By Fran Cronin
Nate Lawrence was born in Winchester Hospital in Massachusetts, December 16, 2010, in severe distress. He was limp, purple and not breathing. Both his lungs had collapsed.
As his parents and grandparents began to descend into panic, the neonatology staff at Winchester went into action.
They took x-rays of Nate’s chest, put a breathing tube down his throat, wrapped a turban around his head and placed him in a clear acrylic transportation box. Children’s Hospital Boston, 13 miles to the east, had been alerted that Nate was on his way. The ambulance team was instructed not to turn on warmers or swaddle Nate. He was to arrive at Children’s a cool 92.3 degrees, more than six degrees below normal.
Nate was born hypoxic, which means that because of his collapsed lungs, insufficient oxygen was flowing through his blood and into his brain. Lack of oxygen, like Nate’s, can lead to cell injury or cell death and ultimately to irreversible brain damage. To halt this potential deterioration, Nate’s body needed to slow down. Cell metabolism had to be lessened and his demand for oxygen reduced. He needed to operate on less energy and to rest.
Since lab trials began almost a decade ago, so-called “cooling” has demonstrated that for every degree a baby’s body temperature is lowered, its body functions and demand for energy slow down by 10 to 15 percent. Putting a “brake” on metabolic demands can prevent an injurious mismatch between oxygen supply and cell need.
Hypoxic-ischemic encephalopathy (HIE), like Nate’s loss of oxygen at birth, is the leading cause of cerebral palsy, an irreversible neonatal brain injury that can result in long-term cognitive, motor, and visual impairments. About 10,000 babies are born each year with CP.
“It’s hard to always protect a baby’s brain at birth,” says Dr. Janet Soul, a neonatal neurologist at Children’s Hospital Boston. “There are unforeseen events that can occur.”
If the placenta peels away from the uterine wall before delivery, it can cause heavy bleeding in the mother and a loss of oxygen and nutrients to the baby. The uterus can rupture or the umbilical cord can prolapse or wrap itself around the baby’s neck. In the case of Nate, a post-delivery exam revealed a uterine infection at the time of birth.
Back at Children’s Hospital, the Neonatal Intensive Care Unit was being readied to receive Nate. Soul and Dr. Anne Hansen, medical director of Children’s NICU, were preparing to lead their hypothermia team in a carefully orchestrated screening of Nate before starting him on the cooling procedure.
“The babies we accept [into our hypothermia protocol] are sick, but not too far gone,” says Soul. “If too severe [and with other complications] we can’t make a difference. Babies that are too well are sent home and remain under observation.”
While induced pediatric hypothermia was approved by the FDA in March 2007, it is not a universal standard of care. That’s because there are fairly strict guidelines to determine a baby’s eligibility. Newborns have to be full-term with no known pre-existing conditions. They also must have neonatal distress and an abnormal neurological exam.
Upon examination, Nate’s condition aligned perfectly with the criteria for induced hypothermia.
Nate was placed in a clear plexiglass bassinet on a sky blue blanket threaded with tubes for circulating cooled water. Sensors maintained the blanket’s water flow to an even 33.5C (normal is 37C) to ensure Nate’s body temperature remained stable. Temperature monitoring was conducted by an esophageal thermometer placed in his throat. Small round electrodes attached to his head and hooked up to an EEG, to monitor brain activity and provide real-time neurological data. To deliver nutrition and sedatives as well as anti-pain and anti-seizure drugs into his string width veins, IVs were inserted alternately in Nate’s feet and hands. He would have to be turned every two hours to ensure even circulation throughout his body.
Hypoxic babies are also prone to a second wave of damage during their first 72 hours of life. If not controlled with cooling, a cascade of toxic byproducts could flood their vulnerable bodies in response to the hypoxic insult, causing seizures, or worse, trigger cells to go through what is called “an unintended programmed death.” For Nate’s parents, Elizabeth (Liz) and TJ, the waiting and inability to cuddle their newborn were the toughest parts of the protocol.
“For us,” says Liz, “Nate’s time on the blanket was very hard. We could help turn him but we couldn’t hold him. Your instinct is to rub your baby’s skin, but for Nate, that was very painful.”
The only physical contact Liz and TJ were allowed was to hold Nate’s hand or place their own hands on his stomach, legs, or feet. They kept a photo of themselves tucked inside his bassinet.
Once babies like Nate successfully clear the three-day danger period, their body temperatures are restored to normal, one degree every 12 hours.
Soul and Hansen agree the loss of bonding time with a newborn is stressful. These babies have to be taught how to breastfeed, and swallowing can be hard for finger-width throats that have been rubbed raw by tubes. “We had to put sugar water on a binky to teach Nate how to suck,” says TJ. It then took Nate 45 minutes to drink his first two ounces.
To date, Children’s Hospital has successfully completed the hypothermia protocol with 36 babies. Soul and Hansen still follow the successful progress of their first patient, now four-years old.
Other Boston-based hospitals — Beth Israel Deaconess, Brigham and Women’s, Mass General and Boston Medical Center — now follow the same cooling protocol.
But the stakes are high. If a baby is cooled or warmed too quickly, heart failure can ensue.
Smaller, less-experienced and less well-equipped hospitals within a 300 mile radius of Boston send their HIE babies to Children’s for assessment. To effectively implement the cooling protocol, these babies must receive “passive” cooling (without warming interventions) en route to the medical center and arrive within the critical first six hour window.
The bustling Boston Medical Center, across town from Children’s Hospital, has cooled seven babies in the past four years. Unlike Children’s, BMC is a birthing hospital. On average, 2500 babies are delivered there each year and their hypothermia program only accepts babies born in their maternity ward.
Dr. Alan Fujii, NICU medical director, and Dr. Laurie Douglass, a pediatric neurologist, lead the BMC hypothermia team. For their hypothermia protocol, they favor “cool caps” over the cooling blanket. The cool cap, they say, allows for selective cooling and is technologically simpler to use than the blankets.
“The cool cap is a well designed product and is easy to use. If we needed a more specialized and trained staff,” says Douglass, “there would be no guarantee the team would be available when needed.”
The first baby BMC ever treated is now two-and-a-half years old and doing well. “We can’t observe subtle issues yet and don’t know her IQ, but the results so far are great,” says Douglass.
Fujii agrees. “Our babies are very sick,” he says. “Before, all we could offer was wait and see. Now we have hope.”
There’s an ongoing debate over which is best, the cap or the blanket.
In a phone interview, Dr. Sonia Bonifacio, a neonatologist at the University of California at San Francisco School of Medicine and co-director of its Neuro-intensive Care Nursery, described their pros and cons. The cap, she says, includes a timing monitor that can sound alerts and has a scaled down, dedicated EEG monitor. This makes it easier to use by less-specialized staff. But, at $20,000 per unit, the cap is at least twice as expensive as the cooling blanket.
Soul agrees the cap may be easier to use but cautions that many induced hypothermia babies are prone to seizures. The blanket, she says, is better for monitoring these types of episodes.
Whether using the blanket or the cap, says Bonifacio, who says she cools 30-40 babies each year using the blanket, the bottom line is that the outcomes from cooling are impressive.
“For the first time we can offer a treatment when loss of blood or oxygen occurs at birth,” says Bonifacio. “Maybe even prevent a lifelong disability, like CP, that could be much more costly to a family and society.”
To reap the financial benefit of the hypothermia protocol, she says, she only needs to treat nine babies. “In medicine,” says Bonifacio, “that’s an amazing number.”
In Winchester, Nate is now pointing and saying his favorite word “bah” as Liz and TJ watch him closely as they sit together on a couch. “We paid a lot of attention to milestones,” says TJ. “Nate’s keeping track. Look at him. He’s fine.”