Clobazam (Epilepsy)

Study	Type of data	Exposure measurement	Outcome assessment	Adjustment
Battino (Epilepsy), 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.
Christensen (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 (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.
Hvas (Epilepsy) (Controls unexposed, disease free), 2000	prospective cohort	Women completed a questionnaire. They were categorised as users or nonusers of anticonvulsant drugs, by self-reported daily intake of any anticonvulsant drug during the first trimester.	Women completed a questionnaire. Information about major congenital malformations was also collected.	Singleton only. All women who reported chronic disease other than epilepsy were excluded. No adjustment for this group of exposure.
Hvas (Epilepsy) (Controls unexposed, sick), 2000	prospective cohort	Women completed a questionnaire. They were categorised as users or nonusers of anticonvulsant drugs, by self-reported daily intake of any anticonvulsant drug during the first trimester.	Women completed a questionnaire. Information about major congenital malformations was also collected.	Singleton only. All women who reported chronic disease other than epilepsy were excluded. No adjustment for this group of exposure.
Kini (Epilepsy) (Controls exposed to Lamotrigine, sick), 2007	prospective cohort	The research nurse took a personal and medical history in accordance with the prospectively designed Patient Basic and Control Basic Record Forms. An epilepsy specialist confirmed antiepileptic medication. Information from the patient was supplemented from clinical records.	Clinical assessment was carried out by a clinical geneticist blinded to the antiepileptic drugs exposure. The EUROCAT list of congenital malformations was used as a guideline to detect major malformations.	No matching for this group of exposure. No adjustment.
Kini (Epilepsy) (Controls unexposed, disease free), 2007	prospective cohort	The research nurse took a personal and medical history in accordance with the prospectively designed Patient Basic and Control Basic Record Forms. An epilepsy specialist confirmed antiepileptic medication. Information from the patient was supplemented from clinical records.	Clinical assessment was carried out by a clinical geneticist blinded to the antiepileptic drugs exposure. The EUROCAT list of congenital malformations was used as a guideline to detect major malformations.	Matched for socio-economic status (via postcode), age and parity. No adjustment.
Kini (Epilepsy) (Controls unexposed, sick), 2007	prospective cohort	The research nurse took a personal and medical history in accordance with the prospectively designed Patient Basic and Control Basic Record Forms. An epilepsy specialist confirmed antiepileptic medication. Information from the patient was supplemented from clinical records.	Clinical assessment was carried out by a clinical geneticist blinded to the antiepileptic drugs exposure. The EUROCAT list of congenital malformations was used as a guideline to detect major malformations.	No matching for this group of exposure. No adjustment.
Thomas (Epilepsy) (Controls exposed to Lamotrigine, sick), 2021	prospective cohort	Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them.	Screening for major congenital malformation with antenatal screening by serum alpha fetoprotein estimation and detailed anomaly scan between 12 and 18 weeks of pregnancy; physical examination at birth, at 3 months of age (at least) and at 1 year of age if possible.	No adjustment for this group of comparison.
Thomas (Epilepsy) (Controls exposed to LTG), 2022	prospective cohort	Each pregnant woman in the Kerala Registry of Epilepsy and Pregnancy (KREP) maintained a pregnancy diary to record the daily use of antiseizure medications (ASMs). Data were then transferred to the clinical records of the registry during their clinic visits.	Developmental paediatricians and developmental therapists, who were blinded to antenatal ASM exposure evaluated motor and mental development of infants (>12 months) using the Developmental Assessment Scale for Indian Infants (an Indian adaptation of the Bayley Scale of Infant Development).	None (the adjusted motor and mental development quotients (aMODQ and aMEDQ) not provided, only their difference from the reference group (unexposed infants)).
Thomas (Epilepsy) (Controls unexposed, sick), 2021	prospective cohort	Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them.	Screening for major congenital malformation with antenatal screening by serum alpha fetoprotein estimation and detailed anomaly scan between 12 and 18 weeks of pregnancy; physical examination at birth, at 3 months of age (at least) and at 1 year of age if possible.	No adjustment (Incidence rate ratio adjusted but not the OR).
Thomas (Epilepsy) (Controls unexposed, sick), 2022	prospective cohort	Each pregnant woman in the Kerala Registry of Epilepsy and Pregnancy (KREP) maintained a pregnancy diary to record the daily use of antiseizure medications (ASMs). Data were then transferred to the clinical records of the registry during their clinic visits.	Developmental paediatricians and developmental therapists, who were blinded to antenatal ASM exposure evaluated motor and mental development of infants (>12 months) using the Developmental Assessment Scale for Indian Infants (an Indian adaptation of the Bayley Scale of Infant Development).	None (the adjusted motor and mental development quotients (aMODQ and aMEDQ) not provided, only their difference from the reference group (unexposed infants)).
Trivedi (Epilepsy) (Controls exposed to Lamotrigine, sick), 2018	prospective cohort	Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them.	Women were under regular antenatal follow up by the obstetricians.	No adjustment for this group of comparison.
Trivedi (Epilepsy) (Controls unexposed, sick), 2018	prospective cohort	Women were instructed to record the use of the antiepileptic drugs on a daily basis in the pregnancy diary that was given to them.	Women were under regular antenatal follow up by the obstetricians.	Adjusted for enrollment status, age at conception, type of epilepsy, folic acid use in pregnancy, seizures in pregnancy, Generalised Tonic Clonic Seizures in pregnancy, prior spontaneous fetal loss, parental major congenital malformation.
Vajda (Epilepsy) (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 (Epilepsy) (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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