海淀区妇幼保健院 北京市 100086
【摘要】目的:研究孕妇孕期(孕8-12周、孕24-28周、孕32-35周)血糖水平与孕晚期(35~37周)B族链球菌(group B Streptococcus,GBS) 检出率的相关性。方法:收集2016年1月~2016年12月在本院产科就诊并建立产前保健档案的孕妇资料,孕8~12周、孕24-28周、孕32-35周进行空腹血糖检测及在孕35~37周进行实时荧光定量-聚合酶链反应(polymerase chain reaction,PCR) GBS DNA检测的孕妇4377例,对不同阶段的血糖糖水平与GBS阳性检出率进行统计分析。结果GBS检测阳性孕妇263例,阴性孕妇4114例,GBS阳性孕妇孕8-12周血糖均值为(4.23±0.36)mmol/L;GBS阴性孕8-12周血糖均值为(4.28±0.37)mmol/L,两组血糖水平差异有统计学意义(T=-2.192,P=0.028),孕24-28周GBS检测阳性孕妇血糖均值为(4.39±0.52)mmol/L;GBS阴性血糖均值为(4.38±0.46)mmol/L,两组血糖水平无明显差异 (T=0.411,P=0.681),孕32-35周GBS检测阳性孕妇血糖均值为(4.19±0.52)mmol/L;GBS阴性血糖均值为(4.20±0.51)mmol/L,两组血糖水平无明显差异 (T=-0.282,P=0.77),结论 孕早期血糖水平与孕晚期GBS检出率呈明显负相关性,孕中期及孕晚期血糖与GBS检出率无明显相关,孕早期血糖水平较低的孕妇应警惕孕后期GBS感染。
【关键词】空腹血糖;B族链球菌;孕早期;孕中期;孕晚期
[Abstract]
Objective: To study the correlation between blood glucose level during pregnancy (8-12 weeks, 24-28 weeks and 32-35 weeks) and the detection rate of group B Streptococcus (GBS) in late pregnancy (35-37 weeks). Methods: Data of 4,377 pregnant women were collected from January 2016 to December 2016 when they visited the obstetrics department of our hospital and established prenatal care files. Fasting blood glucose was detected at 8 to 12 weeks of gestation, 24 to 28 weeks of gestation, 32 to 35 weeks of gestation, and real-time fluorescence quantitative polymerase chain reaction (PCR) GBS DNA detection was performed at 35 to 37 weeks of gestation. Statistical analysis was made on blood glucose and sugar levels and GBS positive detection rates at different stages.
Results 263 cases of GBS positive pregnant women and 4114 cases of GBS negative pregnant women were detected. The mean blood glucose of GBS positive pregnant women was (4.23±0.36) mmol/L during 8-12 weeks of gestation. The mean blood sugar level of GBS negative pregnant women was (4.28±0.37) mmol/L during 8-12 weeks, and the difference between the two groups was statistically significant (T=-2.192, P = 0.028). The mean blood sugar level of GBS positive pregnant women during 24-28 weeks was (4.39±0.52) mmol/L; The mean value of GBS negative blood glucose was (4.38±0.46) mmol/L. There was no significant difference in blood glucose levels between the two groups (T=0.411, P = 0.681). The mean value of blood glucose for GBS positive pregnant women at 32-35 weeks was (4.19±0.52) mmol/L; The mean value of GBS negative blood sugar is (4.20±0.51) mmol/L, and there is no significant difference between the two groups in blood sugar level (T=-0.282, P = 0.77). Conclusion:There is a significant negative correlation between the blood sugar level in early pregnancy and the detection rate of GBS in late pregnancy. There is no significant correlation between the blood sugar level in the second and third trimester of pregnancy and the detection rate of GBS. Pregnant women with low blood sugar level in early pregnancy should be cautious of GBS infection in late pregnancy.
[Key Words]: Fasting plasma glucose; Group b streptococcus; Early pregnancy; Second trimester of pregnancy; Late pregnancy
B族链球菌(group B Streptococcus,GBS),是一种革兰阳性、β-溶血性链球菌,20%-30%的孕妇泌尿生殖道中均有定植,与早产等不良妊娠结局密切相关[[1]],GBS母体阴道定植率在全球发达国家和发展中国家相差不多,范围从8%-18%,总体估计约为12.7%[[2]]。GBS本是存在于健康成人的阴道和胃肠道内的共生细菌,但在某些情况下,可从无症状的黏膜携带状态转变为引起侵袭性感染的致病状态[[3]]。 GBS在阴道内定植需要克服许多困难,包括由黏液和上皮层产生的物理障碍、低 pH环境、抗微生物肽、抗体、杀微生物免疫细胞和由乳杆菌主导的阴道微生物群。我国关于GBS 的流行病学等相关研究甚少。但随着我国对 GBS 疾病的认识逐渐深入,GBS 孕期感染越来越受到重视。血糖水平的升高会使阴道局部糖原含量增多,导致其阴道内酸度增加,有利于阴道霉菌的增长。妊娠期血糖水平与B族链球菌携带是否有相关性,能够为B族链球菌筛查提供参考。
1资料与方法
1.1一般资料
收集2016年1月~2016年12月,在本院产科就诊及建卡的4377名孕妇,年龄19~46岁,平均年龄30.36±3.589,在孕8-12周、孕24-28周、孕32-35周进行空腹血糖检测及在其孕35~37周时进行GBS DNA检测。剔除在送检GBS DNA检测前一周使用抗生素的孕妇。
1.2仪器与方法
1.2.1血糖检测 孕妇在孕8-12周、孕24-28周、孕32-35周时采集清晨空腹血(采血前空腹8h), 2h内完成检测。
1.2.2 GBS DNA检测根据围生期GBS预防指南推荐的取材方法对外阴部位多余的分泌物进行擦拭处理,然后以无菌棉拭子置于阴道的下1/3处并进行旋转取阴道分泌物送检.于24 h内检测.不能及时处理标本放置于-20%℃冰箱保存待检。GBS DNA检测采用实时荧光定量PCR仪.试剂选择泰普生物有限公司生产的GBS核酸检测试剂盒.具体步骤参照试剂说明书进行。
1.3统计学方法
采用SPSS 25.0软件进行统计分析。血糖水平以(X±S)表示,组间比较采用T检验;P
2.结果4377例孕妇GBS检测阳性共263例,GBS检测阴性共4114例。
表1不同孕周空腹血糖与GBS携带T检验
空腹血糖 | t | P | 差值 95% 置信区间 | |
下限 | 上限 | |||
早孕期 | -2.192 | .028 | -.0976 | -.0054 |
中孕期 | .411 | .681 | -.0459 | .0704 |
晚孕期 | -.282 | .778 | -.0739 | .0553 |
GBS阳性孕妇孕8-12周血糖均值为(4.23±0.36)mmol/L;GBS阴性孕8-12周血糖均值为(4.28±0.37)mmol/L,两组血糖水平差异有统计学意义(T=-2.192,P=0.028),孕24-28周GBS检测阳性孕妇血糖均值为(4.39±0.52)mmol/L;GBS阴性血糖均值为(4.38±0.46)mmol/L,两组血糖水平无明显差异 (T=0.411,P=0.681),孕32-35周GBS检测阳性孕妇血糖均值为(4.19±0.52)mmol/L;GBS阴性血糖均值为(4.20±0.51)mmol/L,两组血糖水平无明显差异 (T=-0.282,P=0.77)。
3.讨论
B族链球菌又称无乳链球菌.是一种可正常定植于阴道、尿道和胃肠道内的革兰氏阳性球菌,通常不致病。妊娠期GBS感染易造成孕妇胎膜早破、早产、羊膜囊感染以及导致新生儿出现败血症、脑膜炎等,造成严重的后果[[4]]。妊娠期女性体内雌激素处于高表达水平,糖原大量沉积,从而促使乳酸水平升高,降低了阴道 pH 值水平, 这增强了妊娠期女性外阴阴道的抵抗能力,且pH值水平与孕期呈负相关,明显低于非妊娠期女性[[5]]。吴燕菁等[[6]]研究报道,随着妊娠的进展,血清E2升高,阴道PH呈下降的趋势。妊娠期体内雌激素和孕激素水平升高、糖原含量增加、阴道pH值改变引起菌群失调时,B 族链球菌繁殖增加。妊娠期 B 族链球菌感染的高危因素包括肥胖、高血压、血糖异常、多产、高龄、低龄和既往性生活活跃等[[7]]。其中,PH不仅能影响GBS的存活[[8]]和生物膜形成[[9]],还能通过调节GBS基因表达进而影响阴道定植。例如,在低pH环境下,GBS的双组分系统 CovR/S表达增加,进而负向调控其细胞外黏附素Bsa、菌毛以及溶血素的表达,影响细菌定植。 与CovR/S相反,双组分系统FspR/S,能够上调有关糖运输的基因表达,与6-磷酸果糖反应,进而促进 GBS 长久阴道定植
[[10]]。
目前,对于GBS 阴道定植引起妊娠不良结局的主流理论为上行感染机制[[11]]。体外实验和小鼠模型发现:GBS在阴道定植后,会激活整合素,进而诱导 FAK、AKT 和 GSK3β的依次磷酸化;同时,随着阴道上皮黏附连接的断开,β-连环素被释放到细胞质中,与磷酸化的GSK3β作用,导致β-连环素的稳定化及核移位;一旦 GBS进入细胞核内,β-连环素即可刺激包括驱动内皮间质转化和上皮剥脱的基因在内的各种靶基因的表达;而阴道上皮的剥脱不仅不能减少GBS的阴道定植,反而还可通过降低阴道屏障功能使得GBS上行传播,从而导致早产等不良妊娠结局。
妊娠期体内激素水平的变化容易导致阴道菌群的失调,增加了下生殖道感染的风险,有关研究 表明以假丝酵母菌感染最为多见[[12]]。阴道菌群与阴道上皮应激水平具有一定相关性。当阴道菌群发生改变,其与阴道上皮间平衡也随之改变,表现为阴道上皮因各种原因导致的损伤加重,进而提高自噬与应激水平[[13]]。妊娠期血糖变化导致阴道代谢旺盛,上皮剥脱增加,从而降低阴道屏障功能,导致胎膜早破等不良妊娠结局。宋保志等[[14]]认为孕妇血糖水平的高低与阴道微生态的失衡发生率有关,血糖较高的孕妇较正常健康孕妇阴道微生态失衡率高,增加了阴道感染的几率,进而导致与妊娠期阴道感染相关的不良妊娠的发生。早诊断、早治疗并将血糖控制在正常范围对减少妊娠期糖尿病孕妇阴道感染疾病的发生和不良妊娠结 局具有重要意义。
通过改变母体微生态,发现孕早期阴道菌群的结构组分变化与早产发生率增加密切相关。约1/3阴道乳杆菌量少的孕妇发生早产,甚至分娩时胎儿不足32孕周,而3/4阴道乳杆菌为优势菌群的孕妇成功维持妊娠至足月分娩[[15]]。本研究的结论孕8-12周孕妇的血糖水平与孕晚期GBS的阳性检出率之间存在明显的负相关性,高血糖水平反而有较低的感染风险,具体机制有待深入研究。考虑孕早期低血糖发孕妇孕晚期血糖水平的较大波动导致阴道菌群的改变,进而导致B族链球菌感染率增加,但需进一步研究证明孕期血糖水平的变化与B族链球菌感染的相关性,本研究提示孕期控制血糖稳定水平对妊娠结局有益。
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