Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations
Objective: This study was undertaken to examine the comparative safety of antiseizure medication (ASM) monotherapy in pregnancy with respect to risk of major congenital malformations (MCMs), overall and by MCM subtype. Methods: We conducted a population-based cohort study using national health regis...
Published in: | Annals of Neurology |
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Online Access: | https://hdl.handle.net/11250/3042480 https://doi.org/10.1002/ana.26561 |
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ftunivbergen:oai:bora.uib.no:11250/3042480 2023-05-15T16:51:59+02:00 Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations Cohen, Jacqueline Mallory Alvestad, Silje Cesta, Carolyn E. Bjørk, Marte-Helene Leinonen, Maarit Nørgaard, Mette Einarsdóttir, Kristjana Engeland, Anders Gissler, Mika Karlstad, Øystein Klungsøyr, Kari Odsbu, Ingvild Reutfors, Johan Selmer, Randi Marie Tomson, Torbjörn Ulrichsen, Sinna Pilgaard Zoega, Helga Furu, Kari 2022 application/pdf https://hdl.handle.net/11250/3042480 https://doi.org/10.1002/ana.26561 eng eng Wiley urn:issn:0364-5134 https://hdl.handle.net/11250/3042480 https://doi.org/10.1002/ana.26561 cristin:2099651 Annals of Neurology. 2022. Navngivelse-Ikkekommersiell 4.0 Internasjonal http://creativecommons.org/licenses/by-nc/4.0/deed.no Copyright 2022 the authors Annals of Neurology Journal article Peer reviewed 2022 ftunivbergen https://doi.org/10.1002/ana.26561 2023-03-14T17:41:32Z Objective: This study was undertaken to examine the comparative safety of antiseizure medication (ASM) monotherapy in pregnancy with respect to risk of major congenital malformations (MCMs), overall and by MCM subtype. Methods: We conducted a population-based cohort study using national health register data from Denmark, Finland, Iceland, Norway, and Sweden (1996–2020). We compared pregnancies with first trimester exposure to lamotrigine monotherapy to ASM-unexposed, carbamazepine, valproate, oxcarbazepine, levetiracetam, and topiramate to lamotrigine monotherapy, and stratified monotherapy groups by dose. The outcome was nongenetic MCM and specific subtypes. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) with log-binomial regression and propensity score weights. Results: There was a higher crude risk of any MCM in pregnancies exposed to lamotrigine monotherapy (n = 8,339) compared to ASM-unexposed pregnancies (n = 4,866,362), but not after confounder adjustment (aRR = 0.97, 95% CI = 0.87–1.08). Compared to lamotrigine, there was an increased risk of malformations associated with valproate (n = 2,031, aRR = 2.05, 95% CI = 1.70–2.46) and topiramate (n = 509, aRR = 1.81, 95% CI = 1.26–2.60), which increased in a dose-dependent manner. We found no differences in malformation risk for carbamazepine (n = 2,674, aRR = 0.91, 95% CI = 0.72–1.15), oxcarbazepine (n = 1,313, aRR = 1.09, 95% CI = 0.83–1.44), or levetiracetam (n = 1,040, aRR = 0.78, 95% CI = 0.53–1.13). Valproate was associated with several malformation subtypes, including nervous system, cardiac, oral clefts, clubfoot, and hypospadias, whereas lamotrigine and carbamazepine were not. Interpretation: Topiramate is associated with an increased risk of MCM similar to that associated with valproate, but lower doses may mitigate the risks for both drugs. Conversely, we found no increased risks for lamotrigine, carbamazepine, oxcarbazepine, or levetiracetam, which is reassuring. publishedVersion Article in Journal/Newspaper Iceland University of Bergen: Bergen Open Research Archive (BORA-UiB) Norway Annals of Neurology 93 3 551 562 |
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Open Polar |
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University of Bergen: Bergen Open Research Archive (BORA-UiB) |
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ftunivbergen |
language |
English |
description |
Objective: This study was undertaken to examine the comparative safety of antiseizure medication (ASM) monotherapy in pregnancy with respect to risk of major congenital malformations (MCMs), overall and by MCM subtype. Methods: We conducted a population-based cohort study using national health register data from Denmark, Finland, Iceland, Norway, and Sweden (1996–2020). We compared pregnancies with first trimester exposure to lamotrigine monotherapy to ASM-unexposed, carbamazepine, valproate, oxcarbazepine, levetiracetam, and topiramate to lamotrigine monotherapy, and stratified monotherapy groups by dose. The outcome was nongenetic MCM and specific subtypes. We estimated adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) with log-binomial regression and propensity score weights. Results: There was a higher crude risk of any MCM in pregnancies exposed to lamotrigine monotherapy (n = 8,339) compared to ASM-unexposed pregnancies (n = 4,866,362), but not after confounder adjustment (aRR = 0.97, 95% CI = 0.87–1.08). Compared to lamotrigine, there was an increased risk of malformations associated with valproate (n = 2,031, aRR = 2.05, 95% CI = 1.70–2.46) and topiramate (n = 509, aRR = 1.81, 95% CI = 1.26–2.60), which increased in a dose-dependent manner. We found no differences in malformation risk for carbamazepine (n = 2,674, aRR = 0.91, 95% CI = 0.72–1.15), oxcarbazepine (n = 1,313, aRR = 1.09, 95% CI = 0.83–1.44), or levetiracetam (n = 1,040, aRR = 0.78, 95% CI = 0.53–1.13). Valproate was associated with several malformation subtypes, including nervous system, cardiac, oral clefts, clubfoot, and hypospadias, whereas lamotrigine and carbamazepine were not. Interpretation: Topiramate is associated with an increased risk of MCM similar to that associated with valproate, but lower doses may mitigate the risks for both drugs. Conversely, we found no increased risks for lamotrigine, carbamazepine, oxcarbazepine, or levetiracetam, which is reassuring. publishedVersion |
format |
Article in Journal/Newspaper |
author |
Cohen, Jacqueline Mallory Alvestad, Silje Cesta, Carolyn E. Bjørk, Marte-Helene Leinonen, Maarit Nørgaard, Mette Einarsdóttir, Kristjana Engeland, Anders Gissler, Mika Karlstad, Øystein Klungsøyr, Kari Odsbu, Ingvild Reutfors, Johan Selmer, Randi Marie Tomson, Torbjörn Ulrichsen, Sinna Pilgaard Zoega, Helga Furu, Kari |
spellingShingle |
Cohen, Jacqueline Mallory Alvestad, Silje Cesta, Carolyn E. Bjørk, Marte-Helene Leinonen, Maarit Nørgaard, Mette Einarsdóttir, Kristjana Engeland, Anders Gissler, Mika Karlstad, Øystein Klungsøyr, Kari Odsbu, Ingvild Reutfors, Johan Selmer, Randi Marie Tomson, Torbjörn Ulrichsen, Sinna Pilgaard Zoega, Helga Furu, Kari Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations |
author_facet |
Cohen, Jacqueline Mallory Alvestad, Silje Cesta, Carolyn E. Bjørk, Marte-Helene Leinonen, Maarit Nørgaard, Mette Einarsdóttir, Kristjana Engeland, Anders Gissler, Mika Karlstad, Øystein Klungsøyr, Kari Odsbu, Ingvild Reutfors, Johan Selmer, Randi Marie Tomson, Torbjörn Ulrichsen, Sinna Pilgaard Zoega, Helga Furu, Kari |
author_sort |
Cohen, Jacqueline Mallory |
title |
Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations |
title_short |
Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations |
title_full |
Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations |
title_fullStr |
Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations |
title_full_unstemmed |
Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations |
title_sort |
comparative safety of antiseizure medication monotherapy for major malformations |
publisher |
Wiley |
publishDate |
2022 |
url |
https://hdl.handle.net/11250/3042480 https://doi.org/10.1002/ana.26561 |
geographic |
Norway |
geographic_facet |
Norway |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Annals of Neurology |
op_relation |
urn:issn:0364-5134 https://hdl.handle.net/11250/3042480 https://doi.org/10.1002/ana.26561 cristin:2099651 Annals of Neurology. 2022. |
op_rights |
Navngivelse-Ikkekommersiell 4.0 Internasjonal http://creativecommons.org/licenses/by-nc/4.0/deed.no Copyright 2022 the authors |
op_doi |
https://doi.org/10.1002/ana.26561 |
container_title |
Annals of Neurology |
container_volume |
93 |
container_issue |
3 |
container_start_page |
551 |
op_container_end_page |
562 |
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1766042115000762368 |