Caffeine citrate for very preterm infants: Effects on development, temperament and behaviour.
OBJECTIVE
To compare two dosing regimens for caffeine citrate for neonates born less than 30 weeks gestation in terms of development, temperament and behaviour.


METHODS
A multi-centre, randomised, controlled trial design was undertaken. A total of 287 infants with apnoea of prematurity or in the peri-extubation period were randomised to receive one of two dosage regimens (20 vs. 5 mg/kg/day). The main outcome measure was cognitive development at 1 year of age on the Griffiths Mental Development Scales. Secondary outcome measures included neonatal morbidity, death and disability, temperament at 1 year and behaviour at 2 years of age.


RESULTS
Data on the primary outcome were available for 190 survivors at 12 months corrected for prematurity. A significantly greater mean general quotient was found in the high-dose group (mean (standard deviation), 98.0 (13.8) vs. 93.6 (16.5), P = 0.048). On omission of two infants for whom cognitive assessment was not possible because of disability while the mean general quotient remained higher for infants in the high-dose group, this was no longer statistically significant (P= 0.075). There was a non-significant trend for benefit in the high-dose caffeine group for death or major disability, 15.4% versus 24.2%; relative risk 0.75 (95% confidence interval 0.49-1.14). No differences in the mean values between the two groups were shown for temperament and behaviour.


CONCLUSIONS
Caffeine citrate with a dosage regimen of 20 mg/kg/day did not result in adverse outcomes for development, temperament and behaviour. The borderline benefit in cognition with high-dose caffeine needs further investigation.
Department of Neonatology and Mater Mothers' Research Centre, Mater Mothers' Hospital, The University of Queensland, Australia. peter.gray@mater.org.au
Peter H
PH
Gray
Vicki J
VJ
Flenady
Bruce G
BG
Charles
Peter A
PA
Steer
D001315:Australia / Q000453:epidemiology; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D002657:Child Development / Q000187:drug effects*; D002951:Citrates / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D018730:Infant Behavior / Q000187:drug effects*; D007226:Infant Mortality / Q000639:trends; D007231:Infant, Newborn; D008297:Male; D047928:Premature Birth; D011795:Surveys and Questionnaires; D013694:Temperament / Q000187:drug effects*
D000697:Central Nervous System Stimulants; D002951:Citrates; D002110:Caffeine; C026189:caffeine citrate