Noninvasive prenatal screening for fetal sex chromosome aneuploidies

ABSTRACT

Introduction

Sex chromosome aneuploidies (SCAs) are among the most common chromosome abnormalities observed in humans. Manifestations include low fertility, infertility, delayed language development, and dysfunction in motor development. Noninvasive prenatal screening (NIPS) based on cell-free fetal DNA from the peripheral blood of pregnant women is increasingly used for the screening of fetal chromosome abnormalities, including screening for fetal gender and fetal sex chromosome aneuploidy. A systematic review of the literature about NIPS for SCAs is needed.

Areas covered

This review evaluated a vast array of published studies focusing on the clinical significance, detection methods, performance of NIPS for SCAs, and the management of positive SCA results following screening with the aim of facilitating a comprehensive and systematic understanding of NIPS for SCAs.

Expert commentary

Looking forward, NIPS is expected to become the primary screening test for common aneuploidies as well as other chromosome abnormalities, including some micro-deletions and micro-duplications, with the potential to transition from a screening test to a prenatal diagnosis method. Ultimately, the goal is to provide a safe and accurate method for increasing early diagnosis to improve long-term outcomes for the SCA patients and families by well- informed health care providers.

KEYWORDS:

• Cell-free fetal DNA
• noninvasive prenatal screening
• genetic counseling
• prenatal diagnosis
• sex chromosome aneuploidy

Article highlights

• This review focuses on the clinical significance, detection methods and performance of NIPS for SCAs, as well as the management of positive SCA results following screening with the goal of providing a comprehensive understanding of NIPS for SCAs.

• Clinical manifestations vary among the different types of SCAs, ranging from fetal loss to clinically undetected. Early diagnosis and intervention are known to improve the neurodevelopment, cognitive and functional outcomes of SCAs patients. Prenatal diagnosis also enables pregnant women and their families to make psychological preparations in advance and seek treatment for SCAs as early as possible.

• There are three main NIPS methodologies, all of which can be used to screen for SCAs.

• Although the screening performance of NIPS for SCAs is not as good as that for trisomy 21 and trisomy 18, it still shows a high sensitivity and specificity, as well as a moderate PPV. Maternal, fetal and placental factors, among others, affect the test performance of NIPS screening for SCAs and must be taken into consideration.

• For pregnant women obtaining NIPS results negative and positive for SCAs, the focus of genetic counseling is different. The current guidelines, statements and up-to-date knowledge should be used by health professionals to provide genetic consultation before and after testing for patients who are interested in obtaining fetal sex chromosome information. Prenatal evaluations followed by postnatal examination by a multi-disciplinary team best guides the management of pregnancies with a positive NIPS result for SCAs.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by the Science and Technology Project of The Health Planning Committee of Sichuan Province (No.20PJ073). The authors wish to thank Amber N. Pursley for editing the manuscript.