Preterm birth
Preterm birth, delivery at less than 37 weeks’ gestation, occurs in approximately 12% of all births [
18,
19]. Prematurity is the leading cause of neonatal morbidity and mortality in non-anomalous infants [
20]. There are numerous and heterogeneous factors associated with preterm birth, such as low maternal body mass index, maternal smoking, and maternal infections [
21]. In 1996, Offenbacher and colleagues [
7] first reported a potential association between maternal periodontal disease and delivery of a preterm/low birthweight infant. In a case-control study of 124 pregnant women, they observed that women who delivered at less than 37 weeks’ gestation or an infant <2500 g had significantly worse periodontal disease than control women. The adjusted odds ratio for delivery of a preterm, low birth weight infant was ∼7; these data led the authors to conclude that periodontal disease may represent a previously unrecognized and clinically significant risk factor for delivery of a preterm low birth weight infant [
7]. 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. In a subsequent case-control study, Dasanayake et al. studied 55 pairs of women. Logistic regression indicated that mothers with ‘healthy gingiva’ were at lower risk for low birth weight infants [
22]. Women in both of these case-control studies were examined at the end of pregnancy or after delivery, which does not convincingly prove an antecedent exposure and thus causality. Despite this limitation, 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 [
23]. Additionally, Jeffcoat et al. [
9] examined the relationship between maternal periodontal disease and spontaneous preterm birth among 1313 pregnant women, and found that moderate/severe maternal periodontal disease identified early in pregnancy was associated with an increased risk for spontaneous preterm birth, independent of other traditional risk factors [
9].
Despite these compelling data, it is important to recognize that other studies have failed to demonstrate any association between maternal periodontal disease and preterm birth. In a case control study conducted in London, Davenport et al. [
24] examined 236 infants born at <37 weeks’ gestation or <2500 g and compared them to a random sample of 507 control infants born at ≥38 weeks’ gestation and weighing ≥2500 g. The authors found no evidence for an association between delivery of a preterm, low birth weight infant and periodontal disease and somewhat surprisingly, found that deeper mean tooth pocket depths at delivery was associated with a reduction in the risk of delivery of a preterm, low birth weight infant [
24]. The authors surmised that these discrepant findings might be due at least in part to racial differences in study populations. In a follow-up longitudinal study of 3738 women, Moore et al. [
25] found no association between maternal periodontal disease and preterm birth. However, there was an increase in second trimester fetal loss rates among women with periodontal disease [
25].
In an effort to better understand the possible mechanism behind the association between periodontal disease and preterm delivery, Offenbacher and colleagues [
23] measured gingival crevicular levels of PGE
2 and IL-1ß in 48 mothers who delivered preterm, low birth weight infants compared to control women and discovered that gingival crevicular fluid levels of PGE
2 were significantly higher in case compared to control women. Furthermore, among the primiparous women delivering preterm, low birth weight infants, a significant inverse association was demonstrated between birthweight and gestational age and gingival crevicular PGE
2 levels [
23].
It is not yet clear whether the relationship between periodontal disease and adverse pregnancy outcomes is causal or is a surrogate for another maternal factor. As further evidence to support the concept that maternal oral health is important for normal pregnancy outcome, other investigators have examined the effect of antepartum treatment of periodontal disease on preterm birth risk. Three published studies of antepartum versus delayed (postpartum) treatment of maternal periodontal disease demonstrate promise for this intervention for preterm birth prevention. The effect of periodontal interventions on pregnancy outcome was assessed in a prospective study designed to examine the relationship between periodontal disease and preterm low birthweight infants in a cohort of young, minority, pregnant and postpartum women. Of 164 women for whom birth outcome data were available, 74 were subjected to oral prophylaxis during pregnancy, and 90 received no periodontal treatment. The preterm/low birthweight rate was lower among women who received periodontal treatment compared to those who did not (13.5% vs. 18.9%) [
26]. Lopez et al. conducted a randomized clinical trial to assess the impact of periodontal treatment initiated during pregnancy versus delayed until postpartum on preterm low birthweight infant rates. The incidence of preterm/low birthweight infants in the antepartum treatment group was 1.8% (3/163) and in the delayed/postpartum group was 10.1% (19/188), (odds ratio [OR] 5.5, 95% confidence interval [CI] 1.7–18.2,
P=0.001). Multivariable logistic regression analysis showed that periodontal disease was the strongest factor related to delivery of a preterm/low birthweight infant (OR 4.7, 95% CI 1.3–17.1) [
27]. The data from these two studies suggest that treatment of periodontal disease during pregnancy could reduce preterm/low birthweight infant rates [
26,
27].
In a pilot intervention trial designed to assess the feasibility of conducting a trial to determine whether treatment of periodontal disease reduces the risk of spontaneous preterm birth, Jeffcoat et al. found that among women at high risk for preterm birth and presence of periodontal disease, scaling and root planning therapy initiated during pregnancy is tolerated by pregnant women and may reduce spontaneous preterm birth [
28].
Other adverse pregnancy outcomes
Preeclampsia is a hypertensive disorder of pregnancy responsible for significant, maternal and fetal morbidity and mortality. Preeclampsia affects up to 5% of pregnant women [
29]. The etiology of preeclampsia remains elusive. The underlying pathology may be related to a generalized intravascular hyperinflammatory state [
29]. Some investigators have hypothesized a potential role for maternal periodontal disease as a risk factor for preeclampsia. In a retrospective analysis of data collected as part of the Oral Conditions and Pregnancy Study, Boggess et al. reported that 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) [
30]. In a case-control study, Canakci et al. found that pre-eclamptic patients were 3.5 (95% CI=1.1–11.9) times more likely to have periodontal disease than normotensive patients [
P < 0.01) [
31]. In a study of 30 pregnant women, significantly higher periodontal probing depth and clinical attachment level scores were found among preeclamptic women compared with non-preeclamptic women. Gingival crevicular fluid levels of PGE
2, TNF-
α, and IL-1
β levels were all significantly higher in the preeclamptic group [
32]. Further study on the maternal and fetal inflammatory responses to chronic oral infection and on placental pathology in women with periodontal disease is needed to determine whether the relationship between periodontal disease and preeclampsia is causal or simply associative. If the relationship between maternal periodontal disease and preeclampsia risk proves causal in nature, then prevention of periodontal disease before pregnancy or treatment of periodontal disease during pregnancy may represent a novel approachs to the prevention of preeclampsia.