By far the most common medical problem in newborn infants is jaundice, typically appreciated as a yellowish discoloration of the skin caused by increased blood levels of a pigment called bilirubin. In my role as a newborn hospitalist, I manage jaundice every day. If I am not treating jaundice, in every single baby I see I am at least determining the risk of the child developing jaundice severe enough to require treatment. I then use that assessment to help guide my recommendations on when the infant should follow up with their primary care pediatrician after discharge home.
Fortunately for the millions of infants who develop jaundice every year, in the vast majority it is a self-limited process and often considered to be just a normal part of the first few days of life. But in a significant minority of them, careful management is required in order to prevent complications. Some infants need treatment to prevent neurological symptoms from developing, and to reverse them when they do occur. And in a very small percentage of babies who develop severe jaundice, permanent brain damage and even death can occur.
Because newborn jaundice tends to resolve without any intervention, and complications are now uncommon, it isn’t surprising that a variety of myths and superstitions have arisen that involve preventing or curing the condition. And naturally there are practitioners of unproven alternative medical modalities that can be found claiming to be able to manage it as well. As expected, if you’ve spent any time reading Science-Based Medicine or researching the nonsensical claims of chiropractors, homeopaths and their ilk, their understanding is limited and their recommendations potentially dangerous.
But first a crash course on newborn jaundice.
What is jaundice?
Jaundice occurs when there is an elevation in the amount of bilirubin in the blood. In older kids and adults, anything above 1 mg/dl is considered abnormal. But virtually all babies have levels higher than this within a day or two of birth, and often considerably higher. I routinely see bilirubin levels in newborns of 15-20 mg/dl and occasionally much higher.
The higher the level of bilirubin in the blood, generally the more jaundiced a baby looks and the lower down on the body it progresses. But using a visual assessment is problematic because it doesn’t reliably predict levels in the blood in all babies. We have all been fooled by little pumpkins with low levels as well as babies with high levels despite little apparent jaundice. It can be particularly challenging in infants with more natural pigment in their skin to begin with.
Of course long before the development of techniques to measure serum bilirubin levels, people noticed that newborn infants often developed a transient yellow discoloration of the skin with no apparent associated symptoms. Historically this bore the name Icterus neonatorum, which is based on ikteros, the Greek work for what we now know as jaundice. The word jaundice is derived from the French word for yellow, jaune .
Also known to physicians of the past was a more severe form of newborn jaundice given the name Icterus gravis. They noted severe anemia, neurological effects and typically death in addition to the yellowish skin. It would be many years before the cause of this condition, as well as the many risk factors associated with jaundice in general, would be understood by medical scientists and incorporated into our care of newborns.
Bilirubin in the human body, at least about 90% of it, is a by-product of the breakdown of hemoglobin from our blood. Once produced, bilirubin is bound by the protein albumin in the blood and transported to the liver where it is prepared for excretion by undergoing conjugation with glucuronic acid by the enzyme UGT1A1. This more water-soluble conjugated bilirubin is excreted into the intestines via bile from our gallbladder and leaves our bodies as metabolic waste in our feces.
In the newborn human, there is a problem at every step in this process, which is why even perfectly healthy babies are at risk of developing jaundice. Newborns make more bilirubin normally than at any other time during the lifespan because they have, on average, more hemoglobin than at any other time. Babies can even be born with too much hemoglobin, leading to a condition called polycythemia where the increased viscosity of their blood can reduce oxygen delivery to vital organs. Fetal red blood cells also have a shorter life span than adult. So more blood, and more breakdown of that blood, leads to more bilirubin in the blood.
The ability of the newborn to conjugate bilirubin in the liver is impaired because of a deficiency of the necessary enzyme. This occurs in all babies but can actually be worse in some populations, particularly in families designated as Eastern Asian. It takes over three months for the liver to reach adult capacity to conjugate bilirubin. So babies produce more bilirbubin, and more of it stays in the blood in the unconjugated form that can cause problems. It’s important to note that patients of all ages can develop a buildup of conjugated bilirubin in the blood as well which is typically related to a variety of liver diseases. That, however, is a horse of a different color. Well, technically it’s still yellow.
Finally, there are even problems with the bilirubin that does make it into the gut in the conjugated form. Older kids and adults further break conjugated bilirubin down with the help of bacterial enzymes, but it takes time for the newborn gut to become colonized. As conjugated bilirubin sits in their intestines, a human-produced enzyme deconjugates it, thus allowing it to be reabsorbed back into the body in a process called enterohepatic circulation.
We call the end result of these normal barriers to removing bilirubin from the body “physiologic jaundice” to differentiate it from the many disease states and environmental factors that can also lead to severe elevations in bilirubin. Again, this occurs in every single baby to varying degrees. It can, even without any pathological assistance, lead to jaundice bad enough to cause symptoms or require treatment, although alone it would be extremely unlikely to lead to permanent injury or death. Physiologic jaundice tends to peak at around the fourth day of life, although that peak can be higher and further out in premature and Eastern Asian infants.
What is pathologic jaundice?
There are a variety of diseases and environmental insults which can exacerbate physiologic jaundice in newborns or lead to severely elevated levels of bilirubin all by themselves. Rather than give an exhaustive review, I’ll focus on the two most important. Increased production of bilirubin from excessive destruction of red blood cells is the most common cause of pathologic jaundice. This typically occurs when the blood type of the mother and baby are mismatched, usually with the mother having O+ blood while the baby is A+ or B+, leading to the production of maternal antibodies. These antibodies can cross the placenta and signal baby red blood cells for destruction in the spleen.
ABO incompatibility can be severe, but often isn’t. But there is an extremely severe and often deadly form of this kind of mismatch which I’ve never seen thanks to advances in modern medicine. Rh incompatibility, when a mother with negative blood gives birth to a baby with positive blood, used to kill a lot of babies prior to the development of Rho(D) immune globulin (RhoGAM) because the maternal immune response is so intense. The first use of Rho(D) immune globulin in a mother, which facilitates destruction of fetal red blood cells before an immune response can occur, was in 1968. Research and treatment of Rh disease in the three decades leading up to that year is credited as the impetus for the development of neonatology as a unique specialty within pediatrics.
The second most common cause of pathologic jaundice is known as “breastfeeding jaundice”. Unfortunately, it is a well-established fact that breastfeeding is a major risk factor for the development of a severe elevation of bilirubin, which is why pediatricians tend to want earlier follow up visits after discharge from the nursery with breastfed babies. The process by which breastfeeding can negatively impact bilirubin levels is by increasing the enterohepatic circulation I mentioned earlier. If things are going well with breastfeeding, the risk is actually not much higher than in babies receiving formula. But when breastfeeding is going poorly during the pivotal first few days of life, the inadequate intake of calories and fluid leads to more unconjugated bilirubin being reabsorbed from the gut back into the blood.
The possibility of breastfeeding-failure jaundice is something we take very seriously in the newborn nursery. It isn’t the only reason why there is such a push for improving breastfeeding support of course, but it is a big part of it. We provide extensive education on lactation, document successful latching, track weight loss and the number of wet and dirty diapers, and troubleshoot a variety of potential roadblocks such as nipple pain and maternal fatigue. We are especially careful with breastfeeding premature infants, who are at increased risk of breastfeeding failure and physiologic jaundice already tends to be more pronounced.
A related but benign cause of jaundice in young infants, typically occurring during the 2nd week of life, is “breast milk jaundice.” It occurs after breastfeeding has been well established in exclusively-breastfed babies when physiologic jaundice persists after the usual rapid decline of bilirubin around the fifth day of life, and it can last for several weeks without intervention. Although the exact cause is unknown, it is believed that there is a component within breast milk that promotes intestinal absorption of bilirubin. A brief interruption in breastfeeding, usually just one to two days, leads to rapid resolution, although many pediatricians do not recommend this as there is no harm from the elevated bilirubin at that point.
How does jaundice affect newborns?
In most newborns with jaundice and even moderately elevated levels of bilirubin in the blood, there are likely no adverse acute or long term effects. The standard approach to screening and treatment of the condition, which admittedly can seem overly aggressive at times, is primarily geared towards preventing a very rare outcome known as kernicterus. This involves permanent damage to specific regions of the brain and can result in death in some cases. We believe that it should never happen, that it should be preventable virtually 100% of the time. In fact, The Joint Commission, who certifies health care institutions and programs, designates it as a sentinel, or “never” event.
As with many medical conditions, there is a spectrum of severity when it comes to symptomatic jaundice. At a certain point in any baby, the bilirubin in the blood can reach such a level that it is able to cross the blood-brain barrier and begin binding to neural tissue, which leads to cell death. The more brain tissue involved and the longer a child goes untreated, the more severe the symptoms. Although we can never perfectly predict at what level this will begin to occur in for any individual child, we tend to see subtle symptoms when levels hit around 20 mg/dl, with the more overt injury evident at 25-30 mg/dl. Anything that can impact the permeability of the blood-brain barrier, such as prematurity or infection, can lower the level that causes brain injury.
Bilirubin-induced neurologic dysfunction (BIND) can be broken down into acute encephalopathy, which is reversible with appropriate treatment, and kernicterus, which isn’t. At first, babies with increasing bilirubin levels become sleepy and begin to feed poorly. They may seem floppy or have a different sounding, high-pitched cry. As things progress, a baby can develop fever and extreme lethargy, or they may become extremely irritable and jittery. They may have no suck at all or develop an aggressive suck. Their cry may become more high pitched and urgent sounding and they may be very difficult to console. Stiffness can set in, the first sign of which is often arching of the neck and body when touched.
Without emergency treatment at this point, the damage will become irreversible. They will begin to have periods without respiratory effort and will stop feeding altogether. Fever and seizures are common as they become more persistently stiff and arched at the neck and back and progress into a comatose state. They will ultimately die from either respiratory failure or prolonged seizure activity.
Kernicterus is diagnosed when signs of brain injury become evident during the first year of life. Because bilirubin deposition in the brain tends to occur predominantly in the areas that regulate movement (basal ganglia) and hearing, cerebral palsy and hearing loss are common, as are difficulties with eye movement. The development of the teeth can also be affected. Cognition tends to be unaffected but there is some controversy regarding the possibility that even moderate levels of bilirubin elevation are a risk factor for neurologic problems later in life. At this time, the evidence is mixed but trending against any association with autism, learning disabilities, ADHD or any other psychological disorders.
How is newborn jaundice evaluated?
The key to managing newborn jaundice is awareness of risk factors, such as prematurity, genetics and whether or not the baby is being breastfed. Most hospitals incorporate universal pre-discharge bilirubin screening into our decision-making process and always attempt to establish appropriate follow up post-discharge. Our goal is the prevention of severe elevations of bilirubin in order to prevent the development of symptoms and ultimately of kernicterus.
Since the early 1990s, a systematic approach to newborn jaundice has been recommended. Every baby goes through the process of screening, risk assessment, breastfeeding evaluation (if breastfeeding), and use of an established treatment algorithm based on the bilirubin level and the infant’s hours of age. This has led to a decrease in the number of babies that develop severe elevations of bilirubin. The rarity of kernicterus has made it difficult to assess whether our interventions have successfully decreased its incidence, but it is reasonable to use severe bilirubin elevation as a surrogate outcome for kernicterus. The US Preventive Services Task Force disagrees with the AAP on this, and does not recommend universal screening, which I believe is a good example of the difference between evidence-based and science-based medicine.
I can certainly understand the hesitancy in initiating universal screening of pre-discharge bilirubin levels. Historically this has required a heel stick to obtain a few drops of blood from the baby. Heel sticks hurt without proper procedural pain measures such as use of a pacifier and sucrose, and probably aren’t that comfortable even with them. Labs aren’t free either. A fairly recent development in the management of newborn jaundice has significantly ameliorated these concerns, however.
Rather than the testing of a baby’s blood for elevated bilirubin, an increasing number of hospital nurseries are now using transcutaneous bilirubinometers (TcB). These handheld devices use multiwavelength spectral reflectance from the skin to estimate the level of bilirubin in the blood. A number of large studies have demonstrated their accuracy in various ethnic groups, but they aren’t perfect. They are unreliable once a baby has started phototherapy, possibly even if they’ve just been exposed to direct sunlight, and they have decreased accuracy at high bilirubin levels.
Written By: Clay Jones
continue to source article at sciencebasedmedicine.org