Impact of caffeine on neurodevelopmental outcomes in preterm infants: A systematic review and meta-analysis

Although caffeine is among the commonly used medications in preterm infants, its long-term neurodevelopmental effects have remained uncertain. This systematic review and meta-analysis examined the potential long-term impacts of caffeine administration on the neurodevelopmental outcomes of preterm infants. A comprehensive search was conducted across PubMed, EMBASE, Google Scholar, Web of Science (ISI), Scopus, and the Cochrane Library. Eligible studies included randomized clinical trials or longitudinal studies in which the effects of caffeine administration on neurodevelopmental outcomes were compared to those of placebo or a control group. Neurodevelopmental outcomes, specifically motor, language, cognition, and cerebral palsy, were extracted from the eligible studies and pooled using STATA16 with a random-effects model. Egger's regression test was applied to ascertain the potential for publication bias. Among nine studies comprising 7,041assessments, caffeine indicated a significant positive effect on motor development (WMD = 0.68, 95% CI: 0.27 to 1.09, P < 0.001, I² = 0.00%) and cognitive outcomes (WMD = 2.85, 95% CI: 1.63 to 4.08, P < 0.001, I² = 0.00%). Nevertheless, no significant impact was found on language development (WMD = 0.95, 95% CI: 0.37 to 2.27, P = 0.16, I² = 0.00%). Further, the odds of cerebral palsy diminished by 35% by the use of caffeine (OR = 0.65, 95% CI: 0.53 to 0.79, P < 0.001, I² = 0.00%). No publication bias was detected in any of the quantitative analyses. Both standard and high caffeine doses improved cognitive development but had no influence on language development. In conclusion, caffeine may have beneficial effects on neurodevelopment, particularly motor and cognitive development and may also lower the risk of cerebral palsy.