We review physiologic shifts in hemoglobin and hematocrit, and the role of supplementation and follow-up. We are joined by Martha Pacheco, MD, Assistant Professor of Pediatric Hematology and Oncology 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. Welcome back to the podcast. In today's episode, we will be discussing neonatal anemia. We are recording remotely due to the ongoing COVID pandemic. We're joined today by Dr. Martha Pacheco, Assistant Professor of Pediatric Hematology and Oncology at UT Southwestern.
Dr. Martha Pacheco:
Hello?
Dr. Neeta Goli:
Hi, Dr. Pacheco. Thanks for joining us today.
Dr. Martha Pacheco:
Sure. Thanks so much for having me.
Dr. Neeta Goli:
There are many pathologic causes of anemia in neonates including, but not limited to, anemia of prematurity, iatrogenic anemia, and inherited or genetic causes of anemia. In today's episode, we won't be discussing these in depth. Instead, we'll primarily cover what is sometimes called physiologic anemia or early anemia of infancy. Namely the physiologic shifts that occur in hemoglobin and hematocrit in the immediate postnatal period.
Dr. Neeta Goli:
Let's start with basic definitions. Can you review for us the normal hemoglobin and hematocrit in a neonate, and what we define as anemia?
Dr. Martha Pacheco:
Sure. The mean hemoglobin at birth for a term baby is about 17, with a hematocrit of about 54. Anemia is considered anything that's two standard deviations below the mean. In the first month of life, a hemoglobin of less than 13.5 or a hematocrit of less than about 41, it would be considered anemia.
Dr. Martha Pacheco:
Just keep in mind that the timing of cord clamping significantly influences the hemoglobin. Delayed cord clamping can increase the blood volume by as much as 30%. A normal hemoglobin at birth can vary anywhere from 14 to 19 or even close to 20, but the mean is about 17. So an anemia would be considered less than 13.5.
Dr. Neeta Goli:
Then can you describe to us the expected trajectory of hemoglobin and hematocrit in the first few weeks and months of life?
Dr. Martha Pacheco:
Sure. Immediately after birth, in the first few hours, the hemoglobin will increase a little bit just due to shifts in the blood volume. But then subsequent to that, the hemoglobin slowly drops over the next couple of months. This is due to a fall in the erythropoietin (EPO) levels, and that's secondary to increases in tissue oxygenation due to breathing and closure of the patent ductus arteriosus (PDA).
Dr. Martha Pacheco:
As the EPO level falls, the hemoglobin also falls. Usually, it falls to a nadir at about two months of life. We say that this nadir, what we call a physiologic nadir, is going to happen at about 6 to 11 weeks. And usually, the hemoglobin falls to about 11. If it falls lower than that, lower than 9 is really what we would consider more pathologic. But like I said, it can fall to anywhere from 9 to 11 at about two months of life.
Dr. Neeta Goli:
And then which infants are at increased risk of it becoming pathologic like you mentioned?
Dr. Martha Pacheco:
Good question. Preterm infants definitely are at risk of having a lower nadir, and usually it's earlier. Depending on how early the baby is born, they can have a nadir that comes at a month and can be as low as seven or eight. That would be more concerning.
Dr. Martha Pacheco:
And then any baby who has anemia during the newborn period would be at risk for having a lower nadir and potentially even a pathologic nadir. Things that cause anemia during the newborn period, you alluded to a little bit earlier in the episode, but just to mention these briefly, any kind of hemorrhage, and that could be prenatal, things like fetal-maternal hemorrhage or twin-to-twin transfusion or trauma, such as maternal trauma, or even amniocentesis or something like that. It could be intrapartum, so a cord laceration or a cranial hemorrhage, and then postpartum, even a big subgaleal hemorrhage or think about gastrointestinal or phlebotomy any of those kinds of things could cause anemia in the immediate newborn period.
Dr. Martha Pacheco:
Other things that obviously we think about are hemolysis, so immune hemolysis in particular: an ABO or Rh incompatibility. You can have hemolysis from DIC or sepsis. We call these microangiopathic haemolysis. Vascular-related, which would be any kind of vascular malformation. And then intrinsic hemolysis are things like a G6PD deficiency or hereditary spherocytosis or a hemoglobinopathy, like a thalassemia.
Dr. Martha Pacheco:
And then lastly, we think about impaired production. Even in the newborn period, they can have problems with red blood cell production. Things like congenital infections, such as TORCH infections can often cause sepsis. Other things like Diamond-Blackfan anemia, which is a pure red cell aplasia where the baby just doesn't make red blood cells normally can cause it. And then maternal deficiencies, which is relatively rare, but maternal deficiencies in things like iron, vitamin B12, folate, those can cause some impaired production. Any of these things in the newborn period could cause a lower physiologic nadir and something that could need to be treated.
Dr. Neeta Goli:
And why is it that sickle cell disease is not expected to be a cause of neonatal anemia?
Dr. Martha Pacheco:
Good question. Sickle cell disease actually doesn't show up until a little bit later and that's because babies when they're born, if you remember, they have fetal hemoglobin. So sickle cell is a problem with the beta globin chain, so babies don't switch over to making beta globin until around three to six months is when they start to shift over. And so usually we don't see, even an anemia, until about six months of age for sickle cell. It would be more of a thalassemia with the alpha globin chain, which babies are producing or with the gamma globin chain, which is the one that they make as newborns that makes fetal hemoglobin.
Dr. Neeta Goli:
What is the role, if any, of multivitamin supplementation? For example, with Polyvisol, for healthy term neonates with no diagnosis of anemia.
Dr. Martha Pacheco:
Term babies with no anemia, when they're discharged from the nursery should not need iron supplementation. Term babies should have sufficient iron stores to last them to four to six months of age. But there are a couple of conditions that may cause those iron stores to be lower at birth, and that's low birth weight babies and also infants of diabetic mothers tend to have lower than usual iron stores.
Dr. Martha Pacheco:
As babies get older, we need to think about iron supplementation. Exclusively breastfed babies should start iron supplementation at about four months of age. Breast milk has very little iron in it. It does have a tiny bit and the iron that breast milk has is very bioavailable, so babies are able to absorb it and utilize it. But because it has very little iron in it, they need to start supplementation once their iron stores that they're born with run out.
Dr. Martha Pacheco:
We say a milligram per kilogram per day beginning at four months of age. And that's until they start foods that contain iron, things like a cereal that's fortified with iron or baby foods that are fortified with iron.
Dr. Martha Pacheco:
Partially breastfed babies, it depends on how much breast milk they're getting. If they're getting more than half of their diet from breast milk, those should also supplement beginning at four months of ag. And then formula-fed babies shouldn't need extra iron supplementation if they're taking formula fortified with iron. Fortified formula contains 12 milligrams per liter of iron and if babies are taking an adequate amount for their weight, then they should be taking in at least one milligram per kilogram per day.
Dr. Martha Pacheco:
Supplementation. Polyvisol with iron should be adequate when babies begin supplementation. For the breastfed babies at four months of age, Polyvisol with iron has 10 milligrams per ml and that should be equivalent to at least a milligram per kilogram per day and probably more.
Dr. Martha Pacheco:
Babies that we need to think about sending them home from the nursery are preterm babies. Any baby born at less than 37 weeks gestation actually needs more iron and earlier. At one month of age, preterm babies should start supplementing with at least two milligrams per kilogram per day. If they're formula-fed, they should be getting an adequate amount. There are still formula-fed babies who are preterm, who do have iron deficiency about 14% will develop iron deficiency between four and eight months of age, so we need to think about checking for that. If they're not formula-fed, if they're exclusively breastfed, then they also need to start Polyvisol and they need to start it earlier than the other babies. At least by one month of age.
Dr. Neeta Goli:
Is there any certain degree of anemia at which you would recommend babies get either a multivitamin or ferrous sulfate supplementation on discharged from the nursery?
Dr. Martha Pacheco:
I would consider it if they do have anemia, so less than 13.5, especially babies who are exclusively breastfed, so aren't going to be getting a lot of iron in their diet. If it's a mild anemia and it's not something that's expected to persist, so there's not ongoing blood loss or ongoing hemolysis, then one could consider just repeating in a week or two and making sure it's going to come up. But if it's a baby who is not going to be getting an iron from their formula, we could consider supplementing and really just with a multivitamin with Polyvisol with iron should be adequate.
Dr. Neeta Goli:
At what point would you ever recommend an infant receive ferrous sulfate supplementation on nursery discharge?
Dr. Martha Pacheco:
In general, they shouldn't need it. I guess a severely iron-deficient baby, we might recommend it. But even for more severe iron deficiency in general, three milligrams per kilogram per day is adequate. A baby being discharged from the nursery if they had some iron deficiency or some anemia and we're getting a multi-vitamin with iron, that should actually be plenty. I think for the most part, multi-vitamin with iron is adequate.
Dr. Neeta Goli:
Is there any evidence to support the use of either multivitamin with iron or ferrous sulfate specifically for these babies?
Dr. Martha Pacheco:
No, not really. If you're only giving the iron because of anemia, then ferrous sulfate should be adequate, the multivitamin obviously is going to have other vitamins that they may or may not need. I think either way is fine if you just calculate the dose of the elemental iron. And for anemia, we generally recommend giving 3 mgs per kg per day. If it's very mild, you could even give a little bit less, two mgs per kg per day is an adequate dose for a unit.
Dr. Neeta Goli:
For our listeners guidelines might vary based on your institution, so you can look at your institutional protocols and see what the preference is.
Dr. Martha Pacheco:
I think that's totally appropriate.
Dr. Neeta Goli:
Then to end today's episode, do you have any advice for our listeners while they care for newborns?
Dr. Martha Pacheco:
I think just paying close attention to, first of all, symptoms of anemia, and so obviously the things that we always tell parents to watch out for is if the baby's more tired, not wanting to wake up, not eating enough, not having enough wet diapers. Those are things that we really worry about as being symptoms of anemia. Pay close attention to that, and look for causes to try and figure out what is the cause, because that may be more important to us to treating it then than the actual treating with iron.
Dr. Martha Pacheco:
Then the other thing that I'll say that I haven't commented on much here, but it's just always, if you're looking at anemia, we always want to know what the reticulocyte count is because that actually helps us figure out the cause, as well, and would also be helpful to know whether the baby is making enough red blood cells and can bounce back or does need more help with more iron. And then just close follow-up on discharge is always important.
Dr. Neeta Goli:
And then speaking of close follow-up on discharge. Is there ever a case where you would like these infants to be referred to you all as an outpatient?
Dr. Martha Pacheco:
I think certainly if they have a pathologic anemia that's from hemolysis or from something that's going to be ongoing, we definitely would like to see them. If it's something that we think they may need blood transfusions, we would like to see them because we can definitely take care of that. I think if they have a mild anemia from a subgaleal hemorrhage or something, then we don't need to see them so long as they have a good pediatrician that can follow them up.
Dr. Neeta Goli:
From the general pediatrician standpoint, when should they repeat the CBC or when should we expect this to resolve and we can stop the supplementation?
Dr. Martha Pacheco:
I think I usually say real close follow-up in the newborn period, so like a week or two would be necessary just to make sure that it's not falling even more because babies don't really tolerate a low hemoglobin very well. As far as stopping the iron, it kind of depends on what the cause was and what the hemoglobin is. It may be that you don't end up stopping the supplemental iron for a while, especially for breastfed babies. I probably wouldn't stop the supplemental iron until we feel like they're taking in more iron through their diet. Cereal fortified with iron or baby food. If they're formula-fed, if they're getting plenty of iron in their diet, if the hemoglobin comes up to normal, I probably would say, "You could stop it in a month or two."
Dr. Neeta Goli:
Thanks so much for joining us today, Dr. Pacheco.
Dr. Martha Pacheco:
Sure. Thank you so much for having me.
Dr. Neeta Goli:
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 email me 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.