Background
Arias first described breast milk jaundice (BMJ) in 1963. Breast milk jaundice is a type of neonatal jaundice associated with breastfeeding. It is characterized by indirect hyperbilirubinemia in a breastfed newborn that develops after the first 4-7 days of life, persists longer than physiologic jaundice, and has no other identifiable cause. [1] It should be differentiated from breastfeeding jaundice, which manifests in the first 3 days of life and is caused by insufficient production or intake of breast milk.
Pathophysiology
Breast milk jaundice is a common cause of indirect hyperbilirubinemia. The etiology of breast milk jaundice is not clearly understood, but the following factors have been suggested to play a role:
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An unusual metabolite of progesterone (pregnane-3-alpha 20 beta-diol), a substance in the breast milk that inhibits uridine diphosphoglucuronic acid (UDPGA) glucuronyl transferase
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Increased concentrations of nonesterified free fatty acids that inhibit hepatic glucuronyl transferase
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Increased enterohepatic circulation of bilirubin due to (1) increased content of beta glucuronidase activity in breast milk and, therefore, the intestines of the breastfed neonate and (2) delayed establishment of enteric flora in breastfed infants
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Defects in uridine diphosphate-glucuronyl transferase ( UGT1A1) activity in infants who are homozygous or heterozygous for variants of the Gilbert syndrome promoter and coding region polymorphism. [2]
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Reduced hepatic uptake of unconjugated bilirubin due to a mutation in the solute carrier organic anion transporter protein SLCO1B1.
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Inflammatory cytokines in human milk, especially interleukin (IL)-1 beta and IL-6, are increased in individuals with breast milk jaundice and are known to be cholestatic and reduce the uptake, metabolism, and excretion of bilirubin. [3]
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High epidermal growth factor (EGF) levels in breast milk may be responsible for jaundice in these neonates. EGF is responsible for growth, proliferation, and maturation of the GI tract in newborns and is vital for is adaptation after birth. Higher EGF serum and breast milk levels were noted in patients with breast milk jaundice. [4] The reduced GI motility and increased bilirubin absorption and uptake are thought to be the mechanisms.
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Serum alpha feto-protein levels were found to be higher in infants with breast milk jaundice. [5] The exact significance of this finding is unknown.
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Breast milk is an important source of bacteria in establishing infantile gut flora. A recent study demonstrated that Bifidobacterium species in breast milk may protect against breast milk jaundice. The exact significance of this finding is unknown. [6]
Please see Neonatal Jaundice for an in-depth review of the pathophysiology of hyperbilirubinemia.
Epidemiology
Frequency
United States
Jaundice occurs in 50-70% of newborns. Moderate jaundice (bilirubin level >12 mg/dL) develops in 4% of bottle-fed newborns, compared to 14% of breastfed newborns. Severe jaundice (bilirubin level >15 mg/dL) occurs in 0.3% of bottle-fed newborns, compared to 2% of breastfed newborns. A strong familial predisposition is also suggested by the recurrence of breast milk jaundice in siblings. In the exclusively breast fed infant, the incidence during the first 2-3 weeks has been reported to be 36%. [7]
International
International frequency is not extensively reported but is thought to be similar to that in the United States.
Mortality/Morbidity
The prognosis is excellent, although jaundice in breastfed infants may persist for as long as 12 weeks.
Breast milk jaundice in otherwise healthy full-term infants rarely causes kernicterus (bilirubin encephalopathy). Case reports suggest that some breastfed infants who suffer from prolonged periods of inadequate breast milk intake and whose bilirubin levels exceeded 25 mg/dL may be at risk of kernicterus. Kernicterus (bilirubin encephalopathy) is a preventable cause of cerebral palsy. Another group of breastfed infants who may be at risk of complications is late preterm infants who are nursing poorly.
Bilirubin encephalopathy (kernicterus) may occur in exclusively breastfed infants in the absence of hemolysis or other specific pathologic conditions. Distinguishing between breastfeeding jaundice and breast milk jaundice is important, because bilirubin-induced encephalopathy occurs more commonly in breastfeeding jaundice. Near-term infants are more likely to manifest breastfeeding jaundice because of difficulty achieving adequate nursing, greater weight loss, and hepatic immaturity.
Race
Whether racial differences are observed in breast milk jaundice is unclear, although an increased prevalence of physiologic jaundice is observed in babies of Chinese, Japanese, Korean, and Native American descent.
Sex
No sex predilection is known.
Age
Breast milk jaundice manifests after the first 4-7 days of life and can persist for 3-12 weeks.
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The graph represents indications for phototherapy and exchange transfusion in infants (with a birthweight of 3500 g) in 108 neonatal ICUs. The left panel shows the range of indications for phototherapy, whereas the right panel shows the indications for exchange transfusion. Numbers on the vertical axes are serum bilirubin concentrations in mg/dL (lateral) and mmol/L (middle). In the left panel, the solid line refers to the current recommendation of the American Academy of Pediatrics (AAP) for low-risk infants, the line consisting of long dashes (- - - - -) represents the level at which the AAP recommends phototherapy for infants at intermediate risk, and the line with short dashes (-----) represents the suggested intervention level for infants at high risk. In the right panel, the dotted line (......) represents the AAP suggested intervention level for exchange transfusion in infants considered at low risk, the line consisting of dash-dot-dash (-.-.-.-.) represents the suggested intervention level for exchange transfusion in infants at intermediate risk, and the line consisting of dash-dot-dot-dash (-..-..-..-) represents the suggested intervention level for infants at high risk. Intensive phototherapy is always recommended while preparations for exchange transfusion are in progress. The box-and-whisker plots show the following values: lower error bar = 10th percentile; lower box margin = 25th percentile; line transecting box = median; upper box margin = 75th percentile; upper error bar = 90th percentile; and lower and upper diamonds = 5th and 95th percentiles, respectively.
