Remarks

• The GDG noted that the evidence on increased mortality came from three small trials totalling 129 infants (177-179) and was uncertain due to very low quality, and imprecision. Also, data on “death alone” were not available from a large trial of 423 infants (169), which reported no effect on a combined outcome of death and neurodevelopmental disability. The GDG also noted that the evidence on harms from increased use of mechanical ventilation was uncertain due to very low quality, and imprecision.
• The recommendation is conditional on shared decision-making with parents; this includes informing parents about the benefits and risks and the need for further research.
• The GDG noted that evidence was available only for preterm infants born before 34 weeks’ gestation, but suggests that caffeine (or other methylxanthines) may also be considered for prevention of apnoea in preterm infants born at or after 34 weeks and before 37 weeks if there is clinical indication.
• The GDG noted that there were limited data on the dose, timing of initiation and duration of administration. Based on the largest trial (169) included in the evidence review, the GDG suggested a 20 mg/kg loading dose and a 5 mg/kg per day maintenance dose for six weeks. The duration of caffeine administration should be based on clinical judgement.
• If caffeine is not available, other methylxanthines (aminophylline or theophylline) may be considered.