Title: Epidemiology, Validation, and Clinical Characteristics of Inflammatory Bowel Disease:
The ABIS birth cohort study
Version: 1 Date: 31 Mar 2023
Reviewer:  Rahma Elmahdi
Reviewer's report:
Incidence rate calculation
There is inconsistency in use of IBD diagnosis from the NPR, which is important as this forms
the basis for the IBD validity analysis. It is unclear to me why authors choose only 1 recorded
diagnosis from the NPR as the basis for incidence rate calculation but subsequently include only
a minimum of 2 IBD diagnoses to validate diagnosis against medical records. It is likely that
the use of 1 diagnosis would yield an overall lower validity when verifying diagnosis against
medical records. I therefore suggest that authors use either 1 diagnosis from the NPR as the basis
for all subsequent clinical records validation or use the definition of 2 diagnoses (which is the
standard when using registry-based data of this nature) to calculate overall incidence rates for
the population.
Additionally, the large proportion of unretrieved medical records (27%) is a real challenge to
the core aim of the study i.e. the use of medical records to validate IBD diagnosis from a patient
register.
Clinical and treatment characteristics
The subsequent descriptive analysis of clinical and treatment characteristics of disease from
medical record review does not add a great deal to the paper. It would be interesting to make
use of the comprehensive birth questionnaire data available to authors to assess the relationship
between clinical and treatment characteristics using regression analysis, adjusted for age and
sex. It is understandable that there may be limitations to undertaking such analysis due the small
total number of IBD cases identified (n=113) and therefore limited power to detect differences in
disease characteristics based on these exposures. It would however be of interest to see results of
clinical and treatment characteristics at least stratified by age and sex, if not birth questionnaire
characteristics.
Faecal calprotectin and CRP
The analysis of faecal calprotectin levels and CRP in particular adds very little of interest to the
overall study findings. Such biochemical markers are notoriously variable in individual disease
course, and we expect to see an average decrease following diagnosis and due to remission or
disease management. It might be of interest instead to attempt to assess these markers by patient
birth characteristics. Another way of using this data to better contribute to study findings is an
assessment of temporal trends (marker levels over time) if this data is available to authors. At
the very least, it would be good to present the average duration of follow up between diagnosis
and end of follow-up measurements for these two markers.
Display Items
There are several unnecessary display items. I suggest deleting table 3 and incorporating
cumulative incidence into the incidence rate table (table 2). Table 4 can be removed as no new
information is being presented here that is not described in the results.
Figure 1 is also lacking in useful information and should be removed, description of the
number of exclusions based on birth year and no valid PIN is already in the results. What
is the significance of ‘name’ at the top of the legends for Figure 2 and 3? If this a mistake,
please correct. I suggest that the presentation of this data (faecal calprotectin and CRP) is not
particularly useful (due to reason described above) and so would suggest also removing these
figures.
Comments on manuscript
Line 73 – Would suggest adding citation for increased risk of cancer in paediatric onset IBD
(Elmahdi & Lemser et al., 2022) as example of severe disease course.
Line 78 (+ Additional file, Table 1) – Suggest adding recent incidence study including paediatric
populations in North-Jutland (Larsen et al. Am J Gastroenterol., 2023) published earlier this
month, which gives updated cumulative incidence for paediatric IBD for region.
Line 133 to 139 – Suggest it may be more helpful to specify the qualification of those assessing
medical records and not just author initials (e.g. IBD specialist clinician).
Line 254-255 – Comment on genetics here is vague. Would be more appropriate to discuss how
genetic predisposition alone does not fully explain the trend for increased incidence.
Line 277 – The significance of a Swedish university hospital is unclear here, particularly for
an international audience. Might be better to explain that you do not rely solely on diagnoses
from tertiary hospitals.
Conclusions – Unclear how the findings of the study should stimulate studies exploring
environmental determinants of IBD as these are not assessed in the study and the presentation of
incidence data in this paediatric population is not directly compared with prior incidence data to
illustrate an increase in incidence. Suggest a more tentative conclusion based on interpretation
of actual findings of the study.
Title: Epidemiology, Validation, and Clinical Characteristics of Inflammatory Bowel Disease:
The ABIS birth cohort study
Version: 1 Date: 31 Mar 2023
Reviewer:  Rahma Elmahdi
Reviewer's report:
Incidence rate calculation
There is inconsistency in use of IBD diagnosis from the NPR, which is important as this forms
the basis for the IBD validity analysis. It is unclear to me why authors choose only 1 recorded
diagnosis from the NPR as the basis for incidence rate calculation but subsequently include only
a minimum of 2 IBD diagnoses to validate diagnosis against medical records. It is likely that
the use of 1 diagnosis would yield an overall lower validity when verifying diagnosis against
medical records. I therefore suggest that authors use either 1 diagnosis from the NPR as the basis
for all subsequent clinical records validation or use the definition of 2 diagnoses (which is the
standard when using registry-based data of this nature) to calculate overall incidence rates for
the population.
Additionally, the large proportion of unretrieved medical records (27%) is a real challenge to
the core aim of the study i.e. the use of medical records to validate IBD diagnosis from a patient
register.
Clinical and treatment characteristics
The subsequent descriptive analysis of clinical and treatment characteristics of disease from
medical record review does not add a great deal to the paper. It would be interesting to make
use of the comprehensive birth questionnaire data available to authors to assess the relationship
between clinical and treatment characteristics using regression analysis, adjusted for age and
sex. It is understandable that there may be limitations to undertaking such analysis due the small
total number of IBD cases identified (n=113) and therefore limited power to detect differences in
disease characteristics based on these exposures. It would however be of interest to see results of
clinical and treatment characteristics at least stratified by age and sex, if not birth questionnaire
characteristics.
Faecal calprotectin and CRP
The analysis of faecal calprotectin levels and CRP in particular adds very little of interest to the
overall study findings. Such biochemical markers are notoriously variable in individual disease
course, and we expect to see an average decrease following diagnosis and due to remission or
disease management. It might be of interest instead to attempt to assess these markers by patient
birth characteristics. Another way of using this data to better contribute to study findings is an
assessment of temporal trends (marker levels over time) if this data is available to authors. At
the very least, it would be good to present the average duration of follow up between diagnosis
and end of follow-up measurements for these two markers.
Display Items
There are several unnecessary display items. I suggest deleting table 3 and incorporating
cumulative incidence into the incidence rate table (table 2). Table 4 can be removed as no new
information is being presented here that is not described in the results.
Figure 1 is also lacking in useful information and should be removed, description of the
number of exclusions based on birth year and no valid PIN is already in the results. What
is the significance of ‘name’ at the top of the legends for Figure 2 and 3? If this a mistake,
please correct. I suggest that the presentation of this data (faecal calprotectin and CRP) is not
particularly useful (due to reason described above) and so would suggest also removing these
figures.
Comments on manuscript
Line 73 – Would suggest adding citation for increased risk of cancer in paediatric onset IBD
(Elmahdi & Lemser et al., 2022) as example of severe disease course.
Line 78 (+ Additional file, Table 1) – Suggest adding recent incidence study including paediatric
populations in North-Jutland (Larsen et al. Am J Gastroenterol., 2023) published earlier this
month, which gives updated cumulative incidence for paediatric IBD for region.
Line 133 to 139 – Suggest it may be more helpful to specify the qualification of those assessing
medical records and not just author initials (e.g. IBD specialist clinician).
Line 254-255 – Comment on genetics here is vague. Would be more appropriate to discuss how
genetic predisposition alone does not fully explain the trend for increased incidence.
Line 277 – The significance of a Swedish university hospital is unclear here, particularly for
an international audience. Might be better to explain that you do not rely solely on diagnoses
from tertiary hospitals.
Conclusions – Unclear how the findings of the study should stimulate studies exploring
environmental determinants of IBD as these are not assessed in the study and the presentation of
incidence data in this paediatric population is not directly compared with prior incidence data to
illustrate an increase in incidence. Suggest a more tentative conclusion based on interpretation
of actual findings of the study.
Please review this paper.
user
Title: Epidemiology, Validation, and Clinical Characteristics of Inflammatory Bowel Disease:
The ABIS birth cohort study
Version: 1 Date: 31 Mar 2023
Reviewer:  Rahma Elmahdi
Reviewer's report:
Incidence rate calculation
There is inconsistency in use of IBD diagnosis from the NPR, which is important as this forms
the basis for the IBD validity analysis. It is unclear to me why authors choose only 1 recorded
diagnosis from the NPR as the basis for incidence rate calculation but subsequently include only
a minimum of 2 IBD diagnoses to validate diagnosis against medical records. It is likely that
the use of 1 diagnosis would yield an overall lower validity when verifying diagnosis against
medical records. I therefore suggest that authors use either 1 diagnosis from the NPR as the basis
for all subsequent clinical records validation or use the definition of 2 diagnoses (which is the
standard when using registry-based data of this nature) to calculate overall incidence rates for
the population.
Additionally, the large proportion of unretrieved medical records (27%) is a real challenge to
the core aim of the study i.e. the use of medical records to validate IBD diagnosis from a patient
register.
Clinical and treatment characteristics
The subsequent descriptive analysis of clinical and treatment characteristics of disease from
medical record review does not add a great deal to the paper. It would be interesting to make
use of the comprehensive birth questionnaire data available to authors to assess the relationship
between clinical and treatment characteristics using regression analysis, adjusted for age and
sex. It is understandable that there may be limitations to undertaking such analysis due the small
total number of IBD cases identified (n=113) and therefore limited power to detect differences in
disease characteristics based on these exposures. It would however be of interest to see results of
clinical and treatment characteristics at least stratified by age and sex, if not birth questionnaire
characteristics.
Faecal calprotectin and CRP
The analysis of faecal calprotectin levels and CRP in particular adds very little of interest to the
overall study findings. Such biochemical markers are notoriously variable in individual disease
course, and we expect to see an average decrease following diagnosis and due to remission or
disease management. It might be of interest instead to attempt to assess these markers by patient
birth characteristics. Another way of using this data to better contribute to study findings is an
assessment of temporal trends (marker levels over time) if this data is available to authors. At
the very least, it would be good to present the average duration of follow up between diagnosis
and end of follow-up measurements for these two markers.
Display Items
There are several unnecessary display items. I suggest deleting table 3 and incorporating
cumulative incidence into the incidence rate table (table 2). Table 4 can be removed as no new
information is being presented here that is not described in the results.
Figure 1 is also lacking in useful information and should be removed, description of the
number of exclusions based on birth year and no valid PIN is already in the results. What
is the significance of ‘name’ at the top of the legends for Figure 2 and 3? If this a mistake,
please correct. I suggest that the presentation of this data (faecal calprotectin and CRP) is not
particularly useful (due to reason described above) and so would suggest also removing these
figures.
Comments on manuscript
Line 73 – Would suggest adding citation for increased risk of cancer in paediatric onset IBD
(Elmahdi & Lemser et al., 2022) as example of severe disease course.
Line 78 (+ Additional file, Table 1) – Suggest adding recent incidence study including paediatric
populations in North-Jutland (Larsen et al. Am J Gastroenterol., 2023) published earlier this
month, which gives updated cumulative incidence for paediatric IBD for region.
Line 133 to 139 – Suggest it may be more helpful to specify the qualification of those assessing
medical records and not just author initials (e.g. IBD specialist clinician).
Line 254-255 – Comment on genetics here is vague. Would be more appropriate to discuss how
genetic predisposition alone does not fully explain the trend for increased incidence.
Line 277 – The significance of a Swedish university hospital is unclear here, particularly for
an international audience. Might be better to explain that you do not rely solely on diagnoses
from tertiary hospitals.
Conclusions – Unclear how the findings of the study should stimulate studies exploring
environmental determinants of IBD as these are not assessed in the study and the presentation of
incidence data in this paediatric population is not directly compared with prior incidence data to
illustrate an increase in incidence. Suggest a more tentative conclusion based on interpretation
of actual findings of the study.
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