The risk of morphine for premature babies

Jill ZwickerMorphine, a drug commonly used to help premature babies get through painful procedures, is associated with physical and cognitive impairments and shrinkage of the cerebellum, according to research by UBC and the University of Toronto.

The problem is, the alternatives — either another drug like fentanyl, or not providing any pain relief medication — may pose similar risks to neonatal brain development.

Most premature infants in the neonatal intensive care unit (NICU) undergo a tube insertion to help them breathe; surgical procedures are also common. Morphine is usually the drug provided to blunt the pain.

Jill Zwicker, an occupational therapist who specializes in brain and motor development, decided to take a closer look at morphine’s effects after coming across animal studies that showed the drug affects cells in the cerebellum — a part of the brain previously thought to be involved only in motor functions, such as balance and coordination, but which is now known to play a major role in attention, executive functions, and language.

Her study, published online this month in the Journal of Pediatrics,  looked at 136 babies born very pre-term at BC Women’s Hospital. The infants were categorized according to the amount of morphine they received, and were assessed using standard tests of infant motor skills, infant cognitive skills and magnetic resonance imaging (MRI).

Greater morphine exposure was connected with poorer results on the motor skills and cognitive tests at 18 months, and smaller cerebellar volume during the neonatal period. A 10-fold increase in morphine predicted a 5.5 per cent decrease in cerebellar volume, even after considering other risk factors such as number of painful procedures, other brain injuries, and exposure to steroids.

Impairments in the cerebellum have been associated with various neurodevelopmental problems, such as developmental coordination disorder, attention deficit hyperactivity disorder, learning disabilities, and autism.

The latest findings present a dilemma for physicians and parents when caring for infants who are born prematurely and require medical interventions. Previous research by co-author Ruth Grunau, a Professor in the Department of Pediatrics, showed that not alleviating the pain in pre-term newborns carries risks for brain development as well. An alternative drug, fentanyl, has been shown to affect growth of the cerebellum when given to premature infants.

“Being aware of the association of morphine with smaller cerebellar growth and neurodevelopmental outcomes may alter clinical decision making, but there may be times when morphine may be the best drug of choice for the baby’s care in the NICU,” said Dr. Zwicker, an Assistant Professor in the Department of Occupational Science and Occupational Therapy, who did the research as a postdoctoral fellow at NeuroDevNet, a national network focused on brain development, based at UBC. “Parents should be aware of the benefits and risks of morphine and discuss alternatives with their NICU team.”

At this point, there isn’t evidence-based information about methods of pain control that are better or worse, said senior author Emily Tam, an Assistant Professor of Pediatrics at the University of Toronto and a neurologist at SickKids. “Our finding points to the need for research to optimize pain control in newborns while being mindful to minimize risks for brain development,” she said.

“It is imperative that we find how to treat pain in the neonate in ways that promote optimal brain development,” said co-author Steven Miller, a Professor of Pediatrics at the University of Toronto and Head of Neurology at SickKids, who co-supervised Dr. Zwicker’s research with Dr. Grunau.