History

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 their serum bilirubin concentration, neonates with hyperbilirubinemia may become sleepy and feed poorly.

Physical Examination

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 the 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 bilirubin levels. Skin should have normal perfusion and turgor and show no petechiae.

Neurologic examination findings, 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 the infant's hydration status by an assessment of the percentage of birth weight that may have been lost, as well as observation of the mucous membranes, fontanelle, and skin turgor.

Differential Diagnoses

Arias IM, Gartner LM, Seifter S, et al. Neonatal unconjugated hyperbilirubinemia associated with breast feeding and a factor in milk that inhibits glucuronide formation in vitro. Presented at: The 55th Annual Meeting of the American Society for Clinical Investigation; Atlantic City, New Jersey. April 29, 1963.
Arias IM, Gartner LM, Seifter S, Furman M. Prolonged neonatal unconjugated hyperbilirubinemia associated with breast feeding and a steroid, pregnane-3(alpha), 20(beta)-diol, in maternal milk that inhibits glucuronide formation in vitro. J Clin Invest. 1964 Nov. 43:2037-47. [Medline]. [Full Text].
Gotze T, Blessing H, Grillhosl C, Gerner P, Hoerning A. Neonatal cholestasis - differential diagnoses, current diagnostic procedures, and treatment. Front Pediatr. 2015. 3:43. [Medline].
Ullah S, Rahman K, Hedayati M. Hyperbilirubinemia in neonates: types, causes, clinical examinations, preventive measures and treatments: a narrative review article. Iran J Public Health. 2016 May. 45(5):558-68. [Medline]. [Full Text].
Memon N, Weinberger BI, Hegyi T, Aleksunes LM. Inherited disorders of bilirubin clearance. Pediatr Res. 2016 Mar. 79(3):378-86. [Medline]. [Full Text].
Yoshioka H, Iseki K, Fujita K. Development and differences of intestinal flora in the neonatal period in breast-fed and bottle-fed infants. Pediatrics. 1983 Sep. 72(3):317-21. [Medline].
Fujiwara R, Maruo Y, Chen S, Tukey RH. Role of extrahepatic UDP-glucuronosyltransferase 1A1: advances in understanding breast milk-induced neonatal hyperbilirubinemia. Toxicol Appl Pharmacol. 2015 Nov 15. 289(1):124-32. [Medline].
Zanardo V, Golin R, Amato M, et al. Cytokines in human colostrum and neonatal jaundice. Pediatr Res. 2007 Aug. 62(2):191-4. [Medline].
Kumral A, Ozkan H, Duman N, Yesilirmak DC, Islekel H, Ozalp Y. Breast milk jaundice correlates with high levels of epidermal growth factor. Pediatr Res. 2009 Aug. 66(2):218-21. [Medline].
Manganaro R, Marseglia L, Mami C, Saitta G, Gargano R, Gemelli M. Serum alpha-fetoprotein (AFP) levels in breastfed infants with prolonged indirect hyperbilirubinemia. Early Hum Dev. 2008 Jul. 84(7):487-90. [Medline].
Tuzun F, Kumral A, Duman N, Ozkan H. Breast milk jaundice: effect of bacteria present in breast milk and infant feces. J Pediatr Gastroenterol Nutr. 2013 Mar. 56(3):328-32. [Medline].
Smilowitz JT, Moya J, Breck MA, et al. Safety and tolerability of Bifidobacterium longum subspecies infantis EVC001 supplementation in healthy term breastfed infants: a phase I clinical trial. BMC Pediatr. 2017 May 30. 17 (1):133. [Medline]. [Full Text].
Kuhr M, Paneth N. Feeding practices and early neonatal jaundice. J Pediatr Gastroenterol Nutr. 1982. 1(4):485-8. [Medline].
Maruo Y, Nishizawa K, Sato H, Sawa H, Shimada M. Prolonged unconjugated hyperbilirubinemia associated with breast milk and mutations of the bilirubin uridine diphosphate- glucuronosyltransferase gene. Pediatrics. 2000 Nov. 106(5):E59. [Medline]. [Full Text].
Monaghan G, McLellan A, McGeehan A, et al. Gilbert's syndrome is a contributory factor in prolonged unconjugated hyperbilirubinemia of the newborn. J Pediatr. 1999 Apr. 134(4):441-6. [Medline].
Huang CS, Chang PF, Huang MJ, Chen ES, Hung KL, Tsou KI. Relationship between bilirubin UDP-glucuronosyl transferase 1A1 gene and neonatal hyperbilirubinemia. Pediatr Res. 2002 Oct. 52(4):601-5. [Medline].
Lin Z, Fontaine J, Watchko JF. Coexpression of gene polymorphisms involved in bilirubin production and metabolism. Pediatrics. 2008 Jul. 122(1):e156-62. [Medline].
Chou HC, Chen MH, Yang HI, et al. 211 G to a variation of UDP-glucuronosyl transferase 1A1 gene and neonatal breastfeeding jaundice. Pediatr Res. 2011 Feb. 69(2):170-4. [Medline].
Huang MJ, Kua KE, Teng HC, Tang KS, Weng HW, Huang CS. Risk factors for severe hyperbilirubinemia in neonates. Pediatr Res. 2004 Nov. 56(5):682-9. [Medline].
Watchko JF. Genetics and the risk of neonatal hyperbilirubinemia: commentary on the article by Huang et al. on page 682. Pediatr Res. 2004 Nov. 56(5):677-8. [Medline].
Fujiwara R, Haag M, Schaeffeler E, Nies AT, Zanger UM, Schwab M. Systemic regulation of bilirubin homeostasis: Potential benefits of hyperbilirubinemia. Hepatology. 2018 Apr. 67(4):1609-19. [Medline].
Uras N, Tonbul A, Karadag A, Dogan DG, Erel O, Tatli MM. Prolonged jaundice in newborns is associated with low antioxidant capacity in breast milk. Scand J Clin Lab Invest. 2010 Oct. 70(6):433-7. [Medline].
Bichali S, Brault D, Masserot C, et al. Maternal consumption of quinine-containing sodas may induce G6PD crises in breastfed children. Eur J Pediatr. 2017 Oct. 176(10):1415-8. [Medline].
Schneider AP 2nd. Breast milk jaundice in the newborn. A real entity. JAMA. 1986 Jun 20. 255(23):3270-4. [Medline].
Maisels MJ, Clune S, Coleman K, et al. The natural history of jaundice in predominantly breastfed infants. Pediatrics. 2014 Aug. 134(2):e340-5. [Medline]. [Full Text].
Stark AR, Lannon CM. Systems changes to prevent severe hyperbilirubinemia and promote breastfeeding: pilot approaches. J Perinatol. 2009 Feb. 29 suppl 1:S53-7. [Medline].
Kaplan M, Hammerman C. Understanding and preventing severe neonatal hyperbilirubinemia: is bilirubin neurotoxity really a concern in the developed world?. Clin Perinatol. 2004 Sep. 31(3):555-75, x. [Medline].
Preer GL, Philipp BL. Understanding and managing breast milk jaundice. Arch Dis Child Fetal Neonatal Ed. 2011 Nov. 96(6):F461-6. [Medline].
[Guideline] American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics. 2004 Jul. 114(1):297-316. [Medline].
Maisels MJ, McDonagh AF. Phototherapy for neonatal jaundice. N Engl J Med. 2008 Feb 28. 358(9):920-8. [Medline].
van Dommelen P, van Wouwe JP, Breuning-Boers JM, van Buuren S, Verkerk PH. Reference chart for relative weight change to detect hypernatraemic dehydration. Arch Dis Child. 2007 Jun. 92(6):490-4. [Medline].
Gourley GR, Li Z, Kreamer BL, Kosorok MR. A controlled, randomized, double-blind trial of prophylaxis against jaundice among breastfed newborns. Pediatrics. 2005 Aug. 116(2):385-91. [Medline].
Maisels MJ. Historical perspectives: transcutaneous bilirubinometry. NeoReviews. May 2006. 7(5):e217-e225.
Keren R, Luan X, Friedman S, Saddlemire S, Cnaan A, Bhutani VK. A comparison of alternative risk-assessment strategies for predicting significant neonatal hyperbilirubinemia in term and near-term infants. Pediatrics. 2008 Jan. 121(1):e170-9. [Medline].
Maisels MJ, Deridder JM, Kring EA, Balasubramaniam M. Routine transcutaneous bilirubin measurements combined with clinical risk factors improve the prediction of subsequent hyperbilirubinemia. J Perinatol. 2009 Sep. 29(9):612-7. [Medline].
Maisels MJ, Bhutani VK, Bogen D, Newman TB, Stark AR, Watchko JF. Hyperbilirubinemia in the newborn infant > or =35 weeks' gestation: an update with clarifications. Pediatrics. 2009 Oct. 124(4):1193-8. [Medline].
Harris MC, Bernbaum JC, Polin JR, Zimmerman R, Polin RA. Developmental follow-up of breastfed term and near-term infants with marked hyperbilirubinemia. Pediatrics. 2001 May. 107(5):1075-80. [Medline].
Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics. 1999 Jan. 103(1):6-14. [Medline].
Fontaine P. The first month of life. In: Ratcliffe S, Byrd JE, Sakornbut E, eds. Handbook of Pregnancy and Perinatal Care in Family Practice: Science and Practice. Philadelphia, PA: Hanley & Belfus; 1995. 396-429.
Gartner LM, Herschel M. Jaundice and breastfeeding. Pediatr Clin North Am. 2001 Apr. 48(2):389-99. [Medline].
Grunebaum E, Amir J, Merlob P, Mimouni M, Varsano I. Breast mild jaundice: natural history, familial incidence and late neurodevelopmental outcome of the infant. Eur J Pediatr. 1991 Feb. 150(4):267-70. [Medline].
Hamosh M, Bitman J. Human milk in disease: lipid composition. Lipids. 1992 Nov. 27(11):848-57. [Medline].
Huang MJ, Kua KE, Teng HC, Tang KS, Weng HW, Huang CS. Risk factors for severe hyperbilirubinemia in neonates. Pediatr Res. 2004 Nov. 56(5):682-9. [Medline].
Johnson LH, Bhutani VK, Brown AK. System-based approach to management of neonatal jaundice and prevention of kernicterus. J Pediatr. 2002 Apr. 140(4):396-403. [Medline].
Maisels MJ, Newman TB. Kernicterus in otherwise healthy, breast-fed term newborns. Pediatrics. 1995 Oct. 96(4 pt 1):730-3. [Medline].
Martinez JC, Maisels MJ, Otheguy L, et al. Hyperbilirubinemia in the breast-fed newborn: a controlled trial of four interventions. Pediatrics. 1993 Feb. 91(2):470-3. [Medline].
Yamauchi Y, Yamanouchi I. Breast-feeding frequency during the first 24 hours after birth in full-term neonates. Pediatrics. 1990 Aug. 86(2):171-5. [Medline].
[Guideline] Muchowski KE. Evaluation and treatment of neonatal hyperbilirubinemia. Am Fam Physician. 2014 Jun 1. 89(11):873-8. [Medline]. [Full Text].

Media Gallery

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.

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Author

Prashant G Deshpande, MD Attending Pediatrician, Department of Pediatrics, Christ Hospital Medical Center and Hope Children's Hospital; Assistant Clinical Professor of Pediatrics, Midwestern University

Prashant G Deshpande, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Telemedicine Association

Disclosure: Nothing to disclose.

Coauthor(s)

Sameer Wagle, MBBS, MD Consulting Staff, Division of Neonatology, Northwest Medical Center of Springdale and Willow Creek Women’s Hospital

Sameer Wagle, MBBS, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Brian S Carter, MD, FAAP Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Attending Physician, Division of Neonatology, Children's Mercy Hospital and Clinics; Faculty, Children's Mercy Bioethics Center

Brian S Carter, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Pediatric Society, American Society for Bioethics and Humanities, American Society of Law, Medicine & Ethics, Society for Pediatric Research, National Hospice and Palliative Care Organization

Disclosure: Nothing to disclose.

Chief Editor

Muhammad Aslam, MD Professor of Pediatrics, University of California, Irvine, School of Medicine; Neonatologist, Division of Newborn Medicine, Department of Pediatrics, UC Irvine Medical Center

Muhammad Aslam, MD is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Additional Contributors

Oussama Itani, MD, FAAP, FACN Clinical Associate Professor of Pediatrics and Human Development, Michigan State University; Medical Director, Department of Neonatology, Borgess Medical Center

Oussama Itani, MD, FAAP, FACN is a member of the following medical societies: American Academy of Pediatrics, American Association for Physician Leadership, American Heart Association, American College of Nutrition

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Drugs & Diseases gratefully acknowledge the contributions of previous author Timothy Ramer, MD, to the development and writing of this article.

Breast Milk Jaundice Clinical Presentation

History

Physical Examination

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