Prenatal Microarray Follow-Up Study

Genetic Diseases Clinical Trial

Official title:

Prenatal Cytogenetic Diagnosis by Array-Based Copy Number Analysis: Follow-Up

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02160938
• Other study ID #: AAAL0100
• Secondary ID: 5U01HD055651
• Status: Completed
• Start date: February 2013
• Est. completion date: December 2018

Study information

• Verified date: March 2019
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 184
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Genetic Diseases
• Genetic Diseases, Inborn

Intervention

Other:
• 3-year follow-up
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 the age of 3, 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)

Locations

Country	Name	City	State
United States	Geisinger Health System	Danville	Pennsylvania
United States	Montefiore Medical Center	Larchmont	New York
United States	Center for Fetal Medicine	Los Angeles	California
United States	North Shore LIJ	Manhasset	New York
United States	Columbia University	New York	New York
United States	Mt. Sinai Medical Center	New York	New York
United States	OB/GYN Services PC	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	George Washington University Biostatistics Center	Rockville	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
Columbia University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Human Genome Research Institute (NHGRI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Full Scale Intelligence Quotient (IQ) score	Full Scale IQ score from the Wechsler Preschool and Primary Scale of Intelligence IV or Wechsler Intelligence Scale for Children 5th edition	age 3 years
Secondary	Percent of subjects with specific commonly occurring CNVs		detected prenatally
Secondary	Percent of subjects with seizure disorders		age: up to 3 years
Secondary	Percent of subjects with cerebral palsy		age: up to 3 years
Secondary	Percent of subjects with dysmorphic features diagnosed by dysmorphologist		age 3 years
Secondary	Percent of subjects with structural anomalies		age: up to 3 years
Secondary	Verbal Comprehension composite score	Verbal Comprehension composite score from the Wechsler Preschool and Primary Scale of Intelligence IV	age: up to 3 years
Secondary	Visual Spatial composite score	Visual Spatial composite score from the Wechsler Preschool and Primary Scale of Intelligence IV	age: up to 3 years
Secondary	Working Memory composite score	Working Memory composite score from the Wechsler Preschool and Primary Scale of Intelligence IV	age: up to 3 years
Secondary	Communication domain score	Communication domain score from the Vineland Adaptive Behavior Scale	age: up to 3 years
Secondary	Daily Living Skills domain score	Daily Living Skills domain score from the Vineland Adaptive Behavior Scale	age: up to 3 years
Secondary	Socialization domain score	Socialization domain score from the Vineland Adaptive Behavior Scale	age: up to 3 years
Secondary	Motor Skills domain score	Motor Skills domain score from the Vineland Adaptive Behavior Scale	age: up to 3 years
Secondary	Adaptive Behavior Composite score	Adaptive Behavior Composite score from the Vineland Adaptive Behavior Scale	age: up to 3 years
Secondary	Age-adjusted Z scores for birth weight		birth
Secondary	Age-adjusted Z scores for birth length		birth
Secondary	Age-adjusted Z scores for head circumference		birth

External Links

•   An online community providing information about prenatal chromosome microarray testing for both patients and providers with the goal of engaging families in research.