Prenatal Microarray Follow-Up Study

NCT02160938 | Completed

• 2 other identifiers: AAAL01005U01HD055651
• Study Type: observational
• Target: 184
• Locations: 1 country
• Sites: 9

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.

Conditions

Genetic Diseases

Keywords

microarray; prenatal; copy number variant; CNV; microdeletion; microduplication; genetic

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (16)

• Percent of subjects with specific commonly occurring CNVs

  detected prenatally

• Percent of subjects with seizure disorders

  age: up to 3 years

• Percent of subjects with cerebral palsy

  age: up to 3 years

• Percent of subjects with dysmorphic features diagnosed by dysmorphologist

  age 3 years

• Percent of subjects with structural anomalies

  age: up to 3 years

Study Arms (2)

3 year follow-up cohort

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)

Other: 3-year follow-up

Limited follow-up cohort

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.

Interventions

3-year follow-up OTHER

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)

3 year follow-up cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women undergoing prenatal microarray testing during pregnancy.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Columbia University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Human Genome Research Institute (NHGRI): collaborator

Study Sites (9)

Center for Fetal Medicine

Los Angeles, California, 90048, United States

Location

George Washington University Biostatistics Center

Rockville, Maryland, 20852, United States

Location

Montefiore Medical Center

Larchmont, New York, 10538, United States

Location

North Shore LIJ

Manhasset, New York, 11030, United States

Location

Mt. Sinai Medical Center

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

OB/GYN Services PC

New York, New York, 10075, United States

Location

Geisinger Health System

Danville, Pennsylvania, 17822, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (3)

• 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.

  PMID: 23215555 BACKGROUND

• 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.

  PMID: 22955112 BACKGROUND

• 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.

  PMID: 24569858 RESULT

MeSH Terms

Conditions

Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Ronald Wapner, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Vice Chairman for Research, Department of Obstetrics and Gynecology

Study Record Dates

• First Submitted: June 10, 2014
• First Posted: June 11, 2014
• Study Start: February 1, 2013
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: March 25, 2019

Record last verified: 2019-03

Locations

US (9)