Newborn Treatments

In every class there is always some discussion about the worse case scenarios. This page is the hard to read one that everyone hopes does not happen to their baby. It shows the scary cases and the problems that can happen with HDFN. This may be hard to read, but remember that most babies today survive and thrive. Many antibody babies do not require treatment, but all babies with HDFN should be monitored. Infants born to moms with antibodies are getting better care today than they were even 5 years ago. Antibodies do not have to take your baby’s life. Knowing about the tests and treatment options can help you to be better prepared to advocate for your precious little one.


High Bilirubin

Have you heard this myth: Your antibody levels are low, so you’re good to go. The baby won’t have any problems after birth. This is FALSE. Babies born to mothers with really low levels of antibodies can experience dangerously high bilirubin levels. Babies whose MCA scans were all normal, can be hospitalized for 2 or 3 weeks dealing with high bilirubin levels. Your antibodies are destroying your baby’s blood cells. When blood cells die, they release bilirubin. Even if your antibodies aren’t destroying enough blood cells to cause anemia, the bilirubin will still build up. If bilirubin levels get high enough, permanent brain damage can result. Bilirubin due to HDFN is considered to be more neurotoxic than bilirubin due to other causes. For this reason, babies with HDFN are considered to be at high risk (born before 38 weeks) or medium risk (born 38 weeks or later) for damage from high bilirubin 49. As a result, babies with HDFN need phototherapy treatment at lower levels.It’s really important for parents to be on top of their child’s bili levels and ensure that he gets regular follow up after hospital discharge (bilirubin tests every 1 – 2 days after discharge). Especially if your baby was released before day 4, it is common for babies to be readmitted for treatment. Treatment for high bilirubin includes phototherapy, intravenous immunoglobulin, and an exchange transfusion.

Phenobarbital

The prenatal preventative for hyperbilirubinemia.

Phenobarbital is a pill that may be prescribed to mothers during the last 10 days of their pregnancies. This drug helps to mature the baby’s liver. During pregnancy the placenta filters out the bilirubin. After birth that job passes to the infant’s immature liver. This medication speeds up liver maturity, helping remove bilirubin more quickly. In one study, the use of phenobarbital reduced the incidence of exchange transfusion from 52% down to 9% 58.

Phototherapy

The blue lights to help baby get rid of excess bilirubin.

Phototherapy is a very low-risk treatment option that is used for most babies with high bilirubin levels. These lights emit a certain wavelength of blue light that helps remove the bilirubin from the baby’s system. Their risk is minimal, potential dehydration, and can be negated by nursing your baby as much as possible. You can still touch your baby when he’s under lights, and you can still breastfeed. This can be done by pointing the lights at you, using a bili blanket, or only removing baby for 10-15 minutes to feed, and then putting right back under lights. You want the baby under the lights with as much exposed skin as possible, so expect him to be naked except for a diaper and goggles. Medical literature says that home bili blankets should not be used because they’re not effective enough with HDFN 49.

You need to watch out for rebounding jaundice. Babies with HDFN respond great to phototherapy and have a decrease in bilirubin levels when on lights, but their levels will rapidly increase when the lights are removed. This can occur up to 3-4 days after removal from lights, so it is important to continue checking the bilirubin levels daily after treatment has ended. Below is the American Academy of Pediatrics recommendation for phototherapy graph. By having baby with HDFN, you will need to be looking at the medium (38 weeks or later) or high risk (before 38 weeks) lines depending on how many weeks you were when you gave birth. If your baby falls on or above the lines, you’ll want to get him on a bilirubin light. To make interpreting the graph easier, I have removed the low risk line. To use the graph, determine your risk. If you had a pregnancy with antibodies or your baby had a positive Coombs test after birth, you are either medium or high risk. Next determine your baby’s age in hours and determine which units your hospital uses (US units on the left, UK on the right), and plot your baby’s numbers.

  • Over the blue line for your gestation = phototherapy treatment required.
  • Approaching the red line = consider IVIG.
  • Over the red line = EMERGENCY. Immediate treatment required.

A cord bilirubin of ⩾2.05 mg/dL (pre-term) to 2.15 mg/dL (full-term) indicates need for phototherapy 60.

To help reduce the dangerous of rebounding bilirubin levels and to avoid hospital readmission, it is important to do a trial without lights. For this, baby is removed from the lights and tested again approximately 12-24 hours later to see what his/her levels are. This is a great tool that doctors will use to help keep your baby safe, but it can be used incorrectly. Lights are most effective when left on for a period of time. What you do not want is baby on lights for 12 hours, off overnight, and then back on in the morning. You want to keep the lights on until the bilirubin is at a safe level and declining regularly. Remove them one light at a time, and test for rebounds. If baby rebounds, expect to go back under lights. Once baby isn’t rebounding, and bilirubin is decreasing on it’s own, you’re usually good to go.

Key Points:
  • Even if your levels are low and your pregnancy went great, your baby’s bilirubin can be very dangerous.
  • Babies with HDFN are at high or medium risk for complications from high bilirubin.
  • Bilirubin due to HDFN tends to peak days 4-6. Continued testing after discharge is essential.
  • Babies with HDFN tend to have rebounding jaundice, where their levels shoot back up when lights are removed – to check for this, most doctors will do a 24 hour trial without lights before sending the baby home.
  • Home lights are not strong enough for babies with HDFN and the AAP recommends that phototherapy only be done in the hospital.

The photos below are of babies receiving phototherapy. Remember, even though these pictures look scary, the blue lights do not hurt the baby and they are really effective at quickly removing dangerous bilirubin levels.

Intravenous Immunoglobulin (IVIG)

The medication that treats hyperbilirubinemia due to HDFN.

IVIG stands for intravenous immunoglobulin. It is a product made from human blood plasma. The AAP recommends IVIG if the total bilirubin is rising despite intensive phototherapy or if the level is within 2-3 mg/dL of the exchange level. If necessary, this dose can be repeated in 12 hours 49. IVIG has been shown to reduce the need for exchange transfusions in hemolytic disease of the newborn.

One of the problems with IVIG is that it can affect vaccines. You need to wait 11 months for live vaccines after IVIG. If your child has had a live virus vaccine within 14 days before receiving IVIG, the dose will need to be repeated after the wait period is up 50. Most doctors will not know this. That is why it’s important to talk with a pediatric hematologist, and do your research.

The routinely used live vaccines are:

  • MMR (measles, mumps and rubella) 
  • Varicella (chicken pox)
  • Flumist Live Attenuated Influenza Vaccine(LAIV) which is the influenza vaccine given as a intranasal spray. You can ask for a non-live version that is a shot.
  • Rotavirus 
  • Oral polio vaccine (OPV). This vaccine is no longer used in the U.S.
  • Shingles (Herpes Zoster)
  • BCG(Vaccine against TB-Tuberculosis) This is no longer a routinely used vaccine in the US, but is used under many circumstances. It is still used, especially in countries where TB is prevalent.
  • Live vaccines that are used in special circumstances such as during travel to a foreign country or during an epidemic are: Oral Typhoid Vaccine and the Yellow Fever Vaccine.

Blood products, such as platelets, exchange transfusions, and IVIG, contain significant amounts of antibodies to infectious agents. These products are made from other people’s blood, and therefore contain their antibodies in adult amounts. These antibodies are present because of natural or vaccine induced immunity. Because there’s so many antibodies in the blood products, it can interfere with the baby’s immune response to vaccines. The baby’s body won’t make enough antibodies because it already sees all the adult antibodies 51.

Note: Some babies have an allergic reaction to the IVIG. If this is the case, talk with your doctor about trying a different brand.

Exchange Transfusion

The immediate treatment to prevent permanent brain damage.

Exchange transfusions quickly remove dangerous bilirubin but carry more risk. In this transfusion, doctors remove all of the baby’s blood and replace it with donor blood. This is usually done twice, in what’s called a double volume exchange. It is very helpful when treating HDFN, but it does carry risk and babies have died during the procedure. Not all facilities are equipped or skilled in doing exchange transfusions, so ask the hospital.

A cord bilirubin level of >5 mg/dL, or a rate of rise in serum bilirubin of more than 0.5-1 mg/dL/h is predictive of the ultimate need for exchange transfusion 13. IVIG may prevent the need for an exchange transfusion if initiated early enough.

To use the graph, determine your risk. If you had a pregnancy with antibodies or your baby had a positive Coombs test after birth, you are either medium (born at 38 weeks or later) or high risk (born before 38 weeks). Next determine your baby’s age in hours and determine which units your hospital uses (US units on the left, UK on the right), and plot your baby’s numbers.

If your baby’s numbers are over the blue line for your gestation, he/she needs phototherapy. If your baby’s numbers are approaching the red line, he/she may benefit from IVIG. If your baby’s numbers are over the red line it is an emergency and your baby needs immediate treatment. The exception to this graph is with the cord blood. If at birth your cord bili levels are already over 4.5 5, an exchange transfusion should be considered. At the very least, IVIG should be administered while prepping blood for baby.

The following are indications for exchange transfusion 5:

  • Severe anemia (Hb < 10 g/dL)
  • Cord bilirubin > 4 mg/dL.
  • Rate of bilirubin rises more than 0.5 mg/dL despite intensive phototherapy
  • Severe hyperbilirubinemia
  • Serum bilirubin-to-albumin ratio exceeding levels that are considered safe

IVIG has been shown to reduce the need for an exchange transfusion.


Anemia

Anemia is when the baby does not have enough red blood cells. If the baby is too anemic, a blood transfusion is needed. Untreated anemia can be fatal. You can find out if your baby is anemic by having a hemoglobin or hematocrit test run.

Once a child has become anemic, the only treatment is a blood transfusion. Depending on what symptoms baby is showing, some doctors will choose to delay transfusion to give the baby time to make more of his own blood cells. Transfusions are done through an IV into the arm, umbilical cord, or head. While this may be distressing for mom to watch, it is easier on the baby.

IRON IS NOT AN ACCEPTABLE TREATMENT FOR A BABY with HDFN 47. The anemia faced by a baby with HDFN is caused by red blood cell destruction, not iron deficiency. Many babies with HDFN have normal or even high levels of iron and can be easily overdosed and killed from supplements. Medical literature is adamant that your baby should never be given iron supplements without having his ferritin levels checked. Normal Ferritin levels are 25-200 ng/mL 46.

After treatment, many babies begin doing much better. Babies with HDFN are at risk of developing late onset anemia from 3 – 12 weeks old, so it is important to have your baby’s hemoglobin levels checked until they are at least 12 weeks old. Some babies need checked longer, especially if they have had IUTs. In this case, you may be assigned a neonatologist, or hematologist who will follow your baby closely.

Folic Acid

The first line of defense against anemia.

Maternal antibodies that cross into the baby’s circulation will destroy her red blood cells. Your baby’s body will notice that she is getting low on blood cells and will try to make some more. Making more blood cells is a difficult process which requires a lot of energy and key nutrients. One of these nutrients is folate. Folate is used in large amounts to produce new blood cells. You can help your baby to produce new blood cells by ensuring that she has enough folate. Some mothers take extra folate themselves in the hopes that it will pass through their breast milk. Officially, doctors recommend purchasing liquid folate drops made for infants and administering them on schedule.

Erythropoietin

The medication that can boost baby’s bone marrow

Erythropoietin is a hormone produced by the kidneys. It promotes the formation of red blood cells by the bone marrow. It can be made in a laboratory and used as a treatment for anemia 35. Erythropoietin is a hormone produced by the kidneys. It promotes the formation of red blood cells by the bone marrow. Erythropoietin is done to help prevent late onset anemia. Especially in IUT babies, the bone marrow is suppressed, causing low levels of erythropoietin, and red blood cells are not being made. Erythropoietin is given to decrease the need for a transfusion 33. If your baby has a low retic and continues to have dropping hemoglobin, talk with your doctor about trying erythropoietin.


Blood Transfusion

The treatment that immediately corrects anemia.

Red blood cell transfusions are useful for anemia. These are generally done at 2-12 weeks old for babies with HDFN. This kind of transfusion will not remove the antibodies, but will put new blood that is antigen negative into the baby. For example, if you have anti-K, your baby needs K negative blood. The risks of a RBC transfusion are lower than with an exchange transfusion, and are generally done later, once the bilirubin is taken care of. Think of it as topping off the baby so that they’ve got enough blood.


Iron Supplements

The commonly recommended “treatment” that is actually dangerous.

A common mistake in the treatment of babies with HDFN is recommending iron supplements. The vast majority of the time, doctors will be seeing iron deficiency anemia – this kind of anemia is treated with iron supplements. Our babies have hemolytic anemia – this kind of anemia cannot be treated with iron. In fact, multiple medical articles expose the dangers of giving babies with HDFN iron supplements. While these articles mostly talk about infants who have received IUTs, they also apply to all babies with HDFN, especially those who have received transfusions after birth. The donor blood used in transfusions is adult blood, which has much higher levels of iron than the infant is used to. This can easily lead to iron overload.

Iron status in infants with alloimmune haemolytic disease in the first three months of life 
M. E. A. Rath, V. E. H. J. Smits-Wintjens, D. Oepkes, F. J. Walther & E. Lopriore

“On the contrary, iron overload occurs in 70% of neonates with alloimmune HDFN at birth, 50% at the age of 1 month and 18% at the age of 3 months. Therefore, we advise to measure iron status, and we discourage the use of iron supplementation in the first 3 months of life in neonates with alloimmune HDFN. Haemolysis and intrauterine and postnatal transfusions probably both contribute to the high incidence of iron overload in alloimmune HDFN.” “There are a number of case reports published on the risk of severe iron overload, diagnosed by liver biopsies, following IUTs for Rh HDFN. These infants were all born at 33 or 34 weeks of gestation and received 2–5 IUTs and several postnatal transfusions. Their serum ferritin levels ranged from 2479 to 28 800 lg/l. In addition to transfusions for alloimmune HDFN, the haemolysis itself can also contribute to iron overload in alloimmune HDFN.”

Hemolytic Anemia Treatment & Management Paul Schick, MD
” Iron therapy is contraindicated in most cases of hemolytic anemia. The reason is that iron released from RBCs in most hemolytic anemias is reused and iron stores are not reduced. “


Remember…

  • Poorly managed bilirubin can result in brain damage. Proper monitoring and treatment is essential.
  • Babies with HDFN are at risk for anemia, even if they weren’t anemic at birth. Most babies with HDFN need their first transfusions at 2-6 weeks of age.
  • Iron supplements are contraindicated.
  • Babies with HDFN are usually cleared from the disease around 12 weeks of age.
  • You are your baby’s biggest advocate. If you do not feel like your needs are being met, seek a second opinion.
  • You can have a perfectly healthy baby when this is over. 
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