Noninvasive Prenatal Diagnosis: Using Fetal Cells From Maternal Blood

NCT ID: NCT00064597

Last Updated: 2005-06-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Total Enrollment

3500 participants

Study Classification

OBSERVATIONAL

Study Start Date

1987-12-31

Study Completion Date

2003-12-31

Brief Summary

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This purpose of this study is to develop noninvasive methods of prenatal diagnosis. Fetal cells can be found in maternal blood. This study is designed to isolate these fetal cells from a sample of the pregnant woman's blood and use those cells to test for fetal chromosome abnormalities.

Detailed Description

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Fetal cells can be recovered from maternal blood, suggesting that noninvasive prenatal diagnosis is possible. However, recovery and analysis of fetal cells from maternal blood is complex and sensitivity is low because of the rarity of these cells in the maternal circulation. This study was designed to develop a noninvasive, safe, relatively inexpensive, and accurate technique for the prenatal diagnosis of genetic disorders in the first trimester.

The study included a systematic evaluation of variables involved in separating and enriching fetal cells isolated from maternal blood through fluorescence activated cell sorting (FACS) and magnetic activated cell sorting (MACS) followed by fluorescent in situ hybridization (FISH) with chromosome-specific DNA probes. The results of these tests were compared to those obtained from amniocentesis or chorionic villus sampling (CVS) on the same women. No clinical decision was made based on the results of the experimental diagnostic/screening technique.

Even if the biological risks associated with reproductive genetic technologies are reduced, it is possible that other risks (or benefits) are associated with the procedures. Some of these factors may be: increased or diminished maternal anxiety, increased adjustment or maladaption to the pregnancy, increased feelings of coercion to undertake the procedure, and increased or decreased comfort with reproductive decision-making. The study also assessed whether there were any nonbiological or psychological effects on the women undergoing prenatal diagnostic testing.

After the first five years of the study, preliminary analysis of the data showed that the sensitivity of aneuploidy detection using fetal cell analysis from maternal blood is comparable to single marker prenatal serum screening, but technological advances are needed before fetal cell analysis has clinical application as part of a multiple maker method for noninvasive prenatal screening. Target cell recovery and fetal cell detection were better using MACS than with FACS. The detection rate of finding at least one aneuploid cell in cases of fetal aneuploidy was 74.4%.

Conditions

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Chromosome Disorders

Keywords

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Fetal cells Prenatal diagnosis Cytogenetic disorders Chromosomal disorders Single gene mutation detection Abnormal serum marker profile Fluorescence activated cell sorting (FACS) Magnetic activated cell sorting (MACS) Fluorescence in situ hybridization (FISH) Chromosomal disorders of the fetus Single gene defects of the fetus

Study Design

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Observational Model Type

DEFINED_POPULATION

Study Time Perspective

OTHER

Eligibility Criteria

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Inclusion Criteria

* Pregnant
* Abnormal serum marker profile (alpha-fetoprotein, hCG, estriol)
* Ultrasound abnormalities of the fetus
* Any high risk indicator for aneuploidy as determined by physician
Minimum Eligible Age

16 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role lead

Principal Investigators

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Laird Jackson, MD

Role: PRINCIPAL_INVESTIGATOR

Diana Bianchi, MD

Role: PRINCIPAL_INVESTIGATOR

Mark Evans, MD

Role: PRINCIPAL_INVESTIGATOR

Sherman Elias, MD

Role: PRINCIPAL_INVESTIGATOR

Locations

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University of Illinois at Chicago

Chicago, Illinois, United States

Site Status

New England Medical Center Hospital

Boston, Massachusetts, United States

Site Status

Wayne State University

Detroit, Michigan, United States

Site Status

Jefferson Medical College

Philadelphia, Pennsylvania, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Countries

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United States

References

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Bischoff FZ, Hahn S, Johnson KL, Simpson JL, Bianchi DW, Lewis DE, Weber WD, Klinger K, Elias S, Jackson LG, Evans MI, Holzgreve W, de la Cruz F. Intact fetal cells in maternal plasma: are they really there? Lancet. 2003 Jan 11;361(9352):139-40. doi: 10.1016/S0140-6736(03)12191-5.

Reference Type BACKGROUND
PMID: 12531583 (View on PubMed)

Bianchi DW, Simpson JL, Jackson LG, Elias S, Holzgreve W, Evans MI, Dukes KA, Sullivan LM, Klinger KW, Bischoff FZ, Hahn S, Johnson KL, Lewis D, Wapner RJ, de la Cruz F. Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data. National Institute of Child Health and Development Fetal Cell Isolation Study. Prenat Diagn. 2002 Jul;22(7):609-15. doi: 10.1002/pd.347.

Reference Type BACKGROUND
PMID: 12124698 (View on PubMed)

Bianchi DW. Prenatal exclusion of recessively inherited disorders: should maternal plasma analysis precede invasive techniques? Clin Chem. 2002 May;48(5):689-90. No abstract available.

Reference Type BACKGROUND
PMID: 11978594 (View on PubMed)

Bohmer RM, Stroh HP, Johnson KL, LeShane ES, Bianchi DW. Fetal cell isolation from maternal blood cultures by flow cytometric hemoglobin profiles. Results of a preliminary clinical trial. Fetal Diagn Ther. 2002 Mar-Apr;17(2):83-9. doi: 10.1159/000048014.

Reference Type BACKGROUND
PMID: 11844911 (View on PubMed)

Lee T, LeShane ES, Messerlian GM, Canick JA, Farina A, Heber WW, Bianchi DW. Down syndrome and cell-free fetal DNA in archived maternal serum. Am J Obstet Gynecol. 2002 Nov;187(5):1217-21. doi: 10.1067/mob.2002.127462.

Reference Type BACKGROUND
PMID: 12439507 (View on PubMed)

Other Identifiers

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1N01HD43201

Identifier Type: -

Identifier Source: secondary_id

1N01HD43202

Identifier Type: -

Identifier Source: secondary_id

1N01HD43203

Identifier Type: -

Identifier Source: secondary_id

1N01HD43204

Identifier Type: -

Identifier Source: secondary_id

NICHD-NIFTY

Identifier Type: -

Identifier Source: org_study_id