title: A controlled, randomized, double-blind trial of prophylaxis against jaundice among breastfed newborns.
abstract: OBJECTIVE
  Neonatal jaundice is a greater problem for infants fed breast milk, compared with formula. This study tested the hypotheses that feeding breastfed newborns beta-glucuronidase inhibitors during the first week after birth would increase fecal bilirubin excretion and would reduce jaundice without affecting breastfeeding deleteriously.
  
  
  METHODS
  Sixty-four breastfed newborns were randomized to 4 groups, ie, control or receiving 6 doses per day (5 mL per dose) of L-aspartic acid, enzymatically hydrolyzed casein (EHC), or whey/casein (W/C) for the first week. L-aspartic acid and EHC inhibit beta-glucuronidase. Transcutaneous bilirubin levels (primary outcome) were measured daily (Jaundice Meter [Minolta/Air Shields, Hatboro, PA] and Bilicheck [Respironics, Pittsburgh, PA]). All stools were collected, and fecal bile pigments, including bilirubin diglucuronide, bilirubin monoglucuronides, and bilirubin, were analyzed with high-performance liquid chromatography. Follow-up assessments included day 7 body weight, day 6/7 prebreastfeeding/postbreastfeeding weights, maternal ratings, and ages at formula introduction and breastfeeding cessation.
  
  
  RESULTS
  The groups were comparable at entry. Overall, the L-aspartic acid, EHC, and W/C groups had significantly lower transcutaneous bilirubin levels than did the control group (75.8%, 69.6%, and 69.2%, respectively, of the control mean, 8.53 mg/dL, at the bilirubin peak on day 4). The L-aspartic acid, EHC, and W/C groups had significantly lower transcutaneous bilirubin levels on days 3 to 7. Fecal bile pigment excretion was greatest in the L-aspartic acid group, significantly greater than control values. There were no significant differences in dosages, follow-up measurements, and maternal ratings.
  
  
  CONCLUSIONS
  Use of minimal aliquots of L-aspartic acid and EHC for beta-glucuronidase inhibition results in increased fecal bilirubin excretion and less jaundice, without disruption of the breastfeeding experience. Decreased jaundice in the W/C group, which lacked a beta-glucuronidase inhibitor, suggests a different mechanism.
authors.affiliation: Department of Pediatrics, Oregon Health and Science University, Portland, Oregon 97239-2998, USA. gourleyg@ohsu.edu
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Gourley
authors.forename: Zhanhai
authors.initials: Z
authors.lastname: Li
authors.forename: Bill L
authors.initials: BL
authors.lastname: Kreamer
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kosorok
mesh_terms: D001224:Aspartic Acid / Q000008:administration & dosage*; D001654:Bile Pigments / Q000032:analysis; D001663:Bilirubin / Q000032:analysis / Q000097:blood; D001942:Breast Feeding; D002364:Caseins / Q000008:administration & dosage*; D004311:Double-Blind Method; D005243:Feces / Q000737:chemistry; D005966:Glucuronidase / Q000037:antagonists & inhibitors*; D006801:Humans; D007231:Infant, Newborn; D007567:Jaundice, Neonatal / Q000378:metabolism / Q000517:prevention & control*; D008894:Milk Proteins / Q000008:administration & dosage*; D000067816:Whey Proteins
chemical_list: D001654:Bile Pigments; D002364:Caseins; D008894:Milk Proteins; D000067816:Whey Proteins; D001224:Aspartic Acid; C475729:casein hydrolysate; D005966:Glucuronidase; D001663:Bilirubin