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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Kimford J. Meador, MD, Emory University
ClinicalTrials.gov Identifier:
NCT00021866
First received: August 8, 2001
Last updated: November 8, 2013
Last verified: September 2013
  Purpose

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 Intervention
Epilepsy
Seizure
Cognition Disorders
Behavioral: Differential Abilities Scale
Behavioral: Neuropsychological Testing

Study Type: Observational
Study Design: Observational Model: Family-Based
Time Perspective: Prospective
Official Title: Neurodevelopmental Effects of Antiepileptic Drugs II: the NEAD Study

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • Child IQ as measured by the Differential Abilities Scale at 6 Years of age [ Time Frame: 6 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Executive Functioning,Tower-NEPSY [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
  • Linguistic Functioning via Expressive one word vocabulary test and NEPSY subscales [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
  • Visual-Spatial Motor Functioning via NEPSY subscale and Visual-Motor Integration Scale [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
  • Memory via Children's Memory Scale [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
  • Motor Functioning via Grooved Pegboard [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
  • Academic Functioning via Wide Range Achievement Test [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
  • Adaptive Functioning via Adaptive Behavior System -2nd Edition [ Time Frame: 6 Years ] [ Designated as safety issue: No ]
  • Behavior via Behavior Assessment for Children & Parent Stress Index [ Time Frame: 6 Years ] [ Designated as safety issue: No ]

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


Enrollment: 331
Study Start Date: September 2000
Study Completion Date: August 2012
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

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.

  Eligibility

Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00021866

  Show 21 Study Locations
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Kimford J. Meador, M.D. Emory University, Atlanta
  More Information

Additional Information:
Publications:
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

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Kimford J. Meador, MD, Professor, Emory University
ClinicalTrials.gov Identifier: NCT00021866     History of Changes
Other Study ID Numbers: 0334-2001, 2RO1NS38455, 2R01NS038455-06
Study First Received: August 8, 2001
Last Updated: November 8, 2013
Health Authority: United States: Federal Government

Keywords provided by Emory University:
epilepsy
seizure
pregnancy
antiepileptic
AED
carbamazepine
phenytoin
valproate
lamotrigine
child
behavior

Additional relevant MeSH terms:
Cognition Disorders
Epilepsy
Seizures
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Anticonvulsants
Carbamazepine
Lamotrigine
Analgesics
Analgesics, Non-Narcotic
Antimanic Agents
Calcium Channel Blockers
Cardiovascular Agents
Central Nervous System Agents
Central Nervous System Depressants
Excitatory Amino Acid Agents
Excitatory Amino Acid Antagonists
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Sensory System Agents

ClinicalTrials.gov processed this record on November 20, 2014