Prenatal Diagnostic Testing Following High-Risk Result from Serological Screening: Which Shall We Select?

Abstract

Purpose

We retrospectively analyzed the results of prenatal diagnosis in women with high-risk (HR) serological screening results, and discussed the reasonable application of diagnostic testing.

Patients and Methods

Diagnostic testing was done in 2239 pregnant women who had HR results from serological screening in two prenatal diagnosis centers. According to the HR results, they were divided into simple HR, HR combined with ultrasound abnormalities, and HR combined with other indication groups. After receiving counselling from clinicians, they were allowed to choose either the traditional karyotype analysis and/or chromosomal microarray analysis (CMA).

Results

Those who underwent CMA comprised 49.3%, 97.6%, and 100% of the HR group, HR combined with ultrasound abnormalities, and HR combined with other indication groups, respectively. Among the 100 (4.47%) clinically significant results, 55 (2.46%), 15 (0.67%), and 30 (1.34%) were chromosomal aneuploidies, chromosomal structural abnormalities, and pathogenic copy number variations (CNVs), respectively. The rate of abnormalities was 3.77%, 13.71%, and 19.05% in the simple HR, HR combined with ultrasound abnormalities, and HR combined with other indication groups, respectively. The increasing rate of clinical pathogenic CNVs was 1.34% using CMA in HR pregnant women, 9.52% in the HR combined with other indication group, and 1.24% in the simple HR group. Among the 573 women who chose both diagnostic tests, 45 had abnormal results. Only one case detected using karyotype analysis was missed on CMA. The incidence of chromosomal aneuploidy tended to increase with increase in HR values. However, chromosomal structural abnormalities and pathogenic CNVs did not increase.

Conclusion

CMA should be recommended as the first-line diagnostic testing for women with HR screening results, especially combined with other abnormal indications.

Keywords:

• prenatal screening
• prenatal diagnosis
• karyotype analysis
• chromosomal microarray analysis
• high risk

Ethics Approval and Consent to Participate

The study design and protocol were reviewed and approved by the ethics committee of Changzhou Maternity and Child Health Care Hospital affiliated to Nanjing Medical University (No. 2017003). All pregnant women received genetic counseling and signed a written consent before the test. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent for Publication

Informed consent was obtained from all individual participants included in the study.

Acknowledgments

We thank all the project participants for their contributions.

Disclosure

The authors declare that they have no conflicts of interest.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (81773438), key research and development plan project of Jiangsu Province (BE2018677), Changzhou Key Laboratory of High-tech Research (CM20193009) and Jiangsu Maternal and Children health care key discipline (FXK201754).