Breast Milk Jaundice

Updated: Dec 08, 2017
  • Author: Prashant G Deshpande, MD; Chief Editor: Muhammad Aslam, MD  more...
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Arias first described breast milk jaundice (BMJ) in 1963. [1, 2] This condition is a type of neonatal jaundice associated with breastfeeding that is characterized by indirect hyperbilirubinemia in an otherwise healthy breastfed newborn that develops after the first 4-7 days of life, persists longer than physiologic jaundice, and has no other identifiable cause. [3, 4, 5]

Breast milk jaundice should be differentiated from breastfeeding jaundice, which manifests in the first 3 days of life, peaks by 5-15 days of life, disappears by week 3 of life, and is caused by insufficient production or intake of breast milk. [4]  In contrast to babies with breast milk jaundice, infants suffering from breastfeeding jaundice generally exhibit mild dehydration and weight loss in the first few days of life. [5]



Breast milk jaundice is a common cause of indirect hyperbilirubinemia. The etiology of breast milk jaundice is not clearly understood, but a combination of genetic and environmental factors may play a role. [5] The following factors may contribute:

  • 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 [5]
  • Increased concentrations of nonesterified free fatty acids that inhibit hepatic glucuronyl transferase [5]
  • 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 [6]
  • 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 [7]
  • Reduced hepatic uptake of unconjugated bilirubin due to a mutation in the solute carrier organic anion transporter protein SLCO1B1
  • Increased levels of inflammatory cytokines in human milk, especially interleukin (IL)-1 beta and IL-6,  in individuals with breast milk jaundice; these are known to be cholestatic and reduce the uptake, metabolism, and excretion of bilirubin [8]

Epidermal growth factor (EGF) is responsible for growth, proliferation, and maturation of the gastrointestinal tract in newborns, and it is vital for adaptation after birth. Higher EGF serum and breast milk levels have been noted in patients with breast milk jaundice. [9]  Reduced gastrointestinal motility and increased bilirubin absorption and uptake are thought to be the mechanisms.

Serum alpha fetoprotein levels have been found to be higher in infants with breast milk jaundice. [10] The exact significance of this finding is unknown.

Breast milk is an important source of bacteria in establishing infantile gut flora. Tuzun et al demonstrated that Bifidobacterium species in breast milk may protect against breast milk jaundice. [11]  The exact significance of this finding is unknown. A phase I trial that evaluated the safety and tolerability of Bifidobacterium longus subspecies infantis EVC001 supplementation in 34 healthy term breastfed infants compared to 34 who received lactation support alone found no differences between the groups in mean gestational age at birth, weight at postnatal months 1 and 2, and breast milk intake. [12]  B infantis supplementation was safe and well tolerated, and infants receiving this supplementation had fewer and better formed stools than those in the lactation support–only group.

Please see the Medscape Drugs and Diseases article Neonatal Jaundice for an in-depth review of the pathophysiology of hyperbilirubinemia.



Replacement of  breastfeeding with oral glucose solution does not appear to decrease the prevalence or degree of jaundice. [13]

Note the following causes of breast milk jaundice:

  • Delayed milk production and poor feeding lead to decreased caloric intake,  dehydration, and increased enterohepatic circulation, resulting in higher serum bilirubin concentration.
  • The biochemical cause of breast milk jaundice remains under investigation. Some research reported that lipoprotein lipase, found in some breast milk, produces nonesterified long-chain fatty acids, which competitively inhibit glucuronyl transferase conjugating activity.
  • Glucuronidase has also been found in some breast milk, which results in jaundice.
  • Decreased uridine diphosphate-glucuronyl transferase ( UGT1A1) activity may be associated with prolonged hyperbilirubinemia in breast milk jaundice. [14]  This may be comparable to what is observed in patients with Gilbert syndrome. [15]  Genetic polymorphisms of the  UGT1A1 promoter, specifically the T-3279G and the thymidine-adenine (TA)7 dinucleotide repeat TATAA box variants, were found to be commonly inherited in white individuals with high allele frequency. These variant promoters reduce the transcriptional  UGT1A1 activity. Similarly, mutations in the coding region of the  UGT1A1 (eg, G211A, C686A, C1091T, T1456G) have been described in East Asian populations; these mutations reduce the activity of the enzyme and are a cause of Gilbert syndrome. [16]
  • The G211A mutation in exon 1 (Gly71Arg) is most common, with an allele frequency of 13%. Coexpression of these polymorphism in the promoter and in the coding region are common and further impair the enzyme activity. [17]
  • A study showed that neonates with nucleotide 211GA or AA variation in UGT1A1 genotypes had higher peak serum bilirubin levels than those with GG. This effect was more pronounced in the exclusively breast fed infants compared to exclusively or partially formula fed neonates. [18]
  • The organic anion transporters (OATPs) are a family of multispecific pumps that mediate the sodium independent uptake of bile salts and broad range of organic compounds. In humans, three liver-specific OATPs have been identified: OATP-A, OATP-2, and OATP-8. Unconjugated bilirubin is transported in the liver by OATP-2. A genetic polymorphism for OATP-2 (also known as OATP-C) at nucleotide 388 has been shown to correlate with three-fold increased risk for development of neonatal jaundice (peak serum bilirubin level of 20 mg/dL) when adjusted for covariates. [19, 20]  The combination of the OATP-2 gene polymorphism with the variant  UGT1A1 gene at nucleotide 211 further increased the risk to 22-fold (95% confidence interval [CI], 5.5-88). When these genetic variants were combined with breast milk feeding, the risk for marked neonatal hyperbilirubinemia increased further to 88-fold (95% CI, 12.5-642.5).
  • Bilirubin is a known antioxidant. [21] It has been suggested that there is a homeostasis maintained by external sources such as breast milk and internal production of antioxidants such as bilirubin in the body. In a study by Uras et al, the breast milk of mothers of newborns with prolonged jaundice was found to have increased oxidative stress, whereas there was a reduction in the protective antioxidant capacity. [22] The exact clinical significance of this finding is not known.
  • Breastfeeding women in populations with a high prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency should avoid consumption of fava beans as well as ingestion of quinine-containing sodas. [23] The presence of these pro-oxidant items in breast milk may induce G6PD crises in the breastfed children, leading to jaundice and/or hemolytic anemia. [23]


United States data

Jaundice occurs in 50-70% of newborns. Excess physiologic jaundice (bilirubin level >12 mg/dL) develops in 4% of bottle-fed newborns, compared to 14% of breastfed newborns. Exaggerated physiologic jaundice (bilirubin level >15 mg/dL) occurs in 0.3% of bottle-fed newborns, compared to 2% of breastfed newborns. [24]

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 20-30%, [25]  although a more recent review indicates about 2-4% of exclusively breastfed infants have jaundice with bilirubin levels above 10 mg/dL in week 3 of life. [4]


The international frequency of breast milk jaundice is not extensively reported but is thought to be similar to that in the United States.

Race-, sex-, and age-related demographic

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.

No sex predilection is known.

Breast milk jaundice manifests after the first 4-7 days of life and can persist for 3-12 weeks.



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. Note that kernicterus 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.

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 their difficulty in achieving adequate nursing, greater weight loss, and hepatic immaturity.