How Bilirubin is Produced and Removed in Newborn Babies and Why Fed is Best

Bilirubin Metabolism

This is a review for parents on the physiology of jaundice (hyperbilirubinemia) so that they may understand the reason why higher volumes of milk intake reduce the severity of jaundice in newborn babies.  

Before a baby is born, the baby relies on a type of blood called fetal blood that is specifically tailored to life in the womb.  This fetal blood allows babies to remove oxygen from maternal blood as efficiently as possible.  When a baby is born, he must transition to mature blood.  This occurs by the break down of fetal blood cells and increased production of mature blood cells (see the top of the diagram).

The breakdown of fetal blood results in the accumulation of bilirubin in the newborn.  The primary way that bilirubin is removed from the body is through the liver into the intestines (see the bottom of the diagram).  This bilirubin is carried away by milk that passes through the intestines.  Without this milk, the bilirubin is reabsorbed into the blood stream, which leads to increasing levels of bilirubin in the newborn.

When bilirubin levels are high, about a small percentage of bilirubin can be removed through the urine.  This process is aided by the use of phototherapy (or bilirubin lights).  The phototherapy allows bilirubin to dissolve in the urine allowing it to be removed more efficiently.   In addition, phototherapy converts bilirubin, a known brain toxin, to a form that reduces its entry into the brain while enhancing excretion through urine.

However, even in the face of very high bilirubin levels, the majority of bilirubin is still removed through milk passing through the intestines.  For a mother who does not have enough breast milk to give, particularly in the first days of life, supplementation with donor milk or formula are the most effective ways to remove bilirubin and reduce the toxic effects of bilirubin to the brain.  This is the reason why supplemented newborns have lower bilirubin levels than exclusively breastfed newborns.  Getting more milk reduces bilirubin, regardless of the type of milk fed to a baby.

If a baby has hyperbilirubinemia severe enough to require phototherapy, it has been shown that markers of brain injury are already present in the blood.  Brain injury is irreversible, even with phototherapy and supplementation.  The purpose of phototherapy and supplementation at the point when the bilirubin is high enough to require treatment is to prevent any further brain injury from occurring.

Therefore, the safest way to prevent brain injury in jaundiced newborns is to prevent the excessive jaundice from happening by evaluating the amount of milk a mother has, evaluating the newborn for hyperbilirubinemia and dehydration, and finally, listening to a baby's inconsolable cries.  The baby is the only one who knows when they are in distress and in need for more milk.  Supplementation can save the brain and life of an underfed newborn.

References:

Gartner, L. M. Breastfeeding and jaundice. J Perinatol 21 Suppl 1, S25–29; discussion S35–39 (2001).

Watchko, J. F. & Tiribelli, C. Bilirubin-induced neurologic damage--mechanisms and management approaches. N. Engl. J. Med. 369, 2021–2030 (2013).

Sarici, D. et al. Investigation on malondialdehyde, S100B, and advanced oxidation protein product levels in significant hyperbilirubinemia and the effect of intensive phototherapy on these parameters. Pediatr Neonatol 56, 95–100 (2015).

Markers of Brain Injury is Present in the Blood of Newborns Requiring Phototherapy for Jaundice

A study published in the journal Pediatrics and Neonatology in September, 2014 showed that newborns diagnosed with hyperbilirubinemia, or abnormal jaundice, high enough to require phototherapy had significantly higher blood levels of S100b, a protein known to be released by damaged brain cells when significant brain injury occurs.  They studied 62 jaundiced newborns who required phototherapy and compared them to 30 healthy non-jaundiced newborns and compared the relative levels of S100b in the blood, as well as other molecules that are associated with oxidative stress, a phenomenon that occurs when living cells die.  All except 2 babies in each group were breastfed and none had G6PD, a condition that causes abnormally high bilirubin unrelated to breastfeeding-related dehydration.

They found that the babies who had hyperbilirubinemia high enough to require phototherapy (bilirubin levels of 20.58±2.96 mg/dL) had significantly higher levels of S100b than the healthy babies, (S100B levels 87.3± 2.63 pg/mL in healthy babies vs. 124.97 ± 123.05 pg/mL in phototherapy babies; p = 0.032).  They also found higher levels of MDA, a marker of oxidative stress from cell death, in the babies requiring phototherapy as well (5.55±0.6 nmol/mL vs. 7.72±0.75 nmol/mL; p<0.001).  The levels of S100b was NOT reversed by phototherapy, suggesting that phototherapy neither increased brain cell death nor reversed it.  The purpose of phototherapy is to prevent further brain injury caused by hyperbilirubinemia but it does not reverse brain injury.

As I previously posted, 1 in 10 babies in the Baby-Friendly Hospital System of Kaiser Permanente Northern California were hospitalized for jaundice requiring phototherapy; over 10,000 babies in 3 years alone.  This study suggests that by the time a baby requires phototherapy, brain damage has already occurred. Exclusive breastfeeding at discharge is one of the highest risk factors for hospitalization for hyperbilirubinemia requiring phototherapy. It confers an 11-fold risk for being rehospitalized for dehydration or excessive weight loss.  

When breastfeeding advocates say that the Baby-Friendly protocol protects babies from these complications by teaching correct latch and providing follow-up appointments, they fail to recognize the most significant cause of hyperbilirubinemia, which is insufficient presence of breast milk before lactogenesis II to prevent hyperbilirubinemia.  Insufficient breast milk from delayed lactogenesis II occurs to as many as 22% of exclusively breastfeeding mothers, even with excellent lactation support.  No amount of latch education and supervision can overcome the most powerful determinant of bilirubin accumulation in the blood, which is the amount of milk a baby receives. Supplemented and formula-fed babies have been documented in the scientific literature to have lower bilirubin levels because they receive more milk than exclusively breastfed newborns.  In addition, the percent weight loss, also determined by the amount of milk a newborn receives, has been shown to predict the development of hyperbilirubinemia.  The higher the weight loss, the higher the bilirubin levels in newborns. 

 

These studies combined show that the Baby-Friendly Hospital System fails to protect babies from brain-injuring levels of hyperbilirubinemia at a rate of 1 in 10.  The basic science of brain injury tells us that no amount of fluid and formula resuscitation, phototherapy or breast milk can reverse the brain injury already experienced by the newborn.  

Newborn brain injury is a mistake that can never be taken back. It happens much sooner than we realize.  This is one of the first studies documenting that brain injury is already present in jaundiced newborns requiring phototherapy.  Fed is Best.


Link to original scientific article:
https://drive.google.com/open?id=0B0_MbXCqYazzNGlPdVZFamVkbEU

High Rates of Newborn Hospitalizations for Jaundice Requiring Phototherapy in a Baby-Friendly Hospital System

The true rate of hospitalizations of newborns for phototherapy due to jaundice has been recently published in JAMA Pediatrics published online April 11, 2016. In a study of 104,460 babies born between January 2010 and December 2013 in the Kaiser Permanente Northern California (KPNC) Healthcare System, a total of 10,583 newborns experienced jaundice requiring phototherapy, a rate of 10.1% over the three year period. Seventy-one percent of these hospitalizations were extensions of the original birth admission, which means pathological jaundice was detected before discharge and the newborn's hospital stay was extended to reduce the pathological effects of bilirubin, namely brain injury.

This is an astonishing number of newborns requiring phototherapy for jaundice as the majority of pathologic jaundice cases are related to dehydration or underfeeding from exclusive breastfeeding, an entity that the Academy of Breastfeeding Medicine calls starvation jaundice.  Normally, 100% of bilirubin is removed through the gastrointestinal system carried away by milk or food passing through. When  high bilirubin levels are circulating as typical of the newborn period, a small portion of circulating bilirubin can be excreted by the kidneys through urine, a process assisted by phototherapy. Since the majority of bilirubin is excreted through the gastrointestinal system, a newborn who is underfed through colostrum-only feeding can accumulate abnormally high levels of bilirubin in the blood.  Underfeeding from early exclusive breastfeeding due to poor latch or, more commonly, insufficient breast milk production, results in hyperbilirubinemia or severe jaundice in exclusively breastfed babies.  A minority of babies have increased rates of bilirubin production from blood-type incompatibility, called hemolytic jaundice.  Both starvation-related jaundice as well as hemolytic jaundice are improved with supplemental feeding because the primary means by which the body eliminates bilirubin is through milk passing through the intestines.

The study also reported than an astonishing 17% of babies developed pathological hyperbilirubinemia of greater than 15 mg/dL in the study period, which has been shown in the scientific literature to increase risk of developmental disabilities. The original purpose of the paper was to show a decline in phototherapy and pathological jaundice rates in relation to the recalibration of their total serum bilirubin machines showing this may have led to falsely increased rates of hyperbilirubinemia diagnoses and hospitalizations. Before the recalibration, 20.4% of babies were diagnosed with hyperbilirubinemia of > 15 mg/dL and the total phototherapy hospitalization rate was 13.2% (extended plus repeat hospitalizations). After the recalibration, the hyperbilirubinemia rate was still a remarkable 12.4% affecting 5283 babies and the phototherapy hospitalization rate was 5.7% or 2425 newborns. This is the latest publication showing the true rates of jaundice in a hospital system with high  rates of exclusive breastfeeding at discharge.   

The KPNC system has the highest exclusive breastfeeding rates at discharge in California according to 2014 data from the California Department of Public Health. Similar trends were found in 2013, within the time period examined by the study, which reported Kaiser Walnut Creek and Kaiser Oakland as having the highest exclusive breastfeeding rates at discharge of 97.5% and 95%, respectively. Considering that an estimated 22% of mothers have delayed lactogenesis II, which puts her newborn at risk for excessive weight loss and hyperbilirubinemia, a 95-97.5% exclusive breastfeeding rate predictably results in complications and hospitalizations occurring to 10-20% of newborns, as confirmed by this study. Once again, this study shows complications and hospitalizations for jaundice and dehydration are COMMON and occur at high rates in Baby-Friendly hospitals.  1 in 10 babies are hospitalized for jaundice and 1 in 6 experience levels of hyperbilirubinemia that has been associated with multiple developmental disabilities.  "Baby-Friendly" is in fact, NOT baby-friendly.  Fed is best.

Link to JAMA Pediatrics article: 
https://drive.google.com/open?id=0B0_MbXCqYazzSk1yYzNWM0hxT2M