#346 - CPAP with Purpose: Supporting Babies in the Delivery Room and the NICU (Part 1)

Hello friends 👋

In this episode of The Incubator Podcast, we welcome Dr. Cindy McEvoy, Professor of Pediatrics and Director of Neonatal Research at OHSU, to discuss her work on the use of extended CPAP in preterm infants. CPAP has long been a cornerstone of neonatal care, but how long should stable infants remain on support? Dr. McEvoy shares findings from two randomized controlled trials that explored whether an additional two weeks of CPAP could promote lung growth and improve longer-term outcomes.

We review the physiologic rationale behind extended CPAP, including the role of mechanical stretch in stimulating alveolar and vascular development. Dr. McEvoy explains the stability criteria used to determine eligibility for extended CPAP and how her team measured pulmonary function in neonates. Results from her studies showed significant improvements in lung volume, diffusion capacity, and expiratory flows, with early signals of reduced wheezing at one year of age.

The conversation also touches on feeding tolerance, the practicalities of implementing extended CPAP in the NICU, and the need for larger multicenter studies to confirm these findings. This episode offers an evidence-based look at how a simple extension of an existing therapy might reshape respiratory outcomes for preterm infants.

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This episode is part of a special three-part series on the use of CPAP, supported by Fisher & Paykel Healthcare. Their sponsorship makes possible the logistical production of this podcast series but does not involve curation, moderation, or influence over the content of the discussions.

Fisher & Paykel Healthcare offer a full neonatal care continuum which helps provide the best start possible to our precious babies worldwide.

Watch the design matters video series and discover what drives the innovation behind their neonatal interfaces https://www.fphcare.com/hospital/infant-respiratory/support/design-matters/

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Short Bio: Dr. Cindy McEvoy is a neonatologist and physician-scientist whose work centers on in-utero and early-life interventions designed to optimize fetal lung development and long-term childhood pulmonary function, particularly in the setting of adverse exposures such as maternal nicotine use, maternal obesity, and prematurity. She is widely recognized as an expert in neonatal and infant pulmonary function testing, the conduct of randomized clinical trials, and the retention of high-risk cohorts in longitudinal studies.

Dr. McEvoy earned her medical degree from Loyola University in 1995, followed by a pediatric residency at Kaiser Foundation Hospital in Los Angeles. She then completed a fellowship in neonatal-perinatal medicine at LAC-USC Medical Center. Early in her career, during her husband’s military service in Pensacola, Florida, she practiced in private neonatology and served as Medical Director of the Children’s Hospital at Sacred Heart Hospital.

Since joining Oregon Health & Science University (OHSU) in 2000, Dr. McEvoy has been an active clinician, educator, and leader in research. She currently serves as Director of Child Health Research for the Department of Pediatrics and Director of Neonatal Research in the Division of Neonatology at OHSU, while maintaining her clinical practice as a neonatologist.

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The articles covered on today’s episode of the podcast can be found here 👇

Extended Continuous Positive Airway Pressure in Preterm Infants Increases Lung Growth at 6 Months: A Randomized Controlled Trial.

McEvoy CT, MacDonald KD, Go MA, Milner K, Harris J, Schilling D, Olson M, Tiller C, Slaven JE, Bjerregaard J, Vu A, Martin A, Mamidi R, Schelonka RL, Morris CD, Tepper RS.Am J Respir Crit Care Med. 2025 Apr;211(4):610-618. doi: 10.1164/rccm.202411-2169OC.PMID: 39977011 Free PMC article. Clinical Trial.

Extending CPAP in stable preterm infants to increase lung growth and development as measured by pulmonary function testing.

Mamidi RR, McEvoy CT.Semin Perinatol. 2025 Aug;49(5):152059. doi: 10.1016/j.semperi.2025.152059. Epub 2025 Feb 28.PMID: 40023691 Review.

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The transcript of today's episode can be found below 👇

Ben Courchia: Hello, everybody. Welcome back to the Incubator Podcast. We are back this Sunday with a special interview, and we are joined in the Incubator studio by Dr. Cindy McEvoy. Dr. McEvoy, thank you for being on the podcast and joining us today.

Cindy McEvoy: Thank you so much for having me. I think this is a great opportunity to talk a little bit about CPAP and one of my recent studies.

Ben Courchia: I agree. Daphna is here with us as well. Daphna, good morning. How are you today?

Daphna: I’m doing well. We've both been looking forward to this episode, but I know in particular you have been looking forward to this episode.

Ben Courchia: Yeah, I've been looking forward to this episode number one because Dr. McEvoy has been on my short list of guests I wanted to have on. Then Hot Topics, I think, was the catalyst when we were able to sit down with you and talk a little bit about this. That was the activation energy I needed to send these emails and say, “OK, let's make this happen.”

Dr. McEvoy, for people who are not familiar with who you are: you're a practicing neonatologist. You serve as the director of child health research in the Department of Pediatrics, as well as the director of neonatal research within the neonatology division at OHSU. Your focus on in utero and early-life intervention is designed to maximize fetal lung volume and childhood pulmonary function, especially in the context of maternal substance use, maternal obesity, and prematurity. You’ve brought a wealth of expertise in neonatal and infant pulmonary function testing and in conducting randomized controlled trials.

We're excited to delve into your work about extending CPAP use in the NICU and its broader implications for neonatal care. You’ve written extensively about this topic. One of the earliest papers you wrote was published in 2020 in the Journal of Pediatrics called “The Effect of Extended Continuous Positive Airway Pressure on Changes in Lung Volumes in Stable Premature Infants.” You recently published in the ATS journal another study called “Extended Continuous Positive Airway Pressure and Preterm Infants: Increasing Lung Growth at Six Months, a Randomized Controlled Trial.” Before we begin diving into the studies themselves, can you tell us a little bit about the rationale for extending this intervention in particular? In medicine, if we can stop something, we often feel like we should stop it. So the idea of extending CPAP a little longer can seem counter to everything we were taught. Can you explain the physiologic reason behind this?

Cindy McEvoy: Yeah, that is a great question. And I agree, as neonatologists, when we come on service, we're always looking at how we can simplify care and how we can feel like we’ve made progress with our preterm infants. But if you really delve into it, the history of CPAP is very interesting. This started way back with Dr. Gregory in the 1970s for preterm infants. We know that putting patients on CPAP right after delivery is one of the most effective therapies we have to support lung volume, improve oxygenation, decrease apnea, avoid intubation, and decrease bronchopulmonary dysplasia. This is well established.

But the question of how long we should keep patients on CPAP is one we became very interested in about 10 years ago at OHSU. We reviewed our practices and realized we were all doing things differently when it came to taking patients off CPAP. As we delved into this more, we discovered a vast amount of literature on the potential physiologic benefits of keeping a patient on CPAP and providing mechanical distension. Various animal models show this promotes lung growth, blood vessel growth, and capillary growth. That was the impetus for the first study we published in 2020. We know that in utero, babies have fluid-filled lungs that cause mechanical distension all the way up to delivery. That’s important—consider, for example, oligohydramnios or congenital diaphragmatic hernia, where encroachment on the lungs impairs lung growth and development. So again, there is quite a bit of physiologic literature supporting mechanical stretch and its importance in promoting lung growth and development.

Ben Courchia: Yeah, in a recent article you published in Seminars in Perinatology called “Extending CPAP in Stable Preterm Infants to Increase Lung Growth,” you mentioned an example that should resonate with most of us—the prenatal management of congenital diaphragmatic hernia. By just keeping amniotic fluid in the lungs and preventing alveolar collapse, you can foster better lung development. So the idea of nurturing these mechanical stretch receptors through distension is a mechanism we know has worked in other settings as well.

Cindy McEvoy: Yes, and after a pneumonectomy, there’s also an increase in lung volume that can occur as compensation. Again, mechanical stretch forces are very powerful.

Ben Courchia: So the original study you published in 2020 was based on patients you recruited between 2014 and 2016. Can you tell us a little bit about this? The idea of extending CPAP makes sense, but one big question people have is: while a patient is on CPAP, what are the stability criteria? How do we assess that they’re doing okay on CPAP? And how did you decide who went into which category and whether CPAP was the adequate modality for their support?

Cindy McEvoy: When we did that study, we reviewed the literature and used respiratory stability criteria previously published in other studies on weaning CPAP. We looked at the infant's respiratory rate. We wanted them to be on CPAP +5 and 21% consistently. They had to be tolerating cares, which we did every three to four hours when we took patients off CPAP to check for nasal trauma. We also assessed retractions. So we had a set of respiratory stability criteria we used to decide when infants were stable and ready to be randomized in that initial trial. Those are the same criteria we used in our subsequent study.

Ben Courchia: That’s right. The stability criteria included CPAP of 4–5 cm of water, no oxygen requirement, respiratory rate under 70, a retraction score of one or less, fewer than three self-resolving apneic episodes, bradycardias, or desaturations per hour in the past six hours, and an average saturation above 86% for at least 90% of the time over the past 24 hours. They also could not be treated for PDA or sepsis, and they had to tolerate up to 15 minutes off CPAP during routine care.

While these might sound like stringent criteria, what it highlights is that when we’re talking about extended CPAP, we’re not talking about babies who need the support to survive. We’re talking about babies who could be weaned, but we make the conscious decision to extend the care for an additional two weeks.

Cindy McEvoy: Correct, we’re talking about stable preterm infants who are basically convalescing, or patients you would otherwise be considering for weaning. At the start of care, when we put CPAP on in the delivery room or immediately after birth, we’re really trying to support their FRC and stabilize them. But when they meet stability criteria, instead of stopping CPAP right away, we extended the therapy to promote lung growth.

Ben Courchia: One of the areas where you have a lot of expertise (and which is tied to the outcomes of these two studies) is the measurement of pulmonary function testing in these infants. For those of us who’ve had pulmonary function testing (I have asthma myself), the testing is quite different in babies. Or rather, we measure the same things, but the way infants undergo pulmonary function testing is very different from how adults do it. Can you explain what that looks like in the NICU?

Cindy McEvoy: Great question. I first became interested in this during my fellowship, where I was lucky to have a mentor trained in both neonatology and pediatric pulmonology. I had access to a pulmonary function machine and learned how to do testing in the nursery. Over time, I also learned how to do pulmonary function testing in infants, preschool, and school-aged children, because I’m very interested in looking at pulmonary function trajectories.

In the nursery and in infants, you obviously can’t tell them, “Take a deep breath and blow out as fast as you can” for forced expiratory blows. So the techniques are passive. Up to about 44 weeks corrected age, we can usually get the baby into quiet sleep. That’s what we want: controlled conditions, quiet, stable babies.

The main measurements we do in the nursery include flow-volume loops, which can provide a lot of important information, despite being challenging to obtain. We also measure passive mechanics: passive respiratory compliance and passive respiratory resistance. Again, the baby has to be quiet and not extremely tachypneic. This tells us how much volume we get per change in pressure.

We also measure lung volumes. In the nursery, that’s typically functional residual capacity (the amount of air in the lungs at the end of a normal expiration). We measure this using the nitrogen washout technique, giving them supplemental oxygen briefly to wash out nitrogen, which allows us to calculate lung volume. I’ve done this for a long time, so we get very reproducible numbers. We find it very useful, both for research and clinical care.

Daphna: Thank you for highlighting those parameters. I was also very interested in the respiratory questionnaires that you're administering. I think in the NICU at the bedside, we have this sense that these babies have a kind of reactive airway phenotype. So it was interesting to see how you all were assessing that over the first year, if I’m not mistaken.

Cindy McEvoy: Yeah, we did actually monthly questionnaires in our most recent study, and we based our questions on the ISAAC (International Study of Asthma and Allergies in Childhood) child and adult respiratory questionnaire. We asked parents about any new episodes of wheeze, any cough or colds, whether there was a healthcare provider diagnosis of wheeze, whether the baby was prescribed any medication (such as bronchodilators or corticosteroids), and whether they went to the emergency room.

As you’re mentioning, the phenotypes and endotypes of premature babies are still a very active area of investigation. We know all preterm infants, even those just less than 37 weeks, have altered lung development and are at risk for subsequent respiratory disease. There’s also good evidence that being preterm is a risk factor for developing chronic obstructive pulmonary disease later in life. Looking at the phenotypes, including whether there’s an atopic element, is important. We also asked about allergies in our questionnaires to fine-tune our understanding of premature infant phenotypes.

Ben Courchia: Talking about the intervention itself – you randomized babies in these two studies to either discontinuation of CPAP or extension of CPAP support for two weeks, up to discharge. I want to clarify something, because these two studies may sound like a continuation of one another, but they’re actually separate. The babies studied in the 2020 in Journal of Pediatrics paper were one cohort, and the more recent ATS Journal study represents another. Can you tell us a little bit about why they were separate? Was it necessity, tweaks in the protocol, or something else?

Cindy McEvoy: Great question. Our first study was more of a pilot feasibility study to see if we could consent subjects and randomize them to two extra weeks of CPAP. We based that on an animal study in ferrets, which showed that two weeks of CPAP significantly increased lung volume at the end of treatment. Other lung function tests didn’t change, which suggested true lung growth and parenchymal remodeling.

So we picked two weeks for our first study and used the same in our second. In that initial trial, we measured lung volume (functional residual capacity, or FRC) at randomization, after two weeks, and again before discharge. We found that the infants randomized to extended CPAP had significantly increased FRC at the end of the two weeks. And even after about two weeks after everyone was off CPAP, the patients who had gotten the extra CPAP had an even greater FRC compared to those that came off.

Unfortunately, since that was a pilot study, we couldn’t follow those patients after discharge. That led us to apply for NIH funding for a second study to see if the benefits persisted to six months, whether the lungs worked better, and to measure lung diffusion capacity, and airway function. That’s when we put in the second NIH grant to follow up these patients after discharge, as well as do those extra measurements.

Daphna: And in that first cohort, it wasn’t just that the lungs grew more and then stayed proportionally bigger than the early discontinuation group. It seemed like they kept growing even after CPAP was stopped, which is really cool.

Cindy McEvoy: Yes, exactly. That made us wonder whether genes are being turned on during that period, and whether there’s a critical post-menstrual age when providing extra mechanical stretch has broader effects on lung growth, development, and even possibly epigenetic changes that could impact other organ systems.

Ben Courchia: The difference was quite striking—about a 50% increase in FRC at two weeks, and 60% at discharge. Very pronounced.

I want to ask about practicalities and bedside translation. Speaking with colleagues, I sense more of them are extending CPAP in babies at high risk of chronic lung disease. Many are keeping babies on CPAP until about 32 weeks corrected. In your studies, the treatment allocation happened around 32 weeks on average. So what are your thoughts about keeping babies on CPAP until 32 weeks versus extending even further, say to 34 weeks? And what about the impact on feeding?

Cindy McEvoy: Great question. In both studies, babies met predefined stability criteria. In the first study, the average age was about 32 weeks; in the second, about 32.4. We randomized half to continue CPAP for about two more weeks, so they came off around 34 weeks. I can only speak to our single-center results (since we did sophisticated pulmonary function testing as our outcome), but in our studies extended CPAP improved pulmonary function without affecting time to first feed, time to full feeds, or length of stay. Of course, CPAP has to be delivered well. We used bubble CPAP and chin straps to optimize delivery and improve transpulmonary pressure. At 34 weeks, most of our infants weren’t yet showing readiness to nipple feed, so the extended CPAP didn’t really delay feeding.

I should also mention that we have a primate research center here in Oregon, so I collaborate a lot with one of my mentors out there, Dr. Spindle. We actually did a study randomizing preterm, non-human primates to bubble CPAP versus sham CPAP. It was just like a mini NICU out at the primate center. Half of the primates got the bubble CPAP for 12 hours a day, for nine days. The other half had the prongs in place, but did not get any CPAP. We can only do it for 12 hours a day because, unlike our little preterm babies, the preterm primates have long arms for a reason, which is that they were always pulling the CPAP out no matter how we tried to swaddle. And so we had to sedate them. so ethically, we know we only would sedate them for 12 hours a day. The CPAP group showed significantly more alveoli which we were able to count on stereology. There was also a trend for improved pulmonary function in those primates that got the extra CPAP, which didn't meet significance because of the numbers, but again, has a very strong translational premise, supporting the fact that CPAP improves lung growth and development.

Daphna: Thank you. I wanted to ask more about feeding. First, you mentioned using chin straps routinely. One concern people have is CPAP belly and whether it interferes with feeding tolerance. What did you see in your studies?

Cindy McEvoy: We monitored for adverse events, including feeding intolerance, and found no differences between groups. A former fellow and now junior faculty also analyzed granular pulse oximetry data from 30 patients during feeds, that was blinded to the nurses. So we were able to really quantify very carefully the episodes of hypoxemia that the patients were having.

She looked at these episodes before feeds, during feeds, and after feeds between the two groups of patients. Interestingly enough, the patients who stayed on CPAP during and after their feeds actually had less of the episodes of intermittent hypoxemia (we picked saturation <90% for at least 10 seconds, because that was the primary outcome from the Pre-Vent study that correlated with subsequent neurodevelopmental outcomes). We were very interested to see that staying on CPAP, patients who stayed on CPAP actually had less of these episodes. I think that dismisses kind of one of the old wives’ tales that it increases episodes of intermittent hypoxemia or desaturations.

Daphna: And in your unit, if babies are still on CPAP but showing feeding readiness, do you attempt feeding on CPAP?

Cindy McEvoy: Currently, we don’t routinely feed on CPAP, though some units do. We’re discussing whether to adopt it. If an infant is on extended CPAP for lung promotion but is clearly ready to feed, we will attempt feeding.

Ben Courchia: Very interesting. Dr. McEvoy, looking at your recent ATS Journal study, what were the main takeaways now that you’ve doubled the sample size compared to your 2020 study and followed infants longer?

Cindy McEvoy: I’m very proud of this study, especially since it was done during COVID. We met our sample size and found that babies given two extra weeks of CPAP had increased alveolar volume, improved lung diffusion capacity, and better forced expiratory flows at six months. So both parenchymal and airway function was improved.

Respiratory questionnaires showed less wheeze, though not statistically significant since we weren’t powered for that outcome.

I'm very interested in looking at lung function trajectories and early interventions we can do to help improve where an infant sits on their pulmonary function curve. Because if you start lower, you tend to stay lower on your pulmonary function curve, and you tend to be more prone to respiratory disease as you age. So if we can bump that up initially, hopefully we can improve their lifelong lung function outcomes and respiratory outcomes. I'm hoping to continue to follow these patients so we can do continued follow-up of their pulmonary function and we can see if these benefits persist, in terms of their force expiratory blows. So if you take a deep breath in and breathe out as fast as you can, that is linked to wheeze and potentially subsequent chronic obstructive pulmonary disease.

We're also very interested not only in getting a physiologic outcome, but potentially doing a low dose CT scan so we can actually quantify their airways and quantify their lung volume. We always say a picture is worth a thousand words. That would be very supportive of where we're actually able to show structural improvements.

We also want to look at trying to endotype them to see if we can determine do they have reactive airway disease or something else that causes them to have increased respiratory disease? That way we could come up with a more personalized approach.

That's the thought we have with this current cohort, but of course this is a single center study. We're very optimistic about these initial results, but I think a larger pragmatic study is needed to see if these results are generalizable. We wanted to have about 50% of our patients be less than 29 weeks that were randomized and half be 29 to less than 33 weeks. But the smaller patients didn't meet the respiratory stability criteria we had outlined before our cutoff, which we had set at, 35 weeks of post-memorial age. So I think a larger study where that would be able to recruit potentially smaller patients to also see the impact of extended CPAP on their course in the nursery, but also longer term is needed.

Ben Courchia: Talking about pictures being worth a thousand words, I want to commend you on the figures in all three papers. Beautifully done.

Practically speaking, what advice do you have for units considering implementation? How do you bring everyone on board and address skepticism?

Cindy McEvoy: I think it comes back to physiology and presenting the literature. When I spoke to parents, I would explain that in utero, lungs are fluid-filled and distended, which promotes development. Extended CPAP mimics that environment.

Success requires involving all stakeholders—research staff, parents, physicians, and bedside caregivers. Education, encouragement, and a well-planned rollout are key.

Daphna: Yes, and the breadth of respiratory parameters in your studies is so valuable for the community. My last question is: is two weeks enough? Do we know if there’s a fall-off point when benefit no longer increases?

Cindy McEvoy: Great question, I'm not sure we know. That requires more study about the duration and optimal post-menstrual age that it's administered. Endotyping patients who might respond best to the therapy and the intervention could help us determine what the optimal duration should be.

Ben Courchia: Dr. McEvoy, thank you so much for joining us and sharing your insights from these beautifully designed studies. Any final thoughts for our listeners?

Cindy McEvoy: I encourage everyone to find a passion. I really enjoy clinical translational research, and I think so important to take things from the bench to the bedside so we can really directly impact patient care. Creating the paradigm in your nursery, or wherever your healthcare setting is, of involving the parents as shareholders in the study and getting them excited about participating in these type of trials is key so we can make progress.

Ben Courchia: That’s a wonderful piece of advice. Sometimes going back to physiology is what leads to breakthroughs in clinical care.

Cindy McEvoy: And sometimes the simplest breakthroughs, like extending a therapy we already use, are the most powerful.

Ben Courchia: I agree. Thank you again for your time and congratulations on this important body of work.