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Trends in the Diagnosis of

Vitamin D Deficiency
Emre Basatemur, MBBS, MRCPCH,a Laura Horsfall, PhD,b Louise Marston, PhD,b Greta Rait, MD,b Alastair Sutcliffe, PhDa

BACKGROUND: Vitamin D has attracted considerable interest in recent years, and health abstract
care providers have reported large increases in vitamin D test requests. However, rates
of diagnosis of vitamin D deficiency in clinical practice have not been investigated. We
examined trends in diagnosis of vitamin D deficiency in children in England over time, and
by sociodemographic characteristics.
METHODS: Cohort study using primary care records of 711788 children aged 0 to 17 years,
from the Health Improvement Network database. Incidence rates for diagnosis of vitamin
D deficiency were calculated per year between 2000 and 2014. Rate ratios exploring
differences by age, sex, ethnicity, and social deprivation were estimated using multivariable
Poisson regression.
RESULTS: The crude rate of vitamin D deficiency diagnosis increased from 3.14 per 100000
person-years in 2000 (95% confidence interval [CI], 1.317.54) to 261 per 100000
person-years in 2014 (95% CI, 241281). After accounting for changes in demographic
characteristics, a 15-fold (95% CI, 1021) increase in diagnosis was seen between 2008 and
2014. Older age (10 years), nonwhite ethnicity, and social deprivation were independently
associated with higher rates of diagnosis. In children aged <5 years, diagnosis rates were
higher in boys than girls, whereas in children aged 10 they were higher in girls.
CONCLUSIONS: There has been a marked increase in diagnosis of vitamin D deficiency in
children over the past decade. Future research should explore the drivers for this change in
diagnostic behavior and the reasons prompting investigation of vitamin D status in clinical
practice.

aPopulation, Policy and Practice Programme, UCL Institute of Child Health, London, United Kingdom; and WHATS KNOWN ON THIS SUBJECT: Vitamin D has
bResearch Department of Primary Care and Population Health, University College London, London, United attracted considerable interest in recent years, and
Kingdom health care providers have reported large increases
Dr Basatemur conceptualized and designed the study, conducted the analysis, interpreted the in vitamin D test requests. However, trends in the
data, drafted the initial manuscript, and wrote the nal manuscript; Dr Sutcliffe contributed diagnosis of vitamin D deciency in clinical practice
to the conception and design of the study, the interpretation of data, and critical revision of have not been investigated.
the manuscript; Drs Rait, Horsfall, and Marston contributed to the design of the study, the
WHAT THIS STUDY ADDS: There has been a marked
interpretation of data, and critical revision of the manuscript; and all authors approved the nal
version of the manuscript as submitted. increase in testing and diagnosis of vitamin D
deciency among English children over the past
DOI: 10.1542/peds.2016-2748
decade (15-fold between 2008 and 2014). Older age,
Accepted for publication Nov 29, 2016 nonwhite ethnicity, and social deprivation were
Address correspondence to Emre Basatemur, MBBS, MRCPCH, Population, Policy and Practice associated with higher rates of diagnosis.
Programme, UCL Institute of Child Health, 30 Guilford St, London WC1N 1EH, UK. E-mail: emre.
basatemur@ucl.ac.uk
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright 2017 by the American Academy of Pediatrics To cite: Basatemur E, Horsfall L, Marston L, et al. Trends
in the Diagnosis of Vitamin D Deficiency. Pediatrics.
FINANCIAL DISCLOSURE: The authors have indicated they have no nancial relationships relevant 2017;139(3):e20162748
to this article to disclose.

PEDIATRICS Volume 139, number 3, March 2017:e20162748 ARTICLE


Vitamin D has attracted considerable Improvement Network (THIN) vitamin D deficiency diagnosis in
clinical and academic interest over primary care database, which the first 3 months after registration,
the past 2 decades. Regional studies contains anonymized electronic therefore we excluded this period
and hospital case series in the health records of >11 million from observation for children
United Kingdom, United States, and patients from 639 UK general aged 1 year at registration. The
Australia have suggested an increase practices. The THIN cohort is broadly acceptable mortality recording and
in numbers of children presenting representative of the UK population acceptable computer usage criteria
with symptomatic complications of in terms of age, sex, prevalence of identify periods of incomplete use
vitamin D deficiency (rickets and medical conditions, and mortality of computerized systems in primary
hypocalcemia).13 Furthermore, rates.10 THIN includes data regarding care (eg, following transition
a large body of observational medical diagnoses, laboratory test from paper records), and are
research has stimulated debate results, medication prescriptions, and described elsewhere.12,13 Exit from
regarding the postulated role of sociodemographic characteristics. the observation period for each
vitamin D in modifying the risk Diagnoses are recorded by using a individual was the earliest of the
of developing various diseases hierarchical coding system called date they transferred to a different
beyond its established function Read codes.11 Diagnoses made in practice, the date the practice
in bone metabolism and calcium secondary care may be coded from stopped contributing data to THIN,
homeostasis.4 discharge summaries and outpatient the midpoint of their 18th year after
As vitamin D has attracted increasing letters. A subset of THIN practices birth, the date they died, December
attention, hospitals in Australia and in England (n = 156) are linked 31, 2014, or the date of the earliest
the United Kingdom have reported to patient-level Hospital Episode record meeting the case definition for
a surge in test requests.5,6 Annual Statistics (HES) data, available up diagnosis of vitamin D deficiency.
primary care spending on vitamin D to March 31, 2012. HES contains
prescriptions in England increased records of all hospital care episodes Outcome
from 28 million to 92 million in England, although clinical
Diagnosis of vitamin D deficiency
between 2004 and 2014.7,8 Given diagnoses are recorded only for
was defined as a record of any 1 of
the high prevalence of biochemical inpatient admissions. We used linked
the following criteria in the THIN
vitamin D deficiency in the general HES data to augment information
medical record: (1) a Read code
population, and uncertainty regarding ethnicity.
related to vitamin D deficiency or
that treatment of asymptomatic rickets; (2) prescription of vitamin D
individuals leads to improved Study Population (calciferol) at a treatment dose (see
health outcomes, some authors have later in this article); or (3) a serum
questioned whether the large growth Children aged 0 to 17 years
25-hydroxyvitamin D (25-OH-D)
in testing may result in unnecessary registered with a THIN practice
test result <25 nmol/L (<10 ng/mL).
health care costs and potential linked to HES, at any point between
Read code lists were developed by
overdiagnosis.4,5,9 However, there has January 1, 2000, and December 31,
using published guidelines.15 General
not been any empirical investigation 2014, were included. Children with
practitioners do not always record
of rates of diagnosis of vitamin D chronic renal disease, liver disease,
diagnoses by using Read codes,
deficiency in clinical practice, and or conditions associated with
instead entering data as free text
trends in testing and treatment gastrointestinal malabsorption were
that is not routinely accessible.16
have not been examined in children excluded. The start of the observation
The use of Read codes alone to
specifically. Using a large, population- period for each child was the latest of
identify cases can result in case
based cohort of children in England, the date of practice registration (plus
underascertainment, therefore we
we determined longitudinal trends 3 months for children aged 1 year
also included prescription and test
in rates of vitamin D deficiency at registration), the date the practice
records in the case definition.
diagnosis over the past 15 years, met 2 predefined quality indicators
and explored differences by for electronic data recording To capture prescriptions of
sociodemographic characteristics. (acceptable mortality recording and cholecalciferol or ergocalciferol
acceptable computer usage),12,13 and issued for the treatment of
January 1, 2000. Diagnoses recorded established deficiency, as opposed
METHODS shortly after patient registration to prophylactic supplementation
can represent historical information or maintenance therapy, we used
Data Source transferred from medical records the following dose thresholds: (1)
We conducted a dynamic (open) rather than incident events.14 We 1500 U per day if age <6 months;
cohort study by using The Health observed greater recording of (2) 3000 U per day if age 6 months

2 BASATEMUR et al
to 12 years; (3) 5000 U per day if Children were linked to women Committee in 2003. This study was
age >12 years; (4) one-off (stoss) sharing identical household approved by CSD Medical Researchs
dose of 100000 U at any age. These identifiers with a pregnancy or Scientific Review Committee.
thresholds are higher than doses delivery record in which the expected
recommended for prophylaxis of or recorded date of delivery was in
between 400 and 1000 U per day,17 proximity to the childs month of RESULTS
and represent half of the British birth. Linked mothers were excluded
The study cohort contained 711788
National Formulary for Children if children matched to several women
children from 156 practices, of whom
treatment doses (3000 U per day (0.3% of linked children), or >20
2918 were diagnosed with vitamin D
if age 16 months, 6000 U per people shared the same household
deficiency between 2000 and 2014.
day if age 6 months to 12 years, identifier (likely to represent an
Median observation time was 3.9
and 10000 U per day if age >12 apartment block).
years (interquartile range 1.58.0).
years).18 A range of alternative
Statistical Analysis Descriptive characteristics are shown
dosage thresholds were explored
in Table 1.
by using sensitivity analyses. The Crude incidence rates were
threshold of <25 nmol/L for 25-OH-D calculated for each year between Analysis of time trends showed a
tests represents deficiency in UK 2000 and 2014. Differences in rates marked increase in diagnosis of
guidance.17,19 by sex, age group (<5, 59, 1014, vitamin D deficiency after 2007
and 1517 years), ethnicity, IMD, (Fig 1) (Supplemental Table 3).
Sensitivity analysis was performed
The crude incidence rate increased
additionally including International and calendar year were examined
from 3.14 per 100000 person-years
Classification of Diseases, 10th by using multivariable Poisson
at risk in 2000 (95% confidence
Revision (ICD-10) codes for vitamin regression. Multivariable analysis
was limited to follow-up between interval [CI], 1.317.54) to 261
D deficiency and rickets from
2008 and 2014, due to small numbers per 100000 person-years at risk
HES inpatient records in the case
of cases per year before 2008. in 2014 (95% CI, 241281). After
definition. This analysis was limited
Interactions between explanatory accounting for temporal changes in
to follow-up to December 31, 2011.
variables were examined, and sociodemographic factors, a 15-fold
Covariates interaction terms retained in increase in diagnosis (95% CI, 1021-
the final model if their inclusion fold) was seen between 2008 and
Socioeconomic position (SEP) was 2014 (Table 2).
resulted in both a qualitative change
measured by using the 2004 Index
in parameter rate ratios and a Supplemental Fig 2 shows the
of Multiple Deprivation (IMD), an
significant likelihood ratio test (P < overlap between cases identified
area-level indicator available in
.05). The multivariable model was from diagnosis codes, prescription
national quintiles.20 Recording of
run with and without inclusion of the records, and 25-OH-D test records.
ethnicity in primary care databases
general practice as a random effect to Results did not differ substantially in
is incomplete, but can be augmented
account for data clustering. sensitivity analyses using alternative
by linkage with HES data.21 Ethnicity
was grouped into the 2001 UK Missing data for ethnicity and IMD dosage thresholds for calciferol
Census 5-category classification were handled by using complete prescriptions (Supplemental Fig
(white, mixed, Asian, black, or other). cases in the main analysis, and 3), or addition of ICD-10 diagnosis
As consistency of ethnicity recording by using multivariable multiple codes from HES inpatient records
is greater in primary care data imputation for sensitivity analysis.24 (Supplemental Fig 4), in the case
than HES, ethnicity was assigned The imputation model included all definition.
from THIN where available, and variables in the substantive model,
In multivariable analysis, older
supplemented with HES data.21 For plus auxiliary variables coding
age, nonwhite ethnicity, and
individuals with multiple ethnicity geographical region, and the ethnicity
socioeconomic deprivation were
categories recorded (0.3% of the and IMD distributions of practice
associated with higher rates of
cohort), the most frequently recorded patients and of individuals sharing
vitamin D deficiency diagnosis (Table
category was used. identical household identifiers.
2). There was an interaction between
Analyses were performed by using
For children with missing ethnicity, sex and age; among children aged
Stata 13.1 (Stata Corp, College
maternal ethnicity was taken as 10 years, diagnosis rates were
Station, TX).
a proxy measure for the child if higher in girls, whereas among
available. Child-mother linkage was The THIN data collection was children aged <5 years, they were
performed by using similar methods approved by the NHS South-East higher in boys (Supplemental Fig 5).
to previous THIN studies.22,23 Multicentre Research Ethics No sex difference was seen in

PEDIATRICS Volume 139, number 3, March 2017 3


children aged 5 to 9 years. Although TABLE 1 Descriptive Characteristics of the Study Cohort (n = 711 788)
the magnitude of the effects of Characteristic Value
ethnicity and SEP were attenuated Age at entry to follow-up, y, median (IQR) 4.1 (0.4010.5)
after accounting for clustering by Sex, n (%)
practice, they remained strongly Boys 366 378 (51.5)
associated with the outcome (Table Girls 345 410 (48.5)
Ethnicity, n (%)a
2). There was a moderate proportion
White 491 962 (69.1)
of missing data for ethnicity Asian or Asian British 34 521 (4.9)
(12.7%) and IMD (8.3%). The Black or black British 24 797 (3.5)
results of analyses by using multiple Mixed 15 558 (2.2)
imputation were similar to the Chinese or other ethnic group 13 443 (1.9)
Missing 131 507 (18.5)
main analyses using complete cases
IMD quintile, n (%)
(Supplemental Table 4). 1 (least deprived) 158 866 (22.3)
2 134 765 (18.9)
3 138 264 (19.4)
DISCUSSION 4 136 498 (19.2)
5 (most deprived) 95 656 (13.4)
In this large representative cohort Missing 47 739 (6.7)
of English children, there was a IQR, interquartile range.
15-fold increase in the diagnosis a Ethnicity data were available from the childs THIN or HES record for 67.7% of the cohort, and maternal ethnicity was

of vitamin D deficiency between available as a proxy measure for 13.8%.

2008 and 2013, after which rates


plateaued. Sociodemographic factors
independently associated with higher
rates of diagnosis included nonwhite
ethnicity, socioeconomic deprivation,
older age, female sex in children aged
10 years, and male sex in children
aged <5 years.

Comparison With Other Studies


To the best of our knowledge, this
is the first study to report national
estimates for overall rates of
diagnosis of vitamin D deficiency
in clinical practice, in the United
Kingdom or internationally.
However, a number of studies
have investigated the incidence of
clinical complications of vitamin D
deficiency in children. The annual
incidence of symptomatic vitamin D
FIGURE 1
deficiency presenting to pediatricians Time trends in the diagnosis of vitamin D deciency in children, 2000 to 2014. Crude incidence rates
was reported to be 7.5 per 100000 are shown, with 95% condence limits represented by the dashed lines.
children aged 0 to 5 years in the
West Midlands region of England, Asian and black compared with of vitamin D supplements.3133 The
and between 2.2 and 2.9 per white children, which was expected magnitude of the effects of ethnicity
100000 children in New Zealand,25 given that they have lower vitamin D and SEP were attenuated after
Denmark,26 and Canada.27 The annual levels and higher risk of symptomatic accounting for clustering by practice.
incidence of hypocalcemic seizures deficiency.2830 Diagnosis also was One explanation for this observation
secondary to vitamin D deficiency more frequent in children from is that the sociodemographic
was 3.49 per million children age 0 to deprived backgrounds. Low SEP is characteristics of a practice
15 years in the United Kingdom.28 associated with suboptimal vitamin population may have contextual
Vitamin D deficiency was diagnosed D status in children independent effects on clinicians diagnostic
considerably more frequently in of ethnicity, and with reduced use behavior, separate from the influence

4 BASATEMUR et al
of individual patients characteristics. TABLE 2 Associations Between Sociodemographic Factors and Diagnosis of Vitamin D Deciency
General practitioners working in (n = 414 182)
practices with more deprived and Characteristic Single-level Model Multilevel Model
ethnically diverse populations may Adjusted IRRa Pb Adjusted IRRa (95% Pb
be more likely to test for vitamin D (95% CI) CI)
deficiency even in low-risk patients, Sex, stratied by age group, y <.001 <.001
because of increased awareness of 04 Boys 1 1
the condition. Possible explanations Girls 0.73 (0.570.93) 0.72 (0.570.92)
for greater diagnosis in older 59 Boys 1 1
Girls 1.06 (0.871.29) 1.04 (0.861.27)
compared with younger children may
1014 Boys 1 1
include more frequent presentation Girls 1.97 (1.712.27) 1.97 (1.712.27)
to health care services with chronic 1517 Boys 1 1
pain or other medically unexplained Girls 2.60 (2.183.11) 2.65 (2.213.16)
symptoms,34,35 and higher thresholds Age group, y, stratied by sex <.001 <.001
Boys 04 1 1
for requesting vitamin D tests in 59 1.22 (0.991.50) 1.20 (0.981.48)
younger children in primary care 1014 2.22 (1.832.70) 2.19 (1.802.65)
due to the practical challenges of 1517 2.39 (1.932.96) 2.36 (1.902.93)
phlebotomy. Among older children, Girls 04 1 1
factors contributing to higher 59 1.77 (1.412.23) 1.73 (1.372.18)
1014 6.00 (4.917.34) 5.95 (4.867.27)
diagnosis rates in girls compared 1517 8.52 (6.9310.5) 8.61 (7.0010.6)
with boys may include higher overall Ethnicityc <.001 <.001
primary care consultation rates,36 White 1 1
and the influence of cultural dress in Asian or Asian British 22.4 (20.124.9) 7.98 (6.989.13)
some communities. Black or black British 14.2 (12.516.2) 5.47 (4.706.37)
Mixed 5.64 (4.527.03) 2.99 (2.383.76)
Chinese or other ethnic group 8.91 (7.3810.8) 3.63 (2.964.45)
Strengths and Limitations IMD quintile <.001 <.001
1 (least deprived) 1 1
Study strengths include the large 2 1.98 (1.632.41) 1.34 (1.071.67)
3 2.40 (2.002.88) 1.41 (1.121.77)
sample size, and use of a prospectively
4 2.67 (2.233.20) 1.63 (1.292.05)
collected database of health care 5 (most deprived) 3.54 (2.964.24) 1.96 (1.522.53)
records representative of real-life Calendar year <.001 <.001
clinical practice. As the THIN cohort 2008 1 1
has a similar age and sex distribution 2009 2.20 (1.453.35) 2.19 (1.443.34)
2010 3.87 (2.625.71) 3.66 (2.485.40)
to the general population, our results
2011 6.61 (4.559.60) 6.28 (4.329.12)
should be broadly generalizable 2012 12.7 (8.8318.2) 12.1 (8.4317.4)
to England as a whole. However, it 2013 14.7 (10.221.1) 14.1 (9.8520.3)
is somewhat overrepresentative 2014 14.7 (10.221.2) 15.7 (10.922.6)
of individuals from more affluent Results of multivariable Poisson regression models of rates of incident diagnosis of vitamin D deciency. Missing data are
areas,10 therefore the observed handled using complete case analysis. IRR, incidence rate ratio.
a Adjusted for all variables listed in the table, including an interaction term between age and sex (likelihood ratio test for
diagnosis rates may underestimate interaction P < .001). The multilevel model additionally included the general practice as a random effect.
true national rates to an extent. The b P values from likelihood ratio tests comparing nested models.
c Ethnicity data were taken from the childs THIN or HES record for 84.6% of children. Maternal ethnicity was used as a
inclusion of vitamin D prescriptions
proxy measure for the remaining 15.4%.
and tests in the case definition allowed
identification of children in whom the
diagnosis was not recorded by using by using linked HES data, and taking did not substantially influence the
Read codes, helping to minimize case maternal ethnicity as a proxy measure findings under the missing at random
underascertainment. However, some where the childs ethnicity was assumption.24 Data were not available
cases still may have been missed, for not available. However, the risk of regarding other factors, such as BMI,
example children who were diagnosed misclassification will be greater where that are associated with vitamin D
and received their full course of maternal ethnicity was used. Although status and may influence testing in
treatment in secondary care, if the there was a moderate proportion clinical practice.
diagnosis was not subsequently of missing data for ethnicity and
entered into the primary care record IMD, complete case analysis and Clinical Implications
from hospital correspondence. Missing multiple imputation gave very similar Given the magnitude of the
data for ethnicity were minimized results, suggesting that missing data increase in diagnosis of vitamin D

PEDIATRICS Volume 139, number 3, March 2017 5


deficiency over a short period, it is Biochemical vitamin D deficiency, or the presence of disorders that can
unlikely to be explained by changes as defined by current guidelines, interfere with vitamin D metabolism.
in population vitamin D levels, has a high prevalence in the general Testing outside of this context requires
incidence of clinical complications of population, and testing in any patient careful consideration of whether
vitamin D deficiency, or population group is likely to identify a significant vitamin D deficiency is related to the
demographics. It is likely that the rise proportion of abnormal results.4 childs presentation or is a coincidental
in testing and treatment has been Although the benefits of treatment with finding. The interpretation of 25-OH-D
driven by increased awareness and pharmacological doses of vitamin D results is further complicated by the
consideration of vitamin D deficiency are clear in children with symptomatic inconsistency of commonly used
among clinicians. There are several deficiency, there is no evidence that laboratory assays and the limited
possible contributing factors for testing and treating asymptomatic evidence base underpinning the
this: clinician education through the individuals results in improved health threshold values used to define
development of clinical guidelines outcomes compared with prophylaxis deficiency.40,43,44,53 At the population
and dissemination of Department of with low-dose supplements.4,40 level, unnecessary testing can result
Health recommendations concerning Although numerous observational in avoidable costs from the tests
vitamin D supplementation for high- studies have reported associations themselves and from prescription
risk groups,37 and wide reporting in between low serum 25-OH-D of pharmacological doses of vitamin
the lay media and medical literature levels and increased risk of various D. From a public health perspective,
of research suggesting a link between nonmusculoskeletal diseases, their resources may be better used if
vitamin D status and numerous results are subject to reverse causality, directed toward improving the
nonmusculoskeletal health outcomes.38 confounding and bias, and findings currently low uptake of inexpensive
The data available did not permit from randomized controlled trials are vitamin D supplements, recommended
exploration of the clinical indications generally null or inconsistent.5,4042 by the UK Scientific Advisory
prompting investigation of vitamin The UK Scientific Advisory Committee Committee on Nutrition and the
D status. We do not know how much on Nutrition, US Institute of Medicine, American Academy of Pediatrics for
the increase in diagnosis is being and European Society for Pediatric the prevention of deficiency,
driven by improved recognition Gastroenterology, Hepatology, and by pregnant women and young
of children with clinical features Nutrition have concluded that there children,54,55 particularly among high-
consistent with symptomatic vitamin is insufficient evidence of a causative risk ethnic groups.48,56
D deficiency, or by testing in other role for vitamin D deficiency in the
clinical situations (for example, etiology of nonmusculoskeletal health CONCLUSIONS
screening of asymptomatic children, outcomes.40,43,44 Furthermore, there
There has been a marked increase in
or testing prompted by the presence is limited evidence that optimizing
the testing and diagnosis of vitamin
of nonmusculoskeletal diseases vitamin D status is beneficial for the
D deficiency in children in England
that have been linked to vitamin D management of these conditions once
over the past decade. Future research
deficiency, such as diabetes, atopic they have developed, for example
should explore the drivers for this
disorders, and infectious diseases). in improving glycemic control in
change in clinicians diagnostic
Sharp increases in vitamin D diabetes or reducing disease severity
behavior, and the reasons prompting
test requests in adults have been in asthma.45,46
investigation of vitamin D status in
reported in Australia and the United The UK National Institute for Health clinical practice.
Kingdom over the past decade.5,6 and Care Excellence, US Endocrine
The introduction of a defined set of Society, and European Society for
clinical criteria permitting 25-OH-D Pediatric Endocrinology recommend ABBREVIATIONS
testing in Alberta, Canada, in 2015 that vitamin D status should not
25-OH-D:25-hydroxyvitamin D
resulted in a 92% reduction in the be checked as a routine screening
CI:confidence interval
number of tests ordered, and annual test,4749 a position supported by
HES:Hospital Episode Statistics
cost savings of almost US$4 million.39 the Choosing Wisely campaigns in
ICD-10:International
This suggests that, before the North America and Australia.5052
Classification of Diseases,
intervention, most vitamin D tests in Shaw and Mughal4 proposed a
10th Revision
adults were performed in individuals set of clinical indications for the
IMD:Index of multiple
without specific clinical features or measurement of 25-OH-D in children
deprivation
risk factors for deficiency. Further that relate to symptoms and signs
SEP:socioeconomic position
studies are required to explore the directly attributable to vitamin D
THIN:The Health Improvement
reasons for investigation of vitamin D deficiency, biochemical or radiologic
Network
status in children in clinical practice. evidence of metabolic bone disease,

6 BASATEMUR et al
FUNDING: This study was funded by a Doctoral Research Fellowship grant (DRF-201306037) from the UK National Institute for Health Research (NIHR), and
was supported by the NIHR Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. This
article presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the
Department of Health.
POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conicts of interest to disclose.

REFERENCES
1. Ahmed SF, Franey C, McDevitt H, mortality rates. Inform Prim Care. 19. Arundel P, Ahmed SF, Allgrove J, et al;
et al. Recent trends and clinical 2011;19(4):251255 British Paediatric and Adolescent
features of childhood vitamin D Bone Group. British Paediatric and
11. Booth N. What are the Read Codes?
deciency presenting to a childrens Adolescent Bone Groups position
Health Libr Rev. 1994;11(3):
hospital in Glasgow. Arch Dis Child. statement on vitamin D deciency.
177182
2011;96(7):694696 BMJ. 2012;345:e8182
12. Maguire A, Blak BT, Thompson M.
2. Thacher TD, Fischer PR, Tebben PJ, 20. Noble M, Wright G, Dibben C, et al. The
The importance of dening periods
et al. Increasing incidence of nutritional English Indices of Deprivation 2004.
of complete mortality reporting for
rickets: a population-based study in London, UK: Ofce of the Deputy Prime
research using automated data from
Olmsted County, Minnesota. Mayo Clin Minister; 2004. Available at: http://
primary care. Pharmacoepidemiol
Proc. 2013;88(2):176183 webarchive.nationalarchives.gov.uk/
Drug Saf. 2009;18(1):7683
20100410180038/www.communities.
3. Robinson PD, Hgler W, Craig ME, et al.
13. Horsfall L, Walters K, Petersen I. gov.uk/archived/publications/
The re-emerging burden of rickets: a
Identifying periods of acceptable communities/indicesdeprivation.
decade of experience from Sydney.
computer usage in primary Accessed May 26, 2016
Arch Dis Child. 2006;91(7):564568
care research databases. 21. Mathur R, Bhaskaran K, Chaturvedi
4. Shaw NJ, Mughal MZ. Vitamin D and Pharmacoepidemiol Drug Saf. N, et al. Completeness and usability
child health: part 2 (extraskeletal 2013;22(1):6469 of ethnicity data in UK-based primary
and other aspects). Arch Dis Child.
14. Lewis JD, Bilker WB, Weinstein care and hospital databases. J Public
2013;98(5):368372
RB, Strom BL. The relationship Health (Oxf). 2014;36(4):684692
5. Sattar N, Welsh P, Panarelli M, Forouhi between time since registration and 22. Petersen I, McCrea RL, Sammon CJ,
NG. Increasing requests for vitamin measured incidence rates in the et al. Risks and benets of psychotropic
D measurement: costly, confusing, General Practice Research Database. medication in pregnancy: cohort
and without credibility. Lancet. Pharmacoepidemiol Drug Saf. studies based on UK electronic
2012;379(9811):9596 2005;14(7):443451 primary care health records. Health
6. Bilinski K, Boyages S. Evidence of 15. Dav S, Petersen I. Creating medical Technol Assess. 2016;20(23):1176
overtesting for vitamin D in Australia: and drug code lists to identify 23. Meeraus WH, Petersen I, Gilbert
an analysis of 4.5 years of Medicare cases in primary care databases. R. Association between antibiotic
Benets Schedule (MBS) data. BMJ Pharmacoepidemiol Drug Saf. prescribing in pregnancy and cerebral
Open. 2013;3(6):e002955 2009;18(8):704707 palsy or epilepsy in children born at
7. Health and Social Care Information 16. Ford E, Nicholson A, Koeling R, et al. term: a cohort study using the health
Centre. Prescription Cost Analysis - Optimising the use of electronic health improvement network. PLoS One.
England 2004. HSCIC, 2005. Available at: records to estimate the incidence 2015;10(3):e0122034
www.hscic.gov.uk/catalogue/PUB02249. of rheumatoid arthritis in primary 24. White IR, Royston P, Wood AM. Multiple
Accessed May 26, 2016 care: what information is hidden in imputation using chained equations:
8. Health and Social Care Information free text? BMC Med Res Methodol. issues and guidance for practice. Stat
Centre. Prescription Cost Analysis - 2013;13:105 Med. 2011;30(4):377399
England 2014. HSCIC, 2015. Available at: 17. Pearce SHS, Cheetham TD. Diagnosis 25. Wheeler BJ, Dickson NP, Houghton LA,
www.hscic.gov.uk/catalogue/PUB17274. and management of vitamin D Ward LM, Taylor BJ. Incidence and
Accessed May 26, 2016 deciency. BMJ. 2010;340:b5664 characteristics of vitamin D deciency
9. Bilinski K, Boyages S. The rise and 18. Paediatric Formulary Committee. BNF rickets in New Zealand children: a
rise of vitamin D testing. BMJ. for Children. London, UK: BMJ Group, New Zealand Paediatric Surveillance
2012;345:e4743 Pharmaceutical Press, and RCPCH Unit study. Aust N Z J Public Health.
10. Blak BT, Thompson M, Dattani H, Publications, December 2016. Available 2015;39(4):380383
Bourke A. Generalisability of The at: www.evidence.nhs.uk/formulary/ 26. Beck-Nielsen SS, Brock-Jacobsen
Health Improvement Network bnfc/current/9-nutrition-and-blood/96- B, Gram J, Brixen K, Jensen TK.
(THIN) database: demographics, vitamins/964-vitamin-d/ergocalciferol. Incidence and prevalence of
chronic disease prevalence and Accessed January 13, 2017 nutritional and hereditary rickets in

PEDIATRICS Volume 139, number 3, March 2017 7


southern Denmark. Eur J Endocrinol. 37. Department of Health. Vitamin D: an 48. National Institute for Health and Care
2009;160(3):491497 essential nutrient for all but who Excellence. Vitamin D: increasing
27. Ward LM, Gaboury I, Ladhani M, is at risk of vitamin D deciency? supplement use among at-risk groups.
Zlotkin S. Vitamin D-deciency rickets Important information for healthcare NICE guideline (PH56). NICE, 2014.
among children in Canada. CMAJ. professionals. London, UK: Central Available at: https://www.nice.org.uk/
2007;177(2):161166 Ofce of Information for the guidance/ph56. Accessed May 26, 2016
Department of Health, December 2009
28. Basatemur E, Sutcliffe A. Incidence of 49. Holick MF, Binkley NC, Bischoff-
hypocalcemic seizures due to vitamin 38. Harvey NC, Cooper C. Vitamin D: Ferrari HA, et al; Endocrine
D deciency in children in the United some perspective please. BMJ. Society. Evaluation, treatment, and
Kingdom and Ireland. J Clin Endocrinol 2012;345:e4695 prevention of vitamin D deciency: an
Metab. 2015;100(1):E91E95 39. Ferrari R, Prosser C. Testing vitamin Endocrine Society clinical practice
D levels and choosing wisely. JAMA guideline. J Clin Endocrinol Metab.
29. Absoud M, Cummins C, Lim MJ, 2011;96(7):19111930
Wassmer E, Shaw N. Prevalence and Intern Med. 2016;176(7):10191020
predictors of vitamin D insufciency 40. The Scientic Advisory Committee 50. ABIM Foundation. Choosing Wisely.
in children: a Great Britain on Nutrition. Vitamin D and Health. Available at: www.choosingwisely.
population based study. PLoS One. Public Health England, 2016. Available org/clinician-lists/american-society-
2011;6(7):e22179 at: https://www.gov.uk/government/ clinical-pathology-population-based-
publications/sacn-vitamin-d-and- screening-for-vitamin-d-deciency/.
30. Callaghan AL, Moy RJD, Booth IW,
health-report. Accessed August 19, Accessed May 26, 2016
Debelle G, Shaw NJ. Incidence of
symptomatic vitamin D deciency. Arch 2016 51. Canadian Medical Association.
Dis Child. 2006;91(7):606607 41. Reid IR. What diseases are causally Choosing Wisely Canada. Available
linked to vitamin D deciency? Arch Dis at: www.choosingwiselycanada.
31. Tolppanen AM, Fraser A, Fraser
Child. 2016;101(2):185189 org/recommendations/pathology/.
WD, Lawlor DA. Risk factors for
Accessed May 26, 2016
variation in 25-hydroxyvitamin D3 42. Theodoratou E, Tzoulaki I, Zgaga L,
and D2 concentrations and vitamin D Ioannidis JP. Vitamin D and multiple 52. NPS Medicinewise. Choosing
deciency in children. J Clin Endocrinol health outcomes: umbrella review Wisely Australia. Available at:
Metab. 2012;97(4):12021210 of systematic reviews and meta- www.choosingwisely.org.au/
32. Turer CB, Lin H, Flores G. Prevalence of analyses of observational studies recommendations/rcpa. Accessed May
vitamin D deciency among overweight and randomised trials. BMJ. 26, 2016
and obese US children. Pediatrics. 2014;348:g2035
53. Misra M, Pacaud D, Petryk A, Collett-
2013;131(1). Available at: www. 43. Braegger C, Campoy C, Colomb V, et al; Solberg PF, Kappy M; Drug and
pediatrics.org/cgi/content/full/131/1/ ESPGHAN Committee on Nutrition. Therapeutics Committee of the Lawson
e152 Vitamin D in the healthy European Wilkins Pediatric Endocrine Society.
33. Millette M, Sharma A, Weiler H, Sheehy paediatric population. J Pediatr Vitamin D deciency in children and
O, Brard A, Rodd C. Programme to Gastroenterol Nutr. 2013;56(6):692701 its management: review of current
provide Quebec infants with free 44. Institute of Medicine. Dietary Reference knowledge and recommendations.
vitamin D supplements failed to Intakes for Calcium and Vitamin Pediatrics. 2008;122(2):398417
encourage participation or adherence. D. Washington, DC: The National 54. Perrine CG, Sharma AJ, Jefferds MED,
Acta Paediatr. 2014;103(10):e444e449 Academies Press; 2011 Serdula MK, Scanlon KS. Adherence
34. Roth-Isigkeit A, Thyen U, Stven H, 45. Riverin BD, Maguire JL, Li P. Vitamin D to vitamin D recommendations
Schwarzenberger J, Schmucker P. supplementation for childhood asthma: among US infants. Pediatrics.
Pain among children and adolescents: a systematic review and meta-analysis. 2010;125(4):627632
restrictions in daily living and PLoS One. 2015;10(8):e0136841 55. Moy RJ, McGee E, Debelle GD, Mather
triggering factors. Pediatrics. 46. Seida JC, Mitri J, Colmers IN, et al. I, Shaw NJ. Successful public health
2005;115(2). Available at: www. Clinical review: Effect of vitamin action to reduce the incidence of
pediatrics.org/cgi/content/full/115/2/ D3 supplementation on improving symptomatic vitamin D deciency. Arch
e152 glucose homeostasis and preventing Dis Child. 2012;97(11):952954
35. Eminson DM. Medically unexplained diabetes: a systematic review and 56. Wagner CL, Greer FR; American
symptoms in children and adolescents. meta-analysis. J Clin Endocrinol Metab. Academy of Pediatrics Section on
Clin Psychol Rev. 2007;27(7):855871 2014;99(10):35513560 Breastfeeding; American Academy of
36. Wang Y, Hunt K, Nazareth I, Freemantle 47. Munns CF, Shaw N, Kiely M, et al. Pediatrics Committee on Nutrition.
N, Petersen I. Do men consult less Global consensus recommendations Prevention of rickets and vitamin
than women? An analysis of routinely on prevention and management of D deciency in infants, children,
collected UK general practice data. nutritional rickets. J Clin Endocrinol and adolescents. Pediatrics.
BMJ Open. 2013;3(8):e003320 Metab. 2016;101(2):394415 2008;122(5):11421152

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