190 - Caffeine for Apnoea and the Prevention of Neurodevelopmental Impairment in Preterm Infants: A Systematic Review and Meta-analysis

Caffeine is widely used to treat or prevent apnoea of prematurity and improve neurodevelopment, but effectiveness and optimal dose are unclear.

Objective:

To assess the effectiveness of caffeine in reducing the rate or occurrence of apnoea and reducing long‐term neurodevelopmental impairment in preterm infants (< 37 weeks’ post-menstrual age), and determine if there is any difference in these outcomes between caffeine given at standard doses (≤10 mg/kg caffeine citrate equivalent) and high doses ( >10 mg/kg caffeine citrate equivalent).

Design/Methods:

Systematic review and meta-analysis including randomised controlled trials of preterm infants randomised to caffeine or placebo/no treatment; or preterm infants randomised to low (≤10 mg/kg) or high ( >10 mg/kg) dose caffeine citrate. We searched MEDLINE, EMBASE, CINHAL Plus, and CENTRAL from inception to July 2022.  We studied four epochs: infant (birth-1 year); early childhood (1-5 years); middle childhood (6-11 years) and adolescence (12-19 years) with latest available data in each epoch used. Primary outcome was apnoea (infants) and neurocognitive impairment (other epochs).

Results:

2,968 abstracts were screened, 160 papers reviewed and 15 studies included. Caffeine reduced apnoea compared to placebo/no treatment (Risk Ratio(RR)(95%CI), 0.59(0.46-0.75)) with significant heterogeneity (I²=78%) and high risk of bias. High-dose caffeine may be more effective at reducing apnoea than low-dose caffeine (mean difference 0.22 (0.17-0.27)), although the numbers were small and trials show significant heterogeneity (I²=87%). Only one trial reported long-term outcomes with no effect on neurocognitive impairment in early childhood (RR 0.98(0.63-1.51)) but a trend towards benefit in middle childhood (RR 0.84(0.71-1.01)). Caffeine reduced cerebral palsy (RR 0.60 (0.41-0.88) in early childhood and motor impairment (RR 0.72 (0.57-0.91) in middle childhood. Caffeine reduced bronchopulmonary dysplasia (BPD)(RR 0.70(0.69-0.86), I²=31%), with high doses more effective than lower doses (RR 0.71(0.55-0.91), I²=0%). Data were insufficient to determine the effect of dose on apnoea or neurocognition. High-dose caffeine increased tachycardia compared to lower doses (RR 2.29(1.41-3.72), I²=0%).

Conclusion(s):

Caffeine administered to preterm infants may reduce apnoea, BPD, neurocognitive impairment and motor problems, but evidence is uncertain. Establishing the optimal dose requires more research, including a focus on long-term outcome assessment.