Screening of fetal trisomies 21, 18 and 13 by noninvasive prenatal testing. Rapid assessment of other health technologies using the HTA Core Model for Rapid Relative Effectiveness Assessment.

Abstract

The aim of this collaborative assessment is to evaluate the relative effectiveness and safety of noninvasive prenatal testing (NIPT) for the screening of fetal trisomy 21 (T21), trisomy 18 (T18) and trisomy 13 (T13) in pregnant women of at least 8–9 weeks’ gestation. Five screening pathways are considered for the purpose of NIPT assessment: 1. NIPT as a primary screening test (total replacement of first trimester combined testing (FCT)) 2. NIPT as part of FCT (replacement of serum testing) 3. NIPT as an add-on to FCT for the high-risk population 4. NIPT as an add-on to FCT for the high- and intermediate-risk population 5. NIPT as a replacement for invasive testing

The comparator, chosen by application of EUnetHTA criteria, is first-trimester serum screening (pregnancy-associated plasma protein A (PAPP-A) and β subunit of human chorionic gonadotropin (β-hCG)) and/or an ultrasound scan to measure fetal nuchal translucency (NT) or fetal crown-rump length (CRL) and maternal age. Fetal karyotyping or birth outcomes determined through clinical examination or follow-up of the newborn are considered the reference standards.

The effectiveness of the screening processes is evaluated in terms of secondary outcomes (sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)) but also in terms of primary outcomes, reducing unecessary invasive tests, assessing the impact on children born with undiagnosed T13, T18 and T21, natural miscarriages or stillbirths, and miscarriages related to invasive testing (amniocentesis or chorionic villus sampling (CVS)). False positive (FP) rates, false negative (FN) rates and test failures were chosen as critical safety issues. The increase in the number of children born with other major prenatally undetected chromosomal conditions/ anomalies (not targeted by prenatal aneuploidy screening) and the increase in elective pregnancy termination for other chromosomal anomalies with uncertain significance were considered important safety issues. Several organisational, ethical and social outcomes were also considered of relevance.

Randomised controlled clinical trials, nonrandomised controlled clinical trials and diagnostic test accuracy (DTA) studies on the index test, the comparator and the reference standard (crosssectional studies) are included for the effectiveness and safety domain. In addition, registries are included for the safety domain and qualitative studies and consensus documents are included for the organisational, ethical and social domains.