The April issue of Ultrasound in Obstetrics & Gynecology has a special focus on integrating genomics into obstetric care, with articles on the role of first-trimester ultrasound and combined screening in the cell-free DNA era and the impact of high-resolution genetic technologies in identification of atypical chromosomal abnormalities. Articles on other topics in this issue include an Original Article on home blood-pressure monitoring in a hypertensive pregnant population.
Please see below a selection of articles from the April issue of the Journal chosen specially by the UOG team. To view all UOG content, become an ISUOG member today or login and upgrade.
Genome-wide non-invasive prenatal testing
Non-invasive prenatal testing (NIPT) has been shown to be effective in screening for trisomies 21, 18 and 13. It may be further extended to a broad range of other chromosomal abnormalities, although the clinical utility of genome-wide assessment is questionable. An Editorial by Benn and Grati evaluated the expected performance of genome-wide NIPT based on data from karyotyping of cytotrophoblasts vs NIPT targeted for common trisomies and sex chromosome abnormalities, finding that the genome-wide method would be of limited gain.
A Systematic Review by Srebniak et al. on the frequency of submicroscopic pathogenic chromosomal aberrations, detected using high-resolution cytogenetic testing, in fetuses that are not at increased risk for unbalanced structural chromosomal aberrations, found that a significant proportion carry a submicroscopic pathogenic copy number variant (CNV). As such, the authors advise that, because invasive testing in all pregnancies is not feasible, a reliable, non-invasive whole-genome profiling test to screen for both microscopic and submicroscopic aberrations is highly desirable.
Universal non-invasive prenatal testing
There is an ongoing debate regarding how cell-free DNA (cfDNA) screening can best be incorporated into current prenatal screening. A Randomized Controlled Trial by Kagan et al. compared combined first-trimester screening (CFTS) to a detailed ultrasound examination at 11–13 weeks’ gestation followed by cfDNA analysis for trisomy 21 (T21) risk assessment, with invasive testing offered to high-risk pregnancies, finding that the latter is associated with a significant reduction in the false-positive rate. This article is accompanied by a Referee Commentary by Hui, discussing further the findings of the study.
Contingent screening models
As universal NIPT has limitations in terms of cost-effectiveness, contingent screening models have been proposed. An Original Article by Miltoft et al. compared screening for T21 with referral for invasive testing at a CFTS-T21 risk ≥ 1 in 300, to contingent screening with referral for invasive testing at a CFTS-T21 risk ≥ 1 in 100 and referral for cfDNA testing at a CFTS-T21 risk of between 1 in 100 and 1 in 1000, finding the contingent screening to have similar sensitivity but increased specificity.
Support for contingent screening based on CFTS risk was not provided by Vogel et al., who evaluated the performance of high-resolution chromosomal microarray (CMA) as the standard diagnostic approach for genomic imbalances in pregnancies with increased risk based on CFTS, finding it to be a valuable diagnostic technique, but that a contingent cfDNA analysis strategy would have led to abnormal results being overlooked.
An Original Article by Lindquist et al. analyzed the uptake of invasive diagnostic testing after CFTS and prevalence and ascertainment of atypical chromosome abnormalities according to CFTS risk result, finding that there has been a decline in invasive testing uptake since the introduction of NIPT. Furthermore, their results suggest that concerns regarding missed diagnoses using a contingent model can be mitigated by offering diagnostic testing to women with high risk (> 1 in 100) on CFTS, low maternal serum markers or ultrasound abnormality. An Opinion piece by Vogel and Peterson discusses further the findings of these two articles.
Other related articles
Other articles in this issue related to prenatal genetic screening include a Systematic Review by Pauta et al. on the added value of CMA over conventional karyotyping for the detection of pathogenic CNVs and variants of unknown significance in early pregnancy loss, an Original Article by Kenkhuis et al. which, in view of the introduction of cfDNA testing in Denmark, assessed for the detection of fetal anomaly an early scan performed at 12–13 weeks’ gestation compared with at a currently offered 20-week structural anomaly scan (view the accompanying Journal Club slides), an Original Article by Fu et al. on the promising diagnostic yield of prenatal invasive whole-exome sequencing for monogenic disorders in fetuses with structural malformations and normal results on cytogenetic testing, and a Letter to the Editor by Vogel et al. in which the authors describe an algorithm for sorting chromosomal aberration data.
Other articles in this issue include…
Home blood-pressure monitoring in a hypertensive pregnant population
Monitoring, early recognition and treatment of hypertensive disorders of pregnancy are key to reducing severe complications and mortality. Traditionally, women who develop hypertension in pregnancy are advised to attend an outpatient service or day assessment unit, commonly two to three times a week, for blood pressure monitoring. Home blood-pressure monitoring has the potential to offer a more accurate and acceptable means of monitoring hypertensive patients during pregnancy. This Original Article by Perry et al., assessed if home blood-pressure monitoring using a smartphone application can be used in women at risk of PE, finding that it has the potential to reduce the number of hospital visits required by patients without compromising maternal and pregnancy outcomes.
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Coming up in the next issue is a series of papers reporting on preterm birth.
Also to look out for in May is a Virtual Issue on preterm birth, containing a selection of relevant articles from UOG.