Influence of Caffeine Therapy in Preterm Infants on Sleep and Neurodevelopmental Outcomes During the First Year of Life: a Single Center Experience

Methylxanthines have been prescribed in preterm infants to treat and prevent Apnea of Prematurity (AOP), for extubation success, for reduction of incidence of BPD, need for treatment of PDA, retinopathy of prematurity, IVH, and for neuroprotective effects. Caffeine is the most common drug of choice. Despite its frequent use there are no standardized protocols for optimal timing and dosage. It is suggested to have a neuroprotective effect, and associated with reduction of neurological disabilities, cognitive delay. However, there are studies which found no difference in poor neurological outcomes compared to control.

Premature infants have more active sleep compared to term infants, and their sleep patterns mature gradually. Studies about the effects of caffeine therapy on sleep of premature infants are few. It is known that sleep is associated with child's neurodevelopmental outcomes. Identifying the impact of caffeine therapy on sleep will help clinicians to identify and improve neurodevelopmental problems in this vulnerable study population.

The aim of this study is to evaluate the effects of caffeine therapy on sleep, activity patterns and neurodevelopment in preterm infants during the first year of life.

Based on the assumption that each year approximately 20 infants receive neonatal caffeine therapy in the unit, forty preterm infants aged between 28 to 34 gestational weeks admitted to the Marmara University Neonatal Intensive Care Unit (NICU) from May 2020 to May 2021 will be included. Duration, timing and cumulative dosage of caffeine therapy will be calculated. The routine practice of Marmara University NICU protocol is to administer caffeine prophylaxis to infants born at less than 30 weeks of gestational age and/or infants with less than 1250 grams gestational weight. Infants born between 30 to 34 weeks of gestational age who has AOP are treated with caffeine therapy with the commonly prescribed dose of 20 mg/kg loading, and 5-10 mg/kg/day maintenance. Neonatal caffeine therapy continues until the infants are 34 weeks corrected gestational age and free of any apnea episodes for at least 7 days. Infants with neonatal risk factors for poor neurodevelopmental outcomes such as infants with perinatal asphyxia, intraventricular hemorrhage grade 3 or higher, retinopathy of prematurity(ROP) of stage 3 or higher, infants using sedative or anticonvulsant drugs at the time of data collection will be excluded.

Follow up outcome for sleep architecture and neurodevelopment of preterm infants who received caffeine therapy will be compared with those who did not receive caffeine therapy.