Identifying occult maternal malignancies from 1.93 million pregnant women undergoing noninvasive prenatal screening tests

PurposeMultiple chromosomal aneuploidies may be associated with maternal malignancies and can cause failure of noninvasive prenatal screening (NIPS) tests. However, multiple chromosomal aneuploidies show poor specificity and selectivity for diagnosing maternal malignancies.MethodsThis multicenter retrospective analysis evaluated 639 pregnant women who tested positive for multiple chromosomal aneuploidies on initial NIPS test between January 2016 and December 2017. Women were assessed using genome profiling of copy-number variations, which was translated to cancer risk using a novel bioinformatics algorithm called the cancer detection pipeline (CDP). Sensitivity, specificity, and positive predictive value (PPV) of diagnosing maternal malignancies were compared for multiple chromosomal aneuploidies, the CDP model, and the combination of CDP and plasma tumor markers.ResultsOf the 639 subjects, 41 maternal malignant cancer cases were diagnosed. Multiple chromosomal aneuploidies predicted maternal malignancies with a PPV of 7.6%. Application of the CDP algorithm to women with multiple chromosomal aneuploidies allowed 34 of the 41 (83%) cancer cases to be identified, while excluding 422 of 501 (84.2%) of the false positive cases. Combining the CDP with plasma tumor marker testing gave PPV of 75.0%.ConclusionThe CDP algorithm can diagnose occult maternal malignancies with a reasonable PPV in multiple chromosomal aneuploidies–positive pregnant women in NIPS tests. This performance can be further improved by incorporating findings for plasma tumor markers.     

Post-marketing safety surveillance and reevaluation of Motherwort injection: A clinical study of 10 094 cases

OBJECTIVE

To investigate the safety profiles of Motherwort injection (MI).

孕期增重及总增重与妊娠期糖尿病关系的队列研究

目的 探讨孕期增重及其总增重与妊娠期糖尿病（GDM）的关系。方法 采用前瞻性队列研究,于2013年3-9月选取成都市妇幼医疗机构产前门诊829名单胎健康孕妇作为基线调查对象,通过问卷调查于首次纳入时收集孕妇孕前等基线资料,于孕第（12±1）、（28±1）、（36±1）周及分娩前分别收集孕妇锻炼习惯、膳食摄入情况等信息和测量孕妇体重,分娩后收集分娩孕周等分娩信息。GDM诊断按中国妊娠合并糖尿病防治指南（2014）,采用多因素logistic回归分析孕早、中、晚期增重和孕期总增重与GDM的关系。结果 共682名孕妇纳入数据分析。控制生育年龄、孕前BMI、糖尿病家族史、高血压家族史、孕早期锻炼、产次、文化程度、家庭人均月收入及膳食能量等混杂因素后,多因素logistic回归分析显示：与孕早期增重适宜组相比,孕早期增重不足组和增重过多组GDM发生风险均增加（分别为OR=1.23,95% CI：0.63～2.38和OR=2.20,95% CI：1.12～4.35）;与孕中期增重适宜组相比,孕中期增重不足组和过多组GDM发生风险均降低（OR=0.47,95% CI：0.18～1.19和OR=0.78,95% CI：0.43～1.42）;与孕晚期增重适宜组相比,孕晚期增重不足组GDM发生风险增加（OR=1.48,95% CI：0.77～2.84）,增重过多组GDM发生风险降低（OR=0.53,95% CI：0.28～0.99）;与孕期总增重适宜组相比,总增重不足组GDM发生风险增加（OR=2.16,95% CI：1.04～4.46）,总增重过多组GDM发生风险降低（OR=0.74,95% CI：0.38～1.46）。结论 孕早期增重不足和过多均可能增加GDM发生风险,孕早期可能是影响GDM发生的关键时期,孕中晚期增重对GDM的影响还有待进一步论证。     

Involvement of caspase-1 proteases in hypoxic brain injury. Effects of their inhibitors in developing neurons

To further explore the contribution of caspase-1/interleukin-1β-converting enzyme in the consequences of hypoxia in developing brain neurons, its temporal expression profile was analysed by immunohistochemistry and western blotting in cultured neurons from the embryonic rat forebrain subjected to a hypoxic stress (95% N₂/5% CO₂ for 6 h), and proteolytic activity of caspase-1 was monitored as a function of time by measuring the degradation of a selective colorimetric substrate (N-acetyl-Tyr-Val-Ala-Asp-p-nitroanilide). In addition, the influence of pre- and posthypoxic treatments by caspase-1 inhibitors (N-acetyl-Tyr-Val-Ala-Asp-aldehyde and N-acetyl-Tyr-Val-Ala-Asp-chloromethylketone) was tested on cell outcome. Hypoxia led to delayed apoptotic neuronal death, with an elevation of the expression of both pro-caspase-1 and caspase-1 active cleavage product (ICE p20) for up to 96 h after cell reoxygenation. As reflected by cleavage of the specific substrate, caspase-1 activity progressively increased between 24 h and 96 h posthypoxia, and was blocked by inhibitors in a dose-dependent fashion. The inhibitory compounds, including when given 24 h after hypoxia, prevented neuronal death, reduced apoptosis hallmarks and also increased the number of mitotic neurons, suggesting they might promote neurogenesis. Similar observations were made when neurons were exposed to a sublethal hypoxia (i.e. 3 h).These data emphasize the participation of caspase-1 in neuronal injury consecutive to oxygen deprivation, and provide new insight into the possible cellular mechanisms by which caspase inhibitors may protect developing brain neurons.     

孕期总增重与不良妊娠结局关系的前瞻性研究

目的 探讨孕期总增重与不良妊娠结局之间的关系。方法 选取成都市妇幼医疗机构产前门诊1 220名6~12孕周、单胎健康的妇女为研究对象进行前瞻性研究。通过问卷调查收集孕妇年龄、孕前体重等基本信息,于分娩前测量孕妇体重,计算孕期总增重,参照2009年美国医学研究所发布的孕期增重推荐标准将研究对象分为增重适宜、增重不足和增重过多组。于分娩后通过医院信息系统收集妊娠结局相关信息。采用多因素非条件logistic回归分析探讨孕期总增重与不良妊娠结局关系。结果 共纳入1 045名单胎活产孕妇进行分析。与孕期增重适宜组相比,孕期增重过多组脐带缠绕和大于胎龄儿发生风险升高（分别为OR=1.641,95% CI：1.197~2.252和OR=1.678,95% CI：1.132~2.488）;孕期增重过少组早产发生风险升高（OR=3.189,95% CI：1.604~6.341）。结论 孕期总增重过多和过少均可能导致不良妊娠结局。应重视孕期体重监测,降低不良妊娠结局发生风险。