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 registe...
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crwiley:10.1002/ana.26561 2024-09-15T18:14:28+00:00 Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations Cohen, Jacqueline M. Alvestad, Silje Cesta, Carolyn E. Bjørk, Marte‐Helene Leinonen, Maarit K. Nørgaard, Mette Einarsdóttir, Kristjana Engeland, Anders Gissler, Mika Karlstad, Øystein Klungsøyr, Kari Odsbu, Ingvild Reutfors, Johan Selmer, Randi M. Tomson, Torbjörn Ulrichsen, Sinna Pilgaard Zoega, Helga Furu, Kari NordForsk Norges Forskningsråd University of New South Wales 2022 http://dx.doi.org/10.1002/ana.26561 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ana.26561 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ana.26561 en eng Wiley http://creativecommons.org/licenses/by-nc/4.0/ Annals of Neurology volume 93, issue 3, page 551-562 ISSN 0364-5134 1531-8249 journal-article 2022 crwiley https://doi.org/10.1002/ana.26561 2024-09-05T05:09:25Z 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. ANN NEUROL 2023;93:551–562 Article in Journal/Newspaper Iceland Wiley Online Library Annals of Neurology 93 3 551 562 |
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Wiley Online Library |
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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. ANN NEUROL 2023;93:551–562 |
author2 |
NordForsk Norges Forskningsråd University of New South Wales |
format |
Article in Journal/Newspaper |
author |
Cohen, Jacqueline M. Alvestad, Silje Cesta, Carolyn E. Bjørk, Marte‐Helene Leinonen, Maarit K. Nørgaard, Mette Einarsdóttir, Kristjana Engeland, Anders Gissler, Mika Karlstad, Øystein Klungsøyr, Kari Odsbu, Ingvild Reutfors, Johan Selmer, Randi M. Tomson, Torbjörn Ulrichsen, Sinna Pilgaard Zoega, Helga Furu, Kari |
spellingShingle |
Cohen, Jacqueline M. Alvestad, Silje Cesta, Carolyn E. Bjørk, Marte‐Helene Leinonen, Maarit K. Nørgaard, Mette Einarsdóttir, Kristjana Engeland, Anders Gissler, Mika Karlstad, Øystein Klungsøyr, Kari Odsbu, Ingvild Reutfors, Johan Selmer, Randi M. Tomson, Torbjörn Ulrichsen, Sinna Pilgaard Zoega, Helga Furu, Kari Comparative Safety of Antiseizure Medication Monotherapy for Major Malformations |
author_facet |
Cohen, Jacqueline M. Alvestad, Silje Cesta, Carolyn E. Bjørk, Marte‐Helene Leinonen, Maarit K. Nørgaard, Mette Einarsdóttir, Kristjana Engeland, Anders Gissler, Mika Karlstad, Øystein Klungsøyr, Kari Odsbu, Ingvild Reutfors, Johan Selmer, Randi M. Tomson, Torbjörn Ulrichsen, Sinna Pilgaard Zoega, Helga Furu, Kari |
author_sort |
Cohen, Jacqueline M. |
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 |
http://dx.doi.org/10.1002/ana.26561 https://onlinelibrary.wiley.com/doi/pdf/10.1002/ana.26561 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ana.26561 |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Annals of Neurology volume 93, issue 3, page 551-562 ISSN 0364-5134 1531-8249 |
op_rights |
http://creativecommons.org/licenses/by-nc/4.0/ |
op_doi |
https://doi.org/10.1002/ana.26561 |
container_title |
Annals of Neurology |
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93 |
container_issue |
3 |
container_start_page |
551 |
op_container_end_page |
562 |
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1810452235978539008 |