During pregnancy, due to hormonal changes, there is a certain systemic propensity to periodontal problems. The most pathogenic bacteria of the biofilm, (Socransky’s orange and red cluster bacteria), tend to increase in numbers, and also, due to increased vascular permeability, these bacteria and their products can more easily enter the bloodstream and spread to other parts of the body, such as the fetoplacental unit.
In studies in humans, this link has been demonstrated through different mechanisms. One is by studying the specific antibody immune response to periodontal pathogens. In several studies, mothers with a lack of antibodies for red cluster bacteria and with an increase against orange cluster bacteria, were shown to have a greater pre-term delivery rate. By contrast, other studies proved the opposite, which could have two explanations. Either the lack of antibodies, leaving the foetus unprotected from infection, or an exaggerated response, indicating a hyper-inflammatory profile, could lead to pre-term delivery.
Other human studies were based on microbiological detection using PCR of amniotic fluid. This way periodontal pathogens were found in the placenta of women who had pre-term deliveries and low birth weight babies in several studies. What has proven more difficult is to grow these bacteria, which has only been achieved by one study. Whether these bacteria are alive or dead when they arrive and whether or not they are planktonic or form part of biofilms, remains controversial, although there is one study that found biofilms in placenta. Whether or not the spread of bacteria is by way of the genitourinary tract to the placenta or from the periodontium to the placenta is also a source of dispute, and in 2 studies, identical clonal types were found in dental bacterial plaque and amniotic fluid, while these were not detected in the vaginal or rectal flora.
Finally, studies in humans have also explored the relationship between increased proinflammatory cytokines, IL-1, IL-6, TNF-α and mediators, PGE-2, both in the sulcus and in serum and amniotic fluid, finding mixed results regarding increased adverse pregnancy outcomes. Mixed results have also been found for the increase in C-reactive protein, which tends to occur in the liver from increased systemic inflammation.
Another type of evidence comes from studies in animals and in vitro tests. Most studies have used hamsters, mice and rabbits, whose blood was either injected with periodontopathogenic bacteria or with their virulence factors (LPS), or where the animals were inserted with metallic chambers releasing the bacteria or their products into the bloodstream for a long-distance focal infection. The first experiments were performed on golden hamsters, before and during pregnancy, which were exposed by way of both models (injection and chamber) either to LPS from Pg and Ec or to these same bacteria together with Fn and Cr, and in all cases, adverse effects involving pre-term deliveries, resorptions, limited intrauterine growth, abortions and/or stillbirths were observed. Also, in most cases, genetic material from the bacteria or increased systemic or placental inflammatory markers were found. Both models could occur in pregnant women, since periodontitis is a chronic infection, comparable to the metallic chamber, or since infection in these patients can be transitory, as is the injection of bacteria in animals. Another important point is that bacteria alone, not forming part of biofilms, can penetrate the fetoplacental unit and settle there, due to lower immunity and the fact that it is a nutrient-rich environment, and end up causing disease and inflammation. In mice, it has also been observed that bacteria such as Fn, Pg and Cr can invade and settle in the placenta and provoke an immune inflammatory response with elevated proinflammatory cytokines, and infiltrated neutrophil, also altering the structures for nutrient exchange between mother and child, and causing growth restrictions for the foetus, and potentially, pre-eclampsia in mothers. Lastly, infection by C. rectus could alter the expression of some genes in the foetus and could even cause developmental or cognitive problems in unborn babies.
In order to establish a link between periodontal disease and the various adverse pregnancy outcomes (low birthweight infants, premature babies, low birthweight premature babies and pre-eclampsia), case-control, cross-sectional, prospective studies and meta-analyses have been conducted on all of the above. A moderate association has generally been found between periodontal disease and the different adverse pregnancy outcomes, which is largely due to the heterogeneity of the studies and the varying definition of periodontal disease depending on the type of endpoint used. For low birthweight babies, an OR of 1:2 was found when performing a meta-analysis of the case-control studies that used dichotomous endpoints. When continuous endpoints were used, and in the meta-analyses of prospective studies, the results were mixed. For premature babies, the meta-analyses of case-control studies have also found an association, although for the prospective studies the results are conflicting. When both adverse effects are combined, there are also differences between the data from the different studies, and the results of the meta-analyses greatly depend on the type of endpoints used. Finally, for pre-eclampsia, data from the case-control and prospective studies and from the meta-analyses also show a link between poor oral conditions and pre-eclampsia. In general, the use of continuous endpoints, for example average probing depth, and endpoints related to periodontal disease background such as attachment level, do not normally prove a positive association, while using categorical and inflammatory endpoints do tend to favour this association.
Effects of periodontal treatment on pregnancy
In general, results from randomised clinical trials conducted to date have not found an improvement in adverse pregnancy outcomes when periodontal treatment is performed on pregnant women. There may be more than one reason for this. One is that periodontal disease and adverse pregnancy outcomes both share common risk factors that can muddle the results. The definition of periodontitis may also influence the results, and it is important to distinguish between the different types of pre-term and low birthweight cases by creating sub-categories. Finally, performing treatment during pregnancy may possibly be too late, and perhaps should be done before pregnancy to have positive effects.
Conclusions of PD and pregnancy
During pregnancy, due to alterations in vascular permeability of the gums, the bacteria in biofilm could more easily enter the bloodstream, possibly reaching the placental tissue. Once there, and due to slow blood circulation and to the invasive properties of these microorganisms, these can penetrate the foetus and the amniotic fluid, where an immune response will occur, releasing proinflammatory cytokines. If the body can contain the infection, there will be no consequences, but if it cannot, membranes may rupture, resulting in preterm delivery. These inflammatory compounds can also negatively regulate the gene expression needed for foetal growth, causing low birth weight and causing structural damage in placental blood circulation, increasing the mother’s blood pressure, also known as pre-clampsia. The fetoplacental unit can also be affected by the inflammatory products deriving from the periodontal pocket or liver-derived products such as C-reactive protein. It is important to understand that these associations need further study in humans, as most conclusions have come from animal and in vitro studies. In this sense, we must clarify which bacteria and what amount of bacteria need to reach the fetoplacental unit and when we should intervene so this does not occur. Clinical signs are often not related to the actual microbiological situation, and for this reason, some intervention studies have not obtained the expected results, as the intervention was performed too late.
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