Abstract
Objective: Early-onset neonatal sepsis (EONS) due to ascending infection is a potentially preventable complication of preterm premature rupture of membranes (PPROM). Our objective was to determine whether the analysis of bacteria from vaginal swab samples is predictive of the risk of EONS in PPROM.
Study design: In a prospective 3-center observational cohort, patients with PPROM were enrolled between 22 and 36 weeks’ gestation (WG) + 6 days. Vaginal swab samples at delivery were analyzed using two different approaches, classical bacterial cultures and shotgun metagenomic sequencing analysis. A metagenomics score was constructed combining the characterization of the vaginal microbiome and the presence of pathogens and the optimal cut-off to predict EONS was tested on a receiver operating curve.
Results: 563 PPROM cases were enrolled, with 646 liveborn neonates. PPROM occurred < 32 WG in 41.9% and deliveries were < 34 WG in 41.0%. The incidence of EONS was 29/646 (4.5%). When considering all central and peripheral microbiological samples available for 26 neonates, the main pathogens isolated were Escherichia coli in 14 cases (53.8 %), other gram-negatives in 5 (19.2%), strict anaerobes in 3 (11.5%); there was a single case (3.8%) each with Group B Streptococcus (GBS), Streptococcus anginosus, Staphylococcus aureus and Ureaplasma urealyticum. We studied the prediction of EONS among 272 mothers and their 310 neonates (20 EONS, 6.4%) with both culture and metagenomic data available. A culture positive for a major or intermediate pathogen in the vaginal sample at delivery had a sensitivity of 80.0 % (95% CI=56.3-94.3) and a specificity of 37.9% (95% CI=32.3-43.8), adjusted odds ratio (aOR) of 1.6 (95 % CI [0.5-5.0]) to predict EONS. The presence of E. coli was associated with an EONS risk of 10.6% vs 4.9%, in the absence of E. coli (p=0.07). The metagenomics score was highly associated with EONS, with an area under the receiver operating curve of 0.75 (95% CI, 0.61-0.90). At the optimal cutoff value, sensitivity was 70% (95% CI, 64-95%), specificity was 85% (95% CI, 81-89%). A metagenomics score greater than 40 was associated with a significantly increased risk of EONS with an aOR of 8.9 (95 % CI [3.5; 22.3]) in multivariate analysis adjusted for latency period and gestational age, p<0.001.
Conclusion: In PPROM, conventional microbial culture of maternal vaginal samples was associated with EONS, but its predictive values remain insufficient to guide perinatal care. Metagenomic microbial signatures improved predictive values. This opens the perspective for a rapid point-of-care test.