Incidence of sex chromosome aneuploidy in a prenatal population: 27-year longitudinal study in Northern Italy.

OBJECTIVES: The availability of cell-free (cf) DNA as a prenatal screening tool affords an opportunity for non-invasive identification of sex chromosome aneuploidy (SCA). The aims of this longitudinal study were to investigate the evolution and frequency of both invasive prenatal diagnostic testing, using amniocentesis and chorionic villus sampling (CVS), and the detection of SCA in cfDNA samples from a large unselected cohort in Northern Italy. METHODS: The results of genetic testing from CVS and amniotic fluid samples received from public and private centers in Italy from 1995 to 2021 were collected. Chromosomal analysis was performed by routine Q-banding karyotype. Regression analyses and descriptive statistics were used to determine population data trends regarding the frequency of prenatal diagnostic testing and the identification of SCA, and these were compared with the changes in indication for prenatal diagnostic tests and available screening options. RESULTS: Over a period of 27 years, there were 13 939 526 recorded births and 231 227 invasive procedures were performed, resulting in the prenatal diagnosis of 933 SCAs. After the commercial introduction of cfDNA use in 2015, the frequency of invasive procedures decreased significantly (P = 0.03), while the frequency of prenatal SCA detection increased significantly (P = 0.007). Between 2016 and 2021, a high-risk cfDNA result was the indication for 31.4% of detected sex chromosome trisomies, second only to advanced maternal age. CONCLUSIONS: Our findings suggest that the inclusion of SCA in prenatal cfDNA screening tests can increase the prenatal diagnosis of affected individuals. As the benefits of early ascertainment are increasingly recognized, it is essential that healthcare providers are equipped with comprehensive and evidence-based information regarding the associated phenotypic differences and the availability of targeted effective interventions to improve neurodevelopmental and health outcomes for affected individuals. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

First-trimester chromosome diagnosis by lavage of the uterine cavity.

Fetal karyotyping of trophoblast cells obtained by lavage of the uterine cavity was evaluated on 86 first-trimester irrigation fluid samples. Villus fragments were observed in 72 fluid samples indicating an 83.7 per cent sampling success rate. The amount of villi in these samples ranged from 1 to 32 mg. In most cases, villus fragments showed degeneration of the external syncytiotrophoblast layer and absence of blood vessels. In the first phase of this study (15 samples), a high degree of maternal cell contamination was observed after long-term cultures. In the following phase (71 samples), this obstacle was overcome by the application of a semi-direct method. Chromosome preparations were set up after 24 h incubation of villus fragments and QFQ-banded metaphase spreads were scored for chromosome number and sex. Sixty samples showed the presence of villus fragments and the fetal karyotype was established in 40. Male and female chromosome complements were observed in 16 and 24 cases, respectively. In four cases, an abnormal fetal karyotype was diagnosed. These included trisomy of chromosomes 13, 15, and 16, and one mosaic with trisomy 12. Our results indicate that first-trimester fetal karyotyping might be feasible by a semi-direct method using chorionic villus fragments obtained at intrauterine lavage.