Introduction of a nationwide first-trimester anomaly scan in the Dutch national screening program - 29/08/24

Doi : 10.1016/j.ajog.2024.07.026

Eline E.R. Lust, MSc ^a, Kim Bronsgeest, MSc ^b, Lidewij Henneman, PhD ^c, Neeltje Crombag, PhD ^a, Caterina M. Bilardo, MD, PhD ^d, Robert-Jan H. Galjaard, MD, PhD ^e, Esther Sikkel, MD, PhD ^f, Sanne van der Hout, PhD ^g, Audrey Coumans, MD, PhD ^h, Ayten Elvan-Taşpınar, MD, PhD ⁱ, Attie T.J.I. Go, MD, PhD ^j, Sander Galjaard, MD, PhD ^j, Gwendolyn T.R. Manten, MD, PhD ^k, Eva Pajkrt, MD, PhD ^d, Liesbeth van Leeuwen, MD, PhD ^d, Monique C. Haak, MD, PhD ^b, Mireille N. Bekker, MD, PhD ^a,^⁎
^a Department of Obstetrics and Gynecology, University Medical Center Utrecht, Utrecht, The Netherlands
^b Department of Obstetrics and Gynecology, Leiden University Medical Center, Leiden, The Netherlands
^c Department of Human Genetics and Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
^d Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, The Netherlands
^e Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands
^f Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands
^g University of Midwifery Education & Studies, Zuyd University of Applied Sciences, Maastricht, The Netherlands
^h Department of Obstetrics and Gynecology, Maastricht UMC+, Maastricht, The Netherlands
ⁱ Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
^j Department of Obstetrics and Gynecology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
^k Department of Obstetrics and Gynecology, Isala, Zwolle, The Netherlands

^∗Corresponding author: Mireille N. Bekker, MD, PhD.

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Thursday 29 August 2024

Abstract

Background

A significant proportion of major fetal structural anomalies can be detected in the first trimester by ultrasound examination. However, the test performance of the first-trimester anomaly scan performed in a low-risk population as part of a nationwide prenatal screening program is unknown. Potential benefits of the first-trimester anomaly scan include early detection of fetal anomalies, providing parents with more time for reproductive decision-making.

Objective

To investigate the uptake, test performance, and time to a final prenatal diagnosis after referral.

Study Design

A nationwide implementation study was conducted in the Netherlands (November 2021−November 2022). The FTAS was performed between 12+3 and 14+3 weeks of gestation by certified sonographers using a standard protocol. Women were referred to a tertiary care center if anomalies were suspected. Uptake, test performance, and time to a final prenatal diagnosis (days between referral and date of final diagnosis/prognosis for reproductive decision-making) were determined. Test performance was calculated for first-trimester major congenital anomalies, such as anencephaly and holoprosencephaly and all diagnosed anomalies <24 weeks of gestation.

Results

The first-trimester anomaly scan uptake was 74.9% (129,704/173,129). In 1.0% (1313/129,704), an anomaly was suspected, of which 54.9% (n=721) had abnormal findings on the detailed first-trimester diagnostic scan and 44.6% (n=586) showed normal results. In 0.5% (n=6), intrauterine fetal death occurred. In the total group of 721 cases with abnormal findings, 332 structural anomalies, 117 genetic anomalies, 82 other findings (abnormal fetal biometry, sonomarkers, placental/umbilical cord anomaly, an-/oligohydramnios), and 189 cases with transient findings (defined as ultrasound findings which resolved <24 weeks of gestation) were found, with 1 case having an unknown outcome. 0.9% (n=1164) of all cases with a normal first-trimester anomaly scan were diagnosed with a fetal anomaly in the second trimester. Test performance included a sensitivity of 84.6% (126/149) for first-trimester major congenital anomalies and 31.6% (537/1701) for all types of anomalies. Specificity for all anomalies was 99.2% (98,055/98,830); positive predictive value 40.9% (537/1312); negative predictive value 98.8% (98,055/99,219); positive likelihood ratio 40.3; negative likelihood ratio 0.7; false positive rate 0.8% (775/98,830), and false negative rate 68.4% (1164/1701). The median time to diagnosis for structural anomalies was 20 days (6–43 days; median gestational age 16+3), for genetic anomalies 17 days (8.5–27.5 days; median gestational age 15+6 weeks), and for first-trimester major congenital anomalies 9 days (5–22 days; median gestational age 14+6 weeks).

Conclusion

The performance of a newly introduced nationwide first-trimester anomaly scan in a low-risk population showed a high sensitivity for first-trimester major congenital anomalies and a lower sensitivity for all anomalies combined. The program was accompanied by a referral rate of 1.0%, of which 59.1% involved cases where anomalies were either not confirmed or resolved before 24 weeks gestation. Timing of diagnosis was around 16 weeks of gestation for referred cases. To evaluate the balance between benefits and potential harm of the first-trimester anomaly scan within a nationwide prenatal screening program, it is essential to assess the effectiveness of the program over time and to consider the perspectives of both women and their partners, as well as healthcare professionals.

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Key words : congenital abnormalities, fetal anomalies, first-trimester, first-trimester anomaly scan, FTAS, genetics, implementation, prenatal diagnosis, prenatal screening, prenatal ultrasonography, sensitivity and specificity, test characteristics, test performance

Plan

	E.E.R.L., K.B., M.C.H., and M.N.B. contributed equally to this work.
	The authors report no conflict of interest.
	The IMITAS study is supported by a grant from The Netherlands Organization for Health Research and Development (ZonMw, No. 543010001). The funding source was not involved in study design; the collection, analysis, or interpretation of data; the writing of the report; or the decision to submit the article for publication.
	Cite this article as: Lust EER, Bronsgeest K, Henneman L, et al. Introduction of a nationwide first-trimester anomaly scan in the Dutch national screening program. Am J Obstet Gynecol 2024;XXX:XX–XX.