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dc.contributor.authorCohen, Jacqueline Mallory
dc.contributor.authorAlvestad, Silje
dc.contributor.authorSuarez, Elizabeth A.
dc.contributor.authorSchaffer, Andrea
dc.contributor.authorSelmer, Randi M.
dc.contributor.authorHavard, Alys
dc.contributor.authorBateman, Brian T.
dc.contributor.authorCesta, Carolyn E.
dc.contributor.authorZoega, Helga
dc.contributor.authorOdsbu, Ingvild
dc.contributor.authorHuybrechts, Krista F.
dc.contributor.authorKjerpeseth, Lars J.
dc.contributor.authorStraub, Loreen
dc.contributor.authorLeinonen, Maarit K.
dc.contributor.authorBjørk, Marte-Helene
dc.contributor.authorNørgaard, Mette
dc.contributor.authorGissler, Mika
dc.contributor.authorUlrichsen, Sinna P.
dc.contributor.authorHernandez-Diaz, Sonia
dc.contributor.authorTomson, Torbjörn
dc.contributor.authorFuru, Kari
dc.date.accessioned2024-05-13T10:52:48Z
dc.date.available2024-05-13T10:52:48Z
dc.date.created2024-02-07T09:45:03Z
dc.date.issued2023
dc.identifier.issn0028-3878
dc.identifier.urihttps://hdl.handle.net/11250/3130089
dc.description.abstractBackground and Objectives Valproate 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. Methods We 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. Results Among 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.en_US
dc.language.isoengen_US
dc.publisherWolters Kluweren_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titleComparative Risk of Major Congenital Malformations With Antiseizure Medication Combinations vs Valproate Monotherapy in Pregnancyen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionacceptedVersionen_US
dc.source.articlenumbere207996en_US
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.qualitycode2
dc.identifier.doi10.1212/WNL.0000000000207996
dc.identifier.cristin2243903
dc.source.journalNeurologyen_US
dc.identifier.citationNeurology. 2024, 102 (2), e207996.en_US
dc.source.volume102en_US
dc.source.issue2en_US


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