Developmental Delay in Children Exposed During Pregnancy to Either Lamotrigine,Sodium Valproate, or Carbamazepine

Developmental Delay in Children Exposed During Pregnancy to Either Lamotrigine, Sodium Valproate, or Carbamazepine

This study is investigating the neurodevelopmental effects of prenatal exposure to lamotrigine (LTG), sodium valproate (VPA), or carbamazepine (CBZ) monotherapies. The hypotheses to be tested include:

1. Exposure during pregnancy to CBZ, LTG, and VPA, each as monotherapy, is associated with developmental delay with or without signs of autism.
2. Exposure to each drug (CBZ, LTG, and VPA) as monotherapy is associated with an increased rate of occurrence of major malformations.
3. The child with major malformations is more likely to have developmental delay with or without signs of autism than the child who does not have major malformations.
4. The occurrence of adaptive behavior outcomes will show a dose-response relationship with the dose of medication taken by the mother in the first trimester.

The study population includes children 36-83 months of age who were exposed throughout gestation to one of the three drugs of interest, as treatment for maternal seizure disorder.

Study Overview

• Status: Unknown
• Conditions: Birth Defects; Developmental Delay; Autism

• Study Type: Observational
• Enrollment (Actual): 298

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 6 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Children 36-83 months of age, prenatally exposed to LTG, VPA, or CBZ monotherapies, recruited through mothers enrolled in the North American Antiepileptic Drug Pregnancy Registry.

Description

Inclusion Criteria:

• 36-83 months of age
• Prenatal exposure to LTG, VPA, or CBZ monotherapy
• AED was used by mother to suppress seizures
• Mother was enrolled in the North American AED Pregnancy Registry

Exclusion Criteria:

• Exposure during the first trimester to other known teratogens.
• Mother with mental health issues
• Refusal to release medical records to confirm eligibility.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
LTG-exposed; Children exposed to LTG during pregnancy.
VPA-exposed; Children exposed to VPA during pregnancy.
CBZ-exposed; Children exposed to CBZ during pregnancy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adaptive Behavior Scores	Measures of each child's Adaptive Behavior scores as assessed by the Vineland-II Adaptive Behavior Scales, collected when the child was between 36 and 83 months of age.	36-83 months of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Presence/Absence of Major Malformations	Based on interview with mother and review of medical records, determination is made as to whether or not the child had any major malformations at birth.	36-83 months of age

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: GlaxoSmithKline
• Investigators: Principal Investigator: Lewis B. Holmes, MD, Massachusetts General Hospital; Study Director: Jane Adams, Ph.D., University of Massachusetts, Boston

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): January 1, 2010
• Study Completion (Anticipated): September 1, 2010

Study Registration Dates

• First Submitted: March 31, 2010
• First Submitted That Met QC Criteria: March 31, 2010
• First Posted (Estimate): April 2, 2010

Study Record Updates

• Last Update Posted (Estimate): April 2, 2010
• Last Update Submitted That Met QC Criteria: March 31, 2010
• Last Verified: March 1, 2010

More Information

Terms related to this study

• Keywords: Autism; Lamotrigine; Valproate; Carbamazepine; Antiepileptic; Developmental Delay; Anticonvulsant; Teratogen
• Additional Relevant MeSH Terms: Congenital Abnormalities
• Other Study ID Numbers: 2005P000379