Maternal and Child Health Research Center, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Institute for Genome Sciences and Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
Nat Commun. 2019 Mar 21;10(1):1305. doi: 10.1038/s41467-019-09285-9.
Failure to predict and understand the causes of preterm birth, the leading cause of neonatal morbidity and mortality, have limited effective interventions and therapeutics. From a cohort of 2000 pregnant women, we performed a nested case control study on 107 well-phenotyped cases of spontaneous preterm birth (sPTB) and 432 women delivering at term. Using innovative Bayesian modeling of cervicovaginal microbiota, seven bacterial taxa were significantly associated with increased risk of sPTB, with a stronger effect in African American women. However, higher vaginal levels of β-defensin-2 lowered the risk of sPTB associated with cervicovaginal microbiota in an ethnicity-dependent manner. Surprisingly, even in Lactobacillus spp. dominated cervicovaginal microbiota, low β-defensin-2 was associated with increased risk of sPTB. These findings hold promise for diagnostics to accurately identify women at risk for sPTB early in pregnancy. Therapeutic strategies could include immune modulators and microbiome-based therapeutics to reduce this significant health burden.
未能预测和了解早产的原因，而早产是新生儿发病率和死亡率的主要原因，这限制了有效的干预和治疗措施的发展。我们对 2000 名孕妇进行了一项嵌套病例对照研究，其中包括 107 例自发性早产（sPTB）和 432 例足月分娩的妇女。我们使用宫颈阴道微生物组的创新贝叶斯模型，发现七个细菌分类群与 sPTB 的风险增加显著相关，在非裔美国女性中影响更强。然而，阴道β-防御素-2 水平较高以一种依赖种族的方式降低了与宫颈阴道微生物组相关的 sPTB 风险。令人惊讶的是，即使在乳杆菌为主的宫颈阴道微生物组中，低β-防御素-2 也与 sPTB 的风险增加相关。这些发现为在妊娠早期准确识别有早产风险的妇女的诊断提供了希望。治疗策略可能包括免疫调节剂和基于微生物组的治疗方法，以减轻这一重大健康负担。
