Glutamine is one of the most abundant amino acids in our bodies, but there is relatively little in TPN as it is poorly soluble. During the first few days of limited enteral nutrition preterm babies receive little glutamine from any source, and this probably contributes to gut atrophy and perhaps to later feeding intolerance. So a number of studies have tried to supplement glutamine either enterally or in TPN. The Cochrane review shows no overall effect of either mode of supplementation (the latest version from earlier this year, has changed authors apart from Bill McGuire, and includes 11 RCTs with 2800 babies; pretty good evidence for the field of neonatology, and almost entirely negative).

Just published on-line in Pediatrics is a long term outcome study of one of the trials, with some elegant analysis of MRI data from the participants at about 8,5 years (de Kieviet JF, Oosterlaan J, Vermeulen RJ, Pouwels PJW, Lafeber HN, van Elburg RM: Effects of Glutamine on Brain Development in Very Preterm Children at School Age. Pediatrics 2012.). Only 53 of the 89 surviving infants were imaged, but the study shows some differences favouring the glutamine group. They did however perform 15 statistical comparisons between the groups, with no apparent adjustment for the multiple testing; and showed a larger hippocampus in the glutamine supplemented babies.

Now if you go back to their original publication, (van den Berg A, van Elburg RM, Westerbeek EA, Twisk JW, Fetter WP: Glutamine-enriched enteral nutrition in very-low-birth-weight infants and effects on feeding tolerance and infectious morbidity: a randomized controlled trial. The American Journal of Clinical Nutrition 2005, 81(6):1397-1404.) You find that the primary outcome variable was feeding tolerance. In a study with a total of about 100 babies of less than 32 weeks and less than 1500 grams they showed no effect on feeding tolerance. A secondary outcome of serious infections was however different between groups. They actually had an enormously high rate of serious culture positive infections, 75% in the controls and 50% in the glutamine supplemented group, despite  mean birth weight which was over 1.1 kg.

This new follow up study was therefore analyzed with infections as an important co-variate, and all of the differences in MRI findings are explained by the associations between infection and adverse brain development. Importantly the Cochrane review mentioned above does not show any effect of glutamine on infections. So this study was somewhat of an outlier, it does add weight to the importance of infection as an indicator for future cerebral developmental abnormalities, but does not mean that we should re-open the question of supplemental glutamine supplementation in the preterm. I still think that question is settled. Unless perhaps you have a 75% incidence of serious bacterial infections in your VLBW infants….