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ORIGINAL ARTICLE
Year : 2021  |  Volume : 34  |  Issue : 1  |  Page : 210-215

Association between vitamin D deficiency and sepsis in pediatric ICU


1 Pediatric Department, Faculty of Medicine, Menoufia University, Shebeen El-Kom, Egypt
2 Pediatric Department, Benha Teaching Hospital, Kalubia, Egypt

Date of Submission17-Jun-2019
Date of Decision08-Jul-2019
Date of Acceptance14-Jul-2019
Date of Web Publication27-Mar-2021

Correspondence Address:
Rehab G Naser
Quesna, Menoufia
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mmj.mmj_210_19

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  Abstract 


Objective
To evaluate association between 25-hydroxyvitamin D [25(OH)D] and sepsis in pediatric ICU (PICU).
Background
Vitamin D is a fat-soluble steroid hormone that helps maintain proper calcium homeostasis and has a role in the function of the immune system. Data on the prevalence of vitamin D deficiency (VDD) in PICU in children with sepsis and its association with poor outcome were obtained.
Patients and methods
This study was carried out on 45 patients with sepsis admitted to the PICU, Pediatric Department, Menoufia University Hospital, and 45 controls, who attended the patient clinic and were found to be healthy. Demographic data, history, and general and local clinical examination were done. Investigations such as complete blood count and C-reactive protein were done. For measurement of vitamin D, fresh blood samples were taken within 24 h of admission, and level of vitamin D was measured by ELISA. VDD was defined as less than 10 ng/ml.
Results
Prevalence of VDD [25(OH)D level < 10 ng/ml] was higher among critically ill children with sepsis compared with health controls (33.3 vs. 11.1%; P = 0.02). 25(OH)D was strongly associated with pediatric index of mortality (P = 0.02), duration of mechanical ventilation (P = 0.003), length of PICU stay (P < 0.001), and mortality (P < 0.001). VDD was not associated with age, sex, residence, or admission season.
Conclusion
Lower 25(OH)D levels are associated with sepsis. There was a high prevalence of VDD in critically ill children with sepsis, and it was association with poor outcome.

Keywords: critically ill children, 25-hydroxyvitamin D, intensive care, mortality, sepsis, vitamin D


How to cite this article:
El-Gendy FM, Khattab AA, Naser RG, Abdel-Aziz AA. Association between vitamin D deficiency and sepsis in pediatric ICU. Menoufia Med J 2021;34:210-5

How to cite this URL:
El-Gendy FM, Khattab AA, Naser RG, Abdel-Aziz AA. Association between vitamin D deficiency and sepsis in pediatric ICU. Menoufia Med J [serial online] 2021 [cited 2021 Dec 7];34:210-5. Available from: http://www.mmj.eg.net/text.asp?2021/34/1/210/312016




  Introduction Top


Vitamin D is a fat-soluble steroid hormone that helps maintain normal homeostasis of calcium and skeletal mineralization [1].

Vitamin D also affects immunomodulatory function [2]. It was suggested that by inducing antimicrobial peptides in epithelial cells, neutrophils, and macrophages. it could play a role in the optimal functioning of the innate immune system [3].

The primary circulating form of 25-hydroxyvitamin D [25(OH)D] is capable of inducing its own conversion to active form 1, 25(OH)D (calcitriol) and producing antimicrobial cathelicidin peptides in the presence of an antigen challenge [4].

Vitamin D and vitamin D receptor expression and activity are associated with immunity against various infection and autoimmune diseases [5].

Low serum 25(OH)D levels were associated with an additional hazard of infection, and a latest clinical trial showed that vitamin D supplementation lowered the risk of influenza A infection. The multiple functions of vitamin D in immune system's response to infection suggest that it may be an integral component in combating sepsis. Regarding the prevention of infections, insufficient vitamin D may also be significant in sepsis pathogenesis, the most lethal result of serious infection [6].

So, the aim of this study was to evaluate the status of vitamin D in pediatric patients with sepsis admitted to pediatric ICU (PICU) and assess the link between the status of vitamin D and the clinical outcome.


  Patients and methods Top


This study was approved by the ethics committee in Menoufia Hospital. Eligible children were enrolled in the study after obtaining informed written consent from parents. This prospective study was performed in PICU Menoufia University Hospitals. We studied patients with sepsis admitted to PICU during the period from October 2017 to June 2018. This study was carried out on 45 patients admitted to PICU with sepsis between age of 1 month and 18 years, of either sex. A total of 45 control patients who came to outpatient clinic and were found to be healthy with comparable age, sex, and socioeconomic state were included as well. The exclusion criteria included the following: patients with known or suspected adrenal, pituitary, or hypothalamic disease; patients who received systemic steroids for more than 10 days in the previous month or more than one dose of systemic steroids within 24 h of admission; patients less than 1 month or more than 18 years; patients who transferred from another ICU; patients after trauma; patients with chronic renal disease; patients with gastrointestinal malabsorption conditions; and patients with severe acute malnutrition.

All patients were subjected to full history taking at the time of admission, which included age, sex, residence, order among siblings, and onset of the illness either acute or acute on top of chronic illness. History was taken about child's background, sun exposure, intake of vitamin D supplements, and type of milk supplementation. Thorough clinical examination at the time of admission including all body systems was done. The severity of illness in the first 24 h was assessed as defined by Pediatric Risk of Mortality III (PRISM-III) score. Presence of sepsis and its degree was identified according to International Pediatric Sepsis Consensus Conference. Sepsis was defined as a systemic inflammatory response syndrome in the presence of suspected or confirmed infection by any pathogen in the blood or cerebrospinal fluid. An infection was described as confirmed if it had a positive culture result. During admission in our PICU, the cases were followed up for catecholamine administration: maximum level of vasopressor use during PICU stay was assessed by using the Sequential Organ Failure Assessment (SOFA) cardiovascular (CV) score. Mechanical ventilation duration if the patient was ventilated, PICU length of stay, and outcome were assessed.

The following laboratory tests were performed: complete blood count, C-reactive protein (CRP), serum calcium (Ca), serum alanine amino transferase, aspartate amino transferase, serum urea and creatinine, and serum 25(OH)D. Vitamin D status was defined as vitamin D sufficient [25(OH)D ≥20 ng/ml], vitamin D insufficient [25(OH)D 10–20 ng/ml], and vitamin D deficient (VDD) [25 (OH)D <10 ng/ml].

Venous blood samples were collected in clotted specimen bottles from all cases and controls for analysis of 25(OH)D. Plasma was extracted after centrifugation. Total plasma 25(OH)D was measured by Human 25(OH)D enzyme-linked immunosorbent assay (ELISA) kit [[email protected] (Technical MSN service online)]. The lower limit of detection was 0.503 ng/ml. The intra-assay CV was less than 10%, while the inter-assay CV was less than 12%. Where CV(%) = SD/mean × 100. VDD, insufficiency, and sufficiency were defined as plasma 25(OH)D less than 10 ng/ml, 10–20 ng/ml, and more than 20 ng/ml, respectively.

Statistical analysis

The data were collected, tabulated, and analyzed by statistical package for the social sciences (SPSS) version 17.0 on IBM compatible computer (SPSS Inc., Chicago, Illinois, USA). Two types of statistics were done: descriptive statistics (e.g. percentage, mean and SD), and analytic statistics, which include the following tests: χ2-test was used to study association between two qualitative variables, t-test is a test of significance used for comparison between two groups normally distributed having quantitative variables, Mann–Whitney U-test is a nonparametric test of significance used for comparison between two groups not normally distributed having quantitative variables, Kruskal–Wallis test is a nonparametric test of significance used for comparison between more than two groups not normally distributed having quantitative variables, and Pearson correlation is a measure of the linear correlation or dependence between two variables x and y, giving a value between +1 and −1 inclusive, where 1 is total positive correlation, 0 is no correlation, and − 1 is total negative correlation.

P value of less than 0.05 was considered statistically significant.


  Results Top


This study included two groups: patient group included 45 children admitted to PICU with sepsis and a control group included 45 apparently healthy age-matched and sex-matched children. There was no statistically significant difference between cases and control regarding age (35.15 ± 38.9 vs. 38.44 ± 38.70; P = 0.26), sex (male: 71.1 vs. 53.3%, and female: 28.9 vs. 46.7%; P = 0.08), residence (rural was 48.05% in cases vs. 57.8% in controls; P = 0.4, whereas in urban was 51.5% in cases vs. 42.2% in controls), order of birth (P = 0.1), and season (summer: 57.8% in cases vs. 64.4% in controls, whereas winter: 42.2% in cases vs. 35.6% in control; P = 0.52), as shown in [Table 1].
Table 1: Sociodemographic data among the studied groups

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There was a statistically significant difference between cases and control regarding vitamin D level (16.61 ± 8.46 vs. 23.15 ± 8.57; P = 0.001), as shown in [Table 2]. Vitamin D sufficiency (>20 ng/ml) was 44.4% in cases and 71.1% in controls, with significant difference between them (P = 0.02). Vitamin D insufficiency (10–20 ng/ml) was 22.2% in cases and 17.8% in controls, with significant difference between them. VDD (<10 ng/ml) was 33.3% in cases and 11.1% in controls, with significant difference between them (P = 0.02), as in [Table 2].
Table 2: Vitamin D level among the studied groups

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There was no significant correlation between vitamin D level and age (P = 0.47) and birth order (P = 0.98), as shown in [Table 3]. There was a significant negative correlation between vitamin D level and PRISM-III score (P = 0.02), SOFA score (P = 0.001), duration of ventilation (P = 0.003), and PICU stay (P < 0.001), as shown in [Table 3]. There was a significant positive correlation between vitamin D and serum Ca (P = 0.004), as shown in [Table 4]. There was significant negative correlation between vitamin D and CRP (P = 0.003), as shown in [Table 4]. There was no correlation between vitamin D level and other laboratory investigations [phosphorous (P = 0.72), urea (P = 0.45), creatinine (P = 0.33), platelets (P = 0.47), alanine amino transferase (P = 0.78), aspartate amino transferase (P = 0.85), total leukocytic count (P = 0.07), hydrogen ion concentration (P = 0.65)], as shown in [Table 4]. Vitamin D levels were significantly lower in VDD cases than in nondeficient cases (6.27 ± 1.25 vs. 21.79 ± 4.98) (P < 0.001), as shown in [Table 5]. There was no difference in age (P = 0.31), sex (P = 0.49), milk supplements (P = 0.39), season (P = 0.09), and manifestation of rickets (P = 0.18) between deficient and nondeficient groups, as shown in [Table 5]. Vitamin D supplementation was 6.7% in deficient group, whereas was 36.7% in nondeficient group, with significant difference between them (P = 0.04), as shown in [Table 5]. Overall, 86.7% of the deficient group showed no exposure to the sun, whereas 46.7% of the nondeficient group showed no exposure to the sun, with a significant difference between them (P = 0.02), as shown in [Table 5]. PRISM-III score was 39.58 ± 32.81 in deficient group, whereas in nondeficient group was 22.17 ± 28.32, with significant difference between them (P = 0.03), as shown in [Table 5]. SOFA score was 1.87 ± 1.46 in deficient group, whereas in nondeficient group was 0.60 ± 0.97 (P = 0.002), with significant difference between them, as shown in [Table 5]. There was a statistically significant difference for need of mechanical ventilation (P = 0.02) and length of PICU stay (11.35 ± 3.94 vs. 8.9 ± 2.75; P = 0.004) in both groups, as shown in [Table 5]. Mean level of Ca was 7.13 ± 1.06 in deficient group, whereas it was 7.83 ± 0.72 in nondeficient group, with significant difference between them (P = 0.036), as shown in [Table 5]. There was significant difference in grade of sepsis between deficient and nondeficient groups, as 33.3% of deficient group showed septic shock, whereas septic shock represented 0% of nondeficient group (P < 0.001). Discharged cases were 40% of deficient group, whereas in nondeficient was 96.7%, and died cases were 60% of deficient group, whereas in nondeficient group was 3.3%, with significant difference between them (P < 0.001), as shown in [Table 5].
Table 3: Correlation between vitamin D and the studied parameters

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Table 4: Correlation between vitamin D and laboratory investigations

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Table 5: Relationship between vitamin D level and clinical and laboratory parameters

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  Discussion Top


In this study, the levels of 25(OH)D in patients with sepsis admitted to our PICU were lower than in pediatric controls (P = 0.001), and this finding is consistent with other critical disease studies in pediatric patients, such as Madden et al. [7] and McNally et al. [8].

This prospective study demonstrates that the prevalence of VDD among critically ill children with sepsis was 33.3%, which was significantly higher than in the healthy controls, with 11.1% (P = 0.02). Close to our study results, Rippel et al. [9] reported 34.5% prevalence of VDD among critically ill children.

Our study showed nonsignificant correlation between vitamin D level and age (P = 0.47), and this agree with McNally et al. [8] who found no association between vitamin D level and age, and is contrary to that Madden et al. [7], who found that vitamin D level was lower in older age group.

In this study, there was no significant difference between case and control regarding sex and order of birth (P > 0.05). Moreover, there was no significant difference between case and control regarding residence (rural represented 48.5%, whereas urban represented 51.5% in case group, and for control group rural represented 57.8%, whereas urban represented 42.2%). However, a study by Ahmed et al. [10] found 75% rural and 100% urban patients had low level of vitamin D, with significant difference between them. There was nonsignificant difference between 25(OH)D status and season which is similar to the results of McNally et al. [8]. On the contrary, Hebbar et al. [11] found significant seasonal difference in their study.

Lack of vitamin D supplementation and sun exposure are strongly related to VDD. In this study, there was a significant correlation between VDD and vitamin D supplementation (P = 0.04). Similar to our results, Madden et al. [7] found significant correlation between VDD and vitamin D supplementation (P < 0.0001) and noted that vitamin D supplementation before PICU admission was strongly protective against 25(OH)D deficiency. School age children, those with darker skin, and children not receiving vitamin D supplementation were more likely to have low 25(OH)D levels especially during colder months when sun exposure was limited. On the contrary, Onwuneme et al. [12] found that sun exposure had very small influence on 25(OH)D status.

In this study, there was a significant negative correlation between CV-SOFA score and vitamin D (P = 0.001), which is similar to the study by Madden et al. [7].

Our study shows significant correlation between vitamin D level and sepsis grades. Sepsis severity has been noted, as systemic inflammatory response syndrome cases showed highest vitamin D level, and septic shock showed lowest level (P < 0.001). Similar to our study, Madden et al. [7] found that children admitted to PICU with severe septic shock had lower serum 25(OH)D than other critically ill children in PICU.

This study on critically ill children assessed the severity of critical illness on admission using PRISM-III score. There was a significant negative correlation between vitamin D level and PRISM-III score (P = 0.02). Similar to our study the results of Madden et al. [7] and McNally et al. [8]. On the contrary, Ponnarmeni et al. [13] found no association between vitamin D and severity of illness and Ayulo et al. [14] showed results in agreement with them. In this study, there was a significant correlation between vitamin D level and need for mechanical ventilation (100% of deficient group vs. 66.7% in nondeficient group) (P = 0.02). Similar to our study was the study by Ponnarmeni et al. [13]. In our study, there was a significant association between vitamin D level and length of PICU stay (P = 0.004). It was 11.53 ± 3.99 (mean) in the deficient group, whereas in nondeficient group, it was 8.9 ± 2.75 days. Similar to our study were the results reported by McNally et al. [8] and Ebenezer et al. [15]. This study showed significant positive correlation between vitamin D level and serum Ca level (P = 0.004), which is similar to McNally et al. [8]. However, Prasad et al. [16] showed that the difference was not statistically significant for occurrence of hypocalcemia in cases with vitamin deficiency.

This study observed a significant negative correlation between vitamin D and CRP (P = 0.003) which is in agreement with the data observed by Onwuneme et al. [12], but this was not observed in other studies, such as Grzanka et al. [17].

In this study, there was an association between VDD and mortality (P < 0.001), and this matches with the study done by Ayulo et al. [14]. Contrary to this result was the study by Prasas et al. [16] and Ray et al. [18], who found no association between hypovitaminosis D and mortality.


  Conclusion Top


In this study population, the incidence of VDD was high in critically ill children with sepsis admitted to PICU of Menoufia University Hospital. There was a significant association between degree of VDD and grade of sepsis, SOFA score, PRISM-III score, and mortality. There was a significant association between length of PICU stay and duration of ventilation with 25(OH)D deficiency. Lack of sun exposure and vitamin D supplementation were related to VDD. Hypocalcemia and increased CRP were related to VDD.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 2004; 80:1689S–1696S.  Back to cited text no. 1
    
2.
Clancy N, Onwuneme C, Carroll A, McCarthy R, McKenna MJ, Murphy N, et al. Vitamin D and neonatal immune function. J Matern Fetal Neonatal Med 2013; 26:639–646.  Back to cited text no. 2
    
3.
Kempker JA, Han JE, Tangpricha V, Ziegler TR, Martin GS. Vitamin D and sepsis: an emerging relationship. Dermatoendocrinol 2012; 4:101–108.  Back to cited text no. 3
    
4.
Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR, et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science 2006; 311:1770–1773.  Back to cited text no. 4
    
5.
Kongsbak M, Levring TB, Geisler C, von Essen MR. The vitamin D receptor and T cell function. Front Immunol 2013; 4:148.  Back to cited text no. 5
    
6.
Ginde AA, Mansbach JM, Camargo CA. Association between serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey. Arch Intern Med 2009; 169:384–390.  Back to cited text no. 6
    
7.
Madden K, Feldman HA, Smith EM, Gordon CM, Keisling SM, Sullivan RM, et al. Vitamin D deficiency in critically ill children. Pediatrics 2012; 130:421–428.  Back to cited text no. 7
    
8.
McNally JD, Menon K, Chakraborty P, Fisher L, Williams KA, Al-Dirbashi OY, et al. The association of vitamin D status with pediatric critical illness. Pediatrics 2012; 130:429–436.  Back to cited text no. 8
    
9.
Rippel C, South M, Butt WW, Shekerdemian LS. Vitamin D status in critically ill children. Intensive Care Med 2012; 38:2055–2062.  Back to cited text no. 9
    
10.
Ahmed N, Yadav V, Soni RK, Nagaraj N, Berwal PK, Sengar GS. A study of association between vitamin d deficiency in sepsis. Int J Contemp Pediatr 2016; 3:1419.  Back to cited text no. 10
    
11.
Hebbar KB, Wittkamp M, Alvarez JA, McCracken CE, Tangpricha V. Vitamin D deficiency in pediatric critical illness. J Clin Transl Endocrinol 2014; 1:170–175.  Back to cited text no. 11
    
12.
Onwuneme C, Carroll A, Doherty D, Bruell H, Segurado R, Kilbane M, et al. Inadequate vitamin D levels are associated with culture positive sepsis and poor outcomes in pediatric intensive care. Acta Paediatr 2015; 104:e433–e438.  Back to cited text no. 12
    
13.
Ponnarmeni S, Kumar Angurana S, Singhi S, Bansal A, Dayal D, Kaur R, et al. Vitamin D deficiency in critically ill children with sepsis. Paediatr Int Child Health 2016; 36:15–21.  Back to cited text no. 13
    
14.
Ayulo JM, Katyal CH, Agarwal C, Sweberg T, Rastogi D, Markowitz M, et al. The prevalence of vitamin D deficiency and its relationship with disease severity in an urban pediatric critical care unit. Endocr Regul 2014; 48:69–76.  Back to cited text no. 14
    
15.
Ebenezer K, Job V, Antonisamy B, Dawodu A, Manivachagan MN, Steinhoff M. Serum vitamin D status and outcome among critically ill children admitted to the pediatric intensive care unit in South India. Indian J Pediatr 2016; 83:120–125.  Back to cited text no. 15
    
16.
Prasad S, Raj D, Warsi S, Chowdhary S. Vitamin D deficiency and critical illness. Indian J Pediatr 2015; 82:991–995.  Back to cited text no. 16
    
17.
Grzanka A, Machura E, Mazur B, Misiolek M, Jochem J, Kasperski J, et al. Relationship between vitamin D status and the inflammatory state in patients with chronic spontaneous urticaria. J Inflamm 2014; 11:2.  Back to cited text no. 17
    
18.
Rey C, Sánchez-Arango D, López-Herce J, Martínez-Camblor P, García-Hernández I, Prieto B, et al. Vitamin D deficiency at pediatric intensive care admission. J Pediatr (Rio J) 2014; 90:135–142.  Back to cited text no. 18
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]


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