Using record linkage and manual follow-up to evaluate the Victorian maternal serum screening quadruple test for Down's syndrome, trisomy 18 and neural tube defects

Objectives The Genetic Health Services Victoria maternal serum screening (MSS) quadruple test has been available to pregnant women in Victoria since 1996. The objectives of this study were to follow up the pregnancies screened by MSS between July 1998 and June 2000 and to determine the performance characteristics of the test for Down's syndrome, trisomy 18 and neural tube defects (NTDs). Methods MSS results were matched to pregnancy outcome information from the Perinatal Data Collection Unit and Birth Defects Register, using automated probabilistic record linkage. For unmatched pregnancies, manual follow-up was carried out by contacting referring doctors and hospitals, resulting in a very high follow-up rate of 99.2% (18,989/19,143). Results The sensitivity of MSS for Down's syndrome was 85% (23/27-95%CI 72-99%) with a false-positive rate (FPR) of 6.8% (risk threshold >= 1 in 250). While using a fixed 5% FPR, the sensitivity for Down's syndrome was slightly lower (78%). The sensitivity for trisomy 18 was 44% (4/9-95% CI 12-77%) with a FPR of 0.5% (risk threshold of >= 1 in 200). 11 of the 15 (73-95%CI 51-97%) cases of open NTDs were detected from screening, with a 1% FPR (risk threshold alpha-fetoprotein [AFP] >= 2.5 MoM). All cases of anencephaly had increased AFP levels. Conclusion Probabilistic record linkage and manual follow-up is an efficient method for ascertainment of pregnancy outcomes, with a higher follow-up rate than that reported in similar studies. MSS should remain an available option for all pregnant women in Victoria, with test characteristics comparable with other recent reports of the quadruple test.