Supplementary Material for: Are newer drugs better? An analysis of neonatal pharmacological treatments across generations

Introduction: We evaluated the relative effects of newer versus older medications for neonatal conditions and trends in margin of superiority across generations. Materials and Methods: We assessed network meta-analyses (NMAs) on neonatal pharmacological interventions identified from Medline, Cochrane, and PROSPERO. Interventions were chronologically arranged based on the earliest study and compared for their effects against placebo or no treatment and their immediate predecessor. We assessed the time trend in effect sizes using the Mann-Kendall test. Results: From 8048 retrieved records, 10 neonatal NMAs covering 352 trials and 102,653 participants were included. Compared to placebo, 56/61 (91.8%) interventions showed superiority with 23 (37.7%) statistically significant. Compared to previous generation, 47/72 (65.3%) showed superiority with 3 (4.2%) statistically significant. No significant trends in effect sizes were observed across generations for most conditions (p = 0.09 to 1). Conclusions: We found no evidence that newer-generation medications in neonatal care are consistently more effective than older-generation medications.