Pregabalin (All indications)

Exposed non-exposed, cohort studies

Study Country
Study period
Study design		 Data source Exposure definition Non-exposure definition Exposition period Sample size
(exposed/unexposed) Or (case / control)		 Remarks Risk of bias
Battino (Epilepsy)
2024 		Worldwide (47 countries)
1999 - 2022
prospective cohort 		The International Registry of Antiepileptic Drugs and Pregnancy (EURAP). Pregnant women with epilepsy exposed to Pregabalin monotherapy at the time of conception. exposed to other treatment, sick
Pregnant women with epilepsy exposed to lamotrigine monotherapy at the time of conception. 		early pregnancy 7 / 3584 Overlapping/Update: Battino 2024 (1999-2022) updates and totally includes Tomson 2018 (1999-2016) and Tomson 2011 => Use of Battino 2024 for the 8 (plus 16 in eSupp) ASM monotherapies studied here.
Reporting physicians collected information on drug therapy after each trimester.
Bjørk (Controls exposed to Lamotrigine, sick) (Mixed indications)
2022 		Danemark, Finland, Iceland, Norway and Sweden.
1996 - 2017
population based cohort retrospective 		Social register data from Danemark, Finland, Iceland, Norway, Sweden for SCAN-AED: Nordic register-based study of antiepileptic drugs in pregnancy. Pregnacies in mothers filling at least one pregabalin monotherapy prescription from her last menstrual period until birth. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Pregnacies in mothers filling at least one lamotrigine monotherapy prescription from her last menstrual period until birth. 		during pregnancy (anytime or not specified) 1666 / 7950 Excluded twins and triplets for statistical reasons and children with chromosomal disorders diagnosed before end of follow-up.
Prescriptions through national prescription registers according to Anatomical Therapeutic Chemical classification codes N03, N05BA09, and S01EC01.
Bjørk (Controls unexposed NOS) (Mixed indications)
2022 		Danemark, Finland, Iceland, Norway and Sweden.
1996 - 2017
population based cohort retrospective 		Social register data from Danemark, Finland, Iceland, Norway, Sweden for SCAN-AED: Nordic register-based study of antiepileptic drugs in pregnancy. Pregnacies in mothers filling at least one pregabalin monotherapy prescription from her last menstrual period until birth. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed (general population or NOS)
Pregnacies in mothers without antiseizure medication prescription from her last menstrual period until birth. 		during pregnancy (anytime or not specified) 1666 / 4463879 Excluded twins and triplets for statistical reasons and children with chromosomal disorders diagnosed before end of follow-up.
Prescriptions through national prescription registers according to Anatomical Therapeutic Chemical classification codes N03, N05BA09, and S01EC01.
Bjørk (Controls unexposed, sick) (Mixed indications)
2022 		Danemark, Finland, Iceland, Norway and Sweden.
1996 - 2017
population based cohort retrospective 		Social register data from Danemark, Finland, Iceland, Norway, Sweden for SCAN-AED: Nordic register-based study of antiepileptic drugs in pregnancy. Pregnacies in mothers filling at least one pregabalin monotherapy prescription from her last menstrual period until birth. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Pregnacies in epileptic mothers without antiseizure medication prescription from her last menstrual period until birth. 		during pregnancy (anytime or not specified) 1666 / 21634 Excluded twins and triplets for statistical reasons and children with chromosomal disorders diagnosed before end of follow-up.
Prescriptions through national prescription registers according to Anatomical Therapeutic Chemical classification codes N03, N05BA09, and S01EC01.
Blotière (Controls exposed to Lamotrigine, sick) (Other indications)
2019 		France
2011 - 2015
retrospective cohort (claims database) 		The French national health insurance database (DCIR) and the French hospital discharge database (PMSI). Pregnancies exposed to pregabalin monotherapy between 1 month before and 2 months after the beginning of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Pregnancies exposed to lamotrigine monotherapy between 1 month before and 2 months after the beginning of pregnancy. 		1st trimester 1671 / 2997 Authors excluded twin pregnancies and pregnancies with a chromosomal abnormality identified. Less than 90% of exposed pregnancies have a proxy for epilepsy. Publication's OR were not kept when lower limit of the confidence interval or OR equal to 0.
The French national health insurance database contains all health care claims reimbursed by French National Health Insurance. Include dispensed drugs coded according to the ATC classification. Monotherapy was defined as the absence of any other antiepileptic drug dispensed during the same period.
Blotière (Controls unexposed NOS) (Other indications)
2019 		France
2011 - 2015
retrospective cohort (claims database) 		The French national health insurance database (DCIR) and the French hospital discharge database (PMSI). Pregnancies exposed to pregabalin monotherapy between 1 month before and 2 months after the beginning of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed (general population or NOS)
Pregnancies with no reimbursement for antiepileptic drugs. 		1st trimester 1671 / 1875733 Authors excluded twin pregnancies and pregnancies with a chromosomal abnormality identified. Less than 10% of exposed pregnancies have a proxy for epilepsy. Publication's OR were not kept when lower limit of the confidence interval or OR equal to 0.
The French national health insurance database contains all health care claims reimbursed by French National Health Insurance. Include dispensed drugs coded according to the ATC classification. Monotherapy was defined as the absence of any other antiepileptic drug dispensed during the same period.
Christensen (All indications) (Controls exposed to LTG)
2024 		Denmark, Finland, Iceland, Norway, and Sweden
1996 - 2017
population based cohort retrospective 		Nordic population-based cohort study including register data from Denmark, Finland, Iceland, Norway, and Sweden–the SCAN-AED project. Children of mothers who had redeemed at least one prescription of Pregabalin monotherapy from 30 days before the first day of the last menstrual period to the date of birth (i.e., the exposure period). exposed to other treatment, sick
Children of mothers who had redeemed at least one prescription of Lamotrigine monotherapy from 30 days before the first day of the last menstrual period to the date of birth (i.e., the exposure period). 		during pregnancy (anytime or not specified) 2214 / 8756 Overlapping: For LBW and SGA: Same databases, overlap of study period: Christensen 2024 totally included Kilic 2014 and has a better period of exposure than Dudukina 2023 => use of Christensen 2024 for these outcomes.
Prenatal exposure was identified via national prescription registers. These registers contain the Anatomical Therapeutic Chemical (ATC) classification code (www.whocc.no) and the date of dispensing.
Christensen (All indications) (Controls unexposed, general population)
2024 		Denmark, Finland, Iceland, Norway, and Sweden
1996 - 2017
population based cohort retrospective 		Nordic population-based cohort study including register data from Denmark, Finland, Iceland, Norway, and Sweden–the SCAN-AED project. Children of mothers who had redeemed at least one prescription of Pregabalin monotherapy from 30 days before the first day of the last menstrual period to the date of birth (i.e., the exposure period). unexposed (general population or NOS)
Children of mothers who had not redeemed prescription of anti-seizure medication. 		during pregnancy (anytime or not specified) 2214 / 4467848 Overlapping: For LBW and SGA: Same databases, overlap of study period: Christensen 2024 totally included Kilic 2014 and has a better period of exposure than Dudukina 2023 => use of Christensen 2024 for these outcomes.
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.
Coste (Controls exposed to Lamotrigine, sick) (Mixed indications)
2020 		France
2011 - 2014
retrospective cohort (claims database) 		The French national health data system (SNDS) Children born from mothers exposed to pregabalin monotherapy indicated for the treatment of epilepsy and migraine with at least one dispensing between the month preceding onset of pregnancy and its end. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children born from mothers exposed to lamotrigine monotherapy for mixed indications during pregnancy. 		during pregnancy (anytime or not specified) 1627 / 2916 Children with a diagnosis of brain malformation (ICD-10 codes Q00 to Q04 and Q05.0 to Q05.4) during their stay in the maternity unit are excluded. Results are extracted from Blotière et al. 2020 because they reported aOR for vs LTG.
Defned by at least one dispensing of the drug to the mother between the beginning of the month preceding onset of pregnancy and the end of pregnancy. Mother had used this drug as monotherapy, defined by the use of a single drug during pregnancy.
Coste (Controls unexposed, NOS) (Mixed indications)
2020 		France
2011 - 2014
retrospective cohort (claims database) 		The French national health data system (SNDS) Children born from mothers exposed to pregabalin monotherapy indicated for the treatment of epilepsy and neuropathic pain with at least one dispensing between the month preceding onset of pregnancy and its end. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed (general population or NOS)
Children born from mothers not exposed to any antiepileptic drug during pregnancy. 		during pregnancy (anytime or not specified) 1627 / 1710441 Children with a diagnosis of brain malformation (ICD-10 codes Q00 to Q04 and Q05.0 to Q05.4) during their stay in the maternity unit are excluded.
Defned by at least one dispensing of the drug to the mother between the beginning of the month preceding onset of pregnancy and the end of pregnancy. Mother had used this drug as monotherapy, defined by the use of a single drug during pregnancy.
Dreier (Controls exposed to LTG)
2023 		Denmark, Finland, Iceland, Norway, and Sweden.
1996 - 2017
population based cohort propective 		A prospective, population-based register study within the SCAN-AED project, based on children born in Denmark, Finland, Iceland, Norway, and Sweden. Children prenatally exposed to pregabalin monotherapy, i.e whose mother had redeemed 1 or more prescriptions during the exposure window, which was defined as 30 days before the first day of the last menstrual period (estimated using gestational age in days at birth) until the date of birth. exposed to other treatment, sick
Children prenatally exposed to lamotrigine monotherapy, i.e whose mother had redeemed 1 or more prescriptions during the exposure window, which was defined as 30 days before the first day of the last menstrual period (estimated using gestational age in days at birth) until the date of birth. 		during pregnancy (anytime or not specified) 120 / 5288
Information on use of antiseizure medications was based on the national prescription registers, which contain information on all reimbursed prescription medications dispensed at pharmacies in each country, including date of dispensing and Anatomical Therapeutic Chemical (ATC) classification code.
Dreier (Controls unexposed, sick)
2023 		Denmark, Finland, Iceland, Norway, and Sweden.
1996 - 2017
population based cohort propective 		A prospective, population-based register study within the SCAN-AED project, based on children born in Denmark, Finland, Iceland, Norway, and Sweden. Children prenatally exposed to pregabalin monotherapy, i.e whose mother had redeemed 1 or more prescriptions during the exposure window, which was defined as 30 days before the first day of the last menstrual period (estimated using gestational age in days at birth) until the date of birth. unexposed, sick
Children not prenatally exposed to antiseizure medication. 		during pregnancy (anytime or not specified) 120 / 22203
Information on use of antiseizure medications was based on the national prescription registers, which contain information on all reimbursed prescription medications dispensed at pharmacies in each country, including date of dispensing and Anatomical Therapeutic Chemical (ATC) classification code.
Dudukina (Controls exposed to LTG) (Mixed indications)
2023 		Denmark, Finland, Norway, and Sweden.
2005 - 2016
population based cohort retrospective 		National birth and administrative registries from four Nordic coutries. At least one dispensing of pregabalin monotherapy (no dispensing for any other antipileptic drug) from last menstrual period (LMP) -90 days to LMP 97 days (first trimester) or any trimester to treat epilepsy, generalized anxiety disorder (GAD), and neuropathic pain. exposed to other treatment, sick
At least one dispensing of lamotrigine monotherapy (no dispensing for any other antipileptic drug) from last menstrual period (LMP) -90 days to LMP 97 days (first trimester) or any trimester. 		3 months (or more) before pregnancy or during pregnancy, 3 months or more before pregnancy or1st trimester 2332 / 7005 Overlapping: Dudukina 2023 included in Bjork 2022 (for ASD and Cognitive disorders) and in Christensen 2024 (for LBW/SGA/Microcephaly), that have a better period of exposure => Use of Bjork and Christensen. Use of sensitivity analysis for monotherapy.
Data were obtained from the national health databases, including prescription registries, and linked at secure servers of the participating countries. Population-based healthcare registries routinely captured dispensing of prescription medications to pregnant women.
Dudukina (Controls unexposed, NOS) (Mixed indications)
2023 		Denmark, Finland, Norway, and Sweden.
2005 - 2016
population based cohort retrospective 		National birth and administrative registries from four Nordic countries. At least one dispensing of pregabalin monotherapy (no dispensing for any other antiepileptic drug) from last menstrual period (LMP) -90 days to LMP 97 days (first trimester) or any trimester to treat epilepsy, generalized anxiety disorder (GAD), and neuropathic pain. unexposed (general population or NOS)
Pregnancies without dispensing for pregabalin monotherapy or other antiepileptic drugs including lamotrigine, or duloxetine during the first trimester or any trimester. 		3 months (or more) before pregnancy or during pregnancy, 3 months or more before pregnancy or1st trimester 2332 / 3063173 Overlapping: Dudukina 2023 included in Bjork 2022 (for ASD and Cognitive disorders) and in Christensen 2024 (for LBW/SGA/Microcephaly), that have a better period of exposure => Use of Bjork and Christensen. Use of sensitivity analysis for monotherapy.
Data were obtained from the national health databases, including prescription registries, and linked at secure servers of the participating countries. Population-based healthcare registries routinely captured dispensing of prescription medications to pregnant women.
Källén (Controls exposed to Lamotrigine, sick) (Indications NOS)
2013 		Swedish
1996 - 2011
population based cohort retrospective 		The Swedish Medical Birth Register, the Swedish Register of Prescribed Drugs the Register of Birth Defect and Hospital Discharge Register. Infants whose mothers used pregabalin 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. 		early pregnancy 111 / 1084 Indications for antiepileptic drugs are not specified. Follow-up period known thanks to author's email reply.
At the midwife interview at the first antenatal care visit, the woman was asked if she had used any drugs since she became pregnant. Or determined by the use of the Swedish Register of Prescribed Drugs (since 2006).
Källén (Controls unexposed, NOS) (Indications NOS)
2013 		Swedish
1996 - 2011
population based cohort retrospective 		The Swedish Medical Birth Register, the Swedish Register of Prescribed Drugs, the Register of Birth Defect and Hospital Discharge Register. Infants whose mothers used pregabalin 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. 		early pregnancy 111 / 1575847 Indications for antiepileptic drugs are not specified. Follow-up period known thanks to author's email reply.
At the midwife interview at the first antenatal care visit, the woman was asked if she had used any drugs since she became pregnant. Or determined by the use of the Swedish Register of Prescribed Drugs (since 2006).
Kaskal (Indications NOS)
2024 		Turkey
2013 - 2022
cohort 		The Marmara University Faculty of Medicine, Istanbul, Turkey. Pregnant women who had taken pregabalin during pregnancy. unexposed (general population or NOS)
Pregnant women who did not use pregabalin, who applied to pharmacology outpatient clinic and were exposed to drugs in the lower-risk category such as penicillin group antibiotics and paracetamol-like analgesics. 		during pregnancy (anytime or not specified) 31 / 93 OR provided by authors not consistent with raw data were not reported.
Health information of the patients was acquired from the health recordings and through telephone from the infants’ mothers (no other details).
Kilic (Controls exposed to Lamotrigine, sick) (Mixed indications)
2014 		Denmark
1997 - 2008
population based cohort retrospective 		The Danish Medical Birth Registry, the Danish Civil Registration System, the Danish National Hospital Registry, and the Danish Register of Medicinal Product Statistics. Children whose mothers have been exposed to pregabalin 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. 		during pregnancy (anytime or not specified) 13 / 880 Less than 90% of women are epileptic. Overlapping: For LBW and SGA: Kilic 2014 included in a larger study published by Christensen 2024 ((longer study period, 5 countries and more pregnancies) => use of Christensen 2024 for these outcomes.
The Danish Register of Medicinal Product Statistics holds information on all redeemed prescriptions. Monotherapy exposure was defined as redemption of prescription for one type of AED with the Anatomical Therapeutic Codes.
Kilic (Controls unexposed NOS) (Mixed indications)
2014 		Denmark
1997 - 2008
population based cohort retrospective 		The Danish Medical Birth Registry, the Danish Civil Registration System, the Danish National Hospital Registry, and the Danish Register of Medicinal Product Statistics. Children whose mothers have been exposed to pregabalin 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. 		during pregnancy (anytime or not specified) 13 / 676834 Less than 90% of women are epileptic. Overlapping: For LBW and SGA: Kilic 2014 included in a larger study published by Christensen 2024 ((longer study period, 5 countries and more pregnancies) => use of Christensen 2024 for these outcomes.
The Danish Register of Medicinal Product Statistics holds information on all redeemed prescriptions. Monotherapy exposure was defined as redemption of prescription for one type of AED with the Anatomical Therapeutic Codes.
Kilic (Controls unexposed, sick) (Mixed indications)
2014 		Denmark
1997 - 2008
population based cohort retrospective 		The Danish Medical Birth Registry, the Danish Civil Registration System, the Danish National Hospital Registry, and the Danish Register of Medicinal Product Statistics. Children whose mothers have been exposed to pregabalin 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. 		during pregnancy (anytime or not specified) 13 / 5296 Less than 90% of women are epileptic. Overlapping: For LBW and SGA: Kilic 2014 included in a larger study published by Christensen 2024 ((longer study period, 5 countries and more pregnancies) => use of Christensen 2024 for these outcomes.
The Danish Register of Medicinal Product Statistics holds information on all redeemed prescriptions. Monotherapy exposure was defined as redemption of prescription for one type of AED with the Anatomical Therapeutic Codes.
Madley-Dowd_SE (Pregabalin) (Controls exposed to LTG) (Mixed indications)
2024 		Sweden
1995 - 2020
population based cohort retrospective 		The Swedish Developmental Origins of Health and Disease (DOHaD) cohort, which is a registry study linking several national electronic data sources. Fetal exposure to Pregabalin monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with self-reported consumption during pregnancy or a prescription 30 days before pregnancy or during pregnancy. exposed to other treatment, sick
Fetal exposure to Lamotrigine monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with self-reported consumption during pregnancy or a prescription 30 days before pregnancy or during pregnancy. 		during pregnancy (anytime or not specified) 1307 / 5035 Partial overlapping of swedish data with Bjork 2022 and Dreier 2023 (IQ, ASD, ADHD) => these studies were kept and tagged. => Data extracted from the e-Supp pdf (Table S1; S2; S9) and excel (Figure S9 – Active comparator Analysis).
Self-reported maternal consumption of antiseizure medications were prospectively recorded at antenatal care visits (from a structured interview at the first visit at 8–10 weeks of gestation, supplemented from 2005 with drug all prescription dispensations in Sweden (tetrachoric correlation 0.98).
Madley-Dowd_SE (Pregabalin) (Controls unexposed, general pop) (Mixed indications)
2024 		Sweden
1995 - 2020
population based cohort retrospective 		The Swedish Developmental Origins of Health and Disease (DOHaD) cohort, which is a registry study linking several national electronic data sources. Fetal exposure to Pregabalin monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with self-reported consumption during pregnancy or a prescription 30 days before pregnancy or during pregnancy. unexposed (general population or NOS)
No fetal exposure to antiseizure medication at any time during the pregnancy period. 		during pregnancy (anytime or not specified) 1307 / 2651210 Partial overlapping of swedish data with Bjork 2022 and Dreier 2023 (IQ, ASD, ADHD) => these studies were kept and tagged. => Data extracted from the e-Supp pdf (Table S1; S2 and S6).
Self-reported maternal consumption of antiseizure medications were prospectively recorded at antenatal care visits (from a structured interview at the first visit at 8–10 weeks of gestation, supplemented from 2005 with drug all prescription dispensations in Sweden (tetrachoric correlation 0.98).
Madley-Dowd_SE (Pregabalin) (Controls unexposed, sibling) (Mixed indications)
2024 		Sweden
1995 - 2020
population based cohort retrospective 		The Swedish Developmental Origins of Health and Disease (DOHaD) cohort, which is a registry study linking several national electronic data sources. Siblings with fetal exposure to Pregabalin monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with self-reported consumption during pregnancy or a prescription 30 days before pregnancy or during pregnancy. sibling
Discordant siblings without fetal exposure to antiseizure medication at any time during the pregnancy period. 		during pregnancy (anytime or not specified) -9 / -9 Partial overlapping of swedish data with Bjork 2022 and Dreier 2023 (IQ, ASD, ADHD) => these studies were kept and tagged. => Data extracted from the e-Supp pdf (Table S8) and excel (Figure S8 – Discordant Sibling Analysis).
Self-reported maternal consumption of antiseizure medications were prospectively recorded at antenatal care visits (from a structured interview at the first visit at 8–10 weeks of gestation, supplemented from 2005 with drug all prescription dispensations in Sweden (tetrachoric correlation 0.98).
Madley-Dowd_UK (Pregabalin) (Controls exposed to LTG) (Mixed indications)
2024 		United Kingdom
1995 - 2018
retrospective cohort (claims database) 		The UK primary care-based Clinical Practice Research Datalink (CPRD) GOLD, with linkage to the CPRD Pregnancy Register, the CPRD Mother-Baby link, the Hospital Episode Statistics (HES) database, ... Fetal exposure to Pregabalin monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with a prescription that started or ended during the pregnancy period. exposed to other treatment, sick
Fetal exposure to Lamotrigine monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with a prescription that started or ended during the pregnancy period. 		during pregnancy (anytime or not specified) 408 / 939 Partial overlapping of swedish data with Bjork 2022 and Dreier 2023 (IQ, ASD, ADHD) => these studies were kept and tagged. => Data extracted from the e-Supp pdf (Table S1, S2 and S9) and excel (Figure S9 – Active Comparator Analysis).
Prescriptions were identified from primary care records.
Madley-Dowd_UK (Pregabalin) (Controls unexposed, general pop) (Mixed indications)
2024 		United Kingdom
1995 - 2018
retrospective cohort (claims database) 		The UK primary care-based Clinical Practice Research Datalink (CPRD) GOLD, with linkage to the CPRD Pregnancy Register, the CPRD Mother-Baby link, the Hospital Episode Statistics (HES) database, ... Fetal exposure to Pregabalin monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with a prescription that started or ended during the pregnancy period. unexposed (general population or NOS)
No fetal exposure to antiseizure medication at any time during the pregnancy period. 		during pregnancy (anytime or not specified) 408 / 514066 Partial overlapping of swedish data with Bjork 2022 and Dreier 2023 (IQ, ASD, ADHD) => these studies were kept and tagged. => Data extracted from the e-Supp pdf (Table S1, S2 and S6).
Prescriptions were identified from primary care records.
Madley-Dowd_UK (Pregabalin) (Controls unexposed, sibling) (Mixed indications)
2024 		United Kingdom
1995 - 2018
retrospective cohort (claims database) 		The UK primary care-based Clinical Practice Research Datalink (CPRD) GOLD, with linkage to the CPRD Pregnancy Register, the CPRD Mother-Baby link, the Hospital Episode Statistics (HES) database, ... Siblings with fetal exposure to Pregabalin monotherapy for any indications at any time during the pregnancy period, i.e any pregnancy with a prescription that started or ended during the pregnancy period. sibling
Discordant siblings without fetal exposure to antiseizure medication at any time during the pregnancy period. 		during pregnancy (anytime or not specified) -9 / -9 Partial overlapping of swedish data with Bjork 2022 and Dreier 2023 (IQ, ASD, ADHD) => these studies were kept and tagged. => Data extracted from the e-Supp pdf (Table S8) and excel (Figure S8 – Discordant Sibling Analysis).
Prescriptions were identified from primary care records.
Margulis (Pregabalin) (Indications other than epilepsy)
2019 		Sweden
1996 - 2013
population based cohort retrospective 		Nationwide Swedish register data (the Swedish Medical Birth Register, The Prescribed Drug Register and the National Patient Register). Infants whose mothers reported use of pregabalin monotherapy at any time during pregnancy. exposed to other treatment, sick
Infants whose mothers reported use of lamotrigine at any time during pregnancy. 		during pregnancy (anytime or not specified) 499 / 1812 Monotherapy results available in e-Supp tables (S3 File). For SGA and microcephaly: partial overlapping between Margulis 2019 and Christensen 2024 (7 years in common and 14 years not in common) => the 2 studies were kept.
Information on exposure was obtained from prescriptions dispensed and from self-report in the first prenatal visit and from self-reports in subsequent prenatal visits.
Patorno_MAX and MaketScan (Other indications)
2017 		USA
2000 - 2010
retrospective cohort (claims database) 		Medicaid Analytic eXtract (MAX) for 46 US states and the District of Columbia and the Truven Health MarketScan Commercial Claims and Encounters Database (Marketscan). Infants born to women exposed to pregabalin (at least one filled prescription during the first trimester of pregnancy) but not to other anticonvulsant drugs during the 3 months before the start of pregnancy or during the first trimester. unexposed (general population or NOS)
Infants born to women who had no dispensings for pregabalin or other anticonvulsant medications during the 3 months before the start of pregnancy or during the first trimester. 		1st trimester 471 / 1322955 Reported results are pooled OR of 1st trimester monotherapy of the 2 cohorts (MAX and Market scan). Less than 10% of women have epilepsy. Study design partly completed with cited source [5].
The Medicaid Analytic Extract data include prescriptions filled on an outpatient basis.
Razaz (Epilepsy)
2024 		Denmark, Finland, Iceland, Norway and Sweden.
1996 - 2017
population based cohort retrospective 		The SCAN-AED project, using the Nordic register infrastructures. Mothers with epilepsy who filled a prescription for Pregabalin monotherapy between the date of the last menstrual period (LMP) and the day of birth. unexposed, sick
Mothers with epilepsy who did not fill an antiseizure medication (ASM) prescription in the period between 90 days before the last menstrual period (LMP) and the day of birth. 		during pregnancy (anytime or not specified) 89 / 19043
Prescription for antiseizure medication (ASM) was ascertained using nationwide prescription registers and identified ASMs based on Anatomical Therapeutic Chemical Classification.
The NAAED (Controls exposed to LTG) (Indications NOS)
2023 		North America and Canada
1997 - 2022
prospective cohort 		The North American Antiepileptic Drug Pregnancy Register Infants of pregnant women who used Pregabalin 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. 		1st trimester 62 / 2461 Study design completed with the publication of Hernández-Díaz et al. 2012. Data extracted from the North American AED pregnancy registry website. Overlapping/update with Hernández-Díaz et al. 2012 and previous website reports. Use of internal control.
Women are interviewed at enrollment, at 7 months’ gestation and at 8 –12 weeks after the expected date of delivery. The computer-assisted interviews include questions on start and stop dates of each antiepileptic drugs taken, dose, frequency and changes in medication.
The NAAED (Controls unexposed, disease free) (Indications NOS)
2023 		North America and Canada
1997 - 2022
prospective cohort 		The North American Antiepileptic Drug Pregnancy Register Infants of pregnant women who used Pregabalin 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. 		1st trimester 62 / 1311 Study design completed with the publication of Hernández-Díaz et al. 2012. Data extracted from the North American AED pregnancy registry website. Overlapping/update with Hernández-Díaz et al. 2012 and previous website reports. Use of internal control.
Women are interviewed at enrollment, at 7 months’ gestation and at 8 –12 weeks after the expected date of delivery. The computer-assisted interviews include questions on start and stop dates of each antiepileptic drugs taken, dose, frequency and changes in medication.
Vajda (Controls exposed to Lamotrigine, sick)
2019 		Australia
1999 - 2018
prospective cohort 		The Australian Register of Antiepileptic Drugs in Pregnancy. Offsprings born from women nearly always with epilepsy exposed to pregabalin 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. 		at least 1st trimester 1 / 406 Women with epilepsy accounted for 98.3%. Study design partly completed with Vajda 2013. Malformations results presented in Jazayeri 2018 are already included in this publication.
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.
Vajda (Controls unexposed, sick)
2019 		Australia
1999 - 2018
prospective cohort 		The Australian Register of Antiepileptic Drugs in Pregnancy. Offsprings born from women nearly always with epilepsy exposed to pregabalin 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. 		at least 1st trimester 1 / 176 Women with epilepsy accounted for 98.3%. Study design partly completed with Vajda 2013. Malformations results presented in Jazayeri 2018 are already included in this publication.
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.
Veiby (Controls exposed to Lamotrigine, sick) (Mixed indications)
2014 		Norway
1999 - 2011
population based cohort retrospective 		Medical Birth Registry of Norway Children exposed prenatally to pregabalin as monotherapy indicated for their mothers' epilepsy or other indications. (This is a subgroup of exposure among the whole exposed group considered in the study). exposed to other treatment, sick
Children exposed prenatally to lamotrigine as monotherapy indicated for their mothers' epilepsy or other indications. 		throughout pregnancy 30 / 833 Less than 90% of women are treated with Lamotrigine for epilepsy and indications for Pregabalin is unknown.
A standardised notification form is filled in from the first prenatal visit with the general practitioner until discharge and transferred to the database by practitioners attending the delivery. (According to ATC Classification System).
Veiby (Controls unexposed, disease free) (Mixed indications)
2014 		Norway
1999 - 2011
population based cohort retrospective 		Medical Birth Registry of Norway Children exposed prenatally to pregabalin as monotherapy indicated for their mothers' epilepsy or other indications. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, disease free
All unexposed children born to women without epilepsy. 		throughout pregnancy 30 / 771412 Indications for Pregabalin is unknown.
A standardised notification form is filled in from the first prenatal visit with the general practitioner until discharge and transferred to the database by practitioners attending the delivery. (According to ATC Classification System).
Veiby (Controls unexposed, sick) (Mixed indications)
2014 		Norway
1999 - 2011
population based cohort retrospective 		Medical Birth Registry of Norway Children exposed prenatally to pregabalin as monotherapy indicated for their mothers' epilepsy or other indications. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed, sick
Children born to women with a history of epilepsy but no antiepileptic drug treatment during pregnancy. 		throughout pregnancy 30 / 3773 Indications for Pregabalin is unknown.
A standardised notification form is filled in from the first prenatal visit with the general practitioner until discharge and transferred to the database by practitioners attending the delivery. (According to ATC Classification System).
Winterfeld (Other indications)
2016 		Worldwide (France, United Kingdom, Italy, Finland, Switzerland, the Netherlands, and Turkey)
2004 - 2013
prospective cohort 		Eight participating Teratology Information Services (TIS) Pregnancies in patients with pregabalin monotherapy exposure during the first trimester of pregnancy. (This is a subgroup of exposure among the whole exposed group considered in the study). unexposed (general population or NOS)
Pregnancies in patients who were not exposed to any medications known to be teratogenic or to any antiepileptic drugs. 		1st trimester 19 / 656 Study design completed with cited source [14].
Information on medication exposure were collected at initial contact during pregnancy, and so before the outcome was known.

Case-control studies

Study Country
Study period
Study design		 Data source Case Control Exposition Exposition period Sample size
(exposed/unexposed) Or (case / control)		 Remarks Risk of bias

Risk of bias: : NA;   : low;   : moderate;   : serious;   : critical;   : unclear;  

Empty. There are no case-control studies available for this drug.

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