Prenatal Microarray Follow-Up Study

Columbia University

Status: Completed

Conditions: Genetic Diseases

Treatments: Other: 3-year follow-up

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT02160938

5U01HD055651 (U.S. NIH Grant/Contract)

AAAL0100

Details and patient eligibility

About

The objectives of this multi-center collaborative study are to ascertain the frequency of specific copy number variants (CNVs) identified prenatally and to evaluate in detail through continued follow-up of the children the phenotypes associated with CNVs of known or uncertain clinical significance.

Full description

Specifically the aims are as follows:

1. Determine the intellectual function of the children at age 3 years
2. Determine phenotypic characteristics other than intellectual function of the children at age 3 years
3. Determine the frequency of specific copy number variants discovered during routine prenatal diagnostic testing
4. Evaluate the educational, counseling and psychosocial implications of microarray testing as it is introduced as a standard prenatal diagnostic procedure.

Enrollment: 184 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Eligibility Criteria for Enrollment into the 3 year Follow-up Cohort

Inclusion Criteria

1. Singleton or multi-fetal pregnancy with a prenatal invasive procedure resulting in a diagnosis by microarray analysis of a microdeletion/duplication less than 10 Mbs, either pathogenic or of uncertain significance, which is reported to the patient. This includes:

   • Infants diagnosed during prenatal diagnostic studies performed at the10 pre-specified prenatal diagnostic centers
   • Infants diagnosed by analysis of microarrays performed at the collaborating laboratories
   • Infants referred through the Prenatal Microarray Resource Center website
   • Children who will be at least 3 years of age by January of 2018, and who had a prenatally detected CNV <10 Mbs, either pathogenic or of uncertain significance OR

2. Children whose mothers were enrolled in the initial study (through July 2011) and who met inclusion criteria for follow-up in that phase, referred to as the "Index cohort". This includes:

   • CNVs of uncertain or known significance, some of which were not reported to the patient
   • Mosaic findings by karyotype and/or microarray alone.

Exclusion Criteria

1. Patient refusal to allow infant follow-up through the age of three
2. Patient not fluent in the English language
3. Patient under the age of 18
4. In surrogate pregnancies, the "rearing parents" are unavailable to give consent.

Trial design

184 participants in 2 patient groups

3 year follow-up cohort

Description:

When the infants reach 24 months of age, the Study Follow-up Specialist will send all participants an age- appropriate Ages and Stages Questionnaire (ASQ) for completion. At as close to the age of 3 as possible, the following exams will be performed and are described below: * The Vineland-II Adaptive Behavior Scale (VABS) * Wechsler Preschool and Primary Scale of Intelligence IV (WPPSI-IV), or Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V, for siblings older than 7 years 7 months, when necessary) * Children will also be photographed (for review by the study dysmorphologist)

Treatment:

Other: 3-year follow-up

Limited follow-up cohort

Description:

Women with children who will not reach the age of 2 years 6 months by the end of our study but have a prenatally diagnosed CNV will be recruited into the limited follow-up study. Each center will describe the study to eligible women and will verbally obtain their permission to be contacted by the Study Follow-up Specialist. The Study Follow-Up Specialist will contact the patient, explain the study, and obtain full written informed consent.