First‐trimester screening based on cell‐free DNA vs combined screening: A randomized clinical trial on women's experience

Abstract

Objective: To compare women's experience of first-trimester combined screening (FTCS), with women's experience of an approach that uses the combination of a detailed early anatomy scan and cell-free DNA (cfDNA) analysis. Methods: This was single-center, open label, parallel group, randomized clinical trial. Pregnant women were randomized at the time of their first prenatal visit to either a policy of first-trimester risk assessment based on FTCS, or to a policy of firsttrimester risk assessment based on ultrasound findings and cfDNA. FTCS included ultrasound evaluation with crown-rump length, nuchal translucency (NT) measurement, and a detailed ultrasound scan, along with biochemistry (PAPP-A and free beta hCG). In this group, invasive diagnostic testing was offered to patients with risk >1 in 100, or NT >3.5 mm, or any fetal abnormalities on ultrasound. Women randomized in the intervention group received an approach of first-trimester risk assessment based on ultrasound findings and cfDNA. cfDNA analysis included a simultaneous microarray-based assay of non-polymorphic (chromosomes 13, 18, 21, X and Y) and polymorphic loci to estimate chromosome proportion and fetal fraction. In the intervention group, invasive diagnostic testing was offered to patients with abnormal cfDNA screening results, or NT >3.5 mm, or any fetal abnormalities on ultrasound. Participants received pre-test and post-test questionnaires regarding to measure reassurance, satisfaction, and anxiety. The primary outcome was the post-test reassurance, defined as mean score of reassurance post-test questionnaire. The effect of the assigned screening test on the mean of each outcome was quantified as mean difference (MD) with 95% confidence interval (CI). Results: Forty women with singleton gestations were enrolled in the trial. Mean score for reassurance was significantly higher in the cfDNA group compared to the FTCS group in the pre-test questionnaire (MD 0.80 points, 95% CI 0.27 to 1.33) and in the post-test questionnaire (MD 16.50 points, 95% CI 2.18 to 30.82). Women randomized to the cfDNA group had higher satisfaction and lower mean anxiety score as assessed in the STAI pre-test questionnaire. Conclusions: First-trimester risk assessment for fetal aneuploidy with a combination of a detailed ultrasound examination and cfDNA is associated with better maternal

European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases

“…459 Cell-free DNA testing on a maternal blood sample is emerging as a non-invasive means of aneuploidy screening for foetuses with no apparent structural abnormalities although this approach currently lacks resolution in definition of sub-microscopic chromosomal anomalies. [460][461][462] [439][440][441][442]444,[454][455][456][457] and modified from ref. 458 CHD, congenital heart disease; CMA, chromosome microarray; CNV, copy number variant; ECA, extracardiac anomaly; SNV, single-nucleotide variant; WES, whole-exome sequencing; WGS, whole-genome sequencing.…”

“…Routine antenatal testing on amniocentesis or CVS is focused on the identification of major chromosomal abnormalities including Trisomy 13, 18, 21 and 22q11 deletion, responsible for velocardiofacial syndrome, and should be offered to any patient pursuing invasive prenatal diagnosis without prior knowledge of cardiac or other malformations 459 . Cell‐free DNA testing on a maternal blood sample is emerging as a non‐invasive means of aneuploidy screening for foetuses with no apparent structural abnormalities although this approach currently lacks resolution in definition of sub‐microscopic chromosomal anomalies 460–462 …”

European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the State of Genetic Testing for Cardiac Diseases

“…459 Cell-free DNA testing on a maternal blood sample is emerging as a non-invasive means of aneuploidy screening for foetuses with no apparent structural abnormalities although this approach currently lacks resolution in definition of submicroscopic chromosomal anomalies. [460][461][462] Neonates and infants requiring investigation or procedures for congenital heart disease Testing for pathogenic chromosomal CNVs by CMA or CNV seq should be performed. 434 These techniques have essentially replaced standard karyotype analysis as first line testing, although conventional karyotyping may be performed particularly in assessment of balanced translocations.…”

Current Perspectives of Prenatal Cell-free DNA Screening in Clinical Management of First-Trimester Septated Cystic Hygroma

“…28 Migliorini et al in a randomized clinical trial of patient's experience comparing pre-and post-test survey questionnaires addressing measure reassurance, satisfaction, and anxiety between patients undergoing standard first-trimester screening (nuchal translucency and maternal serum analytes) versus ultrasound findings followed by cfDNA analysis found that mean score for reassurance was significantly higher in the cfDNA group in comparison with standard screening in both pre-and post-test questionnaires. 29 Forty women with singleton gestations were included in the study. Women were randomized at the time of their first prenatal visit to either first-trimester risk assessment based on first-trimester combined screening or first-trimester risk assessment based on sonographic findings and cfDNA.…”

“…These authors thus concluded that first-trimester screening for fetal aneuploidy combined with detailed sonographic examination and cfDNA is associated with improved maternal satisfaction and maternal reassurance compared to the standard first-trimester combined screening with nuchal translucency (NT), and maternal serum analytes. 29 Iwarsson and Conner from the Karolinska Institute, studied detection rates and residual risk for postnatal diagnosis of an atypical chromosomal aberration after combined first-trimester screening. 30 Among 129,493 patients, 852 (0.7%) clinically significant chromosome aberrations, including those detected after birth were noted.…”