BMJ Open...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

For peer review only

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

Primary Subject

Heading: Nutrition and metabolism

Secondary Subject Heading: Epidemiology, Public health

Keywords: Rickets, Immigrant, Vitamin D, Nutrition < TROPICAL MEDICINE

For peer review only - http://bmjopen.bmj.com/site/about/guidelines.xhtml

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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

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: Epub Date]|.

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: Epub Date]|.

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[published Online First: Epub

Date]|.

6. Brunvand L, Brunvatne R. [Health problems among immigrant children in Norway]. Tidsskr Nor

Laegeforen 2001;121(6):715-8

7. 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: Epub Date]|.

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

D deficiency presenting to a children's hospital in Glasgow. Arch Dis Child 2011;96(7):694-6 doi:

10.1136/adc.2009.173195[published Online First: Epub Date]|.

10. 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:

Epub Date]|.

11. 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: Epub Date]|.

12. 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: Epub Date]|.

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13. 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[published Online First: Epub Date]|.

14. Högler W, Munns CF. Rickets and osteomalacia: a call for action to protect immigrants and

ethnic risk groups. The Lancet Global Health 2016;4(4):e229-e30 doi: 10.1016/S2214-

109X(16)00061-9 [published Online First: Epub Date]|.

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Nutritional rickets in Norway:

A nationwide register-based cohort study.

Journal: BMJ Open

Manuscript ID bmjopen-2016-015289.R1


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

Primary Subject Heading:

Nutrition and metabolism




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1 Section for Preventive Medicine and Epidemiology, Department of Community Medicine



2 Norwegian Institute of Public Health, Oslo, Norway


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Abstract:

Objectives: Poor vitamin D status has been reported to be highly prevalent in many non-




Design: Register-based cohort study.






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


(E55.9) 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.


period 2008-12. Nearly all children had a non-western immigrant background.

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• This register-based study covered the complete Norwegian population


• 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


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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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5

studies from the UK indicate that rickets might be an increasing problem among immigrant

children.11 12


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


population in the period 2008-2012.

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The national specialist health care register (Norwegian Patient Registry (NPR)) contains

information on all hospital admissions and outpatient contact in the specialised health






(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.



at the hospitals.


squared test. As a denominator we used the number of children aged 0-4 years in the


Results


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.




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.


- 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.


However, the numbers of cases were small and there was no overall statistically significant


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.


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)


Norway 3 (7.1)

Asia 25 (59.5)

Africa 12 (28.6)



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.



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


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


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



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


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.


collected the data. HEM analysed the data and drafted the article. All authors contributed in


and approved the final version. HEM is the guarantor.



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


Data sharing: No additional data are available.




explained.














(2013/2370/REK sør-øst D).

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References



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]



2005;59(1):57-63.



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.


Laegeforen 2001;121(6):715-8. [published Online First: 2001/04/11]



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]


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


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]


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]



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


sources and methods of case

ascertainment and control

selection. Give the rationale for

the choice of cases and controls

Cross-sectional study - Give the



of participants

(b) Cohort study - For matched

studies, give matching criteria

and number of exposed and

unexposed

Case-control study - For matched


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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Journal: BMJ Open

Manuscript ID bmjopen-2016-015289.R2


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

Primary Subject Heading:

Nutrition and metabolism




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1








1 Department of Community Medicine and Global Health, University of Oslo, P.O. Box 1130

Blindern, 0318, Oslo, Norway.


2 Domain for Mental and Physical Health, Norwegian Institute of Public Health, Oslo,

Norway


Corresponding author: Professor Haakon E. Meyer, Department of Community Medicine



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Abstract:

Objectives: Poor vitamin D status has been reported to be highly prevalent in many non-




Design: Register-based cohort study.






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


(E55.9) 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.


period 2008-12. Nearly all children had a non-western immigrant background.

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• This register-based study covered the complete Norwegian population


• 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


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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


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


population in the period 2008-2012.

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The national specialist health care register (Norwegian Patient Registry (NPR)) contains

information on all hospital admissions and outpatient contact in the specialised health






(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.



at the hospitals.


squared test. As a denominator we used the number of children aged 0-4 years in the


Results


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.




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.


- 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.


However, the numbers of cases were small and there was no overall statistically significant


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.


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)


Norway 3 (7.1)

Asia 25 (59.5)

Africa 12 (28.6)



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.



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


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


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



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


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.


collected the data. HEM analysed the data and drafted the article. All authors contributed in


and approved the final version. HEM is the guarantor.



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


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.




explained.














(2013/2370/REK sør-øst D).

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References



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]



2005;59(1):57-63.



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.


Laegeforen 2001;121(6):715-8. [published Online First: 2001/04/11]



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]


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


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]


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]



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


RECORD 6.1: The methods of study

population selection (such as codes or

Page 5 & 6

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of participants. Describe methods

of follow-up

Case-control study - Give 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



of participants

(b) Cohort study - For matched


and number of exposed and

unexposed

Case-control study - For matched


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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Documents

BMJ Open...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