Ben Welter - Monday, January 07, 2019
An infant warming mat developed at Lawrence Berkeley National Laboratory in California is undergoing approval for a six-month trial at 10 hospitals in Rwanda beginning next fall. The DREAM infant warmer uses biobased phase change material to keep newborns warm in places where electricity is unavailable or unreliable. Dr. Anne Hansen, medical director of the neonatal intensive care unit at Boston Children's Hospital, helped develop the mat and is directing the trial. In an interview, she provided background on the device and explained how it works.
Q: Tell me about the need for this device. What problem does it solve?
A: In low- and middle-income countries, hypothermia is a contributing cause in about one million infant deaths per year. Newborn babies, especially babies who are low birth weight or preterm or both, tend to cool to the temperature of their environment. Therefore even in warm climates like that of sub-Saharan Africa, newborns can become dangerously cold. It's rare for hypothermia to be the primary cause of death, but hypothermia in newborns can contribute to respiratory problems, glucose regulation, immune system function, and most importantly growth, including brain growth, and therefore neuro-developmental outcome. This can perpetuate the cycle of poverty.
Q: Why is this a particular problem for babies born in lower-income countries?
A: Babies born in a rich country receive a heat chain that protects them all the way from the delivery room until they go home from the hospital. This includes electric warming tables and incubators. In poor countries, this heat chain is more difficult to ensure. The supply of electricity can be inconsistent at best, the expensive warmers and incubators may be unaffordable. If they can be acquired, the nurses may not have the training to work these complex medical devices, causing hypo- and hyperthermia, as well as raising infection control concerns given how hard they can be to clean between uses. Finally, unless the facility has advanced biomedical engineers to provide the maintenance and repairs, the warmers do not last long. Because of all these problems, ensuring that newborns in resource-limited settings have access to a consistent heat chain requires a lot of workarounds.
The World Health Organization recommends skin-to-skin care, where you put a newborn directly on the mother's chest and she provides the external heat source. Skin-to-skin is great; we are total fans of skin-to-skin. The problem is that there are times where it's not very feasible, when the mother is sick or the mother dies in childbirth or if she has twins or triplets. If the baby is sick and requires medical assessment and treatments, the skin-to-skin positioning may not be feasible. Also, importantly, it's hard to be a human incubator for weeks to even months while a preterm baby gets old enough and mature enough to not need this external heat source. So providing heat by continuous skin-to-skin all day, all night for a long time, mothers just can't do that. They need to bathe, they may need to cook over a fire, or take care of their other children. So they have to stop; they put the baby down on a regular bed and then the baby gets cold. Finally, for the smallest babies, skin-to-skin may not provide enough heat; they're only getting heat from the part of their skin that is in direct contact with the mother's chest, but they aren't getting any heat from their backs.
We set out to design a warmer both to complement to skin-to-skin care when a mother wants to put her baby down, that could also be additive to skin-to-skin care when it is not providing enough heat. It needed to be electricity-free, inexpensive, intuitive to use, requiring minimal training, easily washed and reused with a goal of a thousand cycles.
Q: What was your role in the development of the device?
A: I've been working with Partners In Health (called Inshuti Mi Buzima in Rwanda) for almost 10 years. They work in very close collaboration with the Rwanda Ministry of Health. When I first went there in 2010, we helped them to develop and implement their national standards for newborn medicine. One of the problems that really stood out for me was that the options for thermoregulation were not working. When I came home, I partnered with Lawrence Berkeley National Lab to think about some other alternatives. We looked at a lot of ideas and ultimately settled on this phase change approach because it's so simple and straightforward.
The engineers did the actual design work, but we worked closely with them over many years to fine-tune it, figuring out how long it needed to be, how heavy it could be, how much people were willing to pay for it. From the outset we worked hand in glove with both Rwandan clinicians and the Ministry of Health. For example, the warmer is heated in thermos that holds boiling water to melt the PCM. The Ministry of Health was insistent that the thermos be wide-based and stable so that it wouldn't tip over when it was being filled with the boiling water and present any risk of burns.
We have completed two clinical studies of the warmer in Rwanda and it has performed extremely well. We are just gearing up to do what I hope will be a definitive large study with 10 hospitals in Rwanda this year. The Rwanda Ministry of Health has been amazing through all of this, supporting and facilitating all of our studies. We' want to have the warmer approved by the Rwandan Standards Bureau, which is like their FDA. They have also expressed interest in sponsoring the warmer for an international approval process, but we are going to wait on this until after we have the results from our large trial that we will be conducting later this year.
Q: Describe how the device functions.
A: We use your phase change material, PureTemp 37, configured as a set of 12 candles, each in its own plastic sleeve. The mat measures about 45.7 cm, by 25.4 cm, by 1.91 cm thick and contains about 1.2 kilograms of PCM. This arrangement allows the mat to be rolled up for charging or storage. Boiling water is used to charge the mat. All human civilizations know how to heat water, whether it is using a tea kettle with electricity or coal without. You heat 1.7 liters of water to boiling temperature, which provides the exact amount of energy needed to melt all the wax. The mat has a little temperature indicator that shows when it is cool enough to be safe to use. Once it has cooled, you dry it off and slip it in a little insulating pad. Then you put the baby, ideally naked, on the pad. This tends to be a population that does not have diapers, so a critical piece of the design was to avoid any fabric, Velcro or anything else that couldn't easily be cleaned with standard hospital cleanser. Ideally you give the baby a hat, and socks if you've got them, and then you wrap the baby and the warmer up in a blanket. The warmer stays hot for up to six hours, exactly at skin temperature.
Q: What's the projected price for a single unit?
A: Our goal is to keep it well under $100.
Q: Tell me about the upcoming study.
A: We're going to start this study in September of 2019 and it will run for six months. It's a complex study design called a step wedge study, specifically chosen to avoid the ethical conflict of having control patients such that one cold baby gets the warmer and another in the next bed does not. Instead, we will collect pre-data prior to introducing the warmer and this will serve as our control data. Then we will introduce the warmer, and use our post-data as our treatment data. Our hope is that we will find a reduction in hypothermia, hospital length of stay, and mortality, with improvement in growth. If so, then we we'll move to full-scale production, first for distribution across the rest of Rwanda and then in other appropriate countries in the sub-Saharan Africa.
Q: Where does the mat stand as far as approval processes in Africa?
A: We are still really at the prototype phase. We met this summer with a representative of the Rwandan Standards Bureau in Kigali. He said that, based on the results of our two preliminary pilot studies with 204 uses, it would be appropriate to for us to submit the paperwork for approval. We have not done that yet because they want to approve the absolutely final design, and we are still doing a bit more work, finding a more robust plastic and temperature indicator. Once we have our final design, we will submit the paperwork to the Rwandan Standards Bureau, sponsored by the Ministry of Health. Based on our feedback from this summer's meeting I am optimistic that they will approve it.
Q: What's been the most satisfying part of this project for you?
A: That is the easiest question. It is absolutely 100 percent the mothers. I will never forget the very first patients that we enrolled, a pair of twins. When we walked into the hospital that very first day, we had just explained to the nurses how to prepare the warmer, we were ready to enroll our first patients, and there was this mother with these twins. She looked so tired, not smiling or really interacting. Through a translator I asked her if she would like to have her babies enrolled in this study. She learned what it was, and signed the consent form.
One of the babies was so cold that we did the combination of the skin-to-skin and warmer across the back, and the other baby went straight on the warmer. She looked at the babies and she saw them getting warm. She just had this unbelievable look of relief - she was so happy. She said, "This is the first time that I've seen my babies look comfortable since they were born."