Title: Obesity at age 20 and weight gain during adulthood increase risk of total and premature
all-cause mortality: Findings from women attending breast screening in Manchester
Version: 3 Date: 03 Nov 2022
Reviewer:  Emmanuel Biracyaza
Reviewer's report:
Title: Obesity at age 20 and weight gain during adulthood increase risk of total and premature
all-cause mortality: Findings from women attending breast screening in Manchester
Comments
First of all I am pleased to thank the authors for their efforts used to made significant and
important revisions and changes are suggested by the reviewers, however, some clarifications
or changes are also substantial to make the study stronger before its acceptance for publication.
Abstract: The abstract is not very informative and still needs some improvement especially in the
background and results sections. The readers need to know the reason why the authors conducted
this study/research gap. They can design it as follows:
Background: “Although obesity in early adulthood was documented to be associated with lower
breast cancer rates in later life, few studies were conducted on obesity and body mass index
(BMI) change in adulthood and all-cause mortality. Thus, this study was conducted to examine
the association between both obesity in early adulthood and BMI change through adulthood,
and all-cause mortality. The potential rationale of this study may be interpreted as a positive
reinforcement of excess weight amongst younger women.”
Methods: The author should describe exposure and outcome assessment, method of trajectory
analysis, and the HR of total and cause-specific mortality.
Results: For the results of abstract, the authors have to improve the ways of interpreting the
results of HR (and this must be applied in the results section. For example; on lines 54-56 “After
a mean 8.7 years follow-up we observed that overweight (HR=1.27, 95%CI: 1.10-1.47) and
obesity at 20years (HR=2.11, 95% CI: 1.67-2.66) had a higher mortality rate compared with
healthy weight.” Please, this should be applied in all sections by paying attention to the use
of the ( ).  Again, the HR is interpreted as the odds ratio or relative risk; please improve the
interpretation in both abstract and in the result sections. For example; 67-68 you can interpret
it as follows “All-cause morality risk was higher in women with overweight or obesity at both
20 years (HRs=1.36, 95%CI=1.06-1.75) and entry (HRs=1.90, 95%CI=1.45-2.48) than women
who were underweight or healthy weight at both points”
Please, provide a good structure for the texts of lines 73-74. You can include a verb.
Background: Background is one of the weakest parts of this study due to not integrating the
relevant literature that indicated the association between BMI and all-cause mortality. On lines
180-182, the authors have to clarify the research gap or what interested them in conducting this
study.  There are several studies conducted in the HIC such Norwegian, Melbourne in Australia,
Finland that are needed to be included.
Please, the authors also have to check well the grammatical and typos errors. For example; on
line 467, you can write “multiple imputations”, line 583; “13-15 years old” instead of “13-15
year old”
It is recommended to use simple past in the background, methods, results, and discussion
sections. For example; one line 473 you have to remove the future.
Methods and results: The authors expressed that they computed the multicollearity using VIF
but it is not indicated in the main document. More clarifications are needed. The results must
be well interpreted.
Add comment:
On line 470-474; the authors have restructure the sentences by avoiding the confusion to the
readers. Please, some sentences are not complete. Example; (why do you this the generalizability
is a limitation? Correct on lines 586-587). The authors can say “Our study encountered several
limitations that warrant discussion. The first limitation was … The second limitation was …,
the third limitation was ….” I mean you have to provide limitations systematically and properly.
It is also better to combine them in one of two paragraphs.
At the end of the conclusion (line 600) the authors have to provide the recommendation to
the further researchers. The recommendations can be provided based on the study results and
limitations found such as study design, miss of several essential data, etc.
All tables and figures must be well referenced in the study using the caption and insertion of
the tables  and figures.
Additional documentations
The followings studies can be used to strengthen the background:
1. Kjøllesdal MKR, Smith GD, Ariansen I, Kinge JM, Degerud E, Næss Ø. The association
between BMI and mortality using early adulthood BMI as an instrumental variable for midlife
BMI. Sci Rep. 2018 Jul 31;8(1):11499. doi: 10.1038/s41598-018-29089-z.
2. Yang Y, Dugué PA, Lynch BM, Hodge AM, Karahalios A, MacInnis RJ, Milne RL, Giles
GG, English DR. Trajectories of body mass index in adulthood and all-cause and cause-specific
mortality in the Melbourne Collaborative Cohort Study. BMJ Open. 2019 Aug 10;9(8):e030078.
doi: 10.1136/bmjopen-2019-030078. PMID: 31401610; PMCID: PMC6701564.
3. Xie W, Lundberg DJ, Collins JM, et al. Association of Weight Loss Between Early Adulthood
and Midlife With All-Cause Mortality Risk in the US. JAMA Netw Open. 2020;3(8):e2013448.
doi:10.1001/jamanetworkopen.2020.13448
4. Chen C, Ye Y, Zhang Y, Pan XF, Pan A. Weight change across adulthood in relation to all
cause and cause specific mortality: prospective cohort study. BMJ. 2019 Oct 16;367:l5584. doi:
10.1136/bmj.l5584.
5. Kivimäki M, Strandberg T, Pentti J, Nyberg ST, Frank P, Jokela M, Ervasti J, Suominen
SB, Vahtera J, Sipilä PN, Lindbohm JV, Ferrie JE. Body-mass index and risk of obesity-related
complex multimorbidity: an observational multicohort study. Lancet Diabetes Endocrinol.
2022 Apr;10(4):253-263. doi: 10.1016/S2213-8587(22)00033-X. Epub 2022 Mar 4. PMID:
35248171; PMCID: PMC8938400.