This article reviews the evidence linking subclinical infection and premature birth. Evidence of subclinical infection as a cause of preterm labor is raised by finding elevated maternal serum C-reactive protein and abnormal amniotic fluid organic acid levels in some patients in preterm labor. Biochemical mechanisms for preterm labor in the setting of infection are suggested by both in vitro and in vivo studies of prostaglandins and their metabolites, endotoxin and cytokines.

Gibbs RS, Romero R, et.al., Am J Obstet Gynecol 166:1515- 28, 1992.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&dopt=Abstract&list_uids=92280938

Periodontitis is a chronic inflammatory disease caused mainly by gram-negative bacteria. It is believed that periodontitis can contribute to adverse outcomes of pregnancy. Toxins or other products generated by periodontal bacteria in the mother can reach the blood circulation, cross the placenta, and harm the foetus. In addition, the response of the mother's immune system to the infection activates the release of inflammatory mediators, growth factors and other potent cytokines, which may trigger preterm labour.

World Health Organization,
http://www.whocollab.od.mah.se/expl/systpreterm.html

Maternal oral infection, caused by bacteria such as C. rectus or P. gingivalis gingivalis, has been implicated as a potential source of placental and fetal infection , and inflammatory challenge, which increases the relative risk for pre-term delivery and growth restriction. Intra-uterine growth restriction has also been reported in various animal models infected with oral organisms. Analyzing placental tissues of infected growth-restricted mice, we found down-regulation of the imprinted Igf2 gene. Epigenetic modification of imprinted genes via changes in DNA methylation plays a critical role in fetal growth and development programming. Here, we assessed whether C. rectus infection mediates changes in the murine placenta Igf2 methylation patterns. We found that infection induced hypermethylation in the promoter region-P0 of the Igf2 gene. This novel finding, correlating infection with epigenetic alterations, provides a mechanism linking environmental signals to placental phenotype, with consequences for development.

Bobetsis YA, Barros SP, et al. Journal of Dental Research, Vol. 86, No. 2, 169-174 (2007).
http://jdr.sagepub.com/cgi/ content/abstract/86/2/169

Background: Preterm low birth weight was reported to be related to periodontal infections that might influence the fetus- placenta complex. The aim of this study was to provide periodontal treatment for pregnant women and to evaluate if this treatment can interfere with pregnancy duration and weight of the newborn.

Methods: The sample consisted of 450 pregnant women who were under prenatal care at a polyclinic in Três Corações, Brazil. Women with risk factors, such as systemic alterations (ischemic cardiopathy, hypertension, tuberculosis, diabetes, cancer, anemia, seizure, psychopathology, urinary tract infection, sexually transmitted diseases, asthma, and human immunodeficiency virus), and/or users of alcohol, tobacco, and drugs were excluded from the study. Data related to age, socioeconomic level, race, marital status, number of previous pregnancies, and previous preterm delivery also were evaluated. Initially, the sample was divided into two groups: 122 healthy patients (group 1) and 328 patients with periodontal disease (group 2). In group 2, 266 patients underwent treatment and 62 patients dropped out. After mothers gave birth, pregnancy duration and the weight of all infants were analyzed and recorded.

Results: There was no statistical difference between the healthy and treated groups. However, there was a difference in the non-treated group, with a 79% incidence of preterm low birth weight. Educational level, previous preterm birth, and periodontal disease were related significantly to preterm delivery (P <0.001). Conclusion: Periodontal disease was related significantly to preterm low birth weight.

Gazolla CM, Ribeiro A, et al. Journal of Periodontology, 2007, Vol. 78, No. 5, Pages 842-848. http://www.joponline.org/doi/abs/10.1902/jop.2007.060295

Obstetric complications not only are a significant health care expense, but also affect the well-being of the affected infants throughout life. Maternal infection with periodontal pathogens has a deleterious effect on fetal growth and viability. Treatments can be provided safely during pregnancy to improve the oral health of the mother. It is the responsibility of the dentist and the profession to inform patients about the biological plausibility that untreated periodontal disease may increase the risk not only of unfavorable pregnancy outcomes, but also of developing conditions that may affect the well-being of the offspring. There is no evidence of a down-side to providing care to mothers, which suggests that such treatment actually may be beneficial for two.

Bobetsis YA, Barros SP, et.al., JADA, vol 137 Oct 2006 Supplement, pp.7s-13s.
http://jada.ada.org/ content/vol137/suppl_2/index.dtl http://jada.ada.org/cgi/content/full/137/suppl_2/7S

The role that infections play in preterm birth (particularly very early preterm birth) has been clearly established, and the interactions that occur with maternal and fetal immunity is increasingly understood. Microbes can cause LBW and preterm birth directly or through activation of maternal and fetal immune processes. Infection causes white blood cells (T-helper lymphocytes, TH 1) to specialize and release proteins called cytokines (i.e., gamma-interferon, tumor necrosis factor and interleukins) that increase the immune response and serve as crucial mediators of the body's immune-inflammatory responses. Considerable information from human studies and animal models is available regarding the mechanisms through which immune functioning mediates LBW and PTB. As part of the body's response to infection, a cascade of maternal and fetal enzymes (metalloproteases) that may precipitate preterm labor and preterm premature rupture of membranes (PPROM) can be released. Infections such as bacterial vaginosis (BV), asymptomatic bacteruria, sexually transmitted infections and periodontal infections have all been associated with increased risk for preterm delivery. Current investigations suggest that genetic variation in response to infection (e.g., increased inflammatory resonse) may place susceptible women at increased risk. A mother's ability to resist infection during pregnancy is dependent upon such factors as stress, nutritional status, and personal habits (e.g., smoking, substance use, douching) as well as genetics. Infection and inflammation during pregnancy may have other adverse consequences for the infant. Proinflammatory cytokines implicated in LBW and PTB have also been implicated in the pathogenesis of cerebral palsy in premature infants and maternal depression.

Los Angeles Best Babies Collaborative.
http://www.first5la.org/docs/Projects/HB/LABBCHealthyBirthsBluePrint.pdf

It has been suggested that periodontitis is associated with systemic alterations such as adverse pregnancy outcomes. However, some conflicting results have been reported. This case-control study was conducted to determine the association between maternal periodontitis and preterm birth (PTB), low birth weight (LBW), and intrauterine growth restriction (IUGR). Maternal periodontitis is associated with an increased risk for PTB, LBW, and IUGR. Results emphasize the importance of periodontal care in prenatal health programs.

Siqueira FM, Cota LOM, Costa JE. Journal of Periodontology 2007, Vol. 78, No. 12, Pages 2266-2276 http://www.joponline.org/doi/abs/10.1902/jop.2007.070196

Mounting evidence suggests that a chronic oral infection may lead to an immune reaction that either triggers premature parturition or contributes to its onset. Rresearchers have measured gingival crevicular levels of PGE2 and IL-1ß in 48 mothers who delivered preterm, LBW infants and compared these levels to those found in control women.23 They discovered that gingival crevicular fluid levels of PGE2 were significantly higher in cases, compared to control women. In addition, among primiparous women with preterm, LBW infants, they found a significant inverse association between birthweight and gestational age and gingival crevicular PGE PGE2 levels.

Bogess KA. Contemporary OB?GYN Aug.1,2003 1,2003. http://www.cedip.cl/Temas/PTDandPERIODONT/Is%20there%20a%20link%20between% 20periodontal%20disease%20and %20preterm%20birth.htm

Periodontal disease has been suggested to be an important risk factor for preterm low birthweight (PLBW). Here we report a case-control study of 236 cases (infants < 37 wks and weighing < 2499 g) and a daily random sample of 507 controls ( 38 wks and weighing 2500 g). Clinical periodontal indices were measured on the labor wards. Associated risk factors for periodontal disease and PLBW were ascertained by means of a structured questionnaire and maternity notes. The risk for PLBW decreased with increasing pocket depth (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.68 to 1.00). After adjustment for maternal age, ethnicity, maternal education, smoking, alcohol consumption, infections, and hypertension during pregnancy, this decreased further (OR 0.78, 95% CI 0.64 to 0.99). We found no evidence for an association between PLBW and periodontal disease. Our results do not support a specific drive to improve periodontal health of pregnant women as a means of improving pregnancy outcomes.

Davenport ES, Williams CECS, et.al. J Dent Res 81(5): 313-318, 2002
http://jdr.iadrjournals.org/cgi/content/abstract/81/5/313

OBJECTIVE: To determine if maternal periodontal disease is associated with the development of preeclampsia.

METHODS: A cohort of 1115 healthy pregnant women were enrolled at less than 26 weeks' gestation and followed until delivery. Maternal demographic and medical data were collected. Periodontal examinations were performed at enrollment and within 48 hours of delivery to determine the presence of severe periodontal disease or periodontal disease progression. Preeclampsia was defined as blood pressure greater than 140/90 on two separate occasions, and at least 1+ proteinuria on catheterized urine specimen. The potential effects of maternal age, race, smoking, gestational age at delivery, and insurance status were analyzed, and adjusted odds ratios for preeclampsia were calculated using multivariable logistic regression.

RESULTS: During the study period, 763 women delivered live infants and had data available for analysis. Thirty-nine women had preeclampsia. Women were at higher risk for preeclampsia if they had severe periodontal disease at delivery (adjusted odds ratio 2.4, 95% confidence interval 1.1, 5.3), or if they had periodontal disease progression during pregnancy (adjusted odds ratio 2.1, 95% confidence interval 1.0, 4.4).

CONCLUSION: After adjusting for other risk factors, active maternal periodontal disease during pregnancy is associated with an increased risk for the development of preeclampsia.

Boggess KA, Lief S, et. al. Obstetrics & Gynecology 2003;101:227-231. http://www.greenjournal.org/cgi/content/abstract/101/2/227

Maternal periodontal disease, a chronic oral infectious and inflammatory disorder, is associated with an increased risk for preeclampsia. Our objective was to determine the relationship between maternal periodontal disease, maternal systemic inflammation, and the development of preeclampsia. Conclusion: Maternal periodontal disease with systemic inflammation as measured by C-reactive protein is associated with an increased risk for preeclampsia.

Ruma M, Boggess K, et al. American Journal of Obstetrics and Gynecology, Vol 198, Issue 4, Pp 389.e1-389.e5 (April 2008), http://www.ajog.org/article/ S0002-9378(07)02266-1/abstract abstract.

Oral Conditions and Pregnancy (OCAP) is a 5-year prospective study of pregnant women designed to determine whether maternal periodontal disease contributes to the risk for prematurity and growth restriction in the presence of traditional obstetric risk factors. Full-mouth periodontal examinations were conducted at enrollment (prior to 26 weeks gestational age) and again within 48 hours postpartum to assess changes in periodontal status during pregnancy. Maternal periodontal disease status at antepartum, using a 3-level disease classification (health, mild, moderate-severe) as well as incident periodontal disease progression during pregnancy were used as measures of exposures for examining associations with the pregnancy outcomes of preterm birth by gestational age (GA) and birth weight (BW) adjusting for race, age, food stamp eligibility, marital status, previous preterm births, first birth, chorioamnionitis, bacterial vaginosis, and smoking. Interim data from the first 814 deliveries demonstrate that maternal periodontal disease at antepartum and incidence/ progression of periodontal disease are significantly associated with a higher prevalence rate of preterm births, BW < 2,500 g, and smaller birth weight for gestational age. .In summary, the present study, although preliminary in nature, provides evidence that maternal periodontal disease and incident progression are significant contributors to obstetric risk for preterm delivery, low birth weight and low weight for gestational age. These studies underscore the need for further consideration of periodontal disease as a potentially new and modifiable risk for preterm birth and growth restriction.

Offenbacher S, Lieff S, et.al. Ann Periodontol. 2001 Dec;6(1):164-74.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&list_uids=11887460&dopt=Abstract

Clinical data from the first 812 deliveries from a cohort study of pregnant mothers entitled Oral Conditions and Pregnancy (OCAP) demonstrate that both antepartum maternal periodontal disease and incidence/progression of periodontal disease are associated with preterm birth and growth restriction after adjusting for traditional obstetric risk factors. In the current study we present measures of maternal periodontal infection using whole chromosomal DNA probes to identify 15 periodontal organisms within maternal periodontal plaque sampled at delivery. In addition, maternal postpartum IgG antibody and fetal exposure, as indexed by fetal cord blood IgM level to these 15 maternal oral pathogens, was measured by whole bacterial immunoblots. The potential role of maternal infection with specific organisms within 2 bacterial complexes most often associated with periodontitis, conventionally termed "Orange" (Campylobacter rectus, Fusobacterium nucleatum, Peptostreptococcus micros, Prevotella nigrescens, and Prevotella intermedia) and "Red" (Porphyromonas gingivalis, Bacteroides forsythus, and Treponema denticola) complexes, respectively, to prematurity was investigated by relating the presence of oral infection, maternal IgG, and fetal cord IgM, comparing full-term to preterm (gestational age < 37 weeks). The prevalence of 8 periodontal pathogens was similar among term and preterm mothers at postpartum. There was a 2.9-fold higher prevalence of IgM seropositivity for one or more organisms of the Orange or Red complex among preterm babies, as compared to term babies (19.9% versus 6.9%, respectively, P = 0.0015, chi square). Specifically, the prevalence of positive fetal IgM to C. rectus was significantly higher for preterm as compared to full-term neonates (20.0% versus 6.3%, P = 0.0002, as well as P. intermedia (8.8% versus 1.1%, P = 0.0003). A lack of maternal IgG antibody to organisms of the Red complex was associated with an increased rate of prematurity with an odds ratio (OR) = 2.2; confidence interval (CI) 1.48 to 3.79), consistent with the concept that maternal antibody protects the fetus from exposure and resultant prematurity. The highest rate of prematurity (66.7%) was observed among those mothers without a protective Red complex IgG response coupled with a fetal IgM response to Orange complex microbes (combined OR 10.3; P < 0.0001). These data support the concept that maternal periodontal infection in the absence of a protective maternal antibody response is associated with systemic dissemination of oral organisms that translocate to the fetus resulting in prematurity. The high prevalence of elevated fetal IgM to C. rectus among premature infants raises the possibility that this specific maternal oral pathogen may serve as a primary fetal infectious agent eliciting prematurity.

Madianos RPN, Lieff S, et.al. Obstetrical & Gynecological Survey.58(7):438-339, July 2003 2003. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&list_uids=11887461&dopt=Abstract

Maternal oral health has significant implications for birth outcomes and infant oral health. Maternal periodontal disease, that is, a chronic infection of the gingiva and supporting tooth structures, has been associated with preterm birth, development of preeclampsia, and delivery of a small-for-gestational age infant. Periodontal disease is a destructive inflammatory condition of the gingiva and bone that supports teeth. It is most commonly associated with a gramnegative anaerobic infection of these structures. Fluid that bathes the tooth at the gingival margin often contains inflammatory mediators and oral pathogens associated with periodontal disease. The mechanisms underlying this destructive process involve both direct tissue damage resulting from plaque bacterial products, and indirect damage through bacterial induction of the host inflammatory and immune responses. Extrapolation from these data suggested that 18% of the preterm, low birth weight infants born annually might be attributable to periodontal disease, and thus account for a significant proportion of the $5.5 billion annual hospital costs associated with the care of preterm/low birthweight infants. These early studies led to the hypothesis that periodontopathic bacteria, primarily Gram-negative anaerobes, may serve as a source for endotoxin and lipopolysaccharides, which then increases local inflammatory mediators including PGE2, and cytokines, and that this increases systemic inflammatory mediators that can then lead to preterm birth.

Boggess KA, Edelstein BL, Matern Child Health J. 2006 September; 10(Suppl 7): 169-174.
http://www.pubmedcentral.nih.gov/ articlerender.fcgi?artid=1592159

This trial indicates that performing SRP in pregnant women with periodontitis may reduce PTB in this population.

Jeffcoat, MK, Hauth JC, et al, J Periodontol 2003;74:1214-1218 1218. http://www.joponline.org/doi/abs/10.1902/jop.2003.74.8.1214?prevSearch=allfield%3A% 28Jeffcoat+Pregnant%29

Babies born prematurely are at a significant risk of developing serious and lasting health problems. Preterm delivery, or PTD, is the major cause of neonatal mortality and of nearly one-half of all serious long-term neurological morbidity. Previous studies have suggested that chronic periodontal infection may be associated with preterm births. Chronic periodontitis has been proposed as a risk factor for preterm birth. The authors conducted a prospective study to test for this association. The authors' data show an association between the presence of periodontitis at 21 to 24 weeks' gestation and subsequent preterm birth. This study provides additional evidence that pre-existing periodontal disease in the second trimester of pregnancy increases the risk of preterm birth. The odds of increased prematurity were increased 4.5- to 7.0-fold.

Jeffcoat MK, Geurs NC, et al., JADA 2001; 132:875-880.
http://jada.ada.org/cgi/content/abstract/132/7/875

There is compelling evidence that a link exists between pre-term low birth weight and periodontitis. A model explaining the plausible relationship is proposed based upon the concept of infection leading to a cascade of inflammatory reactions associated with pre-term labour and periodontal disease. Current evidence has pointed to an interest in dental intervention studies to control periodontal disease as one of the potential strategies to reduce pre-term labour.

Yeo BK, Lim LP, et. al. Annals Academy of Medicine January 2005, Vol. 34 No. 1.
http://www.annals.edu.sg/pdf200502/ YeoBK.pdf

Peridontal diseases are gramnegative anaerobic infections that can occur in women of childbearing age (18 to 34 years). These data indicate that periodontal diseases represent a previously unrecognized and clinically significant risk factor for preterm low birth weight as a consequence of either pre-term labor or preterm rupture of membranes.

Offenbacher S, Katz V., et.al., J Periodontol. 1996 Oct;67(10 Suppl):1103-13.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&list_uids=8910829&dopt=Abstract

Study shows that women with gingivitis who received periodontal therapy before 28 weeks of gestation had a significantly lower incidence of preterm low-birthweight babies than women who did not receive periodontal therapy. There is a significant association between gingivitis and preterm birth after adjusting for the major risk factors for preterm delivery, suggesting that gingivitis, the earliest form of periodontal disease, is an independent risk factor for preterm birth and low birthweight. If periodontal infection is diagnosed at any time during pregnancy, the treatment should be administered as soon as possible in order to reduce the risk of preterm birth and low birthweight.

American Academy of Periodontology Media Release, Nov 2005
http://www.perio.org/consumer/pregnancy-therapy.htm

Pregnant women who receive treatment for their periodontal disease can reduce their risk of giving birth to a low birth-weight or pre- term baby. Of the women who received treatment during pregnancy, 2 percent gave birth to either a low birth-weight or pre-term infant. By comparison, 10 percent of the women who received treatment after birth had either a low birth-weight or pre-term baby.

Lopez NJ, et al. J Periodontology 2002, Vol. 73, No. 8, Pages 911-924. http://www.joponline.org/doi/abs/10.1902/jop.2002.73.8.911

One hypothesis to explain the association between periodontal disease (PD) preterm/ low birth weight (PT/LBW) is that PT/LBW may be indirectly mediated through translocation of bacteria or bacterial products in the systemic circulation. Periodontal treatment significantly reduced the PT/LBW rate in this population of women with pregnancy-associated gingivitis. Within the limitions of this study, we conclude that gingivitis appears to be an independent risk factor for PT/LBW for this population.

Lopez NJ, Da Silva I et.al, J Periodontol 2005, Vol. 76,No.11-s:2144-2153. http://www.joponline.org/doi/abs/10.1902/jop.2005.76.11-S.2144?journalCode=jop

Pregnant women with findings of elevated amniotic fluid levels of PGE2 PGE2, IL-6 and IL-8 in the 15-20 weeks of pregnancy and with , periodontitis are at high risk for premature birth. The implication of this is that periodontitis can induce a primary host response in the chorioamnion leading to preterm birth.

Dörtbudak O, Eberhardt R., Journal Of Clinical Periodontology. Volume 32 Page 45 - January 2005.
http://www.blackwell-synergy.com/links/doi/10.1111/j.1600-051X.2004.00630.x/abs/

Periodontitis has been associated with increased risk of adverse pregnancy outcomes and elevated C-reactive protein (CRP) concentrations in non-pregnant adults. These findings suggest that periodontitis may increase CRP levels in pregnancy. CRP could potentially mediate the association of periodontitis with adverse pregnancy outcomes.

Pitiphat W, Joshipura KJ, Journal of Periodontology, 2006.050193).
http://www.joponline.org/doi/abs/10.1902/jop.2006.050193

Background: Few studies examining the association between periodontal diseases and preterm birth have explored the underlying microbial and antibody responses associated with oral infection.

Methods: A nested case-control study was performed using data from a recent interventional trial following the delayed-treatment control group of 31 subjects with periodontal diseases. The levels of eight oral bacteria and the maternal immunoglobulin G (IgG) responses in serum to these bacteria were measured at antepartum and postpartum visits to determine the relationship to cases (preterm delivery < 37 weeks' gestation) and controls (term delivery).

Results: Antepartum, the levels of periodontal pathogens tended to be higher in the preterm (case group) deliveries compared to the term deliveries (control group). Maternal anti- Porphyromonas gingivalis IgG was significantly lower in the preterm group compared to the term group (P = 0.028). Postpartum, levels of P. gingivalis, Tannerella forsythia, Prevotella intermedia, and Prevotella nigrescens were statistically significantly higher in preterm births compared to term deliveries, adjusting for baseline levels. The joint effects of red and orange microbial clusters were significantly higher in the preterm group compared to the term group.

Conclusions: High levels of periodontal pathogens and low maternal IgG antibody response to periodontal bacteria during pregnancy are associated with an increased risk for preterm delivery. Further studies elucidating the role of the microbial load and maternal immune response as related to pregnancy outcome seem merited.

Lin D, Moss K, et al. Journal of Periodontology. 2007, Vol. 78, No. 5, Pages 833-841. http://www.joponline.org/doi/abs/10.1902/jop.2007.060201

Objective: We examined the association between preterm delivery and polymorphisms at position +3953 of the interleukin-1[beta] gene (IL1B+3953) and in intron 2 of the interleukin-1 receptor antagonist gene (IL1RN). Study Design: This was a case-control study that involved 52 pregnancies that resulted in spontaneous preterm delivery before 34 weeks of gestation and 197 pregnancies that resulted in birth at term. Polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism analysis.

Results: Homozygous carriage of IL1B+3953 allele 1 by fetuses of African descent was associated with a risk of preterm delivery (P =.033). Fetuses of Hispanic descent that carried IL1RN allele 2 were found to be at an increased risk for preterm premature rupture of membranes and subsequent preterm delivery(P =.021; odds ratio, 6.5; 95% CI, 1.25-37.7).

Conclusion: There are associations of spontaneous preterm delivery with the fetal carriage of IL1B+3953*1 and IL1RN*2 alleles in African and Hispanic populations, respectively.

Genc MR, Gerber S, et. al. American Journal of Obstetrics & Gynecology July 2002, 187:1.
http://pt.wkhealth.com/pt/re/ajog/ abstract.00000447-200207000- 00024.htm; jsessionid=GFnPyPB6tdln2WTllFrd4qChqpkqThfGf18hThLvZDcK4yy7p2YN!-377544086!-949 856144!8091!-1

We conclude that poor periodontal health of the mother is a potential independent risk factor for LBW.
Dasanayake AP, Ann Periodontol 1998 Jul;3(1):206-12.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9722704

Maternal inflammatory response appears to be an important effector mechanism underlying preterm low- lowbirth- weight infants. This birth-response involves genetic as well as environmental exposure components. There is a growing body of evidence indicating that periodontist may be a sufficient infectious challenge to result in PLBW. Data presented here indicates that perio disease (in hamster model) can induce elevations in intraamniotic PGE2 and TNF-? and result in fetal growth retardation; and that mothers with PLBW have a significant 2-fold elevation in the BCF-PGE2 levels and a plaque microbiota, which is consistent with progressive periodontitis. The similarities in the mixed anaerobic infection of vaginosis and Periodontitis and the striking parallels in inflammatory mediator responses suggest that there is a common underlying pathophysiologic pathway or mechanism that warrants further investigation of the linkage between these infections and PLBW.

Offenbacher S, Jared HL, et. al., Annals of Periodontology Vol. 3, No. 1, July 1998.
http://medweb.unimuenster. de/institute/zmk/einrichtungen/par/bilder/offenbacher.pdf

African Americans consistently experience higher rates of preterm and low birth weight (LBW) deliveries than do whites. LBW and preterm infants are more likely to die before their first birthday and survivors may suffer from a number of health problems. Therefore, identification of modifiable risk factors for preterm deliveries and LBW has considerable public health significance. Pregnant women's poor periodontal health is emerging as one such factor. Maternal clinical periodontal status and bacteriologic and immunologic profiles related to periodontal disease have been associated with risk of fetal growth and preterm LBW, and periodontal treatment during pregnancy has reduced the incidence of preterm deliveries. This article reviews the literature on the above association and presents data from a previously published prospective study of predominantly African Americans to show that preterm LBW deliveries are associated with higher midtrimester maternal serum antibody levels against Porphyromonas gingivalis.

Dasanayake AP, Russell S. The Dental clinics of North America. 2003, vol. 47, No.1 pp.115-12. 12., http://cat.inist.fr/?aModele=afficheN&cpsidt=14624279

The OCAP study demonstrates that maternal periodontal disease increases relative risk for preterm or spontaneous preterm births. Furthermore, periodontal disease progression during pregnancy was a predictor of the more severe adverse pregnancy outcome of very preterm birth, independently of traditional obstetric, periodontal, and social domain risk factors.

Offenbacher S, Boggess KA, et. al. Obstetrics & Gynecology 2006;107:29-36.
http://www.greenjournal.org/cgi/content/ abstract/107/1/29

The more of the mouth affected with periodontal disease, the more likely a woman is to deliver a premature baby, according to an ongoing study of more than 2,000 pregnant women. The results point to further evidence that periodontal disease may be a significant risk factor for preterm births. Past studies have shown that women with periodontal disease may be up to seven times more likely to deliver a preterm low birth weight baby. Today at the American Academy of Periodontology's Specialty Conference on Periodontal Medicine in Washington, D.C., preliminary research was presented for the first time suggesting that the risk for women who have generalized periodontal disease (meaning it affects at least 30 percent of their mouth) is even higher. Data tells us the best advice continues to be that women considering pregnancy have a periodontal screening and get any problems with their oral health under control before becoming pregnant. Women who are already pregnant should not shy away from dental care. Dentists should perform scaling and root planing, along with any supportive therapy, in the second trimester for pregnant patients with periodontal disease.

Jeffcoat M., American Academy of Periodontology Specialty Conference on Periodontal Medicine in Washington, DC, May 7, 2000. Univ of Alabama Birmingham School of Dentistry. American Academy of Periodontology Press Release May 2000.
http://www.perio.org/consumer/women_risk.htm

Mothers who suffer from gum disease are significantly more likely to deliver their babies prematurely than women without that illness. In the five-year study, researchers evaluated periodontal disease in more than 850 women. This prospective study confirms our earlier case-control studies showing that both periodontal disease and periodontal disease progression during pregnancy have an effect on the fetus. Babies developing in women's wombs are being adversely affected by germs growing in their mothers' mouths such that they are born early or at lower than normal weight. Scientists find antibodies to specific organisms in placental blood at the time of delivery. One in 10 babies in the United States is born too small or too early, which is a major cause of sickness and mortality. This work is very important because it confirms a new and potentially modifiable risk factor that we should be able to reduce. Gum disease may be responsible for up to 18 percent of pre-term deliveries, he said the new study suggests. It's not just that periodontal disease is a surrogate marker for poor oral hygiene or other socioeconomic factors just sort of jumbled together," the scientist said. "The fact that we're finding specific organisms that can cause growth and delivery problems opens up a whole new avenue for preventive care.

Lieff, S., McKaig R.G., University of North Carolina at Chapel Hill, Duke University.
http://www.eurekalert.org/ pub_releases/2002-03/uoncsbs030502. php

Low birth weight infants are about 20 times more likely to die before their first birthday compared to normal birth weight infants. While the rate of LBW has been consistently higher among African Americans compared to whites, there has been a gradual increase in LBW for both African Americans and whites over the last 15 years. In an attempt to identify modifiable risk factors for LBW, we have previously reported that a pregnant woman's poor periodontal health may be an independent risk factor for low birth weight. Porphyromonas gingivalis (P.g.)-specific maternal serum IgG levels were higher in the LBW group compared to the normal birth weight (NBW) group. Women with higher levels of Pg.- specific IgG had higher odds of giving birth to LBW infants. This association remained significant after controlling for smoking, age, IgG levels against other selected periodontal pathogens, and race. Conclusions: Low birth weight deliveries were associated with a higher maternal serum antibody level against P. gingivalis at mid-trimester.

Dasanayake AP, Boyd D, et.al., Journal of periodontology 2001, vol. 72, no11, pp. 1491-1497. http://cat.inist.fr/?aModele=afficheN&cpsidt=13493073

Although two thirds of infant deaths in the United States occur among infants born preterm (<37 weeks of gestation), only 17% of infant deaths are classified as being attributable to preterm birth with the standard classification of leading causes of death. To address this apparent discrepancy, we sought to estimate more accurately the contribution of preterm birth to infant mortality rates in the United States. .On the basis of this evaluation, preterm birth is the most frequent cause of infant death in the United States, accounting for at least one third of infant deaths in 2002. The extreme prematurity of most of the infants and their short survival indicate that reducing infant mortality rates requires a comprehensive agenda to identify, to test, and to implement www.MDReferrals.net 89 effective strategies for the prevention of preterm birth.

Callaghan WM, MacDorman MF, et al. PEDIATRICS Vol. 118 No. 4 October 2006, pp. 1566- 1573. http://pediatrics.aappublications.org/cgi/content/ abstract/118/4/1566

The influence of subject-based and environmental factors on the balance between the subgingival microbial challenge and the host response in periodontal diseases illustrates the intimate link between oral and systemic health. From this stems the hypothesis that the persistent Gram-negative challenge and associated inflammatory sequelae in periodontal disease may have consequences extending beyond the periodontal tissues themselves. This paper addresses the design of a case-control study to examine the relationship between preterm low birth weight (PLBW) and maternal periodontal disease. We present preliminary data on the prevalence of these 2 conditions in a group of mothers at the Royal Hospitals Trust, London, U.K. Cases are defined as mothers delivering an infant weighing less than 2,500g before 37 weeks gestation and controls as mothers delivering an infant of more than 2,500g after 38 weeks. We estimated that a study involving 800 mothers (1:3 case:control) should have sufficient power to detect an association with a minimum odds ration of 3 at the 5% significance level. Demographic details of 177 subjects demonstrated that they were representative of the local population, and the prevalence of PLBW was within the expected range. However, the extent and severity of periodontal disease were higher than predicted and may have reflected elevations in gingival inflammation associated with pregnancy. The final outcome of the study should help determine the need for further interventionist studies to demonstrate a causal relationship between periodontal disease and PLBW, as well as provide information on the prevalence of periodontal diseases in this study population.

Davenport ES, Williams CE, et.al. Ann Periodontol. 1998 Jul;3 (1):213-21.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi? cmd=Retrieve&db=PubMed&list_uids=9722705&dopt=Citation

Preterm birth with its subsequent morbidity and mortality is the leading perinatal problem in the United States. Infants born before the thirtyseventh week of gestation account for approximately 6% to 9% of all births, but 70% of all perinatal deaths and half of all long-term neurologic morbidity. Current approaches focus on symptomatic treatment. Despite widespread use of drugs to arrest preterm labor (tocolytics), there has been no decrease in low birth weight or preterm infants in the last 20 years. It is likely that therapy directed at preventing or treating underlying causes would be more successful. Evidence from many sources links preterm birth to symptomatic infections, for example, of the urinary or respiratory tracts. In the last decade, great interest has been generated to support the hypothesis that subclinical infection is an important cause of preterm labor. Evidence to support this may be categorized as follows: histological chorioamnionitis is increased in preterm births; clinical infection is increased after preterm birth; there is significant association of some lower genital tract organisms and infections with preterm birth or preterm premature rupture of the membranes; there are positive cultures of amniotic fluid or membranes from some patients with preterm labor and preterm birth; there are markers of infections in preterm birth; bacteria or their products induce preterm birth in animal models; and some antibiotic trials have shown a lower rate of preterm birth or have deferred preterm birth. In the last 5 years, additional exciting information has suggested that not only is subclinical infection responsible for preterm birth but also many serious neonatal sequelae including periventricular leukomalacia, cerebral palsy, respiratory distress, and even bronchopulmonary dysplasia and necrotizing enterocolitis. In sum, a large body of clinical and laboratory information suggests that subclinical infection is a major cause of preterm birth, especially those occurring before 30 weeks. This concept holds promise that new approaches can be developed to prevent prematurity.

Gibbs RS. Annals of Periodontology December 2001, Vol. 6, No. 1, Pages 153-163. http://www.joponline.org/doi/abs/10.1902/annals.2001.6.1.153?journalCode=annals