#447 - [Journal Club] - 📌 Does Extended CPAP Reduce Intermittent Hypoxemia in Stable Preterm Infants?

What happens to intermittent hypoxemia when you keep a stable preterm infant on CPAP for two extra weeks? In this Journal Club episode, Ben and Daphna review a secondary analysis from the Journal of Pediatrics by Mamidi and McEvoy. Among 95 infants randomized to either two additional weeks of bubble CPAP on room air or discontinued CPAP, those in the extended CPAP group experienced significantly fewer intermittent hypoxemia episodes (57.6 versus 151.7), higher baseline saturations, and greater functional residual capacity. The episode also touches on the practical implications for units navigating oral feeding protocols alongside extended CPAP.

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Extended Continuous Positive Airway Pressure in Infants Born Preterm Decreases Intermittent Hypoxemia: A Secondary Analysis of a Randomized Controlled Trial. Mamidi RR, Go MDA, Harris J, Olson M, Milner K, Tepper RS, Morris C, Park B, Schelonka R, MacDonald KD, McEvoy CT.J Pediatr. 2026 May 25:115165. doi: 10.1016/j.jpeds.2026.115165. Online ahead of print.PMID: 42190903

Transcript

[00:00] Ben Courchia, MD: Hello everybody, welcome back to the Incubator Podcast Journal Club. We're back today for another episode. Daphna, how are you?

[00:07] Daphna Barbeau: Doing well. Journal Club is invigorating me like it always does.

[00:12] Ben Courchia, MD: Yeah. Casey Neistat, a YouTuber I really enjoy watching, once said that success doesn't matter to him — not in a condescending way, but meaning he'd keep doing what he does because he genuinely enjoys it. I feel the same way about Journal Club. I'll keep doing this as long as we can.

[00:36] Daphna Barbeau: Whoever wants to hang out with us.

[00:38] Ben Courchia, MD: Yeah, because it's really enjoyable to review the evidence. It's really fun.

[00:46] Daphna Barbeau: It's been really fun when something's happening in the unit and one of our nurses will say, "Well, actually, I was just listening and..." and you're like, "Well, Ben reviewed that paper, you're going to have to... I don't remember. So let's talk about it."

[01:01] Ben Courchia, MD: Today I'm reviewing something that has gained a lot of traction on our website. In the Journal of Pediatrics, there's a paper by Rachna Mamidi, last author Cindy McEvoy, titled "Extended Continuous Positive Airway Pressure in Infants Born Preterm Decreases Intermittent Hypoxemia: A Secondary Analysis of a Randomized Controlled Trial." We recorded with Dr. McEvoy a while back to discuss her work on extended CPAP — that's episode 346, and it's one of the most visited pages on our website. And while we're on the topic of extended CPAP, I want to bring attention again to a documentary published by my good friend Dr. Guilherme Santana from Montreal Children's, who is now also a colleague of mine since I've been doing hemodynamics over there. It's about the history of bubble CPAP and the Columbia approach. It's a great documentary, very professionally produced, watches like a movie. It walks you through the history of CPAP, how we arrived at bubble CPAP, and references Dr. McEvoy's work on extending CPAP for better lung function at discharge. You can find it on YouTube by searching "Bubble CPAP and the Columbia Approach." One more thing: you always hear about the Columbia approach, but you hear less about Dr. Wong, who is a very private person. He's prominently featured in this documentary and gets to explain how he came up with bubble CPAP. Worth watching.

[03:39] Daphna Barbeau: Yeah, it's so important to know where we came from. Thank you for sharing it.

[03:46] Ben Courchia, MD: All right. So the background of this paper is interesting. Among preterm infants in the NICU, episodes of intermittent hypoxemia are common, multifactorial, difficult to prevent, and importantly, associated with adverse outcomes down the road. What remains fascinating is that there is still no consensus regarding the saturation threshold and duration that constitutes a clinically significant intermittent hypoxia event. If your unit targets 88% saturations, that might be considered a desaturation in our unit. That variability still exists today on such a fundamental question. In a prior randomized controlled trial, Dr. McEvoy's group demonstrated that among preterm infants who met respiratory stability criteria including breathing room air, extending CPAP therapy by an additional two weeks compared to discontinuation resulted in higher functional residual capacity (FRC) when evaluated in the NICU after extended CPAP was stopped. That intervention also resulted in improved lung growth assessed during infancy following NICU discharge. The hypothesis for this particular secondary analysis was that infants randomized to extended CPAP, compared to those who had CPAP discontinued, would have fewer episodes of intermittent hypoxemia and significantly higher saturations during the two-week treatment period.

[05:30] Ben Courchia, MD: This is a single-center, prospective, pre-specified secondary analysis using physiologic pulse oximetry data collected as part of the NHLBI-funded Extending CPAP Therapy in Stable Preterm Infants to Increase Lung Growth and Function randomized clinical trial. The trial included infants born between 24 and 32 weeks gestation who required CPAP for more than 24 hours and met specific respiratory stability criteria: for more than 12 hours at less than 35 weeks, they were on Hudson prongs with a chin strap. CPAP was exclusively administered using bubble CPAP. There was no standardized supplemental oxygen protocol; oxygen could be administered at the discretion of the clinical team. Infants were stratified by gestational age and randomized to 14 days of extended CPAP or discontinued CPAP on unassisted room air. Of the 100 randomized infants, 95 met the pre-specified inclusion criterion of having pulse oximetry data available for more than 75% of the extended period, consistent with prior published studies, and were included in the analysis: 50 in the extended CPAP group and 45 in the discontinued CPAP group. During the 14-day randomization period, a second pulse oximeter with a two-second sampling rate was placed on each infant with alarms silenced and the display concealed. This was an important methodological decision: as a single-center study, the unit had specific saturation targets, and this additional pulse oximeter allowed faster data averaging and enabled the team to evaluate different thresholds. Bedside caregivers responded to intermittent hypoxia and apnea episodes according to standard NICU practices, including airway repositioning and escalating tactile stimulation for apneas greater than 20 seconds, or shorter apneas associated with bradycardia or desaturation. Desaturation in their unit was defined as less than 88%. In the discontinued CPAP group, intermittent hypoxia episodes alone did not trigger a return to CPAP; supplemental oxygen was permitted per clinical guidelines if saturations remained low. Infants with clinically significant intermittent hypoxia who also met additional failure criteria — increased work of breathing, tachypnea, or increased apnea — were placed back on CPAP. FRC was measured prior to randomization and at the end of the two-week treatment period using a nitrogen washout technique. The predefined primary outcome was the number of intermittent hypoxia episodes with saturations below 90% lasting 10 to 300 seconds during the 14-day treatment period. This is where the second pulse oximeter was particularly useful: for the purposes of this study, hypoxia was defined as below 90%, a threshold below which the clinical team would not have intervened anyway given their unit's targets. A clever methodological workaround.

[09:44] Ben Courchia, MD: Results. Clinical characteristics between the groups were comparable and demographics were similar between the overall randomized cohort and the 95 included patients. For the primary outcome, infants in the extended CPAP group had significantly fewer episodes of intermittent hypoxemia with saturations below 90% compared to the discontinued group. Want to guess the numbers?

[09:51] Daphna Barbeau: I have it pulled up right here, go ahead and tell the people.

[09:56] Ben Courchia, MD: 57.6 events in the extended CPAP group compared to 151.7 in the discontinued group, with an adjusted difference of negative 94.1. Statistically significant, with confidence intervals from minus 132 to minus 56.

[10:14] Daphna Barbeau: That's almost double.

[10:21] Ben Courchia, MD: Secondary outcomes showed that the extended CPAP group experienced significantly fewer standardized episodes of intermittent hypoxemia across all thresholds and durations assessed. Despite both groups requiring no supplemental oxygen, the extended CPAP group had significantly higher mean saturations on room air: 95.9% versus 94.7%, statistically significant. I also want to mention that in our unit we extend CPAP until 32 weeks, but the enrollment data shows that these were quite mature babies, extended all the way to 34 or 35 weeks. Infants randomized to extended CPAP also had significantly increased FRC at the end of the two-week treatment period compared to the discontinued group. There was a statistically significant negative correlation between intermittent hypoxemia counts and increasing FRC per kg on day 14: the more intermittent hypoxemia events, the lower the FRC. There was also a significant treatment effect, with the extended CPAP group shifted toward higher FRC and lower intermittent hypoxemia. The authors also explored the mechanism: since extended CPAP demonstrated increased FRC, decreased intermittent hypoxemia, and increased baseline saturations, they wanted to evaluate whether the treatment effect on intermittent hypoxemia was mediated through the saturation effect. They found that a large portion of the effect on decreasing intermittent hypoxemia was indeed mediated through the increase in saturations. That said, there remained a significant direct effect of extended CPAP on decreasing intermittent hypoxemia independent of that saturation increase. In conclusion, the authors state that among stable preterm infants treated with nasal CPAP in the NICU, extending CPAP for two weeks on room air significantly reduced the number and duration of intermittent hypoxemia episodes compared to unsupported room air. These findings highlight a potentially important benefit of extended CPAP for stable, convalescent preterm infants to reduce intermittent hypoxemia and potentially improve outcomes. A simple, non-pharmacologic approach — though further studies are necessary. Strategies aimed at limiting intermittent hypoxemia could potentially alleviate common morbidities associated with prematurity. Very interesting study. The gift that keeps on giving. Daphna, any thoughts?

[13:52] Daphna Barbeau: I think the key take-home for me was that we thought we were already doing extended CPAP by keeping kids to 32 weeks. But this is kids kept an additional two weeks beyond when someone would have taken them off based on their respiratory scores. For some kids that's 33 weeks, some 34 weeks, some potentially longer.

[14:21] Ben Courchia, MD: And that's where I have some concern, because unit practices play a huge role here. There is data to support feeding babies on CPAP, and if you're a unit that's comfortable doing that, this data is very relevant. But if you're a unit like ours, where the reluctance is to feed babies by mouth while on CPAP, then extending to 34 weeks raises real questions.

[14:46] Daphna Barbeau: Don't get me started. You know how I feel about that.

[14:51] Ben Courchia, MD: I know. But the concern is real: if I were implementing this somewhere, it would have to go hand in hand with a feeding protocol so you don't miss that developmental window for oral skills. That's not a critique of the paper — that's not the point of the study. But it's one of the unintended consequences to consider when implementing certain interventions.

[15:56] Daphna Barbeau: And we discussed this with Dr. McEvoy. Was there a longer time to full oral feeds? Her answer was no. And part of that is because many units don't even start oral feeds until after 34 weeks anyway. So there's still room to play. And it doesn't have to be all or nothing. Maybe we go to 33 weeks instead of 32.

[16:20] Ben Courchia, MD: For sure. And I also want to say that the data does support feeding on CPAP. It's just a significant cultural shift. Easier said than done.

[16:37] Daphna Barbeau: Well, thank you for highlighting that.

[16:39] Ben Courchia, MD: All right, see you tomorrow.