Sex chromosome aneuploidy screened by non-invasive prenatal testing from 35 827 singletons: prenatal diagnosis and pregnancy determinations

Objective To assess the positive predictive value (PPV) of fetal sex chromosome aneuploidy (SCA) identified by non-invasive prenatal testing (NIPT) and investigate families' acceptance of SCA fetus. Methods All suspected SCA cases screened by NIPT from singletons were reviewed in Prenatal Diagnosis Center of Shanghai First Maternity and Infant Hospital from April 1, 2015 to October 31, 2017. Maternal age, NIPT indications, prenatal diagnosis protocols, testing results and their pregnancy determinations were analyzed. Results NIPT was provided to 35 827 singletons and 86 suspected SCA cases were identified out of 35 823 successful ones, giving a positive detection rate of 0.24%. The average maternal age was (31.5±5.0) years. After genetic counseling, 20 patients declined prenatal diagnosis, the rest 66 cases proceeded with aminiocentesis and fetal chromosomal testing, of which 32 were cytogenetically diagnosed as SCA with the PPV of 48.5% . The SCA fetus consisted of 25 sex chromosome trisomies (seven cases of 47,XXX, three cases of 47,XYY and 15 cases of 47,XXY), one monosomy X (45,X), three mosacisms (47,XXY/48,XXYY, 47,XXX/45,X, 45,X/46,XX, one for each) and three microdeletions/microduplications. Besides, two false positive NIPT cases were proved to be low level of maternal mosacism (45,X/46,XX, 5% and 10% for each). After genetic counseling, 17 out of 20 who declined prenatal diagnosis and 9 out of 32 who diagnosed fetal SCAs continued their pregnancies, with a combined proportion of continued pregnancy of 50%. Thirty-four pregnancies were also continued after exclusion of SCA. Interestingly, the proportion of continued pregnancy among those sex chromosomal trisomy fetuses was only 32%(8/25). Conclusions As a safe and rapid prenatal testing for common autosomal aneuploidies, NIPT could also identify some types of SCA, but with relatively low PPV. More long-term researches are required to determine its sensitivity and specificity. For some types of SCA with mild phenotypes, some family would continue the pregnancy. Therefore, limitations of NIPT should be appropriately explained during both pre- and post-testing counseling. Key words: Non-invasive prenatal testing; Sex chromosome aberrations; Prenatal diagnosis; Aneuploidy; Chimera; Predictive value of tests