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:
But it's basically an article called the irritable infant in the neonatal intensive care unit. Risk factors and biomarkers of gastroesophageal reflux disease.
Speaker 2:
I thought this was a very interesting title. It really grabbed my attention. Yeah, I definitely learned more about it.
Speaker 1:
They definitely gave some thoughts to to that title and, yeah, we're, we're thankful for that. The first author is Mina Najé, I think is how we pronounce it, and this is a paper out of the US, so the introduction is actually quite interesting, and I think, if you have some confusion about what is it, again that we are considering disease versus not disease. I think it's a good review. They mentioned how gastroesophageal reflux is not gastroesophageal reflux disease, that GER is physiologic and that when symptoms occurred, then we talk about GERD with a D at the end. Now they do acknowledge, though, that the definition is the definition of like troublesome symptoms is kind of unclear.
Speaker 1:
We're challenged to diagnose, to prescribe therapies for what we perceive to be reflux disease, and we're not always sure whether what we're seeing at the bedside is actually correlated with the pathology itself. They're talking about how empiric prescriptions are a cause for concern there's been a lot of articles about that as the true origin of the infant symptoms are left unaddressed and the medications can have adverse consequential effects. When we give medications for acid suppression, it increases risks of infection and so on. So there's definitely a concern there and could eventually also prolong hospital stay and increase economic burden. Now one of the symptoms that is very frequently reported is arching and irritability, and these are somatic signs, basically, where you have back arching that involves extension of the neck and is often accompanied by fussiness or crying, making it the patient is trying making the infant a periodable something we've all seen in the neck and had to address. Now a few of the international association, naspgan and ESPGAN, the North American and European societies, along with other recent report, have recommended the use of a pH impedance testing for further clarification and identification of potential mechanism of symptoms associated with gastro-sophageal reflux disease, and that really is a key, because that's really how you should be diagnosing GERD, and so it's not. If your institution has access to a gastroenterology team, to pH impedance testing, then that's great, but for many that is not a possibility, and so the aim of this study, what they're then trying to show because of that, is that to basically the goal is to examine the potential risk factors, comorbidities and the reflexates characteristic in relation to arching and irritability and the clinical outcomes among infants. So trying to see a little bit if, how does how do the symptoms that we observe at the bedside correlate with the diagnosis as it is made per the recommendation of these organizations.
Speaker 1:
So the study design is basically the following they took data from 24-hour PH impedance studies that were analyzed retrospectively from patients and infants that were hospitalized in the NICU who were referred to the infant feeding program at Nationwide Children's Hospital for the evaluation of GERD. So I kind of like the sampling bias here, because these are the babies that people were super concerned about. So when I started reading this I'm like, oh boy, these are all going to have reflux. The inclusion criteria that babies were included if they underwent 24-hour PH impedance testing between June 2012 and June 2020, with more than 18 hours of analyzable PH impedance data and values for acid reflux index, ARI, number of reflux events, distal baseline impedance and symptom associated probabilities that were recorded. They excluded infants if they had a postmenstrual age that was above 52 weeks or if these kids were already on a proton pump inhibitor at evaluation and if the one-year outcomes could not be obtained. So what was the intervention? I mean this is like the GERD referral center, so top notch level stuff.
Speaker 1:
The infants underwent 24-hour PH impedance testing using a disposable PH impedance probe with six impedance channels and one distal PH sensor. So for those of us who need a bit of reminders and who are studying for the board. As we are diagnosing gastro-sophageal reflux disease, there are those two things PH impedance testing. You have PH probe where you could just look at the change in PH in the esophagus to see and document reflux, which is not ideal because a lot of the time the reflux in these neonates is not acidic. But you then have impedance testing which looks at the difference in resistance along the esophagus and then that could be diagnostic. So in this case they were using both, so they had PH impedance probe. So very sophisticated.
Speaker 2:
That was a prep question. That's right yeah.
Speaker 1:
So that was very thorough. They defined frequent arching and irritability as more than 72 events in the 24-hour PH impedance study. So I was like that is intense 72 documented events of arching and irritability and the bottom line is that they conducted studies that allowed them to use this cutoff of 72. But what's interesting, obviously, as you're starting to gather, is that it seems like this sample is being selected to really include the most high-risk kits, the one that are being referred, the one that have over 72 events of arching and irritability, and I think, despite all that, we'll be very surprised with the results. They looked at a variety of different clinical outcomes and, in terms of outcome definition, I think that's important because they defined something called acid-girr and bolus-girr, as we were saying. So acid-girr means that when they were doing the PH impedance testing, the PH did was there was any drop in pH less than four to less than four for more than five seconds. And then you had bolus-girr, which were defined as retrograde movement of a bolus, shown by a 50% drop in impedance, beginning in the Z6 channel and reaching at least one channel above. So obviously, if you imagine the probe, it has these different channels and obviously it has to be measured across two different channels to show that it actually moved from one to the next. In terms of the acid reflux index, that was analyzed as the percent of time in the 24-hour PH impedance study in which the esophagus was exposed to acid. Acid-girr was defined as an acid reflux index of more than 7%, as per published guideline, and detailed characteristic of acid exposure events per day were examined. So I'm not going to bore you more with the methods. As you can see, I hope that you gathered that this was a very thoroughly done study. I was trying to read the method and try to poke holes at let's see where this is going to unravel, but this was rigorous methodology. 516 infants born at a median age of 30 weeks were evaluated at a median postmenstrual age of about 42 weeks using the PH impedance methods, and they had data from 10,000 hours of recording.
Speaker 1:
Now, figure 1 shows the possible combination of arching slash irritability events and bolus reflux events on pH impedance. So listen to this, davna 11% of arching and irritability events were associated with bolus reflux. So 11%. I would have expected a much higher number. Now, talking about acid reflux, arching irritability events show the sensitivity of 8%, the specificity in not detecting acid reflux or arching irritability was 94%. The positive predictive value for arching and irritability was 17%, for bolus reflux, 16% for acid reflux, with negative predictive values of 87% for acid reflux and bolus reflux, which is nuts, basically. So to me, if a baby has a bit of a spit up, it's one thing, but if they have arching irritability I'm like, oh, they're symptomatic. But it almost reminds me of when we started realizing that our assessment of clinical seizures is not helpful. It's one of these things where it's quite impressive. I'm going to give you a few more results and then we can discuss this a bit further. No difference were observed in the frequency of distal or proximal reflux rate per day. So again, nothing really there to grab onto.
Speaker 1:
Adjusted comparison for GERD biomarkers and the prevalence of clinical characteristics were performed. These were shown in Figure 2, and I think Figure 2 is quite interesting. What they showed was that there's no acid GERD biomarkers that were attributed to frequent arching and irritability. I think I have that figure here, so I think that's already. Quite. Let me see there right here. I think that's quite interesting.
Speaker 1:
Infants with positive symptom correlation to bolus GERD, with any symptom or signs, were more likely to have frequent arching and irritability event. So now we're seeing a little bit of this relationship where arching and irritability are not necessarily symptoms that could help you specifically diagnose gaseous esophageal reflux disease. However, when they did have confirmed GERD, then you did see arching and irritability. Infants comorbidities associated with frequent arching and irritability were preterm birth, morally feeding at evaluation, moderate or severe neuropathology and chronic lung disease. So probably some of these medically complex infants. The Conclusions of the paper are that from these 500 then change infants referred for GERD confirm that acid gastroesophageal reflux is unlikely to be the primary cause of arching and irritability in infants and that factors such as immaturity or neuropathology might be at play. Therefore, arching and irritability alone should not be a concern to parent or providers when diagnosing GERD in infants. Although future pathophysiology studies are needed, this information should help minimize basically the use of pharmacologic therapies and perhaps showing the duration of such therapies to prevent unintended harm.
Speaker 2:
So a very interesting paper.
Speaker 1:
I think you're muted.
Speaker 2:
Yeah, I think it fits with the literature that we're not good at identifying the symptoms of reflux. But what I thought was particularly interesting is it obviously the arching grimace type symptoms are nonspecific, but babies with reflux do those things when they're uncomfortable. So I mean, I think we can't say it's not for any baby. I think of the babies we know have reflux. When they're showing us those symptoms it may be a sign of less of those behaviors or improving control, worsening those behaviors or worsening control. But for the bulk of babies I guess it's not enough for us to diagnose reflux.
Speaker 1:
Yeah, I would say probably. Hopefully it gives us a bit of pause. I think sometimes when we see a baby with a bit of reflux and arching slash irritability, maybe we may have a looser finger on the trigger to start ordering meds and so on. But maybe this is going to give us time to pause and say well, most of the time that's not what it is, so let's see.
Speaker 2:
Yeah, and I mean that's consistent with this. This isn't the first study to say that. So it's nice to have consistency in the literature, absolutely, but it's tough to explain to, I think, our bedside nurses and parents that the baby may be irritable for so many other reasons.
Speaker 1:
Yeah, I mean to me I'm going to remember this that 11% of arching and irritability are associated with bolus reflux and that for acid reflux, arching irritability events shows a sensitivity of 8%.
Speaker 2:
And there's still a lot of use of acid reducing agents and we know that there are a lot of negative effects. We've reviewed a bunch of papers about that, including now the long-term neurodevelopment and the preterm baby who gets that type of medication. So it's just more fuel to say let's be much more restricted with those things, okay.
