We discuss triaging which newborn metabolic disorders require more urgent assessment, acute and long-term management. We are joined by Luis Umaña, MD, Assistant Professor of Pediatric Genetics at the University of Texas Southwestern Medical Center.
Dr. Neeta Goli:
Welcome to Newborn News, a podcast where we discuss educational topics for medical professionals who care for newborns. I'm your host, Dr. Neeta Goli, a pediatrician in the UT Southwestern Newborn Nursery.
Dr. Neeta Goli:
Welcome back to the podcast. In the last episode we were joined by Dr. Luis Umaña, Assistant Professor of Pediatric Genetics and Metabolism at UT Southwestern, who shared with us the classification of pediatric metabolic disorders. If you haven't already done so, I would encourage you to listen to that episode first. Today, we'll review the management of these disorders. Thanks for joining us again, Dr. Umaña.
Dr. Luis Umaña:
Hello, happy to be here for our second discussion.
Dr. Neeta Goli:
To continue the conversation from the previous episode, if a newborn screen comes back as suspicious for one of these disorders, what would our initial approach be to the evaluation and management of that baby?
Dr. Luis Umaña:
The newborn screen will assess for different disorders. Not all of the disorders that we discussed in our last discussion are present on the newborn screen. The newborn screen will assess for organic acidurias, including propionic, methylmalonic, isovaleric, and maple syrup urine disease. It will detect some of the amino acidopathies, especially homocystinuria, phenylketonuria, which is the first disorder that was screened, and tyrosinemia type 1. It will test for the fatty acid oxidation disorders, it will test for galactosemia, biotinidase deficiency, and a couple of new disorders, which are more chronic, such as X-linked adrenoleukodystrophy. We should hear, from our last discussion when we come to that third group of the chronic and complex molecules.
Dr. Luis Umaña:
So, what happens when you get a newborn screen, either in your office or in the nursery? There are different pieces that must be followed in order to bring this to a good ending.
Dr. Luis Umaña:
The first one is, that we need to ensure the safety of the baby. So whenever there's a positive newborn screen, the first thing that any physician who is in care of this baby needs to do is, look at the baby. Bring him to your office. Or, if you're in the Nursery, or in the NICU, go and look at the baby. And I don't get tired of saying this. Do it yourself. It is your own exam, it is your signature on the paperwork. So, go and check the baby. Don't trust just that mom says that that baby looks fine. That's good because mom knows best. But in the end, we are the physicians, so we need to look at the baby. Because, we can pick up smaller things.
Dr. Luis Umaña:
And things that I would monitor when you bring the baby to that examination, how does the baby look? Does the baby appear happy? Does the baby look interactive? How is the weight gain? Is your baby gaining proper weight? If not, how is the neurologic status of the baby? How are his reflexes? Any hyperreflexia, any hyporeflexia, hypotonia, hypertonia. And then, other things like, does the baby look jaundiced? All of those things should help us suspect, is this baby really healthy? Is this baby safe or not? In the vast majority of the cases, the newborn screen, because of the way it is designed to do, will probably be what we call a false positive. But you can never know that, until you have done all of the testing.
Dr. Luis Umaña:
That's the first step, look at the baby. The second one is, to obtain the confirmatory labs. The newborn screen will... Sometimes, we're going to obtain a second or a third sample. It depends on what the quality of the first one was, or what the circumstances of the first one was. If the patient was on TPN, for example. Then, they may recommend a new one, once the baby is off TPN, to make sure that those abnormalities that were seen, were not an effect of the amino acids or the lipids that are in the TPN, or if the baby was extremely premature. And those things could alter the cutoffs.
Dr. Luis Umaña
Also, the new screen is designed for newborns. We have seen that sometimes, and I have seen it in cases of international adoptions. We have children who are three or four and they undergo the newborn screen. And they might trigger for different things. Again, it's because the cutoffs are designed for newborns, not for older children. So, I don't consider that using the newborn screen card in older children, is the best way for you to assess. You could mimic a newborn screen through other labs and that could be done as well. And probably, that's what we would do in the clinic. It's a little bit more expensive. But, it's much more efficient and effective for you.
Dr. Luis Umaña:
Again, when you repeat the newborn screen, it doesn't necessarily rule out or confirm anything. The newborn screen is not designed to finalize diagnosis. It will just help you move ahead in that pathway. Then, whenever you get a positive newborn screen, you're going to get a mailer from the state. And that will have a list of labs and things that we have to do. That mailer was designed by a group of physicians. All of us who met and we met on a yearly basis, and are the metabolic consultants to the Texas newborn screen. And with that, we decide which labs we anticipate are going to be the most informative and the most time efficient and time effective. To either confirm or rule out the diagnosis.
Dr. Luis Umaña:
So often, I get the calls like, should I get this one or should I not? I would encourage everyone who listens to this to pick up all of those labs that are on that list.
Dr. Luis Umaña:
Often there's urine. I would say the urine that needs to be collected for this is a clean catch. So, there's no need to cath those babies. A urine bag is perfectly fine. Most of those labs don't need to be fasting, so you can collect them any time of the day. But collect them and collect them soon. Because, that way you are going to get an answer soon.
Dr. Luis Umaña:
Another strong advice that I provide and even a pet peeve, I advise against directly sending the patients to the ER before having them being assessed, for many reasons. One is, exposing newborns to infections in the emergency room. Now with COVID-19, even more, we try to protect both mom and baby. Two, it can overwhelm the emergency services. The emergency services are not designed for this. And again, it might lead to more miscommunication. Because, if they come to an emergency service where I have privileges from the same hospital, I can pick up those labs. But if they go to an emergency service in another town, or in another medical system, finding those results, maybe more difficult for us, in the metabolic team. Might be more difficult for the pediatrician. And then, that could delay treatment.
Dr. Luis Umaña:
So if we minimize the steps and the amount of people involved, this tends to go in a much more effective way. So I say, look, see the patient, see him in your clinic. And you take care of ordering and getting those labs resulted. And then those can be sent to us, or to whoever the metabolic team is. There are different teams in Texas that are following metabolic children. And all of us have assigned different areas to receive those newborn screens. And we take the west portion of Texas. We all are on a rotating schedule since there are no metabolic centers, really west of Austin and Fort Worth. So, those are kind of the main things.
Dr. Neeta Goli:
Okay. And that also speaks to the importance of a medical home for these babies as well. As well as all babies. But just in terms of following up and management.
Dr. Luis Umaña:
I agree. And all of this, a lot of it will depend on the PCPs on the primary care pediatricians. I believe that they are one of the most important tools. For my team, is in good communication with the pediatricians. Because, if they send their baby and the pediatrician tells me, I saw the baby and the baby's fine, I'm happy. And I know that we're in a good way. But, if the baby doesn't do well. Well, then we send that baby to the emergency room. I have been able to speak with the emergency room and give them all of their instructions about how are we going to manage this baby. And then, we minimize the risks. And I can tell you, all of the good cases that have had good outcomes, even for very sick babies, it has depended on the pediatrician being really the one leading this effort. So, I depend massively on what the primary care providers do.
Dr. Neeta Goli:
I agree. And then, I do also love your point about examining the baby first. That's one of the things that when I'm working with trainees, residents or medical students, is one of the things I try to impress upon them is, if you ever get a call about a baby, or you're not sure, the best thing to do is just go look at the baby, and examine the baby. So you can use your clinical judgment to come to a conclusion about how worried you need to be. Along those lines, I know you mentioned in our last episode, some of these will present earlier in the newborn period. Some will present later. Are there any of these disorders that would require a more prompt or more urgent or emergent evaluation, compared to the others?
Dr. Luis Umaña:
I would say all of the disorders that we include in the newborn screen, are very high risk in the newborn period. I would say some of them probably lesser let's say, PKU. But there are groups which should make you much more vigilant. I would include in this group first, the organic acidurias. Those conditions, when they decompensate, is going to be quite severe and can be rapidly deadly. We have seen babies who decompensate and in 12 hours, they are beyond anything that we can do to recover. So, often it will be... They will come in the newborn screen as elevations of biochemical markers, C3, C4, and C5, which are just carnitine associated with one of the organic acids. Either be a three, four or five carbon index, that's what the number means. And maple syrup urine disease.
Dr. Luis Umaña:
So, whenever you get a positive newborn screen, this is a baby that you really do need to see in the office. You or one of your physician colleagues at least, to go and look the baby, speak with the mom. How is the baby feeding, is it spitting, anything off? And remember, some of these babies when they come, if they're breathing fast, they look lethargic. Some of them might have this kind of smell. I can say, the few times I have felt the smell in the room, it's quite pungent and it's quite strong. So, it's not minimal. It's that, you go into the room and the room really stinks. So this is the first group that I would say, yeah, you need to see them right away. In the same order of concern is disorders of urea cycle defect. Unfortunately, because of the way their chemistry works, we don't have a good screening for most of them. And actually, we don't have a good screen for the most severe ones.
Dr. Luis Umaña:
So, we have a screening for the milder or moderate ones. So, whenever they call about the significant elevation of citrulline, this is another baby that could have a high risk of being in a crisis, and will be with high ammonia. So this baby would come again, looking lethargic, breathing fast, no smell. These babies may be hyperreflexic. But then again, you would just take your newborn screen. So, it's high citrulline and the baby's breathing fast and doesn't look well, might be hyperammonemic. And that baby does need to go to the ER. And often, they stayed with us, or called me and gave me a heads up that they have a result that is significantly out of range, which would make us much more concerned. So by that time, we will be also working on the background, with the pediatrician trying to figure out what is going on and what is going to be the next step? Well, I would say those are the two main ones, main groups, always really urgency is important.
Dr. Luis Umaña:
The fatty acid oxidation disorders, often as long as the baby's feeding every two hours, you will remember as per our discussion, they tend to be much more stable. The chances of them decompensating are less. And you could say, well, I mean, if the baby's feeding okay, and mom says, everything is fine. I could wait a little bit to see them. A little bit is not long. I would say, early next morning. But it's something that could be done. But these other two, I would say, you need to see the baby at some time.
Dr. Luis Umaña:
And then, for some conditions, I say, when you get the screen, after you see the baby, even if the baby looks fine, I advise you can start treating as if the baby had the disorder. I advise this, when that intervention is a very low risk for the baby and evidence shows that if the baby's affected, would really impact the outcome of the baby. The first condition for which I recommend this is galactosemia. So, if you get a positive screen for galactosemia, I say to the PCPs, start this baby immediately on soy-based formula. And, if mom is breastfeeding, tell her to continue pumping and storing her breast milk. Because remember, many times there will be a false positive, or a milder form of galactosemia in which a baby will be able to return to regular milk. So, start the baby on soy milk, get the confirmatory test. And once that's back, we can discuss, okay, this may be a really has one of the severe forms of galactosemia. So, remains on soy-based formula for the rest of his life. Or, it's a milder form. And he can do some breastfeeding and all the bonding and all of the benefits that it has. So, that's the best one. And again, with this we will minimize all of those symptoms that we discussed in our prior discussion of liver dysfunction or jaundice or cataracts or any of those things.
Dr. Luis Umaña:
The next condition, again at the fatty acid oxidation defects, whenever a baby's positive, we recommend keep feeding the baby every two or three hours around the clock. Which in the end is what the parents have been doing most of the time. So often, that doesn't come as a disruption of their schedule when they have a newborn. And, start doing that, get the lab work on the baby. And on many of these disorders, lab work may allow us to rule it out quite fast. The fatty acid, there's a couple of them in which we have to go to subsequent rounds of testing, until we're able to completely rule them out. These are easier to rule in, than to rule out. And, in those children we have to do more testing and it might take more weeks. We start increasing their fasting because as they get older, their reserves of glycogen are larger. And that prolongs the time between being fed and trying to use fatty acids for glucose production. So often we say, every month of life, we give them one extra hour of fasting to a maximum of probably eight hours on a six-month-old, or seven-month-old, and 10-12 hours on a one-year-old. But often by that time, we already have been able to rule it out, or confirm it.
Dr. Luis Umaña:
And the last group on those for which I recommend to start treatment, is biotinidase deficiency. For this one, the treatment is just to give the babies biotin, at a dose of five milligrams or 5,000 micrograms every day. It can be found over the counter, it is very cheap. You can get it into any pharmacy, either the corner pharmacies and the branded ones, or the big stores that have pharmacies inside. They will have biotin. I often recommend the gel tabs that you can puncture and squeeze a liquid into a spoon or the solutab that you could put on the baby's tongue. They dissolve fast enough, that really babies will not choke on it. You can mix the content of the gel tab in milk. But don't put it into the bottle. Because really, five milligrams is such a small amount, and most of the cap is filler. So, what happens is, if the baby doesn't drink the full amount of milk, he might not be getting the full dose or ad sol biotin attaches to the rubber in the nipple of most bottles. So it ends up being there and being washed out and the baby never get it. And again, none of these recommendations has any significant risks for the baby. You cannot overdose on biotin. And on the other hand, by giving this, you could prevent those babies from going into a crisis, and it will not alter the results of the follow-up testing. So, those are kind of recommendations that I give.
Dr. Neeta Goli:
Okay. And then, once we have confirmed that a newborn has one of these disorders and we have dealt with the acute phase of management and stabilization, what are the things that we can do to make sure that the baby is set on a path for good long-term management?
Dr. Luis Umaña:
So that becomes the next step of pediatricians and us working as a single team. So, for many of these conditions, just as the case of biotinidase, we just tell the families and they continue taking biotin, and they should be otherwise completely normal babies with no restrictions. Some of the conditions, the organic acidurias, the amino acidopathies, those have a more complex management. Because those patients will need specific diets that will be managed by our team. So we will determine exactly what things can they eat, which things they cannot eat. What is the maximum amount? There are restrictions. But we rely a lot on the support to the primary care provider to ensure that the patients are able to comply, to identify potential barriers. In our team, we have nutritionists and social workers that help us do it. But really a lot of the things that they do is, just being in communication with the primary care providers.
Dr. Luis Umaña:
Sometimes many patients live far away from us, and we rely on the primary care providers helping us obtain the labs. Language barriers, cultural barriers. Pediatricians who are more engaged with the family can pick up a lot of things. And they give us a significant amount of very useful information. There is something that they see that will allow us to improve the quality of care. So, that goes back to what you mentioned at the beginning of having a good medical home. We are in that home, but really the pediatrician is the one who is mastering and controlling everything there.
Dr. Luis Umaña:
So, all of these patients, I say immunizations are key. All of the immunizations, because one of these kids with varicella, with measles, that could lead to a devastating metabolic crisis and death. So, vaccinations are of no risk. And sometimes, if there could be a minimal risk, we work with the pediatricians to minimize it.
Dr. Luis Umaña:
Open discussion and questions. We're open all the time to speak. I mean, pediatricians say, you know what? I think that this family is not able to do this, for X or Y or Z, or this is working well or not. That helps. Sometimes pediatricians, they have different views on things, and we welcome them so that we can try to optimize things. And then, there are many things on which we rely. Because, again the primary care pediatrician is the one who is there equipped with. For example, referrals to early childhood interventions and monitoring that the patients are getting services at school, that the patients are getting the proper audiology and vision screening. Some conditions such as PKU, even though they are very well-controlled and it keep them in the target range, many of these patients will develop ADHD. So, we rely a lot on the pediatrician to do the assessments. And, in the vast majority of cases, it is the pediatrician, the one who is managing this portion of this chronic disease.
Dr. Neeta Goli:
So thinking about the big picture too, not just the metabolic effects of the disorders. Very important.
Dr. Luis Umaña:
It is a very big picture. As we say, this is a family issue. And so, it was very important to see what else is going beyond the child. How are the siblings? The siblings often don't come to my clinic and even less now, in COVID-19. But, the pediatrician will know the siblings. And he would say, you know what? This brother is having trouble coping with their condition, with this special diet, or that his little brother has to come to the hospital and see many doctors many times. I think that's extremely important, because that over the long-term affects significantly not only my patient, but the compliance of how they see themselves and how they help. And also, it will have an effect on that sibling who often is slightly neglected. As we know, that is the history for many patients with chronic conditions.
Dr. Neeta Goli:
That's a really good point and something that we might not necessarily talk about all that often. But yeah, very important to consider.
Dr. Luis Umaña:
And, also the parents. It is very important for us. I often ask the parents first, how are you doing? And, not in the conversational way, but I really need to know how they're doing. How they're coping with this. This condition that, yeah, for me, it's very easy to know they have good prognosis and everything is easy. Even for the parents who understand that. They also have what they perceive as a very sick child and a very unique child at home. And it takes quite a toll. And again, here's where PCP really, really is the most important piece.
Dr. Neeta Goli:
And then, earlier you had mentioned that one of your pet peeves was, kids being sent to the emergency room without necessarily having had that pediatrician evaluation first. Along those lines, are there any other common pitfalls that you see in the management of these babies that we can avoid?
Dr. Luis Umaña:
So, things that I've seen, I think that we just touched base on panicking with a newborn screen. And another one of my mottos, is when you get a positive newborn screen, freak out, but don't panic. So it means, taking a baby seriously, bringing in, assessing, get the labs promptly. And, if the baby looks sick, then take him to the ER, and have me informed or whoever is your metabolic contact. So, that's one.
Dr. Luis Umaña:
The other one is, the opposite end of the spectrum. Say, this is probably a false positive. I will see you in two days. I will see you, when you're up for your one-week-old visit. That can be dangerous, because it's quite a gamble that you are taking. It could be a false positive. But, if it's a real positive, this baby could end up dead. Or, could end up with a significant neurological injury.
Dr. Luis Umaña:
Or, the other pitfall is, I know that especially for primary care providers, unfortunately, the system is very unfair. And, they get overwhelmed with the amount of patients and lab work and paperwork that they are supposed to fill. The risk of these newborn screens, not being seen. And, we have had a couple of cases where that has happened, which have ended up with devastating conditions for the children. So I think, those are important pitfalls. I would say, make sure, make it kind of your dogma. That you need to verify and see with your own eyes, I'm kind of an untrustful person in that sense. I don't believe anything I don't see with my own eyes. I don't believe in a reading of an MRI if I don't look at it myself, I would like to see with my own hands, either the paperwork that my team says, all we have a newborn screen for X or Y or Z, may be normal. I need to say it. And I would recommend for you guys to do the same.
Dr. Luis Umaña:
And, something that we had seen in the past. Luckily not as much. We had a couple of cases in which people felt emboldened and tried to treat these patients on their own. And, it has led even on a couple of times to the death of the child. So, we are all trained. But, we have different areas of expertise and consulting with anyone is never a sign of weakness. It's actually providing excellent care. I can tell you, even many geneticists, don't manage inborn errors of metabolism. And they don't like it. And they will say, you know what? I don't know how to do this. Even, for things like PKU, they will know the routine things to stabilize a baby. But then, many places will depend, especially for these very rare disorders, on the expertise of someone else.
Dr. Luis Umaña:
And even myself, most of my decisions are made as part of a committee with my dietician and some of my colleagues. And, we decide as I go like, yeah, we should go high or low on this protein. What do we do? That way we try to improve the quality of care. And I would say that, luckily that doesn't happen as much. But, we have seen it in the past. Children who, for example with PKU that were placed on metabolic formula, without any other supplementation. And the baby died from protein malnutrition really fast. So, those are things to consider. But, the first ones are the two: like don't panic, and don't be too cavalier.
Dr. Neeta Goli:
Okay. Thank you so much. To end today's episode, what is your favorite part of your workday?
Dr. Luis Umaña:
My favorite part of my workday is actually seeing the children of the newborn screen, and seeing how well they do. In genetics, we often see many, many sick children. Children for whom we have very little options. The metabolic children, and in that group, the children of the newborn screen are so promising. We have more therapies. And in the case of newborn screening, many of these kids are completely normal. I tell my students, you could have one of your peers have classical phenylketonuria and you would never know. And that's thanks the newborn screen.
Dr. Neeta Goli:
Wonderful. And that really is such a success story, in terms of being able to catch and manage these better. Well, thank you so much. This has been a really great discussion. I know I have learned a lot. Thanks for joining us today, Dr. Umaña.
Dr. Luis Umaña:
Thank you. Have a wonderful day.
Dr. Neeta Goli:
You too. Thanks for listening to Newborn News. We hope you join us next time. If you like what you hear, make sure to subscribe and leave us a review. If you have questions, comments, feedback, or suggestions for future episodes, please e-mail me at NewbornNews@utsouthwestern.edu. As a reminder, this content is educational and is not meant to be used as medical advice. Views or opinions expressed in this podcast are those of myself and my guests, and do not necessarily reflect the views of the university.