Clinical management of pregnancies with positive screening results for rare autosomal aneuploidies at a single center

Abstract

Objective To review our experiences on clinical management of pregnancies with positive noninvasive prenatal testing (NIPT) results for rare autosomal aneuploidies (RAAs) at a single center. Methods We performed a retrospective study and reviewed data from 18,016 pregnancies undergoing NIPT at a single center in China from March 2017 to February 2020. Depending on the patient’s choice, women with positive screening results for RAAs underwent chromosomal microarray analysis for invasive prenatal diagnosis. Results Thirty-three positive cases for RAAs were identified, with a positive screening rate of 0.18%. The most common RAA was trisomy 7 (33.3%), while trisomies for other chromosomes were less frequent. Monosomies involving chromosomes 16, 14, and 22 were observed. Twenty-eight cases of RAAs underwent invasive diagnosis. Abnormal pregnancy outcomes were observed in four cases, including true fetal mosaicism (n=1), partial uniparental disomy (n=1), miscarriage (n=1), and structural anomalies on ultrasound (n=1). Conclusions RAAs at NIPT might be associated with fetal uniparental disomy, mosaic aneuploidy, and poor pregnancy outcomes, but most positive cases have normal pregnancy outcomes. For RAAs, genetic counseling on the potential risks of abnormal NIPT results, as well as on benefits and limitations of invasive prenatal diagnosis, might help guide clinical management.

Live-Born with a Trisomy 22 Mosaic: A Case Report

“…In our case, the combined first-trimester screening and the NIPT already showed an abnormal result leading to an early diagnosis through amniocentesis. Previous studies on rare autosomal aneuploidies (RAAs) at NIPT showed that these results might suggest an increased risk of confined placental mosaicism (CPM) or fetal mosaic aneuploidy [6]. In our case, the fetus showed many of the previously described typical features of a trisomy 22 mosaic: being female, congenital heart disease, and intrauterine growth restriction [5].…”

Chances and Challenges of New Genetic Screening Technologies (NIPT) in Prenatal Medicine from a Clinical Perspective: A Narrative Review

“…Outcomes with an unremarkable course of pregnancy have been reported, linked to the chromosome involved, with particularly poor outcome for trisomies 15, 16 and 22, and a mostly favorable outcome for trisomy 7, the most frequent RAT found by NIPT [ 89 , 94 , 95 ]. Trisomy 16 is associated with severe intrauterine growth restriction (IUGR), pre-eclampsia and fetal anomalies.…”

Prenatal Screening for Microdeletions and Rare Autosomal Aneuploidies

“…In studies of cfDNA for RAA, the screenpositive rate ranges from 0.12% to 0.91%, depending on the population studied [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] . The rate is higher in "high-risk" populations variably defined as women with ultrasonographic anomalies and prior children with chromosomal abnormalities.…”

“…Among publications, including RAAs detected on cfDNA and confirmed with invasive testing, the PPVs range from 3.8% to 58% 11,[13][14][15][16][17][18][19][20][21][22][23][24][25] . In a recent systemic evidence-based review of cfDNA, Rose et al 4 performed a quantitative analysis of PPVs reported in 17 studies (published through March 2021) and calculated an overall PPV for RATs of 13.42%.…”