Total parenteral nutrition in sick preterm infants: effects of cysteine supplementation with nitrogen intakes of 240 and 400 mg/kg/day. N-acetylcysteine does not prevent bronchopulmonary dysplasia in immature infants: a randomized controlled trial. Cysteine supplementation to cysteine-free intravenous feeding regimens in newborn infants.
The effects of supplementing total parenteral nutrition (TPN) solutions with cysteine were assessed at two different levels of nitrogen intake by determining nitrogen retention, sulfate excretion, and sulfur-containing amino acid concentrations. Ten infants received 72 mg/kg/day of cysteine-HCl in a TPN solution for a period of 6 days. Five of these infants received 251 +/- 48 (mean +/- SD) mg/kg/day of nitrogen, and five received 403 +/- 45 mg/kg/day of nitrogen. Two other groups of five infants each received unsupplemented TPN at nitrogen intakes of 235 +/- 48 and 412 +/- 54 mg/kg/day, respectively. Fluid and nonprotein caloric intakes were similar for all four groups. Cysteine supplementation increased plasma and urine free cyst(e)ine concentrations and enhanced total sulfur retention, but did not enhance nitrogen retention. [Cyst(e)ine refers to the mixture in any proportion of the sulfhydryl (cysteine) and the disulfide (cystine) forms of this compound.] Nitrogen retention, sulfate excretion, cyst(e)ine excretion, and plasma taurine concentrations increased as the result of the increase in nitrogen intake. To evaluate whether N-acetylcysteine (NAC) infusion during the first week of life reduces the risk of death or bronchopulmonary dysplasia (BPD) in infants with extremely low birth weight. Study design In a Nordic multicenter, double-blind trial, infants (n=391) weighing 500 to 999 g and on ventilator or nasal continuous positive airway pressure were randomized before the age of 36 hours to receive NAC 16 to 32 mg/kg/d (n=194) or placebo (n=197) intravenously for 6 days. Primary end points were death or BPD, defined as supplementary oxygen requirement at 36 weeks' gestational age.
                There was no difference in the combined incidence of the primary end points death or BPD, 51% vs. 49%, between the NAC group and control group. Also similar was the incidence of BPD in survivors at 36 weeks' gestational age, 40% vs. 40%, and the mean oxygen requirement at the age of 28 days, 31.2% vs. 30.7%, respectively. The severity of BPD was similar in both groups.
                A 6-day course of intravenous N-acetylcysteine at the dosage used does not prevent BPD or death in infants with extremely low birth weight. To determine if cysteine is an essential amino acid for the intravenously fed newborn infant, growth parameters, nitrogen balance, plasma sulfur amino acid levels, and urinary amino acid excretion of premature and term infants were measured in the presence or absence of infused cysteine. Control intravenous formulations provided amino acids, including adequate methionine, carbohydrate, lipid, minerals, vitamins, and trace elements to all infants. Group and pair-matched comparisons showed that nitrogen retention, weight change, and growth in length and head circumference were not affected by cysteine supplementation of 77 mg/kg/24 h. The failure of cysteine supplementation to alter nitrogen retention was independent of postnatal age or gestational age. Plasma 1/2 cystine concentration was increased by 60% in the supplemented group with a concomitant 3-fold increase in urinary excretion of 1/2 cystine and taurine, but not of urinary methionine or cystathionine. Cysteine-supplemented infants exhibited a small increase in 3-methylhistidine excretion compared to pair-matched controls, suggesting that either an increase in muscle protein catabolism or an increase in muscle mass may have occurred.
Available evidence from RCTs shows that routine short-term cysteine chloride supplementation of cysteine-free PN in preterm infants improves nitrogen balance. However, there is insufficient evidence to assess the risks of cysteine supplementation, especially regarding metabolic acidosis, which has been reported during the first two weeks of cysteine chloride administration. Available evidence from a large RCT trial does not support routine N-acetylcysteine supplementation of cysteine-containing PN in extremely low birth weight infants.