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Repeated measurement of pregnancy‐associated plasma protein‐A (PAPP‐A) in Down syndrome screening: A validation study
Author(s) -
Palomaki Glenn E.,
Wright David E.,
Summers Anne M.,
Neveux Louis M.,
Meier Christian,
O'Donnell Andrea,
Huang Tianhua,
Knight George J.,
Haddow James E.
Publication year - 2006
Publication title -
prenatal diagnosis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.956
H-Index - 97
eISSN - 1097-0223
pISSN - 0197-3851
DOI - 10.1002/pd.1497
Subject(s) - pregnancy associated plasma protein a , medicine , trisomy , estriol , pregnancy , down syndrome , second trimester , obstetrics , first trimester , gynecology , gestation , biology , hormone , psychiatry , genetics
Objectives To confirm that measuring pregnancy‐associated plasma protein‐A (PAPP‐A) in both first‐ and second‐trimester serum samples improves Down syndrome screening. Methods We selected paired first‐ and second‐trimester stored serum samples from 34 Down syndrome pregnancies (cases) and 514 unaffected pregnancies (controls) and tested the second‐trimester samples for PAPP‐A and dimeric inhibin‐A (DIA). First‐trimester PAPP‐A measurements were already available, as were second‐trimester measurements of alpha‐fetoprotein, unconjugated estriol (uE3), and human chorionic gonadotrophin (hCG). Results PAPP‐A was lower among cases than controls (0.47 MoM) in the first trimester (at an average of 12.5 weeks); in the second trimester, it was not different (0.91 MoM). Using repeated measures of PAPP‐A alone, 21 of 34 cases were detected (62%, 95%CI 44% to 78%) with 5% false positives. At an observed 2% false‐positive rate, the detection rates (DR) for the quadruple (69%) and serum integrated (69%) tests were lower than for the repeated measures test (75%). Modelled performance at 12 weeks was similar to these observed findings (70, 75, and 82%, respectively). If the first‐trimester samples were collected at 10 weeks, however, DR would be higher (70, 81, and 91%, respectively). Conclusions Adding a repeated measure of PAPP‐A to existing serum markers improves Down syndrome screening to levels that are currently obtainable only by including ultrasound measurement of nuchal translucency (NT). Serum‐based screening has the advantages of higher availability and reliability at a lower cost, resulting in a more effective screening strategy. A serum‐based repeated measures test has a place in routine Down syndrome screening. Copyright © 2006 John Wiley & Sons, Ltd.