Artemin Serves as a Novel Predictive Biomarker and Exerts a Protective Effect Against Preterm Birth

Background
Preterm birth (PTB) is a major cause of neonatal morbidity and mortality and is closely associated with dysregulated inflammatory responses at the maternal–fetal interface. Excessive activation of inflammatory signaling pathways often represents a terminal event in PTB, highlighting the need to identify upstream immunoregulatory factors involved in disease pathogenesis. This study investigated Artemin (ARTN), a member of the glial cell line-derived neurotrophic factor family, as a potential regulator of inflammation-associated PTB.

Methods
A total of 56 pregnant women, including cases of infectious preterm birth (IPB), non-infectious preterm birth (NIPB), and term birth (TB), were enrolled. Maternal plasma samples were analyzed using OLINK proteomics, and placental tissues were examined by immunohistochemistry and Western blotting. Differentially expressed inflammatory proteins were further evaluated using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. The diagnostic performance of ARTN was assessed using receiver operating characteristic curve analysis. In addition, an LPS-induced mouse model of inflammation-driven PTB was used to evaluate the potential protective effect of exogenous ARTN supplementation.

Results
ARTN expression was significantly reduced in maternal circulation and placental tissues in IPB and showed a strong positive correlation with gestational age. Enrichment analyses indicated that ARTN-associated inflammatory proteins were involved in cytokine–cytokine receptor interactions and JAK–STAT signaling. Receiver operating characteristic analysis demonstrated that ARTN exhibited strong discriminatory power for IPB, with an area under the curve of 0.864, and the predictive performance was further enhanced when ARTN was combined with IL-6. In the LPS-induced mouse model, ARTN supplementation markedly reduced preterm delivery and fetal mortality.

Conclusion
These findings suggest that ARTN may be involved in inflammation-associated PTB and may have potential value as a candidate predictive biomarker. However, because the human plasma samples were collected across a broad gestational age range and largely in a peripartum clinical context, the present data do not establish ultra-early predictive utility. Given the relatively small sample size and lack of independent validation, these results should be interpreted as preliminary and require confirmation in larger prospective cohorts.