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Prenatal Diagnosis by Chromosome Microarray Analysis, An Indian Experience

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Abstract

Background

Karyotyping has been the gold standard for prenatal chromosome analysis. The resolution should be higher by chromosome microarray analysis (CMA). The challenge lies in recognizing benign and pathogenic or clinically significant copy number variations (pCNV) and variations of unknown significance (VOUS). The aim was to evaluate the diagnostic yield and clinical utility of CMA, to stratify the CMA results in various prenatal referral groups and to accumulate Indian data of pCNVs and VOUS for further interpretation to assist defined genetic counseling.

Methods

Karyotyping and CMA were performed on consecutive referrals of 370 prenatal samples of amniotic fluid (n = 274) and chorionic villi (n = 96) from Indian pregnant women with high maternal age (n = 23), biochemical screen positive (n = 61), previous child abnormal (n = 59), abnormal fetal ultrasound (n = 205) and heterozygous parents (n = 22).

Results and Conclusion

The overall diagnostic yield of abnormal results was 5.40% by karyotyping and 9.18% by CMA. The highest percentage of pCNVs were found in the group with abnormal fetal ultrasound (5.40%) as compared to other groups, such as women with high maternal age (0.81%), biochemical screen positive (0.54%), previous abnormal offspring (0.81%) or heterozygous parents group (1.62%). Therefore, all women with abnormal fetal ultrasound must undergo CMA test for genotype–phenotype correlation. CMA detects known and rare deletion/duplication syndromes and characterizes marker chromosomes. Accumulation of CNV data will form an Indian Repository and also help to resolve the uncertainty of VOUS. Pretest and posttest genetic counseling is essential to convey benefits and limitations of CMA and help the patients to take informed decisions.

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Acknowledgements

We are thankful to Indian Council of Medical Research and Department of Health and research, New Delhi, for providing the research grant for this study (Project Code: 1.3.2.183/005). We also thank the patients, the referring clinicians, department of fetal medicine and the cytogenetics laboratory staff for their support.

Funding

This study was supported by funding grants from Indian Council of Medical Research/Department of Health Research (Project Code: 1.3.2.183/005).

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Authors and Affiliations

  1. Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, 110060, India

    Meena Bajaj Lall, Shruti Agarwal, Preeti Paliwal, Pushpa Saviour, Anju Joshi, Arti Joshi, Surbhi Mahajan, Sunita Bijarnia-Mahay, Ratna Dua Puri & I. C. Verma

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  1. Meena Bajaj Lall
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  2. Shruti Agarwal
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Correspondence to Meena Bajaj Lall.

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The authors declare that there is no conflict of interests.

Ethical Approval

The study was performed in accordance with the ethical standards of the responsible committee on human experimentation and with Helsinki Declaration of 1975, as revised in 2008. The study was approved by the ethics committee of our institute (EC/11/12/435).

Informed Consent

Informed consent was obtained from all the patients for being included in the study.

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Dr. Lall Bajaj Meena Ph.D., Senior Consultant and Head, Clinical Cytogenetic Laboratory, Institute of Medical Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi. She is also a Professor and teaching faculty for DNB programme and a Ph.D. guide. Agarwal Shruti Ph.D. Institute of Medical Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi, India. Paliwal Preeti Ph.D. Institute of Medical Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi, India. Saviour Pushpa Ph.D. Institute of Medical Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi, India. Joshi Anju M.Sc. Institute of Medical Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi, India. Joshi Arti M.Sc. Institute of Medical Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi, India. Mahajan Surbhi Ph.D. Institute of Medical Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi, India. Bijarnia-Mahay Sunita MBBS, DNB, DCH Institute of Medical Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi, India. Puri Dua Ratna MBBS, MD, DM Institute of Medical Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi, India. I. C. Verma MBBS, MRCP, DCH, MNAMS Institute of Medical Genetics and Genomics at Sir Ganga Ram Hospital, New Delhi, India.

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Bajaj Lall, M., Agarwal, S., Paliwal, P. et al. Prenatal Diagnosis by Chromosome Microarray Analysis, An Indian Experience. J Obstet Gynecol India 71, 156–167 (2021). https://doi.org/10.1007/s13224-020-01413-6

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