Clinical trial NCT02160938: Prenatal Microarray Follow-Up Study
Official title: Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis: Follow-Up
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Genetic Diseases
Keywords: microarray
prenatal
copy number variant
CNV
microdeletion
microduplication
genetic
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Human Genome Research Institute (NHGRI)
First posted: 2014-06-11
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Women undergoing prenatal microarray testing during pregnancy.

Brief summary: 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.

Detailed 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.

Eligibility 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.

Primary outcomes:
measure: Full Scale Intelligence Quotient (IQ) score
timeFrame: age 3 years
Secondary outcomes:
measure: Percent of subjects with specific commonly occurring CNVs
timeFrame: detected prenatally
measure: Percent of subjects with seizure disorders
timeFrame: age: up to 3 years
measure: Percent of subjects with cerebral palsy
timeFrame: age: up to 3 years
measure: Percent of subjects with dysmorphic features diagnosed by dysmorphologist
timeFrame: age 3 years
measure: Percent of subjects with structural anomalies
timeFrame: age: up to 3 years
measure: Verbal Comprehension composite score
timeFrame: age: up to 3 years
measure: Visual Spatial composite score
timeFrame: age: up to 3 years
measure: Working Memory composite score
timeFrame: age: up to 3 years
measure: Communication domain score
timeFrame: age: up to 3 years
measure: Daily Living Skills domain score
timeFrame: age: up to 3 years
measure: Socialization domain score
timeFrame: age: up to 3 years
measure: Motor Skills domain score
timeFrame: age: up to 3 years
measure: Adaptive Behavior Composite score
timeFrame: age: up to 3 years
measure: Age-adjusted Z scores for birth weight
timeFrame: birth
measure: Age-adjusted Z scores for birth length
timeFrame: birth
measure: Age-adjusted Z scores for head circumference
timeFrame: birth
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Center for Fetal Medicine
state: California
city: Rockville
country: United States
facility: George Washington University Biostatistics Center
state: Maryland
city: Larchmont
country: United States
facility: Montefiore Medical Center
state: New York
city: Manhasset
country: United States
facility: North Shore LIJ
state: New York
city: New York
country: United States
facility: Mt. Sinai Medical Center
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: OB/GYN Services PC
state: New York
city: Danville
country: United States
facility: Geisinger Health System
state: Pennsylvania
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Columbia University
name: Ronald Wapner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, Savage M, Platt LD, Saltzman D, Grobman WA, Klugman S, Scholl T, Simpson JL, McCall K, Aggarwal VS, Bunke B, Nahum O, Patel A, Lamb AN, Thom EA, Beaudet AL, Ledbetter DH, Shaffer LG, Jackson L. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012 Dec 6;367(23):2175-84. doi: 10.1056/NEJMoa1203382.
citation: Bernhardt BA, Soucier D, Hanson K, Savage MS, Jackson L, Wapner RJ. Women's experiences receiving abnormal prenatal chromosomal microarray testing results. Genet Med. 2013 Feb;15(2):139-45. doi: 10.1038/gim.2012.113. Epub 2012 Sep 6.
citation: Bernhardt BA, Kellom K, Barbarese A, Faucett WA, Wapner RJ. An exploration of genetic counselors' needs and experiences with prenatal chromosomal microarray testing. J Genet Couns. 2014 Dec;23(6):938-47. doi: 10.1007/s10897-014-9702-y. Epub 2014 Feb 27.