Vitamin D status among critical children below five years in a tertiary care hospital

Abstract               Background: Vitamin D deficiency/insufficiency is increasing in frequency. Studies have reported reduced Vitamin D concentrations in patients with previous and prevalent cardiovascular or cerebrovascular diseases. Vitamin D deficiency is commonly noticed during admission to intensive care units. Although it is not an independently decisive factor for mortality, it might be related to the worse clinical status at ICU admission. Objective: To assess the Vitamin D level among children admitted to the ICU. Methodology: A prospective observational hospital-based study was conducted at a government tertiary care hospital in Chennai, Tamil Nadu from January 2018 to Dec 2018. Eligible children below 5 years admitted to the ICU with Glasgow coma scale <_8 or shock from any origin were included in the study as cases and children admitted to ICU without the above critical presentations were included in the study as controls. Results: 90.4% of the admitted children presented with one of the categories of vitamin D deficiency. 50.5% of the cases were admitted with symptoms of the respiratory system. 44.7% of the admissions presented with CNS infection symptoms. Severe vitamin D deficiency was seen in 10.6% of the study group. Death was the outcome among 84.1% of the study group. Vitamin D levels were not statistically significant to systems involved on admission, nutritional status and outcome of the admitted children. Statistical significance was noted in the levels of vitamin D between cases and controls. The cases presented with significantly lower serum vitamin D levels compared to the controls.

Key Word: Vitamin D.

INTRODUCTION

Vitamin D deficiency is prevalent in the developed and developing worlds.^1,2 Vitamin D deficiency/insufficiency is increasing in frequency.³ Studies have reported reduced Vitamin D concentrations in patients with previous and prevalent cardiovascular or cerebrovascular diseases.^4,5 Vitamin D deficiency is commonly noticed during admission to intensive care units. Although it is not an independently decisive factor for mortality, it might be related to the worse clinical status at ICU admission. The effect of vitamin D replacement on mortality is controversial.⁶ Prevalence of vitamin D deficiency in India Vitamin D deficiency is on the rise as a major public health problem in India. Skin complexion, poor sun exposure, vegetarian food habits and lower intake of vitamin d fortified foods could be attributed to the high prevalence of Vitamin D deficiency in India. A study conducted amongst apparently healthy subjects to measure their serum Vitamin D level documented that significant Vitamin D deficiency was present in up to 90% of the subjects.⁷ Subsequently, studies conducted in different parts of the country have documented a widespread prevalence of Vitamin D deficiency in all age groups including toddlers, school children residing in rural or urban areas.⁸

OBJECTIVE

To assess the Vitamin D level among children admitted to the ICU.

REVIEW OF LITERATURE

Mehrotra et al ⁹ reported the prevalence of Vitamin D deficiency among infants with hypocalcemic seizures (90%), and controls (41.7%). Mean serum Vitamin D values of study infants (6.54 ng/ml) were significantly lower than those of healthy breastfed infants (9.06 ng/ml). A high prevalence of vitamin D deficiency (86%) in healthy term-born infants at the age of 3 months was attributed to the Vitamin D status of mothers¹⁰. Wayse et al¹¹  documented the prevalence of Vitamin D deficiency (levels below 14ng/ml) amongst children as 82.9 % and 82% in two regions and 2% in the third region. The study reported the prevalence of Vitamin D deficiency as 61.4%. Atalan et al ⁶ reported mortality rate was 21.6%. There was no significant difference between mortality rates of septic patients with normal and low vitamin D levels (p=0.071). Ebenezer K et al. ¹² reported Vitamin D deficiency was seen in 40.3 % of the critically ill children. Shock (30.8 %), CNS conditions (23.1 %) and respiratory illnesses (21.2 %) were the three most common reasons for admission to the ICU. Ponnarmeni S et al.¹³ reported prevalence of Vitamin D Deficiency was higher among critically ill children with sepsis compared to healthy controls. A high prevalence of Vit D Deficiency in critically ill children with sepsis was found, but it was not associated with greater severity of illness or other clinical outcomes.  Sankar J et al. ¹⁴ reported that the prevalence of vitamin D deficiency was 74 %. The duration of ICU stay was significantly longer in ‘vitamin D deficient’ children (7 days) than in those with ‘no vitamin D deficiency’. Rippel C et al. ¹⁵ reported the prevalence of Vitamin D deficiency was 34.5 % but was not associated with longer PICU stay or increased hospital mortality. Rey C et al ¹⁶ reported that the prevalence of Vitamin D deficiency was 29.5%. Pediatric intensive care patients presented an odds ratio of 2.26. Vitamin D deficiency incidence was high in PICU patients. Vitamin D deficiency was not associated with higher risk of mortality. Ayulo M Jr et al. ¹⁷ reported Vitamin D deficiency in 28% of patients, and vitamin D insufficiency was found in 47% of patients. There was 3% mortality, 83% of which occurred in patients with low vitamin D levels.

METHODOLOGY

A prospective observational hospital-based study was conducted at a government tertiary care hospital in Chennai, Tamil Nadu from January 2018 to Dec 2018. Eligible children below 5 years admitted to the ICU with Glasgow coma scale <8 or shock from any origin were included in the study as cases and children admitted to ICU without the above critical presentations were included in the study as controls. Children with chronic diseases, organ failure and treatment history of Vitamin D were excluded. Vitamin D insufficiency was defined as vitamin D level lower than < 30ng/ ml. Deficiency were defined as vitamin D level lower than < 20ng/ml. Descriptive analysis was conducted for quantitative variables. Frequency and proportion analysis was conducted for categorical variables. SPSS version 20 was used for statistical analysis.

RESULTS

Table 1: Demographic and clinical profile

The gender distribution among the cases was 55.8% male and remainder 44.2% female. The control group had 69.2% male and 30.8% female. Age distribution among cases was 33.7% participants aged below 1 year, 37.5% participants were aged 1-3 years and 28.8% participants aged 3-5 years. Moderate malnutrition was seen in 22.1% of the cases and 25% presented with severe malnutrition. Nutrition and Socioeconomic status did not show any significance. 10.6% of cases had severe Vitamin D deficiency, 52.9% presented with moderate Vitamin D deficiency and 26.9% cases presented with mild Vitamin D deficiency.  84.1% of the cases died undergoing treatment. The median Vitamin D level among cases compared to controls was 18 and 23.3 between the two groups, which was statistically significant (p-value <0.001).

Table 2: Comparison of vitamin D levels between age group

Of the 70 children below 1-year age group, 15.6% participants had severe deficiency, 52.9% participants had vitamin D deficiency and 28.6% participants had vitamin D insufficiency. Of 23 children between 1-3 year age group, 5.2% participant had severe deficiency, 61.5% participants had vitamin D deficiency and 21.8% participants had vitamin D insufficiency. Among children between 3-5 year age group, 11.6% participants had severe deficiency, 41.6% participants had vitamin D deficiency and 31.6% participants had vitamin D insufficiency. There was no statistical significance difference in the levels of vitamin D across age groups.

Table 3: Comparison of vitamin D level in cases to involved system on admission

50.5% of the cases were admitted with symptoms of the respiratory system. Of those admitted with respiratory symptoms, 58.1% were categorized as Vitamin D deficient and 18.1% were vitamin D insufficient. 44.7% of the ICU admissions presented with CNS infection symptoms, of which 48.4% participants had vitamin D deficiency and 34.4% had vitamin D insufficiency.

Table 4: Comparison of vitamin D level in cases to nutritional status (N=208)

Severe malnutrition was seen among 55.8% of children diagnosed with vitamin D deficiency and 30.8% of children with vitamin D insufficiency. Moderate malnutrition was seen in 56.5% of children with vitamin D deficiency. The difference in the vitamin D levels between children nutrition statuses was statistically not significant.

Table 5: Comparison of vitamin D level in cases to outcome

Death was the outcome among 84.1% of the study group. The proportion of children among those who died was 53.7% belonging to the vitamin D deficient group. Among the discharged children 48.5% were diagnosed as vitamin deficient. The vitamin D level was found not to be significant to the outcome.

DISCUSSION

Recently published studies reported 40 % ¹², 50 % ¹³ and 74% ¹⁴ Vitamin D deficiency. Various factors like duration and timing of sun exposure, amount of skin exposed, skin pigmentation, dietary and genetic factors ¹⁸, have been implicated as possible reasons for the high incidence of vitamin D deficiency observed in the subcontinent. The deficiency may not be clinically relevant. There are multiple other factors involved for the critically ill population. Vitamin D deficiency is presumed to increase morbidity and mortality by its pleiotropic effects on various organ system functions and its effects on innate and adaptive immunity¹⁷. 84.1% of the study subjects in the present study faced death as an outcome. We observed that children who were vitamin D deficient at admission were more likely to require mechanical ventilation, inotropes, and fluid boluses and have prolonged duration of mechanical ventilation. All these factors in combination might have contributed to the outcome in this group of children. Vitamin D deficiency in children from other countries show variable prevalence, for instance the prevalence among 12–24 month-olds in China was 65.3% ¹⁹; non-malnourished children in Qatar was 68.8% ²⁰, urban children aged 1–6 years in Saudi Arabia was 63% ²¹, in rural Ethiopia  among school-aged children in the community was 49% ²² and hospitalized malnourished  children in Uganda was 43%. Ejaz et al. ²³ reported 79% severely malnourished patients, 20% moderate malnutrition. 42% of the severely malnourished children had severe stunting. Rickets was diagnosed in 36% participants. Ebenezer K et al. ¹² reported Vitamin D deficiency was seen in 40.3 % of the critically ill children. Shock was identified as the cause for admission in 30.8 %, CNS conditions 23.1 % and respiratory illnesses in 21.2%, which were the three common reasons to the ICU. Ponnarmeni S et al.¹³ reported prevalence of Vitamin D Deficiency was higher among critically ill children with sepsis compared to healthy controls. Madden K et al. ²⁴ analysed and reported that after adjusting for factors associated with deficiency, lower Vitamin D levels were associated with higher admission day illness severity.  Mehta S et al. ²⁵ reported the prevalence of Vitamin D deficiency was 32%. These data indicate that Vitamin D deficiency is prevalent among malnourished children. However, Mc Nally et al. ²⁶ have documented a similar observation in the study where the authors observed that children with higher weight for age were more deficient than others. The prevalence of vitamin D deficiency was high in both well-nourished and malnourished groups. 55.8% of children with severe malnutrition nutrition status had vitamin D deficiency in the present study.

CONCLUSION

90.4% of the admitted children presented with one of the categories of vitamin D deficiency. 50.5% of the cases were admitted with symptoms of the respiratory system. 44.7% of the admissions presented with CNS infection symptoms. Severe vitamin D deficiency was seen in 10.6% of the study group. Death was the outcome among 84.1% of the study group. Vitamin D levels were not statistically significant to systems involved on admission, nutritional status and outcome of the admitted children. Statistical significance was noted in the levels of vitamin D between cases and controls. The cases presented with significantly lower serum vitamin D levels compared to the controls.

REFERENCES

1. van Schoor NM, Lips P. Worldwide vitamin D status. Best Pract Res Clin Endocrinol Metab. 2011;25(4):671-80.
2. Mithal A, Wahl DA, Bonjour JP, Burckhardt P, Dawson-Hughes B, Eisman JA, et al. IOF Committee of Scientific Advisors (CSA) Nutrition Working Group. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int. 2009;20(11):1807-20.
3. Forrest KY, Stuhldreher WL. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res. 2011;31(1):48-54.
4. Pilz S, Tomaschitz A, Marz W, Drechsler C, Ritz E, Zittermann A, et al. Vitamin D, cardiovascular disease and mortality. Clin Endocrinol (Oxf). 2011;75(5):575-84.
5. Brewer LC, Michos ED, Reis JP. Vitamin D in atherosclerosis, vascular disease, and endothelial function. Curr Drug Targets. 2011;12(1):54-60.
6. Atalan HK. Serum Vitamin D Level at ICU Admission and Mortality. 2017;45(4):193-6.
7. Goswami R, Gupta N, Goswami D, Marwaha RK, Tandon N, Kochupillai N. Prevalence and significance of low 25-hydroxyvitamin D concentrations in healthy subjects in Delhi. Am J Clin Nutr. 2000;72(2):472-5.
8. Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D, Srinivasarao PV, Sarma KV, et al. High prevalence of low dietary calcium, high phytate consumption, and vitamin D deficiency in healthy south Indians. Am J Clin Nutr. 2007;85(4):1062-7.
9. Mehrotra P, Marwaha RK, Aneja S, Seth A, Singla BM, Ashraf G, et al. Hypovitaminosis d and hypocalcemic seizures in infancy. Indian Pediatr. 2010;47(7):581-6.
10. Jain V, Gupta N, Kalaivani M, Jain A, Sinha A, Agarwal R. Vitamin D deficiency in healthy breastfed term infants at 3 months & their mothers in India: seasonal variation & determinants. Indian J Med Res. 2011;133: 267-73.
11. Wayse V, Yousafzai A, Mogale K, Filteau S. Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y. Eur J Clin Nutr. 2004;58(4):563-7.
12. 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(2):120-5.
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. Paediatrics and International Child Health. 2016;36(1):15-21.
14. Sankar J, Lotha W, Ismail J, Anubhuti C, Meena RS, Sankar MJ. Vitamin D deficiency and length of pediatric intensive care unit stay: a prospective observational study. Ann Intensive Care. 2016;6
15. Rippel C, South M, Butt WW, Shekerdemian LS. Vitamin D status in critically ill children. Intensive Care Med. 2012;38(12):2055-62.
16. Rey C, Sanchez-Arango D, Lopez-Herce J, Martinez-Camblor P, Garcia-Hernandez I, Prieto B, et al. Vitamin D deficiency at pediatric intensive care admission. J Pediatr (Rio J). 2014;90(2):135-42.
17. Ayulo M, Jr., Katyal C, 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(2):69-76
18. Khadilkar A, Das G, Sayyad M, Sanwalka N, Bhandari D, Khadilkar V, et al. Low calcium intake and hypovitaminosis D in adolescent girls. Arch Dis Child. 2007;92(11):1045.
19. Strand MA, Perry J, Jin M, Tracer DP, Fischer PR, Zhang P, et al. Diagnosis of rickets and reassessment of prevalence among rural children in northern China. Pediatr Int. 2007;49(2):202-9
20. Bener A, Al-Ali M, Hoffmann GF. High prevalence of vitamin D deficiency in young children in a highly sunny humid country: a global health problem. Minerva Pediatr. 2009;61(1):15-22.
21. Kensarah OA, Jazar AS, Azzeh FS. Hypovitaminosis D in Healthy Toddlers and Preschool Children from Western Saudi Arabia. Int J Vitam Nutr Res. 2015;85(1-2):50-60.
22. Herrador Z, Sordo L, Gadisa E, Buño A, Gómez-Rioja R, Iturzaeta JM, et al. Micronutrient deficiencies and related factors in school-aged children in Ethiopia: a cross-sectional study in Libo Kemkem and Fogera districts, Amhara Regional State. PLOS ONE. 2015;9(12):e112858.
23. Ejaz MS, Latif N. Stunting and micronutrient deficiencies in malnourished children. J Pak Med Assoc. 2010;60(7):543-7.
24. Madden K, Feldman HA, Smith EM, Gordon CM, Keisling SM, Sullivan RM, et al. Vitamin D deficiency in critically ill children. Pediatrics. 2012;130(3):421-8.
25. Mehta S. Vitamin D levels among children with severe acute malnutrition. World journal of pharmaceutical research. 2017;6(5):781-85.
26. 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(3):429-36.