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

Abstract

Fok TF, Chui KKM, Cheung R, Ng PC, Cheung KL, Hjelm M. Manganese intake and cholestatic jaundice in neonates receiving parenteral nutrition: a randomized controlled study. Acta Paediatr 2001; 90: 1009-1015 Infants requiring parenteral nutrition (n = 244) were randomized to receive either 1 (group 1, n = 121) or 0.0182 mmol/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 mmol/L). Subgroup analysis was carried out on the data of 78 infants in group 1 and 82 in group 2 who had received manganese supplementation and more than three-quarters of their total daily uid 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 1 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 signi cance. 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 uid as parenteral nutrition showed, however, that the high manganese group developed signi cantly 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 signi cant 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 mmol/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 signi cant contributory factor.

Role of trace elements in parenteral nutrition support of the surgical neonate

“…In animals, Mn deficiency is associated with impaired skeletal development and ataxia [49,50]. Carbohydrate and mucopolysaccharide metabolic abnormalities caused by impaired enzymatic function and diminished reproductive ability have also been described.…”

“…Other neurologic symptoms of toxicity include memory loss, weakness, difficulty walking, slowed response time, and seizures [54,55]. Excess Mn has been reported to cause cholestasis in animal models and is correlated with severity of cholestasis in preterm and term infants [49,50].…”

Is manganese an essential supplement for parenteral nutrition?

“…Although chronic overexposure to Mn in parenteral nutrition patients has been recognized as a problem for some time now, there have been further reports of elevated Mn levels since Dickerson's review [4,7,11 ,[16][17][18][19][20][21]22 ,23 ] (Table 1). High Mn levels are particularly problematic in the paediatric setting [16,17,19,24] and in long-term HPN patients [18,[25][26][27]; however, hypermanganesemia has also been reported in acute care [7,20]. In addition to these clinical and laboratory findings, a recent analysis of post-mortem data [22 ] describes the cumulative effect of Mn supplementation in patients who received long-term parenteral nutrition for short bowel syndrome (SBS).…”

“…This predisposes long-term parenteral nutrition patients to tissue accumulation and/or brain deposition of Mn resulting in neurological symptoms. Mn intake has also been implicated in worsening parenteral nutrition associated cholestasis; however, a clear cause-effect relationship has not been established [17]. Data about the temporal relationship between the dose and duration of Mn supplementation and elevated Mn levels have also been to some degree contradictory [4,18].…”

Trace Elements in Parenteral Nutrition: Considerations for the Prescribing Clinician

“…As 90% is excreted in the bile [53], high levels can develop in PN patients with cholestasis, but elevated levels can be seen in patients with normal liver function as well [43,54,55]. In addition, it is possible that manganese can also contribute to cholestasis [56,57,58,59]. Apart from experimental cases of manganese deprivation, there has only been one reported case of manganese deficiency, which occurred in a child with a very short bowel on PN [60].…”