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

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 (similar to 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.