by Juandre Makaka

Most pregnant women encounter a fear of delivering their babies before they are fully developed. Expecting to carry their child and deliver them safely after 39 weeks, delivery before 37 weeks gestation (preterm birth (PTB)) can genuinely cause panic, especially when it spontaneously occurs. As if an unplanned birth is not traumatic enough PTB also has a negative effect on the health of the infant and could lead to death. This indicates an immediate need for better diagnostic and interventions, which researchers have been attempting to address.

Spontaneous preterm birth (sPTB), a leading cause of neonatal morbidity and mortality, is intricately linked to bacterial infections that trigger inflammation, leading to premature labor. However, advances in sequencing and inflammatory marker profiling have shed light on this complex process. These techniques have shown that a balanced vaginal microbiome dominated by Lactobacillus spp. signifies healthy pregnancy, while imbalances elevate the risk of sPTB. Bacterial vaginosis (BV) which is marked by unfavorable bacterial overgrowth, is associated with sPTB. It was also found that vaginal microbiota’s role varies by race and geography, affecting pregnancy outcomes. Racial differences influence sPTB correlates, warranting deeper investigations.

Specific culprits include Gardnerella vaginalis, Fusobacterium nucleatum, Ureaplasma parvum, and Mycoplasma. Certain Lactobacillus spp. reduce risk, while others don’t. Infections like STIs and urinary tract infections also contribute. Functional diversity in bacterial strains and host inflammatory responses complicates universal diagnostics and interventions. Diagnostic tests such as culture, microscopy, nucleic acid tests, and the ‘Gardnerella, Lactobacillus, Ureaplasma (GLU) test have potential. However, early prediction remains elusive except for identifying short cervix cases.

Metaproteomics and metabolomics are transforming microbial research. Mass spectrometry (MS) techniques decipher microbial functions, host responses, and interactions as well as evolve with cost-effective high-throughput platforms, boosting diagnostics accessibility. Metabolites and proteins indicate biomarkers linked to sPTB risk of which metaproteomics extends beyond bacteria to fungi, viruses, and archaea, unlike genomic analysis which usually only covers bacteria.

Proteomics and metabolomics studies unveil protein and metabolite biomarkers, even detecting subclinical infections. Invasive amniocentesis remains key for some markers, yet non-invasive alternatives emerge. Human proteases, protease inhibitors, and protease-linked inflammation add complexity. While there are still many challenges, these approaches promise a deeper understanding of sPTB, potentially transforming prevention and treatment strategies.

Intriguingly, diverse microbial functions, host responses, and individual variability underscore the need for personalized diagnostics and interventions, marking a promising direction for combating sPTB. This with the evolution of mass spectrometry can lead to a clinical breakthrough.

References
Masson, L, Wilson, J, Amir Hamzah, AS, Tachedjian, G, Payne, M. Advances in mass spectrometry technologies to characterize cervicovaginal microbiome functions that impact spontaneous preterm birth. Am J Reprod Immunol. 2023; 90:e13750. https://doi.org/10.1111/aji.13750

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