Details are obtained by four in-depth telephone interviews with the women. Details provided by the participants are confirmed, as far as possible, by the treating medical practitioners and through hospital records.	None.
Vajda (Primidone) (Controls unexposed, sick), 2019	prospective cohort	Details are obtained by four in-depth telephone interviews with the women. Details provided by the participants are confirmed, as far as possible, by the treating medical practitioners and through hospital records.	Details are obtained by four in-depth telephone interviews with the women. Details provided by the participants are confirmed, as far as possible, by the treating medical practitioners and through hospital records.	None.

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