How Useful is Nuchal Translucency in Detecting Chromosomal Abnormalities Missed by Genome-Wide NIPT and What Measurement Threshold Should Be Used?

Introduction: Genome-wide non-invasive prenatal testing (gwNIPT) has screening limitations for detectable genetic conditions and cannot detect microdeletions/microduplications (MD) or triploidy. Nuchal translucency (NT) increases with gestation and with genetic or structural abnormalities. This study aims to determine the utility of NT measurement in detecting genetic abnormalities not identified by gwNIPT and the optimal NT threshold value.

Sonographic Assessment of Fetal Sex: More than External Genitalia.

Early identification of fetal sex is possible due to both improved ultrasound resolution and the incorporation of cell-free DNA testing into routine prenatal screening services. While ultrasound assessment of the external genitalia generally suffices, there are instances where identification of the internal genitalia becomes vital to allow accurate prenatal diagnosis and comprehensive counseling. This manuscript outlines the methodology and clinical utility of assessing fetal genitalia beyond conventional sonography from the second trimester onward and is the first to describe direct visualization of the fetal vagina.

Cell-free DNA screening for rare autosomal trisomies and segmental chromosome imbalances.

Objective: To assess the outcomes of pregnancies at high-risk for rare autosomal trisomies (RATs) and segmental imbalances (SIs) on cell-free DNA (cfDNA) screening.

Method: A retrospective study of women who underwent cfDNA screening between September 2019 and July 2021 at three ultrasound services in Australia. Positive predictive values (PPVs) were calculated using fetal chromosomal analysis.

Increasing maternal age is not a significant cause of false-positive results for monosomy X in non-invasive prenatal testing.

Objective: The accuracy of cell-free DNA aneuploidy screening varies by the chromosome assessed. The positive predictive value is consistently low for monosomy X (MX), at less than 30%. This study aims to investigate maternal age and other possible predictors of false-positive MX screening results in order to guide pre-test and post-test counselling.

Discordant fetal sex on NIPT and ultrasound.

Prenatal diagnosis of sex discordance is a relatively new phenomenon. Prior to cell-free DNA testing, the diagnosis of a disorder of sexual differentiation was serendipitous, either through identification of ambiguous genitalia at the midtrimester morphology ultrasound or discovery of genotype-phenotype discordance in cases where preimplantation genetic diagnosis or invasive prenatal testing had occurred. The widespread integration of cfDNA testing into modern antenatal screening has made sex chromosome assessment possible from 10 weeks of gestation, and discordant fetal sex is now more commonly diagnosed prenatally, with a prevalence of approximately 1 in 1500-2000 pregnancies.

Rare autosomal trisomies: Important and not so rare.

Objective: Noninvasive prenatal testing (NIPT) can assess chromosomes other than 13, 18, 21, X and Y. These rare autosomal trisomies (RATs) can adversely affect pregnancy outcome.

Methods: A prospective study of NIPT using the Illumina sequencing platform assessing all chromosomes were reported for further management.

Sex discordance identification following non-invasive prenatal testing.

Objective: The objectives of this study were to characterise genotype-phenotype discordance identified in the routine clinical setting and to explore the associated diagnostic and counselling challenges.

Method: Cases were derived from a cohort of pregnant women who attended a multisite specialist prenatal screening and ultrasound service for non-invasive prenatal testing by cell-free DNA analysis and midtrimester fetal morphology assessment.

Results: Seven cases of genotype-phenotype discordance were identified from a cohort of 12 919 women between June 2013 and March 2017 (incidence 1/1845 pregnancies).

Non-Invasive Prenatal Testing for Sex Chromosome Aneuploidy in Routine Clinical Practice.

Objectives: To assess the accuracy of non-invasive prenatal testing (NIPT) for sex chromosome aneuploidy (SCA) in routine clinical practice and to review counselling and sonographic issues arising in SCA cases.

Methods: Three specialist Australian obstetric ultrasound and prenatal diagnosis practices offering NIPT after 10 weeks' gestation participated in this study. NIPT was reported for chromosomes 21, 18, 13, X, and Y.

Factors affecting cell-free DNA fetal fraction and the consequences for test accuracy.

Introduction: Biological factors are known to influence the fetal fraction (FF) of cell-free DNA and may also influence the accuracy of non-invasive prenatal testing.

Material And Methods: NIPT from 5267 mixed risk women across three specialist clinics in Australia were analyzed. Multivariable regression analysis was used to determine whether maternal characteristics, ultrasound, and placental biomarkers affect FF and test accuracy.

Noninvasive prenatal testing in routine clinical practice--an audit of NIPT and combined first-trimester screening in an unselected Australian population.

Background: There are limited data regarding noninvasive prenatal testing (NIPT) in low-risk populations, and the ideal aneuploidy screening model for a pregnant population has yet to be established.

Aims: To assess the implementation of NIPT into clinical practice utilising both first- and second-line screening models.

Materials And Methods: Three private practices specialising in obstetric ultrasound and prenatal diagnosis in Australia offered NIPT as a first-line test, ideally followed by combined first-trimester screening (cFTS), or as a second-line test following cFTS, particularly in those with a calculated risk between 1:50 and 1:1000.

Prenatal diagnosis of chromosomal mosaicism in over 1600 cases using array comparative genomic hybridization as a first line test.

Objective: The aim of this study was to assess the detection of chromosomal mosaicism in chorionic villus (CVS) and amniotic fluid (AF) samples using array comparative genomic hybridization (aCGH) and quantitative fluorescent polymerase chain reaction.

Methods: All patients undergoing invasive prenatal testing by aCGH at a specialist prenatal screening service were included in the study. A total of 1609 samples (953 CVS and 656 AF) underwent quantitative fluorescent polymerase chain reaction and targeted aCGH without concurrent conventional G-banded karyotyping.

Pregnancy outcome in the setting of extremely low first trimester PAPP-A levels.

Background: Serum pregnancy-associated plasma protein-A (PAPP-A) is part of first trimester Down syndrome screening. Low levels have been associated with adverse outcome as well as chromosomal abnormality.

Aims: To assess the incidence of adverse outcome when PAPP-A levels are at or below 0.

Perinatal outcome in fetuses with extremely large nuchal translucency measurement.

Background: Studies have suggested that an entirely normal outcome is likely when the nuchal translucency (NT) measurement is very large and the karyotype, morphology and echocardiography scans are normal. Recently this has been questioned as it is based on very small numbers.

Aim: Assess the outcome of pregnancies with an NT measurement of 6.

Prospective evaluation of a first trimester screening program for Down syndrome and other chromosomal abnormalities using maternal age, nuchal translucency and biochemistry in an Australian population.

Background: A combination of maternal age and ultrasound assessment of the nuchal translucency (NT) has been used in the first trimester to screen for chromosomal abnormality. In the United Kingdom, the addition of NT screening was shown to be beneficial.

Aims: To report the sensitivity of combined first trimester biochemistry and ultrasound screening for Down syndrome in an Australian private practice specialising in obstetric ultrasound.

The loss rates for invasive prenatal testing in a specialised obstetric ultrasound practice.

Objectives: To establish the spontaneous miscarriage rate and compare it with the procedure related miscarriage rate for amniocentesis and chorionic villus sampling (CVS) by experienced operators.

Design: Retrospective audit over a two-year period of all patients having a consultation for prenatal diagnosis before 12 weeks gestation.

Setting: A specialised obstetric and gynaecological ultrasound practice.