Reviewer’s report
Title: 
Comparison of levonorgestrel level and creamatocrit in milk following
immediate vs. delayed postpartum placement of the levonorgestrel IUD
Version: 
0 
Date: 
03 Aug 2020
Reviewer's report:
This paper compares levonorgestrel (LNG) levels and creamatocrit in milk
following immediate vs.delayed postpartum insertion of a LNG-IUS. The paper
describes a new technique for measuring LNG in milk among IUS users. The
analysis is limited by the fact that this was a pilot study and it was not powered
to detect meaningful differences. The manuscript is limited by the fact that the
clinical application of these two measurements is not well described. 
Methods:
Page 5, line 90: Why were 12 participants chosen to participate? Is this a
convenience sample? If this is an exploratory study without an a-priori power
calculation and the study was not powered to detect clinically meaningful
differences this should be stated in the conclusions.
Page 7, line 131: Why were medians chosen instead of means? Were the data not
normally distributed? In 2011, the authors previously presented mean
Creamatocrit values which allowed for a presentation of mean differences with
95% Cis which was be helpful in interpreting data. 
Page 7, Line 135: "Sensitivity analysis described in section 2.5 did not
significantly alter results". Is there a section of the manuscript labeled 2.5?
Perhaps this is from a previous submission/version?
Discussion/conclusion:
It is important to contextualize these point estimates with what is known about
measuring LNG and creamatocrit in human milk and what the clinical
implications of these measurements is. 
Has LNG content been measured in human milk prior using this technique? If so,
examples of previous work using this technique should be cited. What assay
validation studies been done? 
Before recommending that these assays be used for future research it is important
to understand their clinical value. Contextualizing the clinical importance of how
milk lipid and LNG content relate to clinical outcomes from other studies would
make this manuscript more relevant to readers in understanding future
application. 
Were any samples collected after IUD insertion in the delayed group because of
a protocol deviation? Could this explain, in part, the presence of LNG in the
milk of women in the delayed group? 
I understand that the original study was an RCT so the group
assignment/randomization has been maintained for presentation of the results. A
per-protocol analysis would provide more valuable clinical data for this
secondary outcome. Please describe when IUDs were actually placed (not just
planned) in the immediate and delayed group relative to milk collection if it
differs from the protocol described.
Fat content in breastmilk is variable so single measurements may not reflect
clinically meaningful values. This should be listed as a limitation of this study.
Can the LNG breastmilk concentrations be compared to the maternal serum
concentrations? 
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Is the study design appropriate to answer the research question (including the use
of appropriate controls), and are the conclusions supported by the evidence
presented?
No
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Yes
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Yes
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Yes
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from apparent manipulation?
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