Caffeine therapy to treat neonatal apnea not linked to increased survival
MedWire News: Very preterm infants whose apnea is treated with caffeine do not have a significantly improved rate of survival without disability at 5 years of age, researchers say.
This finding extends the results of the Caffeine for Apnea of Prematurity trial, which showed that caffeine therapy improves the rate of survival without neurodevelopmental impairment at 18-24 months of age.
"The rates of cognitive impairment were much lower at 5 years than 18 months, suggesting that cognitive delay during the second year of life may not be a lasting outcome after very preterm birth," report Barbara Schmidt (University of Pennsylvania, Philadelphia, USA) and colleagues in JAMA.
Their analysis included 1640 preterm infants with apnea who were randomly allocated to receive treatment with either caffeine citrate (n=833) or saline placebo (n=807) until drug therapy for apnea of prematurity was no longer needed. All children had a birth weight of 500-1250 g.
The primary outcome of the study was a composite of death before a corrected age of 5 years, or survival with one or more of the following: motor impairment, cognitive impairment, behavior problems, poor general health, severe hearing loss, and bilateral blindness.
The findings revealed that the combined outcome of death or disability did not significantly differ between the children who were assigned to receive caffeine and those assigned to receive placebo.
The rates of death, motor impairment (defined as a Gross Motor Function Classification System [GMFCS level] greater than 2), and behavior problems (Total Problem T score >69 on a range of 28 to 100) did not significantly differ between the two groups.
Poor general health, which was defined as one or more of the following: need for supplemental oxygen, positive airway pressure, feeding through a tube or intravenously, seizures occurring more frequently than once a month, or recent admission to an intensive care unit, was not significantly different between the groups.
Severe hearing loss (prescription of hearing aids/cochlear implants) and bilateral blindness (corrected visual acuity >20/200) did not differ significantly either.
The incidence of cognitive impairment (Full Scale IQ of less than 70 on the Wechsler Preschool and Primary Scale of Intelligence III) was significantly lower at 5 years than at 18 months. Indeed, at a corrected age of 18 months, infants had a mean mental development index score of 90, with a cognitive gain of 10 points at a corrected age of 5 years.
In addition, the lower incidence of cognitive impairment at 5 years than 18 months was significantly similar between the group treated with caffeine and those who received placebo.
"The benefits of neonatal caffeine therapy on the rate of survival without disability at 18 months were attenuated during child development," write the authors.
In a related editorial, Nathalie Maitre and Ann Stark from Vanderbilt University in Nashville, Tennessee, USA, commented: "This trial also highlights how fortunate preterm patients have been in the routine use of caffeine, a drug previously untested in newborns."
They conclude: "All along, neonatologists were using the first safe neuroprotective agent in this vulnerable population."
By Piriya Mahendra