Dataset Information

Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging.

ABSTRACT:

Objective

The purpose of this study was to explore the diagnostic yield and clinical utility of trio-based rapid whole exome sequencing (rWES) in pregnancies of fetuses with a wide range of congenital anomalies detected by ultrasound imaging.

Methods

In this observational study, we analyzed the first 54 cases referred to our laboratory for prenatal rWES to support clinical decision making, after the sonographic detection of fetal congenital anomalies. The most common identified congenital anomalies were skeletal dysplasia (n = 20), multiple major fetal congenital anomalies (n = 17) and intracerebral structural anomalies (n = 7).

Results

A conclusive diagnosis was identified in 18 of the 54 cases (33%). Pathogenic variants were detected most often in fetuses with skeletal dysplasia (n = 11) followed by fetuses with multiple major fetal congenital anomalies (n = 4) and intracerebral structural anomalies (n = 3). A survey, completed by the physicians for 37 of 54 cases, indicated that the rWES results impacted clinical decision making in 68% of cases.

Conclusions

These results suggest that rWES improves prenatal diagnosis of fetuses with congenital anomalies, and has an important impact on prenatal and peripartum parental and clinical decision making.

SUBMITTER: Deden C

PROVIDER: S-EPMC7497059 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging.

Deden Chantal C Neveling Kornelia K Zafeiropopoulou Dimitra D Gilissen Christian C Pfundt Rolph R Rinne Tuula T de Leeuw Nicole N Faas Brigitte B Gardeitchik Thatjana T Sallevelt Suzanne C E H SCEH Paulussen Aimee A Stevens Servi J C SJC Sikkel Esther E Elting Mariet W MW van Maarle Merel C MC Diderich Karin E M KEM Corsten-Janssen Nicole N Lichtenbelt Klaske D KD Lachmeijer Guus G Vissers Lisenka E L M LELM Yntema Helger G HG Nelen Marcel M Feenstra Ilse I van Zelst-Stams Wendy A G WAG

Prenatal diagnosis 20200505 8

<h4>Objective</h4>The purpose of this study was to explore the diagnostic yield and clinical utility of trio-based rapid whole exome sequencing (rWES) in pregnancies of fetuses with a wide range of congenital anomalies detected by ultrasound imaging.<h4>Methods</h4>In this observational study, we analyzed the first 54 cases referred to our laboratory for prenatal rWES to support clinical decision making, after the sonographic detection of fetal congenital anomalies. The most common identified co ...[more]

PMID: 32333414

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Project description:BackgroundMaternal hypothyroidism has been reported to have concerns over neonatal outcomes, not only in the context of neurocognitive development but also in the short term as birth weight and neonatal jaundice.Patients and methodsWe conducted a cross-sectional retrospective study on 638 cases who delivered live births in the Aga Khan University Hospital after ethical approval. Data were collected on hypothyroid pregnant females who were diagnosed before conception or during their antenatal visits during the year 2008-2016. Neonatal outcomes were noted for birth weight, maturity, and neonatal jaundice, neonatal hypothyroidism, neonatal respiratory distress syndrome, sepsis, hypocalcaemia, congenital anomalies, need for intensive care admission, and neonatal death. Subgroup analysis was performed on the timing of diagnosis of maternal hypothyroidism. Data analysis was performed on Statistical Package for the Social Sciences version 20.0.ResultsNeonatal jaundice was the most common neonatal outcome (37.6%) in our cohort of 662 live births. Nearly 15% required intensive care unit admission, however, neonatal death was very rare. The most common clinically significant congenital anomalies were cardiovascular defects, whereas Mongolian spots were the commonest congenital condition to report. There is a statistically significant association between low birth weight (OR 1.86, 95% CI 1.0-3.2, p ≤ 0.05) and congenital anomalies (OR 2.39, 95% CI 1.4-4.0, p ≤ 0.05) with women diagnosed with hypothyroidism before pregnancy.ConclusionWe report the neonatal outcomes and spectrum of congenital anomalies of hypothyroid pregnancies diagnosed before and during conception for the first time from the region of Pakistan.KEY MESSAGEOverall, none of the neonates of hypothyroid pregnancies developed congenital hypothyroidism.Cardiovascular defects in these neonates imply extensive screening and monitoring during pregnancy.Low birth weight and congenital anomalies are associated with the timings of diagnosis of hypothyroidism in pregnancy.

Project description:ObjectiveTo evaluate the application of non-invasive prenatal testing (NIPT) as an alternative to invasive diagnostic prenatal testing in pregnancies with abnormal ultrasound findings.MethodsThis was a retrospective analysis of 251 singleton and multiple pregnancies at high risk for fetal chromosomal abnormality based on findings at sonographic examination, in which NIPT was performed as a first-tier genetic test. NIPT was performed by massively parallel sequencing of cell-free DNA in maternal plasma, allowing genome-wide detection of whole-chromosome, as well as partial, autosomal aneuploidy. Sex chromosomes were not analyzed, according to the current protocol in Dutch laboratories.ResultsNIPT was performed at a median gestational age of 20 weeks, indicated by the presence of multiple congenital anomalies (n = 13), isolated structural anomalies (n = 57), increased nuchal translucency ≥ 3.5 mm (n = 58), soft markers (n = 73), growth restriction (n = 40) and other anomalies (n = 10). NIPT results were normal in 224 (89.2%) pregnancies, inconclusive in one (0.4%) and abnormal in 26 (10.4%). Most genetic aberrations detected by NIPT were common whole-chromosome aneuploidies: trisomy 21 (n = 13), trisomy 18 (n = 6) and trisomy 13 (n = 3). Four further NIPT results were abnormal; one was suspected of being confined placental mosaicism and one was of maternal origin. In those with normal NIPT results, sonographic follow-up or examination of the newborn indicated the need for diagnostic genetic testing in 33/224 (14.7%) pregnancies. Clinically relevant genetic aberrations were revealed in 7/224 (3.1%) cases, two of which were whole-chromosome aneuploidies: trisomy 13 and monosomy X. As sex chromosomal aberrations are not included in NIPT analysis, the latter cannot be considered a false-negative result. Other discordant findings were subchromosomal aberrations (< 20 megabases, n = 2) and monogenic aberrations (n = 3).ConclusionsNIPT should not be recommended for genetic evaluation of the etiology of ultrasound anomalies, as both resolution and sensitivity, or negative predictive value, are inferior to those of conventional karyotyping and microarray analysis. Nonetheless, some pregnant women consider NIPT to be an acceptable alternative to invasive diagnostic testing. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

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Dataset Information

Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging.

Objective

Methods

Results

Conclusions

Publications

Rapid whole exome sequencing in pregnancies to identify the underlying genetic cause in fetuses with congenital anomalies detected by ultrasound imaging.

Similar Datasets

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