It is not surprising when I write a blog post about nutrition in the preterm neonate to find that at least one, and on this occasion two, of the articles are from the productive pen of Johannes van Goudoever.
Vlaardingerbroek H, Vermeulen MJ, Carnielli VP, Vaz FM, van den Akker CHP, van Goudoever JB: Growth and fatty acid profiles of vlbw infants receiving a multicomponent lipid emulsion from birth. Journal of Pediatric Gastroenterology & Nutrition 2014, 58(4):417-427.
SMOFLipid is a new-ish lipid emulsion which is made from several different sources, and as as result contains omega-3 fatty acids, as well as omega-6. It has been approved in Canada for TPN in adults, and has been approved in Europe also for neonates. Which I find a bit surprising as we had a recent presentation from our pharmacy, and the total published data from several small trials came to about 100 treated preterm babies, and 100 controls.
The NICU team in Rotterdam now add to that data, they have performed a clinical RCT comparing clinical outcomes among infants randomized to either SMOFLipid or Intralipid. 96 VLBW babies were randomized within 6 hours of birth, starting at 2 g/kg/d on day 1, and 3 g/kg/d on day 2.
The growth on SMOFLipid was improved, and the fatty acid profile was also improved with the DHA and EPA levels being maintained and significantly higher than the controls. There were no adverse effects noted. There were fewer cases of late onset sepsis, 27% rather than 40% had this complication. This is not individually significant, but some of the same authors have previously published a meta-analysis, which showed a 25% reduction in LOS based on 2 small trials and barely significant. If you add the new numbers to the data already in the literature, which which they do in their discussion, you now have a reduction in sepsis of 28% and the upper limit of the 95% CI is 0.94. So a very interesting finding, for which there is some theoretical/basic science support, which needs to be replicated in further larger trials.
I think there is good theoretical justification for using an emulsion which includes omega-3 fatty acids, and if we were to design the first ever intravenous lipid for a trial today we would probably have something like SMOFLipid in mind. However, I think we really should demand robust efficacy and safety data in comparison to the current standard before changing over. Even with the knowledge that when intralipid was introduced for preterm babies there was really no good controlled evaluation. I don’t think there is a single RCT against placebo of intralipid as a component of TPN in preterm infants, which is not that unusual for things that were introduced in the 50’s and 60’s. What to do about that is not entirely clear to me, but I don’t think the answer is to switch to a newer therapy after a few very small RCT’s. I think the time is now to ensure that we have big simple RCTs comparing current usual care to any innovation, even is the current usual care is based on very little, or almost no, data.
Olsen IE, Harris CL, Lawson ML, Berseth CL: Higher protein intake improves length, not weight, z scores in preterm infants. Journal of Pediatric Gastroenterology & Nutrition 2014, 58(4):409-416.This secondary analysis of data from a trial of a concentrated liquid human milk fortifier shows that there was a correlation between higher protein intakes and better length at 28 days.
Christmann V, de Grauw AM, Visser R, Matthijsse RP, van Goudoever JB, van Heijst AFJ: Early postnatal calcium and phosphorus metabolism in preterm infants. Journal of Pediatric Gastroenterology & Nutrition 2014, 58(4):398-403. How much calcium and phosphorus should we supply, and what should be the ratio between them? The answers to these questions are still not entirely clear to me. Avoiding early hypocalcemia, and/or hypophosphatemia, and then ensuring later good bone mineralisation may need different answers to those questions. The data in this study supports the idea that you need a lower calcium/phosphate ratio in the first couple of days, and that gradually changes afterward.
An accompanying editorial gives some guidance, much of which needs confirmation in other studies.