Vaginal Biomarkers Predict Preterm Birth Risks

Premature birth and its complications are the largest contributors to infant death in the USA and globally. Complications of preterm birth are the single largest cause of neonatal deaths and account for 35% of the world’s 3.1 million neonatal deaths each year.

A short cervical length and the depletion of Lactobacillus species are known risk factors for preterm birth. In many resource-poor areas of the world, the technology to test for the occurrence of these risk factors is unavailable, and pregnant women with specific risk factors are neither identified nor treated.

An international team of scientists working with the University of Idaho (Moscow, ID, USA) collected and analyzed vaginal fluid samples from 340 mid-trimester pregnant women to determine correlates of a short cervix. They carried out a prospective study of these women who were undergoing a routine vaginal ultrasound to assess cervical length at the obstetrical outpatient clinic at The Federal University of Sao Paulo (Sao Paulo, Brazil).

Vaginal levels of the D- and L-lactic acid isomers were quantitated by colorimetric assays using the EnzyChrom D-lactic acid and L-lactic acid kits (BioAssay Systems, Haywood, CA, USA). The levels of TIMP-1, TIMP-2, MMP-2, MMP-8, and Hsp70 (all from R&D Systems, Minneapolis, MN, USA) and total protein (Thermo-Fisher Scientific, Waltham, MA, USA) were measured in the vaginal fluid supernatant. The p62 (Enzo Life Sciences, Farmingdale, NY, USA), the a2 isoform of vacuolar ATPase (a2V) (MyBioSource, San Diego, CA, USA), and total protein in the lysed epithelial cell fraction were determined by commercial enzyme-linked immunosorbent assay (ELISA) kits. The compositions of vaginal microbiomes were assessed by analysis of the V1-V3 regions of 16S rRNA genes, while cervical length was determined by transvaginal ultrasonography.

The scientists reported that the vaginal microbiomes could be clustered into five community state types (CSTs), four of which were dominated by a single Lactobacillus species. The dominance of Lactobacillus crispatus or Lactobacillus jensenii in the vaginal microbiome predicted the level of D-lactic acid present. Several of the biomarkers, especially TIMP-1, in combination with the subject’s age and race, were significantly associated with cervical length.

Larry Forney, PhD, a professor and senior author of the study, said, “Measuring levels of TIMP-1 and D-lactic acid in vaginal secretions might be a straightforward way to assess a woman's risk for preterm birth. This is a prime example of the kind of study that can be done when you bring people in from different disciplines. This team of investigators included obstetricians, gynecologists, immunologists, microbial ecologists, and statisticians.

The authors concluded that concluded that measuring levels of TIMP-1 and D-lactic acid in vaginal secretions might be a straightforward way to assess the risk for preterm birth due to a short cervix and microbiome composition. The study was published on October 22, 2019, in the journal mBio.

Related Links:
University of Idaho
The Federal University of Sao Paulo
R&D Systems
BioAssay Systems
Thermo-Fisher Scientific
Enzo Life Sciences
MyBioSource