TY - JOUR
T1 - Specific fetal malformations following intrauterine exposure to antiseizure medication
AU - Vajda, Frank
AU - O'Brien, Terence
AU - Graham, Janet
AU - Hitchcock, Alison
AU - Perucca, Piero
AU - Lander, Cecilie
AU - Eadie, Mervyn
N1 - Funding Information:
We are grateful to professional and lay colleagues and to various lay bodies for referring patients to the APR, and to the Scientific Advisory Board and the Ethical Research Committees of St. Vincent’s Hospital, Melbourne, the Monash Medical Centre, the Royal Melbourne Hospital and other institutions for their successive ethics oversight of the APR. The Epilepsy Society of Australia, The Royal Melbourne Hospital Neuroscience Foundation, Epilepsy Action Australia, NHMRC and pharmaceutical companies Sanofi-Aventis, UCB Pharma, Janssen-Cilag, Novartis, Sci-Gen, Eisai, and Genzyme have provided financial support towards maintaining the APR at various stages of its existence.
Funding Information:
We are grateful to professional and lay colleagues and to various lay bodies for referring patients to the APR, and to the Scientific Advisory Board and the Ethical Research Committees of St. Vincent's Hospital, Melbourne, the Monash Medical Centre, the Royal Melbourne Hospital and other institutions for their successive ethics oversight of the APR. The Epilepsy Society of Australia, The Royal Melbourne Hospital Neuroscience Foundation, Epilepsy Action Australia, NHMRC and pharmaceutical companies Sanofi-Aventis, UCB Pharma, Janssen-Cilag, Novartis, Sci-Gen, Eisai, and Genzyme have provided financial support towards maintaining the APR at various stages of its existence.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/5
Y1 - 2023/5
N2 - Objective: To investigate in the Australian Pregnancy Register of Antiepileptic Drugs patterns of fetal malformation associated with intrauterine exposure to particular currently available antiseizure medications taken by women with epilepsy. Results: There was statistically significant evidence (P < 0.05) of an increased hazard of fetal malformation associated with exposure to valproate, carbamazepine, topiramate, zonisamide, and with conception after assisted fertilization, but a reduced hazard in the offspring of women who continued to smoke during pregnancy. Valproate exposure was associated with malformations in a wide range of organs and organ systems, carbamazepine and topiramate with hydronephrosis, topiramate also with hypospadias, zonisamide with spina bifida and assisted fertilization with heart and great vessel maldevelopment. Conclusions: Prenatal valproate exposure appears to interfere with the development of many if not all, fetal tissues. It seems likely that prenatal exposure to carbamazepine and topiramate, and possibly exposure to zonisamide, but also some process related to in vitro fertilization, may more selectively affect the normal development of particular fetal tissues or organs.
AB - Objective: To investigate in the Australian Pregnancy Register of Antiepileptic Drugs patterns of fetal malformation associated with intrauterine exposure to particular currently available antiseizure medications taken by women with epilepsy. Results: There was statistically significant evidence (P < 0.05) of an increased hazard of fetal malformation associated with exposure to valproate, carbamazepine, topiramate, zonisamide, and with conception after assisted fertilization, but a reduced hazard in the offspring of women who continued to smoke during pregnancy. Valproate exposure was associated with malformations in a wide range of organs and organ systems, carbamazepine and topiramate with hydronephrosis, topiramate also with hypospadias, zonisamide with spina bifida and assisted fertilization with heart and great vessel maldevelopment. Conclusions: Prenatal valproate exposure appears to interfere with the development of many if not all, fetal tissues. It seems likely that prenatal exposure to carbamazepine and topiramate, and possibly exposure to zonisamide, but also some process related to in vitro fertilization, may more selectively affect the normal development of particular fetal tissues or organs.
KW - Antiseizure medication
KW - Assisted fertilization
KW - Smoking
KW - Specific malformation
KW - Teratogenesis
KW - Valproate
UR - http://www.scopus.com/inward/record.url?scp=85153102099&partnerID=8YFLogxK
U2 - 10.1016/j.yebeh.2023.109219
DO - 10.1016/j.yebeh.2023.109219
M3 - Article
C2 - 37088066
AN - SCOPUS:85153102099
SN - 1525-5050
VL - 142
JO - Epilepsy & Behavior
JF - Epilepsy & Behavior
M1 - 109219
ER -