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Developmental Effects On Children Of Women Who Take Antiepileptic Drugs During Pregnancy

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ClinicalTrials.gov Identifier: NCT00021866
Recruitment Status : Completed
First Posted : August 10, 2001
Last Update Posted : November 11, 2013
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Kimford J. Meador, MD, Emory University

Study Description
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
The purpose of this study is to determine if antiepileptic drugs (AEDs) differ in their neurodevelopmental effects. Specifically, do the children of the women with epilepsy differ in their behavioral and cognitive development depending on which AED their mother takes during pregnancy?

Condition or disease Intervention/treatment
Epilepsy Seizure Cognition Disorders Behavioral: Differential Abilities Scale Behavioral: Neuropsychological Testing

Detailed Description:
This is a prospective investigation enrolling 285 to 380 women with epilepsy during the first two trimesters of their pregnancies. There are 25 clinical centers as well as the database center. The women will be taking one of the following AEDs: carbamazepine, phenytoin, valproate, or lamotrigine. Cognitive and behavioral testing of the child will be done up to the age of 6 years. The study does not change the woman's doctor and does not interfere with the care of the treating physician.
Study Design
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Study Type : Observational
Actual Enrollment : 331 participants
Observational Model: Family-Based
Time Perspective: Prospective
Official Title: Neurodevelopmental Effects of Antiepileptic Drugs II: the NEAD Study
Study Start Date : September 2000
Actual Primary Completion Date : August 2010
Actual Study Completion Date : August 2012

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Group/Cohort Intervention/treatment
Carbamazepine
Children and their mothers exposed to Carbamazepine monotherapy in utero
 Behavioral: Differential Abilities Scale
IQ measurement at 3, 4.5 and 6 years of age
Other Name: DAS

Behavioral: Neuropsychological Testing
Tests of memory, attention, and behavior administered at 2,3, 4.5 and 6 Years of age
Other Names:
  • (Toni-3) Test of Nonverbal Intelligence
  • (WAIS) - Wechslers Adult Intelligence Scale -revised
  • Beck Depression Inventory
  • Bayley Scales of Infant Development,
  • NEPSY
  • Trails Preschool
  • Preschool Language Scale-4
  • Expressive One-Word Vocabulary TEst
  • Peabody Picture Vocabulary Test
  • Developmental Test of Visual-Motor Integration
  • Children's Memory Scale
  • Grooved Pegboard
  • Bracken Basic Concepts Scale
  • Wide Range Achievement TEst
  • Adaptive Behavior Assessment Scale
  • Behavioral Assessment for Children
  • Parenting Stress Index
Phenytoin
Children and their mothers exposed to phenytoin in utero
 Behavioral: Differential Abilities Scale
IQ measurement at 3, 4.5 and 6 years of age
Other Name: DAS

Behavioral: Neuropsychological Testing
Tests of memory, attention, and behavior administered at 2,3, 4.5 and 6 Years of age
Other Names:
  • (Toni-3) Test of Nonverbal Intelligence
  • (WAIS) - Wechslers Adult Intelligence Scale -revised
  • Beck Depression Inventory
  • Bayley Scales of Infant Development,
  • NEPSY
  • Trails Preschool
  • Preschool Language Scale-4
  • Expressive One-Word Vocabulary TEst
  • Peabody Picture Vocabulary Test
  • Developmental Test of Visual-Motor Integration
  • Children's Memory Scale
  • Grooved Pegboard
  • Bracken Basic Concepts Scale
  • Wide Range Achievement TEst
  • Adaptive Behavior Assessment Scale
  • Behavioral Assessment for Children
  • Parenting Stress Index
Lamotrigine
Children and their mothers exposed to Lamotrigine in utero
 Behavioral: Differential Abilities Scale
IQ measurement at 3, 4.5 and 6 years of age
Other Name: DAS

Behavioral: Neuropsychological Testing
Tests of memory, attention, and behavior administered at 2,3, 4.5 and 6 Years of age
Other Names:
  • (Toni-3) Test of Nonverbal Intelligence
  • (WAIS) - Wechslers Adult Intelligence Scale -revised
  • Beck Depression Inventory
  • Bayley Scales of Infant Development,
  • NEPSY
  • Trails Preschool
  • Preschool Language Scale-4
  • Expressive One-Word Vocabulary TEst
  • Peabody Picture Vocabulary Test
  • Developmental Test of Visual-Motor Integration
  • Children's Memory Scale
  • Grooved Pegboard
  • Bracken Basic Concepts Scale
  • Wide Range Achievement TEst
  • Adaptive Behavior Assessment Scale
  • Behavioral Assessment for Children
  • Parenting Stress Index
Valproate
Children and their mothers exposed to Valproate in utero
 Behavioral: Differential Abilities Scale
IQ measurement at 3, 4.5 and 6 years of age
Other Name: DAS

Behavioral: Neuropsychological Testing
Tests of memory, attention, and behavior administered at 2,3, 4.5 and 6 Years of age
Other Names:
  • (Toni-3) Test of Nonverbal Intelligence
  • (WAIS) - Wechslers Adult Intelligence Scale -revised
  • Beck Depression Inventory
  • Bayley Scales of Infant Development,
  • NEPSY
  • Trails Preschool
  • Preschool Language Scale-4
  • Expressive One-Word Vocabulary TEst
  • Peabody Picture Vocabulary Test
  • Developmental Test of Visual-Motor Integration
  • Children's Memory Scale
  • Grooved Pegboard
  • Bracken Basic Concepts Scale
  • Wide Range Achievement TEst
  • Adaptive Behavior Assessment Scale
  • Behavioral Assessment for Children
  • Parenting Stress Index


Outcome Measures
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Primary Outcome Measures :
  1. Child IQ as measured by the Differential Abilities Scale at 6 Years of age [ Time Frame: 6 years ]

Secondary Outcome Measures :
  1. Executive Functioning,Tower-NEPSY [ Time Frame: 6 Years ]
  2. Linguistic Functioning via Expressive one word vocabulary test and NEPSY subscales [ Time Frame: 6 Years ]
  3. Visual-Spatial Motor Functioning via NEPSY subscale and Visual-Motor Integration Scale [ Time Frame: 6 Years ]
  4. Memory via Children's Memory Scale [ Time Frame: 6 Years ]
  5. Motor Functioning via Grooved Pegboard [ Time Frame: 6 Years ]
  6. Academic Functioning via Wide Range Achievement Test [ Time Frame: 6 Years ]
  7. Adaptive Functioning via Adaptive Behavior System -2nd Edition [ Time Frame: 6 Years ]
  8. Behavior via Behavior Assessment for Children & Parent Stress Index [ Time Frame: 6 Years ]

Biospecimen Retention:   Samples With DNA
Venous blood for AED levels Cord Blood for G6PD, Homocysteine Saliva for drug metabolizing enzymes, antioxidant enzymes, DNA repair enzymes, drug membrane transporter proteins and folate-related genes

Eligibility Criteria
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Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Mothers and their child(ren) who were exposed to one of the following monotherapies in utero- Lamotrigine, Carbamazepine, Phenytoin, or Valproate. Fathers of the children and a first degree materal relative of the mother are also invited to have IQ testing and medical history
Criteria
  • Subject must be diagnosed with partial seizures and/or secondary generalization or primary generalized seizures (absence, atonic, myoclonic, and generalized tonic-clonic seizures)
  • Subjects must be on either carbamazepine, lamotrigine, phenytoin, or valproate monotherapy.
  • Mothers must not have a history of drug abuse (including alcohol) in the last year and have no sequelae of drug abuse.
  • Mothers must be able to maintain an accurate seizure diary of major motor seizures
  • Subjects must have an IQ greater than or equal to 70 points.
  • Subjects must have a history of a negative RPR and HIV.
  • Subjects must not have progressive cerebral disease or presence of other major medical illness
  • Subjects must not have exposure to known teratogens during pregnancy, except AEDs.
  • Subjects must not have poor compliance with prenatal care.
  • Subjects must have adequate reading skills to perform the cognitive tests.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00021866


Locations
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Sponsors and Collaborators
Emory University
National Institute of Neurological Disorders and Stroke (NINDS)
Investigators
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Principal Investigator: Kimford J. Meador, M.D. Emory University, Atlanta
More Information
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Additional Information:

Publications of Results:
Meador KJ, Chadwick D, Clayton-Smith J, Pennell P, Liporace J, Kalayian L, and NEAD Study Group. Antiepileptic drugs in pregnancy: Differences in U.K. and U.S.A. Epilepsia, 2003;44 (Suppl. 9):289.
Meador KJ, Page P, Liporace J, Kalayjian L, NEAD Study Group. Antiepileptic Drugs in Pregnancy. Neurology 2004;62 (Suppl 5):A311.
Meador KJ, Baker GA, Clayton Smith J, Pennell P, Liporace J, Kalayjian L, Kini U, NEAD Study Group. Differential Effects of Antiepileptic Drugs on Serious Adverse Outcomes in Children Exposed In Utero. Epilepsia 2004;45 (Suppl 3):58
Meador KM, Loring DW, Baker G, Smith JC, Pennell P, Liporace J, Kalayjian L, Kini U, NEAD Study Group. Differential and dose dependent effects of in utero antiepileptic drugs. Neurology 2005;64 (Suppl 1):A427

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Kimford J. Meador, MD, Professor, Emory University
ClinicalTrials.gov Identifier: NCT00021866    
Other Study ID Numbers: 0334-2001
2R01NS038455 ( U.S. NIH Grant/Contract )
2R01NS038455-06 ( U.S. NIH Grant/Contract )
First Posted: August 10, 2001    Key Record Dates
Last Update Posted: November 11, 2013
Last Verified: September 2013
Keywords provided by Kimford J. Meador, MD, Emory University:
epilepsy
seizure
pregnancy
antiepileptic
AED
carbamazepine
 phenytoin
valproate
lamotrigine
child
behavior
Additional relevant MeSH terms:
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Epilepsy
Seizures
Cognition Disorders
Brain Diseases
Central Nervous System Diseases
 Nervous System Diseases
Neurologic Manifestations
Neurocognitive Disorders
Mental Disorders