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Randomized, controlled trial of oral creatine supplementation (not effective) for apnea of prematurity
Bettina Bohnhorst1, Tiana Geuting, Corinna S Peter
1Department of Neonatology and Pediatric Pulmonology, Hannover Medical School, Hannover, Germany.
Insights
Creatine supplementation (CS) did not reduce episodes of hypoxemia and bradycardia in premature infants with apnea of prematurity (AOP). This study found no significant improvement in AOP symptoms despite increased creatine levels.
Area of Science:
- Neonatal Medicine
- Nutritional Science
- Physiology
Background:
- Creatine supplementation (CS) is known to improve hypoxic ventilatory depression in mice and muscle fatigue in humans.
- Apnea of prematurity (AOP) involves hypoxemia and bradycardia, potentially linked to similar physiological mechanisms.
- This study investigated CS as a potential therapeutic intervention for AOP.
Purpose of the Study:
- To determine if creatine supplementation (CS) can reduce episodes of hypoxemia and bradycardia in premature infants diagnosed with apnea of prematurity (AOP).
- To assess the safety and efficacy of oral CS in infants with severe AOP requiring caffeine treatment.
Main Methods:
- A double-blind, controlled trial was conducted with infants born before 32 weeks gestational age experiencing severe AOP.
- Participants received either oral CS (200 mg/kg/day) or placebo for two weeks.
- Infants underwent physiological monitoring for desaturation, bradycardia, and apnea before and during treatment.
Main Results:
- Oral CS was well-tolerated with no reported side effects.
- Urinary creatine excretion significantly increased in the CS group, indicating good enteral absorption.
- CS did not significantly alter the combined rate of bradycardia and desaturation or the frequency of apnea in infants with AOP.
Conclusions:
- Despite demonstrated enteral absorption, creatine supplementation at the tested dose and duration did not improve the clinical symptoms of apnea of prematurity.
- Further research may be needed to explore different dosages or durations of CS for AOP management.
Background:
Hypoxic ventilatory depression in mice and muscle fatigue in adult humans are improved by creatine supplementation (CS). Because these issues may be operative in apnea of prematurity (AOP), we hypothesized that CS reduces episodes of hypoxemia and bradycardia in infants with AOP.
Methods:
Infants were eligible for this double-blind, controlled trial if gestational age was <32 weeks and AOP was severe enough to require treatment with caffeine. If they had > or = 1 desaturation (pulse oximeter saturation [SpO2] < or = 80%) or bradycardia (heart rate < or = two thirds of baseline) per hour in an initial 6-hour recording, they were randomized to a 2-week course of oral CS (200 mg/kg per day) or placebo (P). Infants then underwent 2 additional 6-hour recordings of breathing movements, nasal airflow, heart rate, pulse oximeter saturation (SpO2) and pulse waveforms after 7 and 14 days of treatment. Urinary creatine excretion was measured also. Recordings were analyzed for the frequency of bradycardia and desaturation, the primary outcome parameter, as well as for apnea (> or =10 seconds), baseline heart and respiratory rate, and SpO2.
Results:
Of 38 infants enrolled, 34 completed the study (17 in each group). Median (range) gestational age at birth was 27 (25-30) vs 27 (25-30) weeks, and at study 29 (26-36) vs 29 (27-33) weeks. Oral CS was well tolerated; no side effects were noted. Urinary creatine excretion was low in the P group (median: 27 mmol/mol of creatinine; range: 18-102) and increased in the CS group (6949 mmol/mol of creatinine; range: 1427-11807). CS, however, had no effect on the combined rate of bradycardia and desaturation (P: 2.7 per hour [range: 0.2-10.3]; CS: 4.1 per hour [range: 0.6-12.1]), nor was there any decrease in apnea rate (P: 1.7 per hour [range: 0-4.5]; CS: 2.2 per hour [range: 0.2-5.1]).
Conclusion:
Despite a significant increase in creatine excretion, suggesting good enteral absorption, CS did not, in the dose and for the duration given in this study, improve symptoms of AOP in these infants.
