Effects of caffeine on intermittent hypoxia in infants born prematurely: a randomized clinical trial.
OBJECTIVE
Preterm infants have immature respiratory control and resulting intermittent hypoxia (IH). The extent of IH after stopping routine caffeine treatment and the potential for reducing IH with extended caffeine treatment are unknown.


OBJECTIVE
To determine (1) the frequency of IH in premature infants after discontinuation of routine caffeine treatment and (2) whether extending caffeine treatment to 40 weeks' postmenstrual age (PMA) reduces IH.


METHODS
A prospective randomized clinical study was conducted at 16 neonatal intensive care units in the United States, with an 18-month enrollment period. Preterm infants (<32 weeks' gestation) previously treated with caffeine were randomized to extended caffeine treatment or usual care (controls) at a PMA of at least 34 weeks but less than 37 weeks. Continuous pulse oximeter recordings were obtained through 40 weeks' PMA. Oximeter data were analyzed by persons masked to patient group.


METHODS
Continued treatment with caffeine.


METHODS
Number of IH events and seconds with less than 90% hemoglobin oxygen saturation (Sao2) per hour of recording.


RESULTS
Our analysis included 95 preterm infants. In control infants, the mean (SD) time at less than 90% Sao2 at 35 and 36 weeks' PMA was 106.3 (89.0) and 100.1 (114.6) s/h, respectively. The number of IH events decreased significantly from 35 to 39 weeks' PMA (P = .01). Extended caffeine treatment reduced the mean time at less than 90% Sao2 by 47% (95% CI, -65% to -20%) to 50.9 (48.1) s/h at 35 weeks and by 45% (95% CI, -74% to -17%) to 49.5 (52.1) s/h at 36 weeks.


CONCLUSIONS
Substantial IH persists after discontinuation of routine caffeine treatment and progressively decreases with increasing PMA. Extended caffeine treatment decreases IH in premature infants.


BACKGROUND
clinicaltrials.gov Identifier: NCT01875159.
Newborn Medicine and Respiratory Diseases, Boston Children's Hospital, Boston, Massachusetts.
Lawrence M
LM
Rhein
Department of Pediatrics, Uniformed Services University of Health Sciences, Bethesda, Maryland.
Nicole R
NR
Dobson
Department of Pediatrics, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire.
Robert A
RA
Darnall
Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts5Slone Epidemiology Center at Boston University, Boston, Massachusetts.
Michael J
MJ
Corwin
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
Tim C
TC
Heeren
Department of Neonatology, University of Tübingen, Tübingen, Germany.
Christian F
CF
Poets
American SIDS Institute, Naples, Florida.
Betty L
BL
McEntire
Department of Pediatrics, Uniformed Services University of Health Sciences, Bethesda, Maryland.
Carl E
CE
Hunt
D002110:Caffeine / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D005260:Female; D005865:Gestational Age; D006801:Humans; D000860:Hypoxia / Q000188:drug therapy*; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy*; D008297:Male; D010100:Oxygen / Q000097:blood; D011446:Prospective Studies; D016896:Treatment Outcome; D014481:United States
D000697:Central Nervous System Stimulants; D002110:Caffeine; D010100:Oxygen