Investigation of biomarkers in a rare case of fulminant necrotizing enterocolitis in a preterm infant

Abstract

We encountered a very rare case of fulminant necrotizing enterocolitis (F-NEC) in a preterm male baby. The course of NEC and sepsis in this case was clearly different from the usual course. After onset at 14 days of life, catheter-related bloodstream infection was first assumed, and antibiotics and γ-globulin administration were started. However, 12 hours after onset, the baby's abdominal distension increased remarkably, and his entire abdominal wall turned red to purple. Escherichia coli were isolated from the blood culture, but the catheter tip culture was negative. Exchange transfusion was performed 32 hours after onset, but no significant changes were observed in the baby's general condition, and he died 46 hours after onset. The acute phase reactants of CRP and α1-acid glycoprotein increased, but haptoglobin did not. Although IL-1β and TNFα increased as expected with sepsis, IL-6, IL-8, IL-10, and G-CSF however increased to a greater extent than expected. From the above, we diagnosed the development of intestinal necrosis as a result of widespread intestinal ischemia, and that sepsis was associated with this poor condition.

Keywords: acute phase reactants; cytokine profiles; fulminant necrotizing enterocolitis; high mobility group box-1; preterm infant.

Fig. 1-A.

Transition of clinical symptoms and treatment after onset: The time of onset of vomiting was set to 0 and displayed over time. → in the abdominal radiograph refers to the gas in the portal vein. The bubble gas pattern observed early after onset spread from the lower right half to occupy the entire lower half of the abdomen. Throughout the course, no free air was found in the abdomen. The blood flow in the celiac artery (CA) and superior mesenteric artery (SMA) was followed by abdominal echo. The SMA could be visualized at onset, but visualization of the CA was not possible. We noted that the blood flow velocity of the celiac artery, which seems to be compensatory, was increased. Twenty hours after onset, the abdominal wall rapidly increased in fullness, and the color of the abdominal wall became dark purple instead of inflammatory red.

Fig. 1-B.

Transition of clinical vital signs after onset: The time axis is the same as in Fig. 1-A. From the vital signs 12 hours after the onset, it can be seen that the infant had gone into shock. After that, despite all the possible treatments, there was no recovery from shock.

Fig. 2.

Time course of acute phase reactants, peripheral blood cells, and releasing enzymes before and after onset: Haptoglobin (Hp) remained negative from beginning to end. C-reactive protein (CRP) became positive 12 hours after the onset. The α1-acid glycoprotein (AGP) did not increase prior to CRP during feeding intolerance as has been previously reported. After onset, it increased slightly later than the increase in CRP. A decrease in these two acute phase proteins was seen once after exchange transfusion, but levels returned to the previous value in about half a day. White blood cell count and platelet count dropped sharply after onset. Hemoglobin did not decrease as much as the former two. Three of the releasing enzymes also increased after onset, did not increase to the same degree. Arrows mean blood exchange transfusion.

Fig. 3.

Serial changes of cytokine profiles and the three cytotoxic markers after onset: It can be seen that all six cytokines show high levels, and in particular, IL-6,-8,-10 and G-CSF have markedly elevated levels. Although these cytokines temporarily decreased after exchange transfusion, exacerbation exceeding the previous value was observed in about half a day. Considering the age of the newborn at onset, it is judged that the effect of ischemia-reperfusion injury at birth has disappeared. Based on this hypothesis, it is judged to be abnormal when these cytotoxic markers are present in the blood after onset. Considering adult reports, high mobility group box-1 (HMGB-1) and histone H3 are clearly elevated, but syndecan-1 is not significantly elevated. Serum syndecan-1 concentration in sepsis remains at a level that does not cause disseminated intravasclular coagulopathy. The arrows indicate blood exchange transfusion.