Screening for Chromosomal Abnormalities by First Trimester Combined Screening and Noninvasive Prenatal Testing

Abstract

Purpose: To examine combined first trimester screening (FTS), noninvasive prenatal testing (NIPT) and a two-step policy that combines FTS and NIPT in screening for aneuploidy.

Materials and Methods: Retrospective study involving 21 052 pregnancies where FTS was performed at the Praxis Praenatal.de in Duesseldorf, Germany. In each case, the sum risk of trisomy 21, 18 and 13 was computed. We assumed that NIPT detects 99 %, 98 %, 90 % and 99 % of cases with trisomy 21, 18, 13 and sex chromosomal abnormalities and that the false-positive rate is 0.5 %. The following screening policies were examined: NIPT or FTS with sum risk cut-offs of 1 in 50 and 1 in 250 in all patients or a two-step-policy with FTS in all patients followed by NIPT in the intermediate sum risk group. For the intermediate risk group, sum risk cut-offs of 1 in 50 and 1 in 1000 and 1 in 150 and 1 in 500 were used.

Results: There were 127, 34, 13 and 15 pregnancies with trisomy 21, 18, 13 and sex chromosomal abnormalities. 23 fetuses had other chromosomal abnormalities with an increased risk for adverse outcome that are not detectable by NIPT. 20 840 pregnancies were classified as normal as ante- and postnatal examinations did not show any signs of clinically significant chromosomal abnormalities. FTS with a sum risk cut-off of 1 in 50 and 1 in 250 detects 81 % and 91 % for all aneuploidies. NIPT detects 88 % of the respective pregnancies. The 2-step approach with sum risk cut-offs of 1 in 50 and 1 in 1000 detects 94 % of all aneuploidies. With sum risk cut-offs of 1 in 150 and 1 in 500, the detection rate is 93 %.

Conclusion: A 2-step policy with FTS for all patients and NIPT in the intermediate risk group results in the highest detection rate of all aneuploidies.

Zusammenfassung

Ziel: Beurteilung der Testgüte unterschiedlicher Screening-Ansätze im Aneuploidie-Screening im ersten Trimenon, die auf dem kombinierten Ersttrimester-Screening (ETS), dem non-invasiven prenatal testing (NIPT) und der Kombination beider Ansätze basieren.

Material und Methoden: Retrospektive Studie mit 21 052 Schwangerschaften, die in der Praxis Pränatal.de in Düsseldorf untersucht wurden. In jeder Schwangerschaft wurde das Summenrisiko für Trisomie 21, 18 und 13 berechnet. Wir nahmen an, dass NIPT 99 %, 98 %, 90 % und 99 % der Schwangerschaften mit Trisomie 21, 18, 13 und gonosomale Aberrationen erkennt und dass die Falsch-Positivrate bei 0,5 % liegt. Es wurden folgende Optionen untersucht: für alle Patientinnen NIPT oder ETS (Summenrisiko Cut-off 1 in 50 oder 1 in 250) oder ein 2-Stufen-Ansatz mit ETS für alle Patientinnen und NIPT bei intermediärem Summenrisiko. Als Summenrisiko Cut-offs wurden dabei 1 in 50 und 1 in 1000 sowie 1 in 150 und 1 in 500 verwendet.

Ergebnisse: Trisomien 21, 18, 13 und gonosomale Aberrationen wurden bei 127, 34, 13 und 15 Schwangerschaften gefunden. 23 Feten hatten andere Chromosomenstörungen mit einem adversen Outcome, die methodenbedingt derzeit nicht durch NIPT erkannt werden können. Bei 20 840 Schwangerschaften gab es keinen Hinweis auf eine klinisch relevante Chromosomenstörung. ETS mit einem Summenrisiko Cut-off von 1 in 50 und 1 in 250 würde 81 % und 91 % aller Aneuploidien erkennen. Der alleinige NIPT-Ansatz würde zu einer Detektionsrate von 88 % aller Aneuploidien führen. Der 2-Stufen-Ansatz mit 1 in 50 und 1 in 1000 als Summenrisiko Cut-off hätte 94 % aller Aneuploidien erkannt. Bei einem Summenrisiko Cut-off von 1 in 150 und 1 in 500 93 % erkannt worden.

Schlussfolgerung: Die Kombination aus ETS und NIPT in der intermediären Risikogruppe führt zu der höchsten Erkennungsrate von aneuploiden Feten.

Key words

first trimester - trisomy - nuchal translucency - NIPT

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