SynthesisNeurology2024
Comparative Risk of Major Congenital Malformations With Antiseizure Medication Combinations vs Valproate Monotherapy in Pregnancy.
Open access · goldAbstract readMeta-Analysis
In one paragraph
Synthesis in Neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 pooled it
12.2field-weighted citation impact, top 1% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Effectiveness and safety of single anti-seizure medication as adjunctive therapy for drug-resistant focal epilepsy based on network meta-analysis.Frontiers in pharmacology · 2025Pooled it
- Timing of high-dose folic acid supplementation in the periconceptional period among women taking antiseizure medications and risk of major congenital anomalies: a target trial emulation.Journal of neurology, neurosurgery, and psychiatry · 2026Article
- Lacosamide Safety During Pregnancy and Breastfeeding: A Single-Centre Experience and Comprehensive Narrative Review.Pharmacy (Basel, Switzerland) · 2026Article
- Teratogenic risk of carbamazepine, levetiracetam, and lamotrigine treatment in pregnant women with epilepsy.Revista da Associacao Medica Brasileira (1992) · 2026Observational
- Epilepsy in women of childbearing age: a focused review.Neurological research and practice · 2025Review
- Agreement Between Parental Self-Reported Antiseizure Medication Use and Dispensed Prescription Records From a National Prescription Database.Pharmacoepidemiology and drug safety · 2025Article
- Second-Line Medications for Women Aged 10 to 50 Years With Idiopathic Generalized Epilepsy.JAMA network open · 2025Article
- Adverse effects of antiseizure medications: a review of the impact of pharmacogenetics and drugs interactions in clinical practice.Frontiers in pharmacology · 2025Review
- Depression Treatment in Pregnancy: Is It Safe, or Is It Not?International journal of environmental research and public health · 2024Review
- Use of sodium valproate and other antiseizure drug treatments in England and Wales: quantitative analysis of nationwide linked electronic health records.BMJ medicine · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 1 institution in 1 country.
Jacqueline M CohenFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-7300-0488
Silje AlvestadFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-4655-8109
Elizabeth A SuarezFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-8989-7878
Andrea SchafferFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-3701-4997
Randi M SelmerFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-8331-6363
Alys HavardFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-6563-8804
Brian T BatemanFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-5950-8683
Carolyn E CestaFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-5759-9366
Helga ZoegaFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-0761-9028
Ingvild OdsbuFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-5337-8619
Krista F HuybrechtsFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-5805-8430
Lars J KjerpesethFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-2033-736X
Loreen StraubFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-2623-2726
Maarit K LeinonenFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-7631-4749
Marte-Helene BjørkFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-5745-1094
Mette NørgaardFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-6110-5891
Mika GisslerFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-8254-7525
Sinna P UlrichsenFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-8679-5163
Sonia Hernandez-DiazFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-1458-7642
Torbjörn TomsonFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-0554-5352
Kari FuruFrom the Department of Chronic Diseases (J.M.C., R.M.S., I.O., L.J.K., K.F.) and Centre for Fertility and Health (J.M.C., K.F.), Norwegian Institute of Public Health, Oslo; Department of Clinical Medicine (S.A., M.-H.B.), University of Bergen, Norway; National Center for Epilepsy (S.A.), Oslo University Hospital, Norway; Division of Pharmacoepidemiology and Pharmacoeconomics (E.A.S., B.T.B., K.F.H., L.S.), Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA; Center for Pharmacoepidemiology and Treatment Science (E.A.S.), Rutgers Institute of Health, Health Care Policy and Aging Research & Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ; School of Population Health (A.S., A.H., H.Z.) and National Drug and Alcohol Research Centre (A.H.), Faculty of Medicine and Health, University of New South Wales, Sydney, Australia; Bennett Institute for Applied Data Science (A.S.), Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom; Department of Anesthesiology, Perioperative, and Pain Medicine (B.T.B.), Stanford University, Stanford, CA; Centre for Pharmacoepidemiology (C.E.C., I.O.), Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; Centre of Public Health Sciences (H.Z.), Faculty of Medicine, University of Iceland, Reykjavik; Department of Knowledge Brokers (M.K.L., M.G.), Finnish Institute for Health and Welfare, Helsinki, Finland; Department of Neurology (M.-H.B.), Haukeland University Hospital, Bergen, Norway; Department of Clinical Epidemiology (M.N., S.P.U.), Aarhus University Hospital and Aarhus University, Denmark; Research Centre for Child Psychiatry (M.G.), University of Turku, Finland; Region Stockholm (M.G.), Academic Primary Health Care Centre, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology (S.H.-D.), Harvard T.H. Chan School of Public Health, Boston, MA; and Department of Clinical Neuroscience (T.T.), Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0003-2245-0179
Norwegian Institute of Public Health · NO
Funding
In-utero exposure to psychotropic medications and the risk of neurodevelopmental disordersR01MH116194 · NIMH · BRIGHAM AND WOMEN'S HOSPITAL · PI HUYBRECHTS, KRISTA F · 2018 to 2022
$2.9MNIMH NIH HHS R01 MH116194
Abstract
BACKGROUND AND
objectivesValproate should be avoided in pregnancy, but it is the most effective drug for generalized epilepsies. Alternative treatment may require combinations of other drugs. Our objectives were to describe first trimester use of antiseizure medication (ASM) combinations that are relevant alternatives to valproate and determine whether specific combinations were associated with a lower risk of major congenital malformations (MCM) compared with valproate monotherapy.
methodsWe conducted a population-based cohort study using linked national registers from Denmark, Finland, Iceland, Norway, and Sweden and administrative health care data from the United States and New South Wales, Australia. We described first trimester use of ASM combinations among pregnant people with epilepsy from 2000 to 2020. We compared the risk of MCM after first trimester exposure to ASM combinations vs valproate monotherapy and low-dose valproate plus lamotrigine or levetiracetam vs high-dose valproate (≥1,000 mg/d). We used log-binomial regression with propensity score weights to calculate adjusted risk ratios (aRRs) and 95% CIs for each dataset. Results were pooled using fixed-effects meta-analysis.
resultsAmong 50,905 pregnancies in people with epilepsy identified from 7.8 million total pregnancies, 788 used lamotrigine and levetiracetam, 291 used lamotrigine and topiramate, 208 used levetiracetam and topiramate, 80 used lamotrigine and zonisamide, and 91 used levetiracetam and zonisamide. After excluding pregnancies with use of other ASMs, known teratogens, or a child diagnosed with MCM of infectious or genetic cause, we compared 587 exposed to lamotrigine-levetiracetam duotherapy and 186 exposed to lamotrigine-topiramate duotherapy with 1959 exposed to valproate monotherapy. Pooled aRRs were 0.41 (95% CI 0.24-0.69) and 1.26 (0.71-2.23), respectively. Duotherapy combinations containing low-dose valproate were infrequent, and comparisons with high-dose valproate monotherapy were inconclusive but suggested a lower risk for combination therapy. Other combinations were too rare for comparative safety analyses. DISCUSSION: Lamotrigine-levetiracetam duotherapy in first trimester was associated with a 60% lower risk of MCM than valproate monotherapy, while lamotrigine-topiramate was not associated with a reduced risk. Duotherapy with lamotrigine and levetiracetam may be favored to treat epilepsy in people with childbearing potential compared with valproate regarding MCM, but whether this combination is as effective as valproate remains to be determined. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that in people with epilepsy treated in the first trimester of pregnancy, the risk of major congenital malformations is lower with lamotrigine-levetiracetam duotherapy than with valproate alone, but similar with lamotrigine-topiramate.
Indexed as
Epilepsy, GeneralizedValproic AcidCohort StudiesDrug CombinationsFemaleHumansInfant, NewbornLamotrigineLevetiracetamPregnancyTopiramateZonisamideDrug CombinationsLamotrigineLevetiracetamTopiramateValproic AcidZonisamide
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