Caffeine for apnea of prematurity found safe, effective at 11 years

 

Caffeine for apnea of prematurity was neurobehaviorally safe and significantly improved fine motor coordination, visuomotor integration, visual perception, and visuospatial organization at 11-year follow-up, according to the results of a double-blind, randomized, controlled trial.

“There was little evidence for differences between the caffeine and placebo groups on tests of general intelligence, attention, executive function, and behavior. This highlights the long-term safety and efficacy of caffeine therapy for apnea of prematurity in very-low-birth-weight neonates,” wrote Ines M. Mürner-Lavanchy, PhD, of Monash University, Clayton, Australia, and her associates. The Caffeine for Apnea of Prematurity (CAP) trial, the first to assess long-term neurobehavioral outcomes of neonatal caffeine therapy, was published online April 11 in Pediatrics.

Herjua/Thinkstock

Apnea of prematurity affects more than half of preterm neonates. Respiratory stimulation with caffeine therapy is standard care, having been shown to improve disability-free survival and gross motor skills. In this randomized, multicenter, double-blind trial, very-low-birth-weight infants (500-1,250 g) received either normal saline placebo or caffeine citrate (20 mg/kg loading dose, followed by 5 mg/kg daily maintenance dose; could be increased to up to 10 mg/kg for refractory apnea). Patients started treatment at a median of 3 days and were weaned off by postmenstrual age 35 weeks.

Neonatal caffeine therapy significantly lowered the risk of death before 18 months, cerebral palsy, cognitive delay, severe hearing loss, and bilateral blindness, as has been reported (N Engl J Med. 2007;357:1893-902). By 5 years, caffeine no longer showed significant benefits, apart from improved motor performance, Dr. Mürner-Lavanchy and her associates noted.

 

At 11 years, available data from 870 patients showed generally similar neurobehavioral outcomes between groups, although the caffeine group scored higher on most scales. The most apparent benefits included visuomotor integration (mean difference from placebo, 1.8; 95% confidence interval, 0.0-3.7; P less than .05), visual perception (2.0; 95% CI, 0.3-3.8; P = .02), fine motor coordination (2.9; 95% CI, 0.7-5.1; P = .01), and Rey Complex Figure copy accuracy, a measure of visuospatial organization (1.2; 95% CI, 0.4-2.0; P = .003).

Eleven-year follow-up data were missing for 22% of patients, but their birth characteristics and childhood outcomes resembled those of patients with available data, the investigators said. “Therefore, we are confident that the outcomes of the whole cohort are reflected in the present results with sufficient accuracy.”

The Canadian Institutes of Health Research provided funding. The investigators reported having no relevant conflicts of interest.

SOURCE: Mürner-Lavanchy IM et al. Pediatrics. 2018 Apr 11. doi: 10.1542/peds.2017-4047.

 

Caffeine for apnea of prematurity was neurobehaviorally safe and significantly improved fine motor coordination, visuomotor integration, visual perception, and visuospatial organization at 11-year follow-up, according to the results of a double-blind, randomized, controlled trial.

“There was little evidence for differences between the caffeine and placebo groups on tests of general intelligence, attention, executive function, and behavior. This highlights the long-term safety and efficacy of caffeine therapy for apnea of prematurity in very-low-birth-weight neonates,” wrote Ines M. Mürner-Lavanchy, PhD, of Monash University, Clayton, Australia, and her associates. The Caffeine for Apnea of Prematurity (CAP) trial, the first to assess long-term neurobehavioral outcomes of neonatal caffeine therapy, was published online April 11 in Pediatrics.

Herjua/Thinkstock

Apnea of prematurity affects more than half of preterm neonates. Respiratory stimulation with caffeine therapy is standard care, having been shown to improve disability-free survival and gross motor skills. In this randomized, multicenter, double-blind trial, very-low-birth-weight infants (500-1,250 g) received either normal saline placebo or caffeine citrate (20 mg/kg loading dose, followed by 5 mg/kg daily maintenance dose; could be increased to up to 10 mg/kg for refractory apnea). Patients started treatment at a median of 3 days and were weaned off by postmenstrual age 35 weeks.

Neonatal caffeine therapy significantly lowered the risk of death before 18 months, cerebral palsy, cognitive delay, severe hearing loss, and bilateral blindness, as has been reported (N Engl J Med. 2007;357:1893-902). By 5 years, caffeine no longer showed significant benefits, apart from improved motor performance, Dr. Mürner-Lavanchy and her associates noted.

 

At 11 years, available data from 870 patients showed generally similar neurobehavioral outcomes between groups, although the caffeine group scored higher on most scales. The most apparent benefits included visuomotor integration (mean difference from placebo, 1.8; 95% confidence interval, 0.0-3.7; P less than .05), visual perception (2.0; 95% CI, 0.3-3.8; P = .02), fine motor coordination (2.9; 95% CI, 0.7-5.1; P = .01), and Rey Complex Figure copy accuracy, a measure of visuospatial organization (1.2; 95% CI, 0.4-2.0; P = .003).

Eleven-year follow-up data were missing for 22% of patients, but their birth characteristics and childhood outcomes resembled those of patients with available data, the investigators said. “Therefore, we are confident that the outcomes of the whole cohort are reflected in the present results with sufficient accuracy.”

The Canadian Institutes of Health Research provided funding. The investigators reported having no relevant conflicts of interest.

SOURCE: Mürner-Lavanchy IM et al. Pediatrics. 2018 Apr 11. doi: 10.1542/peds.2017-4047.

 

Caffeine for apnea of prematurity was neurobehaviorally safe and significantly improved fine motor coordination, visuomotor integration, visual perception, and visuospatial organization at 11-year follow-up, according to the results of a double-blind, randomized, controlled trial.

“There was little evidence for differences between the caffeine and placebo groups on tests of general intelligence, attention, executive function, and behavior. This highlights the long-term safety and efficacy of caffeine therapy for apnea of prematurity in very-low-birth-weight neonates,” wrote Ines M. Mürner-Lavanchy, PhD, of Monash University, Clayton, Australia, and her associates. The Caffeine for Apnea of Prematurity (CAP) trial, the first to assess long-term neurobehavioral outcomes of neonatal caffeine therapy, was published online April 11 in Pediatrics.

Herjua/Thinkstock

Apnea of prematurity affects more than half of preterm neonates. Respiratory stimulation with caffeine therapy is standard care, having been shown to improve disability-free survival and gross motor skills. In this randomized, multicenter, double-blind trial, very-low-birth-weight infants (500-1,250 g) received either normal saline placebo or caffeine citrate (20 mg/kg loading dose, followed by 5 mg/kg daily maintenance dose; could be increased to up to 10 mg/kg for refractory apnea). Patients started treatment at a median of 3 days and were weaned off by postmenstrual age 35 weeks.

Neonatal caffeine therapy significantly lowered the risk of death before 18 months, cerebral palsy, cognitive delay, severe hearing loss, and bilateral blindness, as has been reported (N Engl J Med. 2007;357:1893-902). By 5 years, caffeine no longer showed significant benefits, apart from improved motor performance, Dr. Mürner-Lavanchy and her associates noted.

 

At 11 years, available data from 870 patients showed generally similar neurobehavioral outcomes between groups, although the caffeine group scored higher on most scales. The most apparent benefits included visuomotor integration (mean difference from placebo, 1.8; 95% confidence interval, 0.0-3.7; P less than .05), visual perception (2.0; 95% CI, 0.3-3.8; P = .02), fine motor coordination (2.9; 95% CI, 0.7-5.1; P = .01), and Rey Complex Figure copy accuracy, a measure of visuospatial organization (1.2; 95% CI, 0.4-2.0; P = .003).

Eleven-year follow-up data were missing for 22% of patients, but their birth characteristics and childhood outcomes resembled those of patients with available data, the investigators said. “Therefore, we are confident that the outcomes of the whole cohort are reflected in the present results with sufficient accuracy.”

The Canadian Institutes of Health Research provided funding. The investigators reported having no relevant conflicts of interest.

SOURCE: Mürner-Lavanchy IM et al. Pediatrics. 2018 Apr 11. doi: 10.1542/peds.2017-4047.