Risk Factors of Severe Hand, Foot and Mouth Disease: a Meta-analysis

Background: In recent years, outbreaks of hand, foot and mouth disease (HFMD) have increased, and more and more severe cases have appeared. We conducted a meta-analysis to generate large-scale evidence on the risk factors of severe HFMD.

Methods: PubMed, Elsevier Science Direct, China National Knowledge Infrastructure (CNKI), and Wanfang (Chinese) were searched to identify relevant articles. All analyses were performed using Stata 11.0.

Results: We conducted a meta-analysis of 19 separate studies. Duration of fever ≥ 3 days (odds ratio (OR) 10.09, 95% confidence interval (CI) 6.22-16.35), body temperature ≥ 37.5°C (OR 4.91, 95% CI 1.26-19.18), lethargy (OR 7.75, 95% CI 3.78-15.89), hyperglycemia (OR 2.77, 95% CI 2.06-3.71), vomiting (OR 8.83, 95% CI 1.05-74.57), increased neutrophil count (weighted mean difference (WMD) 0.61, 95% CI 0.52-0.70), enterovirus 71 (EV71) infection (OR 5.13, 95% CI 3.11- 8.46), young age (WMD - 0.44, 95% CI - 0.69 to -0.19), and home care (OR 1.65, 95% CI 1.26-2.17) were significantly related to the risk of severe HFMD. We also found that a confirmed diagnosis at first visit to hospital significantly decreased the risk of severe HFMD (OR 0.30, 95% CI 0.09-0.99). We did not find an association between oral rash (OR 1.07, 95% CI 0.82-1.39), increased leukocyte count (WMD 0.51, 95% CI - 0.05-1.06), male sex (OR 1.06, 95% CI 0.91-1.24), or living in a rural area (OR 1.39, 95% CI 0.95-2.02) and the risk of severe HFMD.

Conclusions: Duration of fever ≥ 3 days, body temperature ≥ 37.5°C, lethargy, hyperglycemia, vomiting, increased neutrophil count, EV71 infection, and young age are risk factors for severe HFMD. A confirmed diagnosis at first visit to hospital can significantly decrease the risk of severe HFMD.