Clinical trial demonstrates effectiveness of infant apnea prevention technology
WORCESTER, MA — Scientists and clinicians at the University of Massachusetts Medical School, Wyss Institute for Biologically Inspired Engineering, and the Beth Israel Deaconess Medical Center (BIDMC) have shown in a clinical trial that a new, vibration-based prevention technology tested in a neonatal intensive care unit (NICU) reduces apneic events and improves critical clinical parameters in prematurely born infants. The apnea prevention system, initially conceived at UMass Medical School, was developed at the Wyss Institute and tested in a trial conducted at the BIDMC. The findings are reported in the November 23 issue of Pediatrics.
In the United States, one in nine infants is born prematurely and many of these are at higher risk for apnea of prematurity (AOP), typically defined as a prolonged pause in breathing of at least 20 seconds. In fact, such apneic episodes occur in greater than 50 percent of infants born prior to 37 weeks and in almost every baby of very low birth weight and can be life threatening. Even if treated in NICUs, it can result in insufficient oxygen delivery to critical organs such as the brain, which is suspected to cause developmental delays and long-term cognitive deficits.
"Apneic breathing and its associated risks is a major challenge in NICUs today, and can also lead to prolonged and expensive hospital stays. This prompted us to develop a non-invasive, non-pharmacological solution that can address the immature respiratory control in these premature infants," said David Paydarfar, MD, professor and vice chair of neurology at UMass Medical School and a Wyss Institute associate faculty member, who was the scientific lead on the apnea prevention program.
While others were focused on the moment when the baby stops breathing, Dr. Paydarfar began investigating how to prevent apnea from occurring in the first place. Over a decade ago, he assembled a multi-disciplinary team of basic and clinical scientists at UMass Medical School to figure out not only how sensory processing normally functions in respiratory control, but also how the system experiences problems in an immature infant.
Key to the infant apnea prevention technology is the principle of "stochastic resonance,": early work by the Wyss Institute's Core Faculty member James Collins, PhD, has revealed the counterintuitive phenomenon in which the application of a small amount of "noise" to a complex biological system, such as the human body, increases the sensitivity of that system. Collins is also the Termeer Professor of Medical Engineering & Science at Massachusetts Institute of Technology (MIT) and a professor of biological engineering at MIT.
Paydarfar applied this principle to the problem of AOP. In an early pilot study done at UMass Medical School, Paydarfar showed that adding "noise" in the form of a subtle vibration in the mattresses of premature infants helps to stabilize breathing and improve blood oxygenation without waking the infant. This suggested that a stochastic resonance approach could compensate the infants' still immature respiratory control system and could prevent dangerous apneic events from occurring.
"Our team subsequently developed a new mattress device designed to deliver the same level of therapeutic vibration that was found to be effective in Dr. Paydarfar's previous studies while limiting the vibrations that would otherwise be delivered to the head of the infant," said John Osborne, a senior staff engineer at the Wyss Institute who co-conceptualized the new study and co-authored the publication.
The team has now validated this new mattress device in the BIDMC trial, in a cohort of 36 preterm infants that had at least one previous event of apnea. The results of the trial provide comprehensive clinical evidence for the method's ability to benefit breathing stability.
"By applying alternating intervals of 30-minute therapeutic mattress vibrations with 30-minutes of no vibration, we compared the effects of stimulation to the control period. During the therapy period, we saw a reduction in the incidence of apnea by 50 percent, and, perhaps equally important, we ameliorated every aspect of clinically significant oxygen desaturation events as well as demonstrated reductions in the severity of bradycardia. The technology therefore might be used as a stand-alone or as a supplement to the caffeine therapy that premature infants are commonly treated with," said Vincent Smith, MD, MPH, an assistant professor of pediatrics at Harvard Medical School and Beth Israel Deaconess Medical Center who is also lead author on the published study.
"By de-risking the infant apnea prevention technology, the Wyss Institute and its clinical partners have now advanced it to the stage at which it can be more widely tested and eventually deployed in hospital NICUs. The findings exemplify once more how our translation engine can provide finely tailored solutions that may impact areas of clinical need," said Wyss Institute Founding Director Don Ingber, MD, PhD, who also is the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and professor of bioengineering at SEAS.
About the University of Massachusetts Medical School
The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $249 million in research funding annually, 80 percent of which comes from federal funding sources. The mission of the Medical School is to advance the health and well-being of the people of the commonwealth and the world through pioneering education, research, public service and health care delivery with its clinical partner, UMass Memorial Health Care. For more information, visit http://www.umassmed.edu.
The Wyss Institute for Biologically Inspired Engineering at Harvard University
The Wyss Institute for Biologically Inspired Engineering uses nature's design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing that are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and formation of new start-ups. The Wyss Institute creates transformative technological breakthroughs by engaging in high risk research, and crosses disciplinary and institutional barriers, working as an alliance that includes Harvard's Schools of Medicine, Engineering, Arts & Sciences and Design, and in partnership with Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Boston Children's Hospital, Dana-Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Boston University, Tufts University, and Charité – Universitätsmedizin Berlin, University of Zurich and Massachusetts Institute of Technology. For more information, visit http://wyss.harvard.edu
About Beth Israel Deaconess Medical Center
Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks as a national leader among independent hospitals in National Institutes of Health funding. BIDMC is in the community with Beth Israel Deaconess Hospital-Milton, Beth Israel Deaconess Hospital-Needham, Beth Israel Deaconess Hospital-Plymouth, Anna Jaques Hospital, Cambridge Health Alliance, Lawrence General Hospital, Signature Healthcare, Beth Israel Deaconess HealthCare, Community Care Alliance and Atrius Health. BIDMC is also clinically affiliated with the Joslin Diabetes Center and Hebrew Rehabilitation Center and is a research partner of Dana-Farber/Harvard Cancer Center and the Jackson Laboratory. BIDMC is the official hospital of the Boston Red Sox. For more information, visit http://www.bidmc.org.