The Comparative Efficacy and Safety of Sweet Solutions to Reduce Preterm Infants’ Pain Level: A Systematic Review and Network Meta-analysis

Abstract

Background: The efficacy of sweet solutions in alleviating pain for preterm infants has been extensively investigated, yet the most efficacious sweet solutions remain unknown. Methods: We conducted a search in the CINAHL, MEDLINE, EMBASE, CENTRAL, Scopus, and ProQuest databases for studies. Randomized controlledtrials (RCTs) utilizing glucose, sucrose, or expressed breast milk for managing pain in preterm infants were included in this study. A random-effects frequentist network meta-analysis was conducted to evaluate outcomes in three pain measurement time points. The primary outcome was the pain level in the reactivity phase. The secondary outcomes were pain in the regulation and recovery phases, as well as heart rate, oxygen saturation, respiratory rate, crying time, and adverse events. P-scores and beading plot were utilized to rank the efficacy of the sweet solutions. Results: Of 10,043 references, 42 RCTs (2,733 newborns) were analyzed. Compared to the controls alone, glucose (standardized mean difference [SMD], -0.72; 95% confidence interval [CI], -1.19 to -0.25]) and sucrose (SMD, -0.56; 95% CI, -1.04 to -0.07]) were associated with lower pain responses in reaction phase. In the regulation and recovery phases, pain reduction was consistently linked to glucose, sucrose, and expressed breast milk. Those interventions were supported by results of P-scores that ranged from 0.877 to 0.917 showing glucose's superiority in the three phases. Glucose was associated with a higher risk of adverse events. Half of the 38 trials had a low risk of bias. Meanwhile, the certainty of the evidence was high to very low. Conclusions: Our findings indicate that glucose was ranked best for lowering pain in preterm infants, followed by sucrose and expressed breast milk. Future RCTs are expected to investigate the efficacy of sweet solutions, both alone and combined with other pain management methods, as well as the effects of repeated applications. Systematic review registration: PROSPERO CRD42023389288.