Payne Matthew S, Newnham John P, Doherty Dorota A, Furfaro Lucy L, Pendal Narisha L, Loh Diane E, Keelan Jeffrey A
Division of Obstetrics and Gynaecology, The University of Western Australia, Subiaco, Australia; Women and Infants Research Foundation, Subiaco, Australia.
Division of Obstetrics and Gynaecology, The University of Western Australia, Subiaco, Australia; Women and Infants Research Foundation, Subiaco, Australia.
Am J Obstet Gynecol. 2021 Feb;224(2):206.e1-206.e23. doi: 10.1016/j.ajog.2020.08.034. Epub 2020 Aug 27.
Intrauterine infection accounts for a quarter of the cases of spontaneous preterm birth; however, at present, it is not possible to efficiently identify pregnant women at risk to deliver preventative treatments.
This study aimed to establish a vaginal microbial DNA test for Australian women in midpregnancy that will identify those at increased risk of spontaneous preterm birth.
A total of 1000 women with singleton pregnancies were recruited in Perth, Australia. Midvaginal swabs were collected between 12 and 23 weeks' gestation. DNA was extracted for the detection of 23 risk-related microbial DNA targets by quantitative polymerase chain reaction. Obstetrical history, pregnancy outcome, and demographics were recorded.
After excluding 64 women owing to losses to follow-up and insufficient sample for microbial analyses, the final cohort consisted of 936 women of predominantly white race (74.3%). The overall preterm birth rate was 12.6% (118 births); the spontaneous preterm birth rate at <37 weeks' gestation was 6.2% (2.9% at ≤34 weeks' gestation), whereas the preterm premature rupture of the membranes rate was 4.2%. No single individual microbial target predicted increased spontaneous preterm birth risk. Conversely, women who subsequently delivered at term had higher amounts of Lactobacillus crispatus, Lactobacillus gasseri, or Lactobacillus jensenii DNA in their vaginal swabs (13.8% spontaneous preterm birth vs 31.2% term; P=.005). In the remaining women, a specific microbial DNA signature was identified that was strongly predictive of spontaneous preterm birth risk, consisting of DNA from Gardnerella vaginalis (clade 4), Lactobacillus iners, and Ureaplasma parvum (serovars 3 and 6). Risk prediction was improved if Fusobacterium nucleatum detection was included in the test algorithm. The final algorithm, which we called the Gardnerella Lactobacillus Ureaplasma (GLU) test, was able to detect women at risk of spontaneous preterm birth at <37 and ≤34 weeks' gestation, with sensitivities of 37.9% and 44.4%, respectively, and likelihood ratios (plus or minus) of 2.22 per 0.75 and 2.52 per 0.67, respectively. Preterm premature rupture of the membranes was more than twice as common in GLU-positive women. Adjusting for maternal demographics, ethnicity, and clinical history did not improve prediction. Only a history of spontaneous preterm birth was more effective at predicting spontaneous preterm birth than a GLU-positive result (odds ratio, 3.6).
We have identified a vaginal bacterial DNA signature that identifies women with a singleton pregnancy who are at increased risk of spontaneous preterm birth and may benefit from targeted antimicrobial therapy.
宫内感染占自发性早产病例的四分之一；然而，目前尚无法有效识别有早产风险的孕妇并给予预防性治疗。
本研究旨在为澳大利亚孕中期女性建立一种阴道微生物DNA检测方法，以识别那些有较高自发性早产风险的女性。
在澳大利亚珀斯招募了1000名单胎妊娠女性。在妊娠12至23周期间采集阴道中段拭子。提取DNA，通过定量聚合酶链反应检测23个与风险相关的微生物DNA靶点。记录产科病史、妊娠结局和人口统计学信息。
在排除64名因失访和微生物分析样本不足的女性后，最终队列由936名主要为白人种族的女性组成（74.3%）。总体早产率为12.6%（118例分娩）；妊娠<37周的自发性早产率为6.2%（妊娠≤34周时为2.9%），而胎膜早破早产率为4.2%。没有单一的微生物靶点能预测自发性早产风险增加。相反，随后足月分娩的女性阴道拭子中卷曲乳杆菌、加氏乳杆菌或詹氏乳杆菌的DNA含量更高（自发性早产为13.8%，足月分娩为31.2%；P = 0.005）。在其余女性中，识别出一种特定的微生物DNA特征，该特征强烈预测自发性早产风险，由阴道加德纳菌（进化枝4）、惰性乳杆菌和微小脲原体（血清型3和6）的DNA组成。如果在检测算法中纳入具核梭杆菌检测，风险预测会得到改善。我们将最终算法称为加德纳菌-乳杆菌-脲原体（GLU）检测，该检测能够检测出妊娠<37周和≤34周有自发性早产风险的女性，敏感性分别为37.9%和44.4%，阳性似然比分别为每0.75为2.22和每0.67为2.52。胎膜早破早产在GLU阳性女性中是其两倍多。调整产妇人口统计学、种族和临床病史并不能改善预测。只有自发性早产史在预测自发性早产方面比GLU阳性结果更有效（优势比为3.6）。
我们已经识别出一种阴道细菌DNA特征，可识别单胎妊娠且有较高自发性早产风险的女性，这些女性可能从靶向抗菌治疗中获益。
