Early high-dose caffeine citrate for extremely preterm infants: Neonatal and neurodevelopmental outcomes

J Paediatr Child Health. 2019 Dec;55(12):1451-1457. doi: 10.1111/jpc.14446. Epub 2019 Mar 21.

Abstract

Aim: To examine neonatal morbidities, including the incidence of cerebellar haemorrhage (CBH), and neurodevelopmental outcomes following the administration of high loading dose caffeine citrate compared to standard loading dose caffeine citrate.

Methods: This was a retrospective study of 218 preterm infants <28 weeks' gestation who received a loading dose of caffeine citrate within the first 36 h of life at the Mater Mothers' Hospital over a 3-year period (2011-2013). Two groups were compared, with 158 neonates in the high-dose cohort receiving a median dose of caffeine citrate of 80 mg/kg and 60 neonates in the standard dose cohort receiving a median dose of 20 mg/kg. Routine cranial ultrasound, including mastoid views, was performed during the neonatal period. At 2 years of age, infants presented for follow-up and were assessed with the Neurosensory Motor Developmental Assessment (NSMDA) and the Bayley Scales of Infant and Toddler Development-III (Bayley-III).

Results: There was no difference in the incidence of neonatal morbidities, including CBH, between the two groups. The incidence of CBH in the high-dose group was 2.5% compared to 1.7% in the standard-dose group. There was no difference in the neurodevelopmental follow-up scores as evaluated with the NSMDA and the Bayley-III.

Conclusions: The use of early high loading dose caffeine citrate in extremely preterm infants was not shown to be associated with CBH or abnormal long-term neurodevelopmental outcomes. The overall incidence of CBH, however, was much lower than in studies using magnetic resonance imaging techniques. It is suggested that a large randomised clinical trial is needed to determine the optimal dose of caffeine citrate when given early to very preterm infants.

Keywords: caffeine; cerebellar haemorrhage; cranial ultrasound; neurodevelopment; preterm infants.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Caffeine / administration & dosage*
  • Caffeine / adverse effects*
  • Cerebral Hemorrhage / chemically induced
  • Citrates / administration & dosage*
  • Citrates / adverse effects*
  • Databases, Factual
  • Dose-Response Relationship, Drug*
  • Gestational Age
  • Humans
  • Infant, Extremely Premature*
  • Morbidity
  • Outcome Assessment, Health Care
  • Retrospective Studies
  • Risk Assessment

Substances

  • Citrates
  • Caffeine
  • caffeine citrate