Analysis of 17,428 pregnant women undergoing non-invasive prenatal testing for fetal chromosome in Northeast China.

ABSTRACT: Non-invasive prenatal testing (NIPT) is an incomparable prenatal screening technology, but we should undergo amniocentesis to confirm fetal chromosome when pregnancies receive a positive result via NIPT. We aimed to investigate the detection rate and positive predictive value of NIPT results in pregnancies from Northeast China, and to determine the reasons for false positive and false negative NIPT results.This study evaluates 17,428 singleton pregnancies had undergone NIPT detection. 202 samples were NIPT positive with the detection rate was 1.16% (202/17,428). Among all the positive samples, 160 samples (79.21%) were referred for an amniocentesis procedure to investigate the fetal chromosome. The positive predictive value of T21, T18, and T13 was found to be 75% with a 0.07% false positive rate. Positive predictive value from high to low was as follows: trisomy 21 (84.38%), followed by trisomy 18 (61.54%), autosomal abnormalities (52.94%), sex chromosomal abnormalities (38.46%), and trisomy 13 (33.33%). The positive predictive values for sex chromosome abnormalities turned out to be mosaic sex chromosome aneuploidies (83.33%), followed by XYY (57.14%), XXY (37.50%), XXX (36.36%), and Monosomy X (28.95%). Out of the 160 samples had amniocentesis, the true positive cases in trisomy 21 had a higher percentage of Z-scores compared with the false positive cases in trisomy 21 (P < .05). And the true positive cases in trisomy 18 had a significantly higher percentage of Z-scores compared with the false positive cases in trisomy 18 (P < .01).These findings indicate that the positive predictive value of T21, T18, and T13 was found to be 75% with a 0.07% false positive rate. It is worth noting that the positive predictive value of NIPT for autosomes and sex chromosomes. Moreover, if women receive a positive result via NIPT, they should pay attention to the results with undergoing further prenatal diagnosis.

Convalescent plasma may be a possible treatment for COVID-19: A systematic review.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has spread globally. Therapeutic options including antivirals, anti-inflammatory compounds, and vaccines are still under study. Convalescent plasma(CP) immunotherapy was an effective method for fighting against similar viral infections such as SARS-CoV, and MERS-CoV. In the epidemic of COVID-19, a large number of literatures reported the application of CP. However, there is controversy over the efficacy of CP therapy for COVID-19. This systematic review was designed to evaluate the existing evidence and experience related to CP immunotherapy for COVID-19. METHODS: A literature search was conducted on Pubmed, Cochrane Library, Clinical Key, Wanfang Database; China National Knowledge Infrastructure(CNKI) were used to search for the proper keywords such as SARS-CoV-2, COVID-19, plasma, serum, immunoglobulins, blood transfusion, convalescent, novel coronavirus, immune and the related words for publications published until 15.10.2020. Other available resources were also used to identify relevant articles. The present systematic review was performed based on PRISMA protocol. Data extraction and risk of bias assessments were performed by two reviewers. RESULTS: Based on the inclusions and exclusions criteria, 45 articles were included in the final review. First, meta-analysis results of RCTs showed that, there were no statistically significant differences between CP transfusion and the control group in terms of reducing mortality(OR 0.79, 95% CI 0.52-1.19, I2 = 28%) and improving clinical symptoms(OR 1.21, 95%CI 0.68-2.16; I2 = 0%). The results of controlled NRSIs showed that CP therapy may reduce mortality in COVID-19 patients(RR 0.59, 95% CI 0.53-0.66, I2 = 0%). Second, limited safety data suggested that CP is a well-tolerated therapy with a low incidence of adverse events. But, due to lack of safety data for the control group, it is really not easy to determine whether CP transfusion has an impact on moderate to serious AEs. Thirdly, for children, pregnant, elderly, tumor and immunocompromised patients, CP may be a well-tolerated therapy, if the disease cannot be controlled and continues to progress. Studies were commonly of low or very low quality. CONCLUSIONS: Although the results of limited RCTs showed that CP cannot significantly reduce mortality, some non-RCTs and case report(series) have found that CP may help patients improve clinical symptoms, clear the virus, and reduce mortality, especially for patients with COVID-19 within ten days of illness. We speculate that CP may be a possible treatment option. High-quality studies are needed for establishing stronger quality of evidence and pharmacists should also be actively involved in the CP treatment process and provide close pharmaceutical care.

Specific Interleukin-1 Inhibitors, Specific Interleukin-6 Inhibitors, and GM-CSF Blockades for COVID-19 (at the Edge of Sepsis): A Systematic Review.

Sepsis is a syndrome with high mortality, which seriously threatens human health. During the pandemic of coronavirus disease 2019 (COVID-19), some severe and critically ill COVID-19 patients with multiple organ dysfunction developed characteristics typical of sepsis and met the diagnostic criteria for sepsis. Timely detection of cytokine storm and appropriate regulation of inflammatory response may be significant in the prevention and treatment of sepsis. This study evaluated the efficacy and safety of specific interleukin (IL)-1 inhibitors, specific IL-6 inhibitors, and GM-CSF blockades in the treatment of COVID-19 (at the edge of sepsis) patients through systematic review and meta-analysis. METHODOLOGY: A literature search was conducted on PubMed, EMBASE, Clinical Key, Cochrane Library, CNKI, and Wanfang Database using proper keywords such as "SARS-CoV-2," "Corona Virus Disease 2019," "COVID-19," "anakinra," "tocilizumab," "siltuximab," "sarilumab," "mavrilimumab," "lenzilumab," and related words for publications released until August 22, 2021. Other available resources were also used to identify relevant articles. The present systematic review was performed based on PRISMA protocol. RESULTS: Based on the inclusion and exclusion criteria, 43 articles were included in the final review. The meta-analysis results showed that tocilizumab could reduce the mortality of patients with COVID-19 (at the edge of sepsis) [randomized controlled trials, RCTs: odds ratio (OR) 0.71, 95%CI: 0.52-0.97, low-certainty evidence; non-RCTs: risk ratio (RR) 0.68, 95%CI: 0.55-0.84, very low-certainty evidence) as was anakinra (non-RCTs: RR 0.47, 95%CI: 0.34-0.66, very low-certainty evidence). Sarilumab might reduce the mortality of patients with COVID-19 (at the edge of sepsis), but there was no statistical significance (OR 0.65, 95%CI: 0.36-1.2, low-certainty evidence). For safety outcomes, whether tocilizumab had an impact on serious adverse events (SAEs) was very uncertain (RCTs: OR 0.87, 95%CI: 0.38-2.0, low-certainty evidence; non-RCTs 1.18, 95%CI: 0.83-1.68, very low-certainty evidence) as was on secondary infections (RCTs: OR 0.71, 95%CI: 0.06-8.75, low-certainty evidence; non-RCTs: RR 1.15, 95%CI: 0.89-1.49, very low-certainty evidence). CONCLUSIONS: This systematic review showed that tocilizumab, sarilumab, and anakinra could reduce the mortality of people with COVID-19 (at the edge of sepsis), and tocilizumab did not significantly affect SAEs and secondary infections. The current evidence of the studies on patients treated with siltuximab, mavrilimumab, and lenzilumab is insufficient. In order to establish evidence with stronger quality, high-quality studies are needed. Systematic Review Registration: PROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42020226545.

A novel FGFR2 (S137W) mutation resulting in Apert syndrome: A case report.

RATIONALE: Apert syndrome (AS) is an autosomal dominant inheritance pattern of the most severe craniosynostosis syndrome. AS is characterized by synostosis of cranial sutures and acrocephaly, including brachycephaly, midfacial hypoplasia, and syndactyly of the hands and feet. Patients with AS often present with craniosynostosis, severe syndactyly, and skin, skeletal, brain, and visceral abnormalities. PATIENT CONCERNS: A pregnant Chinese woman presented with a fetus at 23 + 5 weeks of gestation with suspected AS in a prenatal ultrasound examination. Following ultrasound, the pregnancy underwent spontaneous abortion. Gene sequencing was performed on the back skin of the dead fetus. DIAGNOSIS: The diagnosis of AS was confirmed on the basis of clinical manifestations of the fetus, and a de novo mutation in the fibroblast growth factor receptor 2 (FGFR2) gene was identified. INTERVENTIONS: The couple finally chose to terminate the pregnancy based on the ultrasonic malformations and the risk of the parents having a neonate with AS in the future is small. However, any future pregnancy must be assessed by prenatal diagnosis. OUTCOMES: The dead fetus presented with bilateral skull deformation. Additionally, there were bilateral changes to the temporal bone caused by inwards movement leading to concave morphology, a "clover" sign, and syndactyly from the index finger/second toe to the little finger/little toe. AS was diagnosed by genetic testing, which showed a p.S137W (c.410C>G, chr10:123279677) mutation in the FGFR2 gene. LESSONS: Clinicians should be aware that there are a variety of ultrasound findings for AS. Therefore, genetic testing should be used when appropriate to confirm diagnosis of AS.

Prenatal diagnosis of 4953 pregnant women with indications for genetic amniocentesis in Northeast China.

BACKGROUND: Several different technologies are used for prenatal screening procedures and genetic diagnostic technologies. We aimed to investigate the rates of chromosomal abnormalities in cases with different abnormal prenatal indications and to determine the relationships between fetal chromosomal abnormalities and indicators of prenatal abnormalities in Northeast China. METHODS: We evaluated 4953 16- to 23-week singleton gestation cases using amniocentesis and a total of 3583 participants received serological screening. Fetal chromosomal analyses were performed for all samples using fluorescence in situ hybridization and karyotyping. RESULTS: Among these samples, 204 (4.12%) had fetal chromosomal abnormalities. A total of 3583 participants received serological screening, among whom 102 (2.85%) exhibited positive results. A total of 309 participants had ultrasonography; 42 (13.6%) of these had abnormalities. Among 97 participants who had non-invasive prenatal testing (NIPT), 59 (61%) had positive results. Among 1265 participants with advanced maternal age, 78 (6.2%) had abnormal results. CONCLUSION: The serological screening and NIPT that were included in the prenatal screening methods all had false positive and false negative rates. Although they are both prenatal screening techniques, maternal serum screening cannot be replaced by NIPT. The pregnancy women should accept NIPT in a qualified prenatal diagnostic center. We recommend that pregnant women at high or critical risk undergoing prenatal screening should confirm the fetal karyotype through amniocentesis. Moreover, if women receive a positive result via NIPT, they should not have a pregnancy termination without undergoing further prenatal diagnosis.

Chromosomal copy number variations in products of conception from spontaneous abortion by next-generation sequencing technology.

Fetal chromosomal abnormalities are considered to be the main cause of spontaneous abortion (SA). We aimed to determine the differences in the rates and numbers of chromosomal abnormalities between samples from women with a history of one versus more than one SA as well as between samples from first- and second-trimester SAs in women from Northeast China.In total, 1210 products of conception (POCs) from patients with a history of one or more SAs were examined. Of these 1210 samples, 434 were from women with a history of 1 SA, and 776 were from women with a history of more than 1 SA. Additionally, 1071 samples were from the first trimester, 118 were from the second trimester, and 21 were from the third trimester. We identified chromosomal abnormalities by next-generation sequencing (NGS) technology. Among the 1210 POCs in women with SA, 607 (50.17%) had fetal chromosomal abnormalities. There were no significant differences in the rates of chromosomal abnormalities according to the abortion frequency. However, first-trimester SA had a significantly higher percentage of fetal chromosomal abnormalities than second-trimester SA (P < .05). Among 663 chromosomal abnormalities, 633 abnormalities occurred in first-trimester SA; the most frequent karyotype was trisomy 16 (14.38%), followed by monosomy X (13.27%), trisomy 22 (7.90%), and trisomy 15 (5.37%). Thirty abnormalities occurred in second-trimester SA; the most frequent karyotype was trisomy 18 (26.67%), followed by monosomy X (16.67%), trisomy 21 (13.33%), and trisomy 13 (10.00%). No chromosomal abnormalities occurred in the third trimester.These findings indicate the importance of determining the genetic cause of abortion in patients with a history of SA. We also identified a trend suggesting that the percentage of fetal chromosomal abnormalities is significantly higher in first- than second-trimester SA. The detection rate of chromosomal abnormalities in POCs from SA can be increased by NGS, which is beneficial for couples with recurrent miscarriages and offers better genetic counseling in the clinical setting.

Role of male genetic factors in recurrent pregnancy loss in Northeast China.

OBJECTIVE: This study aimed to investigate the roles of male genetic factors, including Y chromosome microdeletions and chromosomal heteromorphism, in recurrent pregnancy loss (RPL) in Northeast China. STUDY DESIGN: We evaluated 1072 male patients from Northeast China whose wives had a history of two or more consecutive miscarriages. We also selected 971 infertile and 200 fertile men as control groups. Semen analysis was carried out by computer-assisted sperm analysis. Y chromosome microdeletions were detected by polymerase chain reaction and chromosomes were evaluated by karyotype analysis. RESULTS: There were no microdeletions in the RPL and fertile control groups, but 112 of the infertile men had Y chromosome microdeletions. Chromosomal heteromorphism was detected in all the groups. Patients in the infertile control group had a significantly higher percentage (2.16%) of Y variation (Yqh±) heteromorphism compared with the RPL group, but there were no significant differences in the incidences of chromosomal heteromorphism among the other groups. CONCLUSION: Y chromosome microdeletions and chromosomal heteromorphism are not associated with RPL in Northeast China. Some RPL males had structural chromosome anomalies, all of which were reciprocal translocations. We suggest that it may not be necessary to detect Y chromosome microdeletions in RPL males with Yqh±.

Effect of maternal age on spontaneous abortion during the first trimester in Northeast China.

OBJECTIVE: We aimed to determine the relationship between fetal chromosomal abnormalities and maternal age among spontaneous first trimester abortions in women in Northeast China. METHODS: We evaluated 497 chorionic villi samples from patients with a history of spontaneous abortion during the first trimester. We divided the samples into five groups according to the maternal age: <25, 25-29, 30-34, 35-39, and ≥40 years. We identified chromosomal abnormalities by fluorescence in situ hybridization. RESULTS: Among the 497 chorionic samples of spontaneous abortion, 180 (36.22%) had fetal chromosomal abnormalities. Patients aged ≥40 years had a significantly higher percentage (60.61%) of fetal chromosomal abnormalities compared with the other groups. More women in the ≥40 and 35- to 39-year groups had a history of three consecutive miscarriages and 10 kinds of abnormalities. The most frequent aneuploidy was trisomy 22, followed by trisomy 16. CONCLUSIONS: These results revealed that the kinds of fetal abnormalities, numbers of abortions, and chromosomal abnormality rates increased with increasing maternal age. The most common trisomy types in spontaneous abortions were closely related to maternal age. We hypothesize whether the larger probability of chromosomal abnormalities is due to increased mutation rate with maternal age, or due to a worse in-utero conditions.

Analysis of Y chromosome microdeletion in 1738 infertile men from northeastern China.

OBJECTIVE: To determine the frequencies and the characteristics of Y chromosome microdeletion in infertile men from northeastern China to perform appropriate therapeutic choices. MATERIALS AND METHODS: The study included 1738 infertile men. Sperm concentration was measured according to standard methods and karyotype analysis was performed on peripheral blood lymphocytes with standard G-banding. Multiplex polymerase chain reaction amplification using 9 specific sequence-tagged sites were selected to detect Y chromosome microdeletions. RESULTS: The data showed that the frequency of Y chromosome microdeletion was 8.57%. The most common microdeletion, among the azoospermia factor (AZF) regions, was detected in the AZFc region, followed by AZFb+c, AZFb, AZFa+b+c, AZFa, and AZFa+c. One-hundred seven patients with Y chromosome microdeletion developed azoospermia, 39 developed severe oligozoospermia (sperm concentration ≤5 × 10(6)/mL), and 3 developed moderate oligozoospermia (sperm concentration >5 × 10(6)/mL and ≤10 × 10(6)/mL). Karyotype analysis was available for 130 patients with Y chromosome microdeletion and abnormal karyotypes were found in 19 patients (14.6%). The most frequent abnormal karyotype was 46,X,Yqh-(n = 7). CONCLUSION: In northeastern China, Y chromosome microdeletion diagnosis should be performed before the use of intracytoplasmic sperm injection in infertile men with sperm count ≤10 × 10(6)/mL, especially in men with azoospermia.

[Y chromosome microdeletions in severe oligospermia men with varicocele].

OBJECTIVE: To investigate Y chromosome microdeletions in severe oligospermia men with varicocele. METHODS: We randomly selected 100 cases of severe oligospermia with left varicocele (sperm concentration <5 x 10(6)/ml, group 1), 100 cases of mild oligospermia with left varicocele (sperm concentration 10 -20 x 10(6)/ml, group 2), 100 cases of idiopathic infertility with severe oligospermia (group 3), 100 cases of idiopathic infertility with moderate oligospermia (group 4) and 30 normal fertile men as controls (group 5). We used polymerase chain reaction (PCR) technology to screen 9 sequence tagged sites (STS) of the AZF a, b and c regions and detect Y chromosome microdeletions. RESULTS: AZF microdeletions were found in 19 patients in group 1 (19%) and 11 in group 3 (11%), with a higher rate in the former than in the latter, but not in the other three groups. CONCLUSION: Screening of Y chromosome microdeletions should be performed before the treatment of severe spermatogenesis with varicocele.

Male infertility in Northeast China: a cytogenetic study of 135 patients with non-obstructive azoospermia and severe oligozoospermia.

PURPOSES: To detect the frequency and types of chromosomal anomalies with non-obstructive azoospermia and severe oligozoospermia in Northeast China, and to compare the frequencies with other regions of China and the world. To investigate the general characteristics of this population. METHODS: Eighty-one men with non-obstructive azoospermia and 54 men with severe oligozoospermia were recruited. Karyotype analyses were performed on peripheral blood lymphocytes using standard G-banding. Measurements of follicle-stimulating hormone, testosterone, prolactin, and inhibin B were obtained. RESULTS: The frequency of chromosomal anomalies for patients with non-obstructive azoospermia (17.28%) was comparable with studies from Europe, Africa, Asia, and other regions of China. However, the frequency for patients with severe oligozoospermia (9.26%) was slightly higher than reported from other Asian countries. The infertile men were more likely than the fertile to smoke and consume alcohol, and to have significantly lower levels of inhibin B. CONCLUSIONS: For infertile men in Northeast China, chromosome analysis is a necessary part of routine genetic testing, and the contributing effects of high smoking and alcohol consumption rates of this population should be discussed during genetic counseling.

Male infertility in China: laboratory finding for AZF microdeletions and chromosomal abnormalities in infertile men from Northeastern China.

PURPOSES: To investigate the frequencies of AZF microdeletions and chromosomal abnormalities in infertile men from Northeastern China. Moreover, to compare the prevalence of these abnormalities with other countries and regions in the world. METHODS: 305 infertile men were enrolled. A complete semen analysis and reproductive hormones were measured according to standard methods. Multiplex polymerase chain reaction (PCR) amplification using nine specific sequence-tagged sites (STS) were used to detect AZF microdeletions. Karyotype analyses were performed on peripheral blood lymphocytes with standard G-banding. RESULTS: Of the 305 infertile men, 28 (9.2%) had AZF microdeletions and 26 (8.5%) had chromosomal abnormalities. The most frequent microdeletions were in the AZFc+d, followed by AZFc, AZFb+c+d and AZFa. A total of 19 patients (82.6%) had Klinefelter's syndrome (47, XXY) in the azoospermic group. CONCLUSIONS: The freqencies of AZF microdeletions and chromosomal abnormalities in infertile men from Northeastern China were comparable with infertile men from other countries and regions. However, there was a slightly higher prevalence rate of AZF microdeletions in oligozoospermic patients than reported in previous studies.