Current genetic counseling practice in the United States following positive non‐invasive prenatal testing for sex chromosome abnormalities

Abstract

The purpose of this study was to describe current genetic counseling practice in the United States following a non‐invasive prenatal testing (NIPT) result positive for a sex chromosome abnormality (SCA). Screening for SCAs can be confounded by confined placental mosaicism, natural loss of the X chromosome from maternal cells during aging, and undiagnosed maternal SCA or copy number variant (CNV). Furthermore, with the exception of 45,X, individuals with SCAs usually have no ultrasound or postnatal findings. This makes follow‐up for unresolved positive NIPT necessary; however, there are currently no clinical guidelines. This study used a cross‐sectional design with an anonymous questionnaire to survey 176 genetic counselors. The majority of prenatal respondents always offered diagnostic testing (>88%) and anatomy ultrasound (~90%), but the percent consistently offering maternal karyotype (22%–52%) and postnatal evaluation (28%–87%) varied. Maternal karyotype was offered more often when NIPT was positive for 45,X or 47,XXX and patients had normal prenatal diagnostic testing (p < 0.02) or declined testing (p < 0.02). Offer of postnatal evaluation was more likely when diagnostic testing was declined (p < 0.001). The majority of pediatric providers always offered a postnatal karyotype for the newborn (>72%) but the percent offering maternal karyotype (6%–46%) varied widely. With the current inconsistencies, many newborns with undiagnosed SCAs who could benefit from growth hormone therapy, early intervention, and/or targeted surveillance may be missed. Therefore, there is a need for professional guidelines to help improve the consistency of clinical care for patients with NIPT results positive for SCAs.

An assessment of the analytical performance of non‐invasive prenatal testing (NIPT) in detecting sex chromosome aneuploidies: 34,717‐patient sample in a single prenatal diagnosis Centre in China

“…32 Once the pregnancies were confirmed as SCAs by prenatal diagnosis, genetic counselling information that is accurate, updated and relevant should be provided to the pregnant woman and her family. 33,34 Genetic counselling should include the SCA prognosis, early intervention or any expected treatment research progress so that the pregnant women and their families could obtain sufficient information to help them make the best decision. Therefore, genetic counselling physicians However, recent research has shown that after conduct SCAs prenatal diagnosis, the baby can allow earlier intervention and care as well as not miss the optimal timing of early medical intervention and education.…”

Efficiency of Noninvasive Prenatal Testing for Sex Chromosome Aneuploidies

“…In a previous study, up to 50% women with 45,X were mosaic and the incidence of SCAs may be higher than the estimation [17]. However, SCAs screening remains controversial as it may lead to an increase in sex selection and NIPT would contribute to screening for relatively benign conditions (e.g., 47,XXX and 47,XYY) which are still difficult for genetic counseling and parental decisions [17,26]. On this basis, it is vital to inform pregnant women and family members about the accuracy of cfDNA testing in the context of SCAs.…”

“…SCAs are the most frequent aneuploidy in human beings with an estimated prevalence of over 1/500 [25]. In a previous study, up to 50% women with 45,X were mosaic and the incidence of SCAs may be higher than the estimation [17]. However, SCAs screening remains controversial as it may lead to an increase in sex selection and NIPT would contribute to screening for relatively benign conditions (e.g., 47,XXX and 47,XYY) which are still difficult for genetic counseling and parental decisions [17,26].…”

“…The positive predictive value (PPV) of SCAs screening was consistently lower in respect of autosomal trisomies. This could be related to confined placental mosaicism (CPM), abnormal maternal SCAs, including full maternal SCA, mosaic maternal SCA, and maternal copy number variants, as well as loss of an X chromosome from maternal cells as a natural part of aging [16][17][18][19][20][21][22]. Therefore, there is a lack of reliable data on SCA rates.…”

IVF and ICSI outcomes of female patients with X chromosome mosaicism: A 5-year retrospective cohort study

“…Non-invasive prenatal testing (NIPT) shouldn't be recommended to them because of the maternal mosaicism [20][21][22].…”