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Background
of any beneficial systemic effect would not contraindicate the peri- odontal therapy. While the most relevant analysis refers to the treatment of periodontitis in patients with co-morbid NCDs ( n = 29 RCTs), data were also combined with that from systemically healthy individuals ( n = 3 RCTs). This approach was not defined a priori and it represents a methodological limitation of the review, but it was deemed to be justified on the basis that there would likely be patients within the systemically healthy group who had undiagnosed NCDs. Sixteen RCTs addressed adverse pregnancy outcomes (pre-term birth <37, <35, and <32 weeks, low birth weight <2500 g and <1500 g, pre-term low birth weight, pre-eclampsia, gestational age at deliv- ery, C-reactive protein [CRP], stillbirth, birthweight, and perina- tal loss). Following an update of the systematic search, five new studies were identified (Buwembo et al., 2020; Montero et al., 2020; Nguyen et al., 2021; Qureshi et al., 2021; Rapone et al., 2021) with data from four of them included in meta-analyses (Montero et al., 2020; Nguyen et al., 2021; Qureshi et al., 2021; Rapone et al., 2021). The updated meta-analyses did not change the inter- pretation of the available evidence apart from the increase in dia- stolic blood pressure previously observed for PICOS #2, which became non-statistically significant (0.15 mmHg 95% CI ( 0.14; 0.44]; p = .311]. Furthermore, a statistically significant reduction in tumour necrosis factor (TNF)- α [ 0.27 pg/ml 95% CI [ 0.53; 0.014]; p = .039) was observed for PICOS #1 and PICOS #2 populations combined.
Intervention
Treatment of periodontitis consisted of step 1 (behaviour change, oral hygiene coaching and supra-gingival PMPR), step 2 (subgingival instrumentation, including removal of dental biofilm and calcified deposits and use of adjunctive therapies), step 3 (surgical periodontal therapy) and step 4 (supportive periodontal care) in order to reduce gingival inflammation (Sanz, Herrera, et al., 2020). Observational evi- dence has linked periodontitis to increased risk of NCDs (Sanz et al., 2018; Sanz, Marco Del Castillo, et al., 2020). Multiple mecha- nisms have been proposed to explain the biological plausibility of a systemic effect of periodontitis (Hajishengallis & Chavakis, 2021). Furthermore, evidence from interventional data suggests that the treatment of periodontitis may have an impact on systemic health outcomes (D'Aiuto et al., 2013; Hajishengallis & Chavakis, 2021; Simpson et al., 2015).
Available evidence
Number and design of included studies Three randomized controlled trials (Fu et al., 2016; Tonetti et al., 2007; Zhou et al., 2017) provided data on the effect of the treatment of peri- odontitis in comparison with no/control treatment on systemic health in systemically healthy participants with periodontitis. Systemic outcomes reported in these trials included high sensitivity C-reactive protein (hs- CRP), fasting plasma glucose, TNF-alpha, interleukin 6 (IL-6), total cho- lesterol (TC), high density lipoprotein (HDL) cholesterol, low density lipo- protein (LDL) cholesterol, triglycerides (TG), flow-mediated dilatation (FMD), systolic blood pressure (SBP), diastolic blood pressure (DBP) and body mass index (BMI), at 6 months follow-up. Meta-analyses were per- formed by systemic outcome for hs-CRP, IL-6, TC, HDL cholesterol, LDL cholesterol, TG, SBP, and DBP, at 6 months. Risk of bias The three trials included in the analysis were considered at low risk of bias according to the RoB 2.0 tool. Effect sizes and their clinical relevance Although reductions in systemic biomarkers of inflammation and meta- bolic control were reported, no statistically significant systemic effect of periodontal therapy was observed after 6-months of follow-up. Consistency Meta-analysis of three studies showed a reduction in eight biomarkers (hs- CRP, IL-6, TC, HDL, LDL, TG, SBP and DBP) with high levels of heterogene- ity in six meta-analyses and wide confidence intervals.
12.1.1 | Impact of periodontal treatment on systemic inflammation and cardio-metabolic risk in people with no reported systemic co-morbidity (presumed systemically healthy)
R12.1. Does periodontal treatment have an impact on systemic inflammation and cardio-metabolic risk in people with no reported systemic co-morbidity (presumed systemically healthy)?
PICOS question addressed by a SR
R12.1: Evidence-based statement Treatment of periodontitis may improve levels of biomarkers of systemic inflammation and cardio-metabolic risk in people with no reported systemic co-morbidity . Supporting literature (Orlandi et al., 2021) Quality of evidence Low — Three RCTs at low risk of bias Grade of recommendation GradeO — $ Statement: unclear, additional research needed Strength of consensus Strong consensus (2.1% of the group abstained due to potential CoI)
Balance of benefit and harm No evidence of harm was reported in any of the clinical trials.
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