Periodontal Infections and Adverse Pregnancy Outcomes: The Oral Health—Fetal Connection

Introduction

Dental infections causing systemic diseases in distant parts of the body have been known for decades. The concept, called focal infection, reported by Miller in 1891 was very popular in the beginning of the twentieth century. ¹ It got an impetus after William Hunter's forceful pleas for action against dental sepsis in 1910. ² The concept fell into oblivion because of thoughtless and unmindful sacrifice of teeth and tonsils for their alleged roles in causing systemic disease. In 1989, the concept got support, when a couple of Danish researchers reported an increasing incidence of coronary heart disease in the presence of periodontal disease. ³ From that point there was a surge of interest in dental infections causing systemic disease. Cardiocavascular disease, stroke, preterm babies, pulmonary disease, total mortality, Alzheimer's disease, dementia, and many other systemic conditions are directly or indirectly attributed to—or associated with chronic periodontal infections—as is total mortality.

Periodontal diseases comprise a group of diseases that affect the supporting structures of the teeth. The involved teeth are normal but the the gums and alveolar bone are affected adversely. Called pyorrhea in earlier literature, periodontal disease is prevalent universally, and no continent or country is unaffected by this chronic ailment. Characterized by gum bleeding, discharge of pus, and progressive mobility of teeth and their ultimate loss, the disease is chronic, painless, and produces no compelling urge for seeking treatment in the absence of severe pain. Contrary to dental caries, which involve few teeth, periodontal disease involves most teeth and is the most common cause of tooth loss (Fig.1). Periodontal disease also represents an infectious disease affecting >23% of women between the ages of 30 and 54. ⁴

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FIG. 1.

Advanced periodontal disease with severe inflammation, gross sepsis, and loosening of teeth.

What the Research Shows

Given that there is a potential association between periodontal disease and preterm births, it makes sense to explore this association. A search of the dental literature, including Medline^®/PubMed through 2009, was conducted focusing on periodontal disease, preterm delivery, low birth weight, and intrauterine growth restriction was undertaken, and a hand search of other gray literature and text books was performed.

Complicated pregnancies include preterm births, low-birth-weight babies, small-for-gestational-age (SGA) infants and cause considerable social, psychologic, and economic burdens on the families affected. Preterm delivery is associated with risk factors such as smoking and alcohol consumption, race, parity, low maternal weight, older and younger maternal age, short cervical length, stress, low socioeconomic status, poor nutritional status of the mother, genitourinary infections, and other generalized systemic infections. These infections trigger the release of proinflammatory mediators such as interleukin 1(IL-1), tumor necrosis factor alpha (TNF-α) and prostaglandin E₂ (PGE₂), which initiate preterm labor and low birth weight. Periodontitis, a chronic and subclinical disease, is also suspected for providing an inflammatory component in the fetal environment.

During pregnancy,the incidence of gingivitis and periodontitis is increased and many pregnant women suffer from bleeding and spongy gums. Changing hormone levels during pregnancy, coupled with lack of oral hygiene, account for most of the gingival changes. Fifty percent (50%)–70% of all pregnant women develop gingivitis; this condition is called “pregnancy gingivitis.” Increases in progesterone and estrogen levels during pregnancy affect small blood vessels of the gingiva, leading to their increased permeability. This increased inflammatory nature of the gingiva predisposes pathogenic bacteria to take advantage of the situation and frank disease results. The result is a host response to the microbial attack by producing increased proinflammatory cytokines.

It has been increasingly reported that pregnant women with periodontitis have more chances of having adverse pregnancy outcomes such as preterm birth, low birth weight infants, preeclampsia, gestational diabetes, SGA infants and fetal loss.

Galloway ⁵ reported in 1931 that focal infection in teeth and tonsils affected the fetus. His was probably the first interventional study. He extracted abscessed teeth in patients and observed no incidents of miscarriage or stillbirth in these patients. He suggested that all foci of infection should be removed or treated early in pregnancy to avoid unwanted sequelae.

Periodontitis and Preterm Birth

It all started 13 years ago, when Offenbacher et al., ⁶ at the University of North Carolina conducted a study to determine whether prevalence of maternal periodontal infection was associated with preterm low birth weight. The researchers controlled for known risk factors and potential covariates in a study of 124 pregnant women or postpartum mothers. Assessing other known obstetric risk factors, the researchers demonstrated that periodontal disease is a statistically significant risk factor for preterm low birth weight and concluded that periodontal disease represents a previously unrecognized and significant risk factor for preterm low birth weight.

Since 1996, there has been a deluge of research papers on this topic. There have been articles supporting the hypotheses, some that do not report any association, and some that report a weak association.

In another study, ⁷ the average weight of the newborns in a periodontitis group was lower than infants in the control group, and it was concluded that localized periodontitis of the patient during pregnancy can be regarded as an important risk factor for preterm birth. In an article published in The Lancet, Pihlstrom and coworkers ⁸ stated that periodontal disease has been associated with adverse pregnancy outcomes, cardiovascular disease, stroke, pulmonary disease, and diabetes, but the causal relationships have not been established. Controlling bacterial biofilm, arresting periodontal disease, and restoring lost periodontal support has been suggested to improve pregnancy.

In a prospective study called the Oral Conditions and Pregnancy (OCAP) study, Offenbacher et al. ⁹ reported an 11.2% incidence of preterm births among periodontally healthy women, compared with an incidence of 28.6% in women with moderate–severe periodontal disease and concluded that maternal periodontal disease increases relative risk for preterm or spontaneous preterm births.

Xiong, ¹⁰ in an article published in the British Journal of Obstetrics and Gynaecology, reviewed status of periodontal disease and adverse pregnancy outcomes. Of twenty-five studies, 18 suggested an association between periodontitis and adverse pregnancy outcomes, and 7 studies found no evidence of an association. In three studies, prior scaling and periodontal treatment led to a 57 % reduction in preterm low birth weight and a 50% reduction in preterm births.

Delivery of an SGA infant in mothers with moderate or severe periodontal disease early in pregnancy was reported by Boggess et al. ¹¹

Linking gingivitis to bacterial vaginosis, Persson ¹² reported that higher vaginal bacterial counts are possible in women with gingivitis in comparison to women with bacterial vaginosis but who have no gingivitis. Organisms such as Prevotella bivia and Prevotella disiens may be specific to a relationship between vaginal and gingival infections.

In a thorough review of literature on the subject, ¹³ twenty-six epidemiologic studies reported an association between periodontal disease and adverse pregnancy outcomes. However, most studies did not control for confounders, thus raising serious doubts about the researchers' conclusions. The conclusions drawn by various researchers also had methodological limitations and could not be relied upon to establish an association between periodontal disease and adverse pregnancy outcomes. Despite conflicting risk factors and contradicting statements, most of the clinical studies indicated a positive correlation between periodontal disease and preterm birth. Microbiologic and immunologic findings strongly support the association. Placental–fetal exposure to periodontal infection and resulting fetal inflammatory response can lead to preterm delivery.

Discussing whether maternal periodontitis was associated with an increased risk of preeclampsia, researchers wrote an article about a case-control study in Brazil that reported such an association. ¹⁴ In a study in Turkey, Tygor ¹⁵ suggested that maternal periodontal disease may be a risk factor for an adverse pregnancy outcome. In a case-controlled study of 1305 Brazilians, ¹⁶ Siqueira and workers reported that maternal periodontitis was associated with an increased risk for preterm birth, low birth weight, and intrauterine growth restriction, and they focused on the importance of periodontal care in prenatal health programs. In a prospective cohort study in Pakistan, 1152 women were assessed for dental status and followed for pregnancy outcomes. ¹⁷ Low birth weight was not related to measures of periodontal disease but stillbirth and neonatal and perinatal deaths increased with severity of periodontal disease.

In a study of 1404 pregnant women in Spain, Lopez ¹⁸ reported a modest association between periodontitis and preterm birth. Although not all of the actual data supported the periodontal–pregnancy connection, assessment of the periodontal status of pregnant women during an early pregnancy might be useful for minimizing future obstetric complications. A review of 31 published studies showed that 22 showed a positive association between premature birth and periodontal disease. ¹⁹ Preterm low birth weight was reported to be related to periodontal infections that might influence the fetus–placenta complex.

If periodontal inflammation is directly or indirectly responsible for adverse pregnancy outcomes, the natural corollary would be treatment or elimination of such inflammation, which would result in fewer occurrences of adverse events. There are contradictory reports in about this strategy. To study this strategy, it would be necessary to expose pregnant women to good oral hygiene and oral prophylaxis, and observe postpartum events and compare these events with those in pregnant women who did not receive any dental treatment. The hypotheses would be tenable only if a significant number of pregnant women who had dental care had fewer adverse outcome events compared to controls. Few studies have examined the potential effects of periodontal treatment during pregnancy on pregnancy outcomes, periodontal status, and inflammatory biomarkers.

In a pilot study in 2003, Jeffcoat ²⁰ and coworkers performed periodontal treatment on pregnant women and observed them for pregnancy outcomes. Performing scaling and root planing produced reduction of preterm births in the women who received this treatment.

Periodontal treatment in another study resulted in a significant decrease in periodontopathic bacteria, serum IL-6, and gingival crevicular fluid IL-1ß. This particular research supports the view that periodontal treatment has beneficial value on pregnancy outcomes. A 3.8-fold decrease in the rate of preterm delivery with periodontal intervention is a welcome development. ²¹

Gazolla et al. ²² also attempted to evaluate the efficacy of periodontal treatment with respect to pregnancy outcomes. Mothers who had treatment for periodontal conditions fared better than those who did not receive such interventions. Periodontal disease was related significantly to preterm delivery.

Another study of particular relevance was an Indian one from Bangalore conducted by Tarannum and Faizuddin ²³ who tested the efficacy of periodontal treatment during pregnancy and versus no treatment for any adverse outcomes. Periodontal treatment during pregnancy included plaque control instructions, scaling, and root planing. There was a significant effect of periodontal treatment on birth outcomes in this study.

Porphyromonas gingivalis is a microorganism involved in periodontal disease and has been found in the amniotic fluid of a few pregnant women, some of whom experienced threatened premature labor. ²⁴ Pregnant mice infected with P. gingivalis had elevated levels of TNF-α, suppressed levels of maternal IL-10, and enhanced fetal-growth restriction.

With respect to awareness of periodontal health and pregnancy outcomes among obstetricians and physicians, an interesting survey in North Carolina ²⁵ showed that most respondents answered correctly that periodontal disease is caused by bacteria and 84% the of respondents considered periodontal disease to be an important a risk factor for adverse pregnancy events. The respondents were aware of periodontal disease and its implications for pregnancy outcomes. However, such a healthy awareness has yet to be disseminated among physicians and obstetricians in many parts of the world.

Contrasting Research

Not all of the evidence supports the oral health–pregnancy connection. In a study of 328 Caucasian women, Heimonnen et al. ²⁶ found no differences between mothers who had preterm births and mothers who had full-term births with respect to periodontal status. Primiparity, low weight-gain, and antimicrobial drug use during pregnancy were the significant predictors for preterm birth in this study. The study could not establish any linkage between periodontal parameters and pregnancy outcomes and attributed the preterm births to only established systemic risk factors.

In a multicenter, randomized controlled clinical trial published in The New England Journal of Medicine, Michalowicz and coworkers ²⁷ could not establish any association between treatment of periodontal disease during pregnancy and subsequent pregnancy outcomes. This has sparked an interesting debate, and the topic continues to enliven researchers to probe the potential relationship further. However, it has also been pointed that a single randomized trial does not have finality, and additional research is critical for supporting this hypothesis.

Wimmer and Pihlstrom ²⁸ were more categorical and forthright in highlighting the inadequacies of research for establishing the association between periodontal status and birth outcome. Definitions of what constitutes periodontal disease and inadequate control of confounding factors make studies in this area difficult. There is no conclusive evidence that treatment of periodontal infection results in better birth outcomes. While maternal treatment of periodontal disease will reduce signs of gum disease, this treatment does not reduce the rate of preterm birth.

Srinivas and coworkers ²⁹ from the Department of Obstetrics and Gynecology, in the University of Pennsylvania Health System, conducted a multicenter prospective cohort study involving 311 patients with and 475 patients without periodontal disease. The researchers could not establish any association between periodontal disease and any composite outcome or preterm birth. They had the last word in this regard when they concluded that “despite the body of literature suggesting an association between periodontal disease and adverse pregnancy outcomes in urban populations, this large prospective study failed to demonstrate an association.” ²⁹

Conclusions

Preterm birth is a major cause of infant mortality and morbidity, and has considerable social, medical, and economic impacts. The rate of preterm birth appears to be increasing worldwide and efforts to prevent or reduce its prevalence have been largely unsuccessful. Adverse pregnancy outcomes have many risk factors. If periodontal disease were recognized as a risk factor, identification of a such causal/contributory relationship to preterm birth would have far reaching and long-lasting effects on society. Conceding that there is an ongoing debate, it has to be borne in mind that reports showing a positive association have come from world-class researchers and have been published in peer-reviewed journals. It pays to be prudent, not ignore shouts and whispers about a potential connection, and continue to remain vigilant about pregnancy and oral health.