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Nutritional rickets in Norway.
A nationwide register based cohort study.
Journal: BMJ Open
Manuscript ID bmjopen-2016-015289
Article Type: Research
Date Submitted by the Author: 29-Nov-2016
Complete List of Authors: Meyer, Haakon; Norwegian Institute of Public Health, Division of Epidemiology; University of Oslo, Department of Community Medicine Skram, Kristina; Oslo Universitetssykehus, Department of Pediatrics Berge, Ingvill; Oslo Universitetssykehus, Department of Pediatrics Madar, Ahmed; Institute of Health and Society, The Medical Faculty, University of Oslo, Department of Community Medicine Bjørndalen, Hilde ; Oslo Universitetssykehus, Department of Pediatrics
<b>Primary Subject
Heading</b>: Nutrition and metabolism
Secondary Subject Heading: Epidemiology, Public health
Keywords: Rickets, Immigrant, Vitamin D, Nutrition < TROPICAL MEDICINE
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Nutritional rickets in Norway.
A nationwide register based cohort study.
Haakon E. Meyer, professor1,2
Kristina Skram, registrar3
Ingvill Almås Berge, registrar3
Ahmed Madar, researcher1
Hilde Johanne Bjørndalen, consultant3
1 Section for Preventive Medicine and Epidemiology, Department of Community Medicine
and Global Health, University of Oslo, P.O. Box 1130 Blindern, 0318, Oslo, Norway.
E-mail: [email protected]
2 Norwegian Institute of Public Health, Oslo, Norway
3 Department of Pediatrics, Oslo University Hospital, Oslo, Norway
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Abstract:
Objectives: Poor vitamin D-status has been reported to be highly prevalent in many non-
western immigrant groups living in Norway and other western countries. However, data on
rickets are scarce, and the aim of the current study was to identify new cases of nutritional
rickets in Norway in the period 2008-2012 among children under the age of five.
Design: Register based cohort study.
Setting: The Norwegian population from 2008-2012.
Participants: Children with nutritional rickets under the age of 5 years.
Main outcome measure: Nutritional rickets. Patients with ICD10 diagnosis code E55.0
(active rickets) treated at all Norwegian hospitals were identified in the Norwegian Patient
Registry. We were able to review 85% of the medical records for diagnosis confirmation. In
addition, we identified patients with the diagnoses E55.9, E64.3 and E83.3 in order to capture
individuals with rickets given other diagnoses.
Results: Nutritional rickets was verified in 39 children aged 0-4 years with the diagnosis of
E55.0. In addition, three patients with the diagnosis of unspecified vitamin D deficiency
(E55.9) were classified as having nutritional rickets, giving the final number of 42 patients.
Mean age at diagnosis was 1.43 years (range 0.1 - 3.5 years), and 93 % had non-western
immigrant background. The incidence rate of rickets was estimated to be 0.3 per 10,000
person-years in the total Norwegian child population under the age of 5 and 3.1 per 10,000
person-years in those with immigrant background from Asia or Africa.
Conclusion: The number of children with nutritional rickets in Norway remained low in the
period 2008-12. Nearly all children had non-western immigrant background.
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Strengths and limitations of this study
• This register based study covered the complete Norwegian population
• All children under the age of five years with a diagnosis code of rickets were identified
• The diagnosis was verified by medical record review at the treating hospital
• We were not able to review the medical record in 15% of the patients
• The study was limited to patients treated in the period 2008-2012
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The classical consequence of vitamin D-deficiency is nutritional rickets in children.
Nutritional rickets is primarily caused by severe vitamin D deficiency and/or a low intake of
calcium [1]. Poor vitamin D-status has been reported in many non-western immigrant groups
living in western countries [2]. In the Oslo Health Study, 43% of the now-western immigrant
women and 31% of the men had vitamin D-deficiency (s-25(OH)D < 25 nmol/l) [3], and 21%
of women born in Pakistan had severe vitamin D-deficiency (s-25(OH)D < 12.5 nmol/l) [4].
The poor vitamin D-status in women in child-bearing age was confirmed in a study among
immigrant mothers (6 weeks after giving birth) with background from Pakistan, Turkey and
Somalia living in Oslo. Fifty-six percent had vitamin D-deficiency, and 15% severe vitamin
D-deficiency [5]. Based on the poor vitamin D-status in the adults, it has been a concern that
rickets could emerge as a large problem in infants with immigrant background. In addition,
the immigrant part of the population has increased, and currently nearly 10% of all Norwegian
children under the age of five have none-western immigrant background. Data on rickets in
Norway and other European countries are scarce. An enquiry sent to all hospitals with
pediatric wards in 2000 reported 65 children with nutritional rickets in Norway during the two
years period 1998-1999, of which 83% had immigrant background [6]. Eighty percent were
younger than 3 years. In a study covering southern Denmark from 1985-2005, only 112
patients with nutritional rickets were identified during a 20-years period, of which 75% had
immigrant background [7]. However, a study reporting hospital admissions for rickets in
England across five decades suggest that the incidence of rickets has increased during recent
years [8]. In that study, the diagnoses were not verified with medical record review, but
according to hospital based studies from the UK, rickets might be an increasing problem in
immigrant children [9 10].
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Prior to this study, no updated information on the occurrence of rickets in Norway was
available, but several efforts to secure a good vitamin D status among children have been
initiated during recent years, including free vitamin D-drops to infants with non-western
immigrant background and vitamin D fortified infant foods. The aim of the study was to
identify new cases of nutritional rickets in children under the age of 5 in the Norwegian
population from 2008 throughout 2012.
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Materials and Methods
The national specialist health care register (The Norwegian Patient Registry (NPR)) contains
information on all hospital admissions and outpatient contacts in the specialized health
services. The register also includes the unique 11-digit personal identification number
provided to all Norwegian residents. We used data from the NPR in the period 2008-2012 and
identified all admissions/contacts with the diagnosis E55.0 (active rickets), which is a sub-
code of E55, vitamin D deficiency. In addition, we identified admissions/contacts with the
diagnosis E55.9 (unspecified vitamin D deficiency), E64.3 (sequelae of rickets) and E83.3
(disorders of phosphorus metabolism and phosphatases) in order to capture patients with
rickets given other diagnoses. The extraction of these data was done by the NPR, and we did
not have access to the background data.
In order to verify the diagnosis, a questionnaire for medical record review was filled in by
doctors at the local hospitals where the children had been treated. Two doctors working at the
pediatric department at Oslo University Hospital (KS and IAB) reviewed all questionnaires
(half each) to confirm the conclusion nutritional rickets or not based on biochemical markers
and clinical symptoms/signs and/or radiological findings. In cases of doubt, the case was
discussed with a pediatric endocrinologist (HJB) before the conclusion was made.
All 23 hospitals treating the identified patients were contacted. The unique personal
identification number made it possible to link the information in NPR to the medical records
at the hospitals.
To test gender differences and differences in number of cases per year we used the chi-
squared test. As denominator we used the number of children aged 0-4 years in the
Norwegian population.
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Results
The flow of patient inclusion is displayed in figure 1. We identified 110 children under the
age of 5 years in the Norwegian Patient Registry given the diagnosis of active rickets (E55.0).
We were able to review medical records from 18 of 23 hospitals, constituting 85% of the
identified patients. Of 94 reviewed medical records in patients with E55.0, the diagnosis of
active rickets was verified in 54% (n=51). Of these patients, 9 were excluded as they were
first diagnosed before 2008, leaving 42 patients with E55.0.
Of these, 39 patients were classified as having nutritional rickets, whereas rickets was linked
to prematurity in three patients. In addition, three patients with the diagnosis of unspecified
vitamin D deficiency (E55.9) were classified as having nutritional rickets, giving the final
number of 42 patients. We did not include six patients with an uncertain diagnosis of
(nutritional) rickets.
Figure 1. Flow diagram, patient inclusion, nutritional rickets.
N=110
N=94
N=51
Excluded, hospital
without feedback
N=16
Excluded, the diagnosis
of E55.0 not verified
N=43
Excluded: Diagnosed
before 2008
N=9
N=42
N=42
Excluded, premature
infants
N=3
Included, other
diagnosis (E55.9)
N=3
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As shown in table 1, mean age at the diagnosis of nutritional rickets was 1.43 years (range 0.1
- 3.5 years), and 57% of the patients were boys (not statistically significant different from
girls, p=0.35). Nearly all patients (93 %) had non-western immigrant background, and around
60% had background from Asia. Whereas 24% had Pakistani and 21% had Iraqi background,
only 7% had ethnic Norwegian background.
Apparently, there were variations in the number of patients with rickets from year to year.
However, the numbers of cases were small, and there was no overall statistically significant
difference between the years of diagnosis (p=0.56).
Around one-third of all children aged 0-4 years with immigrant-background from Asia and
Africa are found in the Norwegian capital of Oslo. Whereas there were 3 to 4 cases each year
in the period 2008-2010, no cases with nutritional rickets was reported from Oslo in the
period 2011-2012.
Table 1. Characteristic of 42 patients under the age of 5 with nutritional rickets in
Norway 2008-2012
Age at diagnosis
(years, mean (SD)) 1.43 (0.71)
Gender (n (%))
Boys 24 (57.1)
Girls 18 (42.9)
Country background (n (%))
Norway 3 (7.1)
Asia 25 (59.5)
Africa 12 (28.6)
Other/unknown 2 (4.8)
Year of diagnosis (n (%))
2008 6 (14.3)
2009 10 (23.8)
2010 12 (28.6)
2011 7 (16.7)
2012 7 (16.7)
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Estimated incidence rate of rickets: According to Statistics Norway, the yearly average of
children aged 0-4 years in Norway in the period 2008-12 was 303,157 children. Of these,
around 24,000 children (8%) had background from Asia or Africa.
Based on this, the incidence rate of rickets was estimated to be 3.1 per 10,000 person-years in
children under the age of 5 with background from Asia or Africa and 0.3 per 10,000 person-
years in the total Norwegian population under the age of 5. This is a slight underestimation as
we were not able to review 15% of the medical records. If all 16 children treated at hospitals
without feedback had nutritional rickets, the incidence rate in the Norwegian population under
the age of 5 would be 0.4 per 10,000 person years.
Discussion
The number of children with nutritional rickets in the Norwegian population during 2008-
2012 was low, and 93% occurred in children with non-western immigrant background.
On average, 8 cases of nutritional rickets were reported yearly. This is considerably lower
than the yearly average of 32 reported in the hospital enquiry for the two-year period 1998-
1999 [6]. In addition, the number of children aged 0-4 years with background from Asia and
Africa increased by around 75% from 2000 to 2012. Although these two studies are not
directly comparable, the risk of rickets seems to have been reduced substantially among
immigrant children during recent years.
In the same period, several measures have been initiated in order to prevent vitamin D
deficiency and rickets. Based on the results from a cluster randomized trial [11], infants with
non-western immigrant background are offered free vitamin D-drops at the child health
clinics from the age of 4 weeks to six months. Since 2002 most baby cereals have been
fortified with vitamin D, and infant formula has been fortified with vitamin D for many years.
In addition, at the child health clinics, routinely visited several times during infancy, the
public health nurses have a long standing commitment to inform the mothers of the
importance of vitamin D. According to a study among Norwegian-Somali and Norwegian-
Iraqi infants, vitamin D-supplements and fortified infant formula and cereals are frequently
used [12].
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Another possible explanation for the low risk of rickets in Norwegian infants is that calcium
intake in general is adequate. In the same study noted above, median daily calcium intake was
777 mg in Norwegian-Somali and 633 Norwegian-Iraqi infants [13].
However, nutritional rickets, a condition easily cured when identified, still occurs. Some
groups are more exposed, and around 50% of the patients had background from two countries,
Iraq and Pakistan.
Some weaknesses of the study should be mentioned. Although the NPR covers the whole
Norwegian population, we were not able to confirm the rickets diagnosis in 15% of the
patients as we did not receive feedback from all hospitals. In addition, the medical record
reviews were made locally at each hospital dependent on available information in the medical
records and the accuracy of the reporting. We might also have missed individuals given
alternative diagnoses to E55.0. However, it is hard to see that this potentially could impact
substantially on our results, and only 3 of 42 patients included were identified via our
extended search (E55.9, E64.3and E83.3), and these patients had the diagnosis of unspecified
vitamin D deficiency (E55.9) in the Norwegian Patient Registry. Another restriction is that the
study was limited to Norway in the period 2008-12, but the main finding of a low risk of
rickets may apply to similar population with similar measures to prevent vitamin D
deficiency, including vitamin D supplementation and targeted vitamin D fortification for
infants. However, awareness is needed as sudden changes, like a high influx of refugees, may
alter the situation in segments of the child population [14].
Conclusion
The number of children with nutritional rickets in Norway remained low in the period 2008-
12, and 93% of the children had non-western immigrant background.
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Acknowledgements: We thank the physicians at the individual hospitals in reviewing the
medical.
Contributors: HEM, IAB, AM and HJB conceived the study. HEM, KS, IAB and HJB
collected the data. HEM analyzed the data and drafted the article. All authors contributed in
the interpretation of the findings, critically revised the paper for important intellectual content
and approved the final version. HEM is the guarantors.
Declaration of competing interests: All authors have completed the ICMJE uniform
disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any
organization for the submitted work; no financial relationships with any organizations that
might have an interest in the submitted work in the previous three years; no other
relationships or activities that could appear to have influenced the submitted work.
Data sharing: No additional data are available.
Transparency declaration: The lead author (HEM) affirms that the manuscript is an honest,
accurate, and transparent account of the study being reported; that no important aspects of the
study have been omitted; and that any discrepancies from the study as planned have been
explained.
The Corresponding Author has the right to grant on behalf of all authors and does grant on
behalf of all authors, a worldwide licence to the Publishers and its licensees in perpetuity, in
all forms, formats and media (whether known now or created in the future), to i) publish,
reproduce, distribute, display and store the Contribution, ii) translate the Contribution into
other languages, create adaptations, reprints, include within collections and create summaries,
extracts and/or, abstracts of the Contribution, iii) create any other derivative work(s) based on
the Contribution, iv) to exploit all subsidiary rights in the Contribution, v) the inclusion of
electronic links from the Contribution to third party material where-ever it may be located;
and, vi) licence any third party to do any or all of the above.
Funding/role of sponsor: This study was funded by the Norwegian Directorate of Health.
The sponsor had no influence on the preparation, review, or approval of the manuscript.
Ethical approval: The study did not include any involvement from the patients, and was
approved by the Regional Committee for Medical and Health Research Ethics
(2013/2370/REK sør-øst D).
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References
1. Munns CF, Shaw N, Kiely M, et al. Global Consensus Recommendations on Prevention and
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3. Holvik K, Meyer HE, Haug E, et al. Prevalence and predictors of vitamin D deficiency in five
immigrant groups living in Oslo, Norway: the Oslo Immigrant Health Study. EurJClinNutr
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4. Meyer HE, Falch JA, Sogaard AJ, et al. Vitamin D deficiency and secondary hyperparathyroidism
and the association with bone mineral density in persons with Pakistani and Norwegian
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5. Madar AA, Stene LC, Meyer HE. Vitamin D status among immigrant mothers from Pakistan,
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7. Beck-Nielsen SS, Brock-Jacobsen B, Gram J, et al. Incidence and prevalence of nutritional and
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8. Goldacre M, Hall N, Yates DGR. Hospitalisation for children with rickets in England: a historical
perspective. Lancet 2014;383:1
9. Ahmed SF, Franey C, McDevitt H, et al. Recent trends and clinical features of childhood vitamin
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11. Madar AA, Klepp KI, Meyer HE. Effect of free vitamin D(2) drops on serum 25-hydroxyvitamin D
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13. Grewal NK, Andersen LF, Kolve CS, et al. Food and Nutrient Intake among 12-Month-Old
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Nutritional rickets in Norway:
A nationwide register-based cohort study.
Journal: BMJ Open
Manuscript ID bmjopen-2016-015289.R1
Article Type: Research
Date Submitted by the Author: 07-Feb-2017
Complete List of Authors: Meyer, Haakon; University of Oslo, Department of Community Medicine and Global Health; Norwegian Institute of Public Health, Division of Epidemiology Skram, Kristina; Oslo Universitetssykehus, Department of Pediatrics Berge, Ingvill; Oslo Universitetssykehus, Department of Pediatrics Madar, Ahmed; Institute of Health and Society, The Medical Faculty, University of Oslo, Department of Community Medicine Bjørndalen, Hilde ; Oslo Universitetssykehus, Department of Pediatrics
<b>Primary Subject Heading</b>:
Nutrition and metabolism
Secondary Subject Heading: Epidemiology, Public health
Keywords: Rickets, Immigrant, Vitamin D, Nutrition < TROPICAL MEDICINE
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Nutritional rickets in Norway:
A nationwide register-based cohort study.
Haakon E. Meyer, professor1,2
Kristina Skram, registrar3
Ingvill Almås Berge, registrar3
Ahmed Madar, researcher1
Hilde Johanne Bjørndalen, consultant3
1 Section for Preventive Medicine and Epidemiology, Department of Community Medicine
and Global Health, University of Oslo, P.O. Box 1130 Blindern, 0318, Oslo, Norway.
E-mail: [email protected]
2 Norwegian Institute of Public Health, Oslo, Norway
3 Department of Pediatrics, Oslo University Hospital, Oslo, Norway
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Abstract:
Objectives: Poor vitamin D status has been reported to be highly prevalent in many non-
western immigrant groups living in Norway and other western countries. However, data on
rickets are scarce, and the aim of the current study was to identify new cases of nutritional
rickets in Norway in the period 2008-2012 among children under the age of five.
Design: Register-based cohort study.
Setting: The Norwegian population from 2008-2012.
Participants: Children with nutritional rickets under the age of 5 years.
Main outcome measure: Nutritional rickets. Patients with ICD10 diagnosis code E55.0
(active rickets) treated at all Norwegian hospitals were identified in the Norwegian Patient
Registry. We were able to review 85% of the medical records for diagnosis confirmation. In
addition, we identified patients with the diagnoses E55.9, E64.3 and E83.3 in order to identify
individuals with rickets who had been given other diagnoses.
Results: Nutritional rickets was confirmed in 39 children aged 0-4 years with the diagnosis of
E55.0. In addition, three patients with the diagnosis of unspecified vitamin D deficiency
(E55.9) were classified as having nutritional rickets, giving a total of 42 patients. Mean age at
diagnosis was 1.40 years (range 0.1 - 3.5 years), and 93 % had a non-western immigrant
background. The incidence rate of rickets was estimated to be 0.3 per 10,000 person-years in
the total Norwegian child population under the age of 5 and 3.1 per 10,000 person-years in
those with an immigrant background from Asia or Africa.
Conclusion: The number of children with nutritional rickets in Norway remained low in the
period 2008-12. Nearly all children had a non-western immigrant background.
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Strengths and limitations of this study
• This register-based study covered the complete Norwegian population
• All children under the age of five years with a diagnosis code of rickets were identified
• The diagnosis was confirmed by medical record review at the treating hospital
• We were not able to review the medical records for 15% of the patients
• The study was limited to patients treated in the period 2008-2012
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The classical consequence of vitamin D deficiency is nutritional rickets in children.
Nutritional rickets is caused primarily by severe vitamin D deficiency and/or a low intake of
calcium.1 Poor vitamin D status has been reported in many non-western immigrant groups
living in western countries.2 In the Oslo Health Study, 43% of the non-western immigrant
women and 31% of the men had vitamin D deficiency with circulating 25-hydroxyvitamin D
(25(OH)D) < 25 nmol/l,3 and 21% of women born in Pakistan had severe vitamin D
deficiency (25(OH)D < 12.5 nmol/l).4 The poor vitamin D status among women of child-
bearing age was confirmed in a study among immigrant mothers (6 weeks after giving birth)
with a background from Pakistan, Turkey and Somalia living in Oslo.5 Fifty-six percent had
vitamin D deficiency, and 15% had severe vitamin D deficiency. Based on the poor vitamin D
status of the adults, it has been a concern that rickets could emerge as a large problem among
infants with an immigrant background. In addition, the immigrant part of the population has
increased and currently nearly 10% of all Norwegian children under the age of five have a
non-western immigrant background.6 Data about rickets in Norway and other European
countries are scarce. An enquiry sent to all hospitals with paediatric wards in 2000 reported
65 children with nutritional rickets in Norway during the two years period 1998-1999, of
which 83% had an immigrant background.7 Eighty percent were younger than 3 years. In a
study covering southern Denmark from 1985-2005, only 112 patients with nutritional rickets
were identified during a 20-year period, of which 75% had an immigrant background.8 In a
population-based study from Olmsted County, Minnesota, 76% of the cases with nutritional
rickets had a non-white ethnic background. Although the incidence was low, it increased in
the period 1970 to 2009.9 A study reporting hospital admissions for rickets in England across
five decades also suggests that the incidence of rickets has increased during recent years.10 In
that study, the diagnoses were not confirmed by a medical record review, but hospital-based
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studies from the UK indicate that rickets might be an increasing problem among immigrant
children.11 12
Prior to this study, no updated information on the occurrence of rickets in Norway was
available. However, several efforts to secure a good vitamin D status among children have
been introduced in recent years, including free vitamin D drops for infants with a non-western
immigrant background and infant food fortified with vitamin D. The aim of the study was to
identify new cases of nutritional rickets in children under the age of 5 in the Norwegian
population in the period 2008-2012.
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Materials and Methods
The national specialist health care register (Norwegian Patient Registry (NPR)) contains
information on all hospital admissions and outpatient contact in the specialised health
services. The register also includes the unique 11-digit personal identification number
provided to all Norwegian residents. We used data from the NPR in the period 2008-2012 and
identified all admissions/contacts with the diagnosis E55.0 (active rickets), which is a sub-
code of E55, vitamin D deficiency. In addition, we identified admissions/contacts with the
diagnosis E55.9 (unspecified vitamin D deficiency), E64.3 (sequelae of rickets) and E83.3
(disorders of phosphorus metabolism and phosphatases) in order to identify patients with
rickets who had been given other diagnoses. Data extraction was performed by the NPR and
we did not have access to the background data.
In order to verify the diagnosis, all hospitals treating the children were contacted. At each
responding hospital, doctors in the paediatric department completed a questionnaire for
medical record review. We requested information about x-ray findings, biochemical tests,
symptoms, the clinical examination and the child’s ethnic background. In addition, the type
and effect of treatment was requested. Finally they were asked if the diagnosis was rickets,
and if so, if it was nutritional rickets.
In order to reconfirm the conclusions, two doctors working at the paediatric department at
Oslo University Hospital (KS and IAB) reviewed all the questionnaires (half each). The
diagnosis of nutritional rickets was based on biochemical markers and clinical
symptoms/signs and/or radiological findings. In addition, the effect of treatment was taken
into account. The following biochemical criteria were used: 25(OH)D < 12.5 nmol/l or
25(OH)D 12.5-25 nmol/l in the presence of elevated plasma alkaline phosphatase (ALP),
elevated serum parathyroid hormone (PTH), or low serum calcium (Ca). As there was a
possibility that some infants had already started to receive vitamin D supplements before the
diagnosis was given, we also included 11 patients with 25(OH)D 25-37 nmol/l of which all
had x-ray findings consistent with rickets.
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In cases of doubt, each case was discussed with a paediatric endocrinologist (HJB) before the
conclusion was made.
All 23 hospitals treating the identified patients were contacted. The unique personal
identification number made it possible to link the information in NPR to the medical records
at the hospitals.
To test gender differences and differences in number of cases per year we used the chi-
squared test. As a denominator we used the number of children aged 0-4 years in the
Norwegian population.
Results
The flow of patient inclusion is displayed in figure 1. We identified 110 children under the
age of 5 years in the Norwegian Patient Registry who had been diagnosed with active rickets
(E55.0). We were able to review medical records from 18 of 23 hospitals, which constituted
85% of the identified patients. Of 94 reviewed medical records in patients with E55.0, the
diagnosis of active rickets was confirmed in 54% (n=51). Of these patients, 9 were excluded
as they were first diagnosed before 2008, leaving 42 patients with E55.0.
Of these, 39 patients were classified as having nutritional rickets, whereas rickets was linked
to prematurity in three patients. In addition, three patients with the diagnosis of unspecified
vitamin D deficiency (E55.9) were classified as having nutritional rickets, giving the final
number of 42 patients. Four of the 42 patients were admitted due to seizure. They were
between 1-3 months old and had very low 25(OH)D concentrations (11-15 nmol/l).
We did not include seven patients with an uncertain diagnosis of (nutritional) rickets.
As shown in table 1, mean age at the diagnosis of nutritional rickets was 1.40 years (range 0.1
- 3.5 years), and 74% of the children were 1 to 2 years at the time of diagnosis.
Fifty-seven percent of the patients were boys (not statistically significant different from girls,
p=0.35), and 48% were diagnosed during winter/early spring (November-April) and 52%
during the rest of the year. Nearly all patients (93 %) had a non-western immigrant
background and around 60% had a background from Asia. With regards to individual
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countries, 24% had a Pakistani background and 21% had an Iraqi background, only 7% had an
ethnic Norwegian background.
Apparently, there were variations in the number of patients with rickets from year to year.
However, the numbers of cases were small and there was no overall statistically significant
difference between the years of diagnosis (p=0.56).
Around one-third of all children aged 0-4 years with an immigrant-background from Asia and
Africa are found in the Norwegian capital of Oslo. Although there were 3 to 4 cases each year
in the period 2008-2010, there were no cases with nutritional rickets reported from Oslo in the
period 2011-2012.
Table 1. Characteristic of 42 patients under the age of 5 with nutritional rickets in
Norway 2008-2012
Age at diagnosis
(years, mean (SD)) 1.40 (±0.73)
< 1 year 10 (24 %)
1 - 21 (50 %)
2 - 10 (24 %)
3 - <4 1 (2 %)
Gender (n (%))
Boys 24 (57.1)
Girls 18 (42.9)
Country background (n (%))
Norway 3 (7.1)
Asia 25 (59.5)
Africa 12 (28.6)
Other/unknown 2 (4.8)
Year of diagnosis (n (%))
2008 6 (14.3)
2009 10 (23.8)
2010 12 (28.6)
2011 7 (16.7)
2012 7 (16.7)
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For 37 of the 42 children with nutritional rickets, information about 25(OH)D was available.
Mean concentration was 17.9 nmol/l, and 86.5% had concentrations less than 30 nmol/l.
Estimated incidence rate of rickets: According to Statistics Norway, the yearly average of
children aged 0-4 years in Norway in the period 2008-12 was 303,157 children. Of these,
around 24,000 children (8%) had an Asian or African background.
Based on this, the incidence rate of rickets was estimated to be 3.1 (95% CI 2.2-4.4) per
10,000 person-years in children under the age of 5 with an Asian or African background and
0.3 (95% CI 0.2-0.4) per 10,000 person-years in the total Norwegian population under the age
of 5. This is a slight underestimate as we were not able to review 15% of the medical records.
If each of the 16 children who were treated at hospitals without feedback had nutritional
rickets, the incidence rate in the Norwegian population under the age of 5 would be 0.4 per
10,000 person years.
Discussion
The number of children with nutritional rickets in the Norwegian population during 2008-
2012 was low and 93% occurred in children with a non-western immigrant background.
On average, 8 cases of nutritional rickets were reported annually. This is considerably lower
than the yearly average of 32 reported in the hospital enquiry for the two-year period 1998-
1999 7. In addition, the number of children aged 0-4 years with an Asian or African
background increased by around 75% from 2000 to 2012. Although these two studies are not
directly comparable, the risk of rickets seems to have declined substantially among immigrant
children during recent years.
In the same period, several measures were introduced in order to prevent vitamin D deficiency
and rickets. Based on the results from a cluster randomised trial,13 infants with a non-western
immigrant background are offered free vitamin D drops at child health clinics from the age of
4 weeks to six months. Since 2002, most infant cereals have been fortified with vitamin D and
infant formula has been fortified with vitamin D for many years. In addition, at routine
appointments at child health clinics during infancy, the public health nurses fulfil their
longstanding commitment to inform mothers of the importance of vitamin D. According to a
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study among Norwegian-Somali and Norwegian-Iraqi infants, vitamin D supplements and
fortified infant formula and cereals are frequently used.14
Another possible explanation for the low risk of rickets in Norwegian infants is that calcium
intake in general is adequate. In the same study noted above, median daily calcium intake was
777 mg in Norwegian-Somali and 633 mg in Norwegian-Iraqi infants.15
However, nutritional rickets still occurs, even though it can be easily treated. Some groups are
more exposed and around 50% of the patients had a background from two countries, Iraq and
Pakistan.
Some weaknesses of the study should be mentioned. Although the NPR covers the entire
Norwegian population, we were unable to confirm the rickets diagnosis in 15% of the patients
as we did not receive feedback from all hospitals. In addition, the medical record reviews
made locally at each hospital depended upon available information in the medical records and
reporting accuracy, and complete information was not always available. We might also have
missed individuals who were given alternative diagnoses to E55.0. However, it is hard to see
that this could impact our results substantially. Only 3 of 42 patients included were identified
via our extended search (E55.9, E64.3 and E83.3) and these patients were diagnosed with
unspecified vitamin D deficiency (E55.9) in the Norwegian Patient Registry. Another
restriction is that the study was limited to Norway in the period 2008-12 but the main finding
of a low risk of rickets may apply to a similar population with similar measures to prevent
vitamin D deficiency, including vitamin D supplementation and targeted vitamin D
fortification for infants. However, awareness is needed as sudden changes, like a high influx
of refugees, may alter the situation in segments of the child population.16
Conclusion
The number of children with nutritional rickets in Norway remained low in the period 2008-
12 and 93% of the children had a non-western immigrant background.
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Acknowledgements: We thank the physicians at the individual hospitals for reviewing the
medical records and Julie Whittle Johansen for proofreading the manuscript.
Contributors: HEM, IAB, AM and HJB conceived the study. HEM, KS, IAB and HJB
collected the data. HEM analysed the data and drafted the article. All authors contributed in
the interpretation of the findings, critically revised the paper for important intellectual content
and approved the final version. HEM is the guarantor.
Declaration of competing interests: All authors have completed the ICMJE uniform
disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any
organisation for the submitted work; no financial relationships with any organisations that
might have an interest in the submitted work in the previous three years; and no other
relationships or activities that could appear to have influenced the submitted work.
Data sharing: No additional data are available.
Transparency declaration: The lead author (HEM) affirms that the manuscript is an honest,
accurate, and transparent account of the study being reported; that no important aspects of the
study have been omitted; and that any discrepancies from the study as planned have been
explained.
The Corresponding Author has the right to grant on behalf of all authors and does grant on
behalf of all authors, a worldwide licence to the Publishers and its licensees in perpetuity, in
all forms, formats and media (whether known now or created in the future), to i) publish,
reproduce, distribute, display and store the Contribution, ii) translate the Contribution into
other languages, create adaptations, reprints, include within collections and create summaries,
extracts and/or, abstracts of the Contribution, iii) create any other derivative work(s) based on
the Contribution, iv) to exploit all subsidiary rights in the Contribution, v) the inclusion of
electronic links from the Contribution to third party material where-ever it may be located;
and, vi) licence any third party to do any or all of the above.
Funding/role of sponsor: This study was funded by the Norwegian Directorate of Health.
The sponsor had no influence on the preparation, review, or approval of the manuscript.
Ethical approval: The study did not include any involvement from the patients, and was
approved by the Regional Committee for Medical and Health Research Ethics
(2013/2370/REK sør-øst D).
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References
1. Munns CF, Shaw N, Kiely M, et al. Global Consensus Recommendations on Prevention and
Management of Nutritional Rickets. The Journal of clinical endocrinology and metabolism
2016;101(2):394-415. doi: 10.1210/jc.2015-2175 [published Online First: 2016/01/09]
2. Lips P. Worldwide status of vitamin D nutrition. The Journal of steroid biochemistry and molecular
biology 2010;121(1-2):297-300. doi: 10.1016/j.jsbmb.2010.02.021 [published Online First:
2010/03/04]
3. Holvik K, Meyer HE, Haug E, et al. Prevalence and predictors of vitamin D deficiency in five
immigrant groups living in Oslo, Norway: the Oslo Immigrant Health Study. EurJClinNutr
2005;59(1):57-63.
4. Meyer HE, Falch JA, Sogaard AJ, et al. Vitamin D deficiency and secondary hyperparathyroidism
and the association with bone mineral density in persons with Pakistani and Norwegian
background living in Oslo, Norway, The Oslo Health Study. Bone 2004;35(2):412-17.
5. Madar AA, Stene LC, Meyer HE. Vitamin D status among immigrant mothers from Pakistan, Turkey
and Somalia and their infants attending child health clinics in Norway. The British journal of
nutrition 2009;101(7):1052-8. doi: 10.1017/S0007114508055712
6. Immigrants and Norwegian-born to immigrant parents Oslo: Statistics Norway; 2016.Available
from:
https://www.ssb.no/statistikkbanken/selecttable/hovedtabellHjem.asp?KortNavnWeb=innv
bef&CMSSubjectArea=befolkning&PLanguage=1&checked=true2016.
7. Brunvand L, Brunvatne R. [Health problems among immigrant children in Norway]. Tidsskr Nor
Laegeforen 2001;121(6):715-8. [published Online First: 2001/04/11]
8. Beck-Nielsen SS, Brock-Jacobsen B, Gram J, et al. Incidence and prevalence of nutritional and
hereditary rickets in southern Denmark. European journal of endocrinology / European
Federation of Endocrine Societies 2009;160(3):491-7. doi: 10.1530/eje-08-0818 [published
Online First: 2008/12/20]
9. Thacher TD, Fischer PR, Tebben PJ, et al. Increasing incidence of nutritional rickets: a population-
based study in Olmsted County, Minnesota. Mayo Clinic proceedings 2013;88(2):176-83. doi:
10.1016/j.mayocp.2012.10.018 [published Online First: 2013/02/05]
10. Goldacre M, Hall N, Yates DGR. Hospitalisation for children with rickets in England: a historical
perspective. Lancet 2014;383:1.
11. Ahmed SF, Franey C, McDevitt H, et al. Recent trends and clinical features of childhood vitamin D
deficiency presenting to a children's hospital in Glasgow. Arch Dis Child 2011;96(7):694-6.
doi: 10.1136/adc.2009.173195
12. Prentice A. Nutritional rickets around the world. The Journal of steroid biochemistry and
molecular biology 2013;136:201-6. doi: 10.1016/j.jsbmb.2012.11.018 [published Online First:
2012/12/12]
13. Madar AA, Klepp KI, Meyer HE. Effect of free vitamin D(2) drops on serum 25-hydroxyvitamin D in
infants with immigrant origin: a cluster randomized controlled trial. Eur J Clin Nutr
2009;63(4):478-84. doi: 10.1038/sj.ejcn.1602982 [published Online First: 2008/01/31]
14. Grewal NK, Andersen LF, Sellen D, et al. Breast-feeding and complementary feeding practices in
the first 6 months of life among Norwegian-Somali and Norwegian-Iraqi infants: the
InnBaKost survey. Public Health Nutr 2016;19(4):703-15. doi: 10.1017/s1368980015001962
[published Online First: 2015/06/25]
15. Grewal NK, Andersen LF, Kolve CS, et al. Food and Nutrient Intake among 12-Month-Old
Norwegian-Somali and Norwegian-Iraqi Infants. Nutrients 2016;8(10) doi:
10.3390/nu8100602
16. Thacher TD, Pludowski P, Shaw NJ, et al. Nutritional rickets in immigrant and refugee children.
Public Health Reviews 2016;37(1):3. doi: 10.1186/s40985-016-0018-3
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Figure legends
Figure 1. Flow diagram, patient inclusion, nutritional rickets, Norway 2008-2012.
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Figure 1. Flow diagram, patient inclusion, nutritional rickets.
279x361mm (300 x 300 DPI)
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The RECORD statement – checklist of items, extended from the STROBE statement, that should be reported in observational studies using
routinely collected health data.
Item
No.
STROBE items Location in
manuscript where
items are reported
RECORD items Location in
manuscript
where items are
reported
Title and abstract
1 (a) Indicate the study’s design
with a commonly used term in
the title or the abstract (b)
Provide in the abstract an
informative and balanced
summary of what was done and
what was found
RECORD 1.1: The type of data used
should be specified in the title or
abstract. When possible, the name of
the databases used should be included.
RECORD 1.2: If applicable, the
geographic region and timeframe within
which the study took place should be
reported in the title or abstract.
RECORD 1.3: If linkage between
databases was conducted for the study,
this should be clearly stated in the title
or abstract.
Page 1 & 2
Introduction
Background
rationale
2 Explain the scientific background
and rationale for the investigation
being reported
Page 4
Objectives 3 State specific objectives,
including any prespecified
hypotheses
Page 5
Methods
Study Design 4 Present key elements of study
design early in the paper
Page 5 & 6
Setting 5 Describe the setting, locations,
and relevant dates, including
periods of recruitment, exposure,
follow-up, and data collection
Page 5 & 6
Participants 6 (a) Cohort study - Give the
eligibility criteria, and the
RECORD 6.1: The methods of study
population selection (such as codes or
Page 5 & 6
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sources and methods of selection
of participants. Describe methods
of follow-up
Case-control study - Give the
eligibility criteria, and the
sources and methods of case
ascertainment and control
selection. Give the rationale for
the choice of cases and controls
Cross-sectional study - Give the
eligibility criteria, and the
sources and methods of selection
of participants
(b) Cohort study - For matched
studies, give matching criteria
and number of exposed and
unexposed
Case-control study - For matched
studies, give matching criteria
and the number of controls per
case
algorithms used to identify subjects)
should be listed in detail. If this is not
possible, an explanation should be
provided.
RECORD 6.2: Any validation studies
of the codes or algorithms used to select
the population should be referenced. If
validation was conducted for this study
and not published elsewhere, detailed
methods and results should be provided.
RECORD 6.3: If the study involved
linkage of databases, consider use of a
flow diagram or other graphical display
to demonstrate the data linkage process,
including the number of individuals
with linked data at each stage.
Variables 7 Clearly define all outcomes,
exposures, predictors, potential
confounders, and effect
modifiers. Give diagnostic
criteria, if applicable.
RECORD 7.1: A complete list of codes
and algorithms used to classify
exposures, outcomes, confounders, and
effect modifiers should be provided. If
these cannot be reported, an explanation
should be provided.
Page 5 & 6
Data sources/
measurement
8 For each variable of interest, give
sources of data and details of
methods of assessment
(measurement).
Describe comparability of
assessment methods if there is
more than one group
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Bias 9 Describe any efforts to address
potential sources of bias
Page 5 & 6
Study size 10 Explain how the study size was The complete
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arrived at population was
selected as
described in the
manuscript
Quantitative
variables
11 Explain how quantitative
variables were handled in the
analyses. If applicable, describe
which groupings were chosen,
and why
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Statistical
methods
12 (a) Describe all statistical
methods, including those used to
control for confounding
(b) Describe any methods used to
examine subgroups and
interactions
(c) Explain how missing data
were addressed
(d) Cohort study - If applicable,
explain how loss to follow-up
was addressed
Case-control study - If
applicable, explain how matching
of cases and controls was
addressed
Cross-sectional study - If
applicable, describe analytical
methods taking account of
sampling strategy
(e) Describe any sensitivity
analyses
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Data access and
cleaning methods
.. RECORD 12.1: Authors should
describe the extent to which the
investigators had access to the database
population used to create the study
population.
RECORD 12.2: Authors should provide
information on the data cleaning
Page 5 & 6
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methods used in the study.
Linkage .. RECORD 12.3: State whether the study
included person-level, institutional-
level, or other data linkage across two
or more databases. The methods of
linkage and methods of linkage quality
evaluation should be provided.
n.a.
Results
Participants 13 (a) Report the numbers of
individuals at each stage of the
study (e.g., numbers potentially
eligible, examined for eligibility,
confirmed eligible, included in
the study, completing follow-up,
and analysed)
(b) Give reasons for non-
participation at each stage.
(c) Consider use of a flow
diagram
RECORD 13.1: Describe in detail the
selection of the persons included in the
study (i.e., study population selection)
including filtering based on data
quality, data availability and linkage.
The selection of included persons can
be described in the text and/or by means
of the study flow diagram.
Page 5, 6
& figure 1
Descriptive data 14 (a) Give characteristics of study
participants (e.g., demographic,
clinical, social) and information
on exposures and potential
confounders
(b) Indicate the number of
participants with missing data for
each variable of interest
(c) Cohort study - summarise
follow-up time (e.g., average and
total amount)
Page 8
Outcome data 15 Cohort study - Report numbers of
outcome events or summary
measures over time
Case-control study - Report
numbers in each exposure
category, or summary measures
of exposure
Cross-sectional study - Report
Page 7 & 8
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numbers of outcome events or
summary measures
Main results 16 (a) Give unadjusted estimates
and, if applicable, confounder-
adjusted estimates and their
precision (e.g., 95% confidence
interval). Make clear which
confounders were adjusted for
and why they were included
(b) Report category boundaries
when continuous variables were
categorized
(c) If relevant, consider
translating estimates of relative
risk into absolute risk for a
meaningful time period
Page 7-9
Other analyses 17 Report other analyses done—e.g.,
analyses of subgroups and
interactions, and sensitivity
analyses
Page 9
Discussion
Key results 18 Summarise key results with
reference to study objectives
Page 9
Limitations 19 Discuss limitations of the study,
taking into account sources of
potential bias or imprecision.
Discuss both direction and
magnitude of any potential bias
RECORD 19.1: Discuss the
implications of using data that were not
created or collected to answer the
specific research question(s). Include
discussion of misclassification bias,
unmeasured confounding, missing data,
and changing eligibility over time, as
they pertain to the study being reported.
Page 10
Interpretation 20 Give a cautious overall
interpretation of results
considering objectives,
limitations, multiplicity of
analyses, results from similar
studies, and other relevant
evidence
Page 9-10
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Generalisability 21 Discuss the generalisability
(external validity) of the study
results
Page 10
Other Information
Funding 22 Give the source of funding and
the role of the funders for the
present study and, if applicable,
for the original study on which
the present article is based
Page 11
Accessibility of
protocol, raw
data, and
programming
code
.. RECORD 22.1: Authors should provide
information on how to access any
supplemental information such as the
study protocol, raw data, or
programming code.
Data sharing
statement
included.
*Reference: Benchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, Sørensen HT, von Elm E, Langan SM, the RECORD Working
Committee. The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement. PLoS Medicine 2015;
in press.
*Checklist is protected under Creative Commons Attribution (CC BY) license.
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Nutritional rickets in Norway:
A nationwide register-based cohort study.
Journal: BMJ Open
Manuscript ID bmjopen-2016-015289.R2
Article Type: Research
Date Submitted by the Author: 04-Apr-2017
Complete List of Authors: Meyer, Haakon; University of Oslo, Department of Community Medicine and Global Health; Norwegian Institute of Public Health, Domain for Mental and Physical Health Skram, Kristina; Oslo Universitetssykehus, Department of Pediatrics Berge, Ingvill; Oslo Universitetssykehus, Department of Pediatrics Madar, Ahmed; Institute of Health and Society, The Medical Faculty, University of Oslo, Department of Community Medicine Bjørndalen, Hilde ; Oslo Universitetssykehus, Department of Pediatrics
<b>Primary Subject Heading</b>:
Nutrition and metabolism
Secondary Subject Heading: Epidemiology, Public health
Keywords: Rickets, Immigrant, Vitamin D, Nutrition < TROPICAL MEDICINE
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Nutritional rickets in Norway:
A nationwide register-based cohort study.
Haakon E. Meyer, professor1,2
Kristina Skram, registrar3
Ingvill Almås Berge, registrar3
Ahmed Madar, researcher1
Hilde Johanne Bjørndalen, consultant3
1 Department of Community Medicine and Global Health, University of Oslo, P.O. Box 1130
Blindern, 0318, Oslo, Norway.
E-mail: [email protected]
2 Domain for Mental and Physical Health, Norwegian Institute of Public Health, Oslo,
Norway
3 Department of Pediatrics, Oslo University Hospital, Oslo, Norway
Corresponding author: Professor Haakon E. Meyer, Department of Community Medicine
and Global Health, University of Oslo, P.O. Box 1130 Blindern, 0318, Oslo, Norway.
E-mail: [email protected]
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Abstract:
Objectives: Poor vitamin D status has been reported to be highly prevalent in many non-
western immigrant groups living in Norway and other western countries. However, data on
rickets are scarce, and the aim of the current study was to identify new cases of nutritional
rickets in Norway in the period 2008-2012 among children under the age of five.
Design: Register-based cohort study.
Setting: The Norwegian population from 2008-2012.
Participants: Children with nutritional rickets under the age of 5 years.
Main outcome measure: Nutritional rickets. Patients with ICD10 diagnosis code E55.0
(active rickets) treated at all Norwegian hospitals were identified in the Norwegian Patient
Registry. We were able to review 85% of the medical records for diagnosis confirmation. In
addition, we identified patients with the diagnoses E55.9, E64.3 and E83.3 in order to identify
individuals with rickets who had been given other diagnoses.
Results: Nutritional rickets was confirmed in 39 children aged 0-4 years with the diagnosis of
E55.0. In addition, three patients with the diagnosis of unspecified vitamin D deficiency
(E55.9) were classified as having nutritional rickets, giving a total of 42 patients. Mean age at
diagnosis was 1.40 years (range 0.1 - 3.5 years), and 93 % had a non-western immigrant
background. The incidence rate of rickets was estimated to be 0.3 per 10,000 person-years in
the total Norwegian child population under the age of 5 and 3.1 per 10,000 person-years in
those with an immigrant background from Asia or Africa.
Conclusion: The number of children with nutritional rickets in Norway remained low in the
period 2008-12. Nearly all children had a non-western immigrant background.
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Strengths and limitations of this study
• This register-based study covered the complete Norwegian population
• All children under the age of five years with a diagnosis code of rickets were identified
• The diagnosis was confirmed by medical record review at the treating hospital
• We were not able to review the medical records for 15% of the patients
• The study was limited to patients treated in the period 2008-2012
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The classical consequence of vitamin D deficiency is nutritional rickets in children.
Nutritional rickets is caused primarily by severe vitamin D deficiency and/or a low intake of
calcium.1 Poor vitamin D status has been reported in many non-western immigrant groups
living in western countries.2 In the Oslo Health Study, 43% of the non-western immigrant
women and 31% of the men had vitamin D deficiency with circulating 25-hydroxyvitamin D
(25(OH)D) < 25 nmol/l,3 and 21% of women born in Pakistan had severe vitamin D
deficiency (25(OH)D < 12.5 nmol/l).4 The poor vitamin D status among women of child-
bearing age was confirmed in a study among immigrant mothers (6 weeks after giving birth)
with a background from Pakistan, Turkey and Somalia living in Oslo.5 Fifty-six percent had
vitamin D deficiency, and 15% had severe vitamin D deficiency. Based on the poor vitamin D
status of the adults, it has been a concern that rickets could emerge as a large problem among
infants with an immigrant background. In addition, the immigrant part of the population has
increased and currently nearly 10% of all Norwegian children under the age of five have a
non-western immigrant background.6 Data about rickets in Norway and other European
countries are scarce. An enquiry sent to all hospitals with paediatric wards in 2000 reported
65 children with nutritional rickets in Norway during the two years period 1998-1999, of
which 83% had an immigrant background.7 Eighty percent were younger than 3 years. In a
study covering southern Denmark from 1985-2005, only 112 patients with nutritional rickets
were identified during a 20-year period, of which 75% had an immigrant background.8 In a
population-based study from Olmsted County, Minnesota, 76% of the cases with nutritional
rickets had a non-white ethnic background. Although the incidence was low, it increased in
the period 1970 to 2009.9 A study reporting hospital admissions for rickets in England across
five decades also suggests that the incidence of rickets has increased during recent years.10 In
that study, the diagnoses were not confirmed by a medical record review, but hospital-based
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studies from the UK indicate that rickets might be an increasing problem among immigrant
children.11 12
Prior to this study, no updated information on the occurrence of rickets in Norway was
available. However, several efforts to secure a good vitamin D status among children have
been introduced in recent years, including free vitamin D drops for infants with a non-western
immigrant background and infant food fortified with vitamin D. The aim of the study was to
identify new cases of nutritional rickets in children under the age of 5 in the Norwegian
population in the period 2008-2012.
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Materials and Methods
The national specialist health care register (Norwegian Patient Registry (NPR)) contains
information on all hospital admissions and outpatient contact in the specialised health
services. The register also includes the unique 11-digit personal identification number
provided to all Norwegian residents. We used data from the NPR in the period 2008-2012 and
identified all admissions/contacts with the diagnosis E55.0 (active rickets), which is a sub-
code of E55, vitamin D deficiency. In addition, we identified admissions/contacts with the
diagnosis E55.9 (unspecified vitamin D deficiency), E64.3 (sequelae of rickets) and E83.3
(disorders of phosphorus metabolism and phosphatases) in order to identify patients with
rickets who had been given other diagnoses. Data extraction was performed by the NPR and
we did not have access to the background data.
In order to verify the diagnosis, all hospitals treating the children were contacted. At each
responding hospital, doctors in the paediatric department completed a questionnaire for
medical record review. We requested information about x-ray findings, biochemical tests,
symptoms, the clinical examination and the child’s ethnic background. In addition, the type
and effect of treatment was requested. Finally they were asked if the diagnosis was rickets,
and if so, if it was nutritional rickets.
In order to reconfirm the conclusions, two doctors working at the paediatric department at
Oslo University Hospital (KS and IAB) reviewed all the questionnaires (half each). The
diagnosis of nutritional rickets was based on biochemical markers and clinical
symptoms/signs and/or radiological findings. In addition, it was taken into account if it was
reported that the patient responded favourably to treatment with vitamin D. The following
biochemical criteria were used: 25(OH)D < 12.5 nmol/l or 25(OH)D 12.5-25 nmol/l in the
presence of elevated plasma alkaline phosphatase (ALP) or elevated serum parathyroid
hormone (PTH), or low serum calcium (Ca). As there was a possibility that some infants had
already started to receive vitamin D supplements before the diagnosis was given, we also
included 11 patients with 25(OH)D 25-37 nmol/l of which all had x-ray findings consistent
with rickets.
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In cases of doubt, each case was discussed with a paediatric endocrinologist (HJB) before the
conclusion was made.
All 23 hospitals treating the identified patients were contacted. The unique personal
identification number made it possible to link the information in NPR to the medical records
at the hospitals.
To test gender differences and differences in number of cases per year we used the chi-
squared test. As a denominator we used the number of children aged 0-4 years in the
Norwegian population.
Results
The flow of patient inclusion is displayed in figure 1. We identified 110 children under the
age of 5 years in the Norwegian Patient Registry who had been diagnosed with active rickets
(E55.0). We were able to review medical records from 18 of 23 hospitals, which constituted
85% of the identified patients. Of 94 reviewed medical records in patients with E55.0, the
diagnosis of active rickets was confirmed in 54% (n=51). Of these patients, 9 were excluded
as they were first diagnosed before 2008, leaving 42 patients with E55.0.
Of these, 39 patients were classified as having nutritional rickets, whereas rickets was linked
to prematurity in three patients. In addition, three patients with the diagnosis of unspecified
vitamin D deficiency (E55.9) were classified as having nutritional rickets, giving the final
number of 42 patients. Four of the 42 patients were admitted due to seizure. They were
between 1-3 months old and had very low 25(OH)D concentrations (11-15 nmol/l).
We did not include seven patients with an uncertain diagnosis of (nutritional) rickets.
As shown in table 1, mean age at the diagnosis of nutritional rickets was 1.40 years (range 0.1
- 3.5 years), and 74% of the children were 1 to 2 years at the time of diagnosis.
Fifty-seven percent of the patients were boys (not statistically significant different from girls,
p=0.35), and 48% were diagnosed during winter/early spring (November-April) and 52%
during the rest of the year. Nearly all patients (93 %) had a non-western immigrant
background and around 60% had a background from Asia. With regards to individual
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countries, 24% had a Pakistani background and 21% had an Iraqi background, only 7% had an
ethnic Norwegian background.
Apparently, there were variations in the number of patients with rickets from year to year.
However, the numbers of cases were small and there was no overall statistically significant
difference between the years of diagnosis (p=0.56).
Around one-third of all children aged 0-4 years with an immigrant-background from Asia and
Africa are found in the Norwegian capital of Oslo. Although there were 3 to 4 cases each year
in the period 2008-2010, there were no cases with nutritional rickets reported from Oslo in the
period 2011-2012.
Table 1. Characteristic of 42 patients under the age of 5 with nutritional rickets in
Norway 2008-2012
Age at diagnosis
(years, mean (SD)) 1.40 (±0.73)
< 1 year 10 (24 %)
1 - 21 (50 %)
2 - 10 (24 %)
3 - <4 1 (2 %)
Gender (n (%))
Boys 24 (57.1)
Girls 18 (42.9)
Country background (n (%))
Norway 3 (7.1)
Asia 25 (59.5)
Africa 12 (28.6)
Other/unknown 2 (4.8)
Year of diagnosis (n (%))
2008 6 (14.3)
2009 10 (23.8)
2010 12 (28.6)
2011 7 (16.7)
2012 7 (16.7)
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For 37 of the 42 children with nutritional rickets, information about 25(OH)D was available.
Mean concentration was 17.9 nmol/l, and 86.5% had concentrations less than 30 nmol/l.
Estimated incidence rate of rickets: According to Statistics Norway, the yearly average of
children aged 0-4 years in Norway in the period 2008-12 was 303,157 children. Of these,
around 24,000 children (8%) had an Asian or African background.
Based on this, the incidence rate of rickets was estimated to be 3.1 (95% CI 2.2-4.4) per
10,000 person-years in children under the age of 5 with an Asian or African background and
0.3 (95% CI 0.2-0.4) per 10,000 person-years in the total Norwegian population under the age
of 5. This is a slight underestimate as we were not able to review 15% of the medical records.
If each of the 16 children who were treated at hospitals without feedback had nutritional
rickets, the incidence rate in the Norwegian population under the age of 5 would be 0.4 per
10,000 person years.
Discussion
The number of children with nutritional rickets in the Norwegian population during 2008-
2012 was low and 93% occurred in children with a non-western immigrant background.
On average, 8 cases of nutritional rickets were reported annually. This is considerably lower
than the yearly average of 32 reported in the hospital enquiry for the two-year period 1998-
1999 7. In addition, the number of children aged 0-4 years with an Asian or African
background increased by around 75% from 2000 to 2012. Although these two studies are not
directly comparable, the risk of rickets seems to have declined substantially among immigrant
children during recent years.
In the same period, several measures were introduced in order to prevent vitamin D deficiency
and rickets. Based on the results from a cluster randomised trial,13 infants with a non-western
immigrant background are offered free vitamin D drops at child health clinics from the age of
4 weeks to six months. Since 2002, most infant cereals have been fortified with vitamin D and
infant formula has been fortified with vitamin D for many years. In addition, at routine
appointments at child health clinics during infancy, the public health nurses fulfil their
longstanding commitment to inform mothers of the importance of vitamin D. According to a
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study among Norwegian-Somali and Norwegian-Iraqi infants, vitamin D supplements and
fortified infant formula and cereals are frequently used.14
Another possible explanation for the low risk of rickets in Norwegian infants is that calcium
intake in general is adequate. In the same study noted above, median daily calcium intake was
777 mg in Norwegian-Somali and 633 mg in Norwegian-Iraqi infants.15
However, nutritional rickets still occurs, even though it can be easily treated. Some groups are
more exposed and around 50% of the patients had a background from two countries, Iraq and
Pakistan.
Some weaknesses of the study should be mentioned. Although the NPR covers the entire
Norwegian population, we were unable to confirm the rickets diagnosis in 15% of the patients
as we did not receive feedback from all hospitals. In addition, the medical record reviews
made locally at each hospital depended upon available information in the medical records and
reporting accuracy, and complete information was not always available. We might also have
missed individuals who were given alternative diagnoses to E55.0. However, it is hard to see
that this could impact our results substantially. Only 3 of 42 patients included were identified
via our extended search (E55.9, E64.3 and E83.3) and these patients were diagnosed with
unspecified vitamin D deficiency (E55.9) in the Norwegian Patient Registry. Another
restriction is that the study was limited to Norway in the period 2008-12 but the main finding
of a low risk of rickets may apply to a similar population with similar measures to prevent
vitamin D deficiency, including vitamin D supplementation and targeted vitamin D
fortification for infants. However, awareness is needed as sudden changes, like a high influx
of refugees, may alter the situation in segments of the child population.16
Conclusion
The number of children with nutritional rickets in Norway remained low in the period 2008-
12 and 93% of the children had a non-western immigrant background.
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11
Acknowledgements: We thank the physicians at the individual hospitals for reviewing the
medical records and Julie Whittle Johansen for proofreading the manuscript.
Contributors: HEM, IAB, AM and HJB conceived the study. HEM, KS, IAB and HJB
collected the data. HEM analysed the data and drafted the article. All authors contributed in
the interpretation of the findings, critically revised the paper for important intellectual content
and approved the final version. HEM is the guarantor.
Declaration of competing interests: All authors have completed the ICMJE uniform
disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any
organisation for the submitted work; no financial relationships with any organisations that
might have an interest in the submitted work in the previous three years; and no other
relationships or activities that could appear to have influenced the submitted work.
Data sharing: The Regional Committee for Medical and Health Research Ethics judged these
data to be highly sensitive. The data can therefore not be shared unless a separate query is sent
to the ethical committee and the data owners.
Transparency declaration: The lead author (HEM) affirms that the manuscript is an honest,
accurate, and transparent account of the study being reported; that no important aspects of the
study have been omitted; and that any discrepancies from the study as planned have been
explained.
The Corresponding Author has the right to grant on behalf of all authors and does grant on
behalf of all authors, a worldwide licence to the Publishers and its licensees in perpetuity, in
all forms, formats and media (whether known now or created in the future), to i) publish,
reproduce, distribute, display and store the Contribution, ii) translate the Contribution into
other languages, create adaptations, reprints, include within collections and create summaries,
extracts and/or, abstracts of the Contribution, iii) create any other derivative work(s) based on
the Contribution, iv) to exploit all subsidiary rights in the Contribution, v) the inclusion of
electronic links from the Contribution to third party material where-ever it may be located;
and, vi) licence any third party to do any or all of the above.
Funding/role of sponsor: This study was funded by the Norwegian Directorate of Health.
The sponsor had no influence on the preparation, review, or approval of the manuscript.
Ethical approval: The study did not include any involvement from the patients, and was
approved by the Regional Committee for Medical and Health Research Ethics
(2013/2370/REK sør-øst D).
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References
1. Munns CF, Shaw N, Kiely M, et al. Global Consensus Recommendations on Prevention and
Management of Nutritional Rickets. The Journal of clinical endocrinology and metabolism
2016;101(2):394-415. doi: 10.1210/jc.2015-2175 [published Online First: 2016/01/09]
2. Lips P. Worldwide status of vitamin D nutrition. The Journal of steroid biochemistry and molecular
biology 2010;121(1-2):297-300. doi: 10.1016/j.jsbmb.2010.02.021 [published Online First:
2010/03/04]
3. Holvik K, Meyer HE, Haug E, et al. Prevalence and predictors of vitamin D deficiency in five
immigrant groups living in Oslo, Norway: the Oslo Immigrant Health Study. EurJClinNutr
2005;59(1):57-63.
4. Meyer HE, Falch JA, Sogaard AJ, et al. Vitamin D deficiency and secondary hyperparathyroidism
and the association with bone mineral density in persons with Pakistani and Norwegian
background living in Oslo, Norway, The Oslo Health Study. Bone 2004;35(2):412-17.
5. Madar AA, Stene LC, Meyer HE. Vitamin D status among immigrant mothers from Pakistan, Turkey
and Somalia and their infants attending child health clinics in Norway. The British journal of
nutrition 2009;101(7):1052-8. doi: 10.1017/S0007114508055712
6. Immigrants and Norwegian-born to immigrant parents Oslo: Statistics Norway; 2016.Available
from:
https://www.ssb.no/statistikkbanken/selecttable/hovedtabellHjem.asp?KortNavnWeb=innv
bef&CMSSubjectArea=befolkning&PLanguage=1&checked=true2016.
7. Brunvand L, Brunvatne R. [Health problems among immigrant children in Norway]. Tidsskr Nor
Laegeforen 2001;121(6):715-8. [published Online First: 2001/04/11]
8. Beck-Nielsen SS, Brock-Jacobsen B, Gram J, et al. Incidence and prevalence of nutritional and
hereditary rickets in southern Denmark. European journal of endocrinology / European
Federation of Endocrine Societies 2009;160(3):491-7. doi: 10.1530/eje-08-0818 [published
Online First: 2008/12/20]
9. Thacher TD, Fischer PR, Tebben PJ, et al. Increasing incidence of nutritional rickets: a population-
based study in Olmsted County, Minnesota. Mayo Clinic proceedings 2013;88(2):176-83. doi:
10.1016/j.mayocp.2012.10.018 [published Online First: 2013/02/05]
10. Goldacre M, Hall N, Yates DGR. Hospitalisation for children with rickets in England: a historical
perspective. Lancet 2014;383:1.
11. Ahmed SF, Franey C, McDevitt H, et al. Recent trends and clinical features of childhood vitamin D
deficiency presenting to a children's hospital in Glasgow. Arch Dis Child 2011;96(7):694-6.
doi: 10.1136/adc.2009.173195
12. Prentice A. Nutritional rickets around the world. The Journal of steroid biochemistry and
molecular biology 2013;136:201-6. doi: 10.1016/j.jsbmb.2012.11.018 [published Online First:
2012/12/12]
13. Madar AA, Klepp KI, Meyer HE. Effect of free vitamin D(2) drops on serum 25-hydroxyvitamin D in
infants with immigrant origin: a cluster randomized controlled trial. Eur J Clin Nutr
2009;63(4):478-84. doi: 10.1038/sj.ejcn.1602982 [published Online First: 2008/01/31]
14. Grewal NK, Andersen LF, Sellen D, et al. Breast-feeding and complementary feeding practices in
the first 6 months of life among Norwegian-Somali and Norwegian-Iraqi infants: the
InnBaKost survey. Public Health Nutr 2016;19(4):703-15. doi: 10.1017/s1368980015001962
[published Online First: 2015/06/25]
15. Grewal NK, Andersen LF, Kolve CS, et al. Food and Nutrient Intake among 12-Month-Old
Norwegian-Somali and Norwegian-Iraqi Infants. Nutrients 2016;8(10) doi:
10.3390/nu8100602
16. Thacher TD, Pludowski P, Shaw NJ, et al. Nutritional rickets in immigrant and refugee children.
Public Health Reviews 2016;37(1):3. doi: 10.1186/s40985-016-0018-3
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Figure legends
Figure 1. Flow diagram, patient inclusion, nutritional rickets, Norway 2008-2012.
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297x420mm (300 x 300 DPI)
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The RECORD statement – checklist of items, extended from the STROBE statement, that should be reported in observational studies using
routinely collected health data.
Item
No.
STROBE items Location in
manuscript where
items are reported
RECORD items Location in
manuscript
where items are
reported
Title and abstract
1 (a) Indicate the study’s design
with a commonly used term in
the title or the abstract (b)
Provide in the abstract an
informative and balanced
summary of what was done and
what was found
RECORD 1.1: The type of data used
should be specified in the title or
abstract. When possible, the name of
the databases used should be included.
RECORD 1.2: If applicable, the
geographic region and timeframe within
which the study took place should be
reported in the title or abstract.
RECORD 1.3: If linkage between
databases was conducted for the study,
this should be clearly stated in the title
or abstract.
Page 1 & 2
Introduction
Background
rationale
2 Explain the scientific background
and rationale for the investigation
being reported
Page 4
Objectives 3 State specific objectives,
including any prespecified
hypotheses
Page 5
Methods
Study Design 4 Present key elements of study
design early in the paper
Page 5 & 6
Setting 5 Describe the setting, locations,
and relevant dates, including
periods of recruitment, exposure,
follow-up, and data collection
Page 5 & 6
Participants 6 (a) Cohort study - Give the
eligibility criteria, and the
RECORD 6.1: The methods of study
population selection (such as codes or
Page 5 & 6
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sources and methods of selection
of participants. Describe methods
of follow-up
Case-control study - Give the
eligibility criteria, and the
sources and methods of case
ascertainment and control
selection. Give the rationale for
the choice of cases and controls
Cross-sectional study - Give the
eligibility criteria, and the
sources and methods of selection
of participants
(b) Cohort study - For matched
studies, give matching criteria
and number of exposed and
unexposed
Case-control study - For matched
studies, give matching criteria
and the number of controls per
case
algorithms used to identify subjects)
should be listed in detail. If this is not
possible, an explanation should be
provided.
RECORD 6.2: Any validation studies
of the codes or algorithms used to select
the population should be referenced. If
validation was conducted for this study
and not published elsewhere, detailed
methods and results should be provided.
RECORD 6.3: If the study involved
linkage of databases, consider use of a
flow diagram or other graphical display
to demonstrate the data linkage process,
including the number of individuals
with linked data at each stage.
Variables 7 Clearly define all outcomes,
exposures, predictors, potential
confounders, and effect
modifiers. Give diagnostic
criteria, if applicable.
RECORD 7.1: A complete list of codes
and algorithms used to classify
exposures, outcomes, confounders, and
effect modifiers should be provided. If
these cannot be reported, an explanation
should be provided.
Page 5 & 6
Data sources/
measurement
8 For each variable of interest, give
sources of data and details of
methods of assessment
(measurement).
Describe comparability of
assessment methods if there is
more than one group
Page 5 & 6
Bias 9 Describe any efforts to address
potential sources of bias
Page 5 & 6
Study size 10 Explain how the study size was The complete
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arrived at population was
selected as
described in the
manuscript
Quantitative
variables
11 Explain how quantitative
variables were handled in the
analyses. If applicable, describe
which groupings were chosen,
and why
Page 5 & 6
Statistical
methods
12 (a) Describe all statistical
methods, including those used to
control for confounding
(b) Describe any methods used to
examine subgroups and
interactions
(c) Explain how missing data
were addressed
(d) Cohort study - If applicable,
explain how loss to follow-up
was addressed
Case-control study - If
applicable, explain how matching
of cases and controls was
addressed
Cross-sectional study - If
applicable, describe analytical
methods taking account of
sampling strategy
(e) Describe any sensitivity
analyses
Page 5, 6, 9
Data access and
cleaning methods
.. RECORD 12.1: Authors should
describe the extent to which the
investigators had access to the database
population used to create the study
population.
RECORD 12.2: Authors should provide
information on the data cleaning
Page 5 & 6
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methods used in the study.
Linkage .. RECORD 12.3: State whether the study
included person-level, institutional-
level, or other data linkage across two
or more databases. The methods of
linkage and methods of linkage quality
evaluation should be provided.
n.a.
Results
Participants 13 (a) Report the numbers of
individuals at each stage of the
study (e.g., numbers potentially
eligible, examined for eligibility,
confirmed eligible, included in
the study, completing follow-up,
and analysed)
(b) Give reasons for non-
participation at each stage.
(c) Consider use of a flow
diagram
RECORD 13.1: Describe in detail the
selection of the persons included in the
study (i.e., study population selection)
including filtering based on data
quality, data availability and linkage.
The selection of included persons can
be described in the text and/or by means
of the study flow diagram.
Page 5, 6
& figure 1
Descriptive data 14 (a) Give characteristics of study
participants (e.g., demographic,
clinical, social) and information
on exposures and potential
confounders
(b) Indicate the number of
participants with missing data for
each variable of interest
(c) Cohort study - summarise
follow-up time (e.g., average and
total amount)
Page 8
Outcome data 15 Cohort study - Report numbers of
outcome events or summary
measures over time
Case-control study - Report
numbers in each exposure
category, or summary measures
of exposure
Cross-sectional study - Report
Page 7 & 8
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numbers of outcome events or
summary measures
Main results 16 (a) Give unadjusted estimates
and, if applicable, confounder-
adjusted estimates and their
precision (e.g., 95% confidence
interval). Make clear which
confounders were adjusted for
and why they were included
(b) Report category boundaries
when continuous variables were
categorized
(c) If relevant, consider
translating estimates of relative
risk into absolute risk for a
meaningful time period
Page 7-9
Other analyses 17 Report other analyses done—e.g.,
analyses of subgroups and
interactions, and sensitivity
analyses
Page 9
Discussion
Key results 18 Summarise key results with
reference to study objectives
Page 9
Limitations 19 Discuss limitations of the study,
taking into account sources of
potential bias or imprecision.
Discuss both direction and
magnitude of any potential bias
RECORD 19.1: Discuss the
implications of using data that were not
created or collected to answer the
specific research question(s). Include
discussion of misclassification bias,
unmeasured confounding, missing data,
and changing eligibility over time, as
they pertain to the study being reported.
Page 10
Interpretation 20 Give a cautious overall
interpretation of results
considering objectives,
limitations, multiplicity of
analyses, results from similar
studies, and other relevant
evidence
Page 9-10
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Generalisability 21 Discuss the generalisability
(external validity) of the study
results
Page 10
Other Information
Funding 22 Give the source of funding and
the role of the funders for the
present study and, if applicable,
for the original study on which
the present article is based
Page 11
Accessibility of
protocol, raw
data, and
programming
code
.. RECORD 22.1: Authors should provide
information on how to access any
supplemental information such as the
study protocol, raw data, or
programming code.
Data sharing
statement
included.
*Reference: Benchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, Sørensen HT, von Elm E, Langan SM, the RECORD Working
Committee. The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement. PLoS Medicine 2015;
in press.
*Checklist is protected under Creative Commons Attribution (CC BY) license.
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