Elevated rates of systemic inflammation among adolescents pervade geography and time: A systematic review and meta-analysis of global mean C-reactive protein levels

IntroductionSystemic chronic inflammation (SCI) is implicated in the aetiology of life-limiting diseases in later life, such as cancer, T2 diabetes and mental health disorders. However, global estimates of adolescent inflammation, indexed by biomarkers such as C-reactive protein (CRP), are unknown. We conducted the first study to establish the overall level of CRP in the general population of adolescents worldwide, determine trends in average CRP from 2011 to 2021 and identify subgroups with heightened levels of inflammation.MethodsA systematic review and meta-analysis was conducted using Ovid MEDLINE, Embase (Elsevier), Cochrane Library (Wiley), and PsychINFO (EBS-COhost) databases. We included observational studies published between 2011-2021 with CRP data from adolescents in the general population. CRP concentrations were assessed by a random effects meta-analysis of log-transformed mean CRP levels. PROSPERO:CRD42021276398.ResultsNinety-one studies (N=37,347) were included in the meta-analysis. The pooled mean CRP was 1.69mg/L (95%CI 1.43;1.98), with an I2 of 99.8% between studies, indicating globally elevated levels of inflammation (≥1mg/L CRP) among adolescents. Importantly, we found consistently elevated inflammation among adolescents over the past 10 years. There was a significant mean difference (P<.001) between overweight/obese (2.63mg/L, 95%CI 1.42-1.98) and healthy-weight adolescents (0.79mg/L, 95%CI 0.47-1.32) and between predominantly-male studies (2.59mg/L, 95%CI 2.03-3.29) and predominantly-female studies (1.49mg/L, 95%CI 2.03-3.29, P=.002). Nearly all studies had low-moderate risk of bias.ConclusionRates of inflammation are raised among adolescents, these heightened rates of SCI have existed for a least a decade, rendering this a major public health issue. We identify sub-groups with a heightened risk of raised inflammatory biomarkers, such as those who are overweight. Our findings highlight the need for tailored prevention programs and enhanced monitoring among adolescents at higher risk. By providing the first global reference level of mean CRP for adolescents our findings significantly advance our understanding of adolescent biological health, providing the impetus for future research.