Guidelines With Gabi:
Code Yellow: New Guidelines for Hyperbilirubinemia

September 30, 2022

Transcript

Dr. Angela Kade Goepferd:  This is Talking Pediatrics, a clinical podcast by Children’s Minnesota, home to The Kid Experts, where the complex is our every day. Each week, we bring you intriguing stories and relevant pediatric health care information as we partner with you in the care of your patients. Our guests, data, ideas and practical tips will surprise, challenge and perhaps change how you care for kids.

Welcome to Talking Pediatrics. I’m your host, Dr. Angela Kade Goepferd. In this episode of Guidelines With Gabi, Dr. Gabi Hester reviews new guidelines recently published by the American Academy of Pediatrics for the diagnosis and management of hyperbilirubinemia in newborns.

Speaker 2: Welcome to Guidelines With Gabi.

Dr. Gabi Hester: For pediatricians providing newborn care, managing babies with jaundice is all in a day’s work as more than 80% of newborns will have some degree of jaundice caused by elevated levels of bilirubin. With how common this is, it’s easy to forget why we screen for and treat high bilirubin levels to prevent the devastating permanent neurological condition of kernicterus. Today I’ll be talking with Dr. Jordan Blessing, a pediatric hospitalist at St. Luke’s Hospital in Duluth, Minnesota to review all things bilirubin and to hear some of the key recommendations for the recently released hyperbilirubinemia guideline from the American Academy of Pediatrics. Hi Jordan, thanks so much for joining me today.

Dr. Jordan Blessing: Hi Gabi. Happy to be here. Thank you.

Dr. Gabi Hester: So I wanted to really just start with the basics. Can you remind me a little bit about what bilirubin is and what does our body do to keep it in balance?

Dr. Jordan Blessing: Bilirubin, you can think of it as one of our many assembly lines within our body. And so bilirubin starts by being part of the heme product in our red blood cells. When we break down the heme, we release bilirubin. When bilirubin’s released, it’s floating out there in the bloodstream and it meets up with albumin. Together albumin and bilirubin float down in harmony towards the liver and once they meet the liver, they’re processed through an enzymatic process with glucuronyl transferase. What that does is it conjugates the bilirubin, makes it more water soluble. It’s excreted in the bio ducts, enters the small bowel where most of it then exits our body through our stool. A small bit of it does get reabsorbed in the [inaudible 00:02:28] enterohepatic circulation and has to go back and get reconjugated. But in general, that’s the process of bilirubin production, processing, and elimination.

Dr. Gabi Hester: And what are some of the causes of high bilirubin levels in babies? Why is it higher there than later in life?

Dr. Jordan Blessing: Basically with babies, just like the baby at large is premature, they’re not running around doing pushups and things like that. This machinery and this processing in babies for how they deal with their bilirubin is also a little bit immature, sorting itself out these first few days. So step one, they’re just making more bilirubin than an adult is. Their red blood cells don’t last as long. They’re recycling them more quickly and so per minute they’re just releasing more bilirubin into the bloodstream. That’s the first thing.

Then the second thing, the bilirubin getting processed in the liver, the enzymes that make that happen are not fully up and running. And so the processing of the bilirubin converting it to the conjugated form is a little bit slower. So they’re making more of it. They’re processing it slower. You could see how it would just build up back in the assembly line in the serum levels. And then lastly, they’re pooping more slowly. They’re still processing the meconium and trying to excrete the meconium these first few days. Oral feedings are still being established and so they’re just excreting less of it those first few days as well. So for those three reasons, normal newborn physiologic jaundice develops because of those three steps in the processing.

Dr. Gabi Hester: So again, back in the glory days of residency, I remember there being a couple of different issues with breast milk and hyperbilirubinemia. Can you talk through a little bit about how breast milk interacts with this whole process and how we should be thinking about these and explaining these to families?

Dr. Jordan Blessing: What is this idea of these terms that have been thrown around breast milk, jaundice or some older terms, which were called breastfeeding jaundice or even things like breastfeeding failure jaundice, some of these more kind of negative sounding terms. And the way breast milk plays into hyperbilirubinemia really comes in two forms. The earlier form, which we’re talking about in those first one to three days of life of a newborn, this is what used to be called breastfeeding failure jaundice, which is now called suboptimal intake jaundice, which is a more appropriate term and a more descriptive term. And as we all know, we’re all promoting exclusively breastfeeding infants whenever safe and feasible to do so. And for the new mom baby unit, that sort of timeframe and success is variable as we’re waiting for the infant to learn how to effectively feed and swallow and coordinate breastfeeding for maternal milk supply to fully come in.

There can be a couple of days where the breast milk intake is suboptimal, but it’s improving. And so what that results in is just overall decreased oral feeding, decreased movement of meconium, decreased stooling, all of which just is slowing down the excretion of bilirubin in our stool, giving that enterohepatic recirculation more time to bring up that unconjugated bilirubin again. And so that’s this term suboptimal intake jaundice, and that’s transient. And attention is given to optimizing breastfeeding formula supplementation as needed and monitoring your intakes, your output, monitoring your weight gain, our weight loss and monitoring for signs of dehydration. That all kind of goes together with just trying to get the infant enough intake.

The second part of that, this term breast milk jaundice, this is more of the long term persistent jaundice that it’s again, unconjugated but it stays elevated for several weeks. Although the infant is otherwise doing well. Feedings are well established, the intake is adequate and the weight gain is appropriate, but yet they have an persistent jaundice, a persistent unconjugated hyperbilirubinemia. And this is a bit sort of still being discussed, what exactly causes it, but in general, the thought is there’s something in the maternal breast milk that’s interacting with the enzymatic processes in the liver somewhat hindering the liver’s ability to conjugate and then excrete bilirubin. This is harmless, it goes away and almost never needs a specific intervention, stopping breastfeeding or anything like that. Most often you carry on life as usual and it sort of self corrects, but it is the cause of that more prolonged jaundice state several weeks into life.

Dr. Gabi Hester: Now, beyond those sort of normal reasons to have a little bit increase bilirubin in newborns, what are some of the causes that might lead to the bilirubin becoming too high?

Dr. Jordan Blessing: Somewhat, they live within those steps, but there are various injuries, disease states or anatomic variations that can affect the steps along the way. So things that might result in overproduction of bilirubin would be anything that would create more of a state of red blood cell breakdown or increased hemolysis. So that could be injury, bruising from a birth injury on the scalp or the body. It could be ABO incompatibility where there’s maternal antibodies destroying newborn red blood cells more quickly. And these sorts of things would of course result in more hemolysis and therefore more bilirubin spilling out into the bloodstream. And then anything that makes the red blood cell more fragile, these can be different disease states like Spherocytosis or glucose-6-phosphate dehydrogenase deficiency, G6PD deficiency. Making the red blood cell more vulnerable to injury would also cause increased bilirubin states.

And then at the level of the liver, anything that’s affecting the liver’s ability to perform that glucuronidation step, these could be enzyme deficiencies or just slowdowns in that enzymatic machinery. Anatomically if there’s any liver abnormalities within the bile ducts, for example, biliary atresia resulting in the bilirubin being unable to leave the liver would cause elevated bilirubin levels often in the conjugated form. And then anything again that results in decreased stooling, more meconium plugging or slow transit would increase that enterohepatic circulation. It would cause more reabsorption and having to conjugate again would all be examples of sort of steps along the way that would lead to a higher than average bilirubin beyond just what we count as physiologic newborn jaundice.

Dr. Gabi Hester: So if we have a baby where we’ve determined that their bilirubin is too high, what steps can we take and how do those work?

Dr. Jordan Blessing: Gets down to one, how do we even know if their bilirubin level is high? We certainly assess babies visually for jaundice, but we all know that just the examiner’s eye alone is not sufficient enough to determine the degree of hyperbilirubinemia. So all babies are being screened for hyperbilirubinemia. Most often we start with a transcutaneous bilimeter, which gets us in the ballpark of what the bilirubin level is. It’s painless, it spares a needle poke. And so that’s our starting point. And off of the transcutaneous bilimeter, if the level is elevated within three points of treatment threshold over an overall number of 15, these are common thresholds. Those would be reasons to then get a confirmatory serum total bilirubin. And all decisions in terms of treatment and ongoing management are really based off of the serum total bilirubin concentration.

Dr. Gabi Hester: So if you have a baby with a transcutaneous reading that’s sort of close to where we should be starting phototherapy, it sounds like the AAP recommends obtaining a serum bilirubin at that time. Is that correct?

Dr. Jordan Blessing: Yes, that’s correct. That would be the normal workflow for determining in a more accurate way what the actual total bilirubin level is.

Dr. Gabi Hester: And how have you at your organization sort of made this easy for people to remember? Do I have to keep it in my mind that at a certain hour I need to be checking this or are there ways that you can hard wire it in?

Dr. Jordan Blessing: We can certainly standardize it and any institution can. And one benefit of these new AAP guidelines is that they really help more clearly define some of the gray zones in terms of screening, intervention, and timeframes. So it sort of helps shape up some of the artistic expression we were all doing already and helps us standardize it in nursing order sets. An example of this would be something as simple as in your newborn order set, you could have it as a routine order that a transcutaneous bilirubin be obtained at 24 to 48 hours of life or prior to hospital discharge, whichever is sooner for all well newborn infants.

You could go one step further and have an order that addresses infants with higher risk factors and a more timely screening of their transcutaneous bilirubin, perhaps say at 12 hours for example. You could also have reflexes built in that says if the transcutaneous bili meter is this, then it would have a reflex order to do a total serum bilirubin. So some of this can be more automatic and built into routine order sets and not requiring necessarily a conversation every time as you start to standardize the screening, testing and treatment interventions.

Dr. Gabi Hester: And when you sort of talk about treatment and interventions, usually we’re talking about phototherapy. Can you remind us a little bit about how phototherapy works?

Dr. Jordan Blessing: Phototherapy has been around quite a while now, and what it really is, it’s narrow wavelength blue light, and that’s part of the visible light spectrum, but specifically this narrow wavelength blue light when exposed to the skin of a newborn, it interacts with the bilirubin near the skin and it converts it to more water soluble forms. So in a way you can sort of think about it as it makes the bilirubin more easily excreted without having to go through that liver conjugation step. So it can speed up bilirubin elimination that way.

Dr. Gabi Hester: I feel like a common question that people get asked from families is, can I just put the baby in the sun? What do you usually say to that?

Dr. Jordan Blessing: It’s true that the light spectrum within the sun does contain as part of its spectrum the narrow blue wavelength light. That’s true, but it also contains some of the more harmful exposures with UV injury, damage, sunburn, and it’s hard to regulate exactly how much exposure they’re getting. So because direct sunlight exposure carries risk, we recommend in the United States where we have access to phototherapy readily that we choose the safer, more concentrated narrow blue wavelength light form for treating the hyperbilirubinemia without adding that increased risk of UV skin injury.

Dr. Gabi Hester: Now, one of the things I found interesting about this new 2022 guideline from the AAP was that they did raise the phototherapy threshold by a narrow range in a few circumstances, and they also called out the risks of overtreatment. So that’s a concept that I think is gaining some traction in medicine where it’s the idea that a patient does have a situation like high bilirubin levels, but it’s not actually a problem that would have any morbidity or mortality. Now of course, that’s not on the extreme ends of things where you’re worried kernicterus. So the AAP sort of talks about some providers actually have over the years decided to recommend treatment below the recommended thresholds, but in this guideline they talk about considering the risks to the infant and family of overtreatment. Can you talk a little bit about the risks of phototherapy and what it does for sort of those early days of life for a family?

Dr. Jordan Blessing: It really gets down to the risks and the benefits and to some degree individual family preferences. And so specific to phototherapy and hyperbilirubinemia, and I’ll keep this within the realm of what we’re presuming to be normal physiologic jaundice with disease states aside, it comes down to where’s the threshold for starting phototherapy? And the AAP new guidelines really did help sort of do two things. They slightly increased the threshold, recognizing that most of our treatment thresholds are far below the dangerous levels that cause neurologic injury. And largely we have an infrastructure where testing and treatment is readily available. It increased the threshold a little bit and it helps better age delineate the threshold at each gestational age in those over 35 weeks, both of which are helpful changes. And then for those infants who are near the threshold, then it’s a conversation piece with families. Oftentimes we’re getting this information before they leave the hospital from their newborn hospital stay, and it depends on family dynamics.

So I really open up the conversation with the family and say, your child’s bilirubin level is this, the treatment level is this. Maybe we’re within one or two points, but we’re below the threshold. What are the risks of staying and doing the phototherapy now versus going home, but having close follow up arranged and I leave it up to the family. How far away do they live from the hospital?

How much of a commute or a hardship is it to come back? What’s their comfort level with taking the risk, that it might climb and they might get readmitted versus what’s their comfort level with having to stay an additional night perhaps and have this separation where the infant is largely spending their time under phototherapy with the exception of feedings. And how does that disrupt bonding and skin to skin and these things? And so I very much keep this treatment option when it’s an option as a conversation and really incorporate the family’s wishes, the family’s values and the family’s needs into the conversation in terms of deciding how do we safely start treatment or how do we safely arrange follow up with a plan B if on follow up that level has now crossed treatment threshold.

Dr. Gabi Hester: Thinking back to my time as a student or a resident, I remember the old question or the question that everybody debated was rebound hyperbilirubinemia and when to check the rebound bili. Can you talk a little bit about what the guideline now recommends for that?

Dr. Jordan Blessing: So once a baby has received phototherapy, the question always has been, when do you check again? Meaning what’s the risk of them rebounding high enough to require treatment again or recrossing their treatment threshold? And this was always sort of loosely defined. Everybody sort of used to have their own ideas. I remember as a resident in the NICU, it depended on which attending was on. Do we check them yes or no? If we do, when? It felt very much like the Wild West. And with these new guidelines, the AAP does to a degree more clearly define how and when do you check rebound bilirubins? And in general, their recommendation is for those well newborn infants who required phototherapy and have now stopped phototherapy if they don’t have additional risk factors, the general recommendation is to get a rebound bilirubin level ballpark around 24 hours after stopping phototherapy.

The range sort of says 12 to 24 hours because you need to give the bilirubin a climb, sufficient time to rise enough where you can calculate the rate of rise. And these new AAP guidelines do talk about rate of rise in terms of bilirubin climbing per hour. And there is additional recommendations. So beyond your average healthy newborn and the 24 hour repeat bilirubin check, sometimes you do want to check a rebound more quickly if there was certain risk factors like hemolysis or prematurity where you might want to check closer to six to 12 hours instead. And much of this ability to perform rebound bilirubins after a baby’s gone home has to do with close coordination with either primary care outpatient laboratory services or something like a lactation clinic where they’re coming back anyway for evaluation and the bilirubin recheck could be seamlessly incorporated. And that also could be made into a hospital based process.

Dr. Gabi Hester: What are some of the red flags that we should look for that would signal that maybe something else is going on beyond those more routine causes of hyperbilirubinemia?

Dr. Jordan Blessing: So I think when we’re talking about bilirubin screens and monitoring things that would raise concern for something beyond normal physiologic jaundice would include early jaundice, meaning jaundice within the first 24 hours of life, jaundice that markedly elevated when you check the first screen and confirmatory serum, meaning above phototherapy threshold and into exchange transfusion thresholds, family histories of hemolytic states or certain genetic illnesses. Again, back to something like G6PD or any other sign that there’s ongoing disease processes that might include anemia or other states that are contributing to an above average high bilirubin level.

Dr. Gabi Hester: I know most of this type of care for infants with hyperbilirubinemia happens in a newborn nursery or even at some cases with home phototherapy. Which babies would need escalation to a higher level of care such as a NICU type setting?

Dr. Jordan Blessing: So a lot of babies being screened for jaundice are at your average well newborn nursery or perhaps a level two nursery. And depending on your hospital’s arrangement, you may or may not have immediate access to a NICU. And part of the new AAP guidelines for hyperbilirubinemia is helping define further when do you escalate care and what sort of factors play into that decision for escalating care. For me, an age old treatment sort of was if you check the bilirubin level and it’s at the exchange transfusion threshold as defined by the AAP algorithms, you should still start with the basics, which is initiating a high intensity phototherapy plus or minus IV fluids to help with dehydration and then monitoring very closely for the next four to six hours. And if you’re unable to bring it below the exchange transfusion threshold, we’ve always then considered transferred to a NICU where they can undergo exchange transfusion or at least have that option of exchange transfusion in a neonatal intensive care unit.

Dr. Gabi Hester: Well, thank you so much, Jordan. It’s been really great talking with you today. As a fellow pediatric hospitalist, it’s a great reminder that for hospitalized children, over 70% of hospitalized children are taken care of in community hospitals like the one where you practice. And so it’s always great to talk with someone who has a little bit different lens and certainly a huge area of expertise in this topic. And thanks so much for sharing that knowledge with me today.

Dr. Jordan Blessing: Gabi, thank you so much for inviting me to be a part of the podcast. This is a fun topic to discuss and it was a pleasure to talk to you.

Speaker 2: Take home points.

Dr. Gabi Hester: Number one, all newborn should have bilirubin screening ideally between 24 and 48 hours of life. Number two, one of the most common causes for hyperbilirubinemia is suboptimal intake. And so optimizing feedings while treating with phototherapy is really essential. Number three, a rebound bilirubin should be checked at approximately 12 to 24 hours after stopping phototherapy for well newborns without additional risk factors for hyperbilirubinemia. Number four, red flags for a more serious cause of hyperbilirubinemia would include jaundice within the first 24 hours of life, a market elevation of bilirubin levels such as reaching exchange transfusion levels, family history of hemolytic disease or G6PD, and prematurity.

Dr. Angela Kade Goepferd: Thank you for joining us for Talking Pediatrics. Come back each week for a new episode with our caregivers and experts in pediatric health. Our executive producer and showrunner is Ilze Vogel. Episodes are engineered, produced, and edited by Jake Beaver. Amy Juba is our marketing representative. For more information and additional episodes, visit us at childrensmn.org/talkingpediatrics, and to rate and review our show, please go to childrensmn.org/survey.