The Comparison of Serum Vitamin D Level in the Term Neonates with and Without Sepsis in Children’s Hospital of Bandar Abbas City, Iran from 2016 to 2017

AUTHORS

Hossein Saadat 1 , Tayebe Mehrvari 2 , * , Rakhshaneh Goodarzi 3 , Fatemeh Kheiry 4

1 Faculty of Medicine, Clinical Research Development Centre of Children’s Hospital, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

2 Pediatrician, Faculty of Medicine, Clinical Research Development Centre of Children’s Hospital, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

3 Assistant Professor, Neonatologist, Faculty of Medicine, Clinical Research Development Centre of Children’s Hospital, Hormozgan University of Medical Sciences, Bandar Abbas, Iran

4 Student Research Committee, School of Nursing and Midwifery, Shiraz University of Medical Sciences, Shiraz, Iran

How to Cite: Saadat H, Mehrvari T, Goodarzi R, Kheiry F. The Comparison of Serum Vitamin D Level in the Term Neonates with and Without Sepsis in Children’s Hospital of Bandar Abbas City, Iran from 2016 to 2017, Hormozgan Med J. Online ahead of Print ; In Press(In Press):e104835. doi: 10.5812/hmj.104835.

ARTICLE INFORMATION

Hormozgan Medical Journal: In Press (In Press); e104835
Published Online: November 19, 2020
Article Type: Research Article
Received: May 11, 2020
Accepted: August 4, 2020
Uncorrected Proof scheduled for 25 (1)
Crossmark
Crossmark
CHECKING
READ FULL TEXT

Abstract

Background: Neonatal sepsis is one of the most important causes of an infant’s death, and the identification of its factors has been the subject of many studies. Some new evidence suggested the role of vitamin D in the occurrence of sepsis in infants.

Objectives: The aim of this study was to compare the serum levels of vitamin D in neonates with sepsis in the first week of birth and healthy neonates.

Methods: This case-control study was performed on 72 term neonates (36 neonates with sepsis as the case and 36 healthy neonates as the control group) who referred to Bandar Abbas children's hospitals, Bandar Abbas, Iran, from 2016 - 2017.

Results: Serum vitamin D levels were measured in all infants and their mothers in both sepsis and control groups. In addition, data were collected, including sex, birth weight, C-reactive protein (CRP), and duration of hospitalization in neonates with sepsis. The mean serum level of vitamin D was 18.52 ± 11.49 ng/mL in sepsis and 20.52 ± 13.75 ng/mL in neonates of the control group (P ≥ 0.05). The mean maternal serum level of vitamin D in sepsis control groups was 22.44 ± 11.26 and 24.36 ± 12.82 ng/mL, respectively (P ≥ 0.05). There was a positive correlation between maternal and neonatal vitamin D levels in the sepsis (r = 0.803) and the control (r = 0.756) groups. However, there was no significant difference between vitamin D level and CRP (P = 0.148) and length of hospital stay (P = 0.396) in the sepsis group.

Conclusions: Although the results of the present study showed a correlation between serum vitamin D levels in mothers and neonates with neonatal sepsis, there was no significant correlation between neonates with and without sepsis regarding vitamin D levels.

1. Background

Neonatal sepsis is characterized by systemic signs of infection that are accompanied by bacteremia in the first month of life (1, 2). It includes septicemia, pneumonia, meningitis, arthritis, osteomyelitis, and urinary tract infections (3).

The most common cause of infants’ death is still sepsis that accounts for 30-50% of total deaths annually in developing countries, and in Iran, it is estimated up to 8% (4). Neonatal sepsis is divided into early-onset sepsis (EOS) and late-onset sepsis (LOS) (4-6). The clinical symptoms of EOS usually present within the first 72 h of birth; however, some physicians report the onset of sepsis before the first 7 days of birth, especially if it originates from the group B Streptococcus (GBS) as EOS (7). LOS is accompanied by symptoms occurring after 3 to 7 days of birth (8). Accordingly, the clinical manifestations of neonatal sepsis usually begin within the first 6 h of birth and typically present within the first 24 h of birth (9). In most neonates, manifestations begin with respiratory distress, which is similar to other cardiopulmonary diseases (7-9). During the first 24 - 48 h of birth, 80 - 90% of patients become symptomatic (10). As mentioned earlier, neonates with LOS have no clinical symptoms of sepsis at birth and subsequently, are affected by community-acquired sepsis after discharge or during long-term hospitalization (11).

Vitamin D regulates cytokines by activating T cells and affects the synthesis of immunoglobulins by activating B lymphocytes (12). Indeed, the immune-modulating effects appear to be mediated by 25-OH vitamin D3 (12). Nearly most immune cells, including B and T lymphocytes, monocytes, and dendritic cells, have a specific vitamin D receptor (VDR). Vitamin D exerts a modulating effect on immune activity in mononuclear and polynuclear cells via the VDR (13). Vitamin D has a direct effect on macrophages and enhances the production and development of cytokines, acid phosphatase, and hydrogen peroxide, as well as prevents the overproduction of inflammatory cytokines (14). It also facilitates neutrophil motility and phagocyte function. It may improve prognosis and decrease both local and systemic inflammatory responses (15).

2. Objectives

According to the role of vitamin D in immune system function and the mortality and morbidity of neonatal sepsis, this study was designed to investigate the association between serum vitamin D level and the prevalence of neonatal sepsis.

3. Methods

3.1. Patients and Study Design

This case-control study was performed on 36 term (gestational age of 37 weeks or more) neonates who were admitted to the neonatal ward or neonatal intensive care unit of Bandar Abbas children's hospitals (Bandar Abbas, Iran) from 2016 - 2017, with a diagnosis of neonatal sepsis as the case group, and 36 term neonates with no sepsis who referred to the hospital or outpatient due to other causes as the control group. Both case and control groups weighed at least 2500 g. The study protocol was approved by the local Ethics Committee of Hormozgan University of Medical Sciences (HUMS.REC.1395.71). Informed parental consent was obtained for the parents of all neonates.

3.2. Inclusion and Exclusion Criteria

Inclusion criteria were gestational age (GA) ≥ 37 weeks, birth weight ≥ 2500 g, the onset of sepsis at the first week of birth, possible sepsis according to Gitto criteria (16), and no signs of sepsis in the control group. Also, neonates with congenital anomalies, the onset of sepsis in the control group, resuscitation and asphyxia at birth, known risk factors for sepsis (e.g., history of GBS infection in neonate, bacteriuria in recent pregnancy, prematurity, maternal fever of 38°C ≤, chorioamnionitis, rupture of the membrane more than 18 h, and low Apgar score) were excluded from the study.

3.3. Data Collection

Demographic information, including sex, birth weight, levels of vitamin D, complete blood count (CBC), C-reactive protein (CRP), and duration of hospital stay were recorded. To determine the vitamin D level, a plasma sample (2 cc) from both mothers and neonates of all groups were obtained, and the 25-OHD level was measured by a commercial kit (Monobind, USA) according to the manufacturer’s instruction. Besides, vitamin D deficiency was classified as a severe deficiency (serum 25-OHD ≥ 10 ng mL-1), insufficiency (serum 25-OHD between 11 and 32 ng mL-1), and adequate (serum 25-OHD between 32 and 100 ng mL-1) (8).

Also, blood samples for whole blood count, CRP, and culture were obtained before initiating antimicrobial therapy.

3.4. Statistical Analysis

Quantitative information was presented as mean, standard deviation, and number (or percentage). Data were analyzed using SPSS software version 23 (SPSS, version 16.0, Chicago, IL, USA) via Independent t-test, Chi-square test, and Pearson correlation. The significant difference was set at less than 0.05.

4. Results

4.1. Demographic Data

In this study, 72 term neonates were studied. The mean GA of neonates in the case and non-sepsis (control) groups was 270.77 ± 7.93 and 296.37 ± 5.95 days, respectively (Table 1). Also, the mean weight of neonates with and without sepsis was 3159±418 and 3135 ± 419 g, respectively. The demographic information of these neonates is presented in Table 1.

Table 1. Demographic Information of Neonates in the Case and Control Groups
VariablesCase GroupControl Group
Gestational age, day (mean ± SD)270.77 ± 7.93296.37 ± 5.95
Weight, g (mean ± SD)3159 ± 4183135 ± 419
Sex, No. (%)
Male16 (44.4)30 (83.3)
Female20 (55.6)6 (16.7)
Mode of Delivery type, No. (%)
NVD23 (63.9)20 (55.5)
C/S13 (36.1)16 (44.5)

4.2. Serum Vitamin D Level

The mean serum level of vitamin D in the sepsis and healthy neonates was 18.52 ± 11.49 ng/mL and 20.52 ± 13.75 ng/mL, respectively (Table 2). The independent t-test showed no significant difference between the two groups. Also, the mean serum level of vitamin D of mothers in the case and control groups was 22.44 ±11.26 and 24.36 ± 12.82 ng/mL, respectively. Independent t-test showed no significant difference between mothers of two groups in terms of vitamin D level (Table 2).

Table 2. Comparison of Vitamin D Levels in Mothers and Neonates of two Studied Groups
Vitamin D LevelCase Group, (Mean ± SD)Control Group, (Mean ± SD)P-Value
Neonates (mL/ng )18.52 ± 11.4920.52 ± 13.750.5
Mothers (mL/ng )22.44 ± 11.2624.36 ± 12.820.5

Pearson correlation coefficient showed no significant correlation between vitamin D level and neonates’ weight in the case (r = -0.188, P = 0.227) and control (r = -0.117, P = 0.502) groups. Also, there was no significant difference between the gender of neonates with serum vitamin D level (P = 0.148).

4.3. The Severity of Vitamin D Deficiency

In this study, the level of vitamin D of neonates and mothers were divided into three groups; adequate, inadequate, and deficiency. According to the Chi-square test, the level of vitamin D deficiency was not significantly different in neonates of the case and control groups (P = 0.829, Table 3). Moreover, the Chi-square test showed no significant difference in the severity of vitamin D deficiency in mothers of the case and control groups (P = 0.448, Table 3).

Table 3. Comparison of the Severity of Vitamin D Deficiency in Mothers and Neonates in the Case and Control Groups
Severity of Vitamin D DeficiencyGroupP-Value
Case, No. (%)Control, No. (%)
Neonates
Deficiency2261.12158.40.829
Inadequate822.2719.4
Adequate616.7822.2
Mothers
Deficiency1747.21233.30.448
Inadequate1336.11541.7
Adequate616.7925

4.4. The Correlation Between Serum Vitamin D Level of Mothers and Neonates

Based on the Pearson’s test, a strong positive correlation was observed between serum vitamin D levels of mothers and neonates in the case and control groups (r = 0.803 and r = 0.756; P < 0.001, respectively). As showed in Table 4, no significant difference was observed between the two groups in terms of the severity of vitamin D deficiency (P = 0.625).

Table 4. Correlation Between Serum Level of Vitamin D in Mothers and Neonates of the Case and Control Groups
GroupsPearson Correlation CoefficientP-Value (Case and Control)
Case (Mothers and Neonates)Control (Mothers and Neonates )
Correlation level0.8030.7560.625
P-value (mothers and neonates )0.001 >0.001 >

4.5. The Relationship Between Serum Vitamin D Level and CRP and Length of Hospitalization in the Sepsis Group

Pearson correlation coefficient indicated a weak positive correlation between vitamin D level and CRP level in neonates with sepsis, which was not statistically significant (r = 0.250, P = 0.142, Figure 1). Also, the correlation between serum vitamin D level and the length of hospitalization in the sepsis group was 0.146, which indicated a weak positive correlation, which was not statistically significant (P = 0.396). According to Table 5, no significant relationship was observed between different levels of vitamin D, and CRP levels (P = 0.213), and length of hospitalization (P = 0.055).

Table 5. Comparison of C-Reactive Protein (CRP) Level and Length of Hospitalization and Vitamin D Levels in Neonates with Sepsis
VariablesVitamin D LevelsP-Value
Deficiency, Mean ± SDInadequate, Mean ± SDAdequate, Mean ± SD
CRP (mg/dL)18.73 ± 18.6525.25 ± 26.2437.33 ± 31.210.213
Length of hospitalization (days)9.09 ± 3.7514.25 ± 7.989.83 ± 4.070.055
Figure 1. Scatter plot of the relationship between vitamin D level and C-reactive protein (CRP) level in the sepsis group

5. Discussion

In the present study, we determined the serum vitamin D level in both neonates with sepsis and their mothers and compared it with healthy cases. Also, some risk factors of sepsis in neonates were investigated. Our results showed that there was no difference between the serum vitamin D level in both neonates and mothers compared with healthy subjects. However, in the sepsis group, a positive correlation was found between maternal and neonatal serum vitamin D.

In line with previous studies (7, 8), our results indicated that there was no significant difference between GA, weight, sex, length of hospitalization, and mode of delivery in neonates with sepsis in comparison with healthy subjects.

In the present study, although vitamin D level in neonates with sepsis was lower than that of the control group, it showed no significant differences. In contrary to our findings, Gamal et al. (7) (2017) in a study on 50 neonates (25 full-term + 25 preterm infants) with sepsis and 30 age- and sex-matched healthy neonates as controls in Egypt found that serum vitamin D levels were significantly lower in mothers and neonates with early onset of sepsis (EOS) than mothers and neonates in the control group. There was also a significant reverse correlation between maternal and neonatal vitamin D levels and all sepsis markers. Also, a direct positive correlation was observed between maternal and neonatal serum vitamin D levels (7).

Seliem et al. (17) performed a study on 30 term neonates with EOS and 30 age-matched healthy neonates as controls. They demonstrated that neonatal and maternal vitamin D levels of the sepsis group were lower than the control group. This study showed a negative correlation between vitamin D and CRP levels in neonates with sepsis (17). In our study, we found a negative correlation between vitamin D levels of the sepsis group in comparison with control neonates; however, it was not statistically significant.

Cetinkaya et al. (2015) indicated that serum vitamin D levels in mothers and neonates in the case group were significantly lower than controls (8). Severe vitamin D deficiency was also more common in the group with sepsis (8). However, in our study, there was no significant difference between vitamin D level severity and neonatal sepsis.

Accordingly, in contrast with our findings, Karatekin et al. (13), Cizmeci et al. (11), Dhandai et al. (18), Ismail et al. (19), and Myint et al. (20) found that serum vitamin D levels were lower in neonates with sepsis than the controls. Also, vitamin D levels were lower in mothers of the sepsis group than mothers of the control group.

In the line with our study, Barak et al. (21) studied 43 neonates with EOS and 43 healthy neonates as the control group in Ardabil, Iran. A high percentage of neonates (94.2%) had moderate to severe vitamin D deficiency, which was higher in neonates with sepsis than in controls, but these differences were not significant. There was also no positive correlation between vitamin D levels and the incidence of sepsis (21). However, Saboute et al. (22) showed that maternal serum vitamin D was inversely correlated with neonatal sepsis occurrence.

Say et al. (2017) (23) reported that 63% of infants had vitamin D deficiency, 24% had insufficient vitamin D levels, and 13% had adequate vitamin D levels. There was no association between vitamin D levels and the risk of neonatal sepsis in preterm infants (23). In our study, most neonates in both case and control groups had vitamin D deficiency.

In our study, there was no significant difference between CRP and the severity of vitamin D deficiency. In line with our results, Prasad et al. (24) in India reported that there was no significant association between the severity of vitamin D and CRP levels in neonates with sepsis.

Tao et al. (25) showed that in neonates with vitamin D levels of less than 25 nmol/L, the increase in vitamin D level by 10 nmol/L resulted in a decrease in CRP by 1.42 mg/L. Moreover, in neonates with vitamin D levels of 25 - 49.9 nmol/L, an increase of 10 nmol/L in vitamin D levels caused a decline in CRP by 0.49 mg/L. There was no correlation between serum CRP levels and serum vitamin D levels ≥ 50 nmol/L (25) in infants.

5.1. Conclusions

The results of the present study showed no association between serum vitamin D levels of mothers and neonates with sepsis in comparison with the control group. There was also no association between vitamin D level, neonates’ weight, sex, CRP, length of hospital stay, and mode of delivery. Hence, future studies with a larger sample size are recommended to investigate vitamin D levels in neonates with EOS and LOS, as well as the maturity of neonates.

Footnotes

References

  • 1.

    Sankar M, Agarwal R, Deorari AK, Paul VK. Sepsis in the newborn. Indian J Pediatr. 2008;75(3):261-6. doi: 10.1007/s12098-008-0056-z. [PubMed: 18376095].

  • 2.

    Ng PC, Lam HS. Diagnostic markers for neonatal sepsis. Curr Opin Pediatr. 2006;18(2):125-31. doi: 10.1097/01.mop.0000193293.87022.4c. [PubMed: 16601490].

  • 3.

    Kale A, jaybhaye D, Bonde V. Neonatal sepsis: An update. Iran J Neonatol. 2014;4(4):39-51. doi: 10.22038/ijn.2013.2012.

  • 4.

    Satar M, Özlü F. Neonatal sepsis: a continuing disease burden. Turk J Pediatr. 2012;54(5):449.

  • 5.

    Døllner H. Early diagnostic markers for neonatal sepsis Comparing C-reactive protein, interleukin-6, soluble tumour necrosis factor receptors and soluble adhesion molecules. J Clin Epidemiol. 2001;54(12):1251-7. doi: 10.1016/s0895-4356(01)00400-0.

  • 6.

    Soori H, Rafiei E, Entezami N, Hasani J, Hossaini SM. A comparison study on rate and causes of under 5 years old deaths in Iran, eastern Mediterranean region and the world. Journal Of Safety Promotion And Injury Prevention. 2016;4(1):1-8.

  • 7.

    Gamal T, Madiha A, Hanan M, Abdel-Azeem M, Marian G. Neonatal and maternal 25-OH Vitamin D serum levels in neonates with early-onset sepsis. Children. 2017;4(5):37. doi: 10.3390/children4050037. [PubMed: 28486434].

  • 8.

    Cetinkaya M, Cekmez F, Buyukkale G, Erener-Ercan T, Demir F, Tunc T, et al. Lower vitamin D levels are associated with increased risk of early-onset neonatal sepsis in term infants. J Perinatol. 2014;35(1):39-45. doi: 10.1038/jp.2014.146. [PubMed: 25102323].

  • 9.

    Moazen M, Mazloom Z, Jowkar F, Nasimi N, Moein Z. Vitamin D, adiponectin, oxidative stress, lipid profile, and nutrient intakes in the females with acne vulgaris: A case-control study. Galen Medical Journal. 2019;8:1515. doi: 10.31661/gmj.v8i0.1515.

  • 10.

    Tappero E, Johnson P. Laboratory evaluation of neonatal sepsis. Newborn Infant Nurs Rev. 2010;10(4):209-17. doi: 10.1053/j.nainr.2010.09.010.

  • 11.

    Cizmeci MN, Kara S, Kanburoglu MK, Simavli S, Duvan CI, Tatli MM. Detection of cord blood hepcidin levels as a biomarker for early-onset neonatal sepsis. Medical Hypotheses. 2014;82(3):310-2. doi: 10.1016/j.mehy.2013.12.017.

  • 12.

    Urrutia-Pereira M, Solé D. Vitamin D deficiency in pregnancy and its impact on the fetus, the newborn and in childhood. Revista Paulista de Pediatria (English Edition). 2015;33(1):104-13. doi: 10.1016/s2359-3482(15)30036-1.

  • 13.

    Karatekin G, Kaya A, Salihoğlu Ö, Balci H, Nuhoğlu A. Association of subclinical vitamin D deficiency in newborns with acute lower respiratory infection and their mothers. Eur J Clin Nutr. 2007;63(4):473-7. doi: 10.1038/sj.ejcn.1602960. [PubMed: 18030309].

  • 14.

    Das B, Patra S, Behera C, Suar M. Genotyping of vitamin D receptor gene polymorphisms using mismatched amplification mutation assay in neonatal sepsis patients of Odisha, eastern India. Infect Genet Evol. 2016;45:40-7. doi: 10.1016/j.meegid.2016.08.013. [PubMed: 27535015].

  • 15.

    Youssef DA, Miller CW, El-Abbassi AM, Cutchins DC, Cutchins C, Grant WB, et al. Antimicrobial implications of vitamin D. Dermato-Endocrinology. 2014;3(4):220-9. doi: 10.4161/derm.3.4.15027. [PubMed: 22259647].

  • 16.

    Gitto E, Karbownik M, Reiter RJ, Tan DX, Cuzzocrea S, Chiurazzi P, et al. Effects of melatonin treatment in septic newborns. Pediatric Research. 2001;50(6):756-60. doi: 10.1203/00006450-200112000-00021. [PubMed: 11726736].

  • 17.

    Seliem MS, Abdel Haie OM, Mansour AI, Salama SSME. The relation between vitamin D level and increased risk for early-onset neonatal sepsis in full-term infants. Med Res J. 2016;15(1):16-21. doi: 10.1097/01.MJX.0000483971.52646.4b.

  • 18.

    Dhandai R, Jajoo M, Singh A, Mandal A, Jain R. Association of vitamin D deficiency with an increased risk of late-onset neonatal xepsis. Paediatr Int Child H. 2018:1-5. doi: 10.1080/20469047.2018.1477388. [PubMed: 30003852].

  • 19.

    Ismail AM, Abdelrahman SH, Elsayed AH, Alkheshen GA, Sadaney MAE. A study of vitamin D status and cathelicidine plasma levels in pediatric population with sepsis. J Am Sci. 2015;11:1-6.

  • 20.

    Myint AA. Serum Vitamin D Levels in Term Neonates with Early Onset Sepsis. Pediatrics & Neonatal Biology Open Access. 2018;3(3). doi: 10.23880/pnboa-16000124.

  • 21.

    Barak M, Mirzarahimi M, Fouladi N, Ekhlasi N, Enteshari-Moghaddam A. Evaluation of the relationship between serum vitamin D level and early onset of sepsis. Archives of Pediatrics and Neonatology. 2019;2(1):28-35.

  • 22.

    Saboute M, Yavar R, Kashaki M, Khaledi FK, Khalesi N, Rohani F. Investigation of association between maternal 25-OH vitamin D serum levels and neonatal early onset sepsis in newborns by evaluating key factors. Lipids in Health and Disease. 2019;18(1). doi: 10.1186/s12944-019-1095-3.

  • 23.

    Say B, Uras N, Sahin S, Degirmencioglu H, Oguz SS, Canpolat FE. Effects of cord blood vitamin D levels on the risk of neonatal sepsis in premature infants. Korean J Pediatr. 2017;60(8):248. doi: 10.3345/kjp.2017.60.8.248. [PubMed: 29042866].

  • 24.

    Prasad R, Shanataram B, Kiran B, Dsa S. Vitamin D levels in late Pre-Term neonates and its association with sepsis. Indian J Public Health Res Dev. 2018;9(10):128. doi: 10.5958/0976-5506.2018.01327.x.

  • 25.

    Tao R, Zhou Q, Xu Z, Hao J, Huang K, Mou Z, et al. Inverse Correlation between Vitamin D and C-Reactive Protein in Newborns. Nutrients. 2015;7(11):9218-28. doi: 10.3390/nu7115468. [PubMed: 26569292].

  • Copyright © 2020, Hormozgan Medical Journal. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.
    COMMENTS

    LEAVE A COMMENT HERE: