As always, feel free to send us questions, comments, or suggestions to our email: nicupodcast@gmail.com. You can also contact the show through Instagram or Twitter, @nicupodcast. Or contact Ben and Daphna directly via their Twitter profiles: @drnicu and @doctordaphnamd. The papers discussed in today's episode are listed and timestamped on the webpage linked below.
As always, feel free to send us questions, comments, or suggestions to our email: nicupodcast@gmail.com. You can also contact the show through Instagram or Twitter, @nicupodcast. Or contact Ben and Daphna directly via their Twitter profiles: @drnicu and @doctordaphnamd. The papers discussed in today's episode are listed and timestamped on the webpage linked below.
Enjoy!
Speaker 1:
Okay, I had a paper. I'm going to see how much time we have. Okay, I had a paper. It's called Developmental Consequences of Short Apneas and Periodic Breathing and Preterm Infants. The lead author, alicia Yee. This is in the Journal of Perinatology.
Speaker 1:
The question really was do respiratory events predict developmental outcomes at six months of age? So they included infants born between 28 to 32 weeks of gestational age recruited between March 2018 and July 2021. And basically what they did is they studied infants longitudinally using a sleep study basically, which is exceedingly difficult to do in patient in US NICUs, but these were done in Melbourne, so they had access to all those things. So they were studied longitudinally on four occasions at 32 to 36 weeks post-menstrual age, at 36 to 40 weeks, either in-house or back in their follow-up that they had been discharged at three and in six months post-term corrected age. And then they were seen either in the sleep center or in their own home, because this was during the COVID pandemic. So, at each of the four sleep studies, physiologic recordings made during two to three hours of daytime sleep in the supine position, and then all of the babies well, most of the babies at six months corrected age, underwent developmental assessments and using the Bailey 3. The exclusion criteria they did not recruit infants who continued to require ventilatory support or oxygen therapy, which I thought was interesting because the first evaluation was at 32 to 36 weeks. So just know that, because they didn't want to use any confounding effect of lung pathology or chronic lung disease, they were not recruited. If they were growth restricted, they had major congenital anomalies, major intracranial abnormalities or significant intraventricular hemorrhage, they excluded grades three and four. Or if they had a hemodynamically significant PDA, because the known independent effects on nerve development, they did not define what they considered hemodynamically significant PDA.
Speaker 1:
So for the baseline characteristics it was a small study, 40 infants were recruited. Many were lost to follow-up, in particular given the COVID precautions after discharge, 26 completed sleep studies and developmental studies. Okay, they had a median gestational age at birth of 30 weeks, a median birth weight of 1.4 kilos, infant apcar scores, median of 7 at 1 minute and a median of 9 at 5 minutes. Other things about the infants they were all administered caffeine after birth and 35% were still on caffeine treatment at the time of study. One which was again between 32 and 36 weeks post-menstrual age Infants on caffeine at the time of the first study had a median caffeine dose of 8.6 milligrams per kilogram. And all infants completed at least three of the four sleep studies for evaluation.
Speaker 1:
Okay, so what did they find on the sleep studies? All infants experienced isolated apneas up to three months corrected age, and this fell to 92% at six months corrected age. But the isolated apnea definition? They used a respiratory cessation, either central or obstructive, lasting greater than or equal to three seconds. Okay, in contrast, sequential apneas, which they defined as two sequential central apneas separated by normal breathing, lasting less than or equal to 20 seconds. So two periods of apnea that were greater than or equal to three seconds, but separated by a brief interruption of normal breathing, were reduced to 63% at three months and below 40% at six months. So you see an improvement over time. They also documented periodic breathing. So periodic breathing that was defined as three or more sequential central apneas lasting greater than or equal to three seconds, interrupted by normal breathing lasting less than or equal to 20 seconds. So these were reduced to 63% percent, I'm sorry, reduced to 47% at three months and below 40% at six months. But all babies, many babies, continued to have these brief apneas even at six months.
Speaker 1:
Periodic breathing occupied a median of 8.5% of the total sleep time at 32 to 36 weeks post menstrual age and 6.8% at 36 to 40 weeks post menstrual age, while the isolated apneas and sequential apneas occupied less than 5% of total sleep time at all ages. They also looked at what happened, what other physiologic things were happening with these brief respiratory events. Falls in heart rate during respiratory events increased with increasing age, which was interesting. In contrast, the falls in SPO2 decreased with increasing age, with falls in SPO2 at three to six months, corrected age, being significantly less when compared to falls at 32 to 36 weeks post menstrual age. So less dips in the oxygen saturation, but they did have more dips in the heart rate during these respiratory events At all ages. The median group average time spent with sats less than 90% was less than 1% of total sleep time. However, there was much individual variability, so some babies spent much more time less than 90%. The median group average time spent with a tissue oxygenation index less than 55% was less than or equal to 1% of total sleep time, with the majority of this time being during the periodic breathing type events again, a wide variability between infants.
Speaker 1:
So then they looked at the six months post menstrual age Bailey. Three infants had immediate cognitive composite score of 100, a language compositive score of 100, motor composite score of 99, social emotional composite score of 100 and adaptive behavior score of 103. All infants scored greater than 85 in the cognition and adaptive behavior domains. One infant scored less than 85 in the language domain, for infant scored less than 85 in the motor domain and three infants scored less than 85 in the social emotional domain. But then they looked at what was predictive of the Bailey scores. Interestingly, in this little group, gestational age, sex and birth weight were not predictive of Bailey three scores.
Speaker 1:
Percent total sleep time with all the respiratory events combined and the percent total sleep time spent in periodic breathing at the term corrected age 36 to 40 weeks were significant predictors of language and motor outcomes.
Speaker 1:
At the six month corrected age, percent total sleep time events and percent total sleep time in the periodic breathing at 32 to 36 weeks, post menstrual age at three months and six months were not associated with any of the Bailey three domains and percent total sleep time in isolated apnea or the sequential apneas were not associated with any of the Bailey three domains. There's no association between the percent change in saturation or the tissue oxygenation index during respiratory events and the Bailey three outcomes. They also looked at a bunch of measures of infant temperament which are interesting other findings but their overall conclusion is that more time spent in respiratory events, particularly these kind of periodic breathing, predicted outcomes at this six month mark. I thought that was interesting because in general I feel like in the unit when babies have these little dips we tell parents oh, they're just little dips. We're really worried about the frequent prolonged dips, not these quick brief dips that babies have, but potentially they add up over time. Thoughts.
Speaker 2:
Well, it's an interesting study. I'm wondering what do we take, practically speaking, back to the bedside, because I think every time a baby leaves our unit on oxygen, you're like man. Did we not try hard enough to get this baby?
Speaker 1:
off oxygen.
Speaker 2:
But then you read a study like this and you wonder maybe we should send more babies on oxygen. I mean, what is the Russian trying to get these kids off oxygen as early as possible if there are going to be long term consequences to having even slight little events during sleep? I think it's a double-edged sword. I mean, I don't really know what the right answer is but yeah, it's always.
Speaker 1:
And you know there are some babies who you take off oxygen, but they're really just making it right.
Speaker 2:
They're really just making it. We always tell the parents your baby has been on some form of respiratory support since birth. It's now five months old. We're going to take your kid off and we're going to wait five days, and if everything is good after five days, you're going to go home. How predictive is that? And are we? Yeah, I don't know. I don't know what the answer to that is. And you compound that with how difficult it is to have oxygen at home, and so on and so forth, it's even makes things more complicated.
Speaker 1:
And to that point I wanted to mention two other quick articles. One is an actual study etiology and mechanism of intermittent hypoxemia episodes and spontaneous breathing extremely preterm infants in the Journal of Pediatrics. Lead author Dr Mishian, with Dr Banklari's group here in Miami and they really wanted to look at the causes behind these intermittent hypoxemia episodes and their conclusion was actually that maybe we've been wrong about the mechanism associated with these intermittent hypoxemia episodes. You know, we think it's mostly related to things like apnea, prematurity, where there's something wrong with, kind of there's something immature about the breathing center. But actually they were talking about that in this group of premature infants, the predominant mechanism associated with the daytime IH or intermittent hypoxemic episodes was this active exhalation and breath holding physiology.
Speaker 1:
There's also in the Journal of Pediatrics this editorial entitled Rethinking the Pathophysiology of Cardio-Respatory Events in Infants Born Preterm, and I guess the reason I'm highlighting these is, you know, when we study it for the boards, like what is apnea, prematurity? Why do the babies have all these events? There's still a lot of stuff we don't know and I feel like for trainees you feel like, oh, pulmonary is kind of we know everything we need to know pulmonary in the NICU, but that is like not the case, and so I think there's just so much opportunity for more exploration here, so I just wanted to bring people's attention to that.
