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Giving ß-Glucuronidase Inhibitors During the First Week of Life Reduces Jaundice in Breastfed Infants


  • Are there simple preventitve measures to prevent hyperbilirubinemia in breastfed infants?

Clinical Bottom Lines

  1. Feeding breastfed newborns ß-glucuronidase inhibitors during the first week after birth increased fecal bilirubin excretion and reduced jaundice compared to breastfeeding only.1
  2. None of the infants developed dehydration, jaundice needing light therapy, or lost more than 10% of birth weight so no clinically significant outcome measures could be assessed. 
  3. While the differences were statistically significant, they were not clinically meaningful. Therefore, I would not recommend using ß-glucuronidase inhibitor supplementation.

Summary of Key Evidence

  1. Sixty-four breastfed newborns were randomized to four groups: 1) control; 2) L-aspartic acid; 3) enzymatically hydrolyzed casein (EHC); or 4) whey/casein (W/C). Each of the intervention supplements were given as six doses per day (5 mL per dose) for the first week. L-Aspartic acid and EHC inhibit ß-glucuronidase.1
  2. The L-aspartic acid, EHC, and W/C groups had significantly lower transcutaneous bilirubin levels on days 3 to 7. At the bilirubin peak (day 4), treatment group levels were 75.8%, 69.6%, and 69.2% of control values (control mean: 8.53 mg/dL) for the L-aspartic acid, EHC, and W/C groups, respectively.
  3. Overall fecal bile pigment excretion was significantly higher than control values in the L-aspartic acid (P < .001) and W/C (P = .0014) groups; the L-aspartic acid group excreted more fecal bile pigments than did the control group on days 4 to 6, and the W/C group excreted more bile pigments than did the control group on days 2 to 4. Bile pigment fecal excretion did not differ significantly between the L-aspartic acid and EHC groups.
  4. Seventeen of the subjects were in a risk zone above the low-risk zone within the first 48 hours after birth (6 in the control group, 5 in the L-aspartic acid group, 1 in the EHC group, and 5 in the W/C group).  The combined inhibitor groups had a significantly shorter decline time than the combined no-inhibitor groups. Only 1 subject in the entire study was in the highest (>95th percentile) risk zone (age: 22.7 hours).

Additional Comments

  • As noted by the authors, the decreased jaundice in the W/C group, which lacked a beta-glucuronidase inhibitor, suggests a different mechanism


  1. Gourley GR, Li Z, Kreamer B, Kosorok M. A controlled, randomized, double-blind trial of prophylaxis against jaundice among breastfed newborns. Pediatrics 2005;116;385-91.

CAT Author: Christine Stahle, MD

CAT Appraisers: Steve Park, MD

Date appraised: January 31, 2007

Last updated August 15, 2007
Department of Pediatrics and Communicable Diseases
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