Will Hyperbilirubinemic Neonates Ever Benefit from Oral Zinc Salt?

Abstract

To the Editor: Neonatal hyperbilirubin is attracting increasing attention (1). In a recent issue of JPGN, Vitek et al. (2) addressed the issue of the effect of zinc salt on serum bilirubin levels in hyperbilirubinemic rats. They showed that administration of oral zinc salts for two weeks decreased serum bilirubin levels in hyperbilirubinemic rats, presumably by inhibiting the enterohepatic circulation of bilirubin. They conclude that administration of zinc salts might be useful in the treatment of severe unconjugated hyperbilirubinemias also in neonates. We feel this conclusion is not warranted, and risks disappointing health givers’ expectations. Indeed, oral therapy with zinc salt for the treatment of neonatal jaundice is far from being applicable in clinical practice for several reasons. Firstly, the most dangerous effect of neonatal hyperbilirubinemia occurs too early for the oral zinc to be efficacious (within the first five or six days of life with a peak in the third day (3)). According to Vitek et al., the therapeutic effect occurs after two weeks-at which point, the infant would have already left the hospital. Secondly, the metabolism of zinc is in a very steady balance with that of copper, and any uncontrolled oral supplementation of zinc salts may alter the absorption of trace elements by the newborn. Thirdly, the human neonatal gut may not absorb zinc as efficiently as rat gut. A study of preterm neonates showed that doubling the zinc intake does not influence serum zinc concentration (4). Consequently, the use of zinc supplementation for the prevention of neonatal jaundice remains, at best, speculative. Finally, we recently showed that neonates with unconjugated jaundice have altered intestinal permeability with a positive significant correlation with serum bilirubin (5). This is secondary to a decrease in mannitole absorption, which is suggestive of impaired intestinal epithelial surface. In such cases of altered intestinal absorptive condition, oral supplementation, of any type, is unlikely to have a therapeutic effect. None of the in vitro studies aimed at identifying alternative therapeutic approaches for the prevention or treatment of neonatal hyperbilirubin, has been confirmed in clinical trials. Currently guidelines treatment for neonatal jaundice (1,3) make difficult. In conclusion, we suggest caution be exercised as to the efficacy of zinc salt supplementation for the treatment of jaundice in the newborns. However, we feel that other types of unconjugated jaundice (such as Gilbert syndrome and Crigler Naijar syndrome) may be more responsive to zinc supplementation, particularly in preventing gallstone formation. Flavia Indrio, MD Maria Elisabetta Baldassarre, MD Ruggiero Francavilla, MD, PhD Department of Pediatrics, Neonatology Section University of Bari Bari, Italy