Non-invasive cell-free DNA prenatal screening for trisomy 21 as part of primary screening strategy in twin pregnancy

N Claudel; M Barrois; A J Vivanti; J Rosenblatt; L J Salomon; J-M Jouannic; O Picone; L Carbillon; F Vialard; E Launay; V Tsatsaris; E Curis; L El Khattabi; APHP non‐invasive prenatal screening group

doi:10.1002/uog.26311

Non-invasive cell-free DNA prenatal screening for trisomy 21 as part of primary screening strategy in twin pregnancy

Ultrasound Obstet Gynecol. 2023 Jul 20. doi: 10.1002/uog.26311. Online ahead of print.

Authors

N Claudel^{1

2

3}, M Barrois^{1

2

3}, A J Vivanti^{4

5}, J Rosenblatt⁶, L J Salomon^{2

7}, J-M Jouannic^{8

9}, O Picone^{10

11}, L Carbillon^{12

13}, F Vialard¹⁴, E Launay¹⁵, V Tsatsaris¹⁶, E Curis^{16

17}, L El Khattabi^{18

19

20}; APHP non‐invasive prenatal screening group

Collaborators

APHP non‐invasive prenatal screening group:
Audrey Rosefort, Marc Dommergues, Morgane Valentin, Hanane Bouchghoul, Pierre François Ceccaldi, Jeremy Sroussi, Jocelyn Brayet, Nathalie Le Dû

Affiliations

¹ Maternité Port Royal, AP-HP Hôpital Cochin, FHU Prema, Paris, France.
² Université Paris Cité, Paris, France.
³ INSERM UMR_S1139, Paris, France.
⁴ Service de Gynécologie-Obstétrique, DMU Santé des Femmes et des Nouveau-nés, AP-HP Hôpital Antoine Béclère, Clamart, France.
⁵ Université Paris-Saclay, Orsay, France.
⁶ Service de Gynécologie-Obstétrique, AP-HP Hôpital Universitaire Robert-Debré, Paris, France.
⁷ Service de Gynécologie-Obstétrique, AP-HP Hôpital Universitaire Necker-Enfants Malades, Paris, France.
⁸ Département de Médecine Fœtale, Pôle ORIGYNE.6, AP-HP Hôpital Armand Trousseau, Paris, France.
⁹ Université Sorbonne Paris Cité, Paris, France.
¹⁰ Service de Gynécologie-Obstétrique, AP-HP Hôpital Louis Mourier, Colombes, France.
¹¹ Université Paris Diderot, INSERM UMR1137, IAME, Paris, France.
¹² Service de Gynécologie-Obstétrique, AP-HP Hôpital Jean-Verdier, Bondy, France.
¹³ Université Paris 13, Bobigny, France.
¹⁴ Service de Cytogénétique, CHI Poissy-Saint Germain en Laye, Poissy, France.
¹⁵ Service de Cytogénétique et Biologie Cellulaire, CHU Rennes, Rennes, France.
¹⁶ UR 7537 BioSTM, UFR de Pharmacie, Faculté de Santé, Université Paris Cité, Paris, France.
¹⁷ Laboratoire d'Hématologie, Hôpital Lariboisière, AP-HP.nord, Paris, France.
¹⁸ Plateforme de Dépistage Prénatal Non Invasif par Analyse de l'ADN Libre Circulant, AP-HP, Hôpital Cochin and Université Paris Cité, Paris, France.
¹⁹ Sorbonne Université, Institut du Cerveau - Paris Brain Institute (ICM), Inserm, CNRS, Hôpital Pitié Salpêtrière, Paris, France.
²⁰ Unité de Génomique Chromosomique, Département de Génétique Médicale, APHP, Hôpitaux Armand Trousseau et Pitié-Salpêtrière, Paris Brain Institute - ICM, Sorbonne Université, Paris, France.

PMID: 37470702
DOI: 10.1002/uog.26311

Abstract

Objectives: The performance of non-invasive prenatal screening using cell-free DNA testing of maternal blood in twin pregnancy is underevaluated, while serum marker-based strategies yield poor results. This study aimed to assess the performance of non-invasive prenatal screening for trisomy 21 in twin pregnancy as a first-tier test. Secondary objectives were to assess its failure rate and factors associated with failure.

Methods: This retrospective cohort study included twin pregnancies in which non-invasive prenatal screening using cell-free DNA was performed as the primary screening strategy between May 2017 and October 2019. We used the NIPT VeriSeq® test for in-vitro diagnosis and set a fetal fraction cut-off of 4% for monochorionic pregnancies and 8% for dichorionic ones. Clinical data and pregnancy outcome were collected from physicians or midwives via a questionnaire or were retrieved directly on-site. We calculated the performance of non-invasive cell-free DNA screening for trisomy 21, analyzed its failure rate and assessed potentially associated factors.

Results: Among 1885 twin pregnancies with follow-up, there were six (0.32%) confirmed cases of trisomy 21. The sensitivity of non-invasive prenatal screening for trisomy 21 was 100% (95% CI, 54.1-100%) and the false-positive rate was 0.23% (95% CI, 0.06-0.59%). The primary failure rate was 4.6%, with 4.0% being due to insufficient fetal fraction. A successful result was obtained for 65.4% of women who underwent a new blood draw, reducing the overall failure rate to 2.8%. Maternal body mass index, gestational age at screening as well as chorionicity were significantly associated with the risk of failure.

Conclusion: This study provides further evidence of the high performance, at an extremely low false-positive rate, of non-invasive prenatal screening in twins as part of a primary screening strategy for trisomy 21. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Keywords: NIPS; NIPT VeriSeq; cell‐free DNA; chorionicity; failure; non‐invasive prenatal screening; trisomy 21; twin pregnancy.