Risk factors of severe hand, foot and mouth disease: a meta-analysis

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.

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.

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.

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.