Integrative model of cervical remodeling: associations between ultrasound, immune and microbiological markers

Aim: to characterize cervical maturity phenotypes identified by cluster analysis of ultrasound cervicometry and elastography parameters through evaluation of local immunological and microbiological markers associated with cervical remodeling.

Materials and Methods. A single-center prospective cohort study with 82 pregnant women in the third trimester was conducted to assess biomechanical, immunological, and microbiological characteristics of the cervix. Compression cervical elastography was performed by assessing hardness ratio (HR), elasticity contrast index (ECI), internal os strain (IOS), and external os strain (EOS). Quantitative assessment by polymerase chain reaction (PCR) of the cervical canal microbiocenosis and analysis of mRNA expression of innate immunity genes were also performed.

Results. There were identified three cervical maturity phenotypes characterized by a progressive decrease in tissue stiffness (HR), cervical shortening, and an increase in the elasticity contrast index (ECI) (p < 0.05). A significant decline in the expression of interleukin-18 (IL-18), GATA binding protein 3 (GATA3) as well as cluster of differentiation 68 (CD68) marker was observed during the transition from the immature to mature phenotype (p < 0.05). No significant differences in the taxonomic cervical microbiota composition were found among the phenotypes (p > 0.05); however, an increased abundance of non-Lactobacillus flora was associated with reduced cervical length and lower tissue stiffness. Predominantly negative correlations were identified between the abundance of opportunistic microorganisms and the expression levels of immune markers.

Conclusion. Cervical remodeling during pregnancy is associated with decreased local immune activity. Lowered expression of IL-18, GATA3, and CD68 may represent one of the mechanisms initiating inflammation followed by structural remodeling of cervical tissue. Although the microbiota does not determine the maturity phenotype, it may modulate magnitude of immune and biomechanical changes.

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