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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.
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
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
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.
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