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The Egyptian Journal of Bronchology
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Relationship between serum 25-hydroxyvitamin D, total antioxidant capacity and pneumonia incidence, severity and outcome in Nigerian children

The Egyptian Journal of Bronchology volume 14, Article number: 29 (2020) Cite this article

Abstract

Background

The pathologic basis of childhood community-acquired pneumonia (CAP) involves the generation of reactive oxygen species by immune cells leading to cellular damage and lung congestion. Serum antioxidants and vitamin D with immunomodulatory properties therefore hold prospects in the prevention and management of pneumonia in children. This case–control study set out to compare the serum 25-hydroxyvitamin D (25-OHD) and total antioxidant capacity (TAC) in Nigerian children with CAP and age- and sex-matched controls and to relate these parameters with pneumonia severity and outcome—length of hospital stay (LOH).

Results

A total of 160 children (80 each for CAP and controls) were recruited. The median (IQR) age was 1.8 (0.6–4.0) years, male:female 1.7:1, 63 (78.8%) and 11 (13.8%) of CAP group had severe pneumonia and parapneumonic effusions, respectively. Serum 25-OHD (33.8 (18.3) ng/ml vs. 41.9 (12.3) ng/ml; p = 0.010) and TAC (6.1 (4.4–8.1) ng/dl vs. 7.2 (4.7–17.5) ng/dl; p = 0.023) were lower in children with CAP than controls. Lower serum 25-OHD was observed in severe than non-severe pneumonia (30.5(17.1) ng/ml vs. 46.3 (17.6) ng/ml; p = 0.001) but LOH did not correlate with serum 25-OHD and TAC.

Conclusion

Children with CAP had lower serum vitamin D and antioxidants than controls, and severe pneumonia was significantly associated with suboptimal serum vitamin D. They however were not related to pneumonia outcome. Optimal serum vitamin D and antioxidants may play a role in reducing the incidence of childhood CAP in Nigerian children.

Background

Community-acquired pneumonia (CAP) remains a leading cause of ill health and deaths in children from developing countries [1]. Over the decades, lots of evidence-based interventions like case-based management of pneumonia at the primary level, reduction of indoor air pollution, and promotion of breastfeeding had been put in place to reduce the burden of childhood CAP [2]. Epidemiological evidences revealed that significant progress had been made in this respect [3]; however, CAP still accounts for about 15% of global under-five mortality causing more than 800,000 deaths in children with over 90% of these deaths occurring in developing countries [1].

The acute inflammation of the lung parenchyma typifies CAP, and this often follows inhalation of microbes or less frequently spread of microbes to the lungs via the haematogenous route. Microbial invasion of the lung stimulates the innate and adaptive immune responses [4], ultimately triggering a cascade of inflammatory reactions via mediators and cytokines [5]. Inflammatory cells (alveolar macrophages and mono- and polymorphonuclear cells) are attracted to the site of infection to phagocytose these microbes in a process that includes respiratory burst and release of oxidants and reactive oxidant species (ROS) [4, 5]. Failure to curtail the infection and inflammation may result in lung congestion, more free radical generation, cellular damages, consolidation and even parapneumonic effusions [4]. These pathologies impair gaseous exchange, increase dead space and cause intrapulmonary shunting and hypoxaemia [4, 5].

Endogenous antioxidants are needed to ameliorate the inflammatory and cellular damage effects of oxidative stresses generated by immune cells [6]. Total antioxidant capacity (TAC) which measures non-enzymatic antioxidant activities [7] has been reported to relate to the severity of sepsis and acute respiratory tract infections (ARTIs) in children [8, 9]. The serum levels of antioxidants in children with CAP may therefore hold prospects in ameliorating the severity and outcome of the infection.

Vitamin D, a fat-soluble vitamin derived from the effects of sunlight on the skin and from dietary sources, plays important roles in calcium–phosphate homeostasis and bone metabolism [10]. Vitamin D also has important pleiotropic immunomodulatory activities [11,12,13]. Vitamin D, most frequently assayed as 25-hydroxyvitamin D (25-OHD), being the most stable form, has been reported to play significant roles in both innate [11, 12] and adaptive immune responses to infections [13]. It increases the production of antimicrobial peptides (β-defensins and cathelicidin) by immune cells in response to microbial agents, hence reducing colonisation of respiratory tract by microorganisms [11, 12]. Vitamin D also induces the expression of the Toll-like receptors (TLRs) which are important pattern recognition receptors on the surfaces of immune cells that allows for prompt recognition of pathogen-associated molecular patterns of microorganisms [12]. Animal studies also showed that vitamin D inhibits T helper cell type 1(Th1)-associated cytokines, hence reducing effects of microbe-induced inflammation on the host [13]. However, there are mixed reports pertaining to the relationship between serum levels of vitamin D and incidence and severity of ARTIs in children [14,15,16,17] and no consensus on the roles of vitamin D on the outcome of children hospitalised with pneumonia [18,19,20,21,22,23].

In the light of the immunoregulatory effects of vitamin D and the important roles of serum antioxidants to maintain oxidative balance in childhood infections, this study aimed to compare the serum 25-OHD and TAC in children with CAP and controls and to relate these to disease severity and length of hospitalisation at a Nigerian teaching hospital.

Methods

The study was case–control in design, conducted at Wesley Guild Hospital (WGH), Ilesa, Nigeria over a 12-month period (January to December, 2019). The hospital is an arm of Obafemi Awolowo University Teaching Hospitals Complex (OAUTHC), Ile-Ife, Nigeria. Ilesa is located on latitude 7° 35’ N of the equator and longitude 4° 51’ E of the meridian in the tropical rain forest region of Nigeria [24].

Sample size estimation

The estimated sample size (160) was derived using open Epi software(R) [25]. The mean difference of serum 25-OHD between children with CAP and controls was 4.8 nmol/l based on a previous study [14], and standard deviations from the mean for the two groups were 23.3 and 23.0 nmol/l, respectively [14]. Five percent significance (alpha) level, 80% study power, and 95% confidence interval and ratio 1:1 for cases to control were used; the calculated sample size was approximately 160, i.e., 80 each for cases and controls.

The cases were children between the ages of 2 months to 14 years with CAP, and the controls were age- and sex-matched apparently healthy children without pneumonia.

CAP was defined as age-specific fast breathing, i.e., respiratory rate > 50 breaths/min for children 2 to < 12 months, > 40 breaths/min for 1 to 5 years and > 30 breaths/min for > 5 years, with evidence of respiratory distress, abnormal breath sounds, i.e., reduced or absent, bronchial breath sound, or coarse crepitation with or without radiologic evidence of pneumonia [4, 26]. Children with any one of lower chest wall in-drawing, convulsions, central cyanosis, lethargy or altered sensorium, and inability to feed or drink were further classified as severe pneumonia [26]. Parapneumonic effusion was defined based on radiological evidence of pleural fluid collection [27] with free-flowing fluid on the pleural tap. Lack of consent, chronic cough > 2 weeks, wheezing, and diagnosis of hospital-acquired pneumonia were the exclusion criteria.

Socio-demographic details including age, sex and socio-economic class (SES) using a validated tool [28] were obtained. Breastfeeding and housing history were also obtained, and crowded homes were defined as ≥ 3 persons sharing the same room with the study participants [29]. Households using biomass and hydrocarbons as fuel for cooking and lighting were categorised as having significant indoor air pollution [30]. Immunisation history of the children was also documented. Nutritional status of the children was determined by comparing their weight for age and BMI for age with the WHO growth reference standards for under-fives [31] and school age children [32], respectively. The children were managed as per unit’s protocol [26] and outcome as well as length of hospital stay (LOH) noted.

Serum 25-OHD and TAC assay

Blood samples were collected from the children in plain tubes and allowed to clot. Samples were then centrifuged at 3000 revs/min for 15 min; supernatant serum was separated into aliquots preserved with acid (10% v/v HNO3) and stored at − 20 °C. Analysis of 25-OHD and TAC was done with high-performance liquid chromatography (HPLC) method using an automated 616/6265 transducer pump (Waters Incorporate, CA, USA) at the Analytical Services Laboratories of the International Institute of Tropical Agriculture (IITA), Ibadan, Nigeria.

TAC was calculated by summing up the individual HPLC peaks of each detectable antioxidant (total carotenoids, flavoids, phenols, antioxidant vitamins and micronutrients). Trolox (R) was used as the background quality control standard. Each blood sample was assayed in duplicate with the mean used as the precise estimated value, and the inter-assay coefficient of variations (CVs) for TAC was 4.8%.

Methanol and acetonitrile were used as solvent and laurophene as internal standard, while 25-OD2 and 25OHD3 were used as reference standard. The lower limit of detection of 25-OHD in serum was 5 ng/ml with a range of 5–100 ng/ml. The coefficient of variations for intra-day accuracy was 4.5%.

Vitamin D deficiency was defined as serum 25-OHD < 20 mg/ml and insufficiency as 20–30 ng/ml, and value > 30 ng/ml was defined as sufficient [33]. Vitamin D deficiency and insufficiency were further categorised as suboptimal vitamin D.

Data analysis

This was done using SPSS for Windows software version 17.0 (SPSS Inc. Chicago 2008). Kolmogorov–Smirnov statistic was used to test for normality of quantitative variables, and these were summarised as mean (standard deviation) or median (interquartile range) as appropriate. Differences between the summaries of quantitative variables were ascertained by Student t test or Mann–Whitney U test. The relationship between serum 25-OHD, TAC and LOH were ascertained by Pearson or Spearman Rho correlation as appropriate. Age range, sex, socioeconomic class categories, and pneumonia severity were summarised using percentages and proportions, and their differences were ascertained by Chi squared (x2) or Fischer’s exact test. Binary logistic regression analysis was undertaken to ascertain the independent determinants of the dichotomised outcomes (suboptimal vs. normal serum vitamin D). Effect size was interpreted as odds ratio (OR), and level of significance at 95% confidence interval (CI) was taken as p < 0.05.

Results

We recruited 160 children (80 each with CAP and controls) for this study. The sample was enriched with infants (37.7%), male gender (51.7%), and children from middle and low SES (66.7%). Exclusive breastfeeding (55.0%) and appropriate immunisation status (71.7%) were common, but few children (8.9%) were obese (Table 1).

Table 1 Characteristics of the study participants
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There was no significant difference in the age and sex distribution of the cases and controls; however, more proportions of the children with pneumonia were from low SES had undernutrition and inappropriate immunisation status (Table 1). The anthropometrics and other information about the study participants are highlighted in Table 2. Of the 80 children with CAP, 63 (78.5%) had features of severe pneumonia at presentation and 11 (13.8%) had parapneumonic effusions.

Table 2 Anthropometrics, serum vitamin D and total antioxidant capacity levels in the study participants
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The mean (SD) serum 25-OHD was 37.9 (16.1) ng/ml which ranged from 3.0 to 68.6 ng/ml. Forty (25.0%) of the children had suboptimal vitamin D including 18 (10.0%) with insufficient and 22 (15.0%) with deficient levels. More proportions of children with pneumonia had suboptimal serum 25-OHD levels (Table 1). Likewise, serum 25-OHD was lower in cases than control (Table 2).

The serum TAC ranged from 0.9 to 53.5 ng/dl with a median (IQR) of 6.4 (4.5–8.9) ng/dl. The CAP cases had significantly lower TAC than controls (Mann–Whitney U 2534.0; p = 0.023) (Table 2)

Serum 25-OHD, TAC and severity of CAP

The cases with severe pneumonia had significantly lower mean (SD) serum 25-OHD than the non-severe cases (30.5 (17.1) ng/ml vs. 46.3 (17.6) ng/ml; t test = 3.356; p = 0.001) (Fig. 1). Although serum TAC was lower in children with severe pneumonia, the difference was not significant (Median (IQR) 6.1 (4.4–8.2) ng/dl vs. 7.4 (3.5–9.1) ng/dl; Mann–Whitney U test = 532.5; p = 0.972) (Fig. 2). Also, no significant association was observed between the presence of parapneumonic effusions and serum vitamin D categories (Table 3).

Fig. 1
figure 1

Boxplot of serum vitamin D and pneumonia severity

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Fig. 2
figure 2

Boxplot of serum total antioxidant capacity and pneumonia severity

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Table 3 Factors associated with suboptimal vitamin D levels in children with pneumonia
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Factors associated with suboptimal vitamin D in children with pneumonia

These are highlighted in Tables 3 and 4. Children from low socio-economic class (OR = 3.789; 95% CI 1.416–10.139; p = 0.008) and those with features of severe pneumonia (OR = 5.154; 95% CI 1.260–21.077; p = 0.023) were more likely to have suboptimal vitamin D among the children with pneumonia using logistic regression analysis.

Table 4 Binary logistic regression analysis to determine the independent predictors of suboptimal vitamin D in children with pneumonia
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Outcome of hospitalisation

There were three (3.8%) cases of mortality. The length of hospital stay ranged from 1 to 22 days with a mean (SD) stay of 5.7 (3.5) days. There was no significant difference in the LOH in those with suboptimal vitamin D compared with those with normal serum vitamin D (Table 3). There was a negative (though insignificant) correlation between serum 25-OHD and LOH (r = − 0.068; p = 0.546) (Fig. 3). Serum TAC however correlated positively with LOH, though the relationship was not significant (Spearman rho = 0.022; p = 0.849) (Fig. 4).

Fig. 3
figure 3

Scattered plot of serum vitamin D and length of hospital stay

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Fig. 4
figure 4

Scattered plot of serum TAC and length of hospital stay

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Discussion

The study highlights significant lower serum 25-OHD in Nigerian children with CAP than apparently healthy controls. Also, serum 25-OHD was lower in those with severe than non-severe pneumonia. These findings were similarly reported by workers from other developing [34] and developed countries [16]. Increased demand for the immune regulatory functions of vitamin D in children with pneumonia and other infections may explain these findings [35, 36]. Vitamin D modulates both innate and adaptive immunity and regulates the inflammatory cascades [11,12,13]. These important immune regulatory function of vitamin D may lead to an increased demand in children with infections including CAP [35, 36], and if this increased demand is not met, it may manifest with suboptimal serum 25-OHD [14,15,16, 34]. Furthermore, children with suboptimal vitamin D may be unduly predisposed to pneumonia and other ARTIs [35, 36], hence the observation of low serum vitamin D in this group of children. Studies have shown that children with clinical rickets and sub-clinical vitamin D deficiency have increased risk of ARTIs [37,38,39]. The association between suboptimal serum vitamin D level and childhood ARTIs is also supported by the fact that there is an upsurge of ARTIs during winter period in temperate regions when serum vitamin D is low due to limited availability of sunshine [10]. Relationship between serum 25-OHD and childhood ARTIs may be a cause-and-effect type, low vitamin D predisposing to, and may also be, an effect of ARTIs.

Conversely, some workers reported no significant relationship between the incidence and severity of childhood ARTIs with serum vitamin D [14, 17]. Also, no significant beneficial effect of vitamin D supplementation was observed as regards the incidence and severity of childhood ARTIs [22, 23]. This may be related to the polymorphic nature of vitamin D receptors (VDRs) needed for optimal functioning of vitamin D [40]. This implies that there may be wide variations between individuals in terms of sensitivities to vitamin D [41]. Hence, serum vitamin D levels may not completely determine vitamin D functionality [40,41,42]. More studies on the genetic variations in VDRs and their effects on childhood ARTIs will be worthwhile.

No significant correlation was observed in this study between serum vitamin D and duration of hospital stay among the children with severe pneumonia. This agrees with reports from other developing countries [22, 23]. Rashmi et al. [20], in a systematic review of two randomised controlled clinical trials to ascertain the effects of vitamin D supplementation on childhood pneumonia-related outcomes, concluded that no effect of vitamin D supplementation on symptom resolution and length of hospital stay in the children. Likewise, a Cochrane review of seven RCTs on the impact of serum vitamin D on childhood pneumonia outcomes yielded inconclusive results [21]. The seemingly insignificant impacts of vitamin D on childhood pneumonia outcome may be explained by the lack of consensus on the definition of normal serum levels of vitamin D that may have immunomodulatory effects [43]. The role and efficacy of VDRs may also play a significant role [40,41,42]; likewise, other factors like hypoxaemia, appropriate oxygen therapy, and undernutrition that may affect pneumonia outcome [44] may also blunt the impacts of vitamin D on the outcome of pneumonia-related morbidity. More studies on the impacts of vitamin D on childhood pneumonia-related morbidity and hospitalisation are advocated.

Worthy of note from the present study is the fact that 25.0% of the Nigerian children with pneumonia had vitamin D deficiency (VDD) despite the abundance of sunshine all year-round. This is similar to 20.0% reported by Oduwole et al. [15] in Lagos, also in Nigeria but much lower than 52.9% reported by Basu et al. [34] in hospitalised children in Eastern Indian. Various factors had been reported to affect vitamin D level in children; these include skin colour, dietary intake including intake of supplements and nutritional status [35, 36]. Nigeria being a tropical country with abundant sunshine expectantly should have low prevalence of VDD in children; however, social practises such as prolonged breastfeeding and poor intake of vitamin D-rich complementary diet [45,46,47,48] may contribute to increased prevalence of hypovitaminosis D observed in the present study and others from similar areas with abundant sunshine. This also explains why low socio-economic class was a predictor of suboptimal vitamin D in our sample population. Children from low social class are often given suboptimal complimentary diets rich in phytates and poor in dairy products that are good sources of vitamin D [46]. These complimentary diets are often given with breast milk for prolonged periods [45, 46]. Unfortunately, breast milk is poor in vitamin D [47] with average amount of 22 U/l (range 15–50 U/l) in a vitamin D-sufficient mother [48]. The introduction of inappropriate maize gruel as main complementary diet further predisposes these children to VDD [49]. Consequently, the WHO recommends the fortification of maize gruel and corn meal with essential minerals and vitamins as a means of preventing deficiency of vitamin D and other essential vitamins [50].

Similar to findings from previous studies [6,7,8,9, 51], we observed that serum non-enzymatic antioxidants measured using TAC was lower in cases with pneumonia than controls. Inflammatory processes are often accompanied by increased oxidative stress due to increased oxidants and reactive oxygen species released by immune cells [6]. This increased the demand for antioxidants, hence the reduction in children with infections and other inflammatory processes.

Unlike the report from other workers [8, 9], we did not find significant relationship between the severity of CAP in our sample population and serum TAC. Neither did we observe significant correlation between serum TAC and LOH in the children with pneumonia. This may be related to the limitation of TAC as a measure of the composite antioxidant capacity of the children [7]. TAC measures the non-enzymatic antioxidant capacity of the body, but the effect of antioxidant enzymes like superoxide dismutase, catalase and peroxidases, among others, have also been described as being very important and may probably be a better measure of antioxidant capacity than TAC [7]. Secondly, many factors have been highlighted to affect LOH including undernutrition which may also affect the antioxidant capacity of the children [52]. High prevalence of undernutrition among the children with CAP in this study may also affect the relationship between the TAC and LOH [52].

This present study reports the serum levels of 25-OHD and total non-enzymatic antioxidants (TAC) assayed using standard HPLC methods with appropriate quality control in children with well-defined pneumonia. We excluded children with wheezes to ensure we studied a homogenous group. We however appreciate the limitations of this study in that the aetiologies of the pneumonia were not defined; likewise, we did not study enzymatic antioxidants in these children. Nevertheless, this study will add to the few reports from developing countries on the association between serum 25-OHD, non-enzymatic antioxidants and pneumonia-related morbidities and outcome in children.

Conclusion

Nigerian children with CAP had significantly lower serum 25-OHD and TAC compared with their age- and sex-matched counterpart without CAP, and lower serum 25-OHD was associated with severe disease, but not with LOH. Vitamin D and antioxidant supplementation may be helpful in reducing the burden of CAP in Nigerian children.

Availability of data and materials

The datasets generated and analysed during this study are available from the corresponding author on reasonable request.

Abbreviations

ARTIs:

Acute respiratory tract infections

CAP:

Community-acquired pneumonia

25-OHD:

25-Hydroxyvitamin D

LOH:

Length of hospitalisation

LMICs:

Low- and middle-income countries

TAC:

Total antioxidant capacity

Th:

T helper cells

TLRs:

Toll-like receptors

ROS:

Reactive oxygen species

VDD :

Vitamin D deficiency

VDR:

Vitamin D receptors

VBP:

Vitamin D binding protein

References

  1. World Health Organization. Pneumonia. Fact sheet. Geneva: World Health Organization; 2019. Available from: www.who.int/news-room/fact-sheets/detail/pneumonia Accessed 2020 Feb 13

  2. Niessen L, Hoves A, Hilderink H, Weber M, Muholland K, Ezzatif M (2009 Jun) Comparative impact assessment of child pneumonia interventions. Bull World Health Organ 87(6):472–480

    Article  Google Scholar 

  3. Levels and Trends in Child Mortality: Report 2017. United Nations Inter Agency Group for Child Mortality Estimation. UNICEF, WHO, The World Bank, United Nations Population Division. New York, 2017. Available at: https://www.unicef.org/publications/index_101071.html. Accessed March 31 2020

  4. Sectish TC, Prober CG (2007) Pneumonia. In: Behrman RE, Kliegman RM, Jensen HB (eds) Nelson textbook of pediatrics, 18th edn. WB Saunders, Philadelphia, pp 1432–1436

    Google Scholar 

  5. Barnes PJ, Bush A (2012) Biology and assessment of airway inflammation. In: Wilmott RW, Boat TF, Bush A, Chernick V, Deterding RR, Ratjen FR (eds) Kendig and Chernick’s disorders of the respiratory tract in children, 8th edn. WB Saunders, Philadelphia, pp 75–88

    Chapter  Google Scholar 

  6. Cemek M, Caksen H, Bayiroğlu F, Cemek F, Dede S (2006) Oxidative stress and enzymic-non-enzymic antioxidant responses in children with acute pneumonia. Cell Biochem Funct 24(3):269–273

    Article  CAS  Google Scholar 

  7. Ghiselli A, Serafini M, Natella F, Scaccini C Total antioxidant capacity as a tool to assess redox status: critical view and experimental data. Free Radic Biol Med (11):1106–1114

  8. Dundaroz R, Erenberk U, Turel O, Demir AD, Ozkaya E, Erel O (2013) Oxidative and antioxidative status of children with acute bronchiolitis. J Pediatr 89(4):407–411

    Article  Google Scholar 

  9. Chuang C, Shiesh S, Chi C et al (2006) Serum total antioxidant capacity reflects severity of illness in patients with severe sepsis. Crit Care 10:R36. https://doi.org/10.1186/cc4826

    Article  PubMed  PubMed Central  Google Scholar 

  10. Holick MF, Chen TC (2008) Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr 87:S1080–S1086

    Article  Google Scholar 

  11. White HJ (2008) Vitamin D signaling, infectious diseases and regulation of innate immunity. Infect Immun 76:3837

    Article  CAS  Google Scholar 

  12. Liu PT, Stenger S, Li H, Wenzel L, Tan BH, Krutzik SR et al (2006) Toll-like receptor triggering of a vitamin D–mediated human antimicrobial response. Science. 311:1770–1773

    Article  CAS  Google Scholar 

  13. Pichler J, Gerstmayr M, Szeepfalusi Z, Urbanek R, Peterlik M, Willheim M (2002) 1-alpha, 25(OH)2D3 inhibits not only Th1 but also Th2 differentiation in human cord blood T cells. Pediatr Res 52:12–18

    CAS  PubMed  Google Scholar 

  14. Adegoke OT, Owa JA, Elusiyan JB, Obiajunwa PO, Adedeji TA, Phillips AS (2019) Serum vitamin D, calcium and phosphate among children with pneumonia. Ann Health Res 5:93–101

    Article  Google Scholar 

  15. Oduwole AO, Renner JK, Disu E, Ibitoye E, Emokpae E (2010) Relationship between vitamin D levels and outcome of pneumonia in children. West Afr J Med 29:373–378

    CAS  PubMed  Google Scholar 

  16. Lin-Ying G, Li W, Cheng X, Li H, Sun C, Guo J et al (2017) Relationship between vitamin D status and viral pneumonia in children. Pediatr Allergy Immunol Pulmonol 30(2):86–91

    Article  Google Scholar 

  17. Roth DE, Jones AB, Prosser C, Robinson JL, Vohra S (2009) Vitamin D status is not associated with the risk of hospitalization for acute bronchiolitis in early childhood. Eur J Clin Nutr 6:297–299

    Article  Google Scholar 

  18. Ahmed P, Babaniyi IB, Yusuf KK, Dodd C, Langdon G, Steinhoff M et al (2015) Vitamin D status and hospitalisation for childhood acute lower respiratory tract infections in Nigeria. Paediatr Int Child Health 35:151–156

    Article  Google Scholar 

  19. Camargo CA, Ganmaa D, Frazier AL, Kirchberg FF, Stuart JJ, Kleinman K et al (2012) Randomized trial of vitamin D supplementation and risk of acute respiratory infection in Mongolia. Pediatrics 130:e561–e567

    Article  Google Scholar 

  20. Rashmi RD, Meenu S, Inusha P, Sushree SN (2013) Vitamin D supplementation for the treatment of acute childhood pneumonia: a systematic review. ISRN Pediatrics, Article ID:459160, 7 pages. https://doi.org/10.1155/2013/459160

  21. Das RR, Singh M, Naik SS (2018) Vitamin D as an adjunct to antibiotics for the treatment of acute childhood pneumonia. Cochrane Database Syst Rev (7):CD011597. https://doi.org/10.1002/14651858.CD011597.pub2

  22. Manaseki-Holland S, Maroof Z, Bruce J, Mughal MZ, Masher MI, Bhutta ZA et al (2012) Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial. Lancet. 379:1419–1427

    Article  CAS  Google Scholar 

  23. Choudhary N, Gupta P (2011) Vitamin D supplementation for severe pneumonia: a randomized controlled trial. Indian Pediatr 49:449–454

    Article  Google Scholar 

  24. Ilesa, Osun state Nigeria. Available at: https://en.climate-data.org/africa/nigeria/osun/ilesa-387432/ Updated 2015 Jan, 01. Accessed Feb, 10, 2020

  25. Dean AG, Sullivan KM, Soe MM. OpenEpi: Open Source Epidemiologic Statistics for Public Health, Version 3.01. Available from: www.OpenEpi.com, Updated 2013 Apr 06, [Last accessed on 2019 Dec 10].

  26. World Health Organization (2015) Revised WHO classification and treatment of childhood pneumonia at health facilities – evidence summaries. WHO, Geneva

    Google Scholar 

  27. Cherian T, Mulholland EK, Carlin JB et al (2005) Standardized interpretation of paediatric chest radiographs for the diagnosis of pneumonia in epidemiological studies. Bull World Health Organ 83:353–359

    PubMed  PubMed Central  Google Scholar 

  28. Ogunlesi AO, Dedeke IO, Kuponiyi OT (2008) Socioeconomic classification of children attending specialist paediatric centres in Ogun state. Niger Med Pract 54:21–25

    Google Scholar 

  29. Park K (2006) Environment and Health. In: Park JE, Park K (eds) Park’s Textbook of preventive and social medicine. Jabalpur, Banarasidas Bhanot and company, pp 521–536

  30. Gordon SB, Bruce NG, Grigg J, Hibberd PL, Kurmi OP, Lam K-BH et al (2014) Respiratory risks from household air pollution in low and middle income countries. Lancet Respir Med 2(10):823–860

    Article  Google Scholar 

  31. World Health Organisation. WHO Growth Reference charts for children 2 to 60 months. Available at: http://www.who.int/childgrowth/standards/ [last accessed Feb 10 2020]

  32. World Health Organisation. WHO growth reference charts for 5-19 Years; 2007. Available at: http://www.who.int/growthref/en/ [Last accessed on Feb, 10 2020].

  33. Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T (2006) Estimation of serum concentrations of 25-hydroxy vitamin D for multiple health outcomes. Am J Clin Nutr 84:18–28

    Article  CAS  Google Scholar 

  34. Basu S, Gupta R, Mitra M, Ghosh A (2015) Prevalence of vitamin D deficiency in a pediatric hospital of Eastern India. Indian J Clin Biochem 30(2):167–173

    Article  CAS  Google Scholar 

  35. Prentice A, Schoenmaker I, Jones KS, Jarjou LMA, Goldberg GR (2009) Vitamin D deficiency and its health consequences in Africa. Clinic Rev Bone Miner Metab 7:94–106

    Article  CAS  Google Scholar 

  36. Esposito S, Lelii M (2015) Vitamin D and respiratory tract infections in childhood. BMC Infect Dis 15:487. https://doi.org/10.1186/s12879-015-1196-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Mohamed WA, Al-Shehri MA (2013) Cord blood 25-hydroxyvitamin D levels and the risk of acute lower respiratory tract infection in early childhood. J Trop Pediatr 59:29–35

    Article  Google Scholar 

  38. Najada AS, Habashneh MS, Khader M (2004) The frequency of nutritional rickets among hospitalized infants and its relation to respiratory diseases. J Trop Pediatr 50:364–368

    Article  Google Scholar 

  39. Wayse V, Yousafzai A, Mogale K, Filteau S (2004) Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 y. Eur J Clin Nutr 58:563–567

    Article  CAS  Google Scholar 

  40. Uitterlinden AG, Fang Y, Van Meurs J.B.J, Pols HAP, JPTM V l. Genetics and biology of vitamin D receptor polymorphism. J Steroid Biochem Mol Biol 2004;89–90:187–193

  41. Haussler MR, Whitfield GK, Haussler CA, Hsier JC, Thompson PD, Selznick SH et al (1998) The nuclear vitamin D receptor: biological and molecular regulatory properties revealed. J Bone Miner Res 13:325–349

    Article  CAS  Google Scholar 

  42. Li W, Guo L, Li H, Sun C, Cui X, Song G et al (2015) Polymorphism rs2239185 in vitamin D receptor gene is associated with severe community-acquired pneumonia of children in Chinese Han population: a case–control study. Eur J Pediatr 174:621–629

    Article  CAS  Google Scholar 

  43. Ross AC, Taylor CL, Yaktine AL, Del Valle HB (2001) Committee to review dietary reference intakes for vitamin D and calcium. Institute of Medicine: Dietary reference intakes for calcium and vitamin D. National Academic Press, Washington, DC

    Google Scholar 

  44. Kuti BP, Adegoke SA, Oyelami OA, Ota MO (2014) Predictors of prolonged hospitalisation in childhood pneumonia in a rural health centre. S Afr J CH 8(1):11–15. https://doi.org/10.7196/SAJCH.663

    Article  Google Scholar 

  45. Global breastfeeding score card, a new report by the UN Children: fund and WHO in collaboration with the global breastfeeding initiative. Available at: www.un.org.substainabledev. Accessed 2/3/2020

  46. Olatona FA, Odozi MA, Amu EO (2014) Complementary feeding practices among mothers of children under five years of age in Satellite Town, Lagos, Nigeria. Food Public Health 4(3):93–98

    Google Scholar 

  47. Bhalala U, Desai M, Parekh P, Mokal R, Chheda B (2007) Subclinical hypovitaminosis D among exclusively breastfed young infants. Indian Pediatr 44(12):897–901

    CAS  PubMed  Google Scholar 

  48. Leerbeck E, Sondergaard H (1980) The total content of vitamin D in human milk and cow’s milk. Br J Nutr 44(1):7–12

    Article  CAS  Google Scholar 

  49. Harinarayan CV, Ramalakshmi T, Prasad UV, Sudhakar D, Srinivasarao PV, Sarma KV et al (2007) High prevalence of low dietary calcium, high phytate consumption, and vitamin D deficiency in healthy south Indians. Am J Clin Nutr 85(4):1062–1067

    Article  CAS  Google Scholar 

  50. WHO Guideline: Fortification of maize flour and corn meal with vitamins and minerals. Geneva: World Health Organization; 2016. Summary of available evidence. Available from: https://www.ncbi.nlm.nih.gov/books/NBK402393/ Accessed 8th April, 2020

  51. Kuti BP, Kuti DK, Smith OS (2020) Serum zinc, selenium and total antioxidant contents of Nigerian children with asthma: association with disease severity and symptoms control. J Trop Pediatr 66:395–402

    Article  Google Scholar 

  52. Oliveras-López MJ, Ruiz-Prieto I, Bolaños-Ríos P, De la Cerda F, Martín F, Jáuregui-Lobera I (2015) Antioxidant activity and nutritional status in anorexia nervosa: effects of weight recovery. Nutrients. 7(4):2193–2208

    Article  Google Scholar 

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Acknowledgements

The authors hereby appreciate the contributions of the doctors and nurses at Wesley Guild Hospital, Ilesa who assisted in the care of the children and Mr. Basil Ohaegbulem of IITA, Ibadan for his assistance with sample analysis.

Funding

This study was self-funded by the authors.

Author information

Authors and Affiliations

  1. Department of Paediatrics and Child Health, Obafemi Awolowo University, Ile-Ife, Nigeria

    Bankole Peter Kuti

  2. Department of Paediatrics, Wesley Guild Hospital, Ilesa, Nigeria

    Alex Ifeoluwa Akinwumi, Demilade Kehinde Kuti & Kazeem Olanrewaju Amoo

Authors
  1. Bankole Peter Kuti
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  2. Alex Ifeoluwa Akinwumi
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  3. Demilade Kehinde Kuti
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  4. Kazeem Olanrewaju Amoo
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Contributions

BPK conceived the study idea, recruited and managed the patients, collected the samples, analysed and interpreted the data and was the major contributor in writing the manuscript. AIA, DKK and KOA recruited and managed the patients and contributed to the critical review of the manuscript. The authors approved the final manuscript.

Corresponding author

Correspondence to Bankole Peter Kuti.

Ethics declarations

Ethics approval and consent to participate

The Ethics and Research Committee of the OAUTHC, Ile-Ife approved this study with approval number ERC/2014/08/04. Written informed consent and assent as appropriate were obtained from the parents and the children.

Consent for publication

Study participants signed an informed written consent form to publish the data provided the privacy of and confidentiality are protected. Patients’ names were replaced by code numbers to confirm their privacy, and the results of the study were used only for scientific purpose.

Competing interests

The authors declare that they have no competing interests.

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Kuti, B.P., Akinwumi, A.I., Kuti, D.K. et al. Relationship between serum 25-hydroxyvitamin D, total antioxidant capacity and pneumonia incidence, severity and outcome in Nigerian children. Egypt J Bronchol 14, 29 (2020). https://doi.org/10.1186/s43168-020-00029-8

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  • DOI: https://doi.org/10.1186/s43168-020-00029-8

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