Immune Markers Linking Chronic Periodontitis with Gestational Complications: A Systematic Review.

Objective: This systematic review aimed to determine how mediators establish a causal association between chronic periodontitis and adverse pregnancy outcomes (APOs). Methodology: The PRISMA 2020 guidelines were followed. Studies were selected using the PECO model to assess the inflammatory mediators linking chronic periodontitis and APOs. Six databases (PubMed, Scopus, Web of Science, Embase, Cochrane Library (CENTRAL) and Google Scholar) were searched from May 15-20, 2025. Inclusion criteria targeted English-language studies (2000-2025) reporting inflammatory markers in periodontitis-affected pregnancies. Case reports, editorials, conference abstracts, grey literature, in vitro studies and studies involving subjects other than humans, rats and baboons were excluded. Two independent reviewers screened and extracted data. The risk of bias was assessed using ROBINS-I, NOS or ROBIS tools. A qualitative synthesis of findings was performed. Results: Periodontitis is strongly linked to APOs, including gestational diabetes mellitus (GDM), preterm deliveries, preeclampsia and low birth weight (LBW). Inflammatory mediators, such as TNF-α, IL-1β, IL-6, IL-8, CRP, PGE2, MCP-1 and MMPs, are elevated, disrupting placental function. Conclusion: Periodontitis is strongly associated with APOs through direct microbial invasion and indirectly through systemic inflammatory mediators, which disrupt placental function and the fetus's development. These findings highlight that a healthy periodontium is crucial in preventing complications like GDM, preeclampsia, preterm deliveries and LBW.