Association of maternal blood high-mobility group box 1 levels and adverse pregnancy outcomes: A systematic review and meta-analysis

Conflicting findings have emerged regarding the levels of high mobility group box 1 (HMGB1) in individuals experiencing adverse pregnancy outcomes. Here we conducted a meta-analysis to assess the association between maternal blood HMGB1 levels and adverse pregnancy outcomes. Utilizing databases such as PubMed, Cochrane Central Register of Controlled Trials, Web of Science, Embase and China National Knowledge Infrastructure (CNKI), a systematic literature search was conducted in January 2024. Eligible literature was screened according to inclusion and exclusion criteria. Quality assessment was evaluated using the Newcastle-Ottawa Scale (NOS). The extracted data were analyzed using Review Manager 5.4 and STATA 12.0 software. 21 observational studies with a total of 2471 participants were included in this meta-analysis. Significantly higher peripheral blood levels of HMGB1 were associated with preeclampsia (PE) (SMD=1.34; 95% CI: 0.72-1.95; P < 0.0001) and gestational diabetes mellitus (GDM) (SMD=1.20; 95% CI: 0.31-2.09; P = 0.009). Additionally, HMGB1 levels in peripheral blood were significantly elevated in patients with unexplained recurrent spontaneous abortion (URSA) than those in pregnancy controls (SMD=4.22; 95% CI: 1.64-6.80; P = 0.001) or non-pregnancy controls (SMD=3.87; 95% CI: 1.81-5.92; P = 0.0002). Interestingly, higher blood HMGB1 levels were observed in women with preterm birth (PTB), however, the results did not reach a statistical difference (SMD=0.54; 95% CI: -0.36-1.44; P = 0.24). In conclusion, overexpressed maternal blood HMGB1 levels were associated with adverse pregnancy outcomes, including PE, GDM and URSA. Further studies should be conducted to validate the efficacy of HMGB1 as a biomarker for assessing the risk of adverse pregnancy outcomes.