Clinical trial NCT00021866: Developmental Effects On Children Of Women Who Take Antiepileptic Drugs During Pregnancy
Official title: Neurodevelopmental Effects of Antiepileptic Drugs II: the NEAD Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Epilepsy
Seizure
Cognition Disorders
Keywords: epilepsy
seizure
pregnancy
antiepileptic
AED
carbamazepine
phenytoin
valproate
lamotrigine
child
behavior
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2001-08-10
Enrollment: 331
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
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

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?

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 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.

Primary outcomes:
measure: Child IQ as measured by the Differential Abilities Scale at 6 Years of age
timeFrame: 6 years
Secondary outcomes:
measure: Executive Functioning,Tower-NEPSY
timeFrame: 6 Years
measure: Linguistic Functioning via Expressive one word vocabulary test and NEPSY subscales
timeFrame: 6 Years
measure: Visual-Spatial Motor Functioning via NEPSY subscale and Visual-Motor Integration Scale
timeFrame: 6 Years
measure: Memory via Children's Memory Scale
timeFrame: 6 Years
measure: Motor Functioning via Grooved Pegboard
timeFrame: 6 Years
measure: Academic Functioning via Wide Range Achievement Test
timeFrame: 6 Years
measure: Adaptive Functioning via Adaptive Behavior System -2nd Edition
timeFrame: 6 Years
measure: Behavior via Behavior Assessment for Children & Parent Stress Index
timeFrame: 6 Years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Tucson
country: United States
facility: Arizona Health Sciences
state: Arizona
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: RUSH University Medical Center
state: Illinois
city: Wichita
country: United States
facility: Via Christi Medical Center
state: Kansas
city: Boston
country: United States
facility: Brigham & Womens' Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: St. Paul
country: United States
facility: Minnesota Epilepsy Group
state: Minnesota
city: New York
country: United States
facility: Columbia University
state: New York
city: Winston Salem
country: United States
facility: Wake Forest University Baptist Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Media
country: United States
facility: Riddle Health Care II
state: Pennsylvania
city: Irving
country: United States
facility: Baylor Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Liverpool
country: United Kingdom
facility: University of Liverpool
Study officials:
affiliation: Emory University, Atlanta
name: Kimford J. Meador, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Meador KJ, Page P, Liporace J, Kalayjian L, NEAD Study Group. Antiepileptic Drugs in Pregnancy. Neurology 2004;62 (Suppl 5):A311.
citation: 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
citation: 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
citation: 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.
citation: 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.
citation: 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.
citation: 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.