Malformation risks of antiepileptic drug monotherapies in pregnancy: updated results from the UK and Ireland Epilepsy and Pregnancy Registers.
OBJECTIVE
Antiepileptic drug (AED) exposure during pregnancy increases the risk of major congenital malformations (MCMs). The magnitude of this risk varies by AED exposure. Here we provide updated results from the UK Epilepsy and Pregnancy Register of the risk of MCMs after monotherapy exposure to valproate, carbamazepine and lamotrigine.


METHODS
Fifteen-year prospective observational study from 1996 until 2012. The main outcome measure is the MCM rate.


RESULTS
Informative outcomes were available for 5206 cases. 1290 women were exposed to valproate monotherapy, 1718 to carbamazepine monotherapy and 2198 to lamotrigine monotherapy. The MCM risk with valproate monotherapy exposure in utero was 6.7% (95% CI 5.5% to 8.3%) compared with 2.6% with carbamazepine (95% CI 1.9% to 3.5%) and 2.3% with lamotrigine (95% CI 1.8% to 3.1%). A significant dose effect was seen with valproate (p=0.0006) and carbamazepine (p=0.03) exposed pregnancies. A non-significant trend towards higher MCM rate with increasing dose was found with lamotrigine. MCM rate for high-dose lamotrigine (>400 mg daily) was lower than the MCM rate for pregnancies exposed to <600 mg daily of valproate, but this was not significant (3.4% vs 5.0%, p=0.31).


CONCLUSIONS
In utero exposure to valproate carries a significantly higher MCM risk than lamotrigine (p=0.0001) and carbamazepine (p=0.0001) monotherapy. In contrast to prior findings, high-dose lamotrigine was associated with fewer MCMs than all doses of valproate. While lamotrigine has a favourable profile compared with valproate for adverse pregnancy outcomes, the requirements for seizure control should not be overlooked.
Neurology Department, Belfast Health and Social Care Trust, Royal Victoria Hospital, Belfast, Co Antrim, UK.
E
E
Campbell
Institute of Neurology, University College London.
F
F
Kennedy
Department of Clinical Neurophysiology, Institute of Neurological Sciences, Southern General Hospital, Glasgow, UK.
A
A
Russell
Academic Unit of Primary Medical Care, Samuel Fox House, University of Sheffield, Northern General Hospital, Sheffield, UK.
W H
WH
Smithson
Neurology Department, Luton & Dunstable Hospitals NHS Trust, Luton, UK.
L
L
Parsons
Department of Medical Genetics, Belfast Health and Social Care Trust, Belfast City Hospital, Belfast, Co Antrim, UK.
P J
PJ
Morrison
RSCI, Beaumont Hospital, Dublin, Ireland.
B
B
Liggan
Neurology Department, Belfast Health and Social Care Trust, Royal Victoria Hospital, Belfast, Co Antrim, UK.
B
B
Irwin
Department of Neurology, Beaumont Hospital, Dublin, UK.
N
N
Delanty
Neurology Department, Belfast Health and Social Care Trust, Royal Victoria Hospital, Belfast, Co Antrim, UK.
S J
SJ
Hunt
Neurology Department, Belfast Health and Social Care Trust, Royal Victoria Hospital, Belfast, Co Antrim, UK.
J
J
Craig
Neurology Department, Belfast Health and Social Care Trust, Royal Victoria Hospital, Belfast, Co Antrim, UK.
J
J
Morrow
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D002220:Carbamazepine / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007494:Ireland / Q000453:epidemiology; D000077213:Lamotrigine; D011247:Pregnancy; D011446:Prospective Studies; D012042:Registries; D014227:Triazines / Q000009:adverse effects; D006113:United Kingdom / Q000453:epidemiology; D014635:Valproic Acid / Q000009:adverse effects; D055815:Young Adult
D000927:Anticonvulsants; D014227:Triazines; D002220:Carbamazepine; D014635:Valproic Acid; D000077213:Lamotrigine
ANTICONVULSANTS; EPILEPSY