Review for 10.1186/s12876-015-0369-0 (2015)

Reviewer's report
Title:Systematic review of the impact of feed protein type and degree of
hydrolysis on gastric emptying in children
Version:3Date:26 August 2015
Reviewer: Sharon Perrella
Reviewer's report:
Major Compulsory Revisions
#11 has not been addressed in the revision with regard to the wide age range.
The authors have explained that the Fried et al (1992) paediatric study has been
excluded because there are some 18yr old subjects (none older than this) and
"GE is different in paediatrics to adults" yet is has not been acknowledged that
GE in the preterm infant is likely different to that of older infants, and children of
up to 16yrs.
#17 has not been addressed
Casein: whey ratios change over time in breast milk. As previously requested,
please state whether the protein composition of breast milk was measured or
assumed in the cited studies.
re use of ratio vs % of casein and whey, the authors state "We have kept to %
and did not use the ratio" however Results line 16 states "...infant formula
containing a ratio of 60:40" and it is described as whey-predominant formula
(60% whey). It is also important to succinctly explain in the Introduction that most
formulas contain both casein and whey, but that the proportions and degree of
hydrolysis differs between products.
INTRODUCTION
line 9-11 'It is known that a variety of factors impact on GE in paediatrics
including the type of protein (ie whey or casein), level of hydrolysis..."
If this were known, this systematic review would not be necessary - please
reword this sentence.
Minor Essential Revisions
ABSTRACT
Results 4th line: please replace "human milk" with "breast milk" so that
manuscript terminology is consistent
INTRODUCTION
(line 17) please replace "have" with "has"
METHODS
Please revise the following sentences to make them more succinct - currently
somewhat difficult to follow...
(lines 22-25) suggest "Twenty studies met the inclusion criteria and were
discussed with RM: 10 were excluded as they did not sufficiently meet the aims
of the review, or insufficient feed composition information was provided"
(lines 25-4) suggest "Of the remaining publications, 4 were further discussed with
NS, with 2 of these subsequently excluded, resulting in only 8 studies deemed
suitable for review"
RESULTS
line 7: please remove hyphen from preterm
line 8: "(gestation ranging from 27 weeks to term)"
By definition, a preterm infant is born at a birth gestation < 37 weeks. It is
possible that the preterm infants were studied at term corrected gestational age
(CGA). Please clarify if you are reporting CGA or correct if reporting birth
gestation.
(Breast milk versus whole whey/casein feeds)
line 18: what measure of GE are you reporting here? T1/2 or another time point?
please clarify
lines 18-21: "However, there was a 3-week difference..." please revise this
sentence to make it more succinct. (Suggest: However, there was a 3-week
difference in the mean gestational age between the two groups (breast fed 36
weeks; formula-fed 33 weeks) that could potentially confound the results.
line 5 states that the Thorkelsson study "does not provide the macronutrient
content of feeds" however the published paper states that only the protein
composition differed between the test feeds. Please correct the statement.
(Whole protein casein versus whey feeds)
line 1: (t1/2 of 33.1 min) please delete "of".
(Whole protein compared to hydrolysed protein)
lines 11-13 not necessary to refer to studies that compared with amino acids and
soya feeds as they are beyond the aims of this review.
line 12 please remove hyphen from "macro-nutrient"
DISCUSSION
line 18-20 Please revise this sentence as the review did not examine the type of
protein and level of hydrolysis in breast milk. Suggest " To the best of our
knowledge, this is the first systematic review to assess the impact of both protein
type and level of hydrolysis in milk formula on paediatric GE, and to also consider
GE of breast milk. Our findings with regard to protein type concur with those of
Woodley who reviewed only the effects of casein and whey dominant formula on
GE."
lines 12-17 Please combine and simplify these sentences. Suggest "To date no
paediatric study has compared GE of 100% whole whey and 100% whole casein
feeds, likely due to the inavailability of commercially prepared 100% casein
based formula. The current evidence suggests that whey-dominant feeds may
faciliate GE in children with GOR.
line 22 "therefor" please correct spelling
Sentence (lines 15-17) please replace the word "concluding" with "suggesting" or
similar as there is insufficient evidence to draw conclusions.
OTHER
The abbreviation for GE half-emptying time needs to be included in the list of
abbreviations, and needs to be consistent throughout the document. It currently
appears as " T 1/2", "t1/2" and "t 1/2" -with the "1/2" as subscript
The abbreviation for 13C octanoic acid breath test needs to be consistent
throughout the document. It currently appears as "CT13-OABT", "13C-OABT",
"C13-OABT", "13OAT-BT" and "13C-based BT"
There are inconsistencies in spacing / no spacing when reporting T1/2 eg.
"74min" or "63.3min"
TABLE 1
Please re-word the title to improve clarity. Suggest "Systematic Review
inclusion/exclusion criteria for studies examining breast milk and formula and the
effects of protein on GE"
TABLE 2
Please replace column heading "Description (number of patients)' with "Study
design and sample"
Please replace column heading "Feed Comparison" with "Test feed protein
composition" (You can then list feeds as Feed 1, Feed 2 etc)
Please remove the hyphen from "fundoplica-tion"
Please remove colons from casein and whey proportions as colons are used to
denote ratios eg 60:40, or 60%, 40%
REFERENCE LIST
Ref#9 Please correct spelling of "emptying" and add a question mark to the end
of the publication title.
DISCRETIONARY REVISIONS
The following suggestions are offered to improve clarity / accuracy
INTRODUCTION
(line 5) please consider replacing "characteristics" with "composition"
(line 11) please consider amending "with established older methods such as
scintigraphy" to "established with scintigraphy" (as correlations with methods
other than the gold standard are of less interest).
METHODS
(lines 18-20) please consider revising / combining the two sentences - not
necessary to report that scintigraphy is regarded the gold standard as this has
already been established in the Introduction
(lines 21-22) please consider revising the sentence to "GE studies performed in
children (age ranges preterm infants to 16 years) were included if they compared
GE of breast milk or milk formula with whole or hydrolysed..."
(line 8) please consider replacing "search of publications" with "literature search"
RESULTS
Please revise the following sentences to make them more succinct - currently
somewhat difficult to follow...
(lines 22-25) suggest "Twenty studies met the inclusion criteria and were
discussed with RM: 10 were excluded as they did not sufficiently meet the aims
of the review, or insufficient feed composition information was provided"
(lines 25-4) suggest "Of the remaining publications, 4 were further discussed with
NS, with 2 of these subsequently excluded, resulting in only 8 studies deemed
suitable for review"
DISCUSSION
lines 12-17 Please combine and simplify these sentences. Suggest "To date no
paediatric study has compared GE of 100% whole whey and 100% whole casein
feeds, likely due to the inavailability of commercially prepared 100% casein
based formula. The current evidence suggests that whey-dominant feeds may
faciliate GE in children with GOR.
lines 2-8 Not necessary to justify exclusion of other methods here as it has been
established in the introduction. Suggest "Other methods of measuring GE...and
imaging procedures, but have not been adequately validated in the paediatric
population."
line 9 suggest replace "low number of recruited patients" with "small sample
sizes"
line 14 suggest replace "by studies that occurred after that review" with "by
subsequent studies".
Sentences can be simplified by leaving out the bracketed words..
p.14 (The first study conducted by) Savage et al compared GE..."
p.16 (The authors found that) the formula containing 50% whole whey had..."
TABLE 2
Please replace column heading "Feed Comparison" with "Test feed protein
composition" (You can then list feeds as Feed 1, Feed 2 etc)
Results column can be further simplified as all but the last 2 studies report T1/2:
you could replace results column heading with "Results (T1/2)" and change the
heaidng for the last 2 studies. By doing this, you could report results for each
study as
Feed 1: 47 min
Feed 2: 65 min (p<0.05)
This would also allow you to report individual and pooled results for Savage
Suggest you abbreviate Nissen fundoplication to simplify reporting eg. CP and
NF, CP no NF
FIGURE 1
Suggest simplifying heading further eg. "Publications identified through database
search" and "Publications identified through other sources"
My impression is that the central boxes indicate the publications retained at each
stage of the selection process, and boxes to the right indicate the reason and
number of publications removed during the process. If my understanding is
correct, I think that
* the first central box should read "n=214"and there should be a box to the right
reading "Duplicated removed (n=88)"
* there should be an arrow connecting the "publications screened (n=126)" box to
the "Full text articles evaluated (n=20)" box (and remove the arrow connecting
the "publications excluded" box from the "full text articles evaluated (n=20) box.
* there should be an arrow connecting the "Full text articles evaluated (n=20)"
box to the "studies included in the qualitative synthesis" (could replace this with
"Studies included in systematic review"
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: No, the manuscript does not need to be seen by a statistician.
Declaration of competing interests:
I have no competing financial or non-financial interests to declare.
My salary is paid from an unrestricted research grant that is paid by Medela AG
to The University of Western Australia