A child presents to your primary care clinic, who is a three-day old exclusively breast-fed female of European descent born at 36 weeks gestation.  Pregnancy, labor, delivery, and post-natal course were uncomplicated.  Mom’s blood type was A+, and this is her first child.  The infant was discharged at 24 hours of life, and her bilirubin level at that time was 6mg/dL, all indirect, which corresponded to a low intermediate risk level for developing severe hyperbilirubinemia.  She appears jaundiced on exam, and you note that she has lost approximately 8% of her birth weight.  Her current total serum bilirubin is 12mg/dL, all indirect.  You continue to trend bilirubin levels in your office throughout the week.  Her total bilirubin level peaks on day of life four and is down-trending by day of life six. What is the most likely etiology of her jaundice?

A. Breast milk jaundice

B. Breastfeeding jaundice

C. ABO incompatibility

D. Biliary atresia

E. G6PD deficiency

 

The correct answer is B, Breastfeeding jaundice.

 

Answer Choice B: Breastfeeding Jaundice

Over 60% of healthy newborns will develop jaundice.  The first step in any question about jaundice is to determine if the bilirubin is direct or indirect.  Breastfeeding jaundice is a form of indirect hyperbilirubinemia which develops between day of life two to four, peaks between day of life four to five, and typically resolves by two weeks of life.  Breastfeeding jaundice is mainly caused by inadequate milk intake.

 

Answer Choice A: Breast Milk Jaundice

This answer is easy to mix up with breast milk jaundice, which was answer A.  Breast milk jaundice develops later in life.  Breast milk jaundice is also a cause of indirect hyperbilirubinemia and peaks on day of life five to fifteen and can take up to 12 weeks to resolve.  In contrast to breast feeding jaundice, these infants are usually feeding well with good weight gain.

 

Answer Choice C: ABO Incompatibility

While ABO incompatibility is another cause of indirect hyperbilirubinemia, it is essentially ruled out in this situation as mom’s blood type is A+.  ABO incompatibility should primarily be considered in infants born to mothers whose blood is type O.

 

Answer Choice D: Biliary Atresia

This is incorrect as it is a cause of direct hyperbilirubinemia as compared to indirect hyperbilirubinemia.  To learn more about this, feel free to look at our episode on direct hyperbilirubinemia.

 

Answer Choice E: Glucose-6-Phosphate Dehydrogenase Deficiency

Finally, G6PD, or glucose-6-phosphate dehydrogenase, deficiency, is another cause of indirect hyperbilirubinemia which is unlikely in this infant.  G6PD deficiency is an X-linked recessive genetic condition that is most common in males of African, Asian, Middle Eastern, and Mediterranean descent.  In the United States, African American males are the most commonly affected.  G6PD deficiency increases the vulnerability of erythrocytes to oxidative stress.  Fava beans and oxidative medications, including many sulfa medications and nitrofurantoin, should be avoided in G6PD deficiency as these may trigger an acute hemolytic reaction.  Fava beans and oxidative medications must also be avoided in breastfeeding mothers as they may be transmitted through breast milk and lead to a hemolytic reaction in the infant.

 

Here are some additional points about hyperbilirubinemia:

  1. The AAP recommends that any infant discharged at 24 hours of life or younger should be seen by their PCP by 72 hours of life.  
  2. Major risk factors for the development of severe hyperbilirubinemia include:
  • Jaundice in the first 24 hours of life
  • Blood group incompatibility with a positive direct Coomb’s test
  • Prematurity
  • Previous siblings requiring phototherapy
  • Cephalohematomas or other bruising
  • Exclusive breastfeeding
  • Infants of East Asian descent

 

Resources

  1. 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. doi: 10.1542/peds.114.1.297. Erratum in: Pediatrics. 2004 Oct;114(4):1138. PMID: 15231951.
  2. Maisels, MJ. Neonatal Jaundice. Pediatrics in Review Dec 2006, 27 (12) 443-454; DOI: 10.1542/pir.27-12-443.
  3. Anderson, NB, Calkins, KL. Neonatal Indirect Hyperbilirubinemia. NeoReviews Nov 2020, 21 (11) e749-e760; DOI: 10.1542/neo.21-11-e749.
  4. Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Fava Beans. [Updated 2018 Dec 3]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK532498/.
  5. Frank JE. Diagnosis and management of G6PD deficiency. Am Fam Physician. 2005 Oct 1;72(7):1277-82. PMID: 16225031.
  6. Kaplan M, Hammerman C. Glucose-6-Phosphate Dehydrogenase Deficiency: A Worldwide Potential Cause of Severe Neonatal Hyperbilirubinemia. NeoReviews Feb 2000, 1 (2) e32-e39; DOI: 10.1542/neo.1-2-e32.
  7. Koosha A, Rafizadeh B. Evaluation of neonatal indirect hyperbilirubinaemia at Zanjan Province of Iran in 2001-2003: prevalence of glucose-6-phosphate dehydrogenase deficiency. Singapore Med J. 2007 May;48(5):424-8. PMID: 17453100.

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