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We performed a random-effects frequentist network meta-analysis across three pain time points (reactivity, regulation, recovery). Pain level served as the primary outcome, while heart rate, oxygen saturation, respiratory rate, crying time, and adverse events were designated as secondary outcomes. Treatment efficacy was subsequently ranked using P-scores and a beading plot.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We screened 10,043 records, included 42 RCTs (2733 infants), and analyzed 38 RCTs (2367 infants) in the network meta-analysis. Compared to the controls alone, glucose (standardized mean difference [\n                      <jats:italic>SMD<\/jats:italic>\n                      ], \u22120.72; 95% confidence interval [\n                      <jats:italic>CI<\/jats:italic>\n                      ], \u22121.19 to \u22120.25) and sucrose (\n                      <jats:italic>SMD<\/jats:italic>\n                      , \u22120.56; 95%\n                      <jats:italic>CI<\/jats:italic>\n                      , \u22121.04 to \u22120.07) were associated with lower pain responses in the 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\u2019s superiority in the three phases. Glucose was associated with a higher risk of adverse events. Half of the 38 trials in the network meta-analysis had a low risk of bias. The evidence certainty for the primary outcome was moderate to very low, while the certainty for the secondary outcomes spanned a range from high to very low.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Glucose ranked most effective for reducing procedural pain in preterm infants, followed by sucrose and expressed breast milk. Future trials should evaluate optimal dosing, repeated administration, and combinations with other non-pharmacological pain-management strategies to maximize efficacy and safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>PROSPERO CRD42023389288<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Tweetable abstract<\/jats:title>\n                    <jats:p>Glucose is the most effective sweet solution in alleviating pain scores in preterm infants, followed by sucrose and expressed breast milk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13643-025-03043-3","type":"journal-article","created":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T02:17:29Z","timestamp":1768011449000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["The comparative efficacy and safety of sweet solutions to reduce preterm infants\u2019 pain levels: a systematic review and network meta-analysis"],"prefix":"10.1186","volume":"15","author":[{"given":"Defi","family":"Efendi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-No","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Natalia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariesta","family":"Milanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Putri M. 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