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SAN FRANCISCO (FRONTLINE MEDICAL NEWS) – The 11-year follow-up results of the Caffeine for Apnea of Prematurity randomized, placebo-controlled trial has established the benefits of methylated xanthine therapy in the form of caffeine for very-low-birth-weight (VLBW) neonates in lessening the risk of motor impairment.
“The latest findings bolster the value of caffeine therapy to address apnea of prematurity in VLBW neonates. The CAP trial has provided compelling evidence for the use of caffeine even before this latest finding of improved motor function at age 11 years,” said presenter and the CAP trial’s principal investigator Barbara Schmidt, MD, of McMaster University, Hamilton, Ont.
“This latest follow-up of CAP trial participants adds one more long-lasting benefit and confirms that there are no apparent risks of this therapy as it was used in our trial,” she said at the Pediatric Academic Societies meeting.
At least 5 of every 1,000 live-born babies are very premature with a VLBW. Up of 40% die or survive with lasting disabilities. One cause of mortality or disability is apnea. Apnea can be lessened by treatment with methylxanthines such as caffeine, she noted. However, at the time the CAP trial began, it was unclear whether the therapy posed a danger by worsening the damage caused by lack of oxygen.
“Very few studies have followed more recent cohorts of very preterm infants to middle school age. Therefore, it was difficult to anticipate actual rates of functional impairment, and the possible effect of caffeine on those rates,” said Dr. Schmidt.
As reported about a decade ago, the CAP trial involving VLBW infants randomized to caffeine therapy or placebo established the short-term safety and effectiveness of the therapy in terms of reducing cerebral palsy and cognitive delay ( N Engl J Med. 2007;357:1893-902 ).
Follow-ups at 18 months and 5 years revealed the benefits of caffeine therapy in reducing the rates of bronchopulmonary dysplasia, severe retinopathy, and neurodevelopmental disability. The present follow-up data assessed academic performance, motor function, and behavior in 1,202 children with a median age of 11 years. Of these, 602 had received caffeine therapy and 600 had been randomized to the placebo group. Data at age 11 years was available for 457 and 463 of the children randomized to caffeine therapy or placebo, respectively.
The primary outcome was functional impairment, which was indicated by at least one of poor academic performance (with at least one standard score more than two standard deviations below the mean on the Wide Range Achievement Test, 4th edition), motor impairment (percentile rank of 5 or less on the Movement Assessment Battery for Children, Second Edition), and behavior problems (Total Problem T score more than two standard deviations above the mean on the Child Behavior Checklist).
Functional impairment was evident in 145 the 457 (32%) children who had received caffeine therapy and 174 of the 463 (38%) who had not. The rates of 32% and 38% were statistically similar (P = .07). In the individual functional outcomes, the caffeine and placebo groups also were similar in terms of poor academic performance (14% vs. 13%; P = .58) and behavior (11% vs. 8%, respectively; P = .22).
However, caffeine therapy was associated with a reduced risk of motor impairment at age 11 years, compared with those in the placebo group (20% vs. 28%, respectively; odds ratio [OR], 0.66; 95% confidence interval [CI], 0.48-0.90; P = .009). The number of children needed to treat to lessen motor impairment in one child was 13 (95% CI, 8-42).
“Caffeine therapy for apnea of prematurity did not significantly reduce the combined rate of academic, motor, and behavioral impairments at age 11 years. However, caffeine therapy reduced the risk of motor impairment 11 years later,” said Dr. Schmidt. Whether caffeine therapy using higher doses or longer treatment duration is equally risk free is uncertain and further studies, which are not planned, would be needed, she said.
These 11-year follow-up findings of the CAP trial were published online in JAMA Pediatrics ( 2017, Apr 24. doi: 10.1001/jamapediatrics.2017.0238 ).
The sponsor of study was McMaster University. The study was funded by the Canadian Institutes of Health Research and the National Health and Medical Research Council of Australia. Dr. Schmidt had no relevant financial disclosures to report.
