Periodontal diseases and adverse pregnancy outcomes Shihoko Komine-Aizawa 1 , Sohichi Aizawa 1,2 and Satoshi Hayakawa 1 1 Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo and 2 Department of Oral Surgery, JCHO Yokohama Chuo Hospital, Kanagawa, Japan Abstract From last decade of the 20th century, numerous epidemiological studies and intervention trials have attempted to prove the relationships between maternal periodontal diseases and adverse pregnancy outcomes (APO). Periodontal diseases are considered a risk factor for APO, including preterm birth, fetal growth restriction, low birthweight, pre-eclampsia and gestational diabetes. However, the efficacy of periodontal treatment during pregnancy is controversial. Two pathogenic mechanisms might explain the potential effect of periodontal dis- eases on pregnancy outcomes. First, periodontal bacteria originating in the gingival biofilm directly affect the feto-placental unit subsequent to bacteremia. Second, inflammatory mediators secreted by the subgingival inflammatory site are carried to the feto-placental unit, where they then cause an inflammatory response. To elucidate these mechanisms, many researchers have been investigating the use of experimental animal models and in vitro models. In the present review, we summarize the current literature on the relationship between periodontal diseases and APO from epidemiological studies, animal models studies and in vitro studies, and speculate on the possible mechanism of periodontal diseases affecting pregnancy outcomes. Key words: low birthweight, periodontal diseases, pre-eclampsia, pregnancy, premature birth. Introduction Periodontal disease, or gum disease, is one of the most common chronic inflammatory disorders that affect the tissues surrounding the teeth (Fig. 1). 1 Gin- givitis is a mild form of periodontal disease that causes redness and swelling (inflammation) of the gingiva. Though gingivitis is localized to only the gin- giva without destroying periodontal tissues, gingivitis can progress to serious gum disease called periodonti- tis. Periodontitis is a severe form of periodontal dis- ease and induces inflammatory changes in the gingival epithelium, periodontal membrane, dental cement and alveolar bone (Fig. 2). The loss of connec- tive tissue and alveolar bone by periodontitis could lead to the loss of teeth. The prevalence of periodonti- tis is more than 50% of the adult population. 2 Periodontal diseases are caused by multiple gram- negative microaerophilic and anaerobic bacteria, such as Porphyromonas gingivalis, Fusobacterium nucleatum, Prevotella intermedia, Actinobacillus actinomycetemcomi- tans and Treponema denticola. Recent epidemiological studies have suggested that periodontitis is a risk factor for other systemic dis- eases, including pneumonia, 3,4 especially aspiration pneumonia in the elderly, 4 diabetes mellitus 5 and ath- erosclerosis. 6 Periodontal diseases are also regarded as a risk factor for pregnancy complications. In the last two decades, many researchers have investigated the relationship between periodontal diseases and various adverse pregnancy outcomes (APO). The potential effect of periodontal diseases might be explained by two mechanisms: the translocation of periodontal pathogens to the feto-placental unit, or the effect of inflammatory mediators, such as interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor-α (TNF-α) or prostaglandin E 2 (PGE 2 ), on the feto- placental unit. In this review article, we summarize the current literature on the relationship between peri- odontal diseases and APO from epidemiological Received: June 9 2018. Accepted: July 13 2018. Correspondence: Dr Shihoko Komine-Aizawa, Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, 173-8610, 30-1 Oyaguchikamicho, Itabashi-ku, Tokyo, Japan. Email: aizawa.shihoko@nihon-u.ac.jp 1 © 2018 Japan Society of Obstetrics and Gynecology doi:10.1111/jog.13782 J. Obstet. Gynaecol. Res. 2018