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Published on: November 2, 2015
Effects of caffeine on intermittent hypoxia in infants born prematurely: a randomized clinical trial
Lawrence M Rhein1, Nicole R Dobson2, Robert A Darnall3
1Newborn Medicine and Respiratory Diseases, Boston Children's Hospital, Boston, Massachusetts.
Insights
Intermittent hypoxia (IH) is common in preterm infants after routine caffeine stops. Extended caffeine treatment significantly reduces IH events in premature infants up to 40 weeks postmenstrual age.
Area of Science:
- Neonatal Medicine
- Pediatric Pulmonology
- Clinical Research
Background:
- Preterm infants often experience immature respiratory control, leading to intermittent hypoxia (IH).
- The impact of discontinuing routine caffeine treatment on IH and the efficacy of extended treatment remain unclear.
Purpose of the Study:
- To quantify IH frequency in preterm infants post-caffeine discontinuation.
- To evaluate if extending caffeine treatment to 40 weeks postmenstrual age (PMA) mitigates IH.
Main Methods:
- A prospective randomized trial involving preterm infants (<32 weeks gestation) across 16 US NICUs.
- Infants received either extended caffeine or usual care, with continuous pulse oximetry monitoring until 40 weeks PMA.
- Intermittent hypoxia events and time with hemoglobin oxygen saturation <90% were analyzed by masked personnel.
Main Results:
- Analysis included 95 preterm infants.
- Control infants experienced significant IH, with mean time <90% SpO2 at 35 and 36 weeks PMA of 106.3 and 100.1 s/h, respectively.
- Extended caffeine treatment reduced mean time <90% SpO2 by 47% at 35 weeks and 45% at 36 weeks PMA.
Conclusions:
- Persistent and significant intermittent hypoxia occurs after routine caffeine discontinuation in preterm infants.
- IH naturally decreases with increasing postmenstrual age.
- Extended caffeine therapy is effective in reducing intermittent hypoxia in premature infants.
Importance:
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.
Objectives:
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.
Design, Setting, And Participants:
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.
Intervention:
Continued treatment with caffeine.
Main Outcomes And Measures:
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 And Relevance:
Substantial IH persists after discontinuation of routine caffeine treatment and progressively decreases with increasing PMA. Extended caffeine treatment decreases IH in premature infants.
Trial Registration:
clinicaltrials.gov Identifier: NCT01875159.
