Abstract
BACKGROUND: Premature infants are prone to having adverse neurodevelopmental outcomes such as cerebral palsy. Some neuroprotective drugs can improve adverse neurological outcomes in premature infants. A network meta-analysis was conducted to compare the effects of four common neuroprotective drugs on neurodevelopmental outcomes in preterm infants. METHODS: To identify eligible randomized clinical trials, three databases (Cochrane Library, PubMed, and EMBASE) were searched from the inception date through March 2024. Neuroprotective drugs included erythropoietin, magnesium sulfate, caffeine, and thyroxine. The primary outcome was whether neurodevelopmental impairment (NDI) or death occurred. Studies that met the eligibility criteria were assessed, and data were extracted. The surface under the cumulative ranking curve (SUCRA) was computed to evaluate and rank the neuroprotective efficacy of various drugs. RESULTS: Caffeine [relative risk (RR) 0.43, 95% confidence interval (CI): 0.22-0.86] showed the most promising effect in reducing the risk of premature infants with NDI. Caffeine (RR 0.55, 95% CI: 0.43-0.70) and magnesium sulfate (RR 0.66, 95% CI: 0.54-0.80) showed promising effects in reducing the risk of premature infants with cerebral palsy. According to the SUCRA value, caffeine (NDI: 87.9%, cerebral palsy: 91.2%) may be the best drug for neurodevelopmental protection in preterm infants. CONCLUSIONS: The neuroprotective effects of caffeine were observed in the reduction of NDI and cerebral palsy, whereas magnesium sulfate, given to pregnant women at risk of preterm birth, had a protective effect in reducing the risk of cerebral palsy. The analysis of the SUCRA value indicated that caffeine may offer greater benefits compared to other medications in the neuroprotection of premature infants. The findings of this network meta-analysis ought to be regarded as theoretical rather than validated. Additional trials are necessary to validate the existing findings.