Year : 2012 | Volume
: 3 | Issue : 2 | Page : 67--71
Is periodontal disease a reason or result for premature birth?
Turgut Demir, Gülnihal Emrem
Department of Periodontology, Atatürk University, Erzurum, Turkey
Department of Periodontology, Atatürk University, Dental faculty, 25240, Erzurum
Introduction: It is a known fact that there is a connection between periodontal disease and certain systemic conditions. Even though there are some contradictory results in the conducted studies, periodontal disease has been accepted as a risk factor affecting the negative terminations of pregnancy in recent years (premature birth [PB], low birth weight). This consideration is associated with a positive correlation between two conditions in some studies. The Hypothesis: Although there is such a relationship between periodontal disease and PB, the linking mechanism has not been explained as presence of the relation cannot reveal the cause-effect relationship. It should be discussed whether or not this positive connection is caused by the fact that periodontal disease is an independent risk factor for PB, or the change (hormonal, inflammatory) in the systemic condition in PB cases causes a risk for periodontal disease. Evaluation of the Hypothesis: The fact that in PB cases the changes in steroid hormone levels might increase the incidence and severity of periodontal disease as in pregnancy, or there could be a common risk factor that may cause both cases, has not been revealed yet and should be taken into consideration.
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Demir T, Emrem G. Is periodontal disease a reason or result for premature birth?.Dent Hypotheses 2012;3:67-71
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Demir T, Emrem G. Is periodontal disease a reason or result for premature birth?. Dent Hypotheses [serial online] 2012 [cited 2019 Apr 21 ];3:67-71
Available from: http://www.dentalhypotheses.com/text.asp?2012/3/2/67/100390
Together with the definition of pathogens that cause periodontal diseases and appearance of the systemic mechanisms of products, number of the studies focusing on the interrelation between periodontal diseases and systemic conditions, and the interest shown toward this subject, have increased in the recent years. These systemic conditions include diabetes, cardiovascular diseases, pulmonary diseases and negative termination of pregnancy (preterm birth [PB], low birth weight [LBW]). It has been concluded during the last decade that pathogenesis of PB is multifactorial, highly complex and variable. Even when the study is restricted with spontaneous PBs, it includes environmental (economic condition), infection (bacterial vaginitis), genetic variations (cytokine polymorphism), social habits (smoking) and many different etiological factors.  Infection, which is the reason for almost 30% of all preterm births that occur before the 32 nd week, is the most important of these etiological factors.  It is determined that the concentrations of many cytokines such as IL-1β, TNF-α, IL-6, IL-8, MIP-1α and IL-4 increase within the amniotic fluid during the infection, and arachidonic acid metabolites are produced by the gestational tissue in response to cytokines. As a consequence, PGE2 production is stimulated from gestational tissues, external amnion membrane, amnion and chorion, and this stimulation causes PB.  Because both local and systemic inflammation are observed during periodontitis, which is a chronic gram negative anaerobic infection,  and low-degree oral infection in animal studies causing maternal-fetal inflammation,  it is thought that periodontitis might be related to PB and LBW. In this context, Offenbacher et al.  conducted the first study suggesting that the increase on the prevalence of moderate and severe periodontitis results in the decrease of the gestational period, and that periodontitis is an important risk factor for pre-term low birth weight (PLBW). While these first results have been supported by some researchers, ,,,,,,,, they have not been supported by others. ,,,, Regarding the obtained inconsistent results and non-controllability of the underlying risk factors, majority of the clinical studies have indicated that although there are potential problems, there is a positive relationship between the periodontal disease and PB,  and periodontal disease is accepted as an independent risk factor for PLBW.  Vegnes and Sixou  proposed that periodontal disease might lead to PB; however, hyperinflammatory response, which might cause both the periodontal disease and the PB, might be caused by some major mechanisms such as genetic susceptibility. The inconsistent results obtained from the studies increased the possibility that the relationship observed between periodontal disease and PLBW cannot be related with any reason. The relationship between periodontal disease and PLBW may not express the cause. 
Early period studies investigated the effects of pregnancy on periodontal health, and revealed that pregnancy affected the periodontal health. This effect of pregnancy on the periodontal health was associated with an increase on the hormone levels. , It is a known fact that P. intermedia and P. gingivalis, among the periodontal pathogens, can use the estrogens such as progesterone and estradiol, as a food source  and tissues supporting the teeth might be damaged by physiological changes on steroid hormone levels in males and females.  Especially the fact that the level of estriol (E3), which is one of the steroid hormones, in the saliva increases has been used to determine the exact risk for PB in recent years, which has revealed the relation of steroid hormones with oral tissues during the PB once again. As a consequence, it is inevitable for the salivary E3 level that increases in PB cause a change in periodontal tissues that are in contact with the saliva and an increase in the number of periodontal pathogens.
It is an inevitable reality that there is a relation between the periodontal diseases and pregnancy, PB and LBW. However, the mechanism of this relation has not been explained yet. Regarding the cases with PLBW, the fact that the incidence and severity of the periodontal disease are greater in comparison with those who have normal delivery reveals that there is a positive relation between these two situations, and it shall be discussed whether this positive relation is caused by the fact that periodontal disease is an independent risk factor for PLBW or the change in the systemic condition in PLBW cases (hormonal, inflammatory) creates a risk for the periodontal disease. As a matter of fact, the pregnancy period might be a reason for the development of periodontal disease. Contrary to what is believed, in terms of the relationship of periodontal disease and PLBW, the changes in steroid hormone levels cause an increase in the incidence and severity of the periodontal disease in PLBW cases, just like in pregnancy. On the other hand, both conditions' having common risk factors (general health and disease condition [e.g., diabetes], smoking, genetic factors, demographic and psychosocial factors, nutritional factors) makes us think that there might be a common risk factor that determines both conditions in this positive relationship. For instance, there is a genetic susceptibility for both the periodontal disease and the PLBW. There might also be a common risk factor that triggers a hyperinflammatory response that may cause both conditions. We think that one of the reasons behind why studies conducted on this subject have inconsistent results is that the study and control groups do not represent the same pregnancy period.
Evaluation of the Hypothesis
Various studies showed that steroid hormones have a role in the birth preparation and birth signal.  Placental estrogens act as biomakers for mammals just before the birth, during the pre-term birth or post-partum pain and during the birth. E3 is the most abundant within the major placental estrogens (estrone [E1], estradiol [E2] and estriol [E3]) during the late pregnancy.  Testing salivary E3 enables the exact estimation for whether or not the possibility of pre-term birth has a high or low risk. The fact that this rate increases was also observed during the timely labour pain and pre-term births caused by the premature rupture of the membrane, revealing that E3 plays the role of an indicator during births and pre-term labour pain.  The salivary E3 level gives precise results, especially for primipara women who do not possess a defined risk factor.  Survival analyses demonstrated that the gestational period shortens if the E3 level is positive on gestations of at least 28, 32 and 34 weeks.  The first studies conducted by Darne et al. revealed that for women who have a spontaneous pre-term birth, the saliva estriol is higher than progesterone throughout the gestation compared with the normal time.  In the oral zone, the saliva directly affects the adjacent periodontal tissues of steroid hormone levels and causes and/or intensifies the periodontal disease. In this case, PLBW and periodontal disease concur and a positive correlation might emerge. As a matter of fact, Tilakaratne et al. revealed that tissues supporting the teeth might be damaged by physiological changes in steroid hormone levels of males and females.  Receptors that are peculiar to estrogen and progesterone were also indicated on the gingival tissue. These receptors are the biochemical evidence that the gingival tissue is a target organ for sex hormones. , Additionally, estrogen and progesterone might affect the connective tissue together. ,, It was emphasised that the plasma levels of estrogen and progesterone hormones gradually increased throughout the pregnancy and there was a positive correlation between the severity of gingival inflammation and amount of such hormones.
Löe and Silness  indicated that the gingivitis rate in pregnant women has the greatest increase between the months 2 and 8 of pregnancy, prominently decreasing just before birth and resuming during the second month after the birth. In their epidemiological study, Cohen et al.  assessed the post-partum period along with the first, second and third trimester periods. They reported that gingivitis increases throughout the pregnancy, significantly decreasing during the post-partum period, and that teeth mobility, which increases during the pregnancy, decreases after birth. As a consequence, the researchers, who emphasised that irritant factors remain the same, asserted that systemic changes shall be taken into consideration during the pregnancy. Because the studies investigating the relation between the periodontal disease and PLBW compared the women with normal delivery to women with PB, compared pregnant women to those who gave birth or assessed the periodontal parameters during the post-partum period, parameters might cause potential deviations as well. It should be kept in mind that the third trimester witnesses rapid changes. We believe that the reason behind inconsistent results obtained from studies examining the relationship between periodontal disease and PLBW was the fact that during the pregnancy, the study and control groups reflected different periods (day-month) during which different hormonal changes are experienced.
Periodontal pathogens are believed to reach the feto-placental tissues through blood and start the development of infection and prostaglandin that accelerate the PB. ,,, If the continuous attack of gram negative bacteria is added to the irregular and/or gradually decreasing host response, it may affect tissues outside of periodontal tissues, such as feto-placental tissues.  This is one of the foundations that claims that periodontal disease poses a risk for the PLBW. Madianos et al.  tried to determine this relationship between clinical periodontal disease and PB as well as immunological and biological mechanisms. In this study, the PB rate was highest in mothers who did not have a strong IgG response on the maternal serum against red complex bacteria, such as P. gingivalis, B. forsythus and T. denticola. The connection of maternal serum IgG levels specific to periodontal pathogens during the second trimester of pregnancy with the birth weight of the infant was investigated; P. gingivalis-specific maternal serum IgG levels in the group with LBW were greater in comparison with the group with the normal birth weight.  The births with LBW were associated with high maternal serum antibody, which is peculiar to P.gingivalis, in the medium trimester.  On the other hand, according to Buduneli et al., while no bacteria creates a risk for PLBW, P. micros and C. rectus might play a role in increasing the risk for PLBW when they are assessed with subgingival bacteria.  F. nucleatum, which is a common type of oral bacterium, was also seen in cultures of the amnion fluid of women with a pre-term birth action.  Periodontal pathogens were also attempted to be isolated from placental tissues that were collected after the PB. Geopfert et al.  isolated the periodontal pathogen on only two of 59 of the placentas of PB and three of 44 of the placentas of those who gave birth in the normal time. Similarly, although Dörtbudak et al.  isolated the periodontal pathogens on dental plaques taken from women who had PB and periodontitis, they could not achieve isolation of the microorganisms in the amniotic fluid. Another study examined the relationship between the existence of F. nucleatum in dental plaque and vaginal swab specimens, and the amniotic fluid was researched and could not be determined.  The fact that periodontal pathogens are found in the serum rather than in the placental tissues makes us think that pathogens are not directly transferred to these tissues through blood. As well as the Igs that are specific to pathogens produced during the periodontal disease, prostaglandins and cytokines that increase as a result of the host response probably leak into the systemic circulation and maternal placental part. These changes influence the normal homeostasis, balance of maternal-fetal nutrition and hormonal and immunological systems.  Apart from the disputable systemic increase, some local changes occur on the rate of periodontal pathogens in the subgingival plaque during pregnancy. P. intermedia and its rate increase on the subgingival plaque in a selective way due to the systemic hormonal changes during the third and fourth months of pregnancy. , It was reported that P. intermedia and P. gingivalis, which are among the periodontal pathogens, could use estrogens such as progesterone and estradiol as a nutrient.  B. melaninogenicus and P. intermedia could transit estradiol and progesterone instead of menadione (Vitamin K), which is the growth factor. ,
The incidence of high hormone levels during the periods of PB cases (especially the salivary E3 level) makes us think that these pathogen bacteria proliferate locally by means of steroid hormones during this period. This naturally enables the development of periodontal disease and/or exacerbation of the present disease.
Susceptibility to PLBW and periodontal disease and genetic hyperinflammatory response might modify the immune system against the increasing bacteria. It is important to consider the possible existence of some underlying mechanisms that cause undesired results of both the periodontal disease and the pregnancy. A possible hyperinflammatory response, which rises basically together with the existence of bacteria in a genetic susceptibility, might be found. 
The effects of periodontal treatment on the PB were investigated; however, the results were found to be inconsistent. Similar to the studies claiming that periodontal treatment might decrease the rate of PB during pregnancy, ,,,, there are also some studies that claim that there is no relationship between the periodontal care and LBW. ,, It is suggested that the treatment of pregnant womens' periodontitis is safe and effective in curing the periodontal disease, and also is unimportant for the restriction and changing the pre-eclampsia rates in the PB, LBW and fetal growth.  As a consequence, both diseases might be in an interaction. Periodontal disease might have an effect on the PB and/or the systemic changes in the PB condition might become effective on the periodontal disease.
Relation mechanism between periodontal disease and PB and/or LBW could not be explained. In order to explain the cause and effect relationship, additional observational studies or randomised-controlled experiments are required.
|1||Stamilio DM, Chang JJ, MaconesGA. Periodontal disease and preterm birth: Do the data haveenough teeth to recommend screening and preventive treatment? Am J Obstet Gynecol 2007;196:93-4.|
|2||Dudley DJ. Immunoendocrinology of preterm labor: The link between corticotropin-releasing hormone and inflammation. Am J Obstet Gynecol 1999;180(1 Pt 3):251-6. |
|3||Vergnes JN, Sixou M. Preterm low birth weight and maternal periodontal status: A meta-analysis. Am J Obstet Gynecol 2007;196:135-7.|
|4||Collins JG, Smith MA, Arnold RR, Offenbacher S. Effects of Escherichia coli and Porphyromonas gingivalis lipopolysaccharide on pregnancy outcome in the golden hamster. Infect Immun 1994;62:4652-5.|
|5||Offenbacher S, Katz V, Fertik G, Collins J, Boyd D, Maynor G, et al. Periodontal infection as a possible risk factor for preterm low-birth-weight. J Periodontol 1996;67(10 Suppl):1103-13.|
|6||Goepfert AR, Jeffcoat MK, Andrews WW, Faye-Petersen O, Cliver SP, Goldenberg RL, et al. Periodontal disease and upper genital tract inflammation in early spontaneous preterm birth. Obstet Gynecol 2004;104:777-83.|
|7||Jeffcoat MK, Geurs NC, Reddy MS, Cliver SP, Goldenberg RL, Hauth JC. Periodontal infection and preterm birth: Results of a prospective study. J Am Dent Assoc 2001;132:875-80.|
|8||Offenbacher S, Boggess KA, Murtha AP, Jared HL, Lieff S, McKaig RG, et al. Progressive periodontal disease and risk of very preterm delivery. Obstet Gynecol 2006;107:29-36.|
|9||Dasanayake AP. Poor periodontal health of the pregnant woman as a risk factor for low birth weight. Ann Periodontol 1998;3:206-12.|
|10||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.|
|11||Jarjoura K, Devine PC, Perez-Delboy A, Herrera-Abreu M, D'Alton M, Papapanou PN. Markers of periodontal infection and preterm birth. Am J Obstet Gynecol 2005;192:513-9.|
|12||Mokeem SA, Molla GN, Al-Jewair TS. The prevalence and relationship between periodontal disease and pre-term low birth weight infants at King Khalid University Hospital in Riyadh, Saudi Arabia. J Contemp Dent Pract 2004;5:40-56.|
|13||Radnai M, Gorzo I, Nagy E, Urban E, Novak T, Pal A. A possible association between preterm birth and early periodontitis. A pilot study. J Clin Periodontol 2004;31:736-41.|
|14||Romero BC, Chiquito CS, Elejalde LE, Bernardoni CB. Relationship between periodontal disease in pregnant women and the nutritional condition of their newborns. J Periodontol 2002;73:1177-83.|
|15||Buduneli N, Baylas H, Buduneli E, Türkoðlu O, Köse T, Dahlen G. Periodontal infections and pre-term low birth weight: A case-control study. J Clin Periodontol 2005;32:174-81.|
|16||Davenport ES, Williams CE, Sterne JA, Murad S, Sivapathasundram V, Curtis MA. Maternal periodontal disease and preterm low birthweight: Case-control study. J Dent Res 2002;81:313-8.|
|17||Moore S, Ide M, Coward PY, Randhawa M, Borkowska E, Baylis R, et al. A prospective study to investigate the relationship between periodontal disease and adverse pregnancy outcome. Br Dent J 2004;197:251-8.|
|18||Moore S, Randhawa M, Ide M. A case-control study to investigate an association between adverse pregnancy outcome and periodontal disease. J Clin Periodontol 2005;32:1-5.|
|19||Holbrook WP, Oskarsdottir A, Fridjonsson T, Einarsson H, Hauksson A, Geirsson RT. No link between low-grade periodontal disease and preterm birth: A pilot study in a healthy Caucasian population. Acta Odontol Scand 2004;62:177-9.|
|20||Bobetsis YA, Barros SP, Offenbacher S. Exploring the relationship between periodontal disease and pregnancy complications. J Am Dent Assoc 2006;137(Suppl):7S-13S.|
|21||Lopez NJ, Smith PC, Gutierrez J. Periodontal therapy may reduce the risk of preterm low birth weight in women with periodontal disease: A randomized controlled trial. J Periodontol 2002;73:911-24.|
|22||Carranza FA, Newman MG, Takei HH. Carranza's Clinical Periodontology. Chapter 37. 9 th ed. Philadelphia, Pa:W.B. Saunders Company; 2002. p. 96-112.|
|23||Lindhe J, Karring T, Lang NP. Clinical Periodontology and Implant Dentistry. Chapter 6. 4 th ed. Blackwell Publishing Company; 2003. p.408-9|
|24||Mascarenhas P, Gapski R, Al-Shammari K, Wang HL. Influence of sex hormones on the periodontium. J Clin Periodontol 2003;30:671-81.|
|25||Tilakaratne A, Soory M, Ranasinghe AW, Corea SM, Ekanayake SL, de Silva M. Periodontal disease status during pregnancy and 3 months post-partum, in a rural population of Sri-Lankan women. J Clin Perodontol 2000;27:787-92.|
|26||McGregor JA, Hastings C, Roberts T, Barrett J. Diurnal variation in saliva estriol level during pregnancy: A pilot study. Am J Obstet Gynecol 1999;180(1 Pt 3):S223-5. |
|27|| Heine RP, McGregor JA, Goodwin TM, Artal R, Hayashi RH, Robertson PA, et al. Serial salivary estriol to detect an increased risk of preterm birth. Obstet Gynecol 2000;96:490-7.|
|28||Darne J, McGarrigle HH, Lachelin GC. Increased saliva oestriol to progesterone ratio before preterm delivery: A possible predictor for preterm labor? Br Med J (Clin Res Ed) 1987;294:270-2.|
|29||Vittek J, Hernendez MR, Wennk EJ, Rappaport SC, Southren AL. Specific estrogen receptors in human gingiva. J Clin Endocrinol Metab 1982;52:608-12.|
|30||Hugoson A, Winberg E, Angström T. Cytologic findings in vaginal and oral smears from pregnant women. Odontol Revy. In: Carranza FA, Newman MG, Takei HH. Carranza's Clinical Periodontology. Chapter 37. 9 th ed. W.B. Saunders Company; th 1 971. 22. 145-52.|
|31||Löe H, Silness J. Periodontal disease in pregnancy. I.Prevalence and severity. Acta Odontol Scand 1963;21:533-51.|
|32||Cohen DW, Friedman L, Shapiro J, Kyle GC. A longitudinal investigation of the periodontal changes during pregnancy. J Periodontol 1969;40:563-70.|
|33||Boggess KA, Moss K, Madianos P, Murtha AP, Beck J, Offenbacher S. Fetal immune response to oral pathogens and risk of preterm birth. Am J Obstet Gynecol 2005;193(3 pt 2):1121-6.|
|34||Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med 2000;342:1500-7.|
|35||Madianos PN, Lieff S, Murtha AP, Boggess KA, Auten RL Jr, Beck JD, et al. Maternal periodontitis and prematurity. Part II: Maternal infection and fetal exposure. Ann Periodontol 2001;6:175-82.|
|36||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.|
|37||Davenport ES, Williams CE, Sterne JA, Sivapathasundaram V, Fearne JM, Curtis MA. The East London study of maternal chronic periodontal disease and preterm low birth weight infants: Study design and prevalence data. Ann Peridontol 1998;3:213-21.|
|38||Dasanayake AP, Boyd D, Madianos PN, Offenbacher S, Hills E. The Association Between Porphyromonas gingivalis-Specific Maternal Serum IgG and Low Birth Weight. J Periodontol 2001;72:1491-7.|
|39||Hill GB. Preterm birth: Associations with genital and possibly oral microflora. Ann Periodontol 1998;3:222-32.|
|40||Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJ. Cognitive and behavioral outcomes of school-aged children who were born preterm: A meta-analysis. JAMA 2002;288:728-37.|
|41||Yeo BK, Lim LP, Paquette DW, Williams RC. Periodontal Disease - The Emergence of a Risk for Systemic Conditions: Pre-term Low Birth Weight. Ann Acad Med Singapore 2005;34:111-6.|
|42||Kornman KS, Loesche WJ. The subgingival microbial flora during pregnancy. J Periodontal Res 1980;15:111-22.|
|43||Muramatsu Y, Takaesu Y. Oral health status releated to subgingival bacterial flora and sex hormones in saliva during pregnancy. Bull Tokyo Dent Coll 1994;35:139-51.|
|44||Jeffcoat MK, Hauth JC, Geurs NC, Reddy MS, Cliver SP, Hodgkins PM, et al. Periodontal disease and preterm birth: Results of a pilot intervention study. J Periodontol 2003;74:1214-8.|
|45||Lopez NJ, Smith PJ, Gutierrez J. Higher risk of preterm birth and low birth weight in women with periodontal disease. J Dent Res 2002;81:58-63.|
|46||Lopez NJ, Da Silva I, Ipinza J, Gutierrez J. Periodontal therapy reduces the rate of preterm low birth weight in women with pregnancy-associated gingivitis. J Periodontol 2005;76(11 Suppl):2144-53.|
|47||Sha YQ, Huang Z, Chen ZB, Kang J, He L, Yu XQ. Association between periodontitis and preterm low birth weight. Beijing Da Xue Xue Bao 2009;41:117-20.|
|48||Hujoel PP, Lydon-Rochelle M, Robertson PB, del Aguila MA. Cessation of periodontal care during pregnancy: Effect on infant birthweight. Eur J Oral Sci 2006;114:2-7.|
|49||Khader YS, Ta'ani Q. Periodontal Diseases and the Risk of Preterm Birth and Low Birth Weight: A Meta-Analysis. J Periodontol 2005;76:161-5.|
|50||Michalowicz BS, Hodges JS, DiAngelis AJ, Lupo VR, Novak MJ, Ferguson JE, et al. Treatment of Periodontal Disease and the Risk of Preterm Birth. N Engl J Med 2006;355:1885-94.|