Prenatal Screening for Down Syndrome With DNAFirst

NCT01966991 | Completed

• 1 other identifier: 13-0013
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This study will explore how maternal plasma circulating cell free DNA (ccfDNA) can be used as a primary screening test for Down syndrome as part of routine clinical care in the general pregnancy population. Plasma ccfDNA testing is currently recommended only for use as a secondary screen for 'high-risk' women (i.e., women whose risk factors for trisomy make them candidates for invasive testing such as chorionic villous sampling or amniocentesis). Because most women in this 'high-risk' category are carrying unaffected fetuses, many 'unnecessary' procedures are completed in order to identify the few women whose fetuses have a chromosomal disorder. This creates expense, anxiety, and most importantly, loss of unaffected fetuses due to procedure related miscarriage. Plasma DNA testing is now being used to reduce significantly the number of women with unaffected fetuses undergoing invasive testing. Applying such testing as a 'first-line' screen has not been well-explored, despite calls from several clinical professional societies to do so. The investigators intent is to introduce, under carefully monitored conditions, ccfDNA testing through Rhode Island primary prenatal practices to the general pregnancy population. Education/orientation of prenatal care providers, their staffs, and their patients will be carefully orchestrated, and implementation issues identified and addressed. Telephone surveys of consented patients will elicit responses to their understanding of the test, their satisfaction with the process, and a comparison of their experience with serum screening in a prior pregnancy. Knowledge gained from this study will help validate new screening paradigms involving ccfDNA testing. The study is not designed to estimate Down syndrome detection rates with any confidence, but can provide information on uptake rates, failure rates, screen positive rates, and the decision-making of women with positive test results.

Conditions

Trisomy 21; Trisomy 18; Trisomy 13; Monosomy X

Keywords

Down syndrome; prenatal screening; trisomy 21; patient satisfaction

Outcome Measures

Primary Outcomes (1)

• Patient satisfaction with ccfDNA testing as a primary screen for aneuploidy

  A telephone survey will be administered to women who have undergone ccfDNA testing (DNAFirst) and who have provided written permission to be contacted specifically for this purpose.Included will be questions designed to elicit understanding of the results, implications of positive and negative results, comparison with earlier serum-screening experience, and reasons for accepting/declining ancillary testing (sex aneuploidy).

  within 90 days of receiving ccfDNA screening results

Study Arms (1)

Surveyed DNAFirst users

Women who opted for DNAFirst testing and who provided written permission (attested by signature and provision of telephone number)for DNAFirst Study staff to telephone them and conduct a brief telephone survey about their experiences.

Eligibility Criteria

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

Study Population

Women with a singleton pregnancy at 10 weeks or later who agree to be contacted by telephone to provide consent and participate in a structured survey to assess comprehension and satisfaction with their experience.

You may qualify if:

• at least 10 weeks pregnant
• opting for DNAFirst testing
• written permission to be contacted by telephone
• providing a usable phone number for contact
• consenting (verbally) to telephone survey

You may not qualify if:

• screen positive DNAFirst result
• non-English speaking

Sponsors & Collaborators

• Women and Infants Hospital of Rhode Island: lead
• Natera, Inc.: collaborator

Study Sites (1)

Women & Infants Hospital of Rhode Island

Providence, Rhode Island, 02905, United States

Location

Related Publications (5)

• Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Deciu C, Grody WW, Nelson SF, Canick JA. DNA sequencing of maternal plasma to detect Down syndrome: an international clinical validation study. Genet Med. 2011 Nov;13(11):913-20. doi: 10.1097/GIM.0b013e3182368a0e.

  PMID: 22005709 BACKGROUND

• Palomaki GE, Deciu C, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, van den Boom D, Bombard AT, Grody WW, Nelson SF, Canick JA. DNA sequencing of maternal plasma reliably identifies trisomy 18 and trisomy 13 as well as Down syndrome: an international collaborative study. Genet Med. 2012 Mar;14(3):296-305. doi: 10.1038/gim.2011.73. Epub 2012 Feb 2.

  PMID: 22281937 BACKGROUND

• Norton ME, Rose NC, Benn P. Noninvasive prenatal testing for fetal aneuploidy: clinical assessment and a plea for restraint. Obstet Gynecol. 2013 Apr;121(4):847-850. doi: 10.1097/AOG.0b013e31828642c6.

  PMID: 23635685 BACKGROUND

• Palomaki GE, Kloza EM, O'Brien BM, Eklund EE, Lambert-Messerlian GM. The clinical utility of DNA-based screening for fetal aneuploidy by primary obstetrical care providers in the general pregnancy population. Genet Med. 2017 Jul;19(7):778-786. doi: 10.1038/gim.2016.194. Epub 2017 Jan 12.

  PMID: 28079901 RESULT

• Palomaki GE, Ashwood ER, Best RG, Lambert-Messerlian G, Knight GJ. Is maternal plasma DNA testing impacting serum-based screening for aneuploidy in the United States? Genet Med. 2015 Nov;17(11):897-900. doi: 10.1038/gim.2015.39. Epub 2015 Apr 2.

  PMID: 25834952 DERIVED

MeSH Terms

Conditions

Down Syndrome; Trisomy 18 Syndrome; Trisomy 13 Syndrome; Turner Syndrome; Patient Satisfaction

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Sex Chromosome Disorders of Sex Development; Male Urogenital Diseases; Sex Chromosome Disorders; Gonadal Disorders; Endocrine System Diseases; Treatment Adherence and Compliance; Health Behavior; Behavior

Study Officials

• Glenn E Palomaki, PhD

  Women and Infants Hospital of Rhode Island

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2013
• First Posted: October 22, 2013
• Study Start: June 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: December 1, 2015
• Last Updated: February 22, 2018

Record last verified: 2018-02

Locations

US (1)