Preterm birth and periodontal disease: A medical ...

[Downloaded free from http://www.jicdro.org on Wednesday, September 28, 2016, IP: 79.124.101.183]

Special Feature

Preterm birth and periodontal disease: A medical perspective Neeta Dhabhai

Department of Obstetrics and Gynaecology, Metro Heart and Multispeciality Hospital, Faridabad, Haryana (Dehi-NCR), India

ABSTRACT Births occurring before 37 weeks resulting in prematurity poses serious hazards to the baby from delayed growth, neurodevelopmental anomalies to death and unfortunately India is in the top four countries with maximum preterm births and leads globally in deaths by prematurity. Infection is a very important component of the etiopathogenesis of preterm labor and periodontal disease is a rather unexplored aspect of infection very often overlooked by the general gynecologist and the dental practitioner equally. Periodontal disease is a potential foci of infectious pathogens which may disseminate hematogenously and effect the fetus. In this article, an effort has been made to find an evidence‑based link between periodontal disease and preterm labor to drive home the conclusion that an early screening and diagnosis in pregnancy followed up with effective treatment of periodontal disease may significantly reduce the burden of preterm births.

Access this article online Website: www.jicdro.org DOI: 10.4103/2231-0754.186421 Quick Response Code:

Key words: Evidence based link, infection, prematurity

INTRODUCTION

ETIOPATHOGENESIS OF PRETERM BIRTHS

Preterm birth is defined as babies born alive before 37 weeks of pregnancy are completed. Globally 15 million babies are born prematurely every year and account for 40% of under‑five deaths. More than one in ten babies are born preterm, affecting families all around the world, and over 1 million children die each year due to complications of preterm birth.[1]

The exact cause of human parturition and its initiation has not been fully understood till date and data from animal experiments demonstrate that the primary stimulus for the initiation of physiological labor arises from the fetal hypothalamo‑pituitary‑adrenal axis. This in turn stimulates steroid synthesis and prostaglandin production leading to dilation of the cervix and the onset of myometrial/uterine contractions.

India is among the top ten countries with maximum preterm births, a rate of 21%[2] and of the 3.6 million preterm births in India, 303,600 do not survive, in short, we have maximum deaths due to prematurity. It is very imperative, hence in the Indian context to prevent preterm births and explore and implement preventive methodology. Being born preterm also exposes the baby to other risks of death due to infection and malnutrition and predisposes the baby to long‑term effects of visual and hearing impairment, chronic lung disease accelerated weight gain in adolescence, neurodevelopmental delay, and psychiatric and behavioral problems. Address for correspondence: Dr. Neeta Dhabhai, 668, Sector 15, Faridabad ‑ 121 007, Haryana, India. E‑mail: [email protected]

98

The basic mechanism of spontaneous preterm labor is inflammation, and similar processes are also responsible for the onset of labor at term. While we do not know what precisely starts the physiological labor, several factors are implicated in preterm labor such as infection, uteroplacental This is an open access article distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as the author is credited and the new creations are licensed under the identical terms. For reprints contact: [email protected] Cite this article as: Dhabhai N. Preterm birth and periodontal disease: A medical perspective. J Int Clin Dent Res Organ 2016;8:98-101.

© 2016 Journal of the International Clinical Dental Research Organization | Published by Wolters Kluwer - Medknow

[Downloaded free from http://www.jicdro.org on Wednesday, September 28, 2016, IP: 79.124.101.183] Dhabhai: Preterm birth and periodontitis

ischemia, and hormonal abnormalities (progesterone‑ or corticotropin‑releasing hormone‑related) and comorbid conditions in mother including malnutrition, low immunity, fever, and stress. Inflammatory processes affect both the mother and the fetus and initiate the fetal inflammatory response syndrome. The role of many risk factors has been shown by results of epidemiological studies such as increasing the age of women giving birth, ethnic origin, tobacco, socioeconomic disparities, maternal body‑mass index, or multiple pregnancies. Cervical incompetence or short cervical length, preeclampsia and numerous maternal infections, systemic like toxoplasmosis, and local infections such as bacterial vaginosis, chorioamnionitis, or urogenital tract infections increase the risk of preterm birth. Unfortunately, around 50% of causes of preterm birth remain unknown. In 1996, Offenbacher et al. introduced the hypothesis that periodontal diseases could be a potential risk factor for preterm birth. Since then many epidemiological or interventional studies have been performed to explore this relationship.[3]

PRETERM BIRTHS AND PERIODONTAL INFECTION……IS THERE A LINK? While lot infections are screened, periodontal inflammation has received scant attention in this regard. The concept that periodontal disease might influence systemic health is not new. Miller originally published his focal infection theory in 1891[4] suggesting that microorganisms or their waste products obtain entrance to parts of the body adjacent to or remote from the mouth. Periodontal infection happens to serve as a bacterial reservoir that may exacerbate systemic diseases. Re s e a rc h s u g g e s t s t h a t t h e b a c t e r i a t h a t c a u s e inflammation in the gums can affect the fetus through blood circulation. Endotoxins resulting from Gram‑negative bacterial infections which stimulate the production of cytokines and prostaglandins (interleukin‑1β (IL‑1β), IL‑6, and tumor necrosis factor‑α) stimulate labor, and the proinflammatory mediators may cross the placenta barrier and cause fetal toxicity resulting in preterm delivery and low‑birth‑weight babies. High concentrations of these cytokines, in pregnant women, are responsible for rupture of the uterine membranes causing premature birth.[5] Numerous epidemiological studies have shown a link between periodontal disease and preterm birth as the risk

factors for periodontal disease are the same as risk factors for preterm birth, but some data are contradictory.[6]

THE EVIDENCE We know that majority of intrauterine infection originates in the lower genital tract. Despite this statement, number of studies report intrauterine infections caused by species not found in the urogenital tract. Analyses of amniotic fluid or placenta have shown the presence of different oral pathogens such as Bergeyella, Eikenella, Fusobacterium nucleatum,[7] or Porphyromonas gingivalis.[8] The frequent gingival inflammation of women presenting periodontal diseases,[9] especially pregnancy‑associated gingivitis, facilitates bacteremia process. Furthermore, the more periodontal pockets are deep, the more important is the exchange surface between bacteria biofilm and blood circulation (15–20 cm2 in the most severe cases).[10] In vivo studies show that the invasiveness of uterine tissues largely depends on the type of bacteria. In a sheep model of intra‑amniotic injection of lipopolysaccharide from different bacterial species, it appears that periodontopathic lipopolysaccharides induce a high rate of fetal lethality. Furthermore, in a rat model, placenta colonization by P. gingivalis is dose and strain dependent.

MECHANISM OF ACTION Potential pathological mechanisms of certain periopathogens, especially for P. gingivalis and F. nucleatum, have been studied. For example, P. gingivalis could infect syncytiotrophoblasts, chorionic trophoblasts, decidual cells, and amniotic epithelial cells and promotes inflammatory process through toll‑like receptor.[11] There is a hematogenous spread and cytokines produced in periodontal tissues diffuse into the blood to cross the placental barrier and promote inflammation in maternal‑fetal unit. Clinically, high gingival crevicular fluid levels of prostaglandin E‑2, IL‑1β, or IL‑6 have been associated with their elevated levels in amniotic fluid.[12] The inflammatory response appears to be the primary pathway of the pathogenic periodontal disease influence on pregnancy as suggested for other major systemic diseases including cardiovascular diseases or diabetes.[13]

PERIODONTAL DISEASE TREATMENT DURING PREGNANCY Though in the annals of antenatal care a dental checkup is the norm, but practically it is hardly ever done unless the woman complains of a specific dental problem.

Journal of the International Clinical Dental Research Organization | July-December 2016 | Vol 8 | Issue 2

99

[Downloaded free from http://www.jicdro.org on Wednesday, September 28, 2016, IP: 79.124.101.183] Dhabhai: Preterm birth and periodontitis

Moreover, among the established risk factors for preterm birth are only two that is a previous preterm birth and a short cervical length.[14] Having said this how do we prevent a primary preterm birth, the only answer is to screen for other risk factors, a foci of infection is not a risk but if associated with other risk factors of low immunity, anemia, poor socioeconomic condition becomes a potential risk for preterm birth, and it would be wise to screen all population in reproductive age group or rather in pregnancy for periodontal disease. The evidence provided by a prospective randomized controlled trial[15] where 1000 women in Perth, Western Australia 2009, were allocated periodontal treatment at 20 weeks and subsequently followed up till delivery did not support the hypothesis that prevention and treatment of periodontal disease would prevent preterm birth, but it also proved that periodontal treatment was safe during pregnancy for both mother and fetus. More recently in 2011, another prospective trial[16] was done by Dr. Marjorie Jeffcoat in University of Pennsylvania on 322 pregnant women, where they were randomly allocated aggressive treatment either by scaling and planning with hygiene advice and only hygiene advice, just 4 of the group of 42 (10.1%) which received successful treatment had preterm births while there were 69 preterm births in the 111 women in whom treatment was unsuccessful (62%).[17] This study clearly highlights the fact that a successful periodontal disease treatment can prevent preterm birth. Treating periodontal disease and conducting minor dental procedures such as scaling, planning, and cleaning are safe during pregnancy. Aggressive treatment should be continued to control the disease, burden of infection if found should be reduced. The ideal time for treatment is the second trimester that is between 14 and 20 weeks of pregnancy as it gives the practitioner ample time to complete the treatment before the risk of preterm birth is manifested. Also later in pregnancy, there may be difficulty in access and exposure with discomfort for the women to sitting for a long time.

CONCLUSION Periodontal disease is a potential risk factor for infection which can increase risk for preterm labor, especially in a country like ours which leads globally in preterm deaths, also risk factors for periodontal disease and preterm births are similar, though certain prospective trials may have not shown a significant relationship, but there is no denying that periodontal disease acts as a foci of infection which in immunocompromised states such as anemia, malnutrition 100

have the potential to disseminate hematogenously to the fetal complex. It seems prudent therefore to screen all women in their reproductive age group for periodontal disease or early in the antenatal period or refer by a dental practitioner and treat it effectively with regular follow‑up.

Financial support and sponsorship Nil.

Conflicts of interest There are no conflicts of interest.

REFERENCES 1. World Health Organization; March of Dimes; The Partnership for Maternal, Newborn & Child Health; Save the Children. Born Too Soon: Global Action Report on Preterm Birth. WHO; 2012. 2. Singh U, Singh N, Shikha S. A prospective analysis of etiology and outcome of preterm labor. J Obstet Gynecol India 2007;57: 48-52. 3. Offenbacher S, Lieff S, Boggess KA, Murtha AP, Madianos PN, Champagne CM, et al. Maternal periodontitis and prematurity. Part I: Obstetric outcome of prematurity and growth restriction. Ann Periodontol 2001;6:164‑74. 4. Miller WD. The human mouth as a focus of infection. Dent Cosm 1891;33:689‑713. 5. Saini R, Saini S, Saini SR. Periodontitis: A risk for delivery of premature labor and low‑birth‑weight infants. J Nat Sci Biol Med 2010;1:40‑2. 6. Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, et al. The worldwide incidence of preterm birth: A systematic review of maternal mortality and morbidity. Bull World Health Organ 2010;88:31‑8. 7. Fardini Y, Chung P, Dumm R, Joshi N, Han YW. Transmission of diverse oral bacteria to murine placenta: Evidence for the oral microbiome as a potential source of intrauterine infection. Infect Immun 2010;78:1789‑96. 8. Katz J, Chegini N, Shiverick KT, Lamont RJ. Localization of P. gingivalis in preterm delivery placenta. J Dent Res 2009;88:575‑8. 9. Loos BG. Systemic markers of inflammation in periodontitis. J Periodontol 2005;76 11 Suppl: 2106‑15. 10. Huck O, Tenenbaum H, Davideau JL. Relationship between periodontal diseases and preterm birth: Recent epidemiological and biological data. J Pregnancy 2011;2011:164654. 11. Gürsoy M, Pajukanta R, Sorsa T, Könönen E. Clinical changes in periodontium during pregnancy and post‑partum. J Clin Periodontol 2008;35:576‑83. 12. Newnham JP, Shub A, Jobe AH, Bird PS, Ikegami M, Nitsos I, et al. The effects of intra‑amniotic injection of periodontopathic lipopolysaccharides in sheep. Am J Obstet Gynecol 2005;193:313‑21. 13. Offenbacher S, Jared HL, O’Reilly PG, Wells SR, Salvi GE, Lawrence HP, et al. Potential pathogenic mechanisms of periodontitis associated pregnancy complications. Ann Periodontol 1998;3:233‑50. 14. Dörtbudak O, Eberhardt R, Ulm M, Persson GR. Periodontitis, a marker of risk in pregnancy for preterm birth. J Clin Periodontol 2005;32:45‑52. 15. Prince AL, Paranthanan MJ, Kanan S. The placental membrane


[Downloaded free from http://www.jicdro.org on Wednesday, September 28, 2016, IP: 79.124.101.183] Dhabhai: Preterm birth and periodontitis microbiome is altered among subjects with spontaneous preterm birth with and without chorioamnonitis. Am J Obstet Gynecol 2016;214:627.e1‑627 16. Newnham JP, Newnham IA, Ball CM, Wright M, Pennell CE, Swain J, et al. Treatment of periodontal disease during

pregnancy: A randomized controlled trial. Obstet Gynecol 2009;114:1239‑48. 17. Jeffcoat M, Parry S, Sammel M, Clothier B, Catlin A, Macones G. Periodontal infection and preterm birth: Successful periodontal therapy reduces the risk of preterm birth. BJOG 2011;118:250‑6.

About the author Dr. Neeta Dhabhai has specialized in obstetrics and gynecology, working as a Senior Consultant in Metro Hospital in Faridabad, and she has over 20 years of clinical experience in India and Abroad. Her special areas of interest are high‑risk obstetrics, menopausal medicine, and adolescent health. She is a keen orator and an advocate of preventive health and regularly holds numerous public health awareness programs in schools, colleges, and women organizations. She has done M.B.B.S and M.S (obstetrics and gynecology) from S.M.S. Medical College, Jaipur, Rajasthan, Senior Residency from Dr. R.M.L. Hospital, New Delhi, after which she trained and worked at University College of Medical Sciences, Cardiff, Wales (UK). She has been working in the field of Adolescent Health since 2004 and is also a Master Trainer in Adolescent Health (National and International) with WHO–SEARO and WPRO, FOGSI and RKSK (GOI). The several administrative positions as held are Vice President Faridabad Obstetrics and Gynecology Society (FOGSI), Member of International Association of Adolescent Health (IAAH), Executive Member Adolescent Health Committee (FOGSI), Executive Member Public Awareness Committee (FOGSI), Founder Member and Secretary General UPHAI (Urogynecology and Pelvic Health Association of India), and Chairman and Director of Unfold Foundation (Registered Trust) and Adolescent and Youth Health initiative started in 2013. She has worked on projects: 1. Adolescent Health training (as Master Trainer) with GOI, WHO, and FOGSI in India and the West Pacific countries with WHO–Maldives, Philippines and Myanmar and trained for the same EUTEACH at University of Laussane, Switzerland 2. Family planning with PSI (Population Services International), and FOGSI 3. Resource Person for Expressions India and Nurture (New Delhi‑based NGOs), working in the field of adolescent mental health.


101