For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
21
views
37
references
 Top references
cited by
12
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      109
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Teratogenicity of Antiepileptic Drugs

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          Antiepileptic drugs (AED) have chronic teratogenic effects, the most common of which are congenital heart disease, cleft lip/palate, urogenital and neural tube defects. The aim of our study is to examine teratogenic effects of AED and the correlation between these malformations and AED in single or multiple pregnancies.

          Methods

          This is a retrospective study of malformations in children born to mothers currently followed up by our outpatient clinics who used or discontinued AED during their pregnancy. Their children were then investigated using echocardiography, urinary ultrasound, cranial magnetic resonance image, and examined by geneticists and pediatric dentists.

          Results

          One hundred and seventeen children were included in the study. Ninety one of these children were exposed to AED during pregnancy. The most commonly used AED were valproic acid and carbamazepine in monotherapy. The percentage of major anomaly was 6.8% in all children. Dysmorphic features and dental anomalies were observed more in children exposed especially to valproic acid. There were 26 mothers with two and four mothers with three pregnancies from the same fathers. No correlation was found between the distribution of malformations in recurring pregnancies and AED usage.

          Conclusion

          Our study has the highest number of dysmorphism examined in literature, found in all the children exposed to valproic acid, which may account for the higher rate of facial dysmorphism and dental anomalies. On lower doses of valproic acid, major malformations are not seen, although the risk increases with polytherapy. Our data also indicate possible effects of genetic and environmental factors on malformations.

          Related collections

          Most cited references37

          • Record: found
          • Abstract: found
          • Article: not found

          Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study.

          Kimford Meador, Gus Baker, Nancy Browning … (2013)
          Many women of childbearing potential take antiepileptic drugs, but the cognitive effects of fetal exposure are uncertain. We aimed to assess effects of commonly used antiepileptic drugs on cognitive outcomes in children up to 6 years of age. In this prospective, observational, assessor-masked, multicentre study, we enrolled pregnant women with epilepsy on antiepileptic drug monotherapy (carbamazepine, lamotrigine, phenytoin, or valproate) between October, 1999, and February, 2004, at 25 epilepsy centres in the UK and the USA. Our primary outcome was intelligence quotient (IQ) at 6 years of age (age-6 IQ) in all children, assessed with linear regression adjusted for maternal IQ, antiepileptic drug type, standardised dose, gestational birth age, and use of periconceptional folate. We also assessed multiple cognitive domains and compared findings with outcomes at younger ages. This study is registered with ClinicalTrials.gov, number NCT00021866. We included 305 mothers and 311 children (six twin pairs) in the primary analysis. 224 children completed 6 years of follow-up (6-year-completer sample). Multivariate analysis of all children showed that age-6 IQ was lower after exposure to valproate (mean 97, 95% CI 94-101) than to carbamazepine (105, 102-108; p=0·0015), lamotrigine (108, 105-110; p=0·0003), or phenytoin (108, 104-112; p=0·0006). Children exposed to valproate did poorly on measures of verbal and memory abilities compared with those exposed to the other antiepileptic drugs and on non-verbal and executive functions compared with lamotrigine (but not carbamazepine or phenytoin). High doses of valproate were negatively associated with IQ (r=-0·56, p<0·0001), verbal ability (r=-0·40, p=0·0045), non-verbal ability (r=-0·42, p=0·0028), memory (r=-0·30, p=0·0434), and executive function (r=-0·42, p=0·0004), but other antiepileptic drugs were not. Age-6 IQ correlated with IQs at younger ages, and IQ improved with age for infants exposed to any antiepileptic drug. Compared with a normative sample (173 [93%] of 187 children), right-handedness was less frequent in children in our study overall (185 [86%] of 215; p=0·0404) and in the lamotrigine (59 [83%] of 71; p=0·0287) and valproate (38 [79%] of 40; p=0·0089) groups. Verbal abilities were worse than non-verbal abilities in children in our study overall and in the lamotrigine and valproate groups. Mean IQs were higher in children exposed to periconceptional folate (108, 95% CI 106-111) than they were in unexposed children (101, 98-104; p=0·0009). Fetal valproate exposure has dose-dependent associations with reduced cognitive abilities across a range of domains at 6 years of age. Reduced right-handedness and verbal (vs non-verbal) abilities might be attributable to changes in cerebral lateralisation induced by exposure to antiepileptic drugs. The positive association of periconceptional folate with IQ is consistent with other recent studies. Copyright © 2013 Elsevier Ltd. All rights reserved.
          Article 0 comments Cited 160 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Dose-dependent risk of malformations with antiepileptic drugs: an analysis of data from the EURAP epilepsy and pregnancy registry.

            Anne Sabers, , Erminio Bonizzoni … (2011)
            Prenatal exposure to antiepileptic drugs is associated with a greater risk of major congenital malformations, but there is inadequate information on the comparative teratogenicity of individual antiepileptic drugs and the association with dose. We aimed to establish the risks of major congenital malformations after monotherapy exposure to four major antiepileptic drugs at different doses. The EURAP epilepsy and pregnancy registry is an observational cohort study representing a collaboration of physicians from 42 countries. We prospectively monitored pregnancies exposed to monotherapy with different doses of four common drugs: carbamazepine, lamotrigine, valproic acid, or phenobarbital. Our primary endpoint was the rate of major congenital malformations detected up to 12 months after birth. We assessed pregnancy outcomes according to dose at the time of conception irrespective of subsequent dose changes. After excluding pregnancies that ended in spontaneous abortions or chromosomal or genetic abnormalities, those in which the women had treatment changes in the first trimester, and those involving other diseases or treatments that could affect fetal outcome, we assessed rates of major congenital malformations in 1402 pregnancies exposed to carbamazepine, 1280 on lamotrigine, 1010 on valproic acid, and 217 on phenobarbital. An increase in malformation rates with increasing dose at the time of conception was recorded for all drugs. Multivariable analysis including ten covariates in addition to treatment with antiepileptic drugs showed that the risk of malformations was greater with a parental history of major congenital malformations (odds ratio 4·4, 95% CI 2·06-9·23). We noted the lowest rates of malformation with less than 300 mg per day lamotrigine (2·0% [17 events], 95% CI 1·19-3·24) and less than 400 mg per day carbamazepine (3·4% [5 events], 95% CI 1·11-7·71). Compared with lamotrigine monotherapy at doses less than 300 mg per day, risks of malformation were significantly higher with valproic acid and phenobarbital at all investigated doses, and with carbamazepine at doses greater than 400 mg per day. The risk of major congenital malformations is influenced not only by type of antiepileptic drug, but also by dose and other variables, which should be taken into account in the management of epilepsy in women of childbearing potential. Eisai, GlaxoSmithKline, Janssen-Cilag, Novartis, Pfizer, Sanofi-Aventis, UCB, Netherlands Epilepsy Foundation, Stockholm County Council, and ALF. Copyright © 2011 Elsevier Ltd. All rights reserved.
            Article 0 comments Cited 124 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Malformation risks of antiepileptic drugs in pregnancy: a prospective study from the UK Epilepsy and Pregnancy Register.

              J. Morrow, A. Russell, E Guthrie … (2006)
              To assess the relative risk of major congenital malformation (MCM) from in utero exposure to antiepileptic drug (AEDs). Prospective data collected by the UK Epilepsy and Pregnancy Register were analysed. The presence of MCMs recorded within the first three months of life was the main outcome measure. Full outcome data were collected on 3607 cases. The overall MCM rate for all AED exposed cases was 4.2% (95% confidence interval (CI), 3.6% to 5.0%). The MCM rate was higher for polytherapy (6.0%) (n = 770) than for monotherapy (3.7%) (n = 2598) (crude odds ratio (OR) = 1.63 (p = 0.010), adjusted OR = 1.83 (p = 0.002)). The MCM rate for women with epilepsy who had not taken AEDs during pregnancy (n = 239) was 3.5% (1.8% to 6.8%). The MCM rate was greater for pregnancies exposed only to valproate (6.2% (95% CI, 4.6% to 8.2%) than only to carbamazepine (2.2% (1.4% to 3.4%) (OR = 2.78 (p<0.001); adjusted OR = 2.97 (p<0.001)). There were fewer MCMs for pregnancies exposed only to lamotrigine than only to valproate. A positive dose response for MCMs was found for lamotrigine (p = 0.006). Polytherapy combinations containing valproate carried a higher risk of MCM than combinations not containing valproate (OR = 2.49 (1.31 to 4.70)). Only 4.2% of live births to women with epilepsy had an MCM. The MCM rate for polytherapy exposure was greater than for monotherapy exposure. Polytherapy regimens containing valproate had significantly more MCMs than those not containing valproate. For monotherapy exposures, carbamazepine was associated with the lowest risk of MCM.
              Article 0 comments Cited 101 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Psychopharmacol Neurosci
                Journal ID (iso-abbrev): Clin Psychopharmacol Neurosci
                Title: Clinical Psychopharmacology and Neuroscience
                Publisher: Korean College of Neuropsychopharmacology
                ISSN (Print): 1738-1088
                ISSN (Electronic): 2093-4327
                Publication date (Print): February 2017
                Publication date (Electronic): 28 February 2017
                Volume: 15
                Issue: 1
                Pages: 19-27
                Affiliations
                [1 ]Department of Neurology, Bakirkoy Research and Training Hospital for Psychiatry, Neurology, and Neurosurgery, Istanbul University, Istanbul, Turkey
                [2 ]Department of Medical Genetics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
                [5 ]Department of Radiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
                [6 ]Department of Biostatistics, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
                [7 ]Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
                [3 ]Department of Pediatric Cardiology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey
                [4 ]Department of Pedodonty, Faculty of Dentistry, Istanbul University, Istanbul, Turkey
                Author notes
                Address for correspondence: Betül Tekin Güveli, MD, Department of Neurology, Bakirkoy Research and Training Hospital for Psychiatry, Neurology, and Neurosurgery, St. No: 25/2, Bakırköy, Istanbul 34147, Turkey, Tel: +90-212-409-15-15, Fax: +90-212-409-15-95, E-mail: betultekin2013@ 123456gmail.com
                Article
                Publisher ID: cpn-15-019
                DOI: 10.9758/cpn.2017.15.1.19
                PMC ID: 5290711
                PubMed ID: 28138106
                SO-VID: 4061badf-746e-4c82-9283-780675b0695c
                Copyright © Copyright © 2017, Korean College of Neuropsychopharmacology
                License:

                This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 06 November 2015
                Date revision received : 06 December 2015
                Date accepted : 25 March 2016
                Categories
                Subject: Original Article

                Keywords: dysmorphic features,dental anomalies,congenital malformations,antiepileptic drugs,teratogenesis
                Data availability:
                Keywords: dysmorphic features, dental anomalies, congenital malformations, antiepileptic drugs, teratogenesis

                Comments

                Comment on this article

                scite_

                Similar content109

                See all similar

                Cited by12

                See all cited by

                Most referenced authors455

                See all reference authors