Table 1 Main characteristics of the eligible studies
Ref | Study design and main aim | Comparison | Population | Caffeine exposure regimen | Sleep results related to caffeine exposure |
|---|---|---|---|---|---|
[21] | This randomised clinical trial evaluated whether neonatal caffeine use resulted in long-term abnormalities in sleep architecture and breathing during sleep | Caffeine versus placebo | Children aged 5–12 years | 20 mg kg−1 loading dose of caffeine citrate followed by a daily maintenance dose of 5 mg kg−1 during the first 10 days of life | Actigraphy: no difference between groups Polysomnography: total sleep time was longer in the caffeine group compared with the placebo group, but there was no difference in sleep efficiency or sleep architecture between the groups Questionaries: no significant difference between the groups, but caregivers in the caffeine group thought that their child needed more sleep than control caregivers (p = 0.007) No long-term effects of neonatal caffeine therapy on objective and subjective measures of sleep at school age |
[22] | This study evaluated data from a large randomised clinical trial with preterm infants to evaluate the validity of commonly used actigraphy compared with polysomnography | Caffeine and placebo groups pooled | Children aged 5–12 years | 20 mg kg−1 loading dose of caffeine citrate followed by a daily maintenance dose of 5 mg kg−1 during the first 10 days of life | Actigraphy: no indication of a caffeine effect Polysomnography: no indication of a caffeine effect |
[23] | This study examined data from a randomised clinical trial to compare sleep–wake patterns in children who were born preterm in Australia and Canada and determined cultural differences in the relationship between parental perception of sleep and actual sleep behaviours | Caffeine and placebo groups pooled | Children aged 5–12 years | 20 mg kg−1 loading dose of caffeine citrate followed by a daily maintenance dose of 5 mg kg−1 during the first 10 days of life | Actigraphy: no indication of a caffeine effect Sleep diaries: no indication of a caffeine effect |
[24] | This study examined data from a randomised clinical trial to determine whether children who were born preterm would have a high prevalence of restless legs syndrome and periodic limb movement disorder | Caffeine and placebo groups pooled | Children aged 5–12 years | 20 mg kg−1 loading dose of caffeine citrate followed by a daily maintenance dose of 5 mg kg−1 during the first 10 days of life | Polysomnography: preterm births had a high prevalence of restless legs syndrome between the ages of 5 and 12 years Caffeine use does not appear to contribute to this disorder |
[25] | This study examined data from a randomised clinical trial to determine perinatal factors associated with obstructive sleep apnoea syndrome at school age | Caffeine and placebo groups pooled | Children aged 5–12 years | 20 mg kg−1 loading dose of caffeine citrate followed by a daily maintenance dose of 5 mg kg−1 during the first 10 days of life | Polysomnography: no indication of a caffeine effect |
[26] | This study examined data from a longitudinal randomised study to determine risk factors with the potential to affect short-term neurobehavioural and sleep outcomes in preterm infants born | Preterm infants accompanied during caffeine exposure | Infants aged 32–36 weeks of gestational age | No specific data available about the caffeine regimen | Videotape recordings: caffeine was significantly related to less quiet sleep Caffeine use was associated with lower scores for alertness and orientation, motor, irritability, cry quality, popliteal angle and scarf sign and higher per cent time asleep |
[10] | This randomised clinical trial aimed to establish the most effective and best tolerated dose of caffeine citrate for the prevention of intermittent hypoxaemia in late preterm infants | Caffeine versus placebo | Infants aged 38–40 weeks of gestational age | Loading dose (10, 20, 30, or 40 mg kg−1) followed by 5, 10, 15, or 20 mg kg−1/day−1 caffeine citrate | Oximetry and questionnaires: no indication of a caffeine effect |
[27] | This observational study aimed to evaluate sleep organisation in neonates hospitalised in a neonatal intensive care unit | Caffeine versus no caffeine | Infants aged 33.9 ± 0.1a weeks of postmenstrual age | 20 mg kg−1 loading dose of caffeine citrate followed by a daily maintenance dose of 5 mg kg−1 | Polysomnography: sleep variables were similar before and after the caffeine dose (or the time of dose in controls) |
[28] | This observational study investigated the characteristics and effects of sleep stage, supplemental oxygen and caffeine on periodic breathing and apnoea of prematurity in preterm infants | Baseline versus before caffeine | Infants aged 35.7b weeks of gestational age | 20 mg kg−1 loading dose of caffeine citrate followed by a daily maintenance dose of 5 mg kg−1 | Polysomnography: caffeine reduced the median sleep time on periodic breathing by 91% (p < 0.001) The average number of desaturations per hour with caffeine decreased from 38 to 24 |
[29] | This observational study investigated short-term effects of caffeine on sleep in late preterm infants using polysomnography | Baseline versus before caffeine | Infants aged 35.7b weeks of gestational age | 20 mg kg−1 loading dose of caffeine citrate followed by a daily maintenance dose of 5 mg kg−1 | Polysomnography: caffeine reduced the number of apnoeic events (p < 0.0001) A high caffeine loading dose of 20 mg kg−1 did not affect sleep stage distribution, sleep efficiency, frequency of sleep stage transitions, rapid eye movement sleep, or the number of spontaneous awakenings |
[30] | This observational study determined whether apnoeic preterm infant currently treated with methylxanthines develops evidence of sleep deprivation from cumulative arousal and motor activational effects | Caffeine versus no caffeine | Infants aged 33.2 ± 1.9a weeks of postmenstrual age | Not clear — standard regimens of caffeine based on a blood range of 13.1–29.2 µg ml−1 | Video recordings and actigraphy: caffeine groups exhibited less wakefulness than untreated infants according to per cent wakefulness, the number of brief awakenings, sustained awakenings and lower scores on the composite arousal index Time of exposure to methylxanthine was associated with a linear increase in wakefulness and motor parameters, especially caffeine, promoting sleep fragmentation The results suggest that chronic treatment with methylxanthine appears to produce sleep deprivation secondary to the stimulating action of methylxanthine on the arousal system |
[31] | This observational study aimed to evaluate sleep problems in preterm infants (at 6 months of age) and compare the sleep of preterm infants with that of full-term infants | Mature infants versus preterm infants treated with caffeine | Infants aged 6 months | 20 mg kg−1 loading dose of caffeine citrate followed by a daily maintenance dose of 5 mg kg−1 | Brief Infant Sleep Questionnaire, actigraphy and polysomnography: no indication of a caffeine effect |
[32] | This observational study aimed to identify the components of the neonatal medical history associated with childhood sleep-disordered breathing in children who were born preterm | Children with or without sleep-disordered breathing treated with caffeine | Children aged 8–11 years | No specific data available about the caffeine regimen | Data collection from chart review of data from hospital and cardiorespiratory recording: xanthine was associated with a more than twofold increase in the chance of sleep-disordered breathing, which was slightly attenuated after adjusting for race Xanthine exposure was associated with childhood sleep-disordered breathing in unadjusted analyses, although it is not proof of a causal association between neonatal xanthine exposure and childhood sleep-disordered breathing |
[33] | This observational study investigated how caffeine treatment affects sleep–wake behaviour in preterm neonates | Caffeine versus no caffeine | Infants aged 30.6b weeks of gestational age | Not clear — caffeine concentration simulated by mathematical model | Videographic recordings: wakefulness increased, and active sleep decreased as the caffeine concentration increased, while quiet sleep remained unchanged |
[34] | This observational study examined patterns of behavioural states of preterm newborns before and after nursing interventions | Caffeine versus no caffeine | Infants aged 32.7 ± 1.3a weeks of gestational age | No specific data available about the caffeine regimen | Videographic recordings: significantly more waking hours before the intervention for the newborns in the control group compared with the newborns receiving xanthine (p = 0.046) The frequency of wake bouts for the newborns receiving xanthine increased slightly after nursing interventions The change in wake bouts was significant in the control group, while the before–after difference in wake bouts for the newborns receiving xanthine was not significant (p = 0.076) |
[35] | This observational study assessed the activity of the peripheral chemoreceptors in relation to sleep stages in preterm neonates treated or not treated with caffeine | Caffeine versus no caffeine | Infants aged 36.1 ± 0.8a weeks of post-conceptional age | 4.0 ± 0.5 mg kg−1 day−1 of caffeine | Electroencephalograms, eye movement (transducer), actigraphy, visual observations and hyperoxia test: regarding sleep parameters, there was no effect of caffeine either on total sleep time or on the durations of sleep stages expressed as a percentage of total sleep time |
[36] | This observational study examined the development of respiration during the preterm and early post-term periods and the effects of biological variables of sleep | Preterm infants followed for 1–3 months | Infants up to 43 weeks of post-conceptional age | No specific data available about the caffeine regimen | Sleep visual observation: there was an interaction between postconceptional age and methylxanthine (theophylline or caffeine) treatment for the variability of respiration rate in active sleep |
[37] | This observational study examined the development of sleeping and waking during the preterm and early post-term periods and the effects of infant health and environmental characteristics | Preterm infants followed until hospital discharge or 44-week post-conceptional age | Infants up to 44 weeks of post-conceptional age | No specific data available about the caffeine regimen | Sleep visual observation, electroencephalograms and respiration record: covariates had minor effects on sleep–wake parameters Greater respiration regularity in active sleep occurred during treatment with methylxanthines |
[38] | This observational study investigated the effects of caffeine on respiratory functions and cerebral activity and the long-term effects on the respiratory system and encephalographic maturation of preterm infants | Caffeine versus no caffeine | Infants aged 36 weeks of postmenstrual age | Loading dose of 20 mg kg−1 of caffeine | Electroencephalograms and sleep state stages: caffeine increased the cerebral cortical activity of preterm infants during infusion (amplitude-integrated electroencephalography continuity [p = 0.002] and arousability after 30 min [p = 0.000]) and results in cerebral cortical maturation at 36 weeks |
[39] | This observational study examined possible effects of incubator covers on sleep patterns in stable preterm infants | Preterm infants using covers versus no covers | Infants aged 32–34 weeks of post-conceptional age | No specific data available about caffeine regimen | Electroencephalograms: there were no effects on quiet sleep (duration, intervals, or per cent) for infants treated with theophylline/caffeine |