OBJECTIVE: This study evaluated the BACs-on-Beads™ (BoBs) efficiency assay in detecting chromosomal anomalies in products of conception (POC) specimens associated with anembryonic pregnancy (AP) among Thai pregnant women.
METHODS: Retrospective analysis applied the BoBs™ assay to examine AP samples from 2010 to 2022. The incidences of AP with chromosomal abnormalities were reported.
RESULTS: Assessment of villi from anembryonic pregnancy samples found normal chromosome complement in 50% of the cases, while the remainder showed chromosomal abnormalities. Trisomy 16 was found in 15% of the cases and trisomies 22, 15, and 19 in 9.6%, 3.8%, and 3.8%, respectively. Advanced maternal age was associated with a higher incidence of aneuploidy.
CONCLUSIONS: The BoBs™ assay effectively detected diverse chromosomal abnormalities in villi samples from POC. The diagnostic utility of the BoBs™ assay was highlighted in identifying chromosomal irregularities in AP cases. Trisomy 16 possessed the most chromosomal abnormalities in the AP samples.

OBJECTIVE: Studies on intestinal Behçet\'s disease (BD) complicated by myelodysplastic syndrome (MDS) are rare, and no established therapeutic guidelines exist. This study aimed to evaluate the clinical presentation and outcomes of patients with intestinal BD complicated by MDS (intestinal BD-MDS) and suggest a treatment strategy.
METHODS: Data from patients with intestinal BD-MDS from four referral centers in Korea who were diagnosed between December 2000 and December 2022 were retrospectively analyzed. Clinical features and prognosis of intestinal BD-MDS compared with age-, sex-matched intestinal BD without MDS were investigated.
RESULTS: Thirty-five patients with intestinal BD-MDS were included, and 24 (70.6%) had trisomy 8. Among the 35 patients, 23 (65.7%) were female, and the median age at diagnosis for intestinal BD was 46.0 years (range, 37.0-56.0 years). Medical treatments only benefited eight of the 32 patients, and half of the patients underwent surgery due to complications. Compared to 70 matched patients with intestinal BD alone, patients with intestinal BD-MDS underwent surgery more frequently (51.4% vs. 24.3%; p=0.010), showed a poorer response to medical and/or surgical treatment (75.0% vs. 11.4%; p<0.001), and had a higher mortality (28.6% vs. 0%; p<0.001). Seven out of 35 patients with intestinal BD-MDS underwent hematopoietic stem cell transplantation (HSCT), and four out of the seven patients had a poor response to medical treatment prior to HSCT, resulting in complete remission of both diseases.
CONCLUSIONS: Patients with intestinal BD-MDS frequently have refractory diseases with high mortalities. HSCT can be an effective treatment modality for medically refractory patients with intestinal BD-MDS.

BACKGROUND: To evaluate the clinical significance of noninvasive prenatal testing (NIPT) for detecting fetal sex chromosome aneuploidies (SCAs) in Korean pregnant women.
METHODS: We retrospectively analyzed NIPT data from 9,176 women with singleton pregnancies referred to the CHA Biotech genome diagnostics center. Cell-free fetal DNA (cffDNA) was extracted from maternal peripheral blood, and high-throughput massively parallel sequencing was conducted. Subsequently, the positive NIPT results for SCA were validated via karyotype and chromosomal microarray analyses.
RESULTS: Overall, 46 cases were SCA positive after NIPT, including 20, 12, 8, and 6 for Turner, triple X, Klinefelter, and Jacob syndromes, respectively. Among 37 women with invasive prenatal diagnosis, 19 had true positive NIPT results. The overall positive predictive value (PPV) of NIPT for detecting SCAs was 51.35%. The PPV was 18.75% for Turner, 88.89% for triple X, 71.43% for Klinefelter, and 60.00% for Jacob\'s syndromes. NIPT accuracy for detecting sex chromosome trisomies was higher than that for sex chromosome monosomy (P = 0.002). No significant correlation was observed between fetal SCA incidence and maternal age (P = 0.914), except for the borderline significance of Jacob\'s syndrome (P = 0.048). No significant differences were observed when comparing NIPT and karyotyping validation for fetal SCA according to pregnancy characteristics.
CONCLUSIONS: Our data suggest that NIPT can reliably screen for SCAs, and it performed better in predicting sex chromosome trisomies compared with monosomy X. No correlation was observed between maternal age and fetal SCA incidence, and no association was observed between different pregnancy characteristics. The accuracy of these findings requires improvements; however, our study provides an important reference for clinical genetic counseling and further management. Larger scale studies, considering confounding factors, are required for accurate evaluation.

UNASSIGNED: Trisomy 18 syndrome, also known as Edwards syndrome, is a chromosomal trisomy. The syndrome has historically been considered lethal owing to its poor prognosis, and palliative care was primarily indicated for trisomy 18 neonates. Although there have been several reports on the improvement of survival outcomes in infants with trisomy 18 syndrome through neonatal intensive care, few studies have compared the impact of neonatal intensive care on survival outcomes with that of non-intensive care. Therefore, we compared the survival-related outcomes of neonates with trisomy 18 between intensive and non-intensive care.
UNASSIGNED: Seventeen infants of trisomy 18 admitted to our center between 2007 and 2019 were retrospectively studied. We divided the patients into a non-intensive group (n = 5) and an intensive group (n = 12) and evaluated their perinatal background and survival-related outcomes of the two groups.
UNASSIGNED: The 1- and 3-year survival rates were both 33% in the intensive group, which was significantly higher than that in the non-intensive group (p < 0.001). Half of the infants in the intensive care group were discharged alive, whereas in the non-intensive care group, all died during hospitalization (p = 0.049).
UNASSIGNED: Neonatal intensive care for neonates with 18 trisomy significantly improved not only survival rates but also survival-discharge rates. Our findings would be helpful in providing 18 trisomy neonates with standard neonatal intensive care when discussing medical care with their parents.

BACKGROUND: Abnormal foetal tissue chromosome karyotypes are one of the important pathogenic factors for spontaneous abortion (SA). To investigate the age and abnormal foetal karyotypes of 1903 couples who experienced SA.
METHODS: A retrospective multicentre study collected age and foetal tissue karyotypes CNV-seq data of 1903 SA couples from 6 hospitals in 5 regions from January 2017 to March 2022. The distribution and correlation of abnormal foetal tissue karyotypes were evaluated by using regions and age.
RESULTS: In our study, 1140 couples (60.5% of the total) had abnormal foetal tissue chromosome karyotypes in all regions. We found that there were differences in the number of abnormal foetal tissue chromosome karyotypes, of which the incidence of trisomy was higher. At the same time, the populations situated in the eastern region had a more triploid (15.5%) distribution, trisomy (58.1%) in the southern region, mosaicism (14.8%) and microduplication (31.7%) in the southwestern region, microdeletion (16.7%) in the northern region. There are variances across areas, and it is more common in the north. The incidence risk of prenatal chromosomal abnormalities varied according to age group.
CONCLUSIONS: The findings of this study suggest that the karyotypes of patients with abnormal foetal tissue chromosome abortion in different regions were different. Meanwhile, patients ≥ 35 years old had a higher risk of abnormal foetal tissue chromosome abortion.

OBJECTIVE: To carry out genetic analysis for a fetus with confined placental mosaicism (CPM) for trisomy 2 (T2) in conjunct with fetal uniparental disomy (UPD).
METHODS: Amniocentesis and chromosomal karyotyping was carried out for a pregnant woman with a high risk for chromosome 2 anomalies indicated by non-invasive prenatal testing (NIPT). Single nucleotide polymorphism array (SNP-array) and trio-whole exome sequencing (Trio-WES) were carried out. Ultrasonography was used to closely monitor the fetal growth. Multifocal sampling of the placenta was performed after delivery for copy number variation sequencing (CNV-seq).
RESULTS: The fetus was found to have a normal chromosomal karyotype. SNP-array has revealed multiple regions with loss of heterozygosity (LOH) on chromosome 2. Trio-WES confirmed the presence of maternal UPD for chromosome 2. Ultrasonography has revealed intrauterine growth restriction and oligohydramnios. Intrauterine fetal demise had occurred at 23+4 weeks of gestation. Pathological examination had failed to find salient visceral abnormality. The placenta was proved to contain complete T2 by CNV-seq.
CONCLUSIONS: T2 CPM can cause false positive result for NIPT and may be complicated with fetal UPD, leading to adverse obstetric outcomes such as intrauterine growth restriction, oligohydramnios and intrauterine fetal demise.

OBJECTIVE: Children with sex chromosome trisomy (SCT) have an increased risk for suboptimal development. Difficulties with language are frequently reported, start from a very young age, and encompass various domains. This cross-sectional study examined social orientation with eye tracking and physiological arousal responses to gain more knowledge on how children perceive and respond to communicative bids and evaluated the associations between social orientation and language outcomes, concurrently and 1 year later.
METHODS: In total, 107 children with SCT (33 XXX, 50 XXY, and 24 XYY) and 102 controls (58 girls and 44 boys) aged between 1 and 7 years were included. Assessments took place in the USA and Western Europe. A communicative bids eye tracking paradigm, physiological arousal measures, and receptive and expressive language outcomes were used.
RESULTS: Compared to controls, children with SCT showed reduced attention to the face and eyes of the on-screen interaction partner and reduced physiological arousal sensitivity in response to direct versus averted gaze. In addition, social orientation to the mouth was related to concurrent receptive and expressive language abilities in 1-year-old children with SCT.
CONCLUSIONS: Children with SCT may experience difficulties with social communication that extend past the well-recognized risk for early language delays. These difficulties may underlie social-behavioral problems that have been described in the SCT population and are an important target for early monitoring and support.

BACKGROUND: In this register-based study of pregnancies in Denmark, we assessed the associations between maternal age and the risk of fetal aneuploidies (trisomy 21, trisomy 18, trisomy 13, triploidy, monosomy X and other sex chromosome aberrations). Additionally, we aimed to disentangle the maternal age-related effect on fetal aneuploidies by cases with translocation trisomies and mosaicisms.
METHODS: We followed a nationwide cohort of 542 375 singleton-pregnant women attending first trimester screening in Denmark between 2008 and 2017 until delivery, miscarriage or termination of pregnancy. We used six maternal age categories and retrieved information on genetically confirmed aneuploidies of the fetus and infant from the national cytogenetic register.
RESULTS: We confirmed the known associations between advanced maternal age and higher risk of trisomy 21, 18, 13 and other sex chromosome aberrations, especially in women aged ≥35 years, whereas we found no age-related associations with triploidy or monosomy X. Cases with translocation trisomies and mosaicisms did not influence the overall reported association between maternal age and aneuploidies.
CONCLUSIONS: This study provides insight into the accurate risk of fetal aneuploidies that pregnant women of advanced ages encounter.

OBJECTIVE: To evaluate cell-free DNA (cfDNA) testing as a non-invasive approach to detecting aneuploidies in clinical miscarriages.
METHODS: A retrospective cohort study of women with pregnancy loss.
METHODS: Hospitals and genetic analysis laboratories.
METHODS: Pregnancy losses in the period 2021-2022.
METHODS: Results derived from non-invasive cfDNA testing (Veriseq NIPT Solution V2) of maternal blood and invasive analysis of products of conception (POC) (Ion ReproSeq) compared in 120 women who suffered a miscarriage.
METHODS: Concordance rate results, cfDNA testing performance, non-informative rate (NIR) and fetal fraction (FF).
RESULTS: We found no significant differences in the NIR between invasive (iPOC) and non-invasive (niPOC) analysis of POC (10.0% [12/120] versus 16.7% [20/120]). Of 120 samples, 90 provided an informative result in iPOC and niPOC groups (75%). cfDNA analysis correctly identified 74/87 (85.1%) samples (excluding triploidies). Sensitivity and specificity were 79.4% and 100%, respectively; all discordant cases were female. A binomial logistic model suggested fetal sex as the only variable influencing the concordance rate (P = 0.035). A Y-chromosome-based FF estimate allowed the optimal reclassification of cfDNA of non-informative male fetuses and a more accurate evaluation of cfDNA testing performance. The difference between the two FF estimates (native algorithm and Y-chromosome-based) suggests that female non-concordant cases may represent non-informative cases.
CONCLUSIONS: Cell-free DNA-based testing provides a non-invasive approach to determining the genetic cause of clinical miscarriage.