Fetal growth and premature delivery in pregnant women on antiepileptic drugs

Objective To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery. Methods This study included singleton liveborn infants born to women enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2016. Da...

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Veröffentlicht in:Annals of neurology Jg. 82; H. 3; S. 457 - 465
Hauptverfasser: Hernández‐Díaz, Sonia, McElrath, Thomas F., Pennell, Page B., Hauser, W. Allen, Yerby, Mark, Holmes, Lewis B.
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States Wiley Subscription Services, Inc 01.09.2017
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ISSN:0364-5134, 1531-8249, 1531-8249
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Abstract Objective To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery. Methods This study included singleton liveborn infants born to women enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2016. Data were collected prospectively through telephone interviews. The prevalence of preterm birth (<37 weeks) and small for gestational age status (SGA) among infants exposed prenatally to AEDs when used by women with epilepsy (WWE) or women without epilepsy (WWOE) was compared with that among infants unexposed to AEDs and born to WWOE. Multivariate log‐binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results The study population included infants born to 6,777 AED‐WWE, 696 AED‐WWOE, and 486 no‐AED‐WWOE. The risk of prematurity was 6.2% for no‐AED‐WWOE, 9.3% for AED‐WWE (RR = 1.5, 95% CI = 1.0–2.1), and 10.5% for AED‐WWOE (RR = 1.5, 95% CI = 1.0–2.4). Prenatal exposure to AEDs in WWE and WWOE was associated with a mean lower birth weight of 110 and 136g, respectively, as compared to no‐AED‐WWOE. The prevalence of SGA was 5.0% for no‐AED‐WWOE, 10.9% for AED‐WWE (RR = 2.0, 95% CI = 1.3–3.0), and 11.0% for AED‐WWOE (RR = 1.9, 95% CI = 1.2–2.9). Within users of AEDs in monotherapy, the prevalence of SGA ranged from 7.3% for lamotrigine to 18.5% for topiramate. Interpretation Women on AEDs during pregnancy, whether for epilepsy or for other neuropsychiatric indications, are at a higher risk of delivering prematurely and giving birth to SGA newborns. The risk may vary by drug. Ann Neurol 2017;82:457–465
AbstractList Objective To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery. Methods This study included singleton liveborn infants born to women enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2016. Data were collected prospectively through telephone interviews. The prevalence of preterm birth (<37 weeks) and small for gestational age status (SGA) among infants exposed prenatally to AEDs when used by women with epilepsy (WWE) or women without epilepsy (WWOE) was compared with that among infants unexposed to AEDs and born to WWOE. Multivariate log‐binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results The study population included infants born to 6,777 AED‐WWE, 696 AED‐WWOE, and 486 no‐AED‐WWOE. The risk of prematurity was 6.2% for no‐AED‐WWOE, 9.3% for AED‐WWE (RR = 1.5, 95% CI = 1.0–2.1), and 10.5% for AED‐WWOE (RR = 1.5, 95% CI = 1.0–2.4). Prenatal exposure to AEDs in WWE and WWOE was associated with a mean lower birth weight of 110 and 136g, respectively, as compared to no‐AED‐WWOE. The prevalence of SGA was 5.0% for no‐AED‐WWOE, 10.9% for AED‐WWE (RR = 2.0, 95% CI = 1.3–3.0), and 11.0% for AED‐WWOE (RR = 1.9, 95% CI = 1.2–2.9). Within users of AEDs in monotherapy, the prevalence of SGA ranged from 7.3% for lamotrigine to 18.5% for topiramate. Interpretation Women on AEDs during pregnancy, whether for epilepsy or for other neuropsychiatric indications, are at a higher risk of delivering prematurely and giving birth to SGA newborns. The risk may vary by drug. Ann Neurol 2017;82:457–465
To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery.OBJECTIVETo evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery.This study included singleton liveborn infants born to women enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2016. Data were collected prospectively through telephone interviews. The prevalence of preterm birth (<37 weeks) and small for gestational age status (SGA) among infants exposed prenatally to AEDs when used by women with epilepsy (WWE) or women without epilepsy (WWOE) was compared with that among infants unexposed to AEDs and born to WWOE. Multivariate log-binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs).METHODSThis study included singleton liveborn infants born to women enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2016. Data were collected prospectively through telephone interviews. The prevalence of preterm birth (<37 weeks) and small for gestational age status (SGA) among infants exposed prenatally to AEDs when used by women with epilepsy (WWE) or women without epilepsy (WWOE) was compared with that among infants unexposed to AEDs and born to WWOE. Multivariate log-binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs).The study population included infants born to 6,777 AED-WWE, 696 AED-WWOE, and 486 no-AED-WWOE. The risk of prematurity was 6.2% for no-AED-WWOE, 9.3% for AED-WWE (RR = 1.5, 95% CI = 1.0-2.1), and 10.5% for AED-WWOE (RR = 1.5, 95% CI = 1.0-2.4). Prenatal exposure to AEDs in WWE and WWOE was associated with a mean lower birth weight of 110 and 136g, respectively, as compared to no-AED-WWOE. The prevalence of SGA was 5.0% for no-AED-WWOE, 10.9% for AED-WWE (RR = 2.0, 95% CI = 1.3-3.0), and 11.0% for AED-WWOE (RR = 1.9, 95% CI = 1.2-2.9). Within users of AEDs in monotherapy, the prevalence of SGA ranged from 7.3% for lamotrigine to 18.5% for topiramate.RESULTSThe study population included infants born to 6,777 AED-WWE, 696 AED-WWOE, and 486 no-AED-WWOE. The risk of prematurity was 6.2% for no-AED-WWOE, 9.3% for AED-WWE (RR = 1.5, 95% CI = 1.0-2.1), and 10.5% for AED-WWOE (RR = 1.5, 95% CI = 1.0-2.4). Prenatal exposure to AEDs in WWE and WWOE was associated with a mean lower birth weight of 110 and 136g, respectively, as compared to no-AED-WWOE. The prevalence of SGA was 5.0% for no-AED-WWOE, 10.9% for AED-WWE (RR = 2.0, 95% CI = 1.3-3.0), and 11.0% for AED-WWOE (RR = 1.9, 95% CI = 1.2-2.9). Within users of AEDs in monotherapy, the prevalence of SGA ranged from 7.3% for lamotrigine to 18.5% for topiramate.Women on AEDs during pregnancy, whether for epilepsy or for other neuropsychiatric indications, are at a higher risk of delivering prematurely and giving birth to SGA newborns. The risk may vary by drug. Ann Neurol 2017;82:457-465.INTERPRETATIONWomen on AEDs during pregnancy, whether for epilepsy or for other neuropsychiatric indications, are at a higher risk of delivering prematurely and giving birth to SGA newborns. The risk may vary by drug. Ann Neurol 2017;82:457-465.
To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery. This study included singleton liveborn infants born to women enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2016. Data were collected prospectively through telephone interviews. The prevalence of preterm birth (<37 weeks) and small for gestational age status (SGA) among infants exposed prenatally to AEDs when used by women with epilepsy (WWE) or women without epilepsy (WWOE) was compared with that among infants unexposed to AEDs and born to WWOE. Multivariate log-binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). The study population included infants born to 6,777 AED-WWE, 696 AED-WWOE, and 486 no-AED-WWOE. The risk of prematurity was 6.2% for no-AED-WWOE, 9.3% for AED-WWE (RR = 1.5, 95% CI = 1.0-2.1), and 10.5% for AED-WWOE (RR = 1.5, 95% CI = 1.0-2.4). Prenatal exposure to AEDs in WWE and WWOE was associated with a mean lower birth weight of 110 and 136g, respectively, as compared to no-AED-WWOE. The prevalence of SGA was 5.0% for no-AED-WWOE, 10.9% for AED-WWE (RR = 2.0, 95% CI = 1.3-3.0), and 11.0% for AED-WWOE (RR = 1.9, 95% CI = 1.2-2.9). Within users of AEDs in monotherapy, the prevalence of SGA ranged from 7.3% for lamotrigine to 18.5% for topiramate. Women on AEDs during pregnancy, whether for epilepsy or for other neuropsychiatric indications, are at a higher risk of delivering prematurely and giving birth to SGA newborns. The risk may vary by drug. Ann Neurol 2017;82:457-465.
Objective To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery. Methods This study included singleton liveborn infants born to women enrolled in the North American Antiepileptic Drug Pregnancy Registry between 1997 and 2016. Data were collected prospectively through telephone interviews. The prevalence of preterm birth (<37 weeks) and small for gestational age status (SGA) among infants exposed prenatally to AEDs when used by women with epilepsy (WWE) or women without epilepsy (WWOE) was compared with that among infants unexposed to AEDs and born to WWOE. Multivariate log-binomial regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). Results The study population included infants born to 6,777 AED-WWE, 696 AED-WWOE, and 486 no-AED-WWOE. The risk of prematurity was 6.2% for no-AED-WWOE, 9.3% for AED-WWE (RR=1.5, 95% CI=1.0-2.1), and 10.5% for AED-WWOE (RR=1.5, 95% CI=1.0-2.4). Prenatal exposure to AEDs in WWE and WWOE was associated with a mean lower birth weight of 110 and 136g, respectively, as compared to no-AED-WWOE. The prevalence of SGA was 5.0% for no-AED-WWOE, 10.9% for AED-WWE (RR=2.0, 95% CI=1.3-3.0), and 11.0% for AED-WWOE (RR=1.9, 95% CI=1.2-2.9). Within users of AEDs in monotherapy, the prevalence of SGA ranged from 7.3% for lamotrigine to 18.5% for topiramate. Interpretation Women on AEDs during pregnancy, whether for epilepsy or for other neuropsychiatric indications, are at a higher risk of delivering prematurely and giving birth to SGA newborns. The risk may vary by drug. Ann Neurol 2017;82:457-465
Author McElrath, Thomas F.
Pennell, Page B.
Holmes, Lewis B.
Yerby, Mark
Hauser, W. Allen
Hernández‐Díaz, Sonia
Author_xml – sequence: 1
  givenname: Sonia
  surname: Hernández‐Díaz
  fullname: Hernández‐Díaz, Sonia
  organization: Harvard T. H. Chan School of Public Health
– sequence: 2
  givenname: Thomas F.
  surname: McElrath
  fullname: McElrath, Thomas F.
  organization: Division of Maternal–Fetal Medicine, Department of Obstetrics and Gynecology, Brigham and Women's Hospital
– sequence: 3
  givenname: Page B.
  surname: Pennell
  fullname: Pennell, Page B.
  organization: Divisions of Epilepsy and Women's Health, Department of Neurology, Brigham and Women's Hospital
– sequence: 4
  givenname: W. Allen
  surname: Hauser
  fullname: Hauser, W. Allen
  organization: Columbia University
– sequence: 5
  givenname: Mark
  surname: Yerby
  fullname: Yerby, Mark
  organization: Oregon Health and Science University
– sequence: 6
  givenname: Lewis B.
  surname: Holmes
  fullname: Holmes, Lewis B.
  email: holmes.lewis@mgh.harvard.edu
  organization: North American Antiepileptic Drug Pregnancy Registry, MassGeneral Hospital for Children
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28856694$$D View this record in MEDLINE/PubMed
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2017 American Neurological Association.
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Notes This article is dedicated to Dr Autumn Klein, whose life was interrupted before she could complete this project for her patients.
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References 2004; 65
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2004; 61
2013; 208
2012
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2015; 72
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1999; 340
2013; 382
1997; 814
1999; 106
2012; 78
2008; 70
1990; 144
2001; 65
2012; 172
2015; 24
2007; 28
2013; 36
2000; 19
2011; 205
2006; 68
2009; 50
2004; 190
2013; 12
2008; 29
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2006; 47
2002; 22
2008; 25
2016; 87
2011; 20
2000; 61
2003; 3
2011; 21
2012; 29
2014; 261
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2008; 83
2012; 24
2003; 289
1992; 45
2014; 55
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Snippet Objective To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery. Methods This study...
To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery. This study included singleton...
Objective To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery. Methods This study...
To evaluate the effects of epilepsy and antiepileptic drugs (AEDs) used during pregnancy on fetal growth and preterm delivery.OBJECTIVETo evaluate the effects...
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StartPage 457
SubjectTerms Adult
Anticonvulsants - adverse effects
Anticonvulsants - pharmacology
Anticonvulsants - therapeutic use
Antiepileptic agents
Birth weight
Childbirth & labor
Confidence intervals
Convulsions & seizures
Drug delivery systems
Drug development
Drugs
Epilepsy
Epilepsy - drug therapy
Female
Fetal Development - drug effects
Fetuses
Gestational age
Health risk assessment
Humans
Infant, Newborn
Infant, Premature
Infant, Small for Gestational Age
Infants
Lamotrigine
Male
Neonates
Obstetric Labor, Premature - chemically induced
Obstetric Labor, Premature - epidemiology
Population studies
Pregnancy
Premature birth
Prenatal experience
Prenatal exposure
Prevalence
Prospective Studies
Registries
Regression analysis
Regression models
Risk
Risk assessment
Small for gestational age
Topiramate
Young Adult
Title Fetal growth and premature delivery in pregnant women on antiepileptic drugs
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