I have published two articles that looked a the relationship between apneas and long term outcome. One was taken from pre-discharge recordings of very preterm babies. We compared the long term neurodevelopmental abilities of preterm babies 18 months later, and compared them to the pattern of apneas that babies, who were ready to be discharged, had on their recordings.

Infants with the more severe apneas had worse outcomes at long term.

Another study examined the number of days that apnea was recorded by the bedside nurse in the hospital chart, and again compared this to long term outcomes. There was a significant correlation, the more days of apnea, the worse the outcomes.

Quantifying apnea from hospital charts is fraught with risk. Many apneas are not noticed by the bedside nurse, especially obstructive apneas; overall about half of apneas are not noted in the charts. That is the reason we decided not to try to count apneas in the CAP trial, the only really reliable method is continuous recordings, which are then analyzed objectively.

Nevertheless, it is probably true that there is a correlation between the apneas recorded in the chart and the true number of apneas that a baby has had. The more ticks in the chart, the more apneas the baby had, probably.

So as a sort of surrogate of  true apnea incidence the number of recorded apneas, or the number of days of apnea, as we studied, is probably of some value.

A newly published study compared the total numbers and severity of bradycardia of apneas as derived from the hospital charts, as well as whether they received stimulation or vigorous stimulation, of extremely low birth weight babies, and their neurodevelopmental outcomes, using the Bayley 3 scales. They found worse language development in infants who had more severe, or more frequent apnea, at 8 months corrected, and at 20 months corrected age. From what I can tell, the authors did a large number of regression analyses, which makes a type 1 error more likely, nevertheless, the results are in the same direction as my older studies, as well as others by Pillekamp et al, and the CHIME study group. CHIME showed that both preterm and preterm babies who had serious apneas at home, had worse developmental outcomes.

Why this might be is presumably related to the frequent hypoxia/re-oxygenation episodes preterm infants experience, episodes which are less frequent with caffeine. This is presumably the reason for the beneficial effects of caffeine (even though other effects, on inflammation, for example, have been shown also.)

One other thing which I noticed previously, and have published 2 abstracts about, is that it is not rare, after an apnea, for a baby to become hyperoxic. I noted that some babies who had an average saturation in the low 90’s before an apnea, would oversaturate after they started breathing again. Although there are one or two possible reasons for this, I thought that some of it, at least, was probably due to caregivers increasing the FiO2 when the baby desaturated. From my data I wasn’t able to be sure, as I didn’t have a record of the oxygen concentration being administered, which is why I never proceeded to produce a full publication. And now I have been beaten to it!

In a study from Leiden the authors analyzed recordings of babies on CPAP who developed apnea, and noted whether they had an increase in SpO2, and whether the FiO2 had been changed around the episode. They found that FiO2 was increased around 11% of the apneas, and when that happened a large majority of the time (79%), the babies became hyperoxic (SpO2>95%) after the apnea, this lasted for an average of 13 minutes! The authors don’t tell us, I think, what happened to post-apneic hyperoxia if there was no change in FiO2, how common it was if the FiO2 was unchanged isn’t described.

It clearly doesn’t help to increase FiO2 if the baby is not breathing. Few of these apneas were likely to have been obstructive, as the babies were on CPAP, so oxygen was increased probably either when the baby was apneic, or afterward during the recovery phase. I guess that most often it was probably when the SpO2 wasn’t coming up as quickly as the nurse expected, so she(he) increased the oxygen, and then took on average 14 minutes to get it back down to the previous concentration.

One thing that I think is surprising is that we have no idea how to treat apneas. We have some idea how to prevent apneas, using caffeine, and CPAP, (I won’t discuss doxapram for the moment).

But when a baby stops breathing, how should we intervene to get him/her breathing again? What usually happens is that the baby is first stimulated (does this work? if so, how? what kind of stimulation works best?) and then, if still apneic, a variety of other interventions may be tried, including repositioning, suctioning, more vigorous stimulation, assisted ventilation, and increasing oxygen concentrations. Do any of these actually work? Which is best? This is one of the commonest interventions in the NICU, something done many times a day, but we have no idea what is the best approach.

I have a design written for a trial of ‘usual therapy’ compared to what I think might be optimal, that is, keeping a self-inflating bag next to the baby, in the same FiO2 as the baby is receiving, and immediately starting positive pressure ventilation. I think that only a couple of breaths would be required for most babies, that this might reduce post-apneic hyperoxia. Certainly some way of deciding how long to wait before increasing the FiO2 of a baby would be really useful.