Late preterm PROM (>33 weeks): the risk of intra-amniotic inflammation and fetal inflammation is influenced by the cervical microbial ecosystem and cervical inflammation.

Abstract

Background: Approximately 25-30% of pregnancies with late preterm prelabor rupture of membranes (PROM) are complicated by the development of fetal inflammatory response syndrome (FIRS), which is characterized by elevated levels of interleukin-6 in fetal blood. FIRS represents a serious condition that can induce temporary or persistent changes in multiple essential fetal organs. Most importantly, FIRS may impact infant neurodevelopment and increase the risk of neuropsychiatric disorders.

Objective: To characterize the cervical microbial ecosystem and cervical fluid interleukin-6 levels in late preterm PROM with respect to i) intra-amniotic inflammation and/or microbial invasion of the amniotic cavity, and ii) the development of FIRS.

Study design: This retrospective cohort study included women with singleton pregnancies complicated by late preterm PROM, in whom amniocentesis was performed at admission to assess intra-amniotic environment. Cervical fluid samples were collected using Dacron swabs upon admission. The samples were used for DNA isolation with sequencing of 16S rRNA gene and analysis of interleukin-6 levels. The cervical microbiota was classified based on the relative abundance of Lactobacillus species. Interleukin-6 levels in cervical fluid were measured using electrochemiluminescence. FIRS was defined as the concentration of interleukin-6 > 11.0 pg/mL in umbilical cord blood.

Results: A total of 114 women with late preterm PROM were included in this study. In total, 378 microbial taxa were identified in the cervical samples. Dominant abundance (≥50%) of L. iners and the depletion (<50%) of L. spp. were the most prevalent cervical ecosystems in women with intra-amniotic infection [63% (5/8)] and microbial invasion of the amniotic cavity without inflammation [82% (9/11)], respectively. Women whose fetuses developed FIRS had a lower prevalence of L. crispatus dominant cervical microbiota [2% (1/42) vs. 43% (31/72); p < 0.0001] and higher prevalences of L. iners dominant [38% (16/42) vs. 19% (14/92); p = 0.05] and L. spp. depleted cervical microbiotas [55% (23/42) vs. 32% (23/72); p = 0.02], compared to those whose fetuses did not develop FIRS. In the group of women with amniotic fluid negative for inflammation and microorganisms, FIRS was associated with a lower prevalence of L. crispatus dominant microbiota [0% (0/25) vs. 46% (29/63); p < 0.0001] and a higher prevalence of L. iners dominant microbiota [44% (11/25) vs. 20% (13/63); p = 0.04]. Cervical IL-6 levels were highest in women with intra-amniotic infection. The presence of FIRS was associated with elevated IL-6 levels.

Conclusion: Intra-amniotic and fetal inflammatory complications were influenced by the cervical microbial ecosystem and local inflammation. The absence of a high relative abundance of L. crispatus in the cervical microbial ecosystem was associated with an increased risk of the development of FIRS, irrespectively on the inflammatory status of amniotic fluid at admission.