Noninvasive prenatal testing (NIPT) is widely used to screen for common fetal chromosomal aneuploidies. However, the ability of NIPT-Plus to detect copy number variation (CNV) is debatable. Accordingly, we assessed the efficiency of NIPT-Plus to detect clinically significant fetal CNV. We performed a prospective analysis of 31,260 singleton pregnancies, included from June 2017 to December 2020. Cell-free fetal DNA was directly sequenced using the semiconductor sequencing platform for women with high-risk CNV with clinically significant results. Fetal karyotyping and chromosomal microarray analysis (or next-generation sequencing) are recommended for invasive diagnostic procedures. Women at low risk with no other abnormal results continued their pregnancies. We analyzed the expanded NIPT results, diagnostic test results, and follow-up information to evaluate its performance in detecting fetal CNV. Of the 31,260 pregnant women who received NIPT-Plus, 31,256 cases were tested successfully, a high risk of clinically significant CNV was detected in 221 cases (0.71%); 18 women refused further diagnosis; 203 women underwent invasive prenatal diagnosis; and 78 true positive cases and 125 false positive cases, with an overall positive predictive value (PPV) of 38.42% and a false positive rate of 0.40%. For known microdeletion/microduplication syndromes (n = 27), the PPVs were 75% DiGeorge syndrome (DGS), 80% 22q11.22 microduplication, 50% Prader–Willi syndrome, and 50% cri-du-chat. For the remaining clinically significant fetal CNVs (n = 175), the combined PPVs were 46.5% (CNVs > 10 Mb) and 28.57% (CNVs ≤ 10 Mb). NIPT-Plus screening for CNV has certain clinical value. NIPT-Plus yielded relatively high PPVs for 22q11.2 microduplication syndrome and DGS, and low to moderate PPVs for other CNVs.

Thalassemia, an inherited hemoglobin synthesis disorder, imposes a significant health burden in Asian regions with high prevalence. Detailed patterns and trends of the disease across countries and territories within these regions remain underexplored. Our study focuses on the disease burden indices of thalassemia within the four GBD-defined Asian regions and the twenty-five included countries and territories. It provides insights into the gender-age distribution, temporal changes, and economic aspects of the thalassemia burden. Data on thalassemia prevalence, incidence, mortality, and Disability-Adjusted Life Years (DALYs) were extracted from the Global Burden of Disease (GBD) 2021 study for South, East, Southeast, and high-income Asia regions, encompassing the relevant countries and territories from 1990 to 2021. The Average Annual Percent Change (AAPC) in age-standardized rates of thalassemia was determined to assess temporal trends. Age-gender cohort proportions were considered. The economic aspect of the disease burden and frontier analysis were evaluated using the GBD Socio-Demographic Index and Global Health Expenditure data. Southeast Asia exhibited notably high age-standardized mortality rate (ASMR), age-standardized prevalence rate (ASPR), and age-standardized DALYs rate among the four studied Asian regions in 2021. The East Asia region had recorded the highest age-standardized incidence rate (ASIR). A general decline in disease burden indices across the four regions from 1990 to 2021 was evident, with the exception of ASIR in Southeast Asia. The ASMR was highest among pediatric population under five years old, with a significant male preponderance. An unusual increase in ASMR was detected among females of childbearing age and the elderly within the studied region. Further analysis had identified six high-burden countries and territories, particularly those with low-middle Socio-Demographic Index (SDI) rankings and limited health expenditure. Although the overall burden of thalassemia has decreased substantially, the disease burden was influenced by gender, age, geography, temporal trends, and economic factors in distinct manners. Based on the current SDI, many countries and regions still have greater improvement potential in the disease burden. There is a necessity for enhanced attention and resource allocation, particularly in low-middle and low SDI countries, with an emphasis on policies that promote early diagnosis and comprehensive care.

Application of chromosomal microarray analysis (CMA) to investigate the genetic characteristics of fetal growth restriction (FGR) without ultrasonic structural anomalies at 18–32 weeks. This study includes singleton fetuses with the estimated fetal weight (EFW) using the formula of Hadlock C below the 10th percentile for gestational age. FGRs without structural anomalies were selected, and the ones at high risk of noninvasive prenatal testing for trisomy 13, 18 and 21 would be excluded. The cases were divided into two groups: early-onset group (< 24+ 0 weeks) and late-onset group (24–33 weeks). All patients were offered invasive prenatal testing with CMA and karyotype analysis. CMA detected 10 pathogenic copy number variants and 2 variant of uncertain significance case. CMA has a 5.5% (7/127) incremental yield of pathogenic chromosomal abnormalities over karyotyping. The positive detected rate was 9.6% (5/52) in early-onset group and 9.3% (7/75) in late-onset group respectively. When FGR without structural anomaly is diagnosed before 33 weeks, an invasive prenatal procedure is strongly recommended. CMA can identify a 5.5% (7/127) incremental detection rate of pathogenic chromosomal abnormalities, which would impact clinical management for FGR.

Background: Some ultrasonic soft markers can be found during ultrasound examination. However, the etiology of the fetuses with ultrasonic soft markers is still unknown. This study aimed to evaluate the genetic etiology and clinical value of chromosomal abnormalities and copy number variations (CNVs) in fetuses with ultrasonic soft markers. Methods: Among 1131 fetuses, 729 had single ultrasonic soft marker, 322 had two ultrasonic soft markers, and 80 had three or more ultrasonic soft markers. All fetuses underwent conventional karyotyping, followed by single nucleotide polymorphism (SNP) array analysis. Results: Among 1131 fetuses with ultrasonic soft markers, 46 had chromosomal abnormalities. In addition to the 46 fetuses with chromosomal abnormalities consistent with the results of the karyotyping analysis, the SNP array identified additional 6.1% (69/1131) abnormal CNVs. The rate of abnormal CNVs in fetuses with ultrasonic soft marker, two ultrasonic soft markers, three or more ultrasonic soft markers were 6.2%, 6.2%, and 5.0%, respectively. No significant difference was found in the rate of abnormal CNVs among the groups. Conclusions: Genetic abnormalities affect obstetrical outcomes. The SNP array can fully complement conventional karyotyping in fetuses with ultrasonic soft markers, improve detection rate of chromosomal abnormalities, and affect pregnancy outcomes.

In Guangxi, Hainan, and Fujian Province in southern China, β-thalassemia is a frequent monogenic hereditary disorder that is primarily defined by hemolytic anemia brought on by inefficient erythropoiesis. It has been found that ineffective erythropoiesis in β-thalassemia is closely associated with a high accumulation of Reactive oxygen species, a product of oxidative stress, in erythroid cells. During recent years, ferroptosis is an iron-dependent lipid peroxidation that involves abnormalities in lipid and iron metabolism as well as reactive oxygen species homeostasis. It is a recently identified kind of programmed cell death. β-thalassemia patients experience increased iron release from reticuloendothelial cells and intestinal absorption of iron, ultimately resulting in iron overload. Additionally, the secretion of Hepcidin is inhibited in these patients. What counts is both ineffective erythropoiesis and ferroptosis in β-thalassemia are intricately linked to the iron metabolism and Reactive oxygen species homeostasis. Consequently, to shed further light on the pathophysiology of β-thalassemia and propose fresh ideas for its therapy, this paper reviews ferroptosis, ineffective erythropoiesis, and the way they interact.

Background: MicroRNAs (miRNAs) participate in the reactivation of γ‐globin expression in β‐thalassemia. However, the miRNA transcriptional profiles of pediatric β‐thalassemia remain unclear. Accordingly, in this study, we assessed miRNA expression in pediatric patients with β‐thalassemia.Methods: Differentially expressed miRNAs in pediatric patients with β‐thalassemia were determined using microRNA sequencing.Results: Hsa‐miR‐483‐3p, hsa‐let‐7f‐1‐3p, hsa‐let‐7a‐3p, hsa‐miR‐543, hsa‐miR‐433‐3p, hsa‐miR‐4435, hsa‐miR‐329‐3p, hsa‐miR‐92b‐5p, hsa‐miR‐6747‐3p and hsa‐miR‐495‐3p were significantly upregulated, whereas hsa‐miR‐4508, hsa‐miR‐20a‐5p, hsa‐let‐7b‐5p, hsa‐miR‐93‐5p, hsa‐let‐7i‐5p, hsa‐miR‐6501‐5p, hsa‐miR‐221‐3p, hsa‐let‐7g‐5p, hsa‐miR‐106a‐5p, and hsa‐miR‐17‐5p were significantly downregulated in pediatric patients with β‐thalassemia. After integrating our data with a previously published dataset, we found that hsa‐let‐7b‐5p and hsa‐let‐7i‐5p expression levels were also lower in adolescent or adult patients with β‐thalassemia. The predicted target genes of hsa‐let‐7b‐5p and hsa‐let‐7i‐5p were associated with the transforming growth factor β receptor, phosphatidylinositol 3‐kinase/AKT, FoxO, Hippo, and mitogen‐activated protein kinase signaling pathways. We also identified 12 target genes of hsa‐let‐7a‐3p and hsa‐let‐7f‐1‐3p and 21 target genes of hsa‐let‐7a‐3p and hsa‐let‐7f‐1‐3p, which were differentially expressed in patients with β‐thalassemia. Finally, we found that hsa‐miR‐190‐5p and hsa‐miR‐1278‐5p may regulate hemoglobin switching by modulation of the B‐cell lymphoma/leukemia 11A gene.Conclusion: The results of the study show that several microRNAs are dysregulated in pediatric β‐thalassemia. Further, the results also indicate toward a critical role of let7 miRNAs in the pathogenesis of pediatric β‐thalassemia, which needs to be investigated further.