Review Reports

1.     Page   2, line 50 - posterior risk of obesity - do authors refer   to obesity later in life? Please clarify and revise accordingly.

Yes,   we meant obesity later in life. It was modified accordingly.

2.     Page   3, line 135 - A z score of <2 should be changed to < -2

Revised,   as suggested.

3.     General   comments - Methods/Results: Does the food frequency questionnaire (FFQ)   include the method of mixing in formula fed babies (both for powder and   liquid conc.). Including this information may help to evaluate the association   between mixing errors with slow/rapid gain of weight.

The   FFQ included the method of mixing formula but we did not detect errors in the   mixing, it was done according to instructions.

4.     General   comments - Methods/Results: Did authors explore the association between   pre-pregnancy BMI and infant weight gain characteristics. Also report any   association noted between pregnancy weight gain and weight changes in   infants.

Yes,   this was already reported in another publication. Please see link to the   reference: https://www-ncbi-nlm-nih-gov.ezproxy.fiu.edu/pubmed/30524746

Major   comment 1:

The   classification of infant formulas as 1) hydrolysate, 2) casein-based, or 3)   soy-based isn’t meaningful. The authors state that casein-based formula was   more common (line 161), but is this 100% casein-based (which will be quite a   surprise in my opinion)? Furthermore, the authors seem to term whey-based   formula as hydrolysate, but hydrolysate formula might also be casein-based   (e.g. Nutramigen from Mead Johnson).

We   agree with the reviewer. After extensive review of type of formulas, we   changed the analysis to:

-   Formulas not hydrolysate.

-   Formulas partially or extensively hydrolysate.

We   changed the results accordingly.

Major   comment 2:

Lines   78-79, “Results from this study could contribute to the new recommendations   being developed for children from birth to 2 years of age in the US.” What   recommendations? And what about the WHO breastfeeding recommendation? This is   not mentioned anywhere.

The   Dietary Guidelines for Americans (DGA) are being prepared for infants from   birth to 24 months. Currently, the DGAs are only for 2 years and older.   However, due to lack of data, more studies among this group has been   requested:

https://www.cnpp.usda.gov/birthto24months

Although   there are WHO recommendations on breastfeeding, and it is the preferred   method for feeding infants, guidelines are needed for formula feeding as most   US infants are not breastfed.

We   added the following to the introduction:

4^th   paragraph: Breastfeeding   is the feeding method recommended by the World Health Organization [17]. However,   this is low in the US. Data from the WIC program, a nutrition supplementation   program in the US with more than 1.93 million infants participating   nationally in 2016, showed that only 30.9% were breastfed (12.9% exclusively   breastfed and 18.0% partially breastfed) while 69.1% were formula fed [18].

Last   paragraph: Results from this study could contribute to the new   Dietary Guidelines for Americans being developed for children from birth to 2   years of age in the US [23]. Although   breastfeeding is the recommended method, this is not the main feeding method   used in the US and studies are needed to understand the contribution of   formula feeding to obesity. 
 

Major   comment 3:

Authors   use weight-for-height Z-score (WHZ) as one of their outcome and defines rapid   weight gain as increase > 0.67 in WHZ. This is not correct, rapid weight   gain is defined as an increase > 0.67 SD in weight-for-age Z-score (WAZ).   I can’t figure out how the authors did calculate the Z-scores – using some of   the packages made for statistical programs, including SPSS, or?

This   relates to table 3 as well – why not investigating WAZ or BMI-for-age Z-score   (BMIZ)? These two are more common within this field of research.

As   explained in the methods section, under Infant’s weight and length, we wrote: Rapid weight gain was defined as a change   greater than 0.67 standard   deviations (SD) in weight-for-length z-score between the first and   second assessment [4]. Adequate weight gain was considered as a change in weight-for-length   z-score between -0.67 to +0.67 SD, while a slow weight gain is that below   -0.67 SD.

These   z scores were calculated at each time point using the WHO AnthroPlus macro [30].

We   used WHZ as this is the method used by WHO and several studies:

https://www.ncbi.nlm.nih.gov/pubmed/27231870

https://www.ncbi.nlm.nih.gov/pubmed/30524746

https://www.ncbi.nlm.nih.gov/pubmed/24204979

https://www.ncbi.nlm.nih.gov/pubmed/22434753

https://www.ncbi.nlm.nih.gov/pubmed/20863516

https://www.ncbi.nlm.nih.gov/pubmed/1594343

https://www.ncbi.nlm.nih.gov/pubmed/30249624

To   clarify, we added the following in the revised manuscript.

Weight-for-length z   scores were calculated at each time point using the WHO AnthroPlus macro [30]…

Major   comment 4:

How   did the authors chose which variables to include in the adjust analyses? For   example, table 5 is adjusted for number of children, age of the infant,   maternal educational level, and pregnancy weight gain. I acknowledge the   possibility, that the latter three are confounding, but how is the number of   children confounding the association between type of feeding and weight at   follow-up?

Did   they consider checking for interaction between their exposure and the child’s   sex?

As   stated in the statistical analysis, we conducted bivariate analyses between   the main outcome variables and socio-demographic variables to identify   confounders. However, based on the reviewer’s suggestion, we also added sex   of the baby. We also included age of the mother as another confounder, as it   has also been shown to be an important determinant of infant obesity. Baby’s sex   was not significant in any of the models.

Major   comment 5:

Lines   201-217, discussion on rapid weight gain, differences between formula-fed and   breastfed infants. I suggest you look into the work by Dewey et al., for   example, Dewey KG, Heinig MJ, Nommsen LA, Peerson JM, Lönnerdal B. Growth of   breast-fed and formula-fed infants from 0 to 18 months: the DARLING Study.   Pediatrics 1992 Jun;89(6 Pt 1):1035-1041.

We   added Dewey’s study (The Darling study in the discussion), as well as other   references based on other comments made by the reviewer. See below the changes   done in the discussion……

Most prospective studies have found a positive   association between formula feeding with rapid weight gain [13–15,33–37], showing   a different pattern of weight gain by type of feeding. For example, the   Darling study following 87 infants (46 breastfed and 41 formula fed) for 12   months showed a similar WHL z   scores between breastfed and formula fed infants during the first 4   months, but then from the 5^th to 18^th month, WHL z   score was consistently higher among formula fed infants [35].

Major   comment 6:

Line   255, catch-up growth: I think you should look for another reference than   reference 43, which relates to (and is published in) Korean infants.

This reference (Cho WK and Suh BK, Catch-up   growth and catch-up fat in children born small for gestational age) was   published as PMC in English. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753194/

But following the suggestion from the   reviewer, we searched for another reference and replaced this reference with   a systematic review that seemed more appropriate. https://www.ncbi.nlm.nih.gov/pubmed/29691880

Minor   comment 1:

The   authors have not complied with the author guidelines of the Nutrients   journal. The affiliations are not set up after the template, i.e. authors’   names should not be listed in front of each affiliation. Furthermore, the   abstract should not be divided into sections and headings should not be   present.

The   affiliations in the front page and the abstract were modified to comply with the   journal’s guidelines.

Minor   comment 2:

There   are some typos and inconsistencies throughout the paper. For example:

·         Line   26 “socio- demopgraphic” should be “sociodemographic”.

·         Lines   33 and 34 “adjOR” and “adj OR” spelled in two different ways. Avoid the usage   of abbreviations in the abstract.

·         Line   38 “larger and longer studies”, longer studies is an odd phrase, I suggest   something like “studies with later (or longer) follow-up.”

·         Line   93, the abbreviation of food frequency questionnaire (“FFQ”) should be   presented here. It isn’t presented until line 109.

·         Line   157 and Table 1: Gender is not a biological term. I suggest “sex” instead.

·         Table   1: “Pregnancy weight gain”, the classification of low, adequate, and   excessive pregnancy weight gain has not presented before.

·         Line   194: There should be an “In” in the beginning of the conclusion.

We   revised the document and corrected these errors.

For   the comment about Table 1, we added the following in methods:

It also included a question about weight gain   during pregnancy; this was classified as low, adequate or high based on the   recommended weight gain by the Institute of Medicine [26]..

Minor   comment 3:

Lines   47-52. I wonder how the authors can mention rapid weight gain without   referring to the work of Rolland-Cachera et al.? For example, Rolland-Cachera   MF. Rate of growth in early life: a predictor of later health? Adv Exp Med   Biol 2005;569:35-39. But also Zheng M, Lamb KE, Grimes C, Laws R, Bolton K,   Ong KK, Campbell K. Rapid weight gain during infancy and subsequent   adiposity: a systematic review and meta-analysis of evidence. Obes Rev 2018   Mar;19(3):321-332.

We   included these reference in the introduction:

Growth is more rapid during early infancy than at   any other time during the human life cycle, and studies have confirmed the   association between rapid weight gain and risk of obesity later in life [4–7],   particularly if the rapid weight gain occurs within the first months of life [8].

Minor   comment 4:

Line   54, breastfeeding and its protection against obesity. This is very debated,   and I think the authors’ statement is too definitive. Otherwise add “compared   to non-breastfeeding”.

We   changed this to:

Breastfeeding has been long recognized to help   reduce the risk of obesity compared to non-breastfeeding [10,11].

Minor   comment 5:

Line   135, reference 25: Is this reference correct? I can’t see how it adds to the   calculation of WHZ?

Thanks   for noticing this mistake, it was replaced with the reference from the WHO Child Growth Standards

Minor   comment 6:

Table   1, Race/ethnicity: The numbers exceed the group total of 162 (and 100%).

In   the US, Hispanics are considered an “ethnicity classification” not race. To   clarify, we separated Ethnicity from Race in the table and the % now sum 100%   in both categories.

Minor   comment 7:

Line   267-271, discussion on longitudinal data and infant feeding practices. You   may find the following useful: Azad et al., Infant feeding and weight gain:   Separating breast milk from breastfeeding and formula from food. Pediatrics   2018 Oct;142(4).

We   agree with the reviewer that this is an important reference. We included the   following in the 2^nd paragraph of the discussion:

The Canadian Healthy Infant Longitudinal   Development (CHILD) birth cohort, which followed 2553 infants from birth up   to 12 months of age also found that non-exclusive or partial breastfeeding   for 3 or 6 months to be associated with rapid weight gain [37].