妊娠早期绒毛活检技术诊断胎儿成人型多囊肾病一例

孕妇25岁,主因"停经10+ 1周,患有成人型多囊肾病(autosomal dominant polyeystic kidney disease,ADPKD) "来北京大学第一医院妇产科就诊.平素月经规律,核对孕周无误.2年前体检时发现患有ADPKD,就诊时肾功能正常.家族中其祖母、父亲、3个姑姑及同胞姐姐均患有ADPKD,姐姐已经患有尿毒症,H前正在透析治疗,其他ADPKD患者肾功能尚正常.父系家族中所有成员均在北京大学医学部医学遗传学系抽取外周血进行DNA提取,用多重聚合酶链虑应(polymerase chain reaction,PCR)测序技术分析多囊肾病基因1(polycystic kidney disease 1 gene,PKD1)的外显子编码序列,在PKD1编码序列上发现杂合突变位点,为c'lds3719-3721之间缺失碱基ACA,导致缺失第1240位氨基酸天门冬酰胺.该突变在该家系所有ADPKD患者中均存在,但在正常个体中均不存在,因此,可以认为该突变是致病突变.确认基因中的致病突变时,该患者已经妊娠.为确定胎儿是否患有ADPKD,来我院行妊娠早期产前诊断.     

阴道分泌物胎儿纤维连接蛋白与宫颈长度联合预测早产的多中心前瞻性研究

Objective To discuss the clinical value of fetal fibronectin (fFN) and cervical length in predicting preterm birth. Methods Totally, 511 pregnant women at 22-35 weeks of gestations were enrolled from Dec. 2006 to Dec. 2007 at 4 tertiary hospitals in Beijing, and all with either symptoms or high risk factors of preterm birth, but without preterm premature rupture of membrane or vaginal bleeding. Cervical fFN were determined and cervical length of each subjects were measured by ultrasound. The pregnancy outcomes were compared. Results The sensitivity, specificity and negative predictive value (NPV) of fFN in predicting preterm birth within 7 d were 77.4%, 69.4% and 97. 9%, respectively; and 70.5%, 70.0% and 96.2% for deliveries within 34 weeks. The above figures changed to 54.8%, 66.3%, 95.8% for deliveries within 7 d and 59.1%, 67.2%, 94.6% for those within 34 weeks, respectively, when cervical length ≤3 cm was applied to predict preterm birth. When fFN and cervical length were combined, the sensitivity, specificity and NPV were 51.6%, 87.1%, 96.5% for deliveries within 7 d, and 45.5%, 87.60/00, 94.5% for those within 34 weeks, respectively. Conclusions FFN has higher NPV and specificity than cervical length in predicting preterm birth within 7 d and 34 weeks, and the positive predictive value and specificity can be improved when combined with cervical length.     

家系分析在产前筛查诊断中的价值

家系分析有助于临床医生了解疾病的传递方式、分析检测结果,进而为家系其他成员提供检测建议。目前遗传学检测技术不断进步并应用于临床,可能发现大量“阳性”结果,更需要重视家系分析在致病性判断中的价值。     

Toll样受体与妊娠期疾病

妊娠期的母-胎界面存在着极强的免疫反应,其中以先天性免疫为主,其主要作用是促进胚胎植入和调节胎盘的发育,从而使母体对半异体来源的胎儿产生耐受[1].与此同时,在这一界面,还需要相当程度的宿主防御反应,应对外界可能的感染.因此,如果机体不能有效地清除感染物质,或者免疫反应过度,都有可能对妊娠结局产生不良影响.临床研究已证实,宫内感染与多种妊娠期并发症相关,提示感染以及其所诱导的先天性免疫反应,可能会影响妊娠结局[2,3].宫内感染与早产有关的研究结论已得到证实.近年研究还发现,子痫前期和宫内发育受限（FGR）也与宫内感染相关[3,4].感染对妊娠的影响究竟通过何种分子机制尚不明确.除巨噬细胞、自然杀伤细胞等免疫细胞以外,近年来许多学者发现,母-胎界面特有的滋养细胞、羊膜细胞等,通过其遗传保守性蛋白--Toll样受体（Toll-like receptors,TLR）,也可以识别病原,参与先天性免疫反应,进而对妊娠结局产生影响[3-7].下面就TLR及其与妊娠期疾病的关系进行阐述.     

阴道分泌物胎儿纤维连接蛋白与宫颈长度联合预测早产的多中心前瞻性研究

Objective To discuss the clinical value of fetal fibronectin (fFN) and cervical length in predicting preterm birth. Methods Totally, 511 pregnant women at 22-35 weeks of gestations were enrolled from Dec. 2006 to Dec. 2007 at 4 tertiary hospitals in Beijing, and all with either symptoms or high risk factors of preterm birth, but without preterm premature rupture of membrane or vaginal bleeding. Cervical fFN were determined and cervical length of each subjects were measured by ultrasound. The pregnancy outcomes were compared. Results The sensitivity, specificity and negative predictive value (NPV) of fFN in predicting preterm birth within 7 d were 77.4%, 69.4% and 97. 9%, respectively; and 70.5%, 70.0% and 96.2% for deliveries within 34 weeks. The above figures changed to 54.8%, 66.3%, 95.8% for deliveries within 7 d and 59.1%, 67.2%, 94.6% for those within 34 weeks, respectively, when cervical length ≤3 cm was applied to predict preterm birth. When fFN and cervical length were combined, the sensitivity, specificity and NPV were 51.6%, 87.1%, 96.5% for deliveries within 7 d, and 45.5%, 87.60/00, 94.5% for those within 34 weeks, respectively. Conclusions FFN has higher NPV and specificity than cervical length in predicting preterm birth within 7 d and 34 weeks, and the positive predictive value and specificity can be improved when combined with cervical length.     

不同检验方法在诊断女性生殖道沙眼衣原体感染的局限性

目的:研究不同方法对宫颈拭子样本沙眼衣原体的检测价值。方法:采集392例20~50岁无感染症状女性宫颈分泌物,分别进行培养、核酸扩增及两种免疫层析法(法国LAB、美国QUICK),进行沙眼衣原体(Chlamydia Trachomatis,CT)检测,培养阳性或其它任意检验结果两种或两种以上阳性,定为真阳性,称为"扩大的金标准"。结果:392例受检查者,按"扩大的金标准"CT感染者共46例,发病率为11.73%(46/392),培养、PCR、LAB、QUICK敏感性分别为58.70%、91·30%、95.65%、54.37%。特异性分别为100%、98.84%、63.29%、96.80%。阳性预测值分别为58.70%、91.30%、25.73%、96·15%。阴性预测值分别94.79%、98.84%、99.10%、94.10%。结论:应用单一实验诊断CT感染具有很大的局限性。     

阴道分泌物胎儿纤维连接蛋白与宫颈长度联合预测早产的多中心前瞻性研究

Objective To discuss the clinical value of fetal fibronectin (fFN) and cervical length in predicting preterm birth. Methods Totally, 511 pregnant women at 22-35 weeks of gestations were enrolled from Dec. 2006 to Dec. 2007 at 4 tertiary hospitals in Beijing, and all with either symptoms or high risk factors of preterm birth, but without preterm premature rupture of membrane or vaginal bleeding. Cervical fFN were determined and cervical length of each subjects were measured by ultrasound. The pregnancy outcomes were compared. Results The sensitivity, specificity and negative predictive value (NPV) of fFN in predicting preterm birth within 7 d were 77.4%, 69.4% and 97. 9%, respectively; and 70.5%, 70.0% and 96.2% for deliveries within 34 weeks. The above figures changed to 54.8%, 66.3%, 95.8% for deliveries within 7 d and 59.1%, 67.2%, 94.6% for those within 34 weeks, respectively, when cervical length ≤3 cm was applied to predict preterm birth. When fFN and cervical length were combined, the sensitivity, specificity and NPV were 51.6%, 87.1%, 96.5% for deliveries within 7 d, and 45.5%, 87.60/00, 94.5% for those within 34 weeks, respectively. Conclusions FFN has higher NPV and specificity than cervical length in predicting preterm birth within 7 d and 34 weeks, and the positive predictive value and specificity can be improved when combined with cervical length.     

宫内重度高血糖及出生后早期过度喂养与子鼠成年期代谢综合征

目的 探讨孕期重度高血糖及出生后早期过度喂养与子鼠成年期代谢表型的关系.方法 成年Wistar雌性大鼠于妊娠第5天腹腔内注射20%链脲霉素50 mg/kg,血糖＞20 mmol/L为孕期重度高血糖模型(severely diabetes mellitus,SDM).子鼠生后通过减少哺乳期胎仔数建立子鼠早期过度喂养模型.根据孕期血糖水平和哺乳期喂养方式将子鼠分为3组:(1)对照组子鼠(control pups,CP组):孕期母鼠血糖正常,哺乳期1只母鼠喂养8只子鼠;(2)SDM正常喂养组:孕期母鼠重度高血糖,哺乳期1只母鼠喂养8只子鼠;(3)SDM过度喂养组:孕期母鼠重度高血糖,哺乳期1只母鼠喂养4只子鼠.各组子鼠于第3周断乳后均给予常规饲料喂养.观察3～26周各组子鼠体重变化,测定26周龄时子鼠收缩压、舒张压、心率以及代谢相关指标,包括空腹总甘油三酯,总胆固醇、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇,根据空腹血糖、空腹胰岛素水平利用胰岛素稳态模型(homeostasis model assessment,HOMA)计算胰岛素抵抗指数(insulin resistance,IR).组间各指标比较采用ANOVA和LSD检验.结果 SDM组母鼠空腹血糖为(28.34±5.14)mmol/L,明显高于对照组(6.25±1.41)mmol/L(P＜0.05).SDM过度喂养组和正常喂养组子鼠3周断乳后体重显著低于CP组[(43.63±4.83)g、(31.45±10.21)g和(55.75±8.4)g,P＜0.05],SDM过度喂养组 3～6周体重均明显高于SDM正常喂养组(P＜0.05).SDM组子鼠3～7周、3～9周体重增长率高于CP组,其中SDM正常喂养组与SDM过度喂养组和CP组间差异均有统计学意义(P＜0.05).生后26周龄时SDM正常喂养组和SDM过度喂养组收缩压[(153.31±13.91)mm Hg和(147.21±12.29)mm Hg]和甘油三酯[(0.73±0.22)mmol/L和(0.71±0.49)mmol/L]水平明显高于CP组[分别为(132.21±11.26)mm Hg和(0.37±0.08)mmol/L](P均＜0.05),但SDM正常喂养组和SDM过度喂养组之间差异无统计学意义(P＞0.05).SDM正常喂养组、SDM过度喂养组和CP组间空腹血糖水平差异无统计学意义,但SDM过度喂养组的空腹胰岛素和HOMA-IR分别为(12.552±3.260)mU/L和2.400±0.624,与SDM正常喂养组[分别为(9.067±1.782)mU/L和1.797±0.508]和CP组[分别为(8.590±0.806)mU/L和1.729±0.246]比较,显著增高(P＜0.05).结论 孕期重度高血糖可导致子鼠低出生体重,生后早期存在明显的追赶生长.子鼠成年期代谢综合征的发病风险增加,早期过度喂养可加速这一进程.     

健康与疾病的发育起源对围产医学实践的启迪

近年来,随着我国经济生活方式迅速转型和饮食结构西方化,使肥胖及与其相关的糖尿病(diabetes mellitus,DM)、高血压等一系列代谢综合征(metabolic syndrome,MS)在我国人群中的发病率逐年上升,且呈现出年轻化的特点.     

妊娠期糖尿病患者治疗前后肠道菌群变化及其与血糖的相关性

目的探讨妊娠期糖尿病(gestational diabetes mellitus,GDM)患者治疗前后肠道菌群的变化特点,及其与75 g口服葡萄糖耐量试验(oral glucose tolerance test,OGTT)血糖水平的关系。方法采用基于前瞻性队列研究的巢式病例对照研究方法。以2016年10月至2017年12月在北京大学第一医院妇产科建档及分娩的孕妇为研究对象。选取45例24~28孕周诊断为GDM的孕妇作为GDM组,并根据年龄和孕前体重指数(body mass index,BMI)按1∶1比例选取45例正常孕妇作为对照组。分别收集GDM治疗前(孕24~28周)及治疗后(孕36~40周)的粪便标本(对照组亦于相应孕周留取标本),利用Illumina Hiseq2500平台针对细菌16S rRNA的V3-V4可变区进行DNA测序,利用QIIME软件对样本进行生物信息学分析。采用t检验、Mann-Whitney U检验或χ2检验进行统计学分析。结果(1)治疗前GDM组肠道菌群Alpha多样性显著低于对照组(Chao1指数分别为443.9±72.9和474.0±63.3,t=2.104;Shannon指数分别为5.6±0.5和6.0±0.5,t=2.002;P值均<0.05),2组肠道菌群Beta多样性也存在明显差异(R2=0.04,P<0.05)。治疗后,GDM组和对照组肠道菌群的Alpha和Beta多样性的差异均无统计学意义。(2)GDM患者治疗前肠道布劳特氏菌和普拉梭菌的相对丰度高于对照组[M(P25~P75),分别为0.016(0.009~0.022)与0.011(0.007~0.016),U=782.000;0.114(0.076~0.141)与0.091(0.061~0.126),U=752.000;P值均<0.05]。阿克曼氏菌、Odoribacter和Butyricimonas的相对丰度低于对照组[分别为0.001(0.000~0.002)与0.001(0.000~0.005),U=745.000;0.001(0.000~0.004)与0.004(0.001~0.006),U=766.500;0.001(0.000~0.003)与0.003(0.001~0.005),U=710.000;P值均<0.05]。(3)OGTT服糖前水平和阿克曼氏菌、Odoribacter和Butyricimonas相对丰度呈负相关(r值分别为-0.325、-0.273和-0.284),服糖后1 h血糖水平和阿克曼氏菌、Butyricimonas相对丰度呈负相关(r值分别为-0.285和-0.265),服糖后2 h血糖水平和普拉梭菌相对丰度呈正相关(r=0.278),和阿克曼氏菌相对丰度呈负相关(r=-0.245);OGTT时间-血糖曲线的曲线下面积和阿克曼氏菌、Butyricimonas相对丰度呈负相关(r值分别为-0.321和-0.264)(P值均<0.05)。结论GDM患者肠道菌群组成和结构较对照组发生变化,GDM特征性菌群与OGTT血糖水平显著相关。通过治疗干预将GDM患者血糖恢复至正常水平,可改善GDM患者肠道菌群紊乱。