Author's response to reviews
Title:Association of environmental chemicals & estrogen metabolites in children
Authors:
Erin S Ihde (eihde@hackensackumc.org)
Ji Meng Loh (loh@njit.edu)
Lawrence Rosen (lrosen@wholechildcenter.org)
Version:5Date:9 December 2015
Author's response to reviews:
December 9, 2015
Dear Editorial Board of BMC Endocrine Disorders:
Thank you for the peer review suggestions for our manuscript. Please find
attached the revised version addressing the recommendations from Jane Burns’
third review, as detailed below.
•Abstract:
-We corrected the phrase “since the data was skewed.”
•Background:
-Page 5, paragraph 1: we spelled out 16aOHE1 and 2OHE1.
-Page 5, paragraph 1: As suggested, we put this sentence at the end of the
paragraph.
•Lab analysis procedure:
-Page 7, paragraph 2: We specified the materials used, i.e. glass collection
container, polypropylene vial and polyethylene pipette. We also added details re:
specimen collection, storage, aliquot procedure, shipping and temperature
controls.
-Page 7, lines 164-165: We clarified that LODs for chemicals are included in
Table 1. As requested, Table 2 has been updated with LODs for estrogen
metabolites. Please note, the 2-16ratio is a ratio and the 2-OHE (1+2) is a sum
and therefore do not have LOD values (though the individual components do).
Regarding CVs for chemicals and estrogen metabolites, we have the values in
the attached PDF. We did not add this information to Table 1 at this time, as we
stated we weren't using the mean or variance because of outliers. Additionally,
with the median and IQR, one ought to be able to have an idea what the CV is by
taking the ratio (median/IQR is not the CV, but one can get a rough sense of the
magnitude, which is all we can hope for given the small sample size). Please let
us know if the CVs should still be included given this explanation.
•Statistical considerations:
-Page 8, paragraph 3: We clarified the statement on incomplete lab results,
which were due to insufficient urine collected and/or inability of the lab to result
all analytes in specific cases.
-Page 8, paragraph 3: We did not perform a statistical analysis for those who
contributed to the analysis versus those who did not.
-Page 9, line 206: We corrected the phrase “since the data was skewed.”
•Results and Discussion:
-Page 10, paragraph 3: We added a sentence clarifying that there were no zero
values for estrogen metabolites so all were above the limit of detection.
-Page 10, paragraph 3: We omitted reference to ratios and clarified the terms for
estrogen metabolites that were used.
-Page 11, lines 261-262: We added this language as suggested, re:
“subpopulations that are particularly at risk.”
•Limitations:
-Page 11, line 267: We inserted “extremely large chemical outlier value” as
suggested.
-Page 12, paragraph 1: We added a sentence to clarify that even if the value isn’t
spurious, an inference can’t be drawn based on one observation.
-Page 12, paragraph 1, lines 275-282: Clarification was added re: reason for lack
of associations based on pubertal status. Reference was added.
•References:
-Reference #24 was formatted.
•Tables:
-We reviewed the formatting of the tables, which were created to be as clear as
possible. We welcome specific suggestions.
-Table 1:
#We updated the caption as suggested.
#We added below the table, “p values are for tests with those <LOD replaced by
LOD/2.”
#Re: comment that chemicals in Table 1 are not adjusted for creatinine, while the
estrogen metabolites are adjusted for creatinine, the Genova Diagnostics report
(https://www.gdx.net/core/sample-reports/0740-Phthalates-Parabens-SR.pdf as
sample) clearly lists that values are reported as mcg/gm creatinine.
-Table 2:
#We updated the caption as suggested.
#A notation was included under the table that the full names of the abbreviated
estrogen metabolites and ratio can be found in the “List of abbreviations” on page
12.
#We omitted the 1-16 ratio (the data row) as it is not a clinically relevant ratio to
report.
#We also omitted the 2-Me1 ratio (the data row) as it is not sufficiently research
based to include.
Thank you for your review of our manuscript. Please let me know if I can provide
further information, and we look forward to hearing from you soon.
Sincerely,
Erin S. Ihde, MA, CCRP