Iron Deficiency Anemia – PediaCast 502
- Dr Amanda Jacobson-Kelly visits the studio as we consider iron deficiency anemia. This common condition affects nearly 10% of young children in the United States. We consider the cause, symptoms, diagnosis, treatment and prevention. We hope you can join us!
- Iron Deficiency Anemia
- Hematology at Nationwide Children’s Hospital
- Anemia in Children and Teens: Parent FAQs
- Boosting Iron Levels in Children (for providers)
- Pump Up the Diet with Iron (for parents)
- Choosing an Infant Formula
- Vitamin D and Iron Supplements for Babies
- Heavy Menstrual Bleeding: What Girls (and Parents) Need to Know
Announcer 1: This is PediaCast.
Announcer 2: Welcome to PediaCast, a pediatric podcast for parents. And now, direct from the campus of Nationwide Children's, here is your host, Dr. Mike.
Dr. Mike Patrick: Hello, everyone and welcome once again to PediaCast. It is a pediatric podcast for moms and dads. This is Dr. Mike, coming to you from Nationwide Children's Hospital. We're in Columbus, Ohio.
It's Episode 502 for September 8th, 2021. We're calling this one "Iron Deficiency Anemia". I want to welcome all of you to the program.
We have another important topic for you this week, one that is not only important for children but also for parents, and in particular, mothers. And it's important because iron deficiency anemia is extremely common particularly among children and women of child-bearing age.
In fact, if you consider the global population, the World Health Organization estimates that 40% of all children, less than five years of age, 40% of all pregnant women and one-third of all women of reproductive age are anemic. And the most common cause of their anemia by far is iron deficiency.
Developing countries are the hardest hit but iron-deficiency anemia is still pretty common in the United States, affecting 9% of all children between the ages of 12 months and 3 years, and 10% of all women of child-bearing age.
And anemia can have a significant impact on child and adult health, as we will discover. It can result in growth and developmental delays, chronic fatigue, weakness, shortness of breath, headaches and it can impact school and work performance.
Now, despite this high prevalence numbers, there is also some good news. Iron deficiency anemia is preventable and fairly straightforward to treat. But in order to treat iron deficiency anemia, we first must recognize the problem.
And so, today, our mission is to raise awareness. We will define the term anemia and explain how iron deficiency causes it. We'll take a closer look at the symptoms and complications of anemia.
We'll consider common causes of iron deficiency, which then can result in anemia, including the overconsumption of cow's milk, particularly by babies and toddlers. And we'll explore the diagnosis and treatment of iron deficiency anemia. We'll also share some useful prevention strategies.
And to help us do all of this in our usual PediaCast fashion, we have a terrific guest joining us. Dr. Amanda Jacobson-Kelly, she is a pediatric hematologist at Nationwide Children's Hospital.
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So, let's take a quick break. We'll get Dr. Amanda Jacobson-Kelly connected to the studio and then we will be back to talk more about iron deficiency anemia. It's coming up right after this.
Dr. Mike Patrick: Dr. Amanda Jacobson-Kelly is a pediatric hematologist at Nationwide Children's Hospital and an assistant professor of Pediatrics at the Ohio State University College of Medicine. She treats young patients and helps families impacted by iron deficiency anemia which affects nearly 10% of all children between the ages of 12 months and 3 years here in the United States of America along with millions of additional children around the world.
That's what she's here to talk about, iron deficiency anemia. But first, a warm PediaCast welcome for Dr. Amanda Jacobson-Kelly. Thank you so much for being here today.
Dr. Amanda Jacobson-Kelly: Thank you for inviting me. I'm excited to talk more about this topic.
Dr. Mike Patrick: Really appreciate you stopping by. So, let's start with a definition, and I think as we think about iron deficiency anemia, we would want to define anemia and then iron deficiency. So, what do we mean by those terms?
Dr. Amanda Jacobson-Kelly: These two terms are used quite interchangeably, iron deficiency and anemia. And not all anemia, and in fact, a lot of anemia is not iron deficiency. But iron deficiency causes anemia once it gets severe enough.
So just to specifically talk about iron deficiency, it is the most common nutritional deficiency in the world and also one of the only nutritional deficiencies that's still quite prevalent in the developed worlds. It affects about 2.3 billion people worldwide.
The anemia part of it is when you get iron deficient enough to have a low hemoglobin and that would be defined by a hemoglobin that's lower limit of normal for age, which is different with each age.
Dr. Mike Patrick: Okay, so anemia, you don't have enough red blood cells.
Dr. Amanda Jacobson-Kelly: Exactly.
Dr. Mike Patrick: In the blood. And that's important because those deliver oxygen to tissues, so they have an important job. And if you don't have enough of them because you're anemic, you're going to have some problems, we'll get into in more detail in a few minutes.
But then iron deficiency, of course, it's just not having enough iron in your blood, right? Again, as you mentioned, very commonly because of a nutritional deficiency, you're not getting enough iron in the food that you eat. And so, iron is an important building block for the hemoglobin, which is inside the red blood cells, right?
Dr. Amanda Jacobson-Kelly: Exactly. And iron also important in other parts of the body, including in the electron transport chain which helps your muscles, and also in some of the neurotransmitters in your brain that help with sleep and concentration. And then, also, it's important to the immune function as well. So, it's not just the red blood cells but that's probably the most important role of iron.
Dr. Mike Patrick: And then, I think we've been making the point that this is a very common condition, including here in the United States. Give us some more numbers surrounding how common this is and then who in particular is affected.
Dr. Amanda Jacobson-Kelly: So, there are two age groups that are the most affected. So, it's the most common in toddlers. So, we're talking about children between the ages of 12 months and 5 years. Up to 15% of toddlers have iron deficiency and about one-third to one-half of those have iron deficiency anemia.
In the school-aged children who have a little bit better diets, they typically have less, only about 7% are iron-deficient. But when you get up to the teenage years, it goes up again. And about upwards of 20% of teenagers, especially teenage girls, are iron deficient, and about half of those are anemic.
Dr. Mike Patrick: So really very, very common issue in the United States even. And in particular, we're looking at the toddler age groups, the teenage girl groups. That's really in our population where you're going to see the most of it, is that right?
Dr. Amanda Jacobson-Kelly: Yeah, absolutely.
Dr. Mike Patrick: And then, explain in a little more detail how iron deficiency then causes anemia. Kind of take us to the building process of the hemoglobin from iron.
Dr. Amanda Jacobson-Kelly: So, you need iron for every red blood cell. And it's part of the heme portion of a red blood cell and it's required. So, when you start off, iron deficiency kind of has stages.
Your body has what's called iron stores or like kind of a total iron volume in your body. And when those stores start to get depleted, you can see some symptoms of just iron deficiency.
And then, once those get more and more depleted, you start to get what we call iron deficiency without anemia. So that's just beyond depleted iron stores. And then further than that, you start to get iron deficiency anemia. And the symptoms progress as you go down the line,
But without iron, you cannot make red blood cells. So, you need iron to make the red blood cells in the bone marrow. So, it's really important, you really can't live your life without iron.
Dr. Mike Patrick: Where are the iron stores? Where does iron get stored in your body?
Dr. Amanda Jacobson-Kelly: So primarily, in the liver and then in macrophages which are immune cells. But probably 75% of iron is incorporated into red blood cells at any given time.
Dr. Mike Patrick: So really, it's an important thing to have enough iron in your body, but you do have some stored iron. And the first thing if you aren't getting enough iron, you're going to deplete that storage up before you're really going to notice that there's much of a problem.
But then, once you stop depleting those stores, then the iron levels in the blood are going to drop and in the bone marrow where you're trying to make new red blood cells. And so then, you're going to have some different blood cells.
And we do have a significant number of pediatric providers in the audience as well. So, the red cells that are made when you are iron deficient are a little bit different than a normal red blood cell would be?
Dr. Amanda Jacobson-Kelly: Yes, the red blood cells in iron deficiency are typically lighter in color and they have kind of a much paler center. And they also can be misshapen, especially in more severe iron deficiency and you can actually see very odd-shaped red blood cells like the shape of pencils. And you can also see different kinds of red blood cells with spikes or broken red blood cells as you get further and further down with iron.
And then also, you can get the red blood cells with iron deficiency are a lot smaller than regular red blood cells.
Dr. Mike Patrick: So, this is what we would call a microcytic hypochromic anemia, if we're talking to our doctor friends, right?
Dr. Amanda Jacobson-Kelly: Exactly.
Dr. Mike Patrick: Okay. So, the next thing that comes to my mind is how do we get iron deficient in the first place? So obviously, the number one reason would be not enough iron in our diet. But there are other reasons too, right?
Dr. Amanda Jacobson-Kelly: Yes, absolutely. So, I think to answer that question, you have to start all the way back from when the baby is in utero. And so, during the third trimester of pregnancy, babies get their iron stores from their moms through placental transfer. So, the babies start off with iron stores that are higher that came from mom.
And as babies grow, they start to deplete their own iron stores and they start to need iron stores from their diet, so formula, breast milk. And as they get past four to five months, their iron stores that they were born with start to really get depleted. And that's when they start to be at risk for iron deficiency if they don't have extra iron in their diet.
Dr. Mike Patrick: What age again does that start to happen?
Dr. Amanda Jacobson-Kelly: Between four and five months.
Dr. Mike Patrick: Okay, about four and five months of age. It's important that we start kids, that they're getting enough iron and we'll talk more about how you do that right from the time that they're born. But in particular, four or five months is when mom's iron that crosses over the placenta and kind of gives them their initial storage of iron is starting to be depleted. And so, we have to make sure that we're replenishing that through diet.
There's also some disease processes too, right, that could cause poor absorption of iron? So, there may be enough iron in the food but if we're not absorbing nutrients very well in our gut… So, things like celiac disease or short gut syndrome, those kinds of things, right?
Dr. Amanda Jacobson-Kelly: Absolutely. And so, celiac disease in children sometimes doesn't have other symptoms that you would classically think of, like gastrointestinal symptoms. So, anemia and iron deficiency can actually be one of the first signs. That's because the area in which iron is absorbed is the same area of the gut that's affected by celiac disease.
Also, short gut patients, the same area that we're talking about, the stomach and proximal duodenum, so kind of the upper part of the GI tract. So, patients, they're missing that part or perhaps in areas beyond that part, like with duodenal tubes may also be at risk for iron deficiency.
Dr. Mike Patrick: And one other thing that can do this is if you have a fast turnover of red blood cells. So, if you have a disease process or you're losing blood, so your body has to make more red blood cells, you're going to use up your iron.
So other things to think about would be sickle cell disease where you are making lots of red blood cells because they're misshapen and they're getting taken out of circulation because of that.
And then, blood loss, especially menstruation, so that's one of the reasons that teenage girls are at high risk for iron deficiency anemia because they… It could be diet too, not getting enough iron in their diet. But menstruation also is blood loss.
And other things where you lose blood is through the GI tract, so peptic ulcers and inflammatory bowel disease and that sort of thing. In the adult world, polyps and cancers that fortunately are less common in kids.
So, a lot of different things that can be related to iron deficiency anemia and end up causing it. But regardless of the cause, the signs and symptoms are going to be the same. And what are those for iron deficiency anemia? How do we pick this up clinically?
Dr. Amanda Jacobson-Kelly: So, there's lots of different symptoms. And I think the most overused or, I guess, most common symptom is fatigue. But I feel that's a hard symptom to really identify because so many patients, especially teenagers are fatigued for one reason or another.
And even without the anemia part but with just the iron deficiency, you can see things like pica. So that's the craving for things that aren't actually food. And the most common is cravings for ice, and we see that a lot in teenagers with iron deficiency.
And then also poor concentration, you can see headaches. You can see dizziness with standing, shortness of breath. Or in the case of athletes, effort intolerance, so they feel kind of fine at baseline, but we'll see athletes where their running times are noticeably decreasing even though they feel like they're trying as hard or they're as conditioned as they usually are.
And then you, also in some cases, can see things like hair loss or restless leg syndrome. And certainly, when you get very very anemic, you start to see things like pallor or extreme fatigue and loss of appetite and stuff like that.
Dr. Mike Patrick: Yeah, and the set of symptoms that you're describing really makes sense when you step back and think, well, there's not enough red blood cells to carry oxygen to tissues. And so, fatigue, exercise intolerance goes well with that. If you do not get enough oxygen to the brain, you can have headaches and dizziness and lightheadedness.
In babies, they may just be irritable and fuzzy. Your body's trying to circulate around those fewer red blood cells. So, if you still want to deliver oxygen to the tissues, you have to recirculate the blood, so you're going to have your elevated heart rate. You may be breathing faster because you're cycling those red blood cells through the lungs and so you have to oxygenate them.
So, all of those symptoms that you describe really do make sense when we think about the underlying problem with anemia. I do find it interesting, the pica thing, like why ice? Some things, you can't explain maybe.
Dr. Amanda Jacobson-Kelly: And we can't, actually. There really hasn't been a great explanation for why you crave those sorts of things. My kind of gut instinct is that it just really is your body feeling like that's what it needs to survive. And I guess like ice being maybe had some sort of kind of metallic taste properties. But your body is basically craving metallic things.
But I mean, some kids, really, when they start having pica symptoms, they like earth supplies, too.
Dr. Mike Patrick: Yeah, so like clay and dirt even. Kids will eat dirt, yes.
Dr. Amanda Jacobson-Kelly: Crayons, wall paint.
Dr. Mike Patrick: Very very interesting.
Dr. Amanda Jacobson-Kelly: Toilet paper. I've seen it all.
Dr. Mike Patrick: One other thing that I find interesting with anemia is that especially when it develops slowly, the body has a great reserve of being able to sort of make up for this in the way that you metabolize, I guess.
So when I was in general pediatrics practicing in an office, you can see kids whose hemoglobin was so low that if you took, you or I, and gave us that hemoglobin, we would have a ton of really severe symptoms. And yet, they're living with it because it was such a gradual decrease. I'm sure you see that in your practice, too.
Dr. Amanda Jacobson-Kelly: Yes, definitely, especially in the toddler group. So, the nutritional iron deficiency in toddlers is such a slow process that they typically are completely compensated until they get to such a low hemoglobin they can't really compensate anymore.
But a lot of these are picked up incidentally on screening labs or it's just something that they're at well visit and mom maybe mentioned, "Oh, he likes to eat dirt and that's just a toddler thing." Just last week, we had a patient that was picked up just because the mom mentioned that he had some pica symptoms.
Dr. Mike Patrick: One of the things I think from a parent's perspective that makes him think about anemia is pale skin. But some kids are really light-complected and have very pale skin. I was always taught you could look at the inside of the lower eyelids where the conjunctiva kind of wraps up from the surface of the eye and then up inside to the eyelid there. Because that's usually pretty vascular and they'll have a nice pink color to it.
Is that a good… Of course, if they're really pale and parent's concerned, let's get a hemoglobin. But that's one way that you can sort of help differentiate just fair-complected?
Dr. Amanda Jacobson-Kelly: Yes, absolutely. That's actually something I check on exams. I find that they have to be pretty significantly anemic, at least more than mild, so moderate or severe anemia to have that.
Another place I also look is the palms. So even in dark-skinned individuals, the palms are light. So, when you have moderate to severe anemia, you get palmar pallor.
And what I do is hold the hand upright and kind of pull back on the fingers. And you can see the palmar crease is usually filled in red if you have normal hemoglobin. But if you're starting to get anemic, you'll see a lot of pallor there and you won't see the palmar creases filling red. So, it's kind of hard to describe without a visual, but that's another place I'll look.
Dr. Mike Patrick: No, you created a great visual. I kind of picture exactly what you're saying. So then, we've talked about some risk factors for developing anemia, one certainly being nutrition and just not eating enough iron-rich foods.
And we'll talk more about what those are, and we'll also talk about teenagers and menstruation. But there's some other risk factors for when you may develop iron deficiency anemia, right?
Dr. Amanda Jacobson-Kelly: Yeah, I think we're learning more and more about the risk factors. So, prematurity is a huge risk factor because as I mentioned before, the iron stores you were born with you got during the third trimester of pregnancy. So, if the baby is premature, they're not going to get that same load of iron. And also, if mom herself is very iron-deficient, that will lead to an increased risk.
Other risk factors or other reasons, so remaining in the toddler-aged group, actually lead toxicity is a huge risk factor for iron deficiency and kind of has a synergistic effect. So, iron deficiency worsens lead toxicity, lead toxicity worsens iron deficiency.
And then a common problem these days is actually obesity as a risk factor for iron deficiency because it's actually poorly understood. Probably it's because there's more iron demand because of more body mass. But also, there's associations with obesity and chronic inflammation and perhaps there's less absorption of iron. And I certainly see that in practice, I more commonly see iron deficiency in obese patients.
Dr. Mike Patrick: And the high calorie foods typically aren't necessarily your high iron foods, either. And so, your diet may be such that you're not malnourished but you're not really getting a lot of iron-rich food in, but you're obese.
Dr. Amanda Jacobson-Kelly: Totally, and I think that iron is in a lot of foods because a lot of foods are fortified with iron. But the problem is, the iron that they use for fortification is non-heme iron, just like the iron you supplement with and it's just not absorbed as well. It's not as bioavailable in the body as iron from meat. So again, vegetarians and vegans are also at risk for iron deficiency.
Dr. Mike Patrick: And athletes, athletes can be at risk too, why is that?
Dr. Amanda Jacobson-Kelly: So, this is kind of a newer area in iron deficiency. So, athletes, we've always known that athletes, especially female athletes are at risk because of heavy periods and perhaps poor diets. They're not eating enough to maintain the consumption needed for their particular sports. But athletes tend to have a higher iron demands, specifically athletes that do endurance sports, like cross-country, running, track.
But we also see it in soccer. We see it even in like volleyball, gymnastics, just with the club sports these days. And I think that sports are becoming more and more competitive. And these school-aged kids, teenagers, they really have a high iron demand and they just can't meet it with just the iron in their diet.
Dr. Mike Patrick: So that's the segment that we maybe should be screening more than we do, do you think?
Dr. Amanda Jacobson-Kelly: Yes, and I think that the sports medicine doctors are starting to look for more, especially in the girls. Certainly, boys are at risk too, but girls are at a much higher risk.
Dr. Mike Patrick: And then, one risk factor that may surprise parents is the overconsumption of cow's milk. Tell us about how that relates to becoming iron deficient and then anemia.
Dr. Amanda Jacobson-Kelly: So, this is one of my favorite topics. So, cow's milk, I think in the United States, there's been such a push for cow's milk, a lot of campaigns like Got Milk? And so, it's just a favorite of most Americans. And don't get me wrong, I love cow's milk myself.
But the problem with cow's milk is several folds. So, there is a lot of calcium in cow's milk and calcium itself blocks iron absorption in the intestine. And then, in addition to that, the casein in the cow's milk also blocks iron absorption so it's kind of a two-fold blocking of iron absorption.
And then, cow's milk is filling, especially for toddlers. So, toddlers who drink a lot of cow's milk will eat less iron rich foods. And that can just lead to a slow decline in their iron stores and eventually lead to anemia. And that's probably the most common reason we see anemia in toddlers. And actually, even some adolescents, I just saw a teenage boy a couple of weeks ago that drinks a gallon of milk a day and had iron deficiency. So, it can happen.
Dr. Mike Patrick: Now, we should point out, infants less than 12 months of age, breast milk is best. And then, you're going to want to use an infant formula if you're not breastfeeding and not cow's milk if you're less than 12 months of age because you really do need it fortified with more iron and more nutrients in there as well, correct?
Dr. Amanda Jacobson-Kelly: Yeah. And that's very important, cow's milk should not be given less than 12 months of age. And in particular, there is actually pretty significant risk. Up to 40% of infants who had given cow's milk early on can actually have gastrointestinal bleeding. And I'm not talking about cow's milk-based formula. I'm talking about straight up cow's milk.
Dr. Mike Patrick: And you may not see blood in their stool. It may just be a very small amount of blood, but over weeks and months, that starts to become an issue.
Dr. Amanda Jacobson-Kelly: Exactly. It's a microscopic blood burst.
Dr. Mike Patrick: So then, for the toddlers, how much milk is too much? What should the limit be?
Dr. Amanda Jacobson-Kelly: So, I think the American Academy of Pediatrics recommends less than 24 ounces of milk a day. I, as a hematologist, I think, maybe because I'm a little biased and I see this a lot, I typically aim for less than 16 ounces. And the reason I say that is because I feel like everyone probably underestimates how much their kids are drinking.
So, I think just having a lower cutoff, knowing that vitamin D is also important. So, it's kind of a battle between the iron and the vitamin D.
Dr. Mike Patrick: So, about two eight-ounce bottles of milk a day are going to be okay, or four four-ounce bottles. But you don't want to go much above that.
Dr. Amanda Jacobson-Kelly: Exactly.
Dr. Mike Patrick: What should you offer kids instead? So, they're thirsty, they want to drink, they're asking for a bottle. What do we substitute milk with?
Dr. Amanda Jacobson-Kelly: I think water is the best answer and the perfect answer. Supplementing with juice is not the answer because they end up having too much sugar. Also, I see patients that substitute their milk for juice and then actually get a lot of diarrhea related to the sugar and the juice.
So, I think water, for sure. If the child really wants milk per se, the other milks, the plant-based milks don't have the same issue as cow's milk does. So, if they want to try rice, almond, cashew, oat, but I still think that those can still be filling like the cow's milk, so encouraging water is the best.
Dr. Mike Patrick: Because that way, they're going to get other nutrient-rich food that hopefully has iron in it. And again, we'll get to what those are here in a minute.
Before we move on to that, there are other things that cause anemia. So, when we screen for anemia, part of a well checkup was to check the hemoglobin level. They come back and they are anemic.
There are other things that can cause anemia, right? What are those?
Dr. Amanda Jacobson-Kelly: Certainly. As you alluded to earlier, there are genetic conditions that cause anemia, like sickle cell disease and thalassemia. Those are typically diagnosed earlier on. But patients can actually carry traits for those diseases that don't actually cause disease but are just genetic traits. And those can actually cause some anemia, too. And that's something we see pretty commonly.
Certainly, there are some autoimmune diseases that cause anemia and cause breakdown of red blood cells. So, things like leukemia, lymphoma, cancers that can cause anemia, mostly because they take over the bone marrow and the bone marrow can't produce red blood cells.
Then, also, just things like fibrosis can cause anemia, at least temporarily, because they can cause bone marrow to temporarily stop production. Or I'd just say kind of get lazy for a little bit. And then it will ramp back up and start to produce again.
And then, of course, blood burst causes anemia, but blood burst also causes iron deficiency because you're losing the iron.
Dr. Mike Patrick: And you mentioned blood poisoning too could also potentially cause anemia.
And then, some vitamin deficiencies, folate, B12, vitamin C, those can also be related to anemia?
Dr. Amanda Jacobson-Kelly: So, we definitely see those. They are a lot less common in iron deficiency, but B12, specifically in patients that are vegan, or babies born to vegan mothers or patients with difficulty with absorption like celiac disease.
Folate, we actually see a lot less frequently, but we check for it a lot. And those patients typically are the ones that have chronic red blood cell breakdown, so like the patients with inherited hemolytic anemia like sickle cell disease or hereditary spherocytosis, which is another really common one.
Vitamin C deficiency can actually cause anemia and it has to be scurvy. It has to be pretty severe and we don't see it very often. But certainly, children that are very very selective in the foods that they eat could develop something like that.
And then another nutritional deficiency we see that causes anemia is copper deficiency. And that doesn't typically happen to normal children without medical problems. It's more patients with impaired gut absorption for one reason or another.
Dr. Mike Patrick: Got you. That must be hard to get. How do you get copper? How do you supplement with copper? I guess it's in their multivitamins?
Dr. Amanda Jacobson-Kelly: Yeah. And there's like a copper specific IV supplement that we will give orally. And it's highly present in cocoa. So, you can actually use cocoa powder. That's what they do in some of the underdeveloped countries for copper deficiency.
Dr. Mike Patrick: So, chocolate.
Dr. Amanda Jacobson-Kelly: Yeah, chocolate. Eat more chocolate.
Dr. Mike Patrick: All right, the doctor said so.
All right, how then do we diagnose iron deficiency anemia?
Dr. Amanda Jacobson-Kelly: So, the easy answer is with ferritin. Anytime a serum ferritin is less than 15, that's always iron deficiency. The anemia part needs like hemoglobin. The American Academy recommends screening hemoglobin somewhere between the first and second year of life. And that can catch the anemia part, but not specifically the iron deficiency part.
So, I think in the future, and kind of knowing some people in the background in the AAP, we may be starting to do ferritins more often. And the AAP may endorse using ferritins for…
Dr. Mike Patrick: So, checking hemoglobin and ferritin together? Or would the ferritin substitute for the hemoglobin?
Dr. Amanda Jacobson-Kelly: I think that you should check them together because you certainly can have anemia with a normal ferritin. And also, ferritin is an acute phase reactant. So, it will go up during times of illness or inflammation. So, it's not a perfect test. There's really no perfect test that we have right now for iron deficiency.
But the great thing about ferritin is if it is low, it is iron deficiency. There's not really anything else that makes it falsely low.
Dr. Mike Patrick: Just to demystify that, ferritin is a protein that the body uses to store iron. And so, if you don't have a lot of iron, you're not going to have a lot of ferritin, this is a fact.
Dr. Amanda Jacobson-Kelly: Yes, exactly.
Dr. Mike Patrick: Okay, so we want to check the hemoglobin. And how low of a hemoglobin is too low?
Dr. Amanda Jacobson-Kelly: So, the cut-off, it basically depends on the age of the patient. With the AAP, they use a hemoglobin of 11 as the cut-off which is the lower limit of a normal for like a toddler-aged group.
And as children age, they need higher hemoglobin, so around 11, 11.5 is the lower limit of normal for school-aged children. And once they get to the teenage years, 12 is the cut-off for girls and actually it's up to 13 for boys.
So, I think you really, if not seeing this every day, have to rely on the reference range for the lab. But the WHO definitions are greater than 13 for boys, teenage boys, and greater than 12 for teenage girls.
Dr. Mike Patrick: So, 11 in babies and more like 12, 13 in the teenage years. And those are really kind of the two periods when we're screening pretty much everybody.
Dr. Amanda Jacobson-Kelly: Exactly. And like little tiny babies can go down around the physiologic nature, so all babies, kind of their hemoglobin falls after they're born and comes back up. So, they can actually go down as low as nine and a half and be okay. But I think that 11 is a good number to remember.
Dr. Mike Patrick: Great. So why don't you just check blood iron level? Is that another thing that you can do?
Dr. Amanda Jacobson-Kelly: That's a great question. And I think this is a very common misconception about iron deficiency. So, the serum iron is very reflective of iron that was recently ingested. So, if that patient takes their iron tablet right before they come to see me, their serum iron may be actually elevated even though they have iron deficiency.
And we actually use the serum iron as a way to see if patients are absorbing iron. So, we can do an iron challenge where we check the serum iron, give them a tablet of iron, and then check two hours later and see it actually increases 100 to 200 points.
So, the serum iron, unless somebody's may be being continuously fed like a patient with a duodenal tube or something like that, is really not a reliable way to check for iron deficiency.
Dr. Mike Patrick: Okay, good to know. So how do we treat iron deficiency then?
Dr. Amanda Jacobson-Kelly: So, the kind of gold standard or the I guess tried and true is oral supplementation. And the old school one is the ferrous sulfate. That's actually very bioavailable and typically corrects iron deficiency quickest among the other oral iron supplements. But it tastes terrible so that can make it limiting for some patients, especially toddlers.
So, there's liquid and there's tablets. And actually, more recently, one of the companies is called NovaFerrum which you can just purchase online has chewable iron supplements that aren't like multivitamins with iron, but it just have iron and some vitamin C.
And those are kind of what I use for the toddlers that really struggle with the liquid. They're spitting it everywhere and aren't quite ready to swallow pills yet.
So, we're getting better and better ways to supplement orally that taste a little bit better and don't necessarily cause many side effects.
Dr. Mike Patrick: What about the teenage girls who may be anemic? What do you treat them with?
Dr. Amanda Jacobson-Kelly: So actually, I typically treat them with ferrous sulfate, just one tablet. What we've always learned is that to correct iron deficiency, you need to supplement with at least three milligrams per kilogram per day of the elemental iron. So, in ferrous sulfate, only 20% of ferrous sulfate is actually iron, the elemental part, and the rest is sulfate. So, it taste so bad.
But in teenage girls, you need that much. Say there are 100 kilograms, they don't need 300 milligrams of elemental iron per day.
Some of the newer literature actually shows that if you give them too high of a dose of iron, or you give iron too often, it actually will not get absorbed as well. Because with each time you take iron, it actually releases the hormone called hepcidin that blocks iron absorption. And then when you subsequently take iron, a little bit of the absorption is blocked.
So, what I typically do for teenage girls is just once a day ferrous sulfate. And if they only have a mild anemia, I will actually do it every other day because that actually works just as well as every day and has less side effects.
Dr. Mike Patrick: And what side effects are we worried about?
Dr. Amanda Jacobson-Kelly: So, the most common side effects are gastrointestinal. So, constipation is a huge side effect and that's a very common problem in pediatrics in general. So, you kind of adding fuel to the fire with the adding iron.
And just general like nausea, GI upset, and you can also see very commonly, that your stool color changes to black or like a very dark color. And that can be alarming for parents, so that's something you have to make sure to warn them about.
And not so much as a side effect but an annoyance, but liquid iron, it really stains, it will never come out. So, I always recommend parents to be giving it to their children in just their diapers. Because otherwise, it will ruin their clothes.
Dr. Mike Patrick: Absolutely. So, supplementation with iron is going to be important. And then, can you fix this through diet if it's a mild iron deficiency?
Dr. Amanda Jacobson-Kelly: So yes and no. I think that if it's very mild, you can just start to add more iron rich foods. There's a number of those. I think that adding more meat into the diet if you are not a vegetarian is really the best way to supplement through diet alone. Because, again, the heme iron is much bioavailable than non-heme iron or vegetable sources of iron.
And you can also, you could just add a multivitamin with iron. I think that it's important to look at the contents of multivitamins and really the popular multivitamins these days are gummy multivitamins. And no gummy multivitamin has really any measurable iron in it because the iron doesn't make it gummy anymore.
So, the kind of good old-fashioned Flintstones chewables are a good way to just supplement with the multivitamin.
Dr. Mike Patrick: Got you. Let's talk about those iron rich foods because then this is one way that we can prevent iron deficiency anemia, right, is by eating more iron rich foods? So, what kind of foods are we talking about that have high levels of available iron in them?
Dr. Amanda Jacobson-Kelly: So, meat, actually, the highest content is in like liver meat. But who likes that? I don't.
Dr. Mike Patrick: And that makes sense because we just said that iron gets stored in the liver, right? Also, in animal livers, too, apparently.
Dr. Amanda Jacobson-Kelly: Yes, exactly, organ meat, specifically liver meat is probably the highest. But any kind of meat, it doesn't have to be red meat. I think people think, oh, steak has a lot of iron in it. But I mean, it does, but fish has a good amount of iron in it. Shellfish, chicken, pork, so any of those, if you are a meat eater.
And vegetable-wise, a lot of the green leafy vegetables have iron in them. And then the vast majority of things like cereals, grains, some of the processed grains, almost all of them have added iron to them. So, they are not a perfect source, but when you have a toddler that's picky, just looking for iron-fortified grains is a good way to incorporate it.
And I think something that's really important in regards to not only to supplementation but in that having an iron-rich diet is if you're going to supplement, or you need to supplement because you have iron deficiency, it's really important to not do it around the time you drink milk. Just like I said earlier with cow's milk causing iron deficiency, it's really kind of not the right thing to do to take your iron supplement with a classic cow's milk because it defeats the point.
Dr. Mike Patrick: Yes, good to know. Vitamin C also helps with iron absorption, is that right?
Dr. Amanda Jacobson-Kelly: Yes, it does. And in a perfect world, the iron is best absorbed on an empty stomach. And the problem with iron on an empty stomach is it causes more GI side effects. So, adding a little bit of food with some vitamin C helps the absorption and mitigates the loss of absorption from having iron with food.
But vitamins are a great enhancer of iron absorption, so we usually encourage patients to take vitamin C or take iron with orange juice.
Something that was pointed out to me that I just really didn't think about is a lot of orange juice is actually fortified with calcium. So, if you're going to take iron with orange juice, you've got to make sure it's not fortified with calcium.
Dr. Mike Patrick: Yeah, good to know. Or just even orange, right?
Dr. Amanda Jacobson-Kelly: Exactly.
Dr. Mike Patrick: So, in terms of dark green leafy vegetables that you mentioned, what are those? So, like spinach?
Dr. Amanda Jacobson-Kelly: Spinach, kale, swiss chard, collard greens, mustard greens. I'm from the south so I think of greens, and things like that.
Dr. Mike Patrick: Okay, and then some beans, peas also, and as you mentioned iron fortified cereals.
This is one of the great things about food in the United States, we have labels you can look at and it will have the iron content in there. Now, it may be 100% of your recommended daily allowance, but that's going to be for adults and may not be the type of iron that's the best available, so you don't necessarily let that fool you. It may seem like it's high in iron, but it might not be the right iron.
Dr. Amanda Jacobson-Kelly: Yeah, exactly.
Dr. Mike Patrick: Okay, so what happens if iron deficiency goes untreated? I mean, at some point, the hemoglobin's going to go so low that it's going to get diagnosed because they have significant medical problems. But the sort of low-level iron deficiency could be easy to miss, that kids might have for a long time, what sort of problem is that?
Dr. Amanda Jacobson-Kelly: So I think that we don't really know, especially for older children, I'm not talking about little kids, but in older children, what long-term effects of just having mild iron deficiency would be/ But in younger children, especially toddler and babies, iron deficiency is highly correlated, especially severe iron deficiency and persistent iron deficiency, highly correlated to lower IQ, poor neurodevelopmental outcomes.
So, there's kind of a really important time during baby infancy and toddlerhood that being iron deficient can really have some long-lasting effects.
And so that's one of the reasons why we screen in that age group, but in addition to them just being high risk. But yes, over time, it can certainly lead to poor developmental outcomes.
Dr. Mike Patrick: So very important that we screen and identify kids who have iron deficiency anemia and get them supplemented and get their iron levels back up and get that anemia corrected. Another population that then affects kids is pregnant women.
And so pregnant women who are anemic and iron deficient, we know that they have an increased incidence of premature births and low birth weight babies. And so, it's going to be important that pregnant moms also are getting enough iron and checking to make sure that they're not anemic too, correct?
Dr. Amanda Jacobson-Kelly: Absolutely. And in pregnancy, iron is really important, and oral iron alone is sometimes hard, if you start out really iron deficient, to catch up to your iron needs from pregnancy because your baby is taking a lot of your iron. Now, we're talking about children, but pregnancy eventually affects children. So, the intravenous iron formulations are actually very safe in the second and third trimester of pregnancy.
So, it's something that I know that the OB population is using a lot more because a lot of times just oral iron alone is hard to optimize yourself for your baby.
Dr. Mike Patrick: Yeah, absolutely. And then, what is a long-term outlook for those impacted by iron deficiency anemia? Once you get their iron levels up and you correct the anemia, is it a done deal? Or are there any issues down the road that we have to think about?
Dr. Amanda Jacobson-Kelly: This is one of the reasons why I love this problem so much, is that it's relatively easy to fix and I can actually fix a lot of symptoms by just adding the supplement or giving a dose of intravenous iron. And it's just really satisfying to have something that's fixable.
But they certainly can recur. So, I guess kind of breaking it down into the different populations, but with the toddlers, if we can get them to not drink nearly as much milk, and add a supplement, we can get their iron stores back up. So usually that requires at least three months of supplementation. And that's like not just multivitamin iron, but I'm talking about dedicated iron supplementation, the three to six mix peculiar of the elemental iron.
If they can get up, do the three months and then replete their iron stores and then not drink as much cow's milk, I mean their long-term outcome is awesome. So, we typically don't even have to treat them again.
In teenagers, once you correct that iron deficiency, they can get depleted again if they continue to have heavy periods. So, we work closely with our adolescent medicine colleagues to help control menstrual cycles in order to prevent further iron deficiency.
And the athletes as well, some of them may, depending on how iron deficient they are and how much they're running or how intense their activities are, we can fix them with iron supplementation. But sometimes, they require intravenous supplementation. And I think that's something that we're doing more and more nowadays is using intravenous supplementation that's kind of underutilized in pediatrics.
Dr. Mike Patrick: How often and how long do you do that? The infusion?
Dr. Amanda Jacobson-Kelly: So, we have several types of IV iron that we use. And it's dependent on certainly the insurance coverage, for instance. But one of the types we use that's called ferric derisomaltose is you can give a higher dose in a single infusion. And some patients, especially those with milder anemia or just iron deficiency without anemia will require a one dose. And that may fix their iron deficiency forever depending on the cause. Or they may have to come back for periodic infusions then which is true, especially in the inflammatory bowel disease population who have trouble with iron absorption.
Another one we have, called the iron sucrose, just requires more doses. But I think IV iron got a bad name back a few decades ago with high molecular weight iron dextran, which caused a lot of allergic reactions and, historically, kind of skewed people's view of IV iron. And IV iron is actually very safe with a very low rate of allergic reaction, although we do monitor patients closely for that.
Dr. Mike Patrick: Very interesting. So, I would imagine in terms of research in iron deficiency anemia, the whole treatment and the development of these newer infusion medicines is probably kind of at the forefront of research now, is that correct? Or are there other things going on?
Dr. Amanda Jacobson-Kelly: So definitely, the intravenous iron is finding newer formulations with the side effects that can give you more iron in each dose. The one I mentioned previously, the ferric derisomaltose, this is actually not FDA approved yet in pediatrics, so we're working on that. We use it a lot as we do in pediatrics, we use a lot of things as off labeled.
So that's kind of coming down the pipeline. There already is research and I think what's going to be really coming down the pipeline is how important iron is even without anemia or how important iron is to other parts of the body.
And for instance, in restless leg syndrome, our pediatric limb movement disorder which is pretty common in pediatrics, iron can be important, and supplementation can really help those patients. And the same is true for the athletes. Obesity, actually even things as simple as breath holding spells can be improved with iron supplementation.
So, I think that what's coming down the pipeline is how do we measure iron levels better? Maybe there's something better than the ferritin to use. And by treating iron deficiency, even without anemia, how much are we actually improving outcomes?
So, are we treating the number, are we actually improving symptoms? I think my personal belief is we absolutely can fix a lot of symptoms. But it may not work in some patients.
Dr. Mike Patrick: As you're describing this, I'm thinking of the kid with growing pains who just had some leg pain at night time. And like every night, but during the day, they're fine. I wonder if we check the ferritin, what it would be for some of those kids?
Dr. Amanda Jacobson-Kelly: Totally. The problem with ferritin is a lot of the time, you can't do it in the office. So, it's not like a hemoglobin point-of-care test. There is not really a point-of-care ferritin on the market. But there's some research coming that way, too.
But it's easy to track and you just have to send them to the lab. In our clinic, it does require a venipuncture, which is stressful to some patients. My own son actually had his ferritin check with a finger stick at one of our close-to-home labs, so…
Dr. Mike Patrick: It can be done.
Dr. Amanda Jacobson-Kelly: It can be done.
Dr. Mike Patrick: All right, so you're a hematologist. That means a doctor who takes care of blood disorders. And iron deficiency anemia is not the only thing that hematologists take care of. Tell us about hematology at Nationwide Children's Hospital, what are some of the other conditions that you guys treat?
Dr. Amanda Jacobson-Kelly: So, we actually treat a wide range of conditions. I would say iron deficiency is common amongst what we treat, but iron deficiency is also really common in general pediatrics. But we treat disorders of bleeding or clotting. So, blood clots are something becoming more and more commonly recognized. I don't know if they're necessarily more common, but more commonly recognized in pediatrics.
And certainly, bleeding disorders like hemophilia or Von Willebrand disease. We treat bone marrow failure syndromes where the barrow stops working, either due to inherited cause or acquired cause, like aplastic anemia.
We treat a lot of rare autoimmune diseases that are associated with problems with your blood. And also, more common autoimmune diseases like ITP or immune thrombocytopenic purpura, which is one of the more common things we see in pediatric hematology. That's just low platelets due to platelet antibodies.
And then, also other hemolytic anemia like sickle cell disease and hereditary spherocytosis are probably the most common to inherited hemolytic anemias.
And on the flip side of iron deficiency, we see patients with iron overload syndromes, too. Because iron is great as it is, when you have way too much of it can cause problems as well.
Those disorders are much more rare. And it's either due to an inherited problem, something called hemochromatosis or getting a lot of blood transfusion to treat things like sickle cell disease or thalassemia, or cancer, for instance.
So, hematology is a huge field. We do a lot of different stuff and we were trained in both oncology and hematology, but they really should become separate fields, because they're so broad.
Dr. Mike Patrick: Yeah, yeah, absolutely. You guys do a lot of terrific work and impact the lives of kids and families every day. So, hats off to you.
For those who would like more information about hematology at Nationwide Children's Hospital, I'll put a link in the show notes, so you can find it easily over at pediacast.org.
I also have some resources from healthychildren.org, which is a product of the American Academy of Pediatrics. So, there will be some articles there that you may find interesting, one on Anemia in Children and Teens: FAQs for Parents.
Boosting Iron Levels in Children, that one's for providers. Pump Up the Diet with Iron, that one's for parents. Choosing an Infant Formula, and Vitamin D and Iron Supplements for Babies, these are all resources from the American Academy of Pediatrics that we'll put in the show notes.
And then there was also a 700 Children's blog post on heavy menstrual bleeding, what girls and parents need to know and that covers some information about iron deficiency anemia in that age group as well.
So, Dr. Amanda Jacobson-Kelly with Pediatric Hematology at Nationwide Children's Hospital, thank you once again for stopping by today.
Dr. Amanda Jacobson-Kelly: Thank you for inviting me.
Dr. Mike Patrick: We are back with just enough time to say thanks once again to all of you for taking time out of your day and making PediaCast a part of it. Really do appreciate that.
Also, thanks to our guest this week, Dr. Amanda Jacobson-Kelly, pediatric hematologist at Nationwide Children's Hospital.
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