Down Syndrome - Comparison of Screening Methods in the 1st and 2nd Trimesters

First and 2nd Trimester Evaluation of the Risk of Aneuploidy

Too much or too little genetic information (chromosome material) can cause abnormal development of the fetus or death. Each year approximately 2.5 million pregnant women are screened for Down Syndrome using invasive screening methods (amniocentesis or chorionic villus sampling). This 11 center study of 38,000 women will compare the accuracy of the several non-invasive tests in the first and second trimesters of pregnancy versus amniocentesis or diagnosis at birth to diagnose aneuploidy or Down Syndrome.

Study Overview

• Status: Unknown
• Conditions: Down Syndrome; Chromosome Abnormalities
• Intervention / Treatment: Procedure: Ultrasound; Procedure: Serum screen

Detailed Description

The FASTER (First and Second Trimester Evaluation of Risk) Trial is a multicenter prospective study comparing the accuracy of first and second trimester non-invasive screening methods for Down syndrome and other aneuploidies to diagnosis at delivery or miscarriage/fetal loss). All women will receive the two non-invasive test batteries in both the first and second trimesters. The accuracy of the results of different combinations of non-invasive tests will be compared with diagnosis at delivery or at miscarriage or later fetal loss.

First trimester screening will involve ultrasound measurement of fetal nuchal translucency (NT) thickness at 10-14 weeks gestation, together with maternal age, and serum levels of pregnancy associated plasma protein-A (PPAP-A) and free-beta human chorionic gonadotropin (FbhCG). Second trimester screening will be based on the current standard of care serum "triple screen", which consists of alpha fetoprotein (AFP), unconjugated estriol (uE3), and hCG, performed at 15-18 weeks gestation, together with maternal age and the new serum marker inhibin-A. If patients screen positive (risk >/= 1 in 380), the patients are notified and offered invasive testing at 15 weeks (a serum "quad" test, an additional tube of blood for analysis of the presence of fetal nucleated erythrocytes in maternal blood [NIFTY: National Institute of Child Health and Human Development Fetal Cell Study]), and amniocentesis on those who accept). True positive cases receive counseling. True negative cases, those who decline invasive testing, and those who screen negative after the serum "quad" test, receive routine care with final pediatric outcome. Patients with an a priori risk for Down Syndrome may elect to have invasive fetal testing at 15 weeks after quad testing. For all fetuses with a NT measurement greater than 3 mm, and where karyotype is found to be normal after amniocentesis, will be followed with a repeat ultrasound examination at 18 to 20 weeks gestation, to evaluate fetal anatomy, particularly fetal cardiac structure. Final pediatric examination information will be obtained following delivery. If pregnancy results in miscarriage or later fetal loss, attempts will be made to karyotype any fetal tissue. This is especially important for those pregnancies that abort spontaneously between the time of the first and second trimester methods of screening. Pregnancy outcome data will be obtained in all cases.

• Study Type: Interventional
• Enrollment: 38000
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado Health Sciences Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • New England Medical Center
  • Michigan
    • Royal Oak, Michigan, United States, 48073-6769
      • William Beaumont Hospital Research Institute
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center
    • New York, New York, United States, 10016
      • New York University School of Medicine
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Women and Infants Hospital
  • Texas
    • Galveston, Texas, United States, 77555-0587
      • University of Texas Medical Branch
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Washington
    • Seattle, Washington, United States, 98104-1377
      • Swedish Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women 16 to 45 years old
• Enrolled by participating obstetrical center before 10-14 weeks gestation
• Gestational age 10 weeks three days to 13 weeks six days, with a minimum sonographic crown rump length of 38 mm, maximum 84mm
• Informed consent of patient
• English fluent or accompanied by appropriate interpreter
• Healthy (although co-existing diseases allowed)

Exclusion Criteria:

• Multiple gestation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Mary E. D'Alton, M. D., Columbia-Presbyterian Hospital Medical Center

Publications and helpful links

General Publications

• Wald NJ, Kennard A, Hackshaw A, McGuire A. Antenatal screening for Down's syndrome. J Med Screen. 1997;4(4):181-246. doi: 10.1177/096914139700400402. Erratum In: J Med Screen 1998;5(2):110. J Med Screen 1998;5(3):166.
• Wald NJ, Hackshaw AK. Combining ultrasound and biochemistry in first-trimester screening for Down's syndrome. Prenat Diagn. 1997 Sep;17(9):821-9.
• Malone FD, D'Alton, MD. Fetal nuchal translucency. Contemporary Obstetrics and Gyncology 1998; 43: 117-31.

Study record dates

Study Registration Dates

• First Submitted: November 4, 2000
• First Submitted That Met QC Criteria: November 4, 2000
• First Posted (Estimate): November 6, 2000

Study Record Updates

• Last Update Posted (Estimate): February 22, 2007
• Last Update Submitted That Met QC Criteria: February 21, 2007
• Last Verified: March 1, 2003

More Information

Terms related to this study

• Keywords: Ultrasound; Pregnancy; Down syndrome; Aneuploidy; Alpha fetoprotein; Serum screen; Pregnancy associated plasma protein-A (PAPP-A); Free-beta human chorionic gonadotropin (FbhCG); Unconjugated estriol; Inhibin-A
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Intellectual Disability; Abnormalities, Multiple; Syndrome; Down Syndrome; Chromosome Disorders; Chromosome Aberrations
• Other Study ID Numbers: NICHD-0511; 1 RO1 HD37523