July 14, 2023
In this “Guidelines with Gabi” episode of Talking Pediatrics, Dr. Gabi Hester discusses with the Kid Expert, Dr. Susan Kuldanek, pediatric hematologist, the new clinical practice guidelines for the diagnosis and management of children 5 years and younger with iron-deficiency anemia.
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. Iron deficiency anemia is not uncommon in the primary care office. On this Guidelines with Gabi episode of Talking Pediatrics, Dr. Gabi Hester discusses the new clinical practice guidelines for the diagnosis and management of iron deficiency anemia in kids five years and younger with our kid expert, Dr. Susan Kuldanek, pediatric hematologist.
Speaker 2: Welcome to Guidelines with Gabi.
Dr. Gabi Hester: Iron deficiency is the most common cause of anemia in children five-years-old or younger, particularly in our dairy-loving region of the country. In the United States, about 15% of toddlers are iron deficient, and around 5% will have iron deficiency anemia. Furthermore, there are disparities in iron deficiency, with higher rates amongst children living at or below the poverty level and in certain racial and ethnic groups. Today, we’ll be speaking with one of our Children’s Minnesota experts, kid expert, Dr. Susan Kuldanek, about iron deficiency anemia and the new clinical guideline available at Children’s Minnesota. So thanks for coming, Sue.
Dr. Susan Kuldanek: Happy to be here.
Dr. Gabi Hester: Well, let’s start today with some numbers. So at what hemoglobin level is a young kiddo considered to have anemia?
Dr. Susan Kuldanek: Well, according to the AAP, 11 grams per deciliter is the cutoff for children five and under. Of course, if you look in our reference range or the textbook, you’ll see slightly different levels. For toddlers aged nine months to 24 months, 10.5 to 13.5 grams per deciliter is considered the normal range. Two years until puberty, 11.5 To 15.5 grams per deciliter. So I just say for practical purposes, 11 is a good rule of thumb.
Dr. Gabi Hester: While our focus today is on iron deficiency, whenever I’m looking at a clinical guideline I always want to think about what’s excluded, or what are the other things on my differential diagnosis? So can you help us think through some other causes of anemia? So if I have a patient I’m seeing and they have a hemoglobin of nine, let’s say, what are some red flags that might be there that I would want to think about a different cause?
Dr. Susan Kuldanek: This guideline is really intended for the kiddo with classic iron deficiency, nutritional issues, heavy milk drinking. Some of the things that you should be thinking about and that should raise a red flag would be significant symptoms like ill appearance, night sweats, signs of bleeding, dark urine, or jaundice. A kid who’s got recurrent infections, not just viral infections, but kind of an ill looking kid, big liver or spleen, big lymph nodes. Any of those sorts of things should be raising your concern for something more significant. Remember that the iron deficient child is often cranky and irritable, sometimes puffy or edematous, but really shouldn’t strike you as toxic or ill.
Dr. Gabi Hester: So since iron deficiency anemia often comes up in that younger toddler age range, are there any causes of anemia that might be picked up on newborn screening that maybe wouldn’t have a ton of clinical symptoms associated with it?
Dr. Susan Kuldanek: Absolutely. The newborn screen is designed to screen for different hemoglobinopathies, including sickle cell disease, which really the state of Minnesota does an excellent job of notifying the hematology department when they do find something like that. These toddlers that we’re talking about in clinic with microcytic anemia oftentimes can be confused with a thalassemia trait.
Dr. Gabi Hester: You mentioned early on that the guideline’s really focused for kids who are five years of age and younger. What’s the deal with toddlers? Why are we talking about this age group in particular?
Dr. Susan Kuldanek: High-risk period for iron deficiency anemia, so many reasons. The diet is really the quintessential thing. Many of these kids are picky eaters, have limited diets, and this is an age where we see a lot of heavy milk drinking. I always remind families and counsel them when I see them in clinic that children really need a tremendous amount of iron to support their increasing blood volumes as they grow. About 85% of our total iron is stored in our red blood cells, but essentially every other cell in the body, including the brain and the heart, need some degree of iron as well. So really, it’s just very important to support metabolism, brain, and muscle tissue. And all in all, kids need about 11 milligrams a day. In utero, the majority of the iron is transferred during the third trimester. So any infant who is born early or those late preterm or even early term infants are at risk for future iron deficiency. Many of the moms were also iron deficient during pregnancy. And as a result, these infants really don’t start out with the stores that the term infants do.
Dr. Gabi Hester: How does breastfeeding impact iron stores in babies?
Dr. Susan Kuldanek: Exclusive breast milk or prolonged breastfeeding is definitely a known risk factor. Although the iron in breast milk is more bioavailable than other forms of iron, the absolute amount in breast milk is really quite low, especially if the mom is also iron deficient.
Dr. Gabi Hester: For infants who are exclusively breastfeeding and thinking too about some of those other high-risk preemie populations, do we ever start iron supplementation empirically in those kiddos?
Dr. Susan Kuldanek: It’s recommended that exclusively breastfed infants are at least started on iron by four months of age, but potentially sooner if they were premature or have other risk factors. I really try to dive deeply into the dietary history with families. Parents will initially say, “Oh, yes, they eat meat.” But when you really ask the diet, the meat ingestion is really maybe a couple of bites of something like a chicken nugget. And I don’t know if you’ve ever looked it up, but there’s essentially no iron in a processed chicken nugget. So I’ve jokingly call this the grape and chicken nugget diet.
Dr. Gabi Hester: And what about milk drinking? I come from Wisconsin, to be totally transparent. So dairy state, dairy state right here. And how does cow’s milk impact iron stores or absorption? I know I’ve heard some things about that. Can you remind me of the mechanism?
Dr. Susan Kuldanek: The recommendation is to limit the amount of cow’s milk after a year of age, at which point the child would either be off formula or off of breast milk. We see a lot of kiddos who drink a lot of milk, or even exclusive milk drinking. Many mechanisms for the iron deficiency associated with that. One, there’s virtually no iron in milk whatsoever, so the majority of the calories are a empty calorie, so to speak, which is part of the reason sometimes the kids look kind of puffy. Also, protein nutrition can be low in some kids and they lose albumin, and that can be part of the reason that they’re a bit edematous. But milk itself can be irritating to the intestines, and so we see some absorption issues just from irritated intestines and lack of iron absorption from other types of foods. We can also see blood loss, which can directly contribute to iron losses as well with milk drinking.
Dr. Gabi Hester: I want to shift a little bit to testing for anemia. Some kids might come in with symptoms that would prompt you to do some lab testing, but what about routine screening for hemoglobin? Is there a time that providers out in the community should be thinking about screening kids?
Dr. Susan Kuldanek: The American Academy of Pediatrics, or AAP, recommends screening for anemia between the ages of nine to 12 months with additional screening between the ages of one to five years for patients at risk. And so they know that this can be modified depending on the population in question.
Dr. Gabi Hester: And then are there other labs, maybe if the hemoglobin comes back low, are there additional labs that outpatient providers should be getting?
Dr. Susan Kuldanek: Really, the ferritin is the most specific finding for iron deficiency. If you have a low hemoglobin with a low MCV and you have a low ferritin, you’ve made the diagnosis of iron deficiency and anemia.
Dr. Gabi Hester: As a hospitalist, I’m often seeing kids who are admitted with some sort of acute illness, and we might detect microcytic anemia as part of the lab testing that they’ve had done for other reasons. Are there any caveats to the ferritin that I should keep in mind in that setting where a kid’s coming in with something else to the hospital?
Dr. Susan Kuldanek: Definitely a kid who’s inflamed, we would recommend getting a CRP at the same time. So ferritin has an activity as an acute phase reactant, and so can be falsely elevated or falsely normal in the iron deficient child. I’ll admit I don’t send it a lot from clinic.
Dr. Gabi Hester: And when should an iron panel be used? And what exactly is on an iron panel?
Dr. Susan Kuldanek: The iron panel is not as good as the ferritin. And the ferritin ironically is not on the iron panel. But the iron panel can provide some good supportive information, including a TIBC, the total iron-binding capacity, which I would say is probably your next most specific binding for iron deficiency. If it’s increased, it indicates that the body is really trying hard to produce proteins and absorb that extra iron. The iron panel also has an iron saturation, which really just looks to see how much iron is complex with the carrier proteins. That and a low serum iron are certainly supportive of iron deficiency, but are more reflective of what’s been going on in the very recent time period. So more of an acute finding, whereas the ferritin is an indication of total body storage of iron.
Dr. Gabi Hester: Now, talking about all these labs and we know that, unfortunately, labs require a poke of a kiddo and come along with other costs. Are there any circumstances where just that heel stick hemoglobin that the outpatient provider has gotten would be sufficient to start a kid on a course of iron?
Dr. Susan Kuldanek: In the case of a mild anemia, so 10 or greater, and the classic history of picky eating or heavy milk drinking, the recommendation by the AAP is actually just to empirically trial iron as both a diagnostic and a therapeutic.
Dr. Gabi Hester: Thinking a little bit about signs and symptoms of anemia, what are some of the things that I might see in a kiddo who is presenting with more moderate levels of anemia or iron deficiency?
Dr. Susan Kuldanek: In the kiddos with more moderate iron deficiency anemia or anemia, they will oftentimes, parents will tell you that they are a little more fatigued. They’re not really keeping up with their peers. They’re just wanting to take more naps or maybe not doing the activities that they normally do. The older kids might tell you that they don’t feel great or that they have difficulty concentrating. But in general, I would say crankiness and exercise intolerance are really the two most common findings in our younger kids.
Dr. Gabi Hester: What about when the anemia is really severe? Are there things I might find on my physical exam when those kiddos are coming into the hospital with a pretty profoundly low hemoglobin?
Dr. Susan Kuldanek: Yeah. Some common signs of more moderate to severe anemia, definitely a systolic ejection murmur. We hear that quite frequently. If the anemia is severe enough or longstanding, the kid might present in some degree of distress or at least with tachypnea, tachycardia, signs of poor perfusion. With very severe anemia, we may see signs of hypoxia, congestive heart failure, or seizure. But the thing to also remember is this is such a slow process that oftentimes kids are pretty well-compensated. And so it can be a little bit more subtle looking for some of these findings.
Dr. Gabi Hester: What are symptoms that might present maybe in the school setting, or other things we might not think about if it goes untreated for a long period of time?
Dr. Susan Kuldanek: The kids with longstanding anemia can have a lot of school performance issues, both behavioral and also attention issues. We’ve found that anemia is associated with neurologic complications, behavior issues like ADHD, even increased mortality. So cognitive, motor, attention memory deficits, all of those things can be associated with iron deficiency anemia the earlier it presents and the more longstanding the problem is.
Dr. Gabi Hester: We’ve talked a little bit about pallor and how that’s a finding that we might see in kiddos with anemia, but we talked at the introduction about how this really is a health equity issue as well. And how might this pallor look differently in kids with differing skin tones, such as having higher melanin content in their skin? How should we as providers be assessing for this?
Dr. Susan Kuldanek: Objectively, I look at the nail beds, the gums, and conjunctiva, all of which I think are a little bit more objective than just skin color alone. Also, ask the family if people have commented, like other relatives or family members who don’t see the child as often, that maybe they’ve noticed some changes in the appearance of the child. And then lastly, you can compare the child with other family members present in the room.
Dr. Gabi Hester: Let’s switch a little bit and talk about treatment. So we talked a little bit about diet earlier, so not treating iron deficiency with chicken nuggets, I guess. What are some of the dietary sources of iron that we all should be eating and putting into our diet?
Dr. Susan Kuldanek: There are two types of dietary iron. There’s heme-based iron that is found in animal meat, and also non-heme iron that comes from vegetarian sources. So good sources of the non-heme iron include legumes, nuts, whole meal pastas and breads, oats, tofu, and green, leafy vegetables. Many foods are fortified with iron and formulated in a way to enhance the iron absorption, like a lot of cereals, actually. Cheerios and other similar cereals have quite a bit of iron in them. In terms of what I tell parents to focus on, I do ask them to focus on cereals because that’s usually pretty easy. I also ask that they really try to increase the animal meat intake. If you look at a serving of an animal meat versus a similar serving of a green, leafy vegetable, you’re going to get about 10 times the amount of absorbable iron from that animal source.
Dr. Gabi Hester: We referenced milk a little bit earlier, but what’s your milk conversation that you have with families?
Dr. Susan Kuldanek: The cold turkey approach to completely stopping milk can be the most effective, and it’s definitely what I recommend for those severe cases.
Dr. Gabi Hester: What about iron supplementation? Tell me a little bit about the different options out there.
Dr. Susan Kuldanek: I generally start with ferrous sulfate, three milligrams per kilogram of elemental iron given once a day, usually in the morning or between meals, without other milk products or dairy products, which can inhibit the absorption. I like to start with ferrous sulfate just because it’s cheap, it’s easy, and it’s a effective. It’s an iron salt, so maybe does have more side effects than some of the other formulations. I counsel that we should take the iron without food but with water or vitamin C, like a juice, apple juice or orange juice to enhance the absorption. And really don’t give with meals, try to give at least 30 minutes before a meal or wait at least 60 minutes after a meal if you can.
Dr. Gabi Hester: What are the side effects that I might be seeing in my kid after we’ve started that?
Dr. Susan Kuldanek: Constipation is one, and so I always ask families if this is already a problem at baseline. And if so, I recommend usually just having a very low threshold to start some MiraLax. A lot of the irons, especially the iron salts, can be very irritating to the stomach, and so some kids really just hate and fight it. But lastly, the icky, yucky taste is a huge barrier for a lot of parents. We can try hiding it in juice, sometimes that works. But oftentimes, we just need to switch to a different type of iron that tastes better.
Dr. Gabi Hester: What are some of those options that taste better? And I’m going to work on the assumption that you’re not getting kickbacks from any of these companies.
Dr. Susan Kuldanek: If a kiddo has tried ferrous sulfate and that has not worked, I oftentimes, if this is a liquid drinker, which most of our under five-year-olds are, I recommend something called NovaFerrum, which is a polysaccharide iron. It’s not an iron salt, it’s a polysaccharide-formulated iron and it’s a lot gentler. It’s gentler in the stomach and it’s a lot tastier. A lot of children also like the iron gummies. These are usually a ferrous fumarate, which is another iron salt, but just doesn’t seem to be as irritating and in the gummy form is pretty tasty to kids. They’re kind of like candies. Just note that the total amount of elemental iron is quite low in the gummies, and so we may be talking a couple or a few gummies a day to get the proper dose.
There are a few others that I recommend quite frequently. One is called Celebrate, also a ferrous fumarate. This comes in different forms, like different chewable tabs. You can get it on Amazon. And it also has vitamin C in it to help enhance the absorption. Lastly, for some kids that have tried multiple different iron saccharides and iron salts, we’ll try something called Proferrin, which is actually a heme-based iron, sort of derived from animal proteins. This is a polypeptide and it can be pretty effective in kids who haven’t shown efficacy with the other formulations. All of these options are a bit more expensive than the ferrous sulfate and may cost as much as 10 to $20 a month.
Dr. Gabi Hester: What About IV iron? So sometimes the oral iron isn’t enough to kick that anemia. When do we start thinking about other options?
Dr. Susan Kuldanek: For any kid that’s in that severe range, less than six, I generally recommend an admission to get started on the IV iron more quickly. This isn’t a hard and fast rule, but I think it’s really a good place to consider starting the admission and starting some IV iron. And that’s why we chose it for our guideline.
Dr. Gabi Hester: And what about blood transfusion? Tell me a little bit about what threshold you guys have on the clinical guideline that you developed, and where does that come from?
Dr. Susan Kuldanek: As far as blood transfusion, this is definitely one of those ask 10 hematologists and you’ll get 10 different answers. We settled on five. Five is a pretty good number, I think, because it’s to a point where if you get much lower than that you’re really getting into the danger range. So I would definitely transfuse or consider transfusing for someone who is under five. Would definitely transfuse for any patient with hemodynamic instability, but that I would also strongly consider transfusion for a severely anemic but hemodynamically stable kid who’s under five grams per deciliter just because that’s so low.
Dr. Gabi Hester: How much do you expect the hemoglobin to rise after you’ve given a blood transfusion?
Dr. Susan Kuldanek: So in pediatrics where we use weight-based dosing, a typical transfusion is about 15 mils per kilogram. Each five mils per kilogram should raise you approximately a gram. I just want to point out that we recommend transfusing pretty slowly just to avoid any fluid overload or cardiac compromise, as these kids have probably slowly equilibrated themselves to these low levels.
Dr. Gabi Hester: When I’m thinking about using IV iron for a patient in the hospital with anemia, can you tell me about the different types of IV iron that might be available to me and when I should use one versus the other?
Dr. Susan Kuldanek: At Children’s Minnesota, we have two different iron formulations that are available inpatient, Venofer, which is iron sucrose, and iron dextran. Our guideline for the kids five and under specifically recommends the use of Venofer or the iron sucrose. This is an iron that can be given in very small aliquots. We recommend doing it once or twice, maybe one day apart, one to two milligrams per kilo. This will not correct the child’s total deficit, but that’s okay. They really just need to work on their diet, and that is really the most important thing. And that’s in contrast to the adolescent menstrual bleeding guideline, which is specifically designed for patients with a uterus and menstrual bleeding. The important thing to remember is that these patients are much bigger with a larger blood volume and a blood loss source. And so giving them a much larger volume of iron is important, which is why we use iron dextran, as it can more completely correct the deficit.
Dr. Gabi Hester: And I know the clinical guideline calls for giving IV iron alongside the blood transfusion, maybe not at the exact same time, but during that same encounter. Why is that? Why are you giving iron to a kid who’s also getting blood?
Dr. Susan Kuldanek: The reason is the blood transfusion is essentially get the child out of the danger zone, just quickly get them to a more safe level. But the safe level is still pretty low. So if I got my kid who started off at three grams up to six grams, now I want to give them a little extra iron to jumpstart that recovery process. And if you think about it, our guideline would tell you to give IV iron probably in a kid at six anyway.
Dr. Gabi Hester: In kids in that more mild, moderate zone who are on oral therapy, at what point do you recommend outpatient providers recheck a hemoglobin?
Dr. Susan Kuldanek: For kids in the more mild to moderate range when they start off with, I think as long as they’ve demonstrated that they can take their iron, at least in the clinic or in the hospital setting, that the family seems pretty reliable. I would be okay checking about two to four weeks out depending on the initial severity. At that point, I would check a hemoglobin or a full CBC with a reticulocyte count. So the reticulocyte count should increase actually very quickly, within 24 hours of getting some iron in the body. You should start to see an increasing reticulocyte count. And at that about, let’s just say two week mark, we should see probably at least a two gram increase at that point with an elevated retic that would let us know that the kid is actually getting iron in the body. And from there, I would check every one to two months until the hemoglobin has normalized.
Dr. Gabi Hester: You are a pediatric hematologist. A lot of people out in the community are managing iron deficiency anemia in their outpatient practice. When should they call you? When should hematology be consulted?
Dr. Susan Kuldanek: I would say any time someone feels uncomfortable. If there’s something that just feels a little different or off, absolutely call hematology. I would say if the PCP has been really working with the family to troubleshoot compliance issues, tastes, they’ve tried different irons, they feel like they’ve really just done everything they can and nothing is changing, absolutely reasonable to send to us. Sometimes, it’s really just that the family hadn’t sufficiently bought in up until that point. And there’s something about coming in to see the specialist that is a wake-up call to families.
I would say if the ferritin is normal and the CRP is normal and your hemoglobin is still low, that’s another reason to send to us. We can do further investigations. If the PCP feels comfortable, they can certainly send an electrophoresis to look for the beta thalassemia trait, but either way, we’re happy to see them. I would say if you’re concerned for something else going on, jaundice, an unusual family history, of course, if there’s any of those significant red flag issues, like two cell lines down, ill appearance, chronic fevers, bone pains, give us a call more on the urgent side.
Dr. Gabi Hester: So for kiddos who have severe iron deficiency anemia and are being taken care of by my colleagues and your team in the hospital, when should they follow up in hematology clinic or with their primary provider after hospital discharge?
Dr. Susan Kuldanek: I really like them to be seen by their primary care provider within about a week just to really ensure that we are moving in the right direction, that that reticulocyte count is higher and that the hemoglobin has improved. And really, within a week it should be a half a gram to a gram increased from where they were prior to leaving the hospital.
Dr. Gabi Hester: Awesome. Well, thanks so much. I learned a lot today. And thanks for the conversation. Really appreciate you coming in.
Dr. Susan Kuldanek: Thank you. It was my pleasure.
Speaker: Take home point.
Dr. Gabi Hester: Number one, ferritin is the best test to diagnose iron deficiency anemia. Number two, iron failure is usually due to not taking iron consistently. Number three, education and dietary counseling are key for families dealing with iron deficiency anemia. Number four, red flags for something else going on include two or more cell lines being down, ill appearance, dysmorphology, weight loss, big liver or spleen, big lymph nodes, bleeding, or GI symptoms. Number five, the clinical guideline for iron deficiency anemia in children five years of age or young is available at www.childrensmn.org on the health professionals page.
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. Amie 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.