Premature Babies Benefit From Caffeine Therapy in the First Hours of Life
Many of us can’t start our day or feel fully awake without that first jolt of caffeine in the morning. Some drink coffee throughout the day to remain alert and on task or to decrease tiredness. It is common for those who are employed to take an afternoon coffee break to stave off the late day loss of motivation and energy and be able to complete their work day. For freelancers, the most common offices they frequent are coffee shops and one of the most frequent queries for Yelp is where to find coffee shops that open early and close late. Coffee and coffee shop culture has become a major industry in North America and many European countries as well.
In neonatal intensive care units, or NICUs, premature babies born under 29 weeks are given a daily dose of caffeine to ensure the best possible start to life. After antibiotics, caffeine is the most frequently used drug in the NICU. A new investigation by University of Calgary supports earlier findings that caffeine administered to premature infants can help reduce a number of negative effects, especially when administered soon after birth.
Premature babies often have a number of medical problems. One of the most serious of these is incomplete lung and brain development such that many of these early babies have respiratory problems and some have to be put on a ventilator until able to breath on their own. Sometime when premature babies are feeding, they can’t coordinate breathing and sucking. Their breathing may slow or even stop, causing their heart rate to decrease to the point they won’t be able to get enough oxygen.
Often times, even when premature babies don’t need to be placed on a ventilator they do require a continuous positive airway pressure, (CPAP), machine to provide constant airflow to their lungs. As these machines provide forced air into their lungs, it can be unpleasant and create stress for the infant, something which can also have negative effects on their immune functioning and ultimately contribute to worse outcomes. Caffeine can help with these difficulties helping babies to breathe on their own and increasing lung function.
Early Investigations of Caffeine Therapy in Premature Babies
Knowledge of the benefits of caffeine for premature infants has existed since the early 2000’s. A clinical trial to examine unanswered questions and address toxicity concerns, was undertaken in 2004 (Steer et al., 2004). Results of this study confirmed significant positive effects of caffeine therapy, including shorter duration of intubation and respiratory support, reduced incidence of chronic lung disease. There were also decreased incidence rates of patent ductus arteriosus, a condition where the blood vessel allowing blood to circulate around the lungs before birth does not close and severity of retinopathy of prematurity, a potential cause of blindness. Additionally, the babies who received caffeine therapy demonstrated improved motor and visual functions.
Other studies supported the use of therapy beginning before 3 days post birth along with higher maintenance doses to safely achieve desirable effects (Natarajan, Lulic-Botica, & Aranda, 2007) and showed therapy had no negative effects on temperament, development or behavior (Gray, Flenady, Charles, Steer, & Caffeine Collaborative Study Group 2011). Overall, caffeine therapy has been found to have a very favorable benefit-to-risk ratio.
Studies Conducted by University of Calgary Researchers
The current study was preceded by earlier work conducted by the same team. A 2015 study by Lodha et al., examined the timing of caffeine administration comparing premature infants who started therapy within the first two days with those who started it on or after the third day. As opposed to using the therapy with babies who had already developed apnea of prematurity, a condition involving difficulty breathing. This study was one of the first to examine caffeine therapy for premature babies who had not developed apnea.
Results showed that starting caffeine therapy within two days after birth shortened the amount of time babies needed to use ventilators and need for treatment for congenital heart defects. It also reduced the risk of death, patent ductus arteriosus, and bronchopulmonary dysplasia (BPD), a form of chronic lung disease caused by damage to the lungs from use of a ventilator. No differences were found for necrotizing enterocolitis (a condition where part of the bowel dies), severe neurological injury, or severe retinopathy of prematurity.
So in this study, early prophylactic caffeine therapy used for very premature infants was associated with a reduction in the rates of death, bronchopulmonary dysplasia and patent ductus arteriosus. No adverse effects were found for any of the other outcomes included.
The current study was designed to determine the relationship between early (within 2 days of birth) versus late caffeine exposure and neurodevelopmental outcomes in premature infants born before 29 weeks gestation (Lodha, Entz, Synnes, Creighton, Yusuf, Lapointe & Shah, 2018). The outcome examined was significant neurodevelopmental impairment. This was defined as the development of cerebral palsy, the need for hearing aid or cochlear implant, the presence of bilateral visual impairment or a score of less than 70 indicating a delay in development on the Bayley Scales of Infant and Toddler Development, an infant IQ test. These outcome measures were assessed at 18 to 24 months. Earlier findings were also replicated.
Previous findings were confirmed as rates of bronchopulmonary dysplasia, patent ductus arteriosus, and severe neurologic injury were lower in the early-caffeine group compared to the late-caffeine group. Significant neurodevelopmental impairment was lower across all measures in the early-caffeine group than in the late-caffeine group. It was concluded that the timing of caffeine therapy for premature infants is important in maximizing the benefits. Early caffeine therapy was associated with better neurodevelopmental outcomes compared with late caffeine therapy in very premature infants born at <29 weeks.
The parents of one of the subjects in the study who is now two years old, are very happy with the results. Their child has undergone multiple follow-up assessments, is in regular school, and is able to participate in dance classes, gymnastics lessons and swimming.
“She’s very mechanical. She likes to build things, take it apart and figure out how it works,” the child’s mom says. “It’s wonderful to know that the caffeine treatment has no adverse effects and that if researchers are getting positive findings, it should continue to be the standard of care for premature babies. In that case, I think parents would have no hesitation in having caffeine as part of their child’s treatment.”
Gray, P. H., Flenady, V. J., Charles, B. G., Steer, P. A., & Caffeine Collaborative Study Group. (2011). Caffeine citrate for very preterm infants: effects on development, temperament and behaviour. Journal of paediatrics and child health, 47(4), 167–172.
Lodha, A., Entz, R., Synnes, A., Creighton, D., Yusuf, K., Lapointe, A.,& Shah, P. S. (2018). Early Caffeine Administration and Neurodevelopmental Outcomes in Preterm Infants. Pediatrics, e20181348.
Natarajan, G., Lulic-Botica, M., & Aranda, J. V. (2007). Pharmacology review: clinical pharmacology of caffeine in the newborn. NeoReviews, 8(5), e214-e221.
Steer, P. et al. (2004). High dose caffeine citrate for extubation of preterm infants: a randomised controlled trial. Arch. Dis. Child Fetal Neonatal Ed. 89, F499–F503.