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Population-based study of antiepileptic drug exposure in utero-Influence on head circumference in newborns

Almgren, Malin; Källén, Bengt LU and Lavebratt, Catharina (2009) In Seizure 18(10). p.672-675
Abstract
Purpose: To study the effect of AED exposure on head circumference in the newborn. Methods: Data on all Swedish singletons births between 1995 and 2005, over 900,000 births, were obtained from the Swedish Medical Birth Registry. The effects of AEDs on birth-weight-adjusted mean head circumference (bw-adj-HC) were estimated by comparison with data from all births in an analysis which was adjusted for year of birth, maternal age, parity, maternal smoking, and maternal body mass index. Results: A significant reduction of mean bw-adj-HC was seen after both carbamazepine (CBZ) (standard deviation scores (SDS) = 0.15, p < 0.001) and valproic acid (VPA) (SDS = 0.10, p = 0.04) in monotherapy. No effect on mean bw-adj-HC was seen for phenytoin,... (More)
Purpose: To study the effect of AED exposure on head circumference in the newborn. Methods: Data on all Swedish singletons births between 1995 and 2005, over 900,000 births, were obtained from the Swedish Medical Birth Registry. The effects of AEDs on birth-weight-adjusted mean head circumference (bw-adj-HC) were estimated by comparison with data from all births in an analysis which was adjusted for year of birth, maternal age, parity, maternal smoking, and maternal body mass index. Results: A significant reduction of mean bw-adj-HC was seen after both carbamazepine (CBZ) (standard deviation scores (SDS) = 0.15, p < 0.001) and valproic acid (VPA) (SDS = 0.10, p = 0.04) in monotherapy. No effect on mean bw-adj-HC was seen for phenytoin, clonazepam, lamotrigine and gabapentin. There was a significant increase in the occurrence of microcephaly (bw-adj-HC smaller than 2 SD below the mean) after any AED polytherapy (OR = 2.85, 95% CI: 1.74-4.78) but not after AED monotherapy or monotherapy with CBZ or VPA. CBZ OF VPA was taken by 71% of the pregnant mothers on AED, and the usage increased over time. Conclusions: CBZ and VPA in monotherapy during pregnancy reduce mean bw-adj-HC. AED polytherapy increases the rate of microcephaly but no significant effect is seen of AED monotherapy. The possible significance for the further development of the child is uncertain but should be explored. (C) 2009 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Lamotrigine, Pregnancy, Valproic acid, Carbamazepine, Microcephaly
in
Seizure
volume
18
issue
10
pages
672 - 675
publisher
Elsevier
external identifiers
  • wos:000273067100002
  • scopus:71549141310
ISSN
1532-2688
DOI
10.1016/j.seizure.2009.09.002
language
English
LU publication?
yes
id
03d20d0e-3ce2-45a2-b810-0a9003a1a7f4 (old id 1531846)
date added to LUP
2010-01-29 11:43:29
date last changed
2017-12-10 04:17:13
@article{03d20d0e-3ce2-45a2-b810-0a9003a1a7f4,
  abstract     = {Purpose: To study the effect of AED exposure on head circumference in the newborn. Methods: Data on all Swedish singletons births between 1995 and 2005, over 900,000 births, were obtained from the Swedish Medical Birth Registry. The effects of AEDs on birth-weight-adjusted mean head circumference (bw-adj-HC) were estimated by comparison with data from all births in an analysis which was adjusted for year of birth, maternal age, parity, maternal smoking, and maternal body mass index. Results: A significant reduction of mean bw-adj-HC was seen after both carbamazepine (CBZ) (standard deviation scores (SDS) = 0.15, p &lt; 0.001) and valproic acid (VPA) (SDS = 0.10, p = 0.04) in monotherapy. No effect on mean bw-adj-HC was seen for phenytoin, clonazepam, lamotrigine and gabapentin. There was a significant increase in the occurrence of microcephaly (bw-adj-HC smaller than 2 SD below the mean) after any AED polytherapy (OR = 2.85, 95% CI: 1.74-4.78) but not after AED monotherapy or monotherapy with CBZ or VPA. CBZ OF VPA was taken by 71% of the pregnant mothers on AED, and the usage increased over time. Conclusions: CBZ and VPA in monotherapy during pregnancy reduce mean bw-adj-HC. AED polytherapy increases the rate of microcephaly but no significant effect is seen of AED monotherapy. The possible significance for the further development of the child is uncertain but should be explored. (C) 2009 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.},
  author       = {Almgren, Malin and Källén, Bengt and Lavebratt, Catharina},
  issn         = {1532-2688},
  keyword      = {Lamotrigine,Pregnancy,Valproic acid,Carbamazepine,Microcephaly},
  language     = {eng},
  number       = {10},
  pages        = {672--675},
  publisher    = {Elsevier},
  series       = {Seizure},
  title        = {Population-based study of antiepileptic drug exposure in utero-Influence on head circumference in newborns},
  url          = {http://dx.doi.org/10.1016/j.seizure.2009.09.002},
  volume       = {18},
  year         = {2009},
}