The neonatal immune system is immature, highly susceptible to many microorganisms and prone to sepsis, especially premature infants and low birth weight infants. Long-term use of invasive procedures and intravenous nutrition increase the incidence of sepsis. Due to the low immunity and weak resistance of the newborn, sepsis often develops rapidly from subclinical symptoms to severe systemic infection symptoms, causing damage to systemic organs and the occurrence of diseases, such as NEC, meningitis, septic shock, DIC, etc, making sepsis become an important cause of neonatal death. Therefore, it is great significance to analyze the specific risk factors of complications and death of sepsis, taking active control measures to reduce the incidence of complications and mortality. Our study found that there was significant difference in HC, decrease of HC, hypoproteinemia within 1 week after the onset and red blood cell transfusion between the complication group and non-complication group. Further logistic regression showed that significant decrease of HC and hypoproteinemia were independent risk factors for complication in infants with sepsis.
4.1 The effect of anemia and decrease of HC on the complications and prognosis of children with sepsis
Sepsis is often accompanied by anemia or a decrease in hemoglobin concentration. Many causes can lead anemia, such as iatrogenic blood loss, reduced serum iron levels, shortened red blood cell life and increased destruction, etc. In addition, vascular endothelial glycocalyx shedding and intravenous fluid administration lead to blood thinning[11-13], which is also manifested by a decrease in HC, causing thinning ‘anemia’. But in the early stage of sepsis, the decrease of HC is mostly caused by increased destruction of red blood cells and damage to the glycocalyx layer. In severe infection, a large number of inflammatory factors are released, on the one hand, directly destroying red blood cells, causing a decrease in HC. On the other hand, a large number of inflammatory factors destroy the glycocalyx layer of the vascular endothelium, causing dilution anemia. Therefore, we speculate that the decrease of HC may reflect the level of inflammation in the body, the more obvious the decrease in HC, the more severe the inflammation. After the occurrence of sepsis, the body may have microcirculation disturbances, leading to tissue ischemia and hypoxia. When severe infection occurs, a large amount of inflammatory factors are secreted in the body, which leads to true anemia or dilute ‘anemia’ through various mechanisms. The significantly reduced HC further causes ischemia and hypoxia, and redistribution of blood in the body, causing or aggravating the microcirculation disorder. Eventually, sepsis and significantly reduced HC complement each other and cause adverse effects on tissue organs. Studies have shown that anemia is a high-risk factor of NEC [14-18], and the incidence of NEC in children with moderate or above anemia is higher than that without anemia or mild anemia . Jung SM  found that low hemoglobin levels ( < 9.0 g/dL) were observed in approximately 20% of patients with septic shock, and the severity of decrease in these levels correlated with mortality, the lower the HC, the higher the mortality rate. Loftus TJ  found that reducing anemia may improve the prognosis of sepsis patients. This study found that the incidence of complications in children with sepsis was closely related to the severity of anemia and the degree of HC reduction at the onset. Moderate or above anemia and significantly reduced HC are more likely to have complications. At the same time, this study found that after the occurrence of sepsis and before the occurrence of complications, the transfusion of red blood cells may increase the incidence of complications. Many studies have also shown that the transfusion of red blood cells can lead to the occurrence of NEC [22-23] , and increase the chance of surgery in children with NEC and reduce the survival rate . A foreign study on blood transfusion after sepsis in children showed that after sepsis-related anemia, compared to the restrictive strategy group, there had a significantly higher incidence of acute respiratory distress syndrome and acute lung injury in the liberal transfusion group. Moreover, mortality was significantly higher, and liberal transfusion might be associated with a worse outcome  . In addition, other studies found that the transfusion of red blood cells may increase the mortality of critically ill patients [26-27] . It should be pointed out that the anemia associated with sepsis is not all true anemia, and sometimes it may be caused by blood dilution related to fluid load [28-29]. Therefore, after the occurrence of sepsis, even if the HC is reduced, it is necessary to strictly grasp the blood transfusion pointer and carefully infuse red blood cells.
Further logistic regression showed that decrease of HC was an independent predictors for complication in infants with sepsis. By comparing the ROC curves of the decrease of HC，the results showed that the AUC was 0.807 for the decrease of HC, which suggests that decrease of HC (cut-off value: 14.5) may predicted the occurrence of complication in infants with sepsis.
4.2 The effect of hypoproteinemia on the complications and prognosis of children with sepsis
This study found that the incidence of hypoproteinemia in the complication group was significantly higher than that in the non-complication group. Logistic regression showed that hypoproteinemia was an independent risk factor for complication in infants with sepsis. Hypoproteinemia is a common complication of sepsis and albumin can be reduced by about 10–15 g/L within 1 week after sepsis. After infection, a large number of inflammatory mediators such as interleukin - 1 (IL - 1), IL - 6 and tumor necrosis factor - α (TNF - α) are released, which can inhibit albumin synthesis. In addition, when the children have sepsis, the body will have fever, stress and inflammation. These symptoms will accelerate metabolism, a large amount of albumin in the body quickly synthesizes acute-phase protein, causing the albumin level to drop . At the same time, increased permeability and destruction of vascular endothelial integrity can also lead to hypoalbuminemia . Hypoproteinemia can cause the plasma colloid osmotic pressure to drop and a large amount of fluid remains in the tissue gap, which reduces the effective blood volume of the body and causes damage to multiple organ functions. In addition, albumin can clear free radicals in the body and inhibit the production of oxygen free radicals by multinuclear cells. But when sepsis occurs, a large number of inflammatory factors are secreted, leading to proinflammatory and anti-inflammatory imbalances in the body, the activity of free radicals is out of control, and a large number of free radicals are produced. The occurrence of hypoalbuminemia leads to a weakening of the body's ability to scavenge free radicals and promote the development of sepsis. Therefore, it is necessary to pay attention to children with hypoalbuminemia after the occurrence of infection. For those with sepsis complicated with hypoalbuminemia, the hypoalbuminemia should be actively corrected to reduce the incidence of complications.
This study has some limitations. This study investigated the relationship between complications among infants with late-onset sepsis and decrease of HC and hypoalbuminemia. The incidence of complications in infants with sepsis in our hospital is not high, so the sample size of the complication group is small, conclusions must be further validated with larger sample sizes. In addition, the retrospective nature of the study is a limitation, as only blood cell count analysis and blood culture at the initial stage of the disease were counted, and the results of other onset times were not recorded. Finally, we only report on the situation in a developing country. Our results may not correlate with those of other countries on the grounds of racial differences, as well as different healthcare systems and medical technologies.