According to an investigation published in the January 18 issue of JAMA, caffeine therapy, which has been demonstrated to lower the rate of cognitive delay and cerebral palsy at 18 months, did not considerably improve the rate of survival without disability at 5 years of age among very low birth weight infants with apnea.

In infants born very prematurely with apnea, who are at increased risk of disability with apnea or death, caffeine therapy is the recommended treatment. “However, outcomes up to 2 years after very preterm birth may not accurately predict function later in childhood”, the researchers explain.

In order to find out if the benefits of neonatal caffeine therapy last or if the treatment has newly apparent risks at early school age, Barbara Schmidt, M.D., M.Sc., of McMaster University, Hamilton, Canada, and the University of Pennsylvania, Philadelphia, and colleagues carried out an investigation.

The 5-year follow-up study from 2005 to 2011 consisted of 2,006 participants in 31 of 35 teaching hospitals in Canada, Europe, Israel, and Australia. 96.3% (1,932 participants) had been enrolled in the randomized, placebo-controlled Caffeine for Apnea of Prematurity trial between 1999 and 2004.

A total of 84.9% (1,640 children) born weighing 500 to 1250 g (17.6 to 44.1 ounces) had sufficient data for the primary outcome at 5 years. The researchers defined the primary outcome as the combined survival or death to 5 years, with 1 or more cognitive impairment, behavior problems, deafness, blindness, poor general health or motor impairment. 176 (21.1%) of the 833 children who received caffeine treatment survived or died with at least 1 impairment, in comparison with 200 of the 807 children (24.8%) who received placebo. The researchers explain:

“The rates of motor impairment, cognitive impairment, behavior problems, poor general health, blindness, and deafness were not significantly different between the 2 groups. Only 2 children in each of the 2 groups died between 18 months and 5 years.”

In a secondary examination, the researchers discovered evidence of an improvement in gross motor function connected with caffeine therapy. In both groups, the incidence of cognitive impairment was lower at 5 years than at 18 months (4.9% compared with 5.1%).

According to the researchers concerns have been raised that treating infants with caffeine therapy may cause harm in the long-term. “The absence of any adverse effects in children who were randomly assigned to neonatal caffeine therapy on the incidence of behavior problems or on any other outcomes is reassuring.”

They conclude:

“In summary, this 5-year follow-up study of participant in the international Caffeine for Apnea of Prematurity trial showed that the benefits of neonatal caffeine therapy on the rate of survival without disability at 18 months were attenuated during child development. The rate of cognitive impairment were much lower at 5 years than at 18 months, suggesting that cognitive delay during the second year of life may not be a lasting outcome after very preterm birth.”

In an associated report, Nathalie L. Maitre, M.D., Ph.D., and Ann R, Stark, M.D., of the Vanderbilt University School of Medicine and Monroe Carell Jr. Children’s Hospital, Nashville, Tenn., comments on the findings of this investigation.

“As the Caffeine for Apnea of Prematurity trial demonstrates, long-term follow-up is essential for reaching accurate conclusions about the efficacy of new therapies in preterm infants. This trial also highlights how fortunate preterm patients have been in the routine use of caffeine, a drug previously untested in newborns. All along, neonatologists were using the first safe neuroprotective agent in this vulnerable population.”

Written By Grace Rattue