Cytokine profiles in an extremely preterm infant with congenital syphilis.

We report the cytokine profiles of an infant with congenital syphilis as a first case. This female infant was born by vaginal delivery at a gestational age of 27 weeks during her mother's treatment for syphilis. Elevation of T helper (Th)-1 cytokines (interleukin (IL)-2, IL-12) and IL-17, which supports immunological mechanisms of Th-1, was similar to that in cases of syphilis in adults. IL-6 and granulocyte colony-stimulating factor (G-CSF), the synergistic effects of which cause the leukemoid reaction, were also elevated. The levels of interferon-γ and IL-17 in cerebral spinal fluid, which are elevated in neurosyphilis in adults, were slightly elevated.

Urinary and serum levels of high mobility group box 1.

Background: High mobility group box 1 (HMGB-1) has been extensively studied in adults and to a certain extent in neonates as well. Clinical examination of neonates, especially unwell neonates soon after birth, should be minimally invasive. Objective: This study aimed to investigate whether the urinary HMGB-1 level is comparable to the serum HMGB-1 level in neonates. Methods: In all, 87 neonates (37.5 ± 2.9 weeks of gestation and a mean birth weight of 2588 ± 649 g) were enrolled. Of these, 53 were males and 34 were females. The umbilical cord blood and the first or second spontaneous voiding urine samples were stored, and the HMGB-1 level in the samples was measured. Results: HMGB-1 was detected in all urinary samples. In these samples, we found acetylated HMGB-1 and may be devoid of nine residues at the N-terminal amino acid sequence. There was a significant correlation between the serum HMGB-1 level and urinary HMGB-1 level (r = 0.73, p < 0.001). Urinary HMGB1 levels in fetal neonatal asphyxia were significantly higher than those in healthy controls (p = 0.09). Conclusion: Urinary excretion may be one of the metabolic pathways of HMGB-1. The urinary HMGB-1 level may be comparable to the serum HMGB-1 level in the early neonatal period.

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

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-1ß 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.

Peripheral platelet phagocytosis in an extremely low birth weight infant:a case report.

A 768 g female neonate, born at 25 weeks' gestation, developed sepsis due to methicillin-resistant Staphylococcus epidermidis on day 14. Severe thrombocytopenia was observed, and hemophagocytic macrophages were identified in her peripheral blood smear. Cytokine profiles at the time of onset suggested that an inflammatory cytokine storm had activated lymphocytes and macrophages, leading to platelet phagocytosis. After administration of vancomycin for 14 days and immunoglobulin therapy, she improved without any complications. Considering the results of cytokine profiles, early intervention for infection may have prevented progression to hemophagocytic lymphohistiocytosis and reduced the severity of clinical symptoms.

A male preterm infant with cow's milk allergy to human milk fortifier showing only severe respiratory symptoms.

We report a male infant with a birthweight of 1,400 g at 29 weeks 2 days gestation diagnosed as having cow's milk allergy (CMA) due to human milk fortifier, who developed severe respiratory symptoms. The infant had no gastrointestinal symptoms; rather, the initial symptoms were apnea attacks and wheezing with a prolonged expiratory phase that progressed to severe ventilatory insufficiency requiring mechanical ventilation. Aggravation of his general condition, which appeared to be due to sepsis, was improved by temporary starvation and respiratory care, but he relapsed on the resumption of enteral feeding of his mother's milk with a human milk fortifier. As a result, this event was interpreted as a positive oral food challenge test. The infant resumed complete breastfeeding without the fortifier and has not relapsed since. Examination of his serial cytokine profiles from residual serum revealed that although interleukin-5 was not increased, interferon (IFN)-γ was increased, suggesting some relation between the time course of IFN-γ and the infant's eosinophil count. These findings may indicate that the involvement of IFN-γ is one cause of the onset of this disease.

Neonatal Leukemoid Reaction with Fetal Inflammatory Response Syndrome Is Associated with Elevated Serum Granulocyte Colony Stimulating Factor and Interleukin-6.

Leukemoid reaction (LR) is a reactive disease that exhibits abnormal blood values similar to leukemia, but not due to leukemia. One report showed that neonatal LR (NLR) was associated with elevated serum granulocyte colony stimulating factor (G-CSF) in only 30% of the study neonates. NLR is not always associated with the elevation of serum G-CSF. NLR was defined as a white blood cell count of ≥ 40 × 103/µL and/or blast cell concentration of > 2%. We have focused on NLR with fetal inflammatory response syndrome (FIRS), defined as a fetal systemic inflammatory reaction triggered by intrauterine infection. FIRS was diagnosed based on a cord serum interleukin-6 (IL-6) concentration ≥ 17.5 pg/mL and histopathological chorioamnionitis. Because NLR is highly associated with FIRS, we have hypothesized that NLR is associated with the elevation of both G-CSF and IL-6. This is the first report to measure multiple cytokines in NLR at the same time. The study comprised 19 preterm infants with FIRS: 8 with NLR (study group) and 11 without NLR (control group). Serum G-CSF and IL-6 concentrations were significantly higher in the study group than the control group. There was a positive correlation between G-CSF and IL-6 levels in the study group but not in the control group. These results suggest that elevated serum G-CSF and IL-6 may underlie NLR. Thus, G-CSF and IL-6 concentrations may be predictive of the onset of NLR. Measuring these cytokines is useful for judging the prognosis of preterm infants and for their post-natal clinical management.

Serial investigation of continuous glucose monitoring in a very low birth weight infant with transient late-onset hyperglycemia.

Transient late-onset hyperglycemia was detected in a very low birth weight (VLBW) infant (gestational age 28 weeks, birth weight 1,082 g) by routine point-of-care glucose monitoring.　The infant had no clinical symptom.　Serial continuous glucose monitoring (CGM) was conducted for 3 days at 31, 35, and 39 weeks' post conceptual age.　The difference values between the maximum and minimum blood glucose levels during the interval from one enteral feeding to the next enteral feeding were 32.3±14.3 mg/dL, 47.5±22.9 mg/dL, and 27.5±12.9 mg/dL for the 1st, 2nd, and 3rd CGM, respectively.　The serial change in the values was statistically significant (p<0.01).CGM is widely used as a routine clinical practice, which is true even in VLBW infants.　Hyperglycemic events detected by only once of CGM in otherwise healthy preterm infants have already been reported on larger numbers of patients.　To our knowledge, this is the first report that the change of glucose intolerance in a VLBW infant with transient late-onset hyperglycemia was investigated by serial CGM.

DOWN'S SYNDROME WITH NEONATAL ALLOIMMUNE THROMBOCYTOPENIA DUE TO HLA-A2 ANTIBODY.

Anti-HLA antibodies reportedly exist in the one third of pregnant women. But few occurrences of neonatal alloimmune thrombocytopenia (NAIT) caused by anti-HLA antibodies have been reported. Here a male baby, who was admitted for low birth weight with Down syndrome (DS), was suffered from thrombocytopenia without transient myeloproliferative disorder (TMD). Positive reactions of HLA-specific antibodies were detected in maternal serum. Cross-matching tests between maternal serum and paternal platelets and lymphocytes were strongly positive. It is most conceivable that the previous pregnancy of the mother induced the production of anti-HLA-A2 antibody, which crossed the placenta and subsequently caused an NAIT in the case presented. This is the first case of DS with NAIT due to anti-HLA antibodies.