Compared to our current threshold for saturations, these standards would lead to many more babies going home on oxygen than at present. As it takes a minimum of 5 days, and sometimes much longer, to organize home oxygen for a baby in our jurisdiction, following these guidelines would actually prolong hospitalisation for many babies! That, without any reliable information that it is necessary or safe. In addition weaning off oxygen at home takes longer than in the hospital. Even if the kids live close to the hospital, and could come to clinic or have a home respiratory therapy visit every week, adjustments of oxygen prescription, and analysis of saturation patterns afterward is much slower and more laborious at home. A baby who is close to coming off oxygen in the hospital, usually in our jurisdiction will have at least one month of HOT.

I think a persuasive statement about the benefits of being home on oxygen, rather than staying in the hospital just for oxygen therapy, would be quite reasonable, but to promote this non-evidence-based definition of hypoxia might lead to the contrary effect of delaying discharge, and increasing and prolonging oxygen therapy. ]]>

1. What was done with any of the information regarding gastric residuals not described. Was the volume considered important? The colour? Presumably they didn’t aspirate prior to each feed in order to ignore the findings.

The aim of this study was not to evaluate gastric residual color or volume but to determine differences between routine pre-feed aspiration and evaluation of gastric residuals and omission of gastric residuals. We have previously published a general set of guidelines (Li YF et al. (2014). Gastric residual evaluation in preterm neonates: a useful monitoring technique or a hindrance? Pediatrics and Neonatology, 55(5), 335-340) that included a suggested response algorithm used in our NICU for responding to gastric residuals.

2. The next big problem is the primary outcome: “weekly enteral nutrition measured in mL/kg for 6 weeks after birth”, I am not sure what that means. Did they add all the intake over 6 weeks and compare between groups? Did they compare after each week, and so do 6 comparisons?

Feeding intake is extremely difficult to measure and compare between infants on a daily basis. So trying to compare days before “full feedings” or day when” full feeding” is reached is difficult. Many babies will regress, thus there is a large problem with noise which has to be modulated for comparison purposes. Analysis for average daily intake for each week was thus used for the primary outcome.

3. Apparently, from the protocol, the plan was to do a t-test, designed for groups with unequal variance (“Welch adjusted” they call it). But the analysis which is presented is a Generalized Linear Mixed Model, which is a term that doesn’t tell me anything, but it seems to have been some sort of repeated measures test, which therefore should account for the multiple comparisons.

Generalized linear model (GML) encompasses linear models that appropriately handle a range of dependent variable types, including continuous, count, and dichotomous (McCullagh P & Nelder JA (1989). Generalized linear models (2nd edition). New York: Chapman & Hall/CRC publishers). A GLM for a continuous variable having 1 independent variable with 2 levels (1 numerator degree of freedom) and some number of error (denominator) degrees of freedom is exactly equivalent to a t-test with that same number of degrees of freedom. As t-tests do not provide the ability to include covariates, a GLM approach was used to evaluate models containing covariates.

4. Nowhere in the manuscript are the primary outcome results given. They do give a p-value however! In table 2 the first group of numbers are for weekly feedings in mL/kg/d and the p-value for Treatment is 0.048, but the actual numbers are written as NA.

The primary outcome was average daily intake in ml/kg for weeks 1-6. The least square means, along with the 95% CI are provided in the simple main effects listed for Weekly Feedings in Table 2. Those values are the results of the Simple main effects analysis, which are required as the treatment by time interaction was statistically significant, indicating that the pattern of differences between groups differed by week.

5. In table 2, the next group of numbers are for the “simple main effect”. I have to guess that the figures in parentheses are mean plus or minus 1 standard deviation, but that is never specified.

While, it may have been clearer had we labeled it Least Square Mean (95% CI) rather than Estimate, the table heading states the values in parentheses are the 95% CI for the value.

6. Many of the results are presented as “least square means” which is an SAS jargon for means, adjusted for covariates, which makes them difficult to interpret. Some of them are presented as the “mean estimated log weights” in the abstract, and sometimes in the abstract they are completely unexplained: “the no residual group were discharged 8 days earlier (4.21 [95% CI, 4.14-4.28] vs 4.28 [95% CI, 4.19-4.36]; P = .01)” 4.21 what?

In table 3, we specified that the gamma distribution was modeled for days to discharge. The gamma distribution uses log of the response as the link function, so the 4.21 and 4.28 values represent log transformed values. As with other transformed values, we provided raw (non-transformed) values as well, as those are more easily interpreted from a clinical standpoint.

7. In the text it is stated that the Odds for developing NEC in the intervention vs control group are 0.58 [95% CI, 0.18-0.19] vs 0.026 [95% CI, 0.006-0.109]).

In the abstract and text is it is stated that the Odds for necrotizing enterocolitis was (0.058 [95%CI, 0.018-0.19] vs 0.026 [95%CI, 0.006-0.109]). Table 5 states that these odds are for the control versus the intervention group. The error in the point estimate (0.58) and the CI (0.18-0.19) was discovered immediately after publication and this information was appropriately communicated to the journal editor.

8. In the discussion the authors state “we found no differences in incidence of NEC” which is clearly untrue, the incidence of NEC was quite different between groups. A true statement would have been “the difference in incidence of NEC that we found has very wide compatability limits, which include a possibility of a large reduction or a major increase in NEC”.

The purpose of this study was not to primarily evaluate NEC. It is very common to do secondary analyses in studies like this to look at potentially adverse outcomes. The number of NEC cases were more in the treatment group but this was not statistically different. To study this in a rigorous manner would require a much larger sample size.

9. As far as I can tell then, by week 6 the babies were receiving inadequate feeds if they didn’t measure gastric residuals, and even more inadequate feeds if they did!

The purpose of this study was not to determine whether the infants were having appropriate growth only to determine differences in growth between groups.

]]>The authors use two different definitions of hypoxemia depending on age: younger than 1 year old, hypoxemia defined as spending 5%of the recording time with SpO2 less than or equal to 90% . In children aged 1 year old and older, hypoxemia defined as spending 5% of the time with SpO2 less than or equal to 93%.

However when it comes time for recommendations the previous definitions are gone and replaced by one definition – that of 5% of the time with SpO2 less than or equal to 93%. It’s not clear why the definition was changed midway through the paper.

The authors see home oxygen therapy not as an alternative to no oxygen therapy but as an alternative to hospital oxygen therapy. Their rationale for HOT is to get these children out of the hospital and into their homes – which is why the recommendation is “Strong”. To quote “The strength of the panel’s recommendation is strong because its primary intention is to prevent the harmful effects of prolonged hospitalization” .They are not claiming any clear-cut health benefits for oxygen but are claiming benefits for being at home.

]]>This is why giving adult platelets to a baby with hypercoagulable plasma is potentially a serious pro-thrombotic risk. ]]>

Best Wishes – Madge E. Buus-Frank DNP, APRN-BC, FAAN

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