First Trimester Screening – Current Status and Future Prospects After Introduction of Non-invasive Prenatal Testing (NIPT) at a Tertiary Referral Center

Abstract

Objective To investigate the uptake of different components of first trimester screening (FTS) and the impact on invasive diagnostic testing (IPT) since the introduction of non-invasive prenatal testing (NIPT) at a level III center.

Methods Retrospective data analysis was conducted for singleton pregnancies that presented for FTS between 01/2019–12/2019 (group 1, n = 990). Patients were categorized into three risk groups: low risk for trisomy 21 (< 1 : 1000), intermediate risk (1 : 101–1 : 1000) and high risk (≥ 1 : 100). Uptake of NIPT and IPT was analyzed for each of the risk groups. Results were compared to a previous cohort from 2012/2013 (immediately after the introduction of NIPT, group 2, n = 1178).

Results Group 1 showed a significant increase in the use of NIPT as part of FTS (29.5% vs. 3.7% for group 2, p = 0.001) in all three risk groups. Overall IPT rates were lower in group 1 (8.6%) vs. group 2 (11.3%, p = 0.038), mainly due to a significant reduction of IPT in the intermediate risk group. IPT rates in the high-risk group remained stable over time.

Conclusion Appropriate clinical implementation of NIPT is still currently a challenge for prenatal medicine experts. Our data suggest that widespread uptake of NIPT is becoming more common these days; however, a contingent approach might prevent redundant uptake.

Zusammenfassung

Zielsetzung Ziel dieser Studie war es, die Inanspruchnahme von verschiedenen Komponenten des Ersttrimesterscreenings zu untersuchen sowie die Auswirkungen auf die Inanspruchnahme von invasiven pränatalen Untersuchungen (IPT) seit der Einführung der nichtinvasiven Pränataldiagnostik (NIPT) in einem Krankenhaus der Tertiärversorgung zu prüfen.

Methoden Es wurde eine retrospektive Datenanalyse von Einlingsschwangerschaften vorgenommen, die im Zeitraum von 01/2019–12/2019 für ein Ersttrimesterscreening vorstellig waren (Gruppe 1, n = 990). Die Patientinnen wurden in 3 Risikogruppen eingeteilt: niedriges Risiko für Trisomie 21 (< 1 : 1000), mittleres Risiko (1 : 101–1 : 1000) und hohes Risiko (≥ 1 : 100). Die Inanspruchnahme von NIPT und IPT wurde für jede der Risikogruppen analysiert. Die Ergebnisse wurden mit denen eines früheren Patientinnenkollektivs aus den Jahren 2012/2013 (gleich nach der Einführung von NIPT, Gruppe 2, n = 1178) verglichen.

Ergebnisse In Gruppe 1 hat sich die Inanspruchnahme von NIPT als Teil des Ersttrimesterscreenings in allen 3 Risikogruppen signifikant erhöht (29,5% vs. 3,7% für Gruppe 2, p = 0,001). Die Inspruchnahme von IPT in Gruppe 1 war niedriger (8,6%) verglichen mit Gruppe 2 (11,3%, p = 0,038), was hauptsächlich auf die signifikante Reduktion von IPT in der mittleren Risikogruppe zurückzuführen war. Die Raten für IPT in der Hochrisikogruppe blieben im zeitlichen Verlauf relativ konstant.

Schlussfolgerung Die angemesse klinische Umsetzung von NIPT stellt zurzeit immer noch eine Herausforderung für Pränatalmediziner dar. Unseren Daten zufolge wird NIPT heute von vielen Schwangeren zunehmend in Anspruch genommen; ein an das Risiko geknüpfter Zugang zu Untersuchungen könnte die redundante Inanspruchnahme von Leistungen verhindern.

Schlüsselwörter

NIPT - zellfreier fetaler DNA-Test - Ersttrimesterscreening - pränatale Beratung

Keywords

NIPT - cell-free DNA screening - first trimester screening - prenatal counseling

Publikationsverlauf

Eingereicht: 09. Mai 2022

Angenommen nach Revision: 24. Juli 2022

Artikel online veröffentlicht:
06. September 2022

• References

• 1 Nicolaides KH. A model for a new pyramid of prenatal care based on the 11 to 13 weeks’ assessment. Prenat Diagn 2011; 31: 3-6 DOI: 10.1002/pd.2685. (PMID: 21210474)
• 2 Kagan KO, Sonek J, Wagner P. et al. Principles of first trimester screening in the age of non-invasive prenatal diagnosis: screening for chromosomal abnormalities. Arch Gynecol Obstet 2017; 296: 645-651 DOI: 10.1007/s00404-017-4459-9. (PMID: 28702698)
• 3 Hyett J, Perdu M, Sharland G. et al. Using fetal nuchal translucency to screen for major congenital cardiac defects at 10–14 weeks of gestation: population based cohort study. BMJ 1999; 318: 81-85 DOI: 10.1136/bmj.318.7176.81. (PMID: 9880278)
• 4 Chaoui R, Benoit B, Entezami M. et al. Ratio of fetal choroid plexus to head size: simple sonographic marker of open spina bifida at 11–13 weeks’ gestation. Ultrasound Obstet Gynecol 2020; 55: 81-86 DOI: 10.1002/uog.20856. (PMID: 31559662)
• 5 Tan MY, Poon LC, Rolnik DL. et al. Prediction and prevention of small-for-gestational-age neonates: evidence from SPREE and ASPRE. Ultrasound Obstet Gynecol 2018; 52: 52-59 DOI: 10.1002/uog.19077. (PMID: 29704277)
• 6 Poon LC, McIntyre HD, Hyett JA. et al. The first-trimester of pregnancy – A window of opportunity for prediction and prevention of pregnancy complications and future life. Diabetes Res Clin Pract 2018; 145: 20-30 DOI: 10.1016/j.diabres.2018.05.002. (PMID: 29852233)
• 7 Nicolaides KH, Azar G, Byrne D. et al. Fetal nuchal translucency: ultrasound screening for chromosomal defects in first trimester of pregnancy. BMJ 1992; 304: 867-869 DOI: 10.1136/bmj.304.6831.867. (PMID: 1392745)
• 8 Kagan KO, Etchegaray A, Zhou Y. et al. Prospective validation of first-trimester combined screening for trisomy 21. Ultrasound Obstet Gynecol 2009; 34: 14-18 DOI: 10.1002/uog.6412. (PMID: 19526452)
• 9 Wapner R, Thom E, Simpson JL. et al. First-trimester screening for trisomies 21 and 18. N Engl J Med 2003; 349: 1405-1413 DOI: 10.1056/NEJMoa025273. (PMID: 14534333)
• 10 Snijders RJ, Noble P, Sebire N. et al. UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10–14 weeks of gestation. Fetal Medicine Foundation First Trimester Screening Group. Lancet 1998; 352: 343-346 DOI: 10.1016/s0140-6736(97)11280-6. (PMID: 9717920)
• 11 Wright D, Syngelaki A, Bradbury I. et al. First-trimester screening for trisomies 21, 18 and 13 by ultrasound and biochemical testing. Fetal Diagn Ther 2014; 35: 118-126 DOI: 10.1159/000357430. (PMID: 24356462)
• 12 Kagan KO, Anderson JM, Anwandter G. et al. Screening for triploidy by the risk algorithms for trisomies 21, 18 and 13 at 11 weeks to 13 weeks and 6 days of gestation. Prenat Diagn 2008; 28: 1209-1213 DOI: 10.1002/pd.2149. (PMID: 19039823)
• 13 Ekelund CK, Petersen OB, Jørgensen FS. et al. The Danish Fetal Medicine Database: establishment, organization and quality assessment of the first trimester screening program for trisomy 21 in Denmark 2008–2012. Acta Obstet Gynecol Scand 2015; 94: 577-583 DOI: 10.1111/aogs.12581. (PMID: 25597330)
• 14 Kozlowski P, Burkhardt T, Gembruch U. et al. DEGUM, ÖGUM, SGUM and FMF Germany Recommendations for the Implementation of First-Trimester Screening, Detailed Ultrasound, Cell-Free DNA Screening and Diagnostic Procedures. Ultraschall Med 2019; 40: 176-193 DOI: 10.1055/a-0631-8898. (PMID: 30001568)
• 15 Sehnert AJ, Rava RP, Bianchi DW. A new era in noninvasive prenatal testing. N Engl J Med 2013; 369: 2164-2165 DOI: 10.1056/NEJMc1311604. (PMID: 24283244)
• 16 Gil MM, Revello R, Poon LC. et al. Clinical implementation of routine screening for fetal trisomies in the UK NHS: cell-free DNA test contingent on results from first-trimester combined test. Ultrasound Obstet Gynecol 2016; 47: 45-52 DOI: 10.1002/uog.15783. (PMID: 26498918)
• 17 Nicolaides KH, Syngelaki A, Ashoor G. et al. Noninvasive prenatal testing for fetal trisomies in a routinely screened first-trimester population. Am J Obstet Gynecol 2012; 207: 374.e1-374.6 DOI: 10.1016/j.ajog.2012.08.033.
• 18 Salomon LJ, Alfirevic Z, Audibert F. et al. ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT) on prenatal ultrasound practice. Ultrasound Obstet Gynecol 2014; 44: 122-123 DOI: 10.1002/uog.13393. (PMID: 25518828)
• 19 Bedei I, Wolter A, Weber A. et al. Chances and Challenges of New Genetic Screening Technologies (NIPT) in Prenatal Medicine from a Clinical Perspective: A Narrative Review. Genes (Basel) 2021; 12: 501 DOI: 10.3390/genes12040501. (PMID: 33805390)
• 20 Miltoft CB, Rode L, Ekelund CK. et al. Contingent first-trimester screening for aneuploidies with cell-free DNA in a Danish clinical setting. Ultrasound Obstet Gynecol 2018; 51: 470-479 DOI: 10.1002/uog.17562. (PMID: 28640470)
• 21 Manegold-Brauer G, Berg C, Flöck A. et al. Uptake of non-invasive prenatal testing (NIPT) and impact on invasive procedures in a tertiary referral center. Arch Gynecol Obstet 2015; 292: 543-548 DOI: 10.1007/s00404-015-3674-5. (PMID: 25716672)
• 22 Abib LPA, de Sá RAM, Peixoto-Filho FM. First-trimester Combined Screening Test for Aneuploidies in Brazilian Unselected Pregnancies: Diagnostic Performance of Fetal Medicine Foundation Algorithm. Rev Bras Ginecol Obstet 2018; 40: 384-389 DOI: 10.1055/s-0038-1666996. (PMID: 30011404)
• 23 Muñoz-Cortes M, Arigita M, Falguera G. et al. Contingent screening for Down syndrome completed in the first trimester: a multicenter study. Ultrasound Obstet Gynecol 2012; 39: 396-400 DOI: 10.1002/uog.9075. (PMID: 21674658)
• 24 Tamminga S, van Schendel RV, Rommers W. et al. Changing to NIPT as a first-tier screening test and future perspectives: opinions of health professionals. Prenat Diagn 2015; 35: 1316-1323 DOI: 10.1002/pd.4697. (PMID: 26411372)
• 25 Galeva S, Konstantinidou L, Gil MM. et al. Routine first-trimester screening for fetal trisomies in twin pregnancy: cell-free DNA test contingent on results from combined test. Ultrasound Obstet Gynecol 2019; 53: 208-213 DOI: 10.1002/uog.20160. (PMID: 30353581)
• 26 Gomes HH, Lourenço I, Ribeiro J. et al. Cell-free DNA and contingent screening: Our first year. J Gynecol Obstet Hum Reprod 2019; 48: 509-514 DOI: 10.1016/j.jogoh.2019.04.001. (PMID: 30951890)
• 27 Santorum M, Wright D, Syngelaki A. et al. Accuracy of first-trimester combined test in screening for trisomies 21, 18 and 13. Ultrasound Obstet Gynecol 2017; 49: 714-720 DOI: 10.1002/uog.17283. (PMID: 27549925)
• 28 Kagan KO, Wright D, Nicolaides KH. First-trimester contingent screening for trisomies 21, 18 and 13 by fetal nuchal translucency and ductus venosus flow and maternal blood cell-free DNA testing. Ultrasound Obstet Gynecol 2015; 45: 42-47 DOI: 10.1002/uog.14691. (PMID: 25307357)
• 29 Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen (IQWiG). Nichtinvasive Pränataldiagnostik (NIPD) zur Bestimmung des Risikos autosomaler Trisomien 13, 18 und 21 bei Risikoschwangerschaften. 11.12.2017: 1-118 Zugriff am 28. Juli 2022 unter: https://www.iqwig.de/download/s16–06_nicht-invasive-praenataldiagnostik-nipd_vorbericht_v1–0.pdf
• 30 Bardi F, Smith E, Kuilman M. et al. Early Detection of Structural Anomalies in a Primary Care Setting in the Netherlands. Fetal Diagn Ther 2019; 46: 12-19 DOI: 10.1159/000490723. (PMID: 30045038)
• 31 Minnella GP, Crupano FM, Syngelaki A. et al. Diagnosis of major heart defects by routine first-trimester ultrasound examination: association with increased nuchal translucency, tricuspid regurgitation and abnormal flow in ductus venosus. Ultrasound Obstet Gynecol 2020; 55: 637-644 DOI: 10.1002/uog.21956. (PMID: 31875326)
• 32 Bardi F, Bosschieter P, Verheij J. et al. Is there still a role for nuchal translucency measurement in the changing paradigm of first trimester screening?. Prenat Diagn 2020; 40: 197-205 DOI: 10.1002/pd.5590. (PMID: 31697852)
• 33 Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin Summary, Number 226. Obstet Gynecol [Anonym]. 2020; 136: 859-867 DOI: 10.1097/AOG.0000000000004107. (PMID: 32976375)