Intensive Care Medicine

, Volume 38, Issue 12, pp 2055–2062

Vitamin D status in critically ill children

Authors

  • Constance Rippel
    • Department of Paediatric Intensive CareThe Royal Children’s Hospital, Melbourne
  • Michael South
    • Department of Paediatric Intensive CareThe Royal Children’s Hospital, Melbourne
    • Department of PaediatricsUniversity of Melbourne
  • Warwick W. Butt
    • Department of Paediatric Intensive CareThe Royal Children’s Hospital, Melbourne
    • Department of PaediatricsUniversity of Melbourne
    • Critical Care MedicineTexas Children’s Hospital and Baylor College of Medicine
Pediatric Original

DOI: 10.1007/s00134-012-2718-6

Cite this article as:
Rippel, C., South, M., Butt, W.W. et al. Intensive Care Med (2012) 38: 2055. doi:10.1007/s00134-012-2718-6

Abstract

Background

Hypovitaminosis D is an independent risk factor for cardiovascular disease, muscle weakness, impaired metabolism, immune dysfunction, and compromised lung function. Hypovitaminosis D is common in critically ill adults and has been associated with adverse outcomes. The prevalence of hypovitaminosis D and its significance in critically ill children are unclear.

Methods

We performed a prospective study to determine the prevalence of hypovitaminosis D in 316 critically ill children, and examined its association with physiological and biochemical variables, length of pediatric intensive care unit (PICU) stay, and hospital mortality.

Results

The prevalence of hypovitaminosis D [25(OH)D3 <50 nmol/L] was 34.5 %. Hypovitaminosis D was more common in postoperative cardiac patients than in general medical ICU patients (40.5 versus 22.6 %, p = 0.002), and the cardiac patients had a higher inotrope score [2.5 (1.9–3.3) versus 1.4 (1.1–1.9), p = 0.006]. Additionally, ionized calcium within the first 24 h was lower in patients with 25(OH)D3 <50 nmol/L [1.07 (0.99–1.14) mmol/L] compared with patients with normal vitamin D3 [1.17 (1.14–1.19) mmol/L, p = 0.02]. Hypovitaminosis D was not associated with longer PICU stay or increased hospital mortality.

Conclusions

Hypovitaminosis D is common in critically ill children, and is associated with higher inotropes in the postoperative cardiac population, but not with PICU length of stay or hospital survival.

Keywords

PediatricsPerioperative careCardiovascular issues in the ICU

Introduction

The role of vitamin D in metabolism and homeostasis in the general population is well established, but there is now growing interest in its potential association with overall health outcomes, and in acute, and critical illness [1]. The key metabolic role of vitamin D is in calcium and phosphate homeostasis, acting on three main target tissues: intestine, kidney, and bone. However, there is now extensive literature highlighting the importance of the vitamin D pathway as a modulator of a variety of fundamental cellular processes. By regulating the expression of more than 200 genes, including those influencing cell growth, 1,25-dihydroxyvitamin D3 plays an important role in the proliferation, maturation, and death of cells [14].

It is now well recognized that low levels of vitamin D are very common in apparently healthy adults and children [5], and in chronically ill patients. Several studies have identified vitamin D deficiency as an independent risk factor for cardiovascular disease, muscle weakness, impaired glucose metabolism, and immune dysfunction as well as compromised lung and endothelial function [610]. Furthermore, in the general adult population, vitamin D deficiency has been shown to be independently associated with increased all-cause mortality [11].

Vitamin D3 is primarily produced through the action of ultraviolet B activity on cutaneous provitamin-D (7-dehydrocholesterol). Vitamin D3 is a prohormone which is metabolized by the liver to 25-hydroxyvitamin D3 [25(OH)D3], which has a half-life of approximately 15 days. Although it is an inactive precursor to the active 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (produced in the kidneys), 25(OH)D3 levels are generally used to reflect an individual’s overall vitamin D status [12, 13].

Several recent studies have investigated vitamin D status in acutely ill patients, and have revealed a high prevalence of hypovitaminosis D in adult intensive care patients, which was associated with adverse outcomes [1416]. The significance of vitamin D status in pediatric intensive care unit (PICU) patients is currently unclear. The aim of this study is to investigate the prevalence of hypovitaminosis D and its association with outcome in critically ill children requiring intensive care admission.

Patients and methods

Patients and clinical data

This prospective study was approved by the Ethics Committee of The Royal Children’s Hospital Melbourne. We measured serum 25(OH)D3 in 316 children on admission to a mixed cardiac and general tertiary PICU between 1 July 2010 and 1 March 2011. Patients with 22q11.2 deletion (which is routinely screened for in our cardiac population) and those with chronic liver, renal, or metabolic bone disease were not included in this study.

Patient demographic and clinical data were recorded, including age, gender, weight, nature of admission (planned/unplanned), principal diagnosis, Pediatric Index of Mortality (PIM)2 [17] probability of death, Risk Adjustment for Congenital Heart Surgery (RACHS) score [18] risk of death (for cardiac patients), duration of ventilation, ICU length of stay, ICU outcome, and hospital length of stay. The following cardiovascular complications were also documented: arrhythmia, hypotension (mean arterial pressure <5th centile for age), hypertension (mean arterial pressure >95th centile for age), inotropic score [19], duration of vasoactive support, need for extracorporeal life support, and cardiac arrest. Details of any proven intercurrent or acquired infection were recorded, as were the following metabolic derangements: hyperglycemia (>10 mmol/L), hypoglycemia (<3 mmol/L), and serum lactate >1.8 mmol/L. Finally, for all patients the ionized and total calcium at admission and serum phosphate were routinely measured and the lowest ionized serum calcium within the first 24 h documented. Additionally, total dose of calcium supplementations (mmol/kg) was recorded during the first 24 h of intensive care stay.

Laboratory assays

25(OH)D3 levels were drawn from indwelling arterial or central venous catheters, alongside other routine blood tests. Serum concentration of 25-hydroxyvitamin D [25(OH)D3] was measured using the immunoassay analyzer Roche Cobas® E 601 (Roche Diagnostics Ltd.). The reference range for this assay is 50–160 nmol/L (20–64 ng/mL; conversion factor × 0.4). Serum calcium and phosphate on admission were measured with the Vitros® 5600 analyzer (OrthoClinical Diagnostics). Ionized calcium (mmol/L), pH, lactate (mmol/L), bicarbonate (mmol/L), and blood glucose (mmol/L) on admission and during the first 24 h were measured with the Siemens Rapidlab® 1265 (Siemens Healthcare Diagnostics Inc.).

Definition of hypovitaminosis D

Hypovitaminosis D was defined as a serum 25-hydroxyvitamin D3 concentration of <50 nmol/L (or <20 ng/mL) [2022].

Statistical methods

Statistical analysis was performed using STATA v.11 (STATA Corp., College Station, TX, USA). Results are presented as number (%) for categorical data, and median (interquartile range) or geometric mean (95 % confidence interval) for continuous variables. Where appropriate, continuous variables were transformed into their natural logarithm before use in the Student’s t test to compare the data of vitamin D deficient and sufficient patients. Associations between categorical variables and groups of patients with different serum 25(OH)D3 concentrations were analyzed using the chi-squared test.

Results

Total population

Three hundred and sixteen children were included in the study, which was carried out during the winter of 2010 through to early autumn of 2011. Demographic data and clinical characteristics are presented in Table 1. The prevalence of hypovitaminosis D [25(OH)D3 <50 nmol/L] in the cohort as a whole was 34.5 %. Of the children, 214 (67.7 %) were Caucasian, and the remainder were Asian (20.2 %), Indigenous (3.8 %) or other (8.3 %). There was no difference in vitamin D status between ethnic groups, nor was there any seasonal variation in vitamin D levels (Fig. 1). Hypovitaminosis D was more common in cardiac than noncardiac patients (40.5 and 22.6 %, respectively, p = 0.002). The cardiac patients were more likely to be intubated and to require vasoactive drugs, and had shorter ICU stay and shorter duration of ventilation than the noncardiac group.
Table 1

Baseline characteristics of the population

Variable

Total cohort (n = 316)

General medical patients (n = 106)

Postoperative cardiac patients (n = 210)

Age (months)

16.5 (3.1–75.2)

32.3 (10.2–129.1)

7.1 (2.2–56.1)*

Weight (kg)

9.5 (4.7–21.4)

13.0 (7.3–25.0)

7.0 (4.2–17.0)*

Gender

 Male, n (%)

186 (58.9)

69 (65.1)

117 (55.7)

 Female, n (%)

130 (41.1)

37 (34.9)

93 (44.3)

Admission

 Emergency, n (%)

103 (32.6)

83 (78.3)

20 (9.5)*

 Elective

213 (67.4)

23 (21.7)

190 (90.5)*

PIM2 probability of death (%)

2.2 (1.5–4.0)

3.4 (1.1–5.5)

2.0 (1.5–2.8)

RACHS probability of death (%)

  

5.6 (3.8–14.4)

ICU stay (h)

46.8 (23.7–135.3)

66.5 (30.5–172.9)

42.5 (23.2–93.6)*

Died, n (%)

10 (3.2)

6 (5.7)

4 (1.9)

Hospital stay (h)

245.1 (143.7–513.0)

356.8 (174.8–862.8)

212.5 (129.0–383.3)*

Intubation, n (%)

276 (87.3)

71 (67.0)

205 (97.6)*

Intubation (h)

18.6 (7.9–69.4)

15.6 (0–84.3)

19.2 (10.9–56.5)*

Respiratory support, n (%)

291 (92.1)

85 (80.2)

206 (98.1)*

Respiratory support (h)

21.6 (10.5–82.1)

32.1 (4.6–116.6)

19.9 (11.3–59.8)*

Inotropic/vasopressor support, n (%)

202 (63.9)

38 (35.8)

164 (78.1)*

25(OH)D3 (nmol/L)

56.5 (44.0–70.0)

65.5 (52.0–84.3)

52.0 (41.3–64.0)*

 Normal (≥50 nmol/L), n (%)

207 (65.5)

82 (77.4)

125 (59.5)*

 Deficient (<50 nmol/L), n (%)

109 (34.5)

24 (22.6)

85 (40.5)*

Serum calcium (mmol/L)a

2.43 (2.23–2.70)

2.30 (2.10–2.45)

2.52 (2.31–2.88)*

Lowest ionized calcium (mmol/L)b

1.17 (1.12–1.22)

1.17 (1.10–1.22)

1.17 (1.13–1.21)

Serum phosphate (mmol/L)a

1.77 (1.49–1.96)

1.49 (1.25–1.86)

1.83 (1.61–1.99)*

Values of variables are expressed as number (percentage) or median (interquartile range)

PIM2 Paediatric Index of Mortality Score 2, RACHS Risk Adjustment for Congenital Heart Surgery

p < 0.05 (medical versus cardiac patients)

aOn admission to the ICU

bDuring the first 24 h in the ICU

https://static-content.springer.com/image/art%3A10.1007%2Fs00134-012-2718-6/MediaObjects/134_2012_2718_Fig1_HTML.gif
Fig. 1

Graph showing vitamin D levels by month. Note that Australian winter months are June, July, and August, and the summer is December, January, and February. The shortest winter days in Melbourne (June) have around 10 daylight hours, and the longest summer days (December) have approximately 14 daylight hours

General medical patients

This patient group comprised 106 children, of whom 24 (22.6 %) had a serum 25(OH)D3 level of <50 nmol/L, and 5 (4.7 %) had a level <30 nmol/L. Of the general medical patients, 78.3 % were unplanned admissions and 21.7 % were planned postoperative admissions (Table 2). Sixty-eight children (64.2 %) suffered from chronic disease. These included neurological or neuromuscular disease (35.3 %), genetic syndrome (25 %), and cancer (20.6 %). Hypovitaminosis D was not associated with age, weight, gender, presence of chronic disease, need for mechanical ventilation, hypotension or hypertension, need for vasoactive support, ICU or hospital length of stay, higher admission PIM2 score, or death.
Table 2

Characteristics and p values for general medical intensive care patients

Variable

25(OH)D3 <50 nmol/L (n = 24)

25(OH)D3 ≥50 nmol/L (n = 82)

p-Value

Age (months)

29.1 (11.5–73.7)

24.1 (16.3–35.5)

0.70

Weight (kg)

16.3 (11.5–23.1)

13.5 (8.2–16.3)

0.32

Male, n (%)

16 (66.7)

53 (64.6)

0.85

PIM2 probability of death (%)

2.3 (1.4–3.80)

3.2 (2.4–4.2)

0.27

ICU stay (h)

58.0 (35.9–94.6)

75.9 (58.6–98.5)

0.34

Died, n (%)

1 (4.2)

5 (6.1)

0.72

Hospital stay (h)

428.4 (265.1–699.2)

387.6 (295.9–507.8)

0.71

Intubation, n (%)

13 (54.2)

56 (68.3)

0.42

Intubation (h)

36.6 (19.9–67.4)

46.1 (29.4–72.2)

0.54

Respiratory support, n (%)

18 (75.0)

67 (82.7)

0.47

Respiratory support (h)

52.5 (30.6–89.1)

45.1 (29.1–69.4)

0.65

Inotropic/vasopressor support, n (%)

10 (41.7)

28 (34.2)

0.50

Serum calcium (mmol/L)a

2.16 (1.96–2.37)

2.31 (2.24–2.38)

0.17

Lowest ionized calcium (mmol/L)b

1.07 (0.99–1.14)

1.17 (1.14–1.19)

0.02*

Serum phosphate (mmol/L)a

1.61 (1.41–1.81)

1.51 (1.41–1.61)

0.38

Lactate >1.8 mmol/Lb

14 (58.3)

39 (47.6)

0.35

Glucose <3 mmol/Lb

1 (4.2)

5 (6.1)

0.72

Glucose >10 mmol/Lb

8 (33.3)

18 (22.0)

0.25

Infection, n (%)

5 (20.8)

16 (19.5)

0.89

Hypotension, n (%)

10 (41.7)

28 (34.2)

0.50

Hypertension, n (%)

4 (16.7)

11 (13.4)

0.69

Arrhythmia, n (%)

2 (8.3)

5 (6.1)

0.70

Cardiac arrest, n (%)

2 (8.3)

5 (6.1)

0.70

Values of variables are expressed as number (percentage) or geometric mean (95 % confidence interval)

PIM2 Paediatric Index of Mortality 2, RACHS Risk Adjustment for Congenital Heart Surgery

p < 0.05

aOn admission to the ICU

bDuring the first 24 h in the ICU

There was no association between the admission levels of calcium or phosphate and vitamin D status. However, the lowest measured ionized calcium within the first 24 h was significantly lower in children with 25(OH)D3 <50 nmol/L [1.07 (0.99–1.14)] compared with those with normal vitamin D3 [1.17 (1.14–1.19), p = 0.02]. The prevalence of hypoglycemia, hyperglycemia or lactic acidosis was not related to vitamin D status, and there was no association between vitamin D status and the presence of culture-positive infections.

Postoperative cardiac patients

Two hundred and ten children were included in this patient group (Table 3). Eighty-five (40.5 %) were found to be vitamin D deficient, of whom 12 (5.7 %) had a serum 25(OH)D3 level of <30 nmol/L. There was no association between admission vitamin D3 and age, weight, gender, PIM2 score, duration of ventilation, ICU or hospital length of stay, RACHS probability of death, or overall hospital mortality. Of the postoperative cardiac patients, 164 (78.1 %) received inotropic and/or vasopressor support, and the need for, or duration of, vasoactive drug therapy was not associated with vitamin D status. However, the inotrope score and the total dose of dobutamine (our first-line agent after cardiac surgery) during the first 24 h were higher in patients with hypovitaminosis D. These patients required more dobutamine within the first 24 h [3.51 (2.68–4.56) mg/kg] compared with vitamin D sufficient children [1.99 (1.47–2.68) mg/kg, p = 0.005], and had a higher inotrope score [2.5 (1.9–3.3) versus 1.4 (1.1–1.9), p = 0.006]. There was no relationship between vitamin D status and the incidence of hypotension or hypertension, the incidence of any postoperative arrhythmia, or the need for extracorporeal support.
Table 3

Characteristics and p values for postoperative cardiac surgical patients

Variable

25(OH)D3 <50 nmol/L (n = 85)

25(OH)D3 ≥50 nmol/L (n = 125)

p-Value

Age (months)

9.2 (5.5–15.5)

8.7 (5.9–12.7)

0.84

Weight (kg)

10.2 (8.2–12.7)

8.2 (7.0–9.5)

0.10

Male, n (%)

43 (50.6)

74 (59.2)

0.22

PIM2 probability of death (%)

2.3 (2.0–2.7)

2.4 (2.1–2.8)

0.60

RACHS probability of death (%)

6.3 (4.6–8.5)

7.0 (5.4–9.1)

0.55

ICU stay (h)

50.4 (40.4–62.2)

50.9 (42.1–61.6)

0.91

Died, n (%)

2 (2.4)

2 (1.6)

0.70

Hospital stay (h)

232.8 (200.3–273.1)

257.2 (221.4–298.9)

0.37

Intubation, n (%)

83 (97.7)

122 (97.6)

0.98

Duration of intubation (h)

24.5 (18.9–31.5)

26.3 (21.1–32.8)

0.67

Respiratory support, n (%)

83 (97.7)

123 (98.4)

0.70

Duration of respiratory support (h)

25.8 (19.7–33.4)

29.4 (23.3–37.3)

0.44

Inotrope/vasopressor support, n (%)

65 (76.5)

99 (79.2)

0.64

Inotrope/vasopressor support (h)

35.9 (26.3–49.4)

31.8 (23.1–43.4)

0.56

Inotrope score

2.5 (1.9–3.3)

1.4 (1.1–1.9)

0.005*

Serum calcium (mmol/L)a

2.52 (2.43–2.62)

2.60 (2.52–2.69)

0.20

Lowest ionized calcium (mmol/L)b

1.16 (1.14–1.17)

1.17 (1.15–1.18)

0.38

Serum phosphate (mmol/L)a

1.85 (1.77–1.94)

1.81 (1.76–1.86)

0.38

Calcium supplementation, n (%)b

40 (47.1)

40 (32.0)

0.027*

Lactate >1.8 mmol/Lb

51 (60.0)

76 (60.8)

0.91

Glucose <3 mmol/Lb

4 (4.7)

9 (7.2)

0.46

Glucose >10 mmol/Lb

18 (21.2)

31 (24.8)

0.54

ECMO, n (%)

4 (4.7)

5 (4.0)

0.63

Infection, n (%)

11 (12.9)

11 (8.8)

0.34

Hypotension, n (%)

21 (24.7)

38 (30.4)

0.37

Hypertension, n (%)

8 (9.4)

17 (13.6)

0.36

Arrhythmia, n (%)

13 (15.3)

13 (10.4)

0.29

Cardiac arrest, n (%)

5 (5.9)

6 (4.8)

0.73

ECMO extracorporeal membrane oxygenation

Values of variables are expressed as number (percentage) or geometric mean (95 % confidence interval)

p < 0.05

aOn admission to the ICU

bDuring the first 24 h in the ICU

There was no relationship between vitamin D status on admission and total calcium and phosphate levels, and the lowest measured ionized calcium within the first 24 h was similar in the two groups. However, the proportion of children who required calcium supplementation within the first 24 h was higher in patients with hypovitaminosis D (51.3 versus 38.2 %, p = 0.027). The occurrence of hypoglycemia and hyperglycemia, lactic acidosis, or proven infection was related to vitamin D status.

Discussion

This study has shown that hypovitaminosis D is present in more than one-third of children on admission to PICU. It is more common in the cardiac than the noncardiac population, in whom this was found in over 40 %, compared with 22 % of noncardiac patients. Of note, none of our patients had 22q11.2 deletion, as this is routinely measured in all patients with congenital heart disease presenting at our institution. Our findings differ from those published to date in the adult population, in that we did not see an association between vitamin D status and survival, nor did we see an association between vitamin D status and duration of mechanical ventilation or ICU stay. In children with congenital heart disease, hypovitaminosis D was associated with greater levels of inotropic support, but was not associated with surgical complexity.

The prevalence of hypovitaminosis D in our population of critically ill Australian children was 34.5 %. This is lower than in the adult ICU population, in which vitamin D deficiency has been reported to range from 38 to 79 % [15, 23], but substantially higher than the reported prevalence of 18 % in Mansbach’s population-based study of healthy American children [5], and 8 % in prepubertal Australian children [24, 25]. The published prevalence of vitamin D deficiency in American and Australian adolescents ranges from 29 to 68 % [21, 2628]. However, given that the median age of our cohort was <3 years, it is reasonable to suggest that hypovitaminosis D in children requiring PICU is more common than in their healthy peers. This would be particularly applicable to patients with cardiac disease, of whom the majority were infants, and would be deemed to have chronic disease burden. The associated vitamin D deficiency can be associated with a lack of sun exposure, chronic nutritional deficiency, as well as subtle impairment of hepatic and renal function. A recent study from our own institution demonstrated low vitamin D levels in 54.9 % of chronically ill (noncardiac) patients or disabled children who were not inpatients [29]. We did not observe this in our cohort, though this is somewhat limited by the heterogeneous nature of “chronic disease” and relatively small numbers.

Vitamin D deficiency has recently been shown to be independently associated with all-cause mortality in some cohorts of critically ill adults [1416], while other investigators have not found this relationship [23, 30]. We saw no association between vitamin D status and actual or predicted (PIM2) mortality. Given that the overall mortality in the PICU is far lower than in the adult ICU population and that our study was not sufficiently powered to pick up differences in survival, we also applied duration of ventilation and length of ICU stay as additional outcome measures. However, we still did not demonstrate any relationship between vitamin D status and these surrogate measures of ICU outcome.

We were interested in examining the association between vitamin D status and the incidence of proven infection. Vitamin D plays a physiological role in regulating innate and adaptive immunity, and in the modulation of T- and B-cell activity, cytokine production, and the expression of antimicrobial peptides [3133]. Animal data have shown that severe vitamin D deficiency leads to reduced lung function [34], and the Third National Health and Nutrition examination survey showed a strong association between vitamin D levels and lung function as well as the risk for upper respiratory tract infections in the general population [34, 35]. Data from adult critical care populations are conflicting, in that some studies demonstrate a clear association between vitamin D deficiency and culture-positive infection [36], whereas others do not [23, 37]. A few studies have associated vitamin D deficiency with severity of disease in infants and children with acute lower respiratory infection [38, 39]. Muhe identified vitamin D deficiency as an important predisposing factor for pneumonia in children in developing countries [40]. We did not identify an association with the incidence of infection or the need for ventilation. Roth et al. did not find an association between vitamin D deficiency and severity of presentation of bronchiolitis, as defined by the need for hospitalization. While we would suggest caution in extrapolating from non-ICU studies, or from studies in adult populations, it is important to note that in our cohort severe vitamin D deficiency (<30 mmol/L) was rare, proven infection rates were relatively low, and the majority of our patients (80 %) were ventilated on, or shortly after, PICU admission. Thus, we cannot with confidence rule out a subtle association in our relatively limited study population.

The association between vitamin D status and inotrope score in the postoperative cardiac patients is a novel finding. Ventricular dysfunction and heart failure are common in children with rickets [41], and myocardial dysfunction, heart failure, and sudden cardiac death have also been associated with vitamin D deficiency [9, 12]. It is now known that vitamin D has both genomic and nongenomic effects in the heart, and influences cardiac systolic and diastolic function through its interaction with cardiac receptors [vitamin D receptor (VDR)], and that disruption of VDR leads to cardiac hypertrophy through interaction with the renin–angiotensin system [42, 43]. Although we did not routinely assess cardiac function or other markers of systemic oxygen delivery in our postoperative cardiac patients, there was no difference in their PIM2 and RACHS scores between the vitamin D deficient and sufficient patients. It is therefore possible that our findings may indicate an association with myocardial dysfunction and impairment of oxygen delivery, which could be systematically addressed in future studies.

Our study confirmed a relationship between ionized calcium and vitamin D levels. In the general PICU population, the lowest measured ionized calcium level was lower in children with hypovitaminosis D. This is in keeping with studies in adult ICU patients. While this relationship was not quite the same in postoperative cardiac patients, the total calcium replacement was higher in those with low levels. It is important to note, however, that the threshold for treating hypocalcemia in cardiac patients is much lower than in noncardiac patients (generally around 1.10–1.20 mmol/L in our practice), so a true untreated “nadir” of untreated ionized calcium would rarely be seen in the cardiac group. Thus, total calcium replacement would be a surrogate for this in the cardiac patients.

Limitations

An important limitation to this current study is that there is no current consensus on a specific (or different) definition for vitamin D deficiency in infants and young children, and that our data (similar to many published studies in other patient groups) do not include measurement of parathyroid hormone. Moreover, we (and others) have measured blood levels of 25(OH)D3 rather than the active form—1,25 dihydroxyvitamin D3, and it is possible that its overall activity may be different in the critically ill population. Indeed, given these uncertainties, we chose to apply the term “hypovitaminosis D” to our population rather than “vitamin D deficiency.” On the basis of the available evidence, several authors have stated that, similar to adults, the 25(OH)D3 concentration for infants and children should be ≥50 nmol/L, which is the basis for the definition in our current study. However, it should be noted that other investigators have suggested that the cutoff should be lowered to 37.5 nmol/L [44]. An additional note of caution relates to the reliability of the currently available vitamin D assays. While there is no absolute consensus on whether immunoassays (as used in our study) are superior or inferior to high-performance liquid chromatography techniques, there is known to be poor reproducibility between the two methods [45]. Another limitation is the relatively small sample size and lack of a control population, which limited our ability to conclude with confidence some important issues, including the association with infection or severity of lung disease. Moreover, for cardiac patients in particular, a preoperative vitamin D level would have been helpful, to address any confounding impact of cardiopulmonary bypass (CPB) and fluid shifts on postoperative vitamin D level. Moreover, an objective measure of cardiac performance, alongside total duration of inotropic support, would undoubtedly be of interest in drawing further conclusions regarding our observation of increased inotropic needs in the deficient group. Finally, we did not investigate serial levels of vitamin D, particularly in patients requiring prolonged ICU stay, nor did we assess in detail the parathyroid axis in our patients. However, given our current observations, future studies could address all of these questions.

Conclusions

Hypovitaminosis D is common in critically ill children in the PICU, particularly in infants and children with heart disease. Hypovitaminosis D was associated with hypocalcemia in the noncardiac population, and increased need for calcium replacement in the cardiac population. In contrast with studies in adults, we did not demonstrate an association between vitamin D status and survival or PICU length of stay, but did find a strong relationship with early postoperative inotropic needs in the cardiac population. Further evaluation of the pediatric population is warranted, particularly with respect to children with congenital heart disease.

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© Springer-Verlag Berlin Heidelberg and ESICM 2012