Pain-Relieving Interventions for Retinopathy of Prematurity: A Meta-analysis

CONTEXT:Retinopathy of prematurity eye examinations conducted in the neonatal intensive care. OBJECTIVE: To combine randomized trials of pain-relieving interventions for retinopathy of prematurity examinations using network meta-analysis. DATA SOURCES: Systematic review and network meta-analysis of Medline, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and the World Health Organization International Clinical Trials Registry Platform. All databases were searched from inception to February 2017. STUDY SELECTION: Abstract and title screen and full-text screening were conducted independently by 2 reviewers. DATA EXTRACTION: Data were extracted by 2 reviewers and pooled with random effect models if the number of trials within a comparison was sufficient. The primary outcome was pain during the examination period; secondary outcomes were pain after the examination, physiologic response, and adverse events. RESULTS: Twenty-nine studies (N = 1487) were included. Topical anesthetic (TA) combined with sweet taste and an adjunct intervention (eg, nonnutritive sucking) had the highest probability of being the optimal treatment (mean difference [95% credible interval] versus TA alone = -3.67 [-5.86 to -1.47]; surface under the cumulative ranking curve = 0.86). Secondary outcomes were sparsely reported (2-4 studies, N = 90-248) but supported sweet-tasting solutions with or without adjunct interventions as optimal. LIMITATIONS: Limitations included moderate heterogeneity in pain assessment reactivity phase and severe heterogeneity in the regulation phase. CONCLUSIONS: Multisensory interventions including sweet taste is likely the optimal treatment for reducing pain resulting from eye examinations in preterm infants. No interventions were effective in absolute terms.