J Periodontol 2013;84(4 Suppl.):S170-S180 doi:10.1902/jop.2013.1340015 Adverse pregnancy outcomes (APOs) and periodontal disease: pathogenic mechanisms Madianos PN, Bobetsis YA, Offenbacher S. Adverse pregnancy outcomes (APOs) and periodontal disease: pathogenic mechanisms. Abstract Aim: To evaluate the evidence on potential biological pathways underlying the possible association between periodontal disease (PD) and adverse pregnancy out- comes (APOs). Material & Methods: Human, experimental and in vitro studies were evaluated. Results: Periodontal pathogens/byproducts may reach the placenta and spread to the foetal circulation and amniotic fluid. Their presence in the foeto-placental compartment can stimulate a foetal immune/inflammatory response characterized by the production of IgM antibodies against the pathogens and the secretion of elevated levels of inflammatory mediators, which in turn may cause miscarriage or premature birth. Moreover, infection/inflammation may cause placental struc- tural changes leading to pre-eclampsia and impaired nutrient transport causing low birthweight. Foetal exposure may also result in tissue damage, increasing the risk for perinatal mortality/morbidity. Finally, the elicited systemic inflammatory response may exacerbate local inflammatory responses at the foeto-placental unit and further increase the risk for APOs. Conclusions: Further investigation is still necessary to fully translate the findings of basic research into clinical studies and practice. Understanding the systemic virulence potential of the individual’s oral microbiome and immune response may be a distinctly different issue from categorizing the nature of the challenge using clinical signs of PD. Therefore, a more personalized targeted therapy could be a more predictive answer to the current “one-size-fits-all” interventions. Phoebus N. Madianos 1 , Yiorgos A. Bobetsis 2 and Steven Offenbacher 3 1 Department of Periodontology, School of Dentistry, University of Athens, Athens, Greece; 2 Department of Periodontology, School of Dentistry, University of Athens, Athens, Greece; 3 Department of Periodontology, University of North Carolina School of Dentistry at Chapel Hill, NC, USA Key words: adverse pregnancy outcomes; experimental studies; in vitro studies; pathogenic mechanisms; periodontal disease Accepted for publication 14 November 2012 The proceedings of the workshop were jointly and simultaneously published in the Journal of Clinical Periodontology and Journal of Periodontology. In 1891, Miller published the theory of “focal infection” which hypothe- sized that oral foci of infection were responsible for a number of regional and systemic diseases, such as tonsilli- tis, pneumonia, endocarditis and sep- ticaemia. (Miller 1891) However, the lack of scientific evidence condemned this theory to dormancy. One hun- dred years later, in the early 1990s, Offenbacher’s group using a bactere- mia model and a “chamber” model to mimic a focal infection on preg- nant hamsters demonstrated that periodontal bacteria and inflamma- tory mediators have the ability to disseminate systematically to the foetal-placenta unit, via the blood circulation and induce pregnancy complications. Hence, the authors proposed that oral infection, such as periodontitis, may act as a distant infectious reservoir and affect preg- nancy outcomes. (Collins et al. 1994a,b) Since these first landmark series of animal studies, many investi- gators have tried to elucidate whether this causal pathway of an oral patho- gen inducing adverse pregnancy out- comes (APOs) in an animal model has analogy with periodontal disease and APOs in humans. Although a large number of epi- demiological and intervention studies demonstrate a positive association Conflict of interest and source of funding statement The authors declare no conflict of interest. The workshop was funded by an unrestricted educational grant from Colgate-Palmolive to the European Federation of Periodontology and the American Academy of Periodontology. © 2013 European Federation of Periodontology and American Academy of Periodontology S170