European Journal of Cardiovascular Medicine

Neonatal sepsis refers to the presence in a newborn baby of a blood stream infection (BSI) in the setting of fever. It is a clinical syndrome in infants aged ≤28 days, manifested by systemic signs of infection with the isolation of bacterial pathogens from blood stream¹. It is a serious complication with relatively low incidence (0.5–1.2 cases per 1,000 live births) and high morbidity and mortality rates^2-4.

 It requires timely recognition, rational antimicrobial therapy and aggressive supportive care^5.  Neonatal sepsis is either early-onset neonatal sepsis (EONS) where the signs and symptoms of sepsis appear in the first 72 hours of birth or late onset neonatal sepsis (LONS) when the onset of sepsis occurs after 72 hours of birth up to 28 days of life⁶.

For diagnosis of sepsis, we need complete blood count (for the number of platelets, neutrophil percent, WBCs), blood culture and C-Reactive Protein⁷.

Vitamin D deficiency may play a role in the pathogenesis of infections and low levels of circulating vitamin D has been shown to be strongly associated with infectious diseases⁸ .Vitamin D receptors and 25-hydroxyvitamin D-1α-hydroxylase (1α-OHase) have been discovered in many extra skeletal tissues and the vitamin D response element (VDRE) is found in over 900 genes⁹.

The effects of vitamin D on the innate immune system encompass not only the modulation of the systemic inflammatory response but also the local control of pathogens. 1,25-dihydroxy vitamin D3 stimulates the innate immune system to increase the production of antimicrobial peptides (AMP), such as cathelicidin, and its activated form LL-37, β2, and β3 defensins have a broad spectrum of antimicrobial actions against bacteria, virus, and fungi 20 Furthermore, recent epidemiologic and clinical trials have suggested that optimal vitamin D status may be protective against several chronic illnesses, including risk of systemic infections, cardiovascular disease, lung disease and diabetes^10-14.Vitamin D has effect on many actions during pregnancy such as response to infection and inflammation and has main role in the mother and the baby’s immune system so consuming enough vitamin D supplements during pregnancy is essential to prevent EONS in term neonates¹⁵. The risk factors for Vitamin D deficiency are inadequate intake of vitamin D, low consumption of enriched foods, seasonal changes, skin colour, inadequate exposure to sunlight, body coverage and etc^16,17.

AIM

To assess the relationship between Vitamin D levels and early onset neonatal sepsis in term neonates.

The study was a hospital-based cross-sectional comparative study conducted at the Department of Pediatrics, Sardar Patel Medical College and PBM Hospital, Bikaner, over a one-year period from December 2023 to November 2024. It aimed to evaluate the association between Vitamin D levels and early onset neonatal sepsis in term neonates admitted to the neonatal ICU. Consecutive sampling was used to select participants, with a minimum sample size determined to be 70 cases and 70 controls, based /  a prevalence of 20.9% for early neonatal sepsis in India, a 95% confidence interval, and a 10% absolute error.

The sample size calculation followed the formula

 N= z2pq/d2

 where  p is the prevalence,

            Q is 1 minus the prevalence,

             d is the allowable error.

 neonates with early onset neonatal sepsis were included if they presented within the first three days of life with symptoms such as temperature instability, apnea, need for oxygen or ventilation, tachycardia or bradycardia, hypotension, feed intolerance, or abdominal distension. Exclusion criteria encompassed maternal clinical chorioamnionitis, premature rupture of membranes, major congenital abnormalities, and refusal of parental consent.

Sepsis screen:

Statistical analysis: Thus the data taken was entered in microsoft excel sheet and analysed in terms of range, mean and standard deviation for qualitative data and in terms of frequency and percentage for quantitative data. The data was analysed using chi square test and student ‘t’ test using Epi info software from CDC

Table 1: Distribution of neonates according to the Age of the mother

Maximum neonates were 57.14% in sepsis group whose mother’s age was in the range of 21-25 year age whereas 58.57% neonates in non-sepsis group were of 21-25 age group mothers.Mean age was 23.74 ± 3.17 yr in sepsis group whereas 23.95 ± 3.20 yr in non sepsis group. (p>0.05)

Table 2:  Distribution of neonates according to their symptoms (chief complaint)

In the sepsis group, maximum (64.29%) had respiratory distress followed by fever (25.71%) followed by less feed acceptance (5.71%) whereas minimum 4.29% had lethargy. In non sepsis group, all were admitted for screening.  The difference between both groups were significant (p<0.05).

Table 3: Distribution of neonates according to their birth weight

In the sepsis group, a maximum of 82.86% had birth weight >2.5 kg whereas in the non sepsis group , 94.29% had birth weight >2.5 kg.  The difference between both groups was significant (p<0.05).

Table 4:  Comparison of Vitamin D levels in sepsis and Non sepsis group

In sepsis group, 57 cases (81.43%) had insufficient vitamin D levels followed by 12 cases (17.14%) had deficient vitamin D levels whereas 1 case (1.43%)  had adequate vitamin D level.In non sepsis group, maximum 34 cases (48.57%) each had insufficient and adequate vitamin D levels whereas minimum 2 cases (2.86%) had deficient levels. 

 Mean Vitamin D level was 16.95 ± 7.2 ng/mL in sepsis group whereas 26.59 ± 7.26 ng/mL in non sepsis group. The difference between Vitamin D levels after 6 months of therapy was statistically significant (p<0.05).

Table 5: Outcome of the neonates in relation to vitamin D levels

In sepsis group, 54 cases (77.14%) were discharged whereas all cases in non sepsis group were discharged.Out of total 16 cases (22.86%) who died in sepsis group, 8 cases (50%) had insufficient vitamin D levels and the 8 cases (50%) had deficient vitamin D levels. The difference between outcome in both groups was statistically significant (p<0.05).

In this study (Table 1), maximum neonates 57.14% in sepsis group whose mother’s age was in the range of 21-25 years whereas 58.57% neonates in non-sepsis group were born to mothers whose age group was 21-25 years. Mean age of mothers was 23.74 ± 3.17 yr in sepsis group whereas 23.95 ± 3.20 yr in non sepsis group (p>0.05). Similarly, Tadesse Yirga Akalu et al. (2023)¹⁸ in a study of total of 368 newborns, mean age of index mothers was 29.5 years with (±7 SD). Also Maryam Saboute et al (2019)¹⁹ in sixty- four mothers the mean age 28.76 ± 6.60 years.

In the present study (Table 2), in sepsis group, maximum (64.29%) had respiratory distress followed by fever (25.71%) followed by less feed acceptance (5.71%) whereas minimum 4.29% had lethargy. In non sepsis group, all were admitted for screening. The difference between both groups were significant (p<0.05). Similarly Manouchehr Barak et al. (2019)²⁰ found that the most common complaints in neonates were restlessness with 74.71%, jaundice with 67.44% and fever with 62.7%.

We have observed in this study (Table 4) that in the sepsis group, 57 cases (81.43%) had insufficient vitamin D levels followed by 12 cases (17.14%) had deficient vitamin D levels whereas 1 case (1.43%) had adequate vitamin D level. In non sepsis group, maximum 34 cases (48.57%) each had insufficient and adequate vitamin D levels whereas minimum 2 cases (2.86%) had deficient levels. Similarly Kamsiah Kamsiah et al. (2021)²¹ 75.6% (31/41) neonates with Vitamin D deficiency, while 24.4% (10/41) had normal Vitamin D levels and did not suffer from deficiency. Also Zebenay Workneh Bitew et al. (2020)²² found that the overall prevalence of vitamin D deficiency among neonates was 61% (95% CI: 44.3, 77.7); 79.4% (95% CI:71.6, 87.3) of neonates with sepsis were vitamin D deficient as were 43.7% (23.4,63.9) of sepsis-free neonates.

 Mean vitamin D level was 16.95 ± 7.2 ng/mL in sepsis group whereas 26.59 ± 7.26 ng/mL in non sepsis group. The difference between vitamin D levels after 6 months of therapy was statistically significant (p<0.05). Similarly POONAM SINGH et al (2020)²³ Mean neonatal vitamin D level in the study group was 16.00 (10.49) ng/mL and in the control group, was29.07(8.36) ng/mL (P =0.061).

In this study( Table 5), in sepsis group, 54 cases (77.14%) were discharged whereas all cases in non sepsis group were discharged. Out of total 16 cases (22.86%) who died in sepsis group, 8 cases (50%) had insufficient vitamin D levels and the 8 cases (50%) had deficient vitamin D levels. The difference between outcome in both groups was statistically significant (p<0.05) Similarly POONAM SINGH et al (2020)²³ found that mortality and highly probable sepsis were more common with vitamin D levels <11ng/mL in the study group (P= 0.005 and P=0.006, respectively). Also Kamsiah Kamsiah et al. (2021)²¹ found that the relationship of Vitamin D levels with mortality was insignificant (p = 0.660).

Our study shows that early onset neonatal sepsis (EONS) was associated with vitamin D deficiency. More the deficiency of vitamin D in the neonate, more is the chance and severity of sepsis

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