Neonatal hyperbilirubinemia increases intestinal protein permeability and the prevalence of cow's milk protein intolerance

Abstract
Bilirubin is a newly discovered modulator of the gut barrier in vitro and in vivo. We studied the effect of bilirubin on the serosal to mucosal intestinal permeability in vivo. We also investigated the prevalence of cow's milk protein intolerance (CMPI) in infants with moderate hyperbilirubinemia versus matched controls.Faecal alpha 1 antitrypsin (a1AT) was used to monitor intestinal protein loss; a large cohort was prospectively followed for 12 months for sign and symptoms of CMPI.Neonates with hyperbilirubinemia had higher stool excretion of a1AT than controls (0.68 +/- 0.28 mg/g vs. 0.25 +/- 0.11 mg/g; p < 0.01). Faecal a1AT correlates with total serum bilirubin (TSB) (r = 0.85; p < 0.01). Also, in the first 12 months of life, formerly hyperbilirubinemic infants had an higher prevalence of CMPI (14/353 vs. 4/339; chi2= 4.018, p = 0.045).Neonatal hyperbilirubinemia increases stool protein loss and is also a mild risk factor for CMPI.