Vitamin D is essential to the optimum function of the immune system, especially the innate immune system which performs efficiently by stimulating the production of antimicrobial peptides in epithelial cells, neutrophils, and macrophages. Hence, vitamin D insufficiency may be considered a substantial risk factor for acquiring infections [16].

This study aimed to correlate the different levels of serum vitamin D with the development of EOS in full-term AGA newborns. In our research, there was no significant difference in the mode of delivery or sex between the cases and controls. This was in line with the findings of Kumar et al. [17]. The current study found newborns with sepsis having a statistically significant decrease in first-minute Apgar scores than controls. Similarly, other studies found significant associations between lower Apgar scores at the first and fifth minutes and the development of neonatal sepsis [18,19,20]. The innate immune system which is the first line of defense is immature at birth. In addition, the adaptive immune system is still not able to efficiently respond to T-cell-dependent antigens. In addition, the WHO classified low Apgar scores as an indicator of perinatal asphyxia. Thus, newborns with low Apgar scores may be at greater risk of infection [21,22,23,24].

Chen et al. reported that vitamin D administration during pregnancy led to a considerable decline in the amount of circulating maternal serum CRP,. This fact reveals the association between vitamin D deficiency and inflammation, infection, and septic shock [25]. The current study identified an association between low vitamin D levels and high neonatal serum CRP, in line with previous studies that found an inverse relationship between CRP levels in septic neonates and blood vitamin D levels [17, 26, 27]. While, Grzanka et al., concluded that there was no significant relationship between vitamin D concentrations and CRP and attributed this finding to the small sample size and single evaluation of vitamin D concentration [28].

In the current research, serum vitamin D levels in the sepsis group were considerably lower than in the control one. This result was consistent with other researches which concluded that full-term newborns with low serum vitamin D levels were more prone to the risk of infection [5, 17, 29, 30]. According to Soliman et al., a multivariate logistic regression analysis used to predict neonatal sepsis showed that a decline in serum vitamin D levels was substantially related to the risk of sepsis in newborns [26]. Another study explained this association by the disruption of the macrophage function and the inflammatory cytokines generation that can result from a vitamin D deficit [7].

We observed in the EOS newborns different statuses of vitamin D: 66% were in the vitamin D deficient range, 11% in the insufficient one, and 22.2% in the sufficient subgroup. Vitamin D insufficiency elevated the risk of EOS by 1.44 times, while vitamin D deficiency elevated the risk of EOS to 53.44 times. As well, Kumar et al. reported the mean serum vitamin D levels were considerably lower in neonates with EOS compared to healthy controls. Out of 100 neonates with EOS, 77.0% had vitamin D deficiency, 23.0% insufficiency, and none had appropriate levels, while in the one hundred healthy controls vitamin D levels were adequate in 31%, insufficient in 28%, and deficient in 41.0% [17].

The link between serum vitamin D levels and EOS in newborns without maternal risk factors has been furthermore investigated by Sarwade et al. They concluded that in preterm and full-term ill neonates, without maternal risk factors, severe vitamin D deficiency of less than 10 ng/ml was considerably correlated with culture-positive EOS in neonates in the first three days of life [31].

In this study, there was an inverse correlation between positive blood culture results and vitamin D levels. This was in agreement with Moromizato et al., who observed a higher rate of infection and culture positivity among vitamin D-deficient patients [32]. Also, mean vitamin D levels were lower among neonates who suffered septic shock confirmed by culture than those with negative cultures [16].

The results of blood cultures in this study reported that 57.8% of those within the sepsis group had positive blood cultures. These results are higher than those reported by Betty and Inderpreet who found that culture-proven sepsis occurred in only 21% of cases with sepsis [33]. The sensitivity of blood cultures in neonatal sepsis is low and depends on the timing and number of cultures taken, blood volume, technique, temperature, culture medium, and organism density. Furthermore, the implementation of peripartum maternal antimicrobial practice makes the diagnostic value of neonatal blood cultures unreliable [1]. In the current study, out of 26 patients with positive blood cultures, 65.4% and 26.9% had coagulase-negative staphylococci (CoNS) and klebsiella respectively. Lee et al. also reported that Gram-positive organisms were the most predominant organisms of EOS in Korea. CoNS was noted as the highest, followed by Staphylococcus aureus [34].

An inverse correlation between serum vitamin D levels and the duration of NICU stay was reported in the current study. In contrast, Saadat et al. found no correlation between vitamin D levels and the length of hospital stay [35].

This study concluded that a serum vitamin D level of 19.7 ng/mL had an AUC of 0.76 for the prediction of EOS with 84.4% sensitivity and 66.7% specificity. The cutoff value of vitamin D as a measure of the risk of developing neonatal sepsis was reported by Behera et al. to be 15.48 ng/ml, with 80% sensitivity and 99.9% specificity [36]. Additionally, Soliman et al. observed that vitamin D, at a cutoff point of 18.75 ng/ml, had a 100% sensitivity, and 80% specificity for the diagnosis of newborn sepsis [26]. Another case–control study which recruited sixty-two infants with EOS and the same number as a control group, revealed that vitamin D levels were considerably lower in EOS with a cutoff value of 25 ng/ml, 88.7% sensitivity, and 79% specificity [4].

In this study, the independent predictors of sepsis among the studied group were serum vitamin D level (AOR = 2.8), vitamin D deficient category (< 20 ng/ml) (AOR = 4.5), presence of respiratory difficulties (AOR = 2.1), and mottling (AOR = 1.9). The overall value of predicted sepsis by these factors combined was 75.6%. Also, it concluded that vitamin D deficiencies and insufficiencies considerably raise the risk of EOS.

Finally, there are few limitations to this study, the first of which is the absence of measurements of maternal serum vitamin D levels. Second, the sample size is small. Lastly, the lack of serum vitamin D level measurement after vitamin D administration to the septic neonates and assessing its correlation with clinical and laboratory parameters of neonatal sepsis hindered revealing its effect on immune modulation.