Thank you for your careful review of this manuscript. Your reviews have expanded our thinking
and strengthened the manuscript. We look forward to your review of our revisions. The changes
in the revised manuscript were highlighted in red. Revisions and answers for the reviewers’
specific comments included the following:
Problem statement
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Reviewer 1 asked for clarification of the primary and secondary purpose of the study.
We revised to clarify there are two specific aims under the combined purpose.
Background/Literature
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As per Reviewer 2’s comments, old literature before 2008 was replaced with more
recent one where possible.
Reviewer 1, 2, and editor asked more comprehensive literature reviews to support
citations introduced in discussion and concepts utilized thereby providing a more strong
foundation for the significance of the study. Literature reviews were extensively added
accordingly.
Based on the editor’s additional comments, the concept of continuous process of
attaining feeding milestone and needs to test further were clarified along with adding the
previous findings from the literature reviews. Also, the information of feeding practice for
preterm infants in NICU was added.
Theoretical Framework
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Reviewer 1 asked the need of a theoretical framework to make a link between the
concepts utilized. A general developmental science perspective, in which development is
viewed as complex, multi-causal, non-linear, and always changing, was used to
conceptualize this exploratory analysis. Given the purpose of the study (exploratory and
descriptive) as well as limited literature to support clear predictive relationships, the
perspective was used but was not able to introduce a clear framework in introduction.
However, the findings from this work provide relationships for future work. Yet we
believe the concepts were well operationalized without a model to depict potential
relationships.
Research design and method
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Reviewer 1 asked to use consistent terminology for medical complications vs. infant
illness characteristics. The consistent terminology of medical complication was used
throughout the paper.
Reviewer 1 was concerned about confounding effects of milk type on the feeding
progression as a major limitation of our study. Thank you for bringing this up. Milk type
data were provided in Table 1 and controlled as a time-varying covariate for all analysis.
Reviewer 2 and editor were concerned about impact of practice changes on our findings
since the data were collected (2003-2006) and suggested providing a background of a
trend in practice cares since then. Within 10 years, there is no clear trend in feeding
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practices; rather it still remains highly variable based on local customs and provider
experience. In addition to adding the information of feeding practice issues in NICU in
introduction, we clearly stated specifics of the feeding protocol used for the study infants
at the time of data collection under sample and setting, and mentioned the protocol has
not been changed since the data were collected in the study setting. Moreover, we also
clearly stated the limited generalizability of our findings to other centers that used
different feeding practices in the limitation section.
Reviewer 2 asked the information about size for GA (SGA, AGA, LGA) in addition to GA
and birth weight and this information was added to sample characteristics. A potential
effect of SGA on feeding progression has been suggested in some literature, but in the
current study the effect of SGA was not analyzed given its small percentage of the total
sample.
As per editor’s comments, justification of using PMA as the outcome and how GA was
determined were added under measures.
The editor asked for providing citation with brief finding of the parent study. The parent
study is submitted for publication and now under review. The citation was provided but it
was hard to provide a brief statement for the parent study findings in this manuscript
given multiple outcome variables and various analysis strategies across the outcomes.
The outcome variables of the parent study are unrelated to the ones used in the study,
which include short term (weekly until discharge) and long term weight gains (at 9 and
18 months), length of hospitalization, hospital cost, neurodevelopmental outcomes at 9
and 18 months by the Bayley Scales of Infant Development, Preferential looking tests at
24 months, and safety outcomes (retinopathy of prematurity (ROP), brainstem
audiological evoked responses (BEAR)). Only weight gain may be related with the
feeding progression but it was not of interest for the current study.
Data Analysis
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As per statistical reviews (Reviewer 3), details about the models and its implementation
were added in data analysis section, including of software used for analysis and model
specification (estimation method, repeated measure terms, covariance structures, and
estimation method for degrees of freedom). Infant’s PMA was treated as fixed analysis
of variance effects (categorical variable). We believe the revisions according to reviewer
3’s comments addressed the editor’s concerns for lack of clarification of the models
used.
The editor asked to provide co-occurrences of medical complications during
hospitalization. This information was provided in Table 1 as part of sample
characteristics as well as clearly addressed our findings should be interpreted with a
caution of co-existing medical conditions as the limitation of the study.
The editor was concerned about impact of excluded infants for the current analysis
because of death and transfer on the conceptual population of our interest, i.e., EP
infants (born ≤ 28 weeks of GA). Sensitivity analysis was conducted to show the study
infants were not different from the excluded infants and clearly defined the impact of
excluded infants on the conceptual population of our interest.
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The editor asked for the clarification how we handled missing values, e.g., infants who
are discharged prior to attaining all milestones and impact of missing values on
parameter estimates. This information is added at the last sentence of the first
paragraph in Data analysis section.
Results
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Reviewer 1 and editor asked to provide a table describing infant characteristics,
including medical complications. Infant characteristics were described in Table 1.
The editor asked to provide tables that include parameter estimate of each model as
supplemental digital content. SAS outputs of all models we ran are attached as a
supplemental digital content.
Discussion
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New citations in discussion were avoided by introducing the literature in advance in
introduction.
Clarification of the phrase of “totally recovered” from NEC was suggested by the editor in
discussion. This sentence was reworded to improve the clarification (page 12, line 1214).
Figure
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The superscript in the x-axis label was deleted.