Abuse of Casein Hydrolysate Formulas for Treating Infants With Severe Hyperbilirubinemia: In Reply

Abstract

In Reply.—We thank Dr Bhutani for the opportunity to provide additional information regarding our controlled, randomized, double-blind trial of prophylaxis against jaundice among 64 breastfed newborns.1 Our study demonstrated that breastfed infants who received minimal aliquots of L-aspartic acid or enzymatically hydrolyzed casein for β-glucuronidase inhibition had increased fecal bilirubin excretion and less jaundice, without disruption of the breastfeeding experience. Although 2 previous studies of ours demonstrated that infants who were exclusively fed a casein hydrolysate formula had significantly less jaundice than infants who were exclusively fed either a routine formula or breast milk,2,3 we agree with Dr Bhutani that additional research would better define the ability of specific casein hydrolysate formula ingredients to reduce bilirubin and prevent excessive hyperbilirubinemia without interrupting breastfeeding.Space consideration prevented us from providing additional information regarding the subgroup analysis of 17 newborn infants with serum bilirubin levels in the first 48 hours of life that were above the low-risk zone (ie, >40th percentile on the nomogram developed by Bhutani et al4 that was included in the 2004 American Academy of Pediatrics hyperbilirubinemia guidelines5). The decline times (in hours) from a risk zone above the low-risk zone within the first 48 hours to a low-risk zone after 48 hours were compared among these 17 subjects and found to be significantly shorter in the combined groups that received a β-glucuronidase inhibitor compared with those that did not receive a β-glucuronidase inhibitor. Additional characteristics of these 17 infants are presented below in Table 1. The single infant in the enzymatically hydrolyzed casein group is particularly interesting because he was the only infant in the highest risk zone. As can be seen from these data, this infant had 2 significant risk factors for hyperbilirubinemia: male gender and a significantly lower gestational age (36 weeks) than the other groups. This infant's bilirubin level of 8.6 mg/dL at 22.7 hours of age (>95th percentile, highest risk zone) decreased to 8.5 mg/dL at 46.3 hours of age (40–75th percentile, low-intermediate–risk zone) and 7.7 mg/dL at 74.9 hours of age (<40th percentile, low-risk zone) and remained in the low-risk zone thereafter. Despite inclusion of this more significantly jaundiced, lower-gestational-age infant along with those in the L-aspartic acid group to form the group receiving β-glucuronidase inhibition, this group had a significantly faster decline from a risk zone above the low-risk zone within the first 48 hours to a low-risk zone after 48 hours than the group receiving no β-glucuronidase inhibition.Although our small study is very encouraging, at this point in time we concur with Dr Bhutani that the use of a casein hydrolysate formula, L-aspartic acid, or enzymatically hydrolyzed casein is premature and that administration of these supplements to infants at risk for severe hyperbilirubinemia requires additional research. Future research regarding use of such nutritional supplements for breastfed infants would be of particular interest in infants with either hour-specific bilirubin levels associated with increased risk for the subsequent development of severe hyperbilirubinemia or in infants with clinical risk factors increasing their risk of severe hyperbilirubinemia. This research should be conducted in a manner to minimize any possible negative effects on breastfeeding and must include careful analysis to assess any possible negative effects on breastfeeding.