From the Journals

Early caffeine therapy linked to improved neurologic outcomes in premature babies


Key clinical point: Earlier caffeine treatment for premature infants may improve neurologic outcomes.

Major finding: Preterm neonates treated with caffeine within 2 days of birth have a significantly lower risk of hearing impairment and cerebral palsy.

Study details: A retrospective observational cohort study in 2,108 preterm neonates.

Disclosures: No funding or conflicts of interest were declared.

Source: Lodha A et al. Pediatrics. 2018 Dec. 5. doi. org/10.1542/peds.2018-1348.



Premature babies may benefit more if caffeine therapy is given within 2 days of birth, based on a retrospective observational cohort study of more than 2,000 newborns.

When caffeine was given within the first 2 days of birth, neonates had an adjusted odds ratio of significant neurodevelopmental impairment of 0.68, compared with neonates who received caffeine after 2 or more days. Further, the early-caffeine group had a 0.67 adjusted odds ratio for having cognitive scores of less than 85 on the Bayley Scales of Infant and Toddler Development, Third Edition, compared with the late-caffeine group. After researchers corrected for small-for-gestational-age status and other risk factors, however, early-caffeine therapy was associated with lower odds of cerebral palsy and hearing impairment only, according to the study published online in Pediatrics.

Caffeine administration should be a priority once extremely preterm neonates are stabilized, Abhay Lodha, MD, of the University of Calgary (Alta.), and his coauthors wrote. “It is rather easy to organize the administration of caffeine as early as possible for Level 3 nurseries, and many units have already accomplished this. However, certain Level 2 nurseries may not have facilities available for such early administration. We do not have data that indicate the earliest that caffeine would have to be given to get maximum benefit, and thus, it should not be counted as an emergency medication yet,” they wrote.

The study examined data from 2,108 neonates born before 29 weeks of gestational age and given caffeine to treat or prevent apnea; 1,545 received the caffeine within 2 days of birth and the remaining 563 were treated with caffeine after 2 days. Data were adjusted for gestational age, sex, antenatal steroids, and SNAP-II (Score of Neonatal Acute Physiology-II) score.

The early-caffeine group had a significantly reduced odds of hearing impairment and cerebral palsy, bronchopulmonary dysplasia, patent ductus arteriosus, and severe neurologic injury. When the data were further analyzed using propensity-matched groups – which also accounted for small-for-gestational-age status – the difference in outcomes was a nonsignificant trend in favor of early caffeine.

The authors noted that the late-caffeine group contained a higher proportion of infants born at or before 24 weeks’ gestational age, and a lower proportion of infants born at 25-28 weeks’ gestational age, compared with the early-caffeine group. The infants in the early-caffeine group also had higher Apgar scores, higher median birth weight, and lower SNAP-II scores, and received a longer median duration of caffeine treatment.

Dr. Lodha and his coauthors said the reason for the differences between the early- and late-caffeine groups was unclear. “However, it could be attributable to an increased growth of dendrites and spines in neurons that is initiated by the especially prolonged use of caffeine in the early-caffeine group,” they wrote. “The other speculation is that caffeine improves cardiac output and blood pressure in infants who are relatively stable.‍”

No funding or conflicts of interest were declared.

SOURCE: Lodha A et al. Pediatrics. 2018 Dec. 5. doi. org/10.1542/peds.2018-1348.

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