Prevalence of 25-Hydroxyvitamin D Deficiency and its severity correlation with Acute Traumatic brain Injury in Indian Patients: A Perspective Observation Study

Ajay Choudhary², Rajesh Sharma², Ashok Kumar¹*, Kuldeep Kinja³, Ravi Berwal⁴, Swapnil Sharma¹

¹Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan - 304022, India.

²Department of Neurosurgery, Atal Bihari Vajpayi Institute of Medical Sciences,

Dr. R.M.L. Hospital, New Delhi - 110001, India.

³Cliniminds Institute of Health Sciences, Noida, U.P - 201301, India.

⁴Guru Jambheshwar University and Science Technology, Hisar - 125001, Haryana, India.

*Corresponding Author E-mail: ashujinagal12@gmail.com

ABSTRACT:

Objective: To study the prevalence of 25-hydroxyvitamin D deficiency pattern during three year (2017-2020) and severity correlation among individuals with acute traumatic brain injury (TBI). Methodology: Subjects with acute TBI admitted from June 1st, 2017 through June 30th, 2020 were recruited. 280 out of 445 met inclusion criteria. The demographic injury related details, assessment of 25 OH vitamin D and Glasgow Comma (GCS) score were done at the time of admission. Results: The year wise enrolled subjects were young with mean age of 28.39±0.86 years with males (73.3%) and female (23.7%), in first year, 27.77±5.35 years with males (81.67%) and female (18.33%), in second year and 23.04±7.10 years with males (88.57%) and female (11.42%), in third years. Mean value of 25(OH) vitamin D in subjects during three years were 23.78±11.79ng/mL, 21.65±12.53 ng/mL and 25.18±18.58ng/mL. The vitamin D deficiency levels in this study were tabulated as: deficient (level <20 ng/mL), insufficient (level 20–29.9ng/mL), and sufficient (level ≥30ng/mL). Which were found during three years as: In First year, Deficient (64.44%), Sufficient (11.11%), insufficient (24.44%), in second years, Deficient (88.33%), Sufficient (2.66%), insufficient (10.00%) and in third year Deficient (88.57%), Sufficient (1.42%), insufficient (10.00%). In which sufficient level were found to be decreased statistically significant with years with P value= 0.0001. The severity assessment through GCS score were found to be statistically increased with deficient levels with P values=0.0447, but found no significance, when comparison were done between years wise GCS score and levels of vitamin D. Conclusion: The study found decreased prevalence of vitamin D deficiency levels with increased severity. Therefore it should be routinely screened and treated as indicated.

KEYWORDS: Traumatic Brain injuries, vitamin D, Deficiency, Glasgow Comma Score, Severity.

INTRODUCTION:

Vitamin D deficiency is prevailing at a rapid rate in society and markedly affecting their physical and mental wellbeing (1). Global prevalence of 25(OH) D (25-hydroxyvitamin D) deficiency levels in healthy individuals is around 80%–100% where India has more than 90% of vitamin D deficient individuals (2). Vitamin D deficiency is getting predominant in society and thus majority of TBI individuals is exhibiting low level of Vitamin D during the admission (3). The incidence of vitamin-D deficiency in TBI patients is becoming very common and is primarily associated with impaired cognitive function and psychiatric illness (4). Worldwide vitamin-D deficiency in individual bearing head injury (≥65%) has emerged as a key indicator of mortality and morbidity amongst young population (3). Early detection of vitamin-D deficiency after traumatic brain injury (TBI) has been established as an important factor in predicting survival rate and quality of life in an individual (5).

Vitamin D, a hormone, has secosteroidal, neuroactive and neurosteroidal action in the central neuronal system (6). Vitamin D gets synthesized at skin in the presence of sunlight and remaining content comes from dietary supplement. (7). The Endocrine Society Clinical Practice Guideline in 2011 released a guideline for proper judgment of vitamin D level in serum concentration, the society defines -25(OH) D serum level below 20ng/ml (50nmol/l) as deficiency, serum 25(OH) D level between 21-29ng/ml as insufficiency and if the 25(OH) D level is greater than 30ng/ml called as sufficient (8).

Vitamin D deficiency may be a causative factor for worsening physical and cognitive health and it can be a risk factor for osteoporosis, osteopenia and bone fractures (9). Insufficient (20–29.9ng/mL) and deficient levels (<20ng/mL) of Vitamin D have also been linked with negative impact on cognitive functions, and may also be associated with dementia and further cognitive disorder (10). Vitamin D shields brain via neural protection through antioxidant process, calcium channels regulation, potentiates nerve conduction, and detoxification actions (11). As proper nerve conductance and protection act as an important factor in TBI recovery (12), these vitamin D arbitrate protection process can be important in a TBI severity.

Although various studies have done on the role of vitamin D insufficiency or deficiency in the local population, still, scant data is available in acute TBI area. A study on brain, spinal and musculoskeletal injuries observed that 83% were vitamin D insufficient or deficient (13). These observation limelight both increased prevalence of vitamin D deficiency in TBI patients and the severe impact of this deficiency.

While early detection of Vitamin D deficiency features the promising issues enclosing insufficient vitamin D in TBI patients, no study Yet has been examined the prevalence and functional associations of insufficient or deficient vitamin D among TBI patients undergoing acute severe traumatic Brain injury.

Therefore, the present study aims to establish vitamin D prevalence rates in acute Severe TBI and investigate the association between vitamin D levels and GCS based severity (14) outcomes. A prospective observational study was done on patients admitted to a north Indian hospital over three year durations.

MATERIALS AND METHODS:

Participants:

A total 280 patients of both genders (male and female) were recruited as per defined criteria of the study. Inclusion for patients with age between 18 to 65 years, Injury within 24 hours referral from trauma centre and Intensive care unit (ICU) of Dr Ram Manohar Lohia Hospital, New Delhi. Individuals bearing glasgow coma scale (GCS) score from 4 to 8.

Patients with GCS higher than 8 or lower than 4 or history of underlying neurologic, and spinal cord injury were excluded from the study.

Ethical approval:

The study was executed according to clinical protocol approved by the Institutional ethics committees of Atal Bihari Vajpayi Institute of Medical Sciences, Dr. Ram Manohar Lohia Hospital (no.-197/EC (16/2017)/ PGIMER/RMLH) 237/18) New Delhi, India. Patient’s screening and enrolment begin from June 2017 until June 2020.

Study procedure and data collection:

Patients with severe traumatic brain insult admitted in ICU at referral trauma centre of Dr Ram Manohar Lohia Hospital and were immediately analyzed for serum vitamin D level. Patients with GCS score 4 to 8 and admitted within 24 hours of injury were undergone informed consent process recruited in the study. Obligatory information including demography, mode of injury and clinical history at the time of admission was recorded. During the course of intervention, GCS of the patient was recorded by a neurosurgery resident every day on round at 8:00 AM, who was blinded to the intervention. Severity outcome analysis like GCS scores and serum vitamin D level was assessed at baseline.

STATISTICAL ANALYSIS:

Descriptive statistics were used to summarize demographic and injury characteristics. Patient data was then separated into three years, each year with three vitamin D groups according to vitamin D levels at admission: deficient (<20ng/mL), insufficient (20–29.9 ng/mL), or sufficient (≥30ng/ml). Comparisons of vitamin D level groups between each year were made using analysis of variance. Spearman’s correlations were employed to assess the relationship between vitamin D levels in each year with GCS score.

RESULTS:

A total 280 patients of both the gender around Delhi areas in India, injured with severe traumatic brain insult were recruited and investigated as per scheme shown in Figure 1.

Table 1 a: Demographic characteristics of subjects recruited in year 2017 -2018

Age, (mean ± SD)	28.39±0.86
Male (%)	73.3%
Female (%)	23.3%
Care provided to reach (No professional care, Ambulance) (%)	No professional care (77.7%), Ambulance (22%)
Mechanism of Injury (Fall from height, RTA, Assault) (%)	Fall from height (44.44%), RTA (47.7 %), Assault (3.33 %), Sport injury (4.44 %)
Vitamin D Level	23.78±11.79
Vitamin D Category (Deficient, Sufficient, insufficient)(%)	Deficient (64.44%), Sufficient (11.11%), insufficient (24.44%)

Table values are presented in mean ± SD and in %

RTA, Road Traffic Accidents

Table 1 b: Demographic characteristics of subjects recruited in year 2018-2019

Age, (mean ± SD)	27.77±5.35
Male (%)	81.67%
Female (%)	18.33%
Care provided to reach (No professional care, Ambulance) (%)	No professional care (88.30%), Ambulance (11.67%)
Mechanism of Injury (Fall from height, RTA, Assault) (%)	Fall from height (36.67%), RTA (55.83 %), Assault (3.33 %), Sport injury (4.16 %)
Vitamin D Level	21.65±12.53
Vitamin D Category (Deficient, Sufficient, insufficient)	Deficient (88.33%), Sufficient (2.66%), insufficient (10.00%)

Table values are presented in mean ± SD and in %

RTA, Road Traffic Accidents

Table 1c: Demographic characteristics of subjects recruited in year 2019-2020

Age, (mean ± SD)	23.04±7.10
Male (%)	88.57%
Female (%)	11.42%
Care provided to reach (No professional care, Ambulance) (%)	No professional care (94.28 %), Ambulance (5.71%)
Mechanism of Injury (Fall from height, RTA, Assault) (%)	Fall from height (45.71%), RTA (50.00 %), Assault (4.28 %), Sport injury (0.00 %)
Vitamin D Level	25.18±18.58
Vitamin D Category (Deficient, Sufficient, insufficient) (%)	Deficient (88.57%), Sufficient (1.42%), insufficient (10.00%)

Table values are presented in mean ± SD and in %

RTA, Road Traffic Accidents

Table 2-Comparison between years wise GCS score and levels of vitamin D

	Year 2017-2018	2018-2019	2019-2020	p-value
Deficient	11.80±4.4	8.53±4.87	8.14±4.22	0.3301
Insufficient	24.18±4.36	22.93±2.64	22.41±2.17	0.6248
Sufficient	35.37±5.79	33.50±2.12	45.00±0.00	0.0001
GCS score	6.14±0.49	6.11±0.14	6.13±0.84	0.9937

Table values are presented in mean ± SD

GCS, Glasgow Comma score

In which sufficient level were found to be decreased statistically significant with years with P value= 0.0001 when Comparison between years wise GCS score and levels of vitamin D was done (Table 2).

At baseline year wise mean GCS scores of the recruited subjects were found as 6.14±0.49 in first years, 6.11±0.14 in second year and 6.13±0.84 in third years respectively. The severity assessment through GCS score were found to statistically increased with deficient levels with P values =0.0447 when Comparisons between GCS score and levels of vitamin D were done (Table 3), but found no significance, when comparison was done between year wise GCS score and levels of vitamin D (Table 2).

Table 3 - Comparison between GCS score and levels of vitamin D

Severity outcome	Deficient	Insufficient	Sufficient	p-value
GCS score	6.01±0.08	6.24±0.22	6.13±0.71	0.0447

Table values are presented in mean ± SD

DISCUSSION:

The current prospective observational study investigates the three years prevalence pattern of vitamin D deficiency, sufficiency and insufficiency in TBI patients. Overall, results revealed 80% of TBI patients were vitamin D insufficient or deficient, which is in accordance with previous result observed by Sharma et al., 2020 (3). However, a very scant year wise assessment of 25-hydroxyvitamin D deficiency prevalence pattern in TBI population data are available in the literature, thus current study provides useful information about prevalence of 25-hydroxyvitamin D deficiency rates and associated severity.

An epidemiology study on TBI conducted in India revealed that 72% of TBIs occurs at roads accidents, 20% at homes, 3% in irrigation lands, 2% in construction sites as due to fall or fall off objects), 1% in play grounds and 0.6% in technical work places (15). Current study also confirms that almost similar kind of ratio where 67% individuals got TBI due to road traffic accidents and 45% fall from heights and 4% assaults and 3.4% individual included were sports injury cases.

Vitamin D deficiency in the selected severe TBI patient population was found 92% in three year in our study. This is similar to the observations of previous study that Global prevalence of 25(OH) D (25-hydroxyvitamin D) deficiency levels in healthy individuals is around 80%–100% whereas India has more than 90% of vitamin D deficit individuals (2).

Majority of previous studies have shown that TBI with vitamin D deficiency at the time of admission is a reliable predictor of prognosis and severity outcome in these patients. (16,3). As seen in a study conducted by Sharma et al.2020, the GCS score 7 with Vitamin D deficiency level 18ng/mL was accurate in determining 80% of outcome predictions in traumatic patients (3). In our study, 85% of patients possessing GCS score > 7 with Vitamin D deficiency level of 21ng/mL. Hence, it can be concluded that traumatic brain injury with vitamin D deficiency leads to poor GCS or severity outcome in TBI patients.

While evidence-based parameters for screening and managing vitamin D deficiency in TBI patients are not available, current study observed that the majority of severe TBI patients have vitamin D deficiency or insufficiency levels in the acute phase. Future research to set up a relation of baseline vitamin D and Severity outcome (Neurological and GCS score) status should be carried among individuals with acute TBI.

LIMITATIONS OF THE STUDY:

The limitations for our current study is that this data collected from only one institution, while vitamin D levels may vary across larger regions.

CONCLUSION:

Current study observed a correlation of vitamin D insufficiency or deficiency 3 years rates with neurological severity in severe acute TBI patients. These observations favors screening 25 OH vitamin D level upon admission. Future interventions should be conducted to investigate prevalence of vitamin D, relationships between vitamin D levels and functional measures, and severity outcomes.

ACKNOWLEDGMENTS:

We would like to appreciate the Nursing staff of Trauma-RR, Nuero trauma 3^rd floor and NS-13 ward for their kind cooperation.

CONFLICT OF INTEREST:

All authors declare no conflicts of interests. All authors agree to submit the manuscript.

REFERENCES:

1. Utiger R D. The need for more Vitamin D. N. Engl. J. Med. 1998; 338: 828–829.

2. Aparna P, Muthathal S, Nongkynrih B, Gupta SK. Vitamin D deficiency in India. J Family Med Prim Care. 2018; 7(2): 324‐330.

3. Sharma S, Kumar A, Choudhary A, Sharma S, Khurana L, Sharma N, et al. Neuroprotective role of oral vitamin D supplementation on consciousness and inflammatory biomarkers in determining severity outcome in acute traumatic brain injury patients: A Double-Blind Randomized Clinical Trial. Clin. Drug. Investig. 2020; 40: 327–334.

4. Jamall A, Feeney C, Zaw, Linn J, Malik A, Niemi E K, et al. Prevalence and correlates of vitamin D deficiency in adults after traumatic brain injury. Clin. Endocrinol. 2016; 85(4): 636-644.

5. Toman E, Bishop J, Davies D, Su Z, Criseno S, Mason A, et al. Vitamin D deficiency in traumatic brain injury and its relationship with severity of injury and quality of Life: a prospective, observational Study. J. Neurotrauma. 2017; 1(7): 1448-1456.

6. Atif F, Sayeed I, Ishrat T, Stein DG. Progesterone with Vitamin D affords better neuroprotection against excitotoxicity in cultured cortical neurons than progesterone alone. Mol Med. 2009; 15: 328-36.

7. Kadoura S, Alhalabi M, Nattouf A H. Effect of calcium and vitamin D supplements as an adjuvant therapy to metformin on lipid profile in vitamin D deficient/insufficient polycystic ovary syndrome patients: A Randomized, Placebo-Controlled Clinical Trial. Research J. Pharm. and Tech. 2019; 12(5):2 327-2332.

8. Shah P, Kulkarni S, Sureka SND, Dutta S, Vipat AS, et al. Prevalence Study of vitamin D deficiency and to evaluate the efficacy of vitamin D3 granules 60,000 IU supplementation in vitamin D deficient apparently healthy adults. Indian J Clin Pract. 2013 May; 23(12): 827-832.

9. Subashree R., Arjunkumar R. Vitamin D Deficiency in Periodontal Health. Research J. Pharm. and Tech. 7(2): Feb. 2014; Page 248-252.

10. Van der Schaft, J., Koek, H., Dijkstra, E., Verhaar, H., Van der Schouw, Y., & Emmelot-Vonk, M. The association between vitamin D and cognition: a systematic review. Ageing Res. Rev.2013; 12 (4), 1013-1023.

11. Burje S, Rungta S, Shukla A. Detection and Classification of MRI Brain Images for Head/Brain Injury Using Soft Computing Techniques. Research J. Pharm. and Tech. 2017; 10(3): 715-720.

12. Povlishock, J. T., and Katz, D. I. Update of neuropathology and neurological recovery after traumatic brain injury. J Head Trauma Rehab.2005; 20(1): 76-94.

13. Shinchuk, L. M., Morse, L., Huancahuari, N., Arum, S., Chen, T. C., & Holick, M. F. Vitamin D deficiency and osteoporosis in rehabilitation inpatients. Arch. Phys. Med. Rehabil.2006; 87(7): 904-908.

14. Oretha Istiqomah Sunarto, Abdul Hafid Bajamal, Abdurachman. Outcome of Brain Injury Patients After Decompressive Craniectomy in Tertiary Referral Hospital in East Java Indonesia. Research J. Pharm. and Tech. 2019; 12(12): 6057-6061.

15. Gururaj G, Kolluri S.V.R, Chandramouli B.A, Subbakrishna D.K, Kraus JF. Traumatic Brain Injury. National Institute of Mental Health & Neuro Sciences, Publication no. 61, Bangalore - 560029, India. 2005.

16. Udekwu P, Schiro SK, Vaslef, Baker C, Oller D. Glasgow coma scale score, mortality and functional outcome in head injured patients. J. Trauma. 2004; 56 (5):1084-1089.