Question

• 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

Citation

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