Vitamin D Deficiency in Critically Ill Children

Published online August 6, 2012
Kate Madden, MDa,b, Henry A. Feldman, PhDc,d,e, Ellen M. Smith, BSa, Catherine M. Gordon, MD, MScc,e,f, Shannon M. Keisling, BAa, Ryan M. Sullivan, RNa, Bruce W. Hollis, PhDg, Anna A. Agan, BAa, and Adrienne G. Randolph, MD, MSca,b
A Division of Critical Care Medicine, Department of Anesthesia, Perioperative and Pain Medicine,
C Division of Endocrinology,
D Clinical Research Program, and
F Division of Adolescent and Young Adult Medicine, Department of Pediatrics, Children’s Hospital Boston, Boston, Massachusetts;
Departments of B Anaesthesia and
E Pediatrics, Harvard Medical School, Boston, Massachusetts; and
G Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina

OBJECTIVE: Vitamin D influences cardiovascular and immune function.
We aimed to establish the prevalence of vitamin D deficiency in critically ill children and identify factors influencing admission 25-hydroxy vitamin D (25(OH)D) levels.
We hypothesized that levels would be lower with increased illness severity and in children with serious infections.

METHODS: Participants were 511 severely or critically ill children admitted to the PICU from November 2009 to November 2010.
Blood was collected near PICU admission and analyzed for 25(OH)D concentration by using Diasorin radioimmunoassay.

RESULTS: We enrolled 511 of 818 (62.5%) eligible children.
The median 25(OH)D level was 22.5 ng/mL; 40.1% were 25(OH)D deficient (level <20 ng/mL).

In multivariate analysis, age and race were associated with 25(OH)D deficiency; summer season, vitamin D supplementation, and formula intake were protective;

25(OH)D levels were not lower in the 238 children (46.6%) admitted with a life-threatening infection, unless they had septic shock (n = 51, 10.0%) (median 25(OH)D level 19.2 ng/mL; P = .0008).

After adjusting for factors associated with deficiency, lower levels were associated with higher admission day illness severity (odds ratio 1.19 for a 1-quartile increase in Pediatric Risk of Mortality III score per 5 ng/mL decrease in 25(OH)D, 95% confidence interval 1.10–1.28; P < .0001).

CONCLUSIONS: We found a high rate of vitamin D deficiency in critically ill children. Given the roles of vitamin D in bone development and immunity, we recommend screening of those critically ill children with risk factors for vitamin D deficiency and implementation of effective repletion strategies.
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Summary by Vitamin D Life

40% of critically ill children less than 20 ng
5 ng less vitamin D associated with illness severity increase by 20%
Notice that they factor out race . Children with dark skins almost always have much lower levels of vitamin D (dark skin is a natural sunscreen)
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The Association of Vitamin D Status With Pediatric Critical Illness

J. Dayre McNally, MD, PhDa,b, Kusum Menon, MD, MSca,b, Pranesh Chakraborty, MDb,c, Lawrence Fisher, BSc, ARTb,c, Kathryn A. Williams, MScb, Osama Y. Al-Dirbashi, PhDb,c, Dermot R. Doherty, MD, MB, BCh, BAOa,b,d,e, and on behalf of the Canadian Critical Care Trials Group
A Division of Critical Care, Department of Pediatrics, and
D Department of Anesthesia, Faculty of Medicine, University of Ottawa, Children’s Hospital of Eastern Ontario, Canada;
B Research Institute and
C Ontario Newborn Screening Laboratory, Children’s Hospital of Eastern Ontario, Canada; and
E University College, Dublin, Ireland

OBJECTIVES: Vitamin D is a pleiotropic hormone important for the proper functioning of multiple organ systems. It has been hypothesized that vitamin D deficiency could contribute to or worsen outcomes in critical illness. The study objective was to determine the prevalence of vitamin D deficiency, risk factors for its presence, and potential association with clinically relevant outcomes in critically ill children.

METHODS: A prospective cohort study, conducted from 2005 to 2008 in 6 tertiary-care PICUs in Canada. Data and biological samples from 326 critically ill children up to 17 years of age were available for analysis. Total serum 25 hydroxyvitamin D or 25(OH)D was measured by using liquid chromatography-mass spectrometry.

RESULTS: The prevalence of 25(OH)D <50 nmol/L was 69% (95% confidence interval, 64–74), and 23% (95% confidence interval, 19–28) for 25(OH)D between 50 to 75 nmol/L. Lower levels were associated with hypocalcemia, catecholamine utilization, and significant fluid bolus administration.

Vitamin D deficiency was independently associated with a longer PICU length of stay (+1.92 days, P = .03) and increasing severity of illness as determined by the Pediatric Risk of Mortality score with every additional point increasing the likelihood of being vitamin D deficient by 8% (P = .005).

CONCLUSIONS: This study provides evidence that vitamin D deficiency is both common among critically ill children and associated with greater severity of critical illness. Further research will determine whether targeted vitamin D supplementation or rapid restoration will improve outcome.
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Summary by Vitamin D Life

69% < 20 ng of vitamin D and 1.9 days longer in hospital
92% < 30 ng of vitamin D
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Article with an interesting title in the same issue has no abstract

Vitamin D Deficiency in Critically Ill Children: A Roadmap to Interventional Research

Abrams, et al. Pediatrics peds.2012-1752

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See also Vitamin D Life

• All items in category infant/child and vitamin D 606 items
• All items in category youth and vitamin D 148 items
• All items in category surgery/trauma and vitamin D 278 items
• Day care vitamin D grant being offered in the UK – July 2012
• Child Bone health – (incorrect) recommendations by US Pediatric and Bone Health groups – Sept 2014
  - this later paper in the same journal concluded that screening is never cost-effective
• UK pediatricians have a lot to learn about vitamin D – May 2012 which has the following
  Identify additional groups of children who are also at high risk, not just dark skin (e.g. excess fat)
  Test for a rare allergic reaction to vitamin D before giving high doses.
  Dose size should increase with the number of high risk categories a child is in
  Also provide some cofactors, not just vitamin D
  Followup with maintenance doses after the loading dose.
• Sunlight for babies – US Govt 1933
• Vitamin D for children – translated from Spanish – July 2012
• Septic shock and low vitamin D in children – Oct 2011
• Critical Care patients need vitamin D 2011
• Critical Care patients with less than 15 ng vitamin D were 85 percent more likely to die – Sept 2011
• Infants lacking vitamin D supplementation were 19X more likely to be deficient – April 2012
• Recommend 100 IU of vitamin D per kg of infant weight in Poland – July 2011
• Death of Babies in UK due to vitamin D deficiency – Jan 2012 Dr. Gillie

Many groups of people with low Vitamin D levels

• 5 out of 6 UK dark skinned kids who were vitamin D deficient had no symptoms – May 2012
• Arab pre-term infants often have less than 10 ng of vitamin D - 2010
• Low D in developing countries – less than 5 ng in some children in China – Oct 2010
• Vitamin D less than 22 ng in Greece half of the year– May 2011
• Less than 4 ng is more common in Saudis than diabetic Saudis – July 2010
• Vitamin D insufficiency in UK youths – 37X more likely if dark skin – July 2011
• 96 % of young Koreans had less than 30 ng of vitamin D – March 2012
• 92 % of ALL Germans less than 30 ng - Jan 2012
• 92 % of German elderly less than 30 ng - Jan 2012
• 90 % of Canadian youth less than 30 ng vitamin D – Oct 2010
• 90 % of young health care professionals had less than 30 ng of vitamin D – Nov 2011
• 87 % of Tennessee general medicine patients had less than 32 ng of vitamin D – Jan 2011
• 86 % of UK elderly less than 30 ng - Jan 2010
• 82 % of Swedes did not have the recommended amount of vitamin D – Feb 2011
• 80 % of teens in Europe had less than 30 ng of vitamin D – Aug 2011
• 70 % of Koreans in their twenties had less than 20ng of vitamin D – Dec 2010
• 50 % of Quebec kids had less than 20 ng of vitamin D – Mar 2011
• 42 % of US adults less than 20 ng of vitamin D and 82 % of blacks – Jan 2011
• 33 % of pre-teens in Tehran had less than 5 ng of vitamin D – Feb 2011
• Teens increasingly indoors - especially if dark skin - July 2010
• 2X more people have less than 30 ng of vitamin D in a decade – Feb 2010
• Percent of population with less than 20 ng of vitamin D has the following graph

Large % of people in many countries have less than 20 nanograms (from the graph):
Australia 31, Canada 61, China 45, India 75, Korea 56, Malaysia 74, Middle East 90, Mongolia 98, New Zealand 56, North Africa 60, Northern Europe 92, United States 36

Comment by Vitamin D Life

Pediatricians are starting to notice low levels of vitamin D in children
Only 3 articles on vitamin D compared to >60 articles on other subjects in the current issue of the journal.
Wonder which group of doctors will lose the most business with vitamin D: OBGYN or Pediatricians.
See: Vitamin D before, during, and after pregnancy