An observational, multicenter, registry-based cohort study of Turkish Neonatal Society in neonates with Hypoxic ischemic encephalopathy.

BACKGROUND: Hypoxic ischemic encephalopathy (HIE) is a significant cause of mortality and short- and long-term morbidities. Therapeutic hypothermia (TH) has been shown to be the standard care for HIE of infants ≥36 weeks gestational age (GA), as it has been demonstrated to reduce the rates of mortality, and adverse neurodevelopmental outcomes. This study aims to determine the incidence of HIE in our country, to assess the TH management in infants with HIE, and present short-term outcomes of these infants. METHODS: The Turkish Hypoxic Ischemic Encephalopathy Online Registry database was established for this multicenter, prospective, observational, nationally-based cohort study to evaluate the data of infants born at ≥34 weeks GA who displayed evidence of neonatal encephalopathy (NE) between March, 2020 and April 2022. RESULTS: The incidence of HIE among infants born at ≥36 weeks GA (n = 965) was 2.13 per 1000 live births (517:242440), and accounting for 1.55% (965:62062) of all neonatal intensive care unit admissions. The rates of mild, moderate and severe HIE were 25.5% (n = 246), 58.9% (n = 568), and 15.6% (n = 151), respectively. Infants with severe HIE had higher rates of abnormal magnetic resonance imaging (MRI) findings, and mortality (p<0.001). No significant difference in mortality and abnormal MRI results was found according to the time of TH initiation (<3 h, 3-6 h and >6 h) (p>0.05). TH was administered to 85 (34.5%) infants with mild HIE, and of those born of 34-35 weeks of GA, 67.4% (n = 31) received TH. A total of 58 (6%) deaths were reported with a higher mortality rate in infants born at 34-35 weeks of GA (OR 3.941, 95% Cl 1.446-10.7422, p = 0.007). CONCLUSION: The incidence of HIE remained similar over time with a reduction in mortality rate. The timing of TH initiation, whether <3 or 3-6 h, did not result in lower occurrences of brain lesions on MRI or mortality. An increasing number of infants with mild HIE and late preterm infants with HIE are receiving TH; however, the indications for TH require further clarification. Longer follow-up studies are necessary for this vulnerable population.

Effect of partially hydrolyzed synbiotic formula milk on weight gain of late preterm and term infants-a multicenter study.

Introduction: Data on the effectiveness of hydrolyzed infant formula containing both pre- and probiotics (synbiotic formula) on the growth of infants is still scarce. This retrospective study was designed to evaluate the effect of a partially hydrolyzed synbiotic formula on growth parameters and the possible occurrence of major gastrointestinal adverse events or morbidities in infants born via cesarean section (C-section) delivery. Methods: C-section-delivered term and late preterm infants who received either partially hydrolyzed synbiotic formula, standard formula, or maternal milk and followed at seven different hospitals from five different regions of Turkey, during a 1-year period with a minimum follow-up duration of 3 months were evaluated retrospectively. All the included infants were evaluated for their growth patterns and any kind of morbidity such as diarrhea, constipation, vomiting, infection, or history of hospitalization. Results: A total of 198 infants (73 in the human milk group, 61 in the standard formula group, and 64 in the partially hydrolyzed synbiotic formula group) reached the final analysis. The groups were similar regarding their demographic and perinatal characteristics. No difference was observed between the three groups regarding gastrointestinal major side effects. Growth velocities of the infants in the human milk and partially hydrolyzed synbiotic formula groups during the first month of life were similar whereas the weight gain of infants in the standard formula group was significantly less than these two groups (p < 0.001). Growth velocities were similar among the three groups between 1st and 3rd months of age. Discussion: A partially hydrolyzed synbiotic formula provided better weight gain in late-preterm and term infants who were delivered via C-section delivery compared to the standard formula during the first month of life. This weight gain was similar to the infants receiving exclusively human milk. This difference was not observed in length and head circumference gain. No difference was observed in any of the parameters during the 1st-3rd months of age. Specially formulated partially hydrolyzed synbiotic formulas may reverse at least some of the negative impacts of C-section delivery on the infant and help to provide better growth, especially during the early periods of life.

Molsidomine decreases hyperoxia-induced lung injury in neonatal rats.

BACKGROUND: The study's objective is to evaluate if Molsidomine (MOL), an anti-oxidant, anti-inflammatory, and anti-apoptotic drug, is effective in treating hyperoxic lung injury (HLI). METHODS: The study consisted of four groups of neonatal rats characterized as the Control, Control+MOL, HLI, HLI + MOL groups. Near the end of the study, the lung tissue of the rats were evaluated with respect to apoptosis, histopathological damage, anti-oxidant and oxidant capacity as well as degree of inflammation. RESULTS: Compared to the HLI group, malondialdehyde and total oxidant status levels in lung tissue were notably reduced in the HLI + MOL group. Furthermore, mean superoxide dismutase, glutathione peroxidase, and glutathione activities/levels in lung tissue were significantly higher in the HLI + MOL group as compared to the HLI group. Tumor necrosis factor-α and interleukin-1ß elevations associated with hyperoxia were significantly reduced following MOL treatment. Median histopathological damage and mean alveolar macrophage numbers were found to be higher in the HLI and HLI + MOL groups when compared to the Control and Control+MOL groups. Both values were increased in the HLI group when compared to the HLI + MOL group. CONCLUSIONS: Our research is the first to demonstrate that bronchopulmonary dysplasia may be prevented through the protective characteristics of MOL, an anti-inflammatory, anti-oxidant, and anti-apoptotic drug. IMPACT: Molsidomine prophylaxis significantly decreased the level of oxidative stress markers. Molsidomine administration restored the activities of antioxidant enzymes. Molsidomine prophylaxis significantly reduced the levels of inflammatory cytokines. Molsidomine may provide a new and promising therapy for BPD in the future. Molsidomine prophylaxis decreased lung damage and macrophage infiltration in the tissue.

Mortality related factors on hypoxic ischemic encephalopathic patients treated with therapeutic hypothermia: an 11-year single-center experience.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is a condition that may cause multiple organ dysfunction and has a high rate of mortality and morbidity. Therapeutic hypothermia is the only proven treatment that decreases the sequel and mortality rate of neonates that are born after 36 weeks of pregnancy and have moderate-severe HIE. METHODS: Our study was a single-center, retrospective study that includes newborns (gestational age ≥ 36 weeks) who underwent therapeutic hypothermia due to hypoxic-ischemic encephalopathy between 2010 and 2020. We evaluated 125 patients who were diagnosed with moderate to severe HIE and received therapeutic hypothermia. Demographic and clinical data were obtained from electronic medical records and patient files. The patients were separated into two groups as exitus group (n = 39) and discharged group (n = 86). We aimed to evaluate factors affecting mortality. RESULTS: We determined that the median resuscitation times were longer in the delivery room [retrospectively, 10th minutes (0-30) vs. 1 min (0-20), p < 0.05], the tenth min APGAR scores were lower [respectively, 4 (0-7) vs. 6 (3-10), p < 0.05], and the median pH value in the first blood gas taken was lower [respectively, 6.87 (6.4-7.14) vs. 6.90 (6.58-7.12), p < 0.05] in the exitus group. We also determined that multiple organ dysfunction is seen more often in the exitus group. DISCUSSION: This study demonstrated that the depth of acidosis in the blood gas, multiple organ dysfunction, and the existence of early-onset seizures are the signs of poor prognosis. Therefore, physicians need to be aware of such prognostic factors to follow these patients more closely in terms of possible complications and to inform their parents.

Safety, efficiency, and treatment satisfaction in children with primary immunodeficiency receiving subcutaneous immunoglobulin treatment.

OBJECTIVE: Patients with Inborn Errors of Immunity, also known as Primary Immunodeficiency (PID), are prone to recurrent bacterial infections and these patients often require lifelong IgG replacement therapy. The aim of this presentation is to evaluate the efficacy, safety, and patient satisfaction in PID patients receiving subcutaneous immunoglobulin (SCIG) treatment and to share our expe-riences. METHODS: Twenty-one patients who were followed up with the diagnosis of PID by our Pediatric Allergy and Immunology Clinic and received regular intravenous immunoglobulin therapy (IVIG) befo-re starting SCIG treatment were included in the study. RESULTS: A total of 21 patients were included in the study. 10 of the patients (47.6%) were female, 11 (52.4%) were male, and the mean age was 8.8±4.42 years. Five of the patients were Syrian patients living in the refugee camp. Threshold IgG levels of the patients were evaluated every 3 months. IgG levels were significantly higher than baseline IVIG levels at weeks 3, 6, and 12 of SCIG treatment, respectively. There was no significant difference between 3rd, 6th and 12th months of SCIG treatment. A statistically significant decrease was observed in the frequency of infections in patients who received SCIG treatment (p=0.003). During SCIG treatment, the total infection rate was 4.1/person/year. According to the TSQM-9 satisfaction questionnaire, the annual hospitalization rate was 0.9/patient/year for IVIG and 0.4/patient/year for SCIG (p>0.005), and 61.9% of patients were moderately satisfied, 14.2%. 19% were very satisfied and 4.7% were not satisfied with the treatment. When the satisfaction criteria were evaluated, it was observed that the patients mostly (71%) were satisfied with the absence of vascular access prob-lems and the comfort of self-application at home. CONCLUSION: SCIG therapy causes high serum IgG levels and a reduced frequency of infections and can be a safe, effective, and well-tolerated treatment alternative in patients with PID with high patient satisfaction.

The protective effects of apocynin in hyperoxic lung injury in neonatal rats.

AIM: Inflammation and oxidate stress are significant factors in the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of this study is to investigate the efficacy of apocynin (APO), an anti-inflammatory, antioxidant, and antiapoptotic drug, in the prophylaxis of neonatal hyperoxic lung injury. METHOD: This experimental study included 40 neonatal rats divided into the control, APO, BPD, and BPD + APO groups. The control and APO groups were kept in a normal room environment, while the BPD and BPD + APO groups were kept in a hyperoxic environment. The rats in the APO and BPD + APO groups were administered intraperitoneal APO, while the control and BPD rats were administered ordinary saline. At the end of the trial, lung tissue was evaluated with respect to the degree of histopathological injury, apoptosis, oxidant and antioxidant capacity, and severity of inflammation. RESULT: The BPD and BPD + APO groups exhibited higher mean histopathological injury and alveolar macrophage scores compared to the control and APO groups. Both scores were lower in the BPD + APO group in comparison to the BPD group. The BPD + APO group had a significantly lower average of TUNEL positive cells than the BPD group. The lung tissue examination indicated significantly higher levels of mean malondialdehyde (MDA), total oxidant status (TOS), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) in the BPD group compared to the control and APO groups. While the TNF-α and IL-1ß levels of the BPD + APO group were similar to that of the control group, the MDA and TOS levels were higher compared to the controls and lower compared to the BPD group. The BPD group demonstrated significantly lower levels/activities of mean total antioxidant status, glutathione reductase, superoxide dismutase, glutathione peroxidase in comparison to the control and APO groups. While the mean antioxidant enzyme activity of the BPD + APO group was lower than the control group, it was significantly higher compared to the BPD group. CONCLUSION: This is the first study in the literature to reveal through an experimental neonatal hyperoxic lung injury that APO, an anti-inflammatory, antioxidant, and antiapoptotic drug, exhibits protective properties against the development of BPD.