Breast Milk Jaundice Clinical Presentation

Aspects of history may include the following:

• Physiologic jaundice usually manifests after the first 24 hours of life. This can be accentuated by breastfeeding, which, in the first few days of life, may be associated with suboptimal milk and suboptimal caloric intake, especially if milk production is delayed. This is known as breastfeeding jaundice. Jaundice that manifests before the first 24 hours of life should always be considered pathologic until proven otherwise. In this situation, a full diagnostic workup with emphasis on infection and hemolysis should be undertaken.
• True breast milk jaundice (BMJ) manifests after the first 4-7 days of life. A second peak in serum bilirubin level is noted by age 14 days.
• In clinical practice, differentiating between physiologic jaundice from breast milk jaundice is important so that the duration of hyperbilirubinemia can be predicted. Identifying the infants who become dehydrated secondary to inadequate breastfeeding is also important. These babies need to be identified early and given breastfeeding support and formula supplementation as necessary. Depending on serum bilirubin concentration, neonates with hyperbilirubinemia may become sleepy and feed poorly.

The following physical findings may be noted:

• Clinical jaundice is usually first noticed in the sclera and the face. Then it progresses caudally to reach the abdomen and extremities. Gentle pressure on the skin helps to reveal the extent of jaundice, especially in darker-skinned babies; however, clinical observation is not an accurate measure of the severity of the hyperbilirubinemia.
• A rough correlation is observed between blood levels and the extent of jaundice (face, approximately 5 mg/dL; mid abdomen, approximately 15 mg/dL; soles, 20 mg/dL). Therefore, clinical decisions should always be based on serum levels of bilirubin. Skin should have normal perfusion and turgor and show no petechiae.
• Neurologic examination, including neonatal reflexes, should be normal, although the infant may be sleepy. Muscle tone and reflexes (eg, Moro reflex, grasp, rooting) should be normal.
• Evaluate hydration status by an assessment of the percentage of birth weight that may have been lost, observation of mucous membranes, fontanelle, and skin turgor.

The following causes may be noted:

• Supplementation of breastfeeding with dextrose 5% in water (D5W) can actually increase the prevalence or degree of 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.^[5] This may be comparable to what is observed in patients with Gilbert syndrome.^[6] 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 whites 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.^[7]
• 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.^[8]
• A 2011 study has shown 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 with exclusively or partially formula fed neonates.^[9]
• The organic anion transporters (OATPs) are a family of multispecific pumps that mediate the Na- independent uptake of bile salts and broad range of organic compounds. In humans, 3 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 3-fold increased risk for development of neonatal jaundice (peak serum bilirubin level of 20 mg/dL) when adjusted for covariates.^{[10, 11]} When the combination of the OATP-2 gene polymorphism with the variant UGT1A1 gene at nucleotide 211 further increased the risk to 22-fold (95% 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).
• In a 2012 study, researchers measured antioxidant properties of breast milk. Bilirubin is a known antioxidant in vitro. It is suggested that there is a homeostasis maintained by the external sources such as breast milk and internal production of antioxidants like bilirubin in the body. In this study, in the breast milk of mothers of newborns with prolonged jaundice, oxidative stress was found to be increased and the protective antioxidant capacity was found to be decreased. The exact clinical significance of this finding is not known.^[12]