Doctors once believed that infants—especially premature babies—did not feel pain, and if they did, they would not remember it.
This might sound like Medieval medicine. But as recently as the 1980s, babies undergoing surgery were given a muscle relaxant to paralyse them while in the operating room but were not given any pain medication, says Fiona Moultrie, a paediatrician and researcher at the University of Oxford who focuses on neonatal pain. “At the time, it was assumed that most of the behaviours that infants were exhibiting were just reflexes.”
Over the next decades, studies documented changes in infant behaviour, stress hormones, and brain activity, proving that even the tiniest babies did indeed suffer pain. Research also revealed that continued pain could derail a child’s short- and long-term neurological, social, and motor development, especially in fragile, preterm babies born earlier than 37 weeks, says Björn Westrup, a neonatologist and researcher at the Karolinska Institute near Stockholm, Sweden.
Rapid advances in medicine now allow very fragile, tiny, preterm babies to survive. But ‘preemies’ may spend weeks or months in the hospital undergoing the constant, often painful procedures needed to save their lives. Strategies to make such procedures less traumatic are vital, as premature births are rising globally. In the United States alone, about 380,000 babies are born prematurely each year, or about one in 10 births. Worldwide, it’s about 15 million.
The medical profession tries to manage or prevent infant suffering with drugs such as ibuprofen (for mild to moderate pain) and fentanyl (used to alleviate extreme pain). For most analgesic drugs, though, the proper dosage, effectiveness, or effects on the brain remain unknown, so increasingly, hospitals are incorporating non-pharmaceutical interventions that centre on techniques known as developmental care, which keep babies and their families together rather than isolating infants in incubators.
That’s critical, says Manuela Filippa, a researcher at the University of Geneva who studies prematurity, because separating sick babies from their parents compounds pain with toxic stress that creates serious developmental problems. Inside a neonatal intensive care unit, or NICU, lights are bright and monitors blink. It’s loud, with machines beeping, alarms going off, people talking, and ventilators thumping and hissing.
“Brain maturation is based on sensory experience,” Filippa explains, “and the [traditional] neonatal intensive care unit is very stressful.”
How do babies express pain?
Babies born extremely early are whisked from the delivery room to the NICU. The youngest, those under 36 weeks, have underdeveloped lungs and may be intubated and hooked up to a ventilator. They are too weak to suckle and must be fed through tubes in the nose or mouth. Nurses need to lance their tiny heels for blood tests up to 10 times a day, and they are engulfed in IV lines, tubes, and wires.
In the early 1980s, Canadian newborn medicine researcher Celeste Johnston, an emeritus professor at McGill University in Montreal, was approached by nurses working in the NICU who wanted a way to measure pain in infants. In 1986, she was among the first to publish evidence that infants’ heart rates and oxygen levels changed when they were subjected to painful procedures. Their cries and facial expressions revealed what she calls “honest signalling,” behaviours that babies are born with that communicate distress.
“There is a particular grimace that was described by Darwin in the 1800s that is recognised universally as pain,” she says. That’s ironic, Moultrie notes, “as Darwin’s celebrated work on evolutionary theory and the expression of emotions in man promoted the concept of infants as primitive beings with under-developed senses and merely reflexive behaviours.”
Johnston was later horrified to learn that in intensive care, babies averaged about 14 painful procedures each day.
But understanding how these small, nonverbal beings experience pain is extremely difficult. “One of the biggest challenges in caring for preterm and sick infants is that they can’t tell us,” says Erin Keels, a nurse practitioner and director of advanced neonatal providers at Nationwide Children's Hospital in Columbus, Ohio. “We can only infer by their behaviours and their vital signs.”
Forty different pain scores have been compiled over the last three decades, which can be used to evaluate pain levels. They each include various combinations of heart rate, oxygen saturation, facial expressions, or body movements. But since physiology can change for many reasons, and a baby may be too sick or too medicated to grimace, these are not always objective markers. There is an ongoing quest to better understand how infants perceive and experience painful stimuli.
“Although there has been great progress, we still don't fully understand pain in neonates,” says the University of Oxford’s Moultrie. She and others have been trying to measure pain by observing bursts of electrical activity in the brain using electroencephalogram (EEG) testing. They identified a pain-related pattern of brain activity in infants, which is now being used in clinical trials to test the efficacy of medications. It could revolutionise pain treatment.
In a later studies, researchers at the University of Oxford used MRI scans to pinpoint brain activity. They found that 20 out of 22 brain regions activated in an adult’s brain in response to pain are also activated in a newborn baby’s brain. One area that did not register was the amygdala, which is associated with fear and anxiety, likely because days-old babies may not yet make these associations, Moultrie says.
But there’s still a lot researchers still don’t know about exactly what's going on in the infant brain. “When you're tiny and underdeveloped, differentiation between pain and stress is not clear,” says Johnston.
At the same time, researchers are uncovering the potential long-lasting physiological consequences of preemie pain, Filippa notes. The amount of pain-related stress predicts the thickness of the brain’s cortex, for instance. One study found that at school age, children who were born very preterm—at 24 to 32 weeks gestational age—had a thinner cortex in 21 of 66 cerebral regions, predominately in the frontal and parietal lobes. This has been linked to motor and cognitive impairments.
Preterm babies also face significant risk for lowered IQ, attention deficit disorder, memory issues, and difficulty with social interactions and emotional control. Heidelise Als, a pioneer in understanding physical and behavioural risks for both preterm and sick infants, attributes this at least partly to the vastly altered sensory experiences that can influence preterm babies’ immature nervous systems.
Paediatric Neuroimaging research group