Carrots anyone? This is interesting, but I am afraid I can’t figure out a number of things in the manuscript. The authors report that they randomized 203 babies <33 weeks to get supplemented with carotenoids, they wanted to look at effects on the blood levels of the 3 carotenoids. I am not sure why you would want to do that, surely if you give carotenoids, it would be weird if the carotenoid levels didn’t go up. I guess they were really interested in the secondary outcomes, growth, feeding tolerance and electroretinograms.
where it starts to get confusing is in the analysis, of the 203 enrolled infants, they select 183 babies to be the ITT group, 91 controls and 92 supplemented. That is a perversion of the term ‘Intention To Treat’. An ITT analysis includes all of the randomized subjects. It is not clear what was wrong with the other 20 babies, why weren’t they analyzed? The authors supply a Consort flow sheet in the supplemental data, but nowhere on that flow sheet are there 12 controls and 8 supplemented babies who were not analyzed mentioned, the flow sheet introduces even more confusion, there were 70 controls and 73 supplemented who completed the study, but only 50 and 58 of them completed ‘on assigned feeding’. In the results, they state that 52 and 46 infants respectively were ‘evaluable’ which apparently means they strictly adhered to the feeding protocol.
In fact none of the numbers in the flow sheet match the numbers in the text.
The primary outcome variable, that is the blood carotenoid concentrations, wasn’t even measured in most of the infants, at 40 weeks, only 43 controls and 36 supplemented infants had plasma concentrations measured. This is another number that doesn’t appear anywhere else, or in the flow sheets, and is unexplained. To only measure the primary outcome variable on a third of the randomized patients doesn’t sound like good research planning.
Even more bizarre the sample size was calculated as being 68 patients per group, for each of the 3 groups, but there were only 2 groups. The authors talk about a 3rd human milk group in the methods, but they then are very hard to find in the results, and don’t appear at all in the flow sheet. I think what they did was randomize infants to 2 groups, of formulae with or without carotenoids, and then when an infant was receiving a lot of breast milk, they took them out of the assigned group and called them a 3rd group. But the only data presented from them that I can see are the CRP values. The carotenoid concentration comparison group that they show in the figures as the human milk group is from previously unpublished data from Abbott, from term breast fed babies.
The ERG results are from a very small subset of infants, 16 controls and 25 supplemented.
I can’t see any indication that this trial was registered, which most IRBs now insist on, and most journals also require. The Consort flow diagram is missing a lot of information, such as numbers of babies eligible, and doesn’t explain most of the terms.
I was just planning to write a little note to point out this study which might show something, but after re-reading it, the post started growing and growing; I am very confused if they found anything, other than giving carotenoids might increase carotenoid concentrations in the 1/3 of the infants who had them measured.
Neonatal Research 