A newborn quickly has to adapt to breathing air, which calls for a large set of events to take place. In the fluid-filled environment of the uterus, the lung is essentially closed, and the infant has to expand the lung quickly, in order to take over the placenta’s business of putting oxygen into the bloodstream and getting rid of carbon dioxide.
That becomes a tricky thing to do for a baby who is born prematurely and extremely small — less than 1,000 grams — because the infant must have good muscle power to generate the high opening pressure required for its first breath to establish lung volume. This is where a research maneuver being studied by a multicenter, international clinical trial led by Haresh Kirpalani, BM, MSc, of The Children’s Hospital of Philadelphia, and Sarah J. Ratcliffe, PhD, of the University of Pennsylvania Perelman School of Medicine fits in.
Previously, several large trials have looked at helping infants who weigh less than 1,000 grams to expand their lungs using a simple, low level continuous positive airway pressure, called CPAP, which is administered in the delivery room via a facemask at about 5 to 7 cmH2O. And while it’s been shown that CPAP can help the baby transition into a postnatal, oxygen-enriched environment satisfactorily, many of these babies end up requiring placement of an endotracheal tube in the windpipe that breathes for the baby. Intubation imposes an additional burden and risk of bronchopulmonary dysplasia, one of the main problems that face premature babies if they survive.
The research maneuver being tested in the Sustained Aeration of Infant Lungs Trial (SAIL) launched this summer will impose a higher peak inspiratory pressure of about 20 cmH20 and hold the breath for about 15 seconds immediately after birth to facilitate uniform lung aeration. Half the babies enrolled in the trial will receive the low level CPAP, and the other half will receive the research intervention delivered by a physician trained to implement the study protocol. A potential concern is that the higher pressure will increase the chance of air leaks, but so far the literature is not convincing that this is a problem, Dr. Kirpalani said.
“The results of the trial should enable us to take a near definitive look at the standard of care for resuscitation of these babies at delivery, and begin to give some guidance to the Neonatal Resuscitation Program as to whether sustained inflation is a useful strategy or not,” Dr. Kirpalani said.
The NRP is an educational program sponsored by the American Academy of Pediatrics and the American Heart Association to teach an evidence-based approach to resuscitation to multidisciplinary hospital staff who care for newborns at the time of delivery.
The SAIL research team expects over three years to enroll 600 infants with a gestational age of at least 23 weeks but less than 27 weeks who require resuscitation or respiratory intervention at birth. A particular challenge of this study is approaching parents during the stressful and uncertain time of preterm labor and gaining full parental consent to participate in the trial.
In a Pediatric Perspectives article published in the July issue of Pediatrics, Dr. Kirpalani and his neonatology colleagues at CHOP, Sara B. DeMauro, MD, and Barbara Schmidt, MD, MSc, and also at McMaster University, Canada, Janice Cairnie, RN, and Judy D’Ilario, RN, examined the importance of honesty, trust, and respect during consent discussions in neonatal clinical trials.
“We’ve always been of the mind that an ongoing dialogue after consent is extremely important to enable the parents to understand what the issues are and also to reinforce throughout the trial duration that we are conducting it largely because we do not know whether treatment A or treatment B is better,” Dr. Kirpalani said. “That gives parents multiple opportunities to revisit the informed consent question, allows them to voice their concerns, and understand their child’s potential benefits and risks. In a way, it should be like an ongoing part of the therapeutic relationship.”
The SAIL trial is supported by funding through the Eunice Kennedy Shriver National Institute of Child Health and Development.