Caffeine Therapy Given Soon After Birth May Prevent Long-term Neurologic Injury to Preterm Babies, Study Finds

Treating premature babies in the first days after birth with caffeine may aid in development of the central nervous system and lessen their likelihood of cerebral palsy, a study from Canada reports.

This research, “Early Caffeine Administration and Neurodevelopmental Outcomes in Preterm Infants,” was published at Pediatrics, the official journal of the American Academy of Pediatrics.

Numerous risk factors are associated with the development of cerebral palsy. Two leading factors, however, are injury during the neonatal period, which spans birth through the first month of life, and preterm or premature birth, defined as birth before 37 weeks of pregnancy.

Preterm infants are at particular risk because of problems that often accompanies prematurity: poorer respiratory function and apnea (interrupted breathing during sleep), marked by when a baby pauses breathing for more than 15 to 20 seconds, or pauses breathing for less than 15 seconds but has a slow heart rate or low oxygen level.

Clinicians at neonatal intensive care units (NICUs) often use caffeine as therapy for these reasons, particularly in treating apnea.

Previous clinical studies report that treatment with caffeine, started between 3 and 10 days of age, can reduce the incidence of bronchopulmonary dysplasia (damage to the lungs caused by mechanical ventilation), shorter the need for mechanical ventilation by one week, and prevent neurodevelopmental disability up until 21 months of age.

These positive results prompted some clinicians to begin therapy sooner after birth than the age span suggested, with researchers reporting that caffeine therapy given quite early (within two days of birth) may improve outcomes. Still, evidence associating early caffeine therapy with better long-term neurodevelopmental outcomes is lacking.

Researchers with the Canadian Neonatal Network (CNN) and the Canadian Neonatal Follow-up Network (CNFUN) explored the long-term potential of caffeine therapy in preterm infants when administrated early after birth.

They reviewed outcomes of 2,108 infants born prematurely (less than 29 weeks of gestation) between April 2009 and September 2011, who admitted and followed for up to two years at one of the 26 participating NICUs. A total of 1,545 infants were treated with caffeine within two days of birth, and 563 treated after their second day of life.

Doses given were not recorded, the study noted, but “the usual practice in most Canadian NICUs is to give a 10 mg/kg loading dose of caffeine base (20 mg/kg of caffeine citrate) with a maintenance dose of 2.5 to 5 mg/kg per day (5–10 mg/kg per day of caffeine citrate) starting 24 hours after the initial loading dose.”

Infants in the early treatment group had a lower risk of developing bronchopulmonary dysplasia and severe neurologic injury, compared to those who were treated later, the researchers found. Early treatment also improved cognitive abilities when these children reached 18 to 24 months.

Caffeine therapy given soon after birth associated with a lesser likelihood of neurodevelopmental impairment, but the difference between the two groups here was not statistically significant.

But the incidence of cerebral palsy was significantly lower in the early caffeine treatment group than in the late caffeine group (3.9% vs. 7.9%, respectively). The timing of the therapy, however, was not found to be associated with the severity of cerebral palsy.

“In this large, multicenter, population-based cohort study we identified that early caffeine therapy was associated with reduced odds of sNDI [significant neurodevelopmental impairment] and reduced odds of lower cognitive scores compared with late caffeine therapy among very preterm infants at 18 to 24 months’ CA [corrected age],” the researchers wrote.

Further analysis also linked early caffeine therapy to a significant reduction in the risk of hearing impairment in preterm infants.

“It is not clear how early caffeine therapy can lead to improved outcomes,” the researchers wrote, suggesting that this prolonged use of caffeine might stimulate the growth of new communication bridges between neurons. The median duration of treatment was longer in the early caffeine group than in those started at later ages, the study noted.

This treatment may also enhance cardiac output and blood pressure with a generalized beneficial effect, and reduced risk of neurological damage, they added.

“If confirmed by other studies, implications of our results are significant for both practicing neonatologists and pediatricians,” the researchers concluded. “One aspect will be to administer early caffeine and the other will be the timing of administration.”