First Trimester Contingent Screening for Aneuploidies with Cell-Free Fetal DNA in Singleton Pregnancies – a Swiss Single Centre Experience

Abstract

Introduction

Switzerland was amongst the first countries to offer cell-free fetal DNA (cffDNA) testing covered by the health insurance to pregnant women with a risk ≥ 1:1000 for trisomies at first trimester combined screening (FTCS). The aim of this study is to evaluate the implementation of this contingent model in a single tertiary referral centre and its effect on gestational age at diagnosing trisomy 21.

Materials and Methods

Between July 2015 and December 2020 all singleton pregnancies at 11–14 weeks of gestation without major fetal malformation were included and stratified according to their risk at FTCS. Statistical analysis was performed by GraphPad Version 9.1 for Windows.

Results

4424 pregnancies were included. Of 166 (3.8%) pregnancies with a NT ≥ 3.5 mm and/or a risk ≥ 1:10 at FCTS, 130 (78.3%) opted for direct invasive testing. 803 (18.2%) pregnancies had an intermediate risk, 692 (86.2%) of them opted for cffDNA first. 3455 (78.1%) pregnancies had a risk < 1:1000. 63 fetuses were diagnosed with trisomy 21, 47 (74.6%) directly by invasive procedures after FTCS, 16 (25.4%) by cffDNA first.

Conclusions

Most women choose cffDNA or invasive testing as second tier according to national guidelines. Despite the delay associated with cffDNA testing after FCTS, 75% of all trisomy 21 are still diagnosed in the first trimester with this contingent screening model.

Zusammenfassung

Einleitung

Die Schweiz war eines der ersten Länder, das schwangeren Frauen mit einem ≥ 1:1000-Risiko für Trisomien von den Krankenkassen vergütete cffDNA-Tests (cffDNA: zellfreie fetal DNA) nach dem kombinierten Ersttrimesterscreening (FTCS) angeboten hat. Ziel dieser Studie war es, die Umsetzung dieses Screeningmodells in einem Level-3-Referenzzentrum und die Auswirkungen auf das Schwangerschaftsalter bei der Trisomie-21-Diagnose auszuwerten.

Material und Methoden

Zwischen Juli 2015 und Dezember 2020 wurden alle Einlingsschwangerschaften ohne fetale Fehlbildungen in den Schwangerschaftswochen 11–14 in die Studie aufgenommen und gemäß ihrem Risiko beim FTCS in Risikogruppen unterteilt. Die statistische Analyse wurde mit GraphPad Version 9.1 für Windows durchgeführt.

Ergebnisse

Insgesamt wurden 4424 Schwangerschaften in die Studie eingeschlossen. Von 166 (3,8%) Schwangerschaften mit einer Nackentransparenz (NT) von ≥ 3,5 mm und/oder einem Risiko von ≥ 1 : 10 beim FTCS entschieden sich 130 (78,3%) für direkte invasive Testmethoden. Bei 803 (18,2%) Schwangerschaften wurde das Risiko als intermediär eingestuft, und 692 (86,2%) der Schwangeren entschieden sich, erst einen cffDNA-Test durchzuführen. Bei 3455 (78,1%) Schwangerschaften war das Risiko < 1 : 1000. 63 Feten wurden mit Trisomie 21 diagnostiziert, davon 47 (74,6%) direkt durch invasive Eingriffe nach dem FTCS und 16 (25,4%) erst mit cffDNA.

Schlussfolgerungen

Die meisten Frauen wählten cffDNA oder eine invasive Testmethode als Folgeuntersuchung gemäß den nationalen Richtlinien. Obwohl eine cffDNA-Analyse nach dem FCTS zu Verzögerungen führt, werden mit diesem Kontingent-Screening immer noch 75% aller Fälle mit Trisomie 21 im 1. Trimester diagnostiziert.

Keywords

first trimester screening - trisomies - cell-free fetal DNA - non-invasive prenatal testing

Schlüsselwörter

Ersttrimesterscreening - Trisomien - cell-free fetal DNA - nicht invasive Pränataldiagnostik

Publication History

Received: 15 April 2023

Accepted after revision: 31 October 2023

Article published online:
03 January 2024

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