European Journal of Cardiovascular Medicine

It is already well known about the role of Vitamin D in calcium homeostasis[1]. But recent studies have shown that Vitamin D has a role in immunity and its deficiency is associated with various infections[2]. Sepsis is defined as SIRS resulting from a suspected or proven infectious etiology The clinical spectrum of sepsis begins when a systemic (ex: bacteremia, viremia, fungemia etc) or localised (ex: meningitis, pneumonia, necrotizing fasciitis etc) infection progresses from sepsis to severe sepsis (ie, presence of combined sepsis and organ dysfunction) and later to septic shock(severe sepsis with hypotension/ organ hypoperfusion)[3]. Vitamin D is associated with anti-inflammatory and anti-proliferative mechanisms, and its deficiency may result in an increased risk of mortality in various diseases[4]. It is also seen that Vitamin D deficiency is associated with prolonged hospital stay, increased infection rates and other adverse outcome. Severe sepsis, sepsis-related mortality, and an overall increase in mortality in adult intensive care units have been reported with vitamin D deficiency[5].

There have been various animal studies and studies in adult population regarding an association between Vitamin D and immunity and thus adverse outcomes in sepsis [6]. However data regarding similar association in the pediatric population, in an Indian setting are minimal.

Hence, we are conducting a prospective observational study of the association between vitamin D levels and outcome, among patients admitted to the PICU.

AIM OF THE STUDY

To find if a relation exists between vitamin D status and outcomes in children with sepsis.

A total of 40 children aged between one months and 18 years who got admitted to the pediatric intensive care unit as per surviving sepsis guidelines [7] during the study period. Written and informed consent was obtained from the parents/guardian of all children included in the study.History of pre existing chronic illnesses like chronic renal illness, SAM, Protein energy malnutrition are not included in the study.

Parents/Guardians are questioned via proforma and information will be collected from the parents regarding the child’s health status, duration of illness, exposure to sunlight by outdoor activities and intake of vitamin supplements.

A body temperature above 100 F was considered high fever. The radiological findings, white cell counts, presence of shifting to left on peripheral smear, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values, treatment given and hospitalization were recorded. A C-reactive protein value of 0-6 mg/L and an ESR value of <20 mm/h were considered normal. The patients were diagnosed with sepsis according to the clinical and laboratory findings.

Also blood will be collected as early as possible by drawing 2ml of venous blood from children within 24hrs of admission to the PICU for estimation of Vitamin D levels. After collection, blood is allowed to clot at room temperature and serum separated by centrifugation and 25-hydroxyvitamin D levels are estimated and the values are not revealed until the end of the study.

Those who were blood cultures positive will be followed up for outcomes during the hospital stay. Once the predefined endpoints (death or discharge) are achieved, patients are divided based on the serum Vitamin D levels at admission into 3 groups: a sufficient group (25(OH)D level ≥ 20 ng/mL), an insufficient group (25(OH)D level = 12-20 ng/mL), and a deficient group (25(OH)D level < 12 ng/mL).

Outcome are measured in the following parameters:

1. Duration of hospital stay
2. Duration for on ventilator/ HFNC.
3. Number of death during hospital stay.

Table No.1: Age and gender wise distribution of children

NS= not significant, S=significant, HS=highly significant

  Study observes that, maximum number of children17 (42.5%) were belongs to the age group of ≤ 1 year, Minimum age of patient was 2 months and maximum 17 years. The mean age of male children was 3.94years; the mean age of female children was 6.51 years. There was no statistical significant difference of age in gender (P>0.05)

Study observed; male children were predominant 25 (62.5%) and female children were 15 (37.5%). The sex ratio male to female was 1.7:1

Multiple bar diagram represents age wise distribution of children

Table No.2: Descriptive Statistic of variables

Table No.3: Vitamin D level classification

In the present study; 18 (45%) of children had sufficient vitamin D level, 12 (30%) of children had insufficient Vitamin D and 10 (25%) of children were observed deficiency of vitamin D. Total insufficient and deficient children were 22 (55.0%)

Pie chart present vitamin D level classification

Table No.3: Association between demographical profiles with vitamin D levels

Out of 22 vitamin D insufficient and deficient children 14 (63.6%) of children were seen in the age group of ≤ 1 year. Out of 18 vitamin D sufficient children 12 (66.7%) of children were seen in the age group of 6-18 years. This shows that lower age group children had more number of insufficient and deficient of vitamin D, this is statistically significant (P<0.05). There was statistically significant positive correlation between age and vitamin D levels (P<0.01).Whereas there was statistically no association of vitamin D level with gender (P>0.05).

Table No.4: Association between measurements with vitamin D levels

Study reveals that there was statistically significant difference of mean height, weight, BMI and WC between the vitamin D levels (P<0.05) and (P<0.01). The mean values of variables were higher in sufficient vitamin D level, as compare to insufficient and deficient. There was statistically significant positive correlation between height, weight, BMI and WC with vitamin D levels (P<0.01). Study reveals that there was statistically significant positive correlation between Height, Weight, BMI and WC with respect to vitamin D levels (P<0.05).

Table No.5: Correlation between investigations with vitamin D levels

Study reveals that; there was significant negative correlation between HR, Temperature and ESR with vitamin D levels (P<0.05) and (P<0.01). Whereas there was significant positive correlation between PC with vitamin D levels (P<0.01)

All other variables are not shown correlation with vitamin D levels (P>0.05).

Table No.6: correlation between hospital stay with vitamin D levels

Study observed that; the mean duration of hospital stay and duration of ventilator stay in the vitamin D level of sufficient shows lower as compare to insufficient and deficient vitamin D level children. This shows statistically significant difference of mean duration of hospital stay and duration of ventilator stay with vitamin D levels (P<0.05) and (P<0.01). There was significant negative correlation between duration of hospital stay and duration of ventilator stay with respect to vitamin D levels {r = -0.414 and r = -0.435} (P<0.01)

Statistical data analysis:

Statistical data was analyzed by IBM SPSS 20.0 version software. Collected data were spread on excel sheet and prepared master chart. Through the master chart tables and graphs were constructed. For quantitative data analysis mean and standard deviations were calculated and applied t-test and ANOVA test. For qualitative data analysis chi-square test and Fisher exact probability tests were applied for statistical significance. If P-value was less than 0.05 considered as significant.

Vitamin D deficiency’s effect on the patient outcomes such as higher mortality could not be demonstrated but longer PICU stay demonstrated. Although vitamin D deficiency has been shown to be independently associated with all-cause mortality in critically ill children, a definite effect on survival has not yet been demonstrated in any of the reported pediatric studies [8].

In my study prevalence of vitamin D deficiency (serum 25(OH) D) levels <12 ng/ml among critically ill children admitted to tertiary care centre PICU in GIMS hospital Kalaburagi was 25% and showed prevalence of vitamin D insufficiency levels

(12-20ng/ml)30%.

Among Delhi over 80% of young children (9 months- 30 months of age ) from 2 slum areas had serum vitamin D levels of < 14ng/ml (35nmol/l ). Among Delhi school children of age group 10- 18 years showed hypovitaminosis D (serum vitamin D levels of < 20 ng/ml ) was seen in 92.6% of low socioeconomic group and 84.9% of upper socioeconomic status group with over a third of them having 25(OH) D value of <9 ng/ml [9].

Nearly 42.5 % of the study population were infants (<1 year age group) and this showed that lower age group children are more prone for infections subsequently leading them to sepsis and this showed that lower age group children are more prone for sepsis which led to the death of 5%. Although there was no co-relation exists between vitamin D levels and sepsis statistically but the clinical outcomes measured in terms of the duration of hospital stay and requirements of respiratory support (ventilator/ HFNC) was found to be statistically significant and highly significant respectively. So it is recommended that vitamin D levels should be measured in children with sepsis and all children should be given vitamin D supplementation especially in infants considering the efforts of vitamin D on infection, pulmonary functions and immunity. Studies with larger series with long follow up periods and age group above 1 year should be conducted for definite results.

consent –

to be attached

Written informed consent was obtained from the patient attenders for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient.

Funding

None

Authors contribution

Dr Vijaylakshmi: Corresponding author, writing the paper.

Dr Sandeep V H: Study concept 

Dr Sachin S Hatti: Study concept

CTRI NUMBER - NOT APPLICABLE

Conflict of interest

The authors declare having no conflicts of interest for this article.

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