Zonisamide safety in pregnancy: Data from the UK and Ireland epilepsy and pregnancy register.
Abnormalities, Drug-Induced
/ epidemiology
Anticonvulsants
/ adverse effects
Epilepsy
/ drug therapy
Female
Follow-Up Studies
Humans
Ireland
/ epidemiology
Pregnancy
Pregnancy Complications
/ chemically induced
Pregnancy Outcome
/ epidemiology
Registries
United Kingdom
/ epidemiology
Zonisamide
/ therapeutic use
Epilepsy
Major congenital malformation
Pregnancy
Teratogenicity
Zonisamide
Journal
Seizure
ISSN: 1532-2688
Titre abrégé: Seizure
Pays: England
ID NLM: 9306979
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
received:
09
06
2021
revised:
01
07
2021
accepted:
02
07
2021
pubmed:
18
7
2021
medline:
14
9
2021
entrez:
17
7
2021
Statut:
ppublish
Résumé
Animal data suggest teratogenic effects with zonisamide use and risk of pregnancy losses. Human data following zonisamide exposure are presently limited, but suggest low risk of malformation with elevated risk of low birth weight. To calculate the major congenital malformation (MCM) rate of zonisamide in human pregnancy and assess for a signal of any specific malformation pattern and associations with birth weight. Data were obtained from the UK and Ireland Epilepsy and Pregnancy register (UKIEPR) which is an observational, registration, and follow up study from December 1996 to July 2020. Eligibility criteria were use of zonisamide and to have been referred to the UKIEPR before the outcome of the pregnancy was known. Primary outcome was evidence of MCM. From December 1996 through July 2020 there were 112 cases of first trimester exposure to zonisamide, including 26 monotherapy cases. There were 3 MCM for monotherapy cases (MCM rate 13.0% (95% confidence interval 4.5-32.1)), and 5 MCM for polytherapy cases (MCM rate 6.9% (95% confidence interval 3.0-15.2)). While the median birth weight was on 71st and 44th centile for monotherapy and polytherapy cases respectively, there was a high rate of infants born small for gestational age (21% for both). These data raise concerns about a signal for potential teratogenicity with zonisamide in human pregnancy. Given the low numbers reported, further data will be required to adequately counsel women who use zonisamide in pregnancy.
Sections du résumé
BACKGROUND
BACKGROUND
Animal data suggest teratogenic effects with zonisamide use and risk of pregnancy losses. Human data following zonisamide exposure are presently limited, but suggest low risk of malformation with elevated risk of low birth weight.
OBJECTIVE
OBJECTIVE
To calculate the major congenital malformation (MCM) rate of zonisamide in human pregnancy and assess for a signal of any specific malformation pattern and associations with birth weight.
METHODS AND MATERIALS
METHODS
Data were obtained from the UK and Ireland Epilepsy and Pregnancy register (UKIEPR) which is an observational, registration, and follow up study from December 1996 to July 2020. Eligibility criteria were use of zonisamide and to have been referred to the UKIEPR before the outcome of the pregnancy was known. Primary outcome was evidence of MCM.
RESULTS
RESULTS
From December 1996 through July 2020 there were 112 cases of first trimester exposure to zonisamide, including 26 monotherapy cases. There were 3 MCM for monotherapy cases (MCM rate 13.0% (95% confidence interval 4.5-32.1)), and 5 MCM for polytherapy cases (MCM rate 6.9% (95% confidence interval 3.0-15.2)). While the median birth weight was on 71st and 44th centile for monotherapy and polytherapy cases respectively, there was a high rate of infants born small for gestational age (21% for both).
CONCLUSION
CONCLUSIONS
These data raise concerns about a signal for potential teratogenicity with zonisamide in human pregnancy. Given the low numbers reported, further data will be required to adequately counsel women who use zonisamide in pregnancy.
Identifiants
pubmed: 34273670
pii: S1059-1311(21)00233-8
doi: 10.1016/j.seizure.2021.07.002
pii:
doi:
Substances chimiques
Anticonvulsants
0
Zonisamide
459384H98V
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
311-315Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.