Clinical Application of Chromosomal Microarray Analysis in Pregnant Women with Advanced Maternal Age and Fetuses with Ultrasonographic Soft Markers

Overview

Journal Med Sci Monit

Specialties General Medicine
Pathology

Date 2021 Apr 10

PMID 33837172

Citations 4

Authors

Zhu-Ming Hu

Lei-Lei Li

Han Zhang

Hong-Guo Zhang

Rui-Zhi Liu

Yang Yu

Affiliations

Soon will be listed here.

Abstract

BACKGROUND In pregnant women with advanced maternal age (AMA) and fetuses with ultrasonographic (USG) soft markers it is always challenging to decide whether to implement chromosomal microarray analysis (CMA) or not. It is unclear whether CMA should be used in the fetuses with isolated USG soft markers, and there is still a lack of extensive sample research. MATERIAL AND METHODS We enrolled 1521 cases in our research and divided them into 3 groups as follows: pregnant women with isolated AMA (group 1, n=633), pregnant women whose fetuses had isolated USG soft markers (group 2, n=750), and pregnant women with AMA whose fetuses had isolated USG soft markers (group 3, n=138). All pregnant women underwent prenatal ultrasound and amniocentesis, and fetal cells in the amniotic fluid were used for genetic analysis of CMA. All participants signed a written informed consent prior to CMA. RESULTS Abnormal findings were detected by CMA in 330 (21.70%) fetuses, including 37 (2.43%) clinically significant copy number variations (CNVs), 52 (3.42%) benign or likely benign CNVs, and 240 (15.78%) variants of unknown significance. The frequency of clinically significant CNVs in group 1 and group 2 were significantly lower than that in group 3 (2.37% and 2.0% vs 5.07%, P<0.01). More than a half (59.46%, 22/37) of the pregnant women decided to continue their pregnancy despite having a fetus diagnosed with clinically significant CNV. CONCLUSIONS CMA can increase the diagnostic yield of fetal chromosomal abnormality for pregnant women with isolated AMA or/and their fetuses had isolated USG soft markers.

Citing Articles

Comparison of Chromosomal Microarray Analysis and Noninvasive Prenatal Testing in Pregnant Women with Fetal Ultrasonic Soft Markers.

Hu X, Hu Y, Wang H, Yu C, Zheng J, Zhang H Risk Manag Healthc Policy. 2024; 17:29-40.

PMID: 38196919 PMC: 10775152. DOI: 10.2147/RMHP.S437441.

Clinical Experience of Prenatal Chromosomal Microarray Analysis in 6159 Ultrasonically Abnormal Fetuses.

Song T, Xu Y, Li Y, Zheng J, Guo F, Jin X Reprod Sci. 2023; 31(4):1089-1107.

PMID: 38012523 DOI: 10.1007/s43032-023-01399-2.

Prenatal Diagnosis Using Chromosomal Microarray Analysis in High-Risk Pregnancies.

Hsiao C, Chen J, Shiao Y, Chen Y, Chen C, Chu W J Clin Med. 2022; 11(13).

PMID: 35806909 PMC: 9267905. DOI: 10.3390/jcm11133624.

Molecular Approaches in Fetal Malformations, Dynamic Anomalies and Soft Markers: Diagnostic Rates and Challenges-Systematic Review of the Literature and Meta-Analysis.

Mastromoro G, Guadagnolo D, Khaleghi Hashemian N, Marchionni E, Traversa A, Pizzuti A Diagnostics (Basel). 2022; 12(3).

PMID: 35328129 PMC: 8947110. DOI: 10.3390/diagnostics12030575.

References

Kim Y, Lee J, Kim S, Shim S, Cha D . Maternal age-specific rates of fetal chromosomal abnormalities in Korean pregnant women of advanced maternal age. Obstet Gynecol Sci. 2013; 56(3):160-6. PMC: 3784117. DOI: 10.5468/ogs.2013.56.3.160. View

Buse M, Cuttaia H, Palazzo D, Mazara M, Lauricella S, Malacarne M . Expanding the phenotype of reciprocal 1q21.1 deletions and duplications: a case series. Ital J Pediatr. 2017; 43(1):61. PMC: 5518118. DOI: 10.1186/s13052-017-0380-x. View

Scott F, Murphy K, Carey L, Greville W, Mansfield N, Barahona P . Prenatal diagnosis using combined quantitative fluorescent polymerase chain reaction and array comparative genomic hybridization analysis as a first-line test: results from over 1000 consecutive cases. Ultrasound Obstet Gynecol. 2013; 41(5):500-7. DOI: 10.1002/uog.12429. View

Fiorentino F, Caiazzo F, Napolitano S, Spizzichino L, Bono S, Sessa M . Introducing array comparative genomic hybridization into routine prenatal diagnosis practice: a prospective study on over 1000 consecutive clinical cases. Prenat Diagn. 2011; 31(13):1270-82. DOI: 10.1002/pd.2884. View

Su L, Huang H, An G, Cai M, Wu X, Li Y . Clinical application of chromosomal microarray analysis in fetuses with increased nuchal translucency and normal karyotype. Mol Genet Genomic Med. 2019; 7(8):e811. PMC: 6687862. DOI: 10.1002/mgg3.811. View

Zhu Y, Lu S, Bian X, Wang H, Zhu B, Wang H . A multicenter study of fetal chromosomal abnormalities in Chinese women of advanced maternal age. Taiwan J Obstet Gynecol. 2016; 55(3):379-84. DOI: 10.1016/j.tjog.2016.01.002. View

Van Opstal D, de Vries F, Govaerts L, Boter M, Lont D, van Veen S . Benefits and burdens of using a SNP array in pregnancies at increased risk for the common aneuploidies. Hum Mutat. 2014; 36(3):319-26. DOI: 10.1002/humu.22742. View

Hillman S, Mcmullan D, Hall G, Togneri F, James N, Maher E . Use of prenatal chromosomal microarray: prospective cohort study and systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2013; 41(6):610-20. DOI: 10.1002/uog.12464. View

de Kovel C, Trucks H, Helbig I, Mefford H, Baker C, Leu C . Recurrent microdeletions at 15q11.2 and 16p13.11 predispose to idiopathic generalized epilepsies. Brain. 2009; 133(Pt 1):23-32. PMC: 2801323. DOI: 10.1093/brain/awp262. View

10.

South S, Lee C, Lamb A, Higgins A, Kearney H . ACMG Standards and Guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: revision 2013. Genet Med. 2013; 15(11):901-9. DOI: 10.1038/gim.2013.129. View

11.

Sagi-Dain L, Cohen Vig L, Kahana S, Yacobson S, Tenne T, Agmon-Fishman I . Chromosomal microarray vs. NIPS: analysis of 5541 low-risk pregnancies. Genet Med. 2019; 21(11):2462-2467. DOI: 10.1038/s41436-019-0550-x. View

12.

Shaffer L, Dabell M, Fisher A, Coppinger J, Bandholz A, Ellison J . Experience with microarray-based comparative genomic hybridization for prenatal diagnosis in over 5000 pregnancies. Prenat Diagn. 2012; 32(10):976-85. PMC: 3491694. DOI: 10.1002/pd.3945. View

13.

Nagai K, Shima H, Kamimura M, Kanno J, Suzuki E, Ishiguro A . Xp22.31 Microdeletion due to Microhomology-Mediated Break-Induced Replication in a Boy with Contiguous Gene Deletion Syndrome. Cytogenet Genome Res. 2017; 151(1):1-4. DOI: 10.1159/000458469. View

14.

Smeets D . Historical prospective of human cytogenetics: from microscope to microarray. Clin Biochem. 2004; 37(6):439-46. DOI: 10.1016/j.clinbiochem.2004.03.006. View

15.

Wu X, An G, Xie X, Su L, Cai M, Chen X . Chromosomal microarray analysis for pregnancies with or without ultrasound abnormalities in women of advanced maternal age. J Clin Lab Anal. 2019; 34(4):e23117. PMC: 7171339. DOI: 10.1002/jcla.23117. View

16.

Konialis C, Pangalos C . Dilemmas in Prenatal Chromosomal Diagnosis Revealed Through a Single Center's 30 Years' Experience and 90,000 Cases. Fetal Diagn Ther. 2015; 38(3):218-32. DOI: 10.1159/000368604. View

17.

Srebniak M, Joosten M, Knapen M, Arends L, Polak M, van Veen S . Frequency of submicroscopic chromosomal aberrations in pregnancies without increased risk for structural chromosomal aberrations: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2017; 51(4):445-452. DOI: 10.1002/uog.17533. View

18.

Papoulidis I, Sotiriadis A, Siomou E, Papageorgiou E, Eleftheriades M, Papadopoulos V . Routine use of array comparative genomic hybridization (aCGH) as standard approach for prenatal diagnosis of chromosomal abnormalities. Clinical experience of 1763 prenatal cases. Prenat Diagn. 2015; 35(13):1269-77. DOI: 10.1002/pd.4685. View

19.

Wang R, Yu Y, Xi Q, Jiang Y, Zhu H, Li S . Analysis of prenatal diagnosis before and after implementation of the two-child policy in northeastern China. Medicine (Baltimore). 2019; 98(38):e17200. PMC: 6756619. DOI: 10.1097/MD.0000000000017200. View

20.

Armour C, Dougan S, Brock J, Chari R, Chodirker B, DeBie I . Practice guideline: joint CCMG-SOGC recommendations for the use of chromosomal microarray analysis for prenatal diagnosis and assessment of fetal loss in Canada. J Med Genet. 2018; 55(4):215-221. PMC: 5869456. DOI: 10.1136/jmedgenet-2017-105013. View