Comparison of Three First Trimester Screening Algorithms for Trisomy 21 with and without Adjustment for Maternal Characteristics

Abstract

Purpose: Comparison of three algorithms (DoE 2007 and DoE 2011 algorithm of the FMF Germany and MoM algorithm of the FMF UK) in first trimester biochemical screening for trisomy 21 based on maternal and gestational age, free ß-hCG, and PAPP-A and assessment of relevant maternal characteristics.

Materials and Methods: Data from 22 449 euploid singleton pregnancies undergoing combined screening for trisomy 21 at 11 to 13 weeks of gestation were examined. The measured maternal free β-hCG and PAPP-A concentrations were converted into DoE 2007 and DoE 2011 values according to the algorithm of the FMF Germany and into MoM values according to the algorithm of the FMF UK. In each pregnancy, patient-specific risks and false-positive rates (FPR) were computed according to the three algorithms and were stratified according to gestational age, maternal ethnicity, maternal weight, and smoking status.

Results: Free ß-hCG and PAPP-A MoM and DoE 2011 were acceptably independent from maternal characteristics and gestational age, while there was a strong relationship between maternal weight and the DoE 2007 values. For a risk cut-off that corresponds to an overall 5 % FPR rate for each algorithm, the FPR in each group were around 5 % at gestational week 11 – 13. The FPR of the DoE 2007 algorithm increased linearly with maternal weight from 3.6 % in women of 50 kg or less to 11.8 % in women of more than 110 kg.

Conclusion: Especially maternal weight has a significant impact on the risk calculation. In contrast to the DoE 2007 algorithm, the DoE 2011 and MoM algorithms both adjust for maternal weight.

Zusammenfassung

Ziel: Vergleich von 3 biochemischen Screening-Algorithmen (DoE-2007- und DoE-2011-Algorithmus der FMF Deutschland und MoM-Algorithmus der FMF UK) im Ersttrimester-Screening auf Trisomie 21, basierend auf dem mütterlichen Alters- und Gestationsalters-spezifischen Risiko, dem freien ß-hCG und PAPP-A sowie Beurteilung der maternalen und schwangerschaftsspezifischen Einflussfaktoren.

Material und Methoden: Für die Auswertung wurden die Ergebnisse von 22 449 Ersttrimester-Screening-Untersuchungen auf Trisomie 21 in den Schwangerschaftswochen 11 bis 13 verwendet. Die gemessenen mütterlichen Serum-Konzentrationen des freien β-hCG und PAPP-A wurden in DoE-2007- und DoE-2011-Werte entsprechend den Algorithmen der FMF Deutschland und in MoM-Werte entsprechend dem Algorithmus der FMF UK umgerechnet. Für jede Schwangerschaft wurden mit Hilfe der drei Algorithmen Patientinnen-spezifische Risiken und Falsch-Positivraten (FPR) berechnet und entsprechend dem Gestationsalter, der Ethnizität, dem mütterlichen Gewicht und dem Raucherstatus stratifiziert.

Ergebnisse: Während die DoE-2007-Werte eine starke Abhängigkeit vom mütterlichen Gewicht aufwiesen, waren die DoE-2011- und MoM-Werte weitgehend unabhängig von mütterlichen und schwangerschaftsspezifischen Einflussfaktoren. Bei einem Risiko-Cut-off, der einer FPR von 5 % im gesamten Kollektiv entspricht, lag die FPR in den Wochen 11 – 13 ebenfalls um 5 %. Mit diesem Cut-off stieg die FPR bei Verwendung des DoE-2007-Algorithmus von 3,6 % bei einem mütterlichen Gewicht von 50 kg oder weniger auf 11,8 % bei einem Gewicht über 110 kg.

Schlussfolgerung: Insbesondere das mütterliche Gewicht hat einen signifikanten Einfluss auf die Risikoberechnung. Im Gegensatz zum DoE-2007-Algorithmus verfügen die DoE-2011- und MoM-Algorithmen über eine entsprechende Korrektur.

Key words

first trimester screening - PAPP-A - free beta hCG - MoM - DoE

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