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

NCT00021866 | Completed DMC

• 3 other identifiers: 0334-20012R01NS0384552R01NS038455-06
• Study Type: observational
• Target: 331
• Locations: 2 countries
• Sites: 21

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?

Conditions

Epilepsy; Seizure; Cognition Disorders

Keywords

epilepsy; seizure; pregnancy; antiepileptic; AED; carbamazepine; phenytoin; valproate; lamotrigine; child; behavior

Outcome Measures

Primary Outcomes (1)

• Child IQ as measured by the Differential Abilities Scale at 6 Years of age

  6 years

Secondary Outcomes (8)

• Executive Functioning,Tower-NEPSY

  6 Years

• Linguistic Functioning via Expressive one word vocabulary test and NEPSY subscales

  6 Years

• Visual-Spatial Motor Functioning via NEPSY subscale and Visual-Motor Integration Scale

  6 Years

• Memory via Children's Memory Scale

  6 Years

• Motor Functioning via Grooved Pegboard

  6 Years

Study Arms (4)

Carbamazepine

Children and their mothers exposed to Carbamazepine monotherapy in utero

Behavioral: Differential Abilities Scale; Behavioral: Neuropsychological Testing

Phenytoin

Children and their mothers exposed to phenytoin in utero

Behavioral: Differential Abilities Scale; Behavioral: Neuropsychological Testing

Lamotrigine

Children and their mothers exposed to Lamotrigine in utero

Behavioral: Differential Abilities Scale; Behavioral: Neuropsychological Testing

Valproate

Children and their mothers exposed to Valproate in utero

Behavioral: Differential Abilities Scale; Behavioral: Neuropsychological Testing

Interventions

Differential Abilities Scale BEHAVIORAL

IQ measurement at 3, 4.5 and 6 years of age

Also known as: DAS

Carbamazepine; Lamotrigine; Phenytoin; Valproate

Neuropsychological Testing BEHAVIORAL

Tests of memory, attention, and behavior administered at 2,3, 4.5 and 6 Years of age

Also known as: (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

Carbamazepine; Lamotrigine; Phenytoin; Valproate

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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

* 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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Emory University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (21)

University of Alabama

Birmingham, Alabama, 32294, United States

Location

Arizona Health Sciences

Tucson, Arizona, 85724, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Medical College of Georgia

Augusta, Georgia, 30912, United States

Location

RUSH University Medical Center

Chicago, Illinois, 60612, United States

Location

Via Christi Medical Center

Wichita, Kansas, 67214, United States

Location

Brigham & Womens' Hospital

Boston, Massachusetts, 02115, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Minnesota Epilepsy Group

Saint Paul, Minnesota, 55102, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Wake Forest University Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44102, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Riddle Health Care II

Media, Pennsylvania, 19063, United States

Location

Baylor Medical Center

Irving, Texas, 75061, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

University of Washington

Seattle, Washington, 98104, United States

Location

University of Liverpool

Liverpool, L9 7LJ, United Kingdom

Location

Related Publications (8)

• 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.

  RESULT

• Meador KJ, Page P, Liporace J, Kalayjian L, NEAD Study Group. Antiepileptic Drugs in Pregnancy. Neurology 2004;62 (Suppl 5):A311.

  RESULT

• 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

  RESULT

• 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

  RESULT

• Meador KJ, Baker GA, Finnell RH, Kalayjian LA, Liporace JD, Loring DW, Mawer G, Pennell PB, Smith JC, Wolff MC; NEAD Study Group. In utero antiepileptic drug exposure: fetal death and malformations. Neurology. 2006 Aug 8;67(3):407-12. doi: 10.1212/01.wnl.0000227919.81208.b2.

  PMID: 16894099 RESULT

• Meador KJ, Pennell PB, May RC, Brown CA, Baker G, Bromley R, Loring DW, Cohen MJ; NEAD Investigator Group. Effects of periconceptional folate on cognition in children of women with epilepsy: NEAD study. Neurology. 2020 Feb 18;94(7):e729-e740. doi: 10.1212/WNL.0000000000008757. Epub 2019 Dec 23.

  PMID: 31871217 DERIVED

• Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, Clayton-Smith J, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, Loring DW; Neurodevelopmental Effects of Antiepileptic Drugs (NEAD) Study Group. Breastfeeding in children of women taking antiepileptic drugs: cognitive outcomes at age 6 years. JAMA Pediatr. 2014 Aug;168(8):729-36. doi: 10.1001/jamapediatrics.2014.118.

  PMID: 24934501 DERIVED

• Meador KJ, Baker GA, Browning N, Cohen MJ, Bromley RL, Clayton-Smith J, Kalayjian LA, Kanner A, Liporace JD, Pennell PB, Privitera M, Loring DW; NEAD Study Group. Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study. Lancet Neurol. 2013 Mar;12(3):244-52. doi: 10.1016/S1474-4422(12)70323-X. Epub 2013 Jan 23.

  PMID: 23352199 DERIVED

Related Links

• Click here for more information about this study and a list of recruiting centers

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

MeSH Terms

Conditions

Epilepsy; Seizures; Cognition Disorders; Behavior

Interventions

amsonic acid; Neuropsychological Tests; Psychological Tests

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Behavioral Disciplines and Activities

Study Officials

• Kimford J. Meador, M.D.

  Emory University, Atlanta

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: FAMILY BASED
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 8, 2001
• First Posted: August 10, 2001
• Study Start: September 1, 2000
• Primary Completion: August 1, 2010
• Study Completion: August 1, 2012
• Last Updated: November 11, 2013

Record last verified: 2013-09

Locations

GB (1); US (20)