Late preterm prelabor rupture of membrane (>33 weeks): the risk of intraamniotic inflammation and fetal inflammation is influenced by the cervical microbial ecosystem and cervical inflammation.

Abstract

Background: Approximately 25% to 30% of pregnancies with late preterm prelabor rupture of membranes are complicated by the development of fetal inflammatory response syndrome, which is characterized by elevated levels of interleukin 6 in fetal blood. Fetal inflammatory response syndrome represents a serious condition that can induce temporary or persistent changes in multiple essential fetal organs. Most importantly, fetal inflammatory response syndrome 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 prelabor rupture of membrane (34 0/7 - 36 6/7 weeks) with respect to intraamniotic inflammation and microbial invasion of the amniotic cavity and the development of fetal inflammatory response syndrome.

Study design: This retrospective cohort study included women with singleton pregnancies complicated by late preterm prelabor rupture of membrane, in whom amniocentesis was performed at admission to assess intraamniotic environment. Cervical fluid samples were collected using Dacron swabs upon admission. The samples were used for DNA isolation with sequencing of 16S ribosomal RNA 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. Fetal inflammatory response syndrome 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 prelabor rupture of membrane were included in this study. In total, 378 microbial taxa were identified in the cervical samples. Dominant abundance (≥50%) of Lactobacillus iners and the depletion (<50%) of Lactobacillus spp. were the most prevalent cervical ecosystems in women with intraamniotic infection (63% [5/8]) and microbial invasion of the amniotic cavity without inflammation (82% [9/11), respectively. Women whose fetuses developed fetal inflammatory response syndrome had a lower prevalence of Lactobacillus crispatus dominant cervical microbiota (2% [1/42] vs 43% [31/72]); P<.0001) and higher prevalences of Lactobacillus iners dominant (38% [16/42] vs 19% [14/92]; P=.05) and Lactobacillus spp. depleted cervical microbiotas (55% [23/42] vs 32% [23/72]; P=.02), compared to those whose fetuses did not develop fetal inflammatory response syndrome. In the group of women with amniotic fluid negative for inflammation and microorganisms, fetal inflammatory response syndrome was associated with a lower prevalence of Lactobacillus crispatus dominant microbiota (0% [0/25] vs 46% [29/63]; P<.0001) and a higher prevalence of Lactobacillus iners dominant microbiota (44% [11/25] vs 20% [13/63]; P=.04). Cervical fluid interleukin 6 levels were highest in women with intraamniotic infection. The presence of fetal inflammatory response syndrome was associated with elevated cervical fluid interleukin 6 levels.

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