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Biomarkers of Preterm Birth

A recent study has found that levels of lactic-D acid and TIMP-1 protein can serve as biomarkers for cervix length in pregnant women, helping to assess women’s risk of preterm birth.

Preterm birth, which is birth that occurs before week 37 of pregnancy is associated with many medical complications for mother and baby, imposing both medical and economic burden. As a common practice, in the developed countries, women have ultrasound measurements for cervix length, and those who are identified with a short cervix are treated with progesterone to prevent preterm birth.  The problem arises for populations in non-developed regions, with no immediate access for medical equipment and those are at a higher risk for not being treated for preterm labor.

As part of an Integrative human microbiome project, previous studies analyzing sequencing data of thousands of microbiomes, have reported that women who delivered preterm, exhibited lower levels of Lactobacillus crispatus strain. These data imply that together with genetic and environmental factors, vaginal microbiome composition plays an important role in the progression of a healthy pregnancy.

In a multidisciplinary collaboration between researchers from the Obstetrics and Gynecology and Biological Science departments from USA and Brazil, and bioinformaticians from the University of Idaho, Moscow, Idaho, USA, potential biomarkers predicting cervical length and risk of preterm birth, without the need for complex medical equipment were identified. The researchers assessed whether measuring specific compounds in the vaginal fluids, through a non-invasive, and cost-effective approach, can predict the two major risk factors of preterm birth, which are cervix length and Lactobacillus abundance, and whether this has the potential to be developed into a point-of-care preterm birth test.

A total of 340 women, with a mean age of about 29, and a mean BMI of about 28 were enrolled in the study.  Mean cervical length was 32.9 mm, and about 11% of women had a short cervix (<25mm). About 17% of women had preterm birth (defined as before 37 weeks gestation).  Levels of Lactic-D acid, tissue inhibitor of matrix metalloproteinases TIMP-1 and TIMP-2, were quantified by an enzyme-linked immunosorbent assay (ELISA), while vaginal microbiomes compositions were assessed by sequencing of the ribosomal rRNA, and cervical length was determined by transvaginal ultrasound.

The researchers reported that Lactic Acid-D levels can indicate which bacterial strain is dominated in vaginal fluid, while levels of TIMP-1 protein, negatively correlates with cervical length.

Dr Forney, one of the authors, optimistically noted “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.”

Written by Bella Groisman


Witkin SS, Moron AF, Ridenhour BJ, Minis E, Hatanaka A, Sarmento SGP, Franca MS, Carvalho FHC, Hamamoto TK, Mattar R, Sabino E, Linhares IM, Rudge MVC, Forney LJ. 2019. Vaginal biomarkers that predict cervical length and dominant bacteria in the vaginal microbiomes of pregnant women. mBio, 10:e02242-19.

Fettweis, JM et al., (2019). The vaginal microbiome and preterm birth. Nature. 25, 1012-1021.

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Image by Mario D from Pixabay




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