Review for 10.1186/1471-230X-14-75 (2014)

Reviewer's report
Title:Antibiotic exposure in pregnancy and risk of coeliac disease in offspring: a
cohort study
Version:1Date:21 January 2014
Reviewer: Satu Simell
Reviewer's report:
The paper of Mårild et al. investigated antibiotic exposure in pregnancy as a
possible risk factor for celiac disease in offspring. The study subject is very
interesting, yet this paper requires major revisions in order to be acceptable for
publication.
Major Compulsory Revisions
1) Authors describe the study as being a prospective population-based cohort
study, yet the data of most interest, i.e. antibiotic use during pregnancy, was
asked retrospectively. Even though the study participants seemed to remember
quite well their time of pregnancy, retrospectively asked information is always
less accurate than prospectively collected data. The study depicts that less than
13% (235/1836) of the mothers who had used antibiotics during pregnancy
remembered the specific name of the antibiotic they had used.
The authors write: "Additionally, we largely lack data on type of antibiotic agent,
its dosage, duration of treatment as well as the indication for treatment, which all
influence the extent of effect on the mother’s microbiota". To make conclusions
based on data without knowledge on the type of antibiotic used calls for the
question of validity of the conclusions with regards of influence on development
of celiac disease.
2) In Sweden the Swedish Prescribed Drug Register contains all individual data
of antibiotic use (group, date of prescription etc). The authors should use that
available information to address the use of antibiotics within the study cohort.
3) Is there any data of intrapartum antibiotics used? As the authors write,
"antibiotic treatment during the last trimester of pregnancy and particularly during
the perinatal period may have a more profound impact on infant gut colonization,
as compared with antibiotic treatment early in pregnancy". Because of this
mentioned effect, information about intrapartum antibiotics and more specific
data about antibiotics used during pregnancy (timing, group of antibiotics) are
needed.
4) Authors inform that 16285 parents completed the at-birth questionnaire and
that they included 8729 individuals with complete breastfeeding diary data and
time of gluten introduction. Later they say that they excluded mothers who were
uncertain of their antibiotic use in pregnancy or who had only used non-systemic
antibiotics. Same definitions have been used in Figure 1.
- How many mothers were excluded because they were uncertain of their
antibiotic use in pregnancy or had only used non-systemic antibiotics?
- Antibiotic use during pregnancy is the main issue in this article, so it should be
more clearly expressed both in text and the flow chart
5) Is there any data on the antibiotics used by the study children? This is
confounding data and should be taken into account
6) Prevalence of CD in this study compared to other studies made in Sweden is
very low. This means that as the only basis for disease discovery is to have
symptoms, this study has missed an estimated 150-200 children with CD from
the study population. The possible effect of antibiotics is thus only investigated
with overt cases of the disease, which is known to represent a minority of
disease subjects. These missing data might have an effect on the statistical
results. At least the mention of estimated missing cases should have been more
thoroughly discussed with thought given to possible problems to the study
caused by this.
Minor Essential Revisions
1) There is some repetition in the methods part of the text that should be
removed.
2) The term follow-up implies regular prescheduled observation of study subjects
as a group. This terminology should be altered to better describe the study.
3) References 18 and 25 are incomplete
4) Tables 2 and 3 contain too much information
Level of interest: An article whose findings are important to those with closely
related research interests
Quality of written English: Needs some language corrections before being
published
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare that I have no competing interests