Chromosomal Microarray Analysis in Fetuses With Ultrasonographic Soft Markers: A Meta-Analysis of the Current Evidence

Overview

Journal J Korean Med Sci

Specialty General Medicine

Date 2024 Mar 5

PMID 38442716

Authors

Uisuk Kim

Young Mi Jung

Sohee Oh

Ji Hye Bae

Jeesun Lee

Chan-Wook Park

Joong Shin Park

Jong Kwan Jun

Seung Mi Lee

Affiliations

Soon will be listed here.

Abstract

Background: Ultrasonographic soft markers are normal variants, rather than fetal abnormalities, and guidelines recommend a detailed survey of fetal anatomy to determine the necessity of antenatal karyotyping. Anecdotal reports have described cases with ultrasonographic soft markers in which chromosomal microarray analysis (CMA) revealed pathogenic copy number variants (CNVs) despite normal results on conventional karyotyping, but CMA for ultrasonographic soft markers remains a matter of debate. In this systematic review, we evaluated the clinical significance of CMA for pregnancies with isolated ultrasonographic soft markers and a normal fetal karyotype.

Methods: An electronic search was conducted by an experienced librarian through the MEDLINE, Embase, and Cochrane CENTRAL databases. We reviewed 3,338 articles (3,325 identified by database searching and 13 by a hand search) about isolated ultrasonographic soft markers, and seven ultrasonographic markers (choroid plexus cysts, echogenic bowel, echogenic intracardiac focus, hypoplastic nasal bone, short femur [SF], single umbilical artery, and urinary tract dilatation) were included for this study.

Results: Seven eligible articles were included in the final review. Pathogenic or likely pathogenic CNVs were found in fetuses with isolated ultrasonographic soft markers and a normal karyotype. The overall prevalence of pathogenic or likely pathogenic CNVs was 2.0% (41 of 2,048). The diagnostic yield of CMA was highest in fetuses with isolated SF (9 of 225, 3.9%).

Conclusion: CMA could aid in risk assessment and pregnancy counseling in pregnancies where the fetus has isolated ultrasonographic soft markers along with a normal karyotype.

References

Prabhu M, Kuller J, Biggio J . Society for Maternal-Fetal Medicine Consult Series #57: Evaluation and management of isolated soft ultrasound markers for aneuploidy in the second trimester: (Replaces Consults #10, Single umbilical artery, October 2010; #16, Isolated echogenic.... Am J Obstet Gynecol. 2021; 225(4):B2-B15. DOI: 10.1016/j.ajog.2021.06.079. View

Maillard A, Ruef A, Pizzagalli F, Migliavacca E, Hippolyte L, Adaszewski S . The 16p11.2 locus modulates brain structures common to autism, schizophrenia and obesity. Mol Psychiatry. 2014; 20(1):140-7. PMC: 4320286. DOI: 10.1038/mp.2014.145. View

Kirov G, Rees E, Walters J, Escott-Price V, Georgieva L, Richards A . The penetrance of copy number variations for schizophrenia and developmental delay. Biol Psychiatry. 2013; 75(5):378-85. PMC: 4229045. DOI: 10.1016/j.biopsych.2013.07.022. View

Singer A, Maya I, Koifman A, Samra N, Baris H, Falik-Zaccai T . Microarray analysis in pregnancies with isolated echogenic bowel. Early Hum Dev. 2018; 119:25-28. DOI: 10.1016/j.earlhumdev.2018.02.014. View

Moczulska H, Serafin M, Wojda K, Borowiec M, Sieroszewski P . Fetal Nasal Bone Hypoplasia in the Second Trimester as a Marker of Multiple Genetic Syndromes. J Clin Med. 2022; 11(6). PMC: 8954562. DOI: 10.3390/jcm11061513. View

Nyberg D, Souter V . Sonographic markers of fetal trisomies: second trimester. J Ultrasound Med. 2001; 20(6):655-74. DOI: 10.7863/jum.2001.20.6.655. View

. Committee Opinion No. 581: the use of chromosomal microarray analysis in prenatal diagnosis. Obstet Gynecol. 2013; 122(6):1374-7. DOI: 10.1097/01.AOG.0000438962.16108.d1. View

Bromley B, Lieberman E, Shipp T, Benacerraf B . The genetic sonogram: a method of risk assessment for Down syndrome in the second trimester. J Ultrasound Med. 2002; 21(10):1087-96; quiz 1097-8. DOI: 10.7863/jum.2002.21.10.1087. View

. Screening for Fetal Chromosomal Abnormalities: ACOG Practice Bulletin, Number 226. Obstet Gynecol. 2020; 136(4):e48-e69. DOI: 10.1097/AOG.0000000000004084. View

10.

Cai M, Lin N, Chen X, Fu M, Guo N, Xu L . Evaluation of chromosomal abnormalities and copy number variations in fetuses with ultrasonic soft markers. BMC Med Genomics. 2021; 14(1):19. PMC: 7802188. DOI: 10.1186/s12920-021-00870-w. View

11.

Chang H, Li L, Li M, Xiao X . Rare and common variants at 16p11.2 are associated with schizophrenia. Schizophr Res. 2016; 184:105-108. DOI: 10.1016/j.schres.2016.11.031. View

12.

Ko H, Kwak D, Oh S, Choi S, Hong J, Hwang H . Clinical significance of soft markers in second trimester ultrasonography for pregnant Korean women: a multicenter study and literature review. Obstet Gynecol Sci. 2022; 65(2):145-155. PMC: 8942751. DOI: 10.5468/ogs.21216. View

13.

Huang H, Cai M, Ma W, Lin N, Xu L . Chromosomal Microarray Analysis for the Prenatal Diagnosis in Fetuses with Nasal Bone Hypoplasia: A Retrospective Cohort Study. Risk Manag Healthc Policy. 2021; 14:1533-1540. PMC: 8054820. DOI: 10.2147/RMHP.S286038. View

14.

Manning M, Hudgins L . Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities. Genet Med. 2010; 12(11):742-5. PMC: 3111046. DOI: 10.1097/GIM.0b013e3181f8baad. View

15.

Hassfurther A, Komini E, Fischer J, Leipoldt M . Clinical and Genetic Heterogeneity of the 15q13.3 Microdeletion Syndrome. Mol Syndromol. 2016; 6(5):222-8. PMC: 4772713. DOI: 10.1159/000443343. View

16.

Hu T, Tian T, Zhang Z, Wang J, Hu R, Xiao L . Prenatal chromosomal microarray analysis in 2466 fetuses with ultrasonographic soft markers: a prospective cohort study. Am J Obstet Gynecol. 2020; 224(5):516.e1-516.e16. DOI: 10.1016/j.ajog.2020.10.039. View

17.

Lichtenbelt K, Knoers N, Schuring-Blom G . From karyotyping to array-CGH in prenatal diagnosis. Cytogenet Genome Res. 2011; 135(3-4):241-50. DOI: 10.1159/000334065. View

18.

Pizzo L, Andrieux J, Amor D, Girirajan S . Clinical utility gene card for: 16p12.2 microdeletion. Eur J Hum Genet. 2016; 25(2). PMC: 5255956. DOI: 10.1038/ejhg.2016.158. View

19.

Maya I, Sharony R, Yacobson S, Kahana S, Yeshaya J, Tenne T . When genotype is not predictive of phenotype: implications for genetic counseling based on 21,594 chromosomal microarray analysis examinations. Genet Med. 2017; 20(1):128-131. DOI: 10.1038/gim.2017.89. View

20.

Michelson D, Shevell M, Sherr E, Moeschler J, Gropman A, Ashwal S . Evidence report: Genetic and metabolic testing on children with global developmental delay: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2011; 77(17):1629-35. DOI: 10.1212/WNL.0b013e3182345896. View