Manganese intake and cholestatic jaundice in neonates receiving parenteral nutrition: a randomized controlled study

Infants requiring parenteral nutrition (n = 244) were randomized to receive either 1 (group 1, n = 121) or 0.0182 mu mol/kg/d (group 2, n = 123) of manganese supplementation. The whole-blood manganese and serum direct bilirubin concentrations of the infants were monitored, as was the development of cholestasis (peak serum direct bilirubin concentration > 50 mu mol/L). Subgroup analysis was carried out on the data of 78 infants in group I and 82 in group 2 who had received manganese supplementation and more than three-quarters of their total daily fluid as parenteral nutrition for > 14 d. Of all the infants randomized, the high manganese group (group 1) showed a trend towards developing higher peak whole-blood manganese concentration [group I versus group 2: median (interquartile range): 606.0 (421.0; 1005.0) vs 566.0 (336.0; 858.0); p=0.061] and higher peak serum direct bilirubin concentration [37.0 (10.5; 122.5) vs 19.0 (8.0, 112.5); p = 0.153], but the differences between the 2 groups did not reach statistical significance. The 2 groups did not differ in terms of the occurrence of cholestasis during parenteral nutrition (63/121 vs 57/123; P = 0.444). Subgroup analysis of infants who had received more than three-quarters of their total daily fluid as parenteral nutrition showed, however, that the high manganese group developed significantly higher whole-blood manganese concentration [743.5 (498.0; 1211.0) vs 587.0 (438.0; 982.0); p = 0.037] and serum direct bilirubin concentration [84.0 (28.0; 170.0) vs 25.5 (9.0; 117.0); p < 0.001]. Although there was no significant difference in the occurrence of cholestasis (58/78 vs 49/82; p = 0.073), more infants in the high manganese group developed a more severe degree of direct hyperbilirubinaemia, with peak serum direct bilirubin > 100 mu mol/L (32/78 vs 20/82; p = 0.038). Conclusion: We conclude that the pathogenesis of parenteral nutrition-related cholestasis is probably multifactorial, and that high manganese intake is a significant contributory factor.