APA scoring system: a novel predictive model based on risk factors of pregnancy loss for recurrent spontaneous abortion patients.

The aim of this study was to analyse the risk factors of pregnancy loss of patients with recurrent spontaneous abortion (RSA) and develop a scoring system to predict RSA. Clinical data of 242 cases, with RSA who were treated at Fujian Provincial Maternity and Children's Hospital, were selected. The factors of pregnancy loss for RSA patients were evaluated by univariate and multivariate analyses. There were 242 RSA patients, of whom 34 (14.0%) developed pregnancy loss. A multivariate analysis showed the following adverse risk factors for RSA: antinuclear antibody spectrum, protein s deficiency and antiphospholipid antibodies. The pregnancy loss rates of antinuclear antibody spectrum group, protein S deficiency group and antiphospholipid antibodies group were 25.0%, 22.5% and 19.4%, respectively. Each of these factors contributed 1 point to the risk score. The pregnancy loss rates were 6.3%, 24.6%, 50% for the low-, intermediate- and high-risk categories, respectively (p < .001). The area under the receiver operating characteristic curve for the score of RSA was .733. Our findings suggest that this validated and simple scoring system could accurately predict the risk of pregnancy loss of RSA patients. The score might be helpful in the selection of risk-adapted interventions to decrease the incidence. Impact StatementWhat is already known on this subject? The live birth rate increases to 80%-90% after anticoagulant and/or immunosuppressive treatment in patients with RSA. However, there is still a high rate of re-abortion even after active treatment.What do the results of this study add? Antinuclear antibody spectrum, protein s deficiency and antiphospholipid antibodies were independent risk factors for pregnancy loss. A novel predictive model based on these factors was then established and validated.What are the implications of these findings for clinical practice and/or further research? The newly developed score might be helpful in the selection of risk-adapted interventions to decrease the incidence. For patients in the intermediate-risk and high-risk groups, we should conduct more targeted studies and formulate corresponding therapies to improve the success rate of treatment.

[Effectiveness of non-invasive prenatal screening for the detection of fetal sex chromosome anomalies].

OBJECTIVE: To evaluate the efficacy of non-invasive prenatal screening (NIPS) for fetal sex chromosome anomalies. METHODS: A retrospective analysis was carried out for 20 802 women undergoing NIPS screening. For 165 cases suspected for fetal sex chromosomal anomalies, the results of invasive prenatal diagnosis were obtained. RESULTS: Among the 165 cases suspected for fetal sex chromosome anomalies, 129 have accepted invasive prenatal diagnosis, and 45 were confirmed, which yielded a positive predictive value of 34.88%. These included 16 cases of 47,XYY, 10 cases of 47,XXY, 6 cases of 45,X/46,XX, 5 cases of 47,XXX, 3 cases of 45,X, 1 case of 45,X/46,X,i(X)(q10), 1 case of 45,X/46,X,del(X)(q22), 1 case of 46,X,del(X)(q22), 1 case of 46,X,del(X)(p11) and 1 case of Xp22.31 1.2 Mb deletion. CONCLUSION: NIPS has limited value for detecting fetal sex chromosome anomalies. Karyotyping analysis combined with other diagnostic techniques can offer effective prenatal diagnosis for suspected cases.

Detection of copy number disorders associated with congenital anomalies of the kidney and urinary tract in fetuses via single nucleotide polymorphism arrays.

BACKGROUND: While congenital anomalies of the kidney and urinary tract (CAKUT) constitute one-third of all congenital malformations, the mechanisms underlying their development are poorly understood. Some studies have reported an association between CAKUT and copy number variations (CNVs) in children and adults, but few have focused on chromosomal microarray analysis (CMA) findings in fetuses with CAKUT. Therefore, we aimed to perform a CMA on fetuses with CAKUT and normal karyotypes in the presence and absence of other structural anomalies. METHOD: The study was conducted in 147 fetuses with CAKUT and normal karyotypes between January 2016 and January 2019 in the Fujian Provincial Maternal and Child Health Hospital. Single nucleotide polymorphism (SNP) analysis was performed using the Affymetrix CytoScan HD platform. RESULTS: The SNP array identified abnormal CNVs in 13 cases (8.8%): Six were pathogenic, and seven were variations of uncertain clinical significance (VOUS). The detection rate of abnormal CNVs in non-isolated CAKUT was higher than that in isolated CAKUT (22.7% vs 6.4%, P = .038). Within the abnormal CNV groups, the highest frequency of CNVs was identified in fetuses with polycystic kidney dysplasia (13.5%), followed by those with renal agenesis (10.5%). CONCLUSION: SNP array is effective for identifying chromosomal abnormalities in CNVs in fetuses with CAKUT and normal karyotypes, and help counseling.

Experience of copy number variation sequencing applied in spontaneous abortion.

PURPOSE: We evaluated the value of copy number variation sequencing (CNV-seq) and quantitative fluorescence (QF)-PCR for analyzing chromosomal abnormalities (CA) in spontaneous abortion specimens. METHODS: A total of 650 products of conception (POCs) were collected from spontaneous abortion between April 2018 and May 2020. CNV-seq and QF-PCR were performed to determine the characteristics and frequencies of copy number variants (CNVs) with clinical significance. The clinical features of the patients were recorded. RESULTS: Clinically significant chromosomal abnormalities were identified in 355 (54.6%) POCs, of which 217 (33.4%) were autosomal trisomies, 42(6.5%) were chromosomal monosomies and 40 (6.2%) were pathogenic CNVs (pCNVs). Chromosomal trisomy occurs mainly on chromosomes 15, 16, 18, 21and 22. Monosomy X was not associated with the maternal or gestational age. The frequency of chromosomal abnormalities in miscarriages from women with a normal live birth history was 55.3%; it was 54.4% from women without a normal live birth history (P > 0.05). There were no significant differences among women without, with 1, and with ≥ 2 previous miscarriages regarding the rate of chromosomal abnormalities (P > 0.05); CNVs were less frequently detected in women with advanced maternal age than in women aged ≤ 29 and 30-34 years (P < 0.05). CONCLUSION: Chromosomal abnormalities are the most common cause of pregnancy loss, and maternal and gestational ages are strongly associated with fetal autosomal trisomy aberrations. Embryo chromosomal examination is recommended regardless of the gestational age, modes of conception or previous abortion status.

Contribution of uniparental disomy to fetal growth restriction: a whole-exome sequencing series in a prenatal setting.

Fetal growth restriction (FGR), a leading cause of perinatal morbidity and mortality, is caused by fetal, maternal, and placental factors. Uniparental disomy (UPD) is a rare condition that leads to imprinting effects, low-level mosaic aneuploidies and homozygosity for pathogenic variants. In the present study, UPD events were detected in 5 women with FGR by trio exome sequencing (trio-WES) of a cohort of 150 FGR cases. Furthermore, noninvasive prenatal testing results of the 5 patients revealed a high risk of rare autosomal trisomy. Trio-WES showed no copy-number variations (CNVs) or nondisease-causing mutations associated with FGR. Among the 5 women with FGR, two showed gene imprinting, and two exhibited confined placental mosaicism (CPM) by copy number variant sequencing (CNV-seq). The present study showed that in FGR patients with UPD, the detection of imprinted genes and CPM could enhance the genetic diagnosis of FGR.

Genetic disorders and pregnancy outcomes of non-immune hydrops fetalis in a tertiary referral center.

OBJECTIVES: Non-immune hydrops fetalis (NIHF) is a non-specific symptom associated with a wide range of disorders. The prognosis of NIHF depends on the underlying etiology. In this study, we investigated the incidence of chromosomal abnormalities and Bart's hydrops fetalis in pregnancies associated with NIHF in South China. METHODS: We conducted a retrospective review of NIHF pregnancies referred to the Fujian Provincial Maternity and Children's Hospital between 2014 and 2018, excluding pregnancies with maternal alloimmunization. Routine karyotyping was performed on all 129 enrolled patients, and chromosomal microarray analysis was performed for 35 cases with a normal karyotype. In addition, α-thalassemia genotyping was performed to confirm the presence of Bart's hydrops fetalis. RESULTS: Chromosomal abnormalities were detected in 29.5% (38/129) of the cohort, including 37 cases with aneuploidy and one case with unbalanced structural rearrangement. Chromosomal microarray analysis performed on the 35 cases with a normal karyotype did not reveal any additional pathogenic variants. The proportions of chromosomal abnormalities declined with trimester progression, with frequencies of 65%, 30.1%, and 8.3% in the first, second, and third trimesters, respectively (p < 0.05). Bart's hydrops fetalis was detected in 34.9% (45/129) of the cohort. Among the 46 (35.6%) cases with unknown etiology, 23 cases had other ultrasonic abnormalities characterized by poor outcomes, whereas seven cases with multiple cavity effusions that resolved or remitted prior to birth showed normal development during the 3-4 years of follow-up. CONCLUSIONS: In South China, Bart's hydrops fetalis and chromosomal abnormalities are the most common genetic etiologies of NIHF. Generalized skin edema and accompanying ultrasonic abnormalities are predictive of adverse outcomes, highlighting the need for intensive monitoring and better pregnancy management of NIHF patients.

Comprehensive Assessment of Fetal Bilateral Ventriculomegaly Based on Genetic Disorders, Cytomegalovirus Infection, Extra Prenatal Imaging and Pregnancy Outcomes in a Tertiary Referral Center.

OBJECTIVE: This retrospective study aimed to systematically evaluate the genetic disorders, cytomegalovirus (CMV) infection, extra ultrasound findings and outcomes of fetuses with bilateral ventriculomegaly (BVM). METHODS: Data from pregnancies with fetal BVM were obtained between 2014 and 2020. The cases were divided into groups of isolated bilateral ventriculomegaly (IBVM) and non-isolated bilateral ventriculomegaly (NIBVM) according to the presence of extra prenatal imaging. Subgroups of mild, moderate, and severe were determined according to lateral ventricle widths. The NIBVM group was further classified into pregnancies with soft markers, non-structural abnormalities, and structural abnormalities. RESULTS: A total of 353 pregnancies were enrolled, including 153 cases of IBVM and 200 cases of NIBVM. Conventional karyotyping was performed on 192 samples, and 15 cases of numerical abnormalities and 3 cases of unbalanced structural abnormalities were identified. Chromosomal microarray analysis (CMA) was concurrently performed on 108 of them and revealed additional 5 cases (4.7%) of copy number variants with clinical significance. CMV DNA testing was performed on 154 of the 192 cases that underwent invasive prenatal diagnosis, and a positive result was found in 2 (1.3%) cases. In the IBVM group, the percentage of favorable prognosis in the mild, moderate and severe pregnancies were 94.4%, 79.2%, and 4.8%, respectively, and the termination of pregnancy (TOP) rates were 4.6%, 20.8%, and 85.7%, respectively. In both the mild and moderate NIBVM, the TOP rates progressively increased and the favorable prognosis survival rates progressively decreased relative to the soft markers, non-structural abnormalities, and structural abnormalities, respectively. Approximately 94.1% of severe NIBVM ended in termination. CONCLUSION: Genetic disorders and fetal infection are important etiology of BVM. CMA is highly recommended for genetic disorders' evaluation. Pregnancies with severe BVM always ended in TOP, while in mild-to-moderate NIBVM, prenatal imaging by ultrasound and/or MRI plays important roles in the pregnancy outcomes.

LZAP promotes the proliferation and invasiveness of cervical carcinoma cells by targeting AKT and EMT.

Objective: To explore the relationship and mechanism of LZAP in the occurrence and development of cervical cancer and to provide a new target and intervention method for the treatment of cervical cancer. Methods: Data mining and analysis of LZAP expression levels were performed using several online databases, including The Cancer Genome Atlas (TCGA). A cervical cancer cell line that stably overexpresses LZAP was established, and the effect of LZAP overexpression on cell proliferation, invasion, migration and tumor formation in vivo as well as its mechanism were explored. Results: Our study shows that the expression of LZAP is upregulated in cervical cancer. The overexpression of LZAP can significantly promote the proliferation, colony formation, and invasion and migration abilities of cervical cancer cells. The tumorigenesis test in nude mice showed that overexpression of LZAP could promote the tumorigenicity of cervical cancer cells in vivo. LZAP could also promote the phosphorylation of AKT at position 473 and the epithelial-mesenchymal transition (EMT). Conclusion: The expression of LAZP is increased in cervical cancer, which can enhance the invasion, metastasis, and EMT in cervical cancer cells by promoting AKT phosphorylation.

Rubidium ion Capture with a phosphotungstic acid-functionalized finger-citron-residue-based carbon.

To solve the contradiction of diffusion and selectivity, we reported a novel finger-citron-residue-based mesoporous carbon (FMC) as a support to prepare a novel adsorbent PTA@FMC (PTA represents phosphotungstic acid) for rubidium ion capture. This new adsorbent was characterized by X-ray diffraction, thermogravimetric analysis, scanning electron microscopy, Fourier transform infrared spectroscopy, and N2 adsorption, and the results showed that the PTA was immobilized in the FMC structure. Based on the results of batch tests, we demonstrated that PTA@FMC is the most distinctive adsorbent with a superior uptake capacity compared with some of those previously reported in the literatures. The adsorption tests in the presence of interfering ions (Na+, K+ and Cs+) showed that the more the added amount of the different types of interfering ions, the more severe is the degree by which the adsorption of Rb+ is weakened. In addition, the Rb+ sorption selectivity was moderately influenced by the co-ion effect in the presence of any ions (K+, Na+ and Cs+) due to PTA doping. In a word, due to its relatively facile preparation process and good uptake capacity, PTA@FMC might be a promising adsorption material for Rb+.

Prognostic significance of solitary lymph node metastasis in patients with stages IA2 to IIA cervical carcinoma.

Objective To investigate the prognostic significance of and risk factors for solitary lymph node metastasis (SLNM) of patients with cervical carcinoma. Methods Clinical data from patients with International Federation of Gynecology and Obstetrics (FIGO) stages IA2 to IIA cervical carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy between January 2003 and December 2010 were analysed retrospectively. Histopathological analysis was used to identify SLNM. Long-term survival and risk factors associated with SLNM were analysed. Results The study enrolled 302 patients with cervical cancer: 48 with SLNM (SLNM group) and 254 patients with no lymph node metastases (nLNM group). FIGO stage, tumour grade, depth of tumour invasion, uterine body involvement, parametrial involvement and lymphovascular invasion differed significantly between the two groups. Logistic regression analysis revealed that FIGO stage, depth of tumour invasion and lymphovascular invasion were independent factors associated with SLNM. The 5-year survival rates of the SLNM and nLNM groups were 54.2% and 87.8%, respectively. Multivariate analysis identified SLNM as an independent factor affecting survival. Conclusions The occurrence of just one solitary lymph node metastasis significantly worsened the prognosis in patients with cervical carcinoma compared with patients without lymph node metastases.