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早产与足月产女性早孕期阴道微生态差异分析

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目的 比较早产和足月产女性早孕期阴道微生态的差异,探寻早产的预测方法。方法 采用回顾性病例对照研究法,以2022年6月至2023年12月在清华大学附属北京清华长庚医院分娩的2247例妊娠期女性为研究对象,其中98例早产(早产组),2149例足月产(足月产组)。采用倾向性评分匹配法,以年龄、孕次、产次作为协变量,匹配足月产妇98例。回顾分析入选对象在孕6~8周时阴道微生态检测结果,比较早产和足月产女性孕早期阴道分泌物功能、形态和阴道炎发生情况。结果 倾向性评分匹配前后早产组女性平均分娩孕周和新生儿平均体重均小于足月产组(均P<0。001),且匹配前后两组女性年龄、孕次和产次差异均无统计学意义(均P>0。050)。早产组女性阴道优势菌G+b(L)比例为82。5%,低于足月产组的91。8%(x2=10。260,P=0。001);早产组阴道乳杆菌分级为Ⅰ~Ⅱa的比例为84。5%,低于足月产组的91。4%(x2=5。039,P=0。021)。经倾向性评分匹配后,早产组以上两项指标亦显著低于足月产组(x2=8。000,P=0。005;x2=4。765,P=0。029);两组女性阴道菌群密度和多样性差异无统计学意义(x2=0。002,P=0。963;x2=0。416,P=0。519);经倾向性评分匹配后,两组女性阴道菌群密集度差异无统计学意义(x2=0。200,P=0。655),但早产组菌群多样性++~+++比例显著高于足月产组(x2=5。120,P=0。024)。早产组阴道分泌物平均pH值为5。09±0。37,显著高于足月产组的4。96±0。43(t=3。470,P<0。001);经倾向性评分匹配后,早产组亦显著高于足月产组(t=4。570,P<0。001)。两组女性阴道过氧化氢阳性率在倾向性评分匹配前后差异均无统计学意义(x2=0。725,P=0。338;x2=0。014,P=0。906)。早产组女性需氧菌性阴道炎(AV)检出率为12。4%,高于足月产组的5。2%(x2=9。049,P=0。003);经倾向性评分匹配后,早产组亦显著高于足月产组(x2=6。727,P=0。009)o两组女性细菌性阴道病(BV)、外阴阴道假丝酵母菌病(VVC)、混合性阴道炎检出率差异均无统计学意义(x2=0。790,P=0。374;x2=0。046,P=0。830;x2=3。915,P=0。064);经倾向性评分匹配后两组间 BV、VVC 和混合性阴道炎检出率差异均无统计学意义(均P>0。050)。条件Logistic多因素回归分析显示,优势菌G+b(L)(P=0。021,调整后 OR=0。218,95%CI:0。060~0。793)和 pH 值(P<0。001,调整后 OR=4。555,95%CI:1。992~10。419)保留在模型中。模型结果提示,早孕期阴道优势菌为G+b(L)者,相较于其他优势菌者,早产发生概率降低了约80%;而早孕期阴道分泌物pH值每增加1个单位,早产的概率将增加约4。6倍。在默认0。5的阈值情况下,包含了优势菌G+b(L)和pH值的条件Logistic模型的阳性检出率(灵敏度)为77。6%(95%CI:0。690~0。860),排除病例的能力(特异度)为75。5%(95%CI:0。670~0。840)。结论 建议女性在早孕期进行阴道微生态筛查。阴道分泌物中优势乳杆菌、阴道pH值和AV感染有望成为早产的预测指标。早孕期可利用阴道G+b(L)优势菌和pH值来预测早产风险。
Differences in vaginal microbiome between preterm and full-term delivery parturients
Objective To compare the differences in vaginal microbiome between preterm and full-term parturients in early pregnance,and explore the potential factors that predict preterm birth.Methods A total of 2,247 pregnant women who gave birth in our hospital from June 2022 to December 2023 were selected,including 98 cases of preterm delivery par-turients(preterm group)and 2,149 cases of full-term delivery parturients(full-term group),among which 98 full-term par-turients were matched with the baseline indicators of maternal age,gravidity and parity as covariables by propensity score matching(PSM).The results of vaginal microbiota testing at 6-8 weeks of pregnancy were retrospectively analyzed,and the differences in the function and morphology of vaginal microbiome,and onset of vaginitis between the two groups were compared.Results Before and after PSM,the mean gestational age and mean weight of newborns in the preterm delivery group were lower than those in the full-term delivery group(all P<0.050).There were no significant differences in age,gravidity and parity between the two groups(all P>0.050).Before and after PSM,the proportion of G+b(L)and Lactoba-cillary grades(LBG)in the preterm group were lower than those in the full-term group(all P<0.050).There were no signi-ficant differences in vaginal flora density and diversity between the two groups(x2=0.002,P=0.963;x2=0.416,P=0.519),but the difference in vaginal flora diversity was statistically significant after PSM(x2=5.120,P=0.024).The average pH value of vaginal discharge in the preterm group was 5.09±0.37,higher than the 4.96±0.43 in the full-term group(t=3.470,P<0.001);the difference in pH value was statistically significant after PSM(t=4.570,P<0.001).There was no significant difference in the positive rate of hydrogen peroxide(H2O2)between the two groups before and after PSM(x2=0.725,P=0.338;x2=0.014,P=0.906).The detection rate of aerobic vaginitis(AV)in the preterm group was 12.4%,higher than the 5.2%in the full-term group(x2=9.049,P=0.003);the difference in AV was statistically significant after PSM(x2=6.727,P=0.009).Before and after PSM,There were no significant differences in the detection rates of bacterial vaginosis(BV),vulvovaginal candidiasis(VVC)and mixed vaginitis between the two groups(all P>0.05).Dominant bacteria G+b(L)(P=0.021,adjusted OR=0.218,95%CI:0.060-0.793)and pH values(P<0.001,adjusted OR=4.555,95%CI:1.992-10.419)were retained in the model.The results of the model suggested that the preterm birth rate of the women with dom-inant bacteria G+b(L)in early pregnancy reduced by about 80%compared with non-G+b(L).For every one increment in the pH of vaginal secretions during early pregnancy,the probability of preterm birth increased by about 4.6 times.The sensitiv-ity of the final conditional Logistic model that included the dominant bacteria G+b(L)and pH value was about 0.78(95%CI:0.690-0.860)at the default threshold of 0.5;the specificity was about 0.76(95%CI:0.670-0.840).Conclusion Va-ginal microecological screening is recommended in early pregnancy.Dominant bacteria G+b(L),pH value and AV in vagin-al secretions are expected to predict premature delivery.Both less G+b(L)and rising pH value can be used to predict the risk of preterm birth in early pregnancy.

Prediction of preterm birthVaginal microbiomeEarly pregnanceVagina dominant bacteriapH valueVa-ginitis

陈华云、王昱洁、黄振宇、张琼琼、王颖、张蕾、吕涛、赵萌、廖秦平

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清华大学附属北京清华长庚医院妇产科,清华大学临床医学院,北京 102218

清华大学附属北京清华长庚医院医学数据科学中心,清华大学临床医学院

早产预测 阴道微生态 早孕期 阴道优势菌 pH值 阴道炎

国家自然科学基金委员会重点仪器研发项目清华大学精准医学院重点实验室项目北京市培育计划北京清华长庚医院研究基金

6192781920219990012PX202203912023C01009

2024

中国微生态学杂志
中华预防医学会 大连医科大学

中国微生态学杂志

CSTPCD北大核心
影响因子:1.115
ISSN:1005-376X
年,卷(期):2024.36(9)