Funded Projects

Improved Prenatal Down Syndrome Screening: PAIRED Testing

Grantee: Foundation for Blood Research
Principal Investigator: George Knight
Project Number: R40MC00195
Project Date: 08/01/2001

Final Report

Improved Prenatal Down Syndrome Screening: PAIRED Testing Final Report (PDF)

Age group(s)

• Women/Maternal
• Prenatal

Abstract

Down syndrome screening has technically evolved to the point that approximately 2.4 million pregnant women are now provided with prenatal screening for Down syndrome, annually. Nevertheless, despite the widespread screening, the false positive rate for Down syndrome remains high. This results in unnecessary morbidity and psychological stress. Pregnant women who are found to have positive screening test results (most of which are false positives) experience considerable anxiety and usually require invasive studies to identify whether or not Down syndrome is present in the fetus. It is therefore important to minimize screen positive test results to avoid raising anxiety and keep procedure related fetal losses to a minimum. This study is designed to test and validate a new approach to serum based prenatal screening for fetal Down syndrome that is expected to reduce dramatically the false positive rate as compared to the current standard of care: the triple test [alpha fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotrophin (hCG)]. The test identifies 69 per 1000 women as high risk. This prenatal Down Syndrome screening, initially referred to as the Practical Approach to Integrated Risk Evaluation for Down Syndrome (PAIRED) serum test in the earlier protocol and now renamed as the Integrated Serum Test (IST), will reduce the number of women with false positive test results to 21 per 1,000. The IST combines both first and second trimester maternal serum biochemical measurements with maternal age to assign each pregnancy a Down syndrome risk. Those risks are then used to identify women at sufficient risk to warrant offering second trimester amniocentesis and fetal karyotyping. Compared to the current standard of care (the triple test), the IST serum test will maintain high Down syndrome detection (75%) but will reduce the false positive (and amniocentesis) rate by more that two-thirds (from 6.9 to 2.1%). This IST for Down syndrome screening addresses the following questions: 1) will the predicted reduction in the false positive rate be achieved, 2) will women receiving prenatal care in the first trimester agree to IST screening, 3) will women agreeing in the first trimester to IST screening submit a second trimester serum sample, 4) will health care practices now providing second trimester prenatal screening for Down syndrome agree to offer the IST, 5) will a high percentage of screen positive women opt for diagnostic testing, 6) is the Down syndrome detection rate consistent with expectations based on modeling and 7) will IST screening be cost effective (in both financial and medical terms), when compared to the current standard of practice (triple test)? The following endpoints will be determined: 1) percent of women opting for the IST in the first trimester, 2) percent of women providing a second trimester serum sample, 3) percent of women with positive screening results, 4) percent of women opting for amniocentesis, 5) cost effectiveness of the IST as measured by the reduction in amniocentesis/karyotypes compared with the cost for PAPP-A testing. If successful, the IST will provide a high performance screening method that can be used in all types of primary care practices in rural and urban settings. The study population will consist of women in Maine receiving first trimester prenatal care (11,000 annually). When the woman's serum for second trimester screening comes to the laboratory, AFP, uE3 (unconjugated estriol), hCG as well as dimeric inhibin A (DIA) will be measured. DIA is in the process of being added to the triple test. The first trimester sample will be thawed and assayed simultaneously for pregnancy-associated plasma protein-A (PAPP-A). Results of all tests will be combined into a single risk estimate. Women with high risks will be managed according to current practice. The primary benefit will be a significant decrease in the number of screen positive women, and a corresponding decrease in ultrasound examinations, amniocenteses and procedure related fetal loss. An additional benefit will be a reduction in maternal anxiety known to be associated with false positive screening results.