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Understanding Hemolytic Anemia In Newborns
Hemolytic disease of the newborn is a type of anemia that begins during pregnancy. It can cause serious illness in a newborn, but it may be diagnosed during prenatal screening and treated to avoid complications.
Hemolytic anemia is low hemoglobin caused by the destruction of your red blood cells.
In newborns, hemolytic anemia can result from a mismatch between maternal and fetal blood types. This mismatch provokes the maternal immune system to attack fetal red blood cells.
The resulting hemolytic disease of the fetus and newborn (HDFN) can cause your baby to develop anemia and jaundice. Symptoms can begin during pregnancy or after delivery, and range from mild to life threatening.
However, doctors can screen, identify, and closely monitor pregnancies at high risk of HDFN. Preventive therapy is also available for some blood group mismatches.
If your baby has been diagnosed with hemolytic disease of the newborn, effective treatment is available.
Learn more about hemolytic anemia.
When you're pregnant, some of your antibodies cross the placenta and enter your baby's bloodstream to help protect your newborn.
But if your baby has a different blood type than you, this can become a problem. In this case, your antibodies can attack your baby's red blood cells, causing hemolytic disease of the fetus and newborn (HDFN), also known as erythroblastosis fetalis.
We're all born with blood type O, A, B, or AB, determined by the antigen proteins on our red blood cells. Everyone's blood is also either positive or negative for the Rhesus (Rh) antigen. There are also many less-common blood group antigens.
ABO blood type mismatch occurs in up to 25% of pregnancies. But HDFN only develops in about 1% of these pregnancies, usually when birth parents with type O blood carry babies with blood type A or B. This type of HDFN is caused by pre-existing, naturally occurring anti-A or B antibodies found in people with type O blood.
Rh antigen mismatch happens when an Rh-negative parent carries an Rh-positive baby. In Rh mismatches, HDFN is triggered by fetomaternal hemorrhage. If even a tiny amount (as little as 0.1 mL) of Rh+ fetal blood enters the maternal bloodstream during the pregnancy or delivery, the maternal immune system can recognize it as foreign and begin producing antibodies against the baby's red blood cells.
To help prevent and monitor for HDFN, your doctor will test your blood type, Rh antigen, and red blood cell antibodies early in your pregnancy.
Symptoms of HDFN can appear during pregnancy or after birth.
During pregnancy, babies with HDFN can develop:
Newborns with HDFN might also have:
Jaundice is yellow discoloration of the skin and eyes caused by excess bilirubin in the bloodstream. Many healthy newborns develop mild jaundice.
But in HDFN, many red blood cells are bursting and rapidly releasing their bilirubin, so jaundice can quickly become severe. Left untreated, this can lead to neurologic complications (kernicterus).
During pregnancy, doctors will review your medical and obstetric history, determine your blood type, and check for pre-existing red blood cell antibodies that could affect your baby.
If your tests reveal a risk for HDFN, your doctors might:
If you have type O blood but otherwise normal prenatal testing, your baby's blood type and direct antibody test will still be checked shortly after birth to check for newborn hemolytic disease.
If your newborn develops symptoms of HDFN, doctors will monitor blood counts and bilirubin levels, and order further blood tests to clarify the diagnosis.
If your newborn has received a diagnosis of HDFN, doctors may recommend:
When HDFN is diagnosed prenatally, doctors will monitor using ultrasounds, amniocentesis, and fetal and maternal blood tests. Depending on severity, doctors might recommend:
Left untreated, HDFN can result in marked anemia and/or jaundice. In the most severe cases, this results in hydrops fetalis, organ failure (including heart failure), and brain damage.
The good news is that when HDFN is identified early and treated promptly, doctors can help manage any risks to your baby.
Some circumstances increase the risk of HDFN:
With advances in prenatal screening and treatment, the outlook is good for most babies with hemolytic disease.
Research has shown that 94% of fetuses diagnosed with HDFN will survive with treatment (including intrauterine transfusions). Even in cases with prenatal evidence of early hydrops fetalis, survival is 74%.
A 2023 study found that 22% of newborns with HDFN required phototherapy for jaundice, 1% required blood transfusion, and 0.5% required exchange transfusion or IVIg infusion.
What's the most common cause of hemolytic disease in newborns?Though it's declined since the advent of RhoGAM, Rh antigen incompatibility remains the most common cause of serious HDFN.
The number of people with Rh-negative blood types varies between countries around the globe ranging from 2.4% to 17%. With prenatal screening and RhoGAM treatment, about 1 per 3000 Rh-negative birthing parents still develop Rh antibodies, placing their future pregnancies at risk of HDFN.
The most common cause of HDFN overall is ABO blood group incompatibility. But because maternal A/B antibody levels can be low, and fetal red blood cells do not express A/B antigen at a high level, this type of HDFN is often milder.
Is hemolytic anemia of the newborn life threatening?Severe HDFN can lead to critical anemia and hydrops fetalis, which is a life threatening condition. However, treatment is readily available and can significantly reduce the risk to your baby.
Hemolytic disease of the fetus and newborn (HDFN) occurs during pregnancy when your antibodies cross the placenta and attack your baby's red blood cells. This process can be triggered by a variety of different blood antigen mismatches between you and your baby but is most often due to ABO or Rh incompatibility.
Signs and symptoms of HDFN can begin in utero or neonatally. They include fetal or newborn anemia, hyperbilirubinemia, and in severe cases, life threatening hydrops fetalis.
With prompt identification and treatment, the majority of babies with HDFN survive and thrive.
Jaundice: A Common Condition That Requires Medical Attention In Newborns
According to Dr Adnaan Mustafa, Consultant Pediatrician at The Nairobi West Hospital, infant jaundice or neonatal hyperbilirubinemia is a common condition, particularly in babies born before 38 weeks gestation (preterm babies) and some breastfed babies.
Jaundice is a condition that causes the skin and the whites of the eyes to turn yellow. Infant jaundice occurs because the baby's blood contains an excess of bilirubin (bil-ih-ROO-bin), a yellow pigment of red blood cells. It usually occurs because a baby's liver isn't mature enough to get rid of bilirubin in the bloodstream.
Dr Mustafa reveals that an estimated 6 out of every 10 babies develop jaundice, including 8 out of 10 babies born prematurely before the 37th week of pregnancy.
Most infants born between 35 weeks gestation and full term need no treatment for jaundice. Rarely, an unusually high blood level of bilirubin can place a newborn at risk of brain damage, particularly in the presence of certain risk factors for severe jaundice but only around 1 in 20 babies has a blood bilirubin level high enough to need treatment.
"The causes can be obstruction of the bile duct-like a cyst or gall stones or biliary atresia which is narrowing of the bile duct from birth," Dr Mustafa says. "It can also be autoimmune -- the body's immune system attacking the liver cells thus, another cause is when specific enzymes and hormones are deficient like the thyroid hormone, tyrosinemia, galactosemia, G6PD enzyme deficiency," he says. He reveals that cancer of the liver like hepatoblastoma can also cause jaundice with an obvious mass on the liver.
"Excessive breakdown of red blood cells can also cause jaundice in infants because of excess bilirubin than the liver can handle," Dr Mustapha adds. "Conditions like sickle cell disease and hemolytic anaemia are also listed causes of this chronic condition."
Depending on the cause, he adds, symptoms of jaundice are abdominal pain, abdominal swelling due to fluid or enlarged liver, anaemia (low haemoglobin), lethargy, failure to thrive, and not gaining weight which should be experienced by infants just within a short period after birth.
He explains the yellowing of the skin and the whites of the eyes — the main sign of infant jaundice — usually appear between the second and fourth day after birth.
"A baby who has jaundice has a yellowish colour that usually appears on his face. It may then spread to his chest, belly, arms, legs and white parts of his eyes. The best way to see jaundice is in good light, like in daylight or under fluorescent lights since it can be harder to see in babies with darker skin," Dr Mustapha says.
Intermountain Tests A Smartphone App To Identify Jaundice In Newborns
Intermountain Health is developing a digital health app for smartphones that will help parents identify jaundice in their babies at home.
The Salt Lake City-based health system is partnering with Norwegian digital health company Picterus AS to create the app, which would use a smartphone camera and a laminated card to measure bilirubin levels in newborns without the need for a return trip to the hospital or clinic and a blood draw.
"Bilirubin and jaundice management has long been based in the hospital and the clinic," Tim Bahr, MD, an neonatologist who is leading the study, said in a press release. "Taking a newborn to the clinic or laboratory for frequent blood tests in the first days of life can be a huge inconvenience and burden on families. We hope to simplify this care and move more of it into the home. This is a win for families and for our healthcare system."
The app addresses a care management pain point for hospitals. According to the March of Dimes, three of every five babies born in the US develop jaundice within days after birth. Many recover quickly with little medical intervention, but jaundice can lead to serious health concerns, including Hyperbilirubinemia, brain damage, or hearing loss, if untreated.
Intermountain, which greets and tests 33,000 newborns a year, aims to turn the smartphone into a diagnostic tool that would enable parents to quickly check their baby's health at home after discharge from the hospital, and to contact their care providers if jaundice is evident. Parents would use their phone to snap roughly six photos of the laminated calibration card placed on the chest of their baby, and the app would translate those photos into a diagnosis.
"We do know that parents are pretty good at taking pictures of their babies," Bahr noted in the press release.
"This technology is exciting to us because it makes it possible to measure the bilirubin in a baby without taking blood," he added. "Right now, the only way to measure bilirubin levels in babies is to take them to a laboratory and draw blood. By having this technology available on a smartphone, we will eventually empower parents to make these measurements without having to leave their homes with an easily accessible and affordable tool."
The health system is testing the digital health tool on about 300 term babies born at Intermountain Utah Valley Hospital in Provo, Intermountain McKay-Dee Hospital in Ogden, and Intermountain Medical Center in Murray, as well as on about 100 pre-term babies. They'll test the app against the traditional method of drawing blood.
If proven reliable and introduced to clinical care, the app could not only save new parents the hassle of return trips and treatment, but help providers identify and treat jaundice earlier and more effectively, improving clinical outcomes and reducing costs.
Eric Wicklund is the associate content manager and senior editor for Innovation, Technology, and Pharma for HealthLeaders.
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