Down Syndrome Screening Based on Dried Blood Spots and Cell-free Fetal DNA (DBS&CFF)

A Clinical Trial to Explore a New Prenatal Screening and Diagnosis Pattern for Fetal Chromosomal Abnormalities With Dried Blood Spots and Cell-free Fetal DNA.

There are 26,600 Down Syndrome newborns every year in China. The economic burden of this disease is 65,000 USD for lifetime of every patient. The common prenatal screening and diagnosis procedure for fetal chromosomal abnormalities in China is maternal serum prenatal screening in second trimester followed by amniocentesis. The detection rate of MSS is 70%-75% with 5% false positive rate. There are only 13.9% of pregnant women can receive prenatal screening testing in China. It is very urgent that we build a training system and convenient, efficient, cost-effective procedure suitable to rural China.

The use of dried blood spots (DBS) technology in conjunction with the second trimester prenatal screening protocol has been proved to be as efficient as serum screening by our previous study. Noninvasive prenatal testing that uses cell free fetal DNA (cff DNA) from the plasma of pregnant women offers a tremendous potential for fetal chromosomal abnormalities. A positive test should be followed by invasive prenatal diagnosis to confirm the test results. Cff DNA is a good supplement to the DBS technology in rural China. A combination of the two methods can increase the screening rate and accuracy without increasing the demand of amniocentesis and cytogenetic test. This procedure with adequate training system should be suitable to rural China.

Our study will build a training system for DBS and cffDNA prenatal screening procedure in Pinggu, Beijing. Two thousand pregnant women will receive prenatal screening. DBS sample will be collected in the second trimester, Cff DNA is offered to confirm the positive screening test results, and lastly amniocentesis is offered for confirmation of the test results. All of the pregnancy and neonatal outcomes will be followed. We can estimate the efficiency and cost-effectiveness of DBS followed with cff DNA screening procedure.

Study Overview

• Status: Unknown
• Conditions: Trisomy 21
• Intervention / Treatment: Procedure: cell-free fetal DNA

Detailed Description

Goals To build a training system and DBS and cffDNA prenatal screening procedure that is suitable to rural China.

Objectives Develop a standardized prenatal screening test training program. Evaluate the efficiency and cost-effectiveness of DBS and cffDNA prenatal screening procedure in rural China.

Specific activities

• Train the medical staff: Select two hospitals in Pinggu Village. Train all of the obstetricians and family doctors, nurses in these counties about the prenatal screening test as well as DBS and cff DNA technology. Build a series of standardized training profiles for the doctors and nurses. Evaluate the knowledge of the trained staff and compare the prenatal screening rate as well as some key health outcome variables pre and post the training.
• collect DBS sample in the 2nd trimestaer: Two thousand pregnant women will receive prenatal screening. DBS sample together with serum screening samples will be collected in the second trimester.
• Cff DNA for DBS high risk pregnant women: Cff DNA is offered to confirm the positive screening test results.
• amniocentesis for Cff DNA high risk pregnant women: Amniocentesis is offered for confirmation of the test results.
• Follpw-up the neonatal outcome: All of the pregnancy and neonatal outcomes will be followed.
• Statistical analysis: We can estimate the efficiency and cost-effectiveness of DBS followed with cff DNA screening procedure. We can give the recommendation to the government for a potential expansion of new screening diagnosis procedure to be used in the countryside.

Analytic methods Build the database by visual Foxpro 5.0. Use the SAS9.2 software to do statistical analysis.

Expected results and products Develop standardized prenatal screening test training program for the doctors and nurses in rural China. Estimate the training outcome. Estimate the detection rate of DBS and compare with maternal serum screening test. Estimate the sensitivity of specificity of cffDNA test. Estimate the efficiency and cost-effectiveness of DBS and cff DNA screening procedure. Make sure if DBS and cffDNA is suitable to rural China and successfully decreases the birth defects.

Timetable

• Year 1 Select the hospitals and form the contracts with local staff. Develop the training program and finish training. Evaluate the training outcome. Start to collect DBS samples followed with cffDNA. Enroll the pregnant women in the second trimester who sign the consent form.
• Year 2 Follow-up the pregnancy and neonatal outcomes. Finish the statistical analysis and paper writing.

• Study Type: Observational
• Enrollment (Anticipated): 2000

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Department of ob gyn, Peking Union Medical College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

pregnant women with 15-20+6 weeks of gestation

Description

Inclusion Criteria:

• Single gestation;
• Chinese natives or non-Chinese citizen of Chinese ancestry;
• 15-20+6 weeks of gestation;
• be able to accept follow-ups of the pregnancy outcome;
• healthy, without other major or chronic diseases;

Exclusion Criteria:

• N/A

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
DBS screening test; cell-free fetal DNA for Dried blood spots samples in high risk pregnant women.	Procedure: cell-free fetal DNA; cell-free fetal DNA for DBS and maternal serum screening high risk pregnant women. Comparison of multiple Down's syndrome screening tests.
maternal serum screening test; cell-free fetal DNA for maternal serum screening test samples in high risk pregnant women.	Procedure: cell-free fetal DNA; cell-free fetal DNA for DBS and maternal serum screening high risk pregnant women. Comparison of multiple Down's syndrome screening tests.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
detection rate	Detection rate of trisomy 21 based on dried blood spots and cell-free fetal DNA. Compare the detection rate of screening test on dried blood spots with maternal serum screening test.	April, 2015

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
positive predictive value and negative predictive value	the number of patients can be detected in Down syn and the proportion of the actual number of cases to screening positive cases number	3 years

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Investigators: Study Director: Liangkun MA, MD, Peking Union Medical College

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Anticipated): January 1, 2015
• Study Completion (Anticipated): January 1, 2015

Study Registration Dates

• First Submitted: April 14, 2013
• First Submitted That Met QC Criteria: April 18, 2013
• First Posted (Estimate): April 23, 2013

Study Record Updates

• Last Update Posted (Estimate): April 23, 2013
• Last Update Submitted That Met QC Criteria: April 18, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: cost-effectiveness; prenatal testing for fetal aneuploidy; dried blood spots; cell-free fetal DNA; detection rate
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Congenital Abnormalities; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Chromosome Disorders; Chromosome Aberrations; Aneuploidy; Chromosome Duplication; Down Syndrome; Trisomy
• Other Study ID Numbers: Down syndrome screening

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No