An Early Prediction Model for Estimating Bronchopulmonary Dysplasia in Preterm Infants.

INTRODUCTION: Accurate assessment of the risk for bronchopulmonary dysplasia (BPD) is critical to determine the prognosis and identify infants who will benefit from preventive therapies. Clinical prediction models can support the identification of high-risk patients. In this study, we investigated the potential risk factors for BPD and compared machine learning models for predicting the outcome of BPD/death on days 1, 7, 14, and 28 in preterm infants. We also developed a local BPD estimator. METHODS: This study involved 124 infants. We evaluated the composite outcome of BPD/death at a postmenstrual age of 36 weeks and identified risk factors that would improve BPD/death prediction. SPSS for Windows Version 11.5 and Weka 3.9 software were used for the data analysis. RESULTS: To evaluate the combined effect of all variables, all risk factors were taken into consideration. Gestational age, birth weight, mode of respiratory support, intraventricular hemorrhage, necrotizing enterocolitis, surfactant requirement, and late-onset sepsis were risk factors on postnatal days 7, 14, and 28. In a comparison of four different time points (postnatal days 1, 7, 14, and 28), the day 7 model provided the best prediction. According to this model, when a patient was diagnosed with BPD/death, the accuracy rate was 89.5%. CONCLUSION: The postnatal day 7 model was the best predictor of BPD or death. Future validation studies will help identify infants who may benefit from preventive therapies and develop individualized care.

Evaluation of the efficacy and associated complications of regional citrate anticoagulation in neonates: experience from a fourth level neonatal intensive care unit.

Continuous kidney replacement therapy (CKRT) use has increased in recent years, but anticoagulation is a challenge for neonates. Regional citrate anticoagulation (RCA) is rarely preferred in neonates because of citrate accumulation (CA) and metabolic complications. We aimed to demonstrate the efficacy and safety of RCA in neonates. We retrospectively analyzed the medical records of 11 neonates treated with RCA-CKRT between 2018 and 2023. The initial dose of RCA was 2.1-3 mmol/l, and then, its dose was increased according to the level of ionized calcium (iCa+2) in the circuit and patients. The total/iCa+2 ratio after-treatment > 2.5 was indicated as CA. We evaluated to citrate dose, CA, circuit lifespan, and dialysis effectivity. The median gestational age was 39 (36.4-41.5) weeks, the median body weight (BW) was 3200 (2400-4000) grams, and the mean postnatal age was 4 (2-24) days. The most common indication for CKRT was hyperammonemia (73%). All neonates had metabolic acidosis and hypocalcemia during CKRT. Other common metabolic complications were hypophosphatemia (90%), hypokalemia (81%), and hypomagnesemia (63%). High dialysate rates with a median of 5765 ml/h/1.73 m2 allowed for a rapid decrease in ammonia levels to normal. Four patients (36.3%) had CA, and seven (63.7%) did not (non-citrate accumulation, NCA). Mean BW, median postnatal age, biochemical parameters, coagulation tests, and ammonia levels were similar between the CA and NCA groups. Low pH, low HCO3, high lactate, and SNAPPE-II scores could be associated with a higher T/iCa ratio. CONCLUSION:  RCA was an efficient and safe anticoagulation for neonates requiring CKRT. Metabolic complications may occur, but they could be managed with adequate supplementation. WHAT IS KNOWN: • Continuous kidney replacement therapy (CKRT) has become popular in recent years due to its successful treatment of fluid overload, electrolyte imbalance, metabolic acidosis, multi-organ failure, and hyperleucinemia/hyperammonemia associated with inborn errors of metabolism. • The need for anticoagulation is the major difficulty in neonatal CKRT. In adult and pediatric patients, regional citrate anticoagulation has been shown to be effective. WHAT IS NEW: • RCA is an effective and safe anticoagulation method for neonates who require CKRT. • Electrolyte imbalances and metabolic acidosis could be managed with adequate supplementation and appropriate treatment parameters such as citrate dose, blood flow rate, and dialysate flow rate.

Comparison of Definitions for Bronchopulmonary Dysplasia: A Cohort Study.

We aimed to compare the definitions of National Institute of Child Health and Human Development (NICHD) for bronchopulmonary dysplasia (BPD) for determining the incidences, and predicting late death and respiratory outcome. This retrospective cohort study included infants born at<32 weeks' gestation who survived up to 36 weeks' postmenstrual age (PMA). Infants were classified as having BPD or no BPD per thedefinitions of NICHD 2001 and 2018. The incidences of BPD were 49 and 32% according to the 2001 and 2018 NICHD definitions. Gestational age, birth weight and intubation after birth were associated with BPD by both definitions. The NICHD 2018 definition displayed similar sensitivity (100%) and negative predictive value (100%), and higher specificity (70 vs. 52%) for predicting death after 36 weeks' PMA; a higher specificity (72 vs. 53%), comparable negative predictive value (77 vs.76%), but lower sensitivity for predicting adverse respiratory outcome within 12 months corrected age compared with the NICHD 2001 definition. The NICHD 2018 definition is as powerful as the 2001 definition for predicting late death and seems to be a better indicator for long-term respiratory outcome. The use of supplemental oxygen or oxygen plus respiratory support should be considered while predicting both late death and long-term respiratory outcome.

Pediatric Invasive Aspergillosis: a Retrospective Review of 59 Cases.

Invasive aspergillosis (IA) is a major cause of morbidity and mortality. This study aimed to present our 10-year IA experience at a single center. Fifty-nine pediatric patients with IA were included in this study. The male-to-female ratio was 42/17. The median age was 8.75 years. Hematologic malignancy was present in the majority of the patients (40/59, 68%). The mean neutropenia duration was 18.5 days. Cytosine arabinoside was the most common immunosuppressive therapy directed at T cells during IA diagnosis. IA cases were categorized as proven (27%), probable (51%), or possible (22%) according to the 2008 European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. The lungs (78%) were the most common site of IA, and nodules were the most frequent radiological findings (75.5%). In 38 patients (64.4%) receiving antifungal prophylaxis, prophylactic agents included fluconazole (30.5%), liposomal amphotericin B (23.7%), posaconazole (8.5%), and voriconazole (1.7%). Initial treatment was most commonly administered as monotherapy (69.5%). The median antifungal treatment duration was 67 days. Eleven deaths (18.6%) were due to aspergillosis. With the increased use of corticosteroids, biological agents, and intensive immunosuppressive chemotherapy, IA will most likely continue to occur frequently in pediatric patients.

Nasal Continuous Positive Airway Pressure vs. Nasal Intermittent Positive Pressure Ventilation as Initial Treatment After Birth in Extremely Preterm Infants.

Objective: Non-invasive respiratory support strategies are known to reduce the complications of invasive mechanical ventilation in preterm infants. Nasal continuous positive airway pressure (NCPAP) and nasal intermittent positive pressure ventilation (NIPPV) are commonly used ones. The recent meta-analyses indicated that early NIPPV did appear to be superior to NCPAP for decreasing respiratory failure and the need for intubation among preterm infants with respiratory distress syndrome (RDS). The aim of the study was to compare the short-term outcomes of extremely preterm infants who received NCPAP or NIPPV as an initial treatment of RDS. Methods: This retrospective study included infants born before 29 weeks' gestation between 1 January 2018 and 31 December 2021 who received non-invasive respiratory support with NCPAP or NIPPV. For every infant included in the cohort, only the first episode of NCPAP or NIPPV as initial treatment was evaluated. The primary outcome was the need for intubation within 72 h, and the secondary outcomes were the need for intubation within 7 days, administration of surfactant, prematurity-related morbidities, mortality, and death or bronchopulmonary dysplasia (BPD). Results: During the study period, there were 116 inborn admissions of preterm infants born <29 weeks' gestation and 60 of them met the inclusion criteria. Of these, 31 (52%) infants received NCPAP while 29 (48%) infants received NIPPV at the first hours after birth. There were no differences in the baseline demographics between the groups (p > 0.05). Blood gas parameters (pH, pCO2, HCO3, and lactate) at admission were not different. The need for intubation within 72 h as the primary outcome was similar between NCPAP and NIPPV groups (35.5 vs. 34.5%, p = 0.935). The rates of surfactant requirement, need for intubation within 7 days, prematurity-related morbidities, mortality, and death/BPD were similar among the groups (p > 0.05). Conclusion: Nasal intermittent positive pressure ventilation is non-inferior to NCPAP as an initial treatment in extremely preterm infants with RDS. Although the rate of intubation in the first week, mortality, and BPD did not differ between groups, additional studies are needed and the synchronization of NIPPV should be evaluated.

Effects of Umbilical Cord Management Strategies on Stem Cell Transfusion, Delivery Room Adaptation, and Cerebral Oxygenation in Term and Late Preterm Infants.

Background: The umbilical cord blood contains a high concentration of stem cells. There is not any published study evaluating the amount of stem cells that have the potential to be transferred to the infant through placental transfusion methods as delayed cord clamping (DCC) and umbilical cord milking (UCM). The aim of this study is to measure the concentrations of endothelial progenitor cell (EPC) and CD34+ hematopoietic stem cell (HSC) in the placental residual blood volume (PRBV), and evaluate the delivery room adaptation and cerebral oxygenation of these infants. Methods: Infants with ≥36 gestational weeks were randomized to receive DCC (120 s), UCM, or immediate cord clamping (ICC). EPC and CD34+ HSC were measured by flow cytometry from the cord blood. PRBV was collected in the setup. The cord blood gas analysis and complete blood count were performed. The heart rate (HR), oxygen saturation (SpO2), and cerebral regional oxygen saturation (crSO2) were recorded. Results: A total of 103 infants were evaluated. The amount of PRBV (in ml and ml/kg) was higher in the ICC group (p < 0.001). The number of EPCs in the PRBV content (both ml and ml/kg) were the highest in the ICC group (p = 0.002 and p = 0.001, respectively). The number of CD34+ HSCs in PRBV content (ml and ml/kg) was similar in all groups, but nonsignificantly higher in the ICC group. The APGAR scores at the first and fifth min were lower in the ICC group (p < 0.05). The mean crSO2 values were higher at the 3rd and 10th min in the DCC group (p = 0.042 and p = 0.045, respectively). cFOE values were higher at the 3rd and 10th min in the ICC group (p = 0.011 and p < 0.001, respectively). Conclusion: This study showed that placental transfusion methods, such as DCC and UCM, provide both higher blood volume, more stem cells transfer to the infant, and better cerebral oxygenation in the first minutes of life, whereas many lineages of stem cells is lost to the placenta by ICC with higher residual blood volume. These cord management methods rather than ICC do not require any cost or technology, and may be a preemptive therapeutic source for diseases of the neonatal period.

Alternative Methods of Surfactant Administration in Preterm Infants with Respiratory Distress Syndrome: State of the Art.

For preterm infants with respiratory distress syndrome, delivery of surfactant via brief intubation (INtubate, SURfactant, Extubate; InSurE) has been the standard technique of surfactant administration. However, this method requires intubation and positive pressure ventilation. It is thought that even the short exposure to positive pressure inflations may be enough to initiate the cascade of events that lead to lung injury in the smallest neonates. In an effort to avoid tracheal intubation and positive pressure ventilation, several alternative and less invasive techniques of exogenous surfactant administration have been developed over the years. These have been investigated in clinical studies, including randomized clinical trials, and have demonstrated advantages such as a decrease in the need for mechanical ventilation and incidence of bronchopulmonary dysplasia. These newer techniques of surfactant delivery also have the benefit of being easier to perform. Surfactant delivery via pharyngeal instillation, laryngeal mask, aerosolization, and placement of a thin catheter are being actively pursued in research. We present a contemporary review of surfactant administration for respiratory distress syndrome via these alternative methods in the hope of guiding physicians in their choices for surfactant application in the neonatal intensive care unit.

Early neonatal outcomes of very-low-birth-weight infants in Turkey: A prospective multicenter study of the Turkish Neonatal Society.

OBJECTIVE: To investigate the early neonatal outcomes of very-low-birth-weight (VLBW) infants discharged home from neonatal intensive care units (NICUs) in Turkey. MATERIAL AND METHODS: A prospective cohort study was performed between April 1, 2016 and April 30, 2017. The study included VLBW infants admitted to level III NICUs. Perinatal and neonatal data of all infants born with a birth weight of ≤1500 g were collected for infants who survived. RESULTS: Data from 69 NICUs were obtained. The mean birth weight and gestational age were 1137±245 g and 29±2.4 weeks, respectively. During the study period, 78% of VLBW infants survived to discharge and 48% of survived infants had no major neonatal morbidity. VLBW infants who survived were evaluated in terms of major morbidities: bronchopulmonary dysplasia was detected in 23.7% of infants, necrotizing enterocolitis in 9.1%, blood culture proven late-onset sepsis (LOS) in 21.1%, blood culture negative LOS in 21.3%, severe intraventricular hemorrhage in 5.4% and severe retinopathy of prematurity in 11.1%. Hemodynamically significant patent ductus arteriosus was diagnosed in 24.8% of infants. Antenatal steroids were administered to 42.9% of mothers. CONCLUSION: The present investigation is the first multicenter study to include epidemiological information on VLBW infants in Turkey. Morbidity rate in VLBW infants is a serious concern and higher than those in developed countries. Implementation of oxygen therapy with appropriate monitoring, better antenatal and neonatal care and control of sepsis may reduce the prevalence of neonatal morbidities. Therefore, monitoring standards of neonatal care and implementing quality improvement projects across the country are essential for improving neonatal outcomes in Turkish NICUs.

An observational, prospective, multicenter study on rescue high-frequency oscillatory ventilation in neonates failing with conventional ventilation.

BACKGROUND: To achieve gas exchange goals and mitigate lung injury, infants who fail with conventional ventilation (CV) are generally switched to high-frequency oscillatory ventilation (HFOV). Although preferred in many neonatal intensive care units (NICUs), research on this type of rescue HFOV has not been reported recently. METHODS: An online registry database for a multicenter, prospective study was set to evaluate factors affecting the response of newborn infants to rescue HFOV treatment. The study population consisted of 372 infants with CV failure after at least 4 hours of treatment in 23 participating NICUs. Patients were grouped according to their final outcome as survived (Group S) or as died or received extracorporeal membrane oxygenation (ECMO) (Group D/E). Patients' demographic characteristics and underlying diseases in addition to their ventilator settings, arterial blood gas (ABG) analysis results at 0, 1, 4, and 24 hours, type of device, ventilation duration, and complications were compared between groups. RESULTS: HFOV as rescue treatment was successful in 58.1% of patients. Demographic and treatment parameters were not different between groups, except that infants in Group D/E had lower birthweight (BW) (1655 ± 1091 vs. 1858 ± 1027 g, p = 0.006), a higher initial FiO2 setting (83% vs. 72%, p < 0.001), and a higher rate of nitric oxide exposure (21.8% vs. 11.1%, p = 0.004) in comparison to infants who survived (Group S). The initial cut-offs for a successful response on ABG were defined as pH >7.065 (OR: 19.74, 95% CI 4.83-80.6, p < 0.001), HCO3 >16.35 mmol/L (OR: 1.06, 95% CI 1.01-1.1, p = 0.006), and lactate level <3.75 mmol/L (OR: 1.09%95 CI 1.01-1.16, p = 0.006). Rescue HFOV duration was associated with retinopathy of prematurity (p = 0.005) and moderate or severe chronic lung disease (p < 0.001), but not with patent ductus arteriosus or intraventricular hemorrhage, in survivors (p > 0.05). CONCLUSION: Rescue HFOV as defined for this population was successful in more than half of the patients with CV failure. Although the response was not associated with gestational age, underlying disease, device used, or initial MV settings, it seemed to be more effective in patients with higher BW and those not requiring nitric oxide. Initial pH, HCO3, and lactate levels on ABG may be used as predictors of a response to rescue HFOV.

Placenta, Secret Witness of Infant Morbidities: The Relationship Between Placental Histology and Outcome of the Premature Infant.

OBJECTIVE: The microscopic and macroscopic features of the placenta can contribute to the clinical understanding of premature delivery. The aim of our study was to figure out the relationship between the histopathological findings of the placentas of premature deliveries and its effects on neonatal morbidity and mortality. MATERIAL AND METHOD: The placentas of 284 singleton preterm infants with < 35 weeks of gestation were examined. Three groups were created as the normal, chorioamnionitis and vasculopathy groups according to the histopathological findings in the placentas of the subjects. RESULTS: The mean gestational age of the infants in the study group was 30.5 ± 3.2 weeks, and the mean birth weight was 1588 ± 581 g. The pathology was normal in ninety-six (33.8%), vasculopathy in 153 (53.9%) and chorioamnionitis in 35 (12.3%). The gestation age of the infants was lower in the chorioamnionitis group. Moreover, retinopathy of prematurity, early onset neonatal sepsis, and duration of respiratory support were found to be higher in the chorioamnionitis group. In the vasculopathy group, preeclampsia and small for gestational age were found to be significantly higher. CONCLUSION: Histopathological findings of the placentas from preterm deliveries provided important data in determining the etiology of preterm delivery and outcomes of infants. Infants delivered by mothers with chorioamnionitis were particularly found to be more preterm, and these preterm infants would have a longer hospital stay, higher respiratory support requirement, and more serious morbidities.

Síndrome de Netherton: el caso de un recién nacido con insuficiencia respiratoria / Netherton syndrome: A neonatal case with respiratory insufficiency

El síndrome de Netherton (SN) es una enfermedad autosómica recesiva, muy poco frecuente, que se caracteriza por la presencia de eritrodermia ictiosiforme congènita, anomalías capilares y manifestaciones atópicas. Este síndrome es consecuencia de una mutación recesiva en el gen SPINK5. Las manifestaciones del síndrome de SN varían considerablemente entre las personas que lo padecen. Aquí informamos el caso de un recién nacido que presentaba insuficiencia respiratoria grave, hipotermia y eritrodermia, al que se le diagnosticó SN, confirmado mediante pruebas genéticas moleculares.

Netherton syndrome (NS) is a rare, autosomal recessive disease characterized with congenital ichthyosiform erythroderma, hair abnormality and atopic manifestations. This syndrome is caused by recessive mutation in the SPINK5 gene. Disease manifestations vary considerably among NS individuals. We report a newborn presented with severe respiratory insufficiency, hypothermia and erythroderma, was diagnosed as having NS and confirmed with molecular genetic testing.

Effects of umbilical cord milking on the need for packed red blood cell transfusions and early neonatal hemodynamic adaptation in preterm infants born ≤1500 g: a prospective, randomized, controlled trial.

OBJECTIVE: The aim of this study was to evaluate the effects of umbilical cord milking (UCM) on the need for packed red blood cell (PRBC) transfusion and hematologic and hemodynamic parameters in very-low-birth-weight infants. METHODS: The infants were randomized into 2 groups: group 1 (UCM) and group 2 (control). The primary outcome was the number of PRBC transfusions during the first 35 days of life. The secondary outcome measures were the hemodynamic variables during the first 24 hours of life. RESULTS: A total of 44 infants were included with 22 infants in each group. Two of 21 infants in group 1 and 4 of 21 infants in group 2 received transfusion in the first 3 days of life (P=0.384). The number and volume of PRBC transfusions were similar in both groups. However, the levels of hemoglobin (Hb) at the first and 24th hour of life were significantly higher in group 1. Phlebotomy volume was found as a statistically significant risk factor for the need for PRBC transfusion (P=0.005). CONCLUSIONS: UCM in delivery room results in a higher Hb level in the first day of life. In these groups of infants, phlebotomy losses may impact the transfusion need.

The role of tumor necrosis factor-alpha -308 G/A and transforming growth factor-beta 1 -915 G/C polymorphisms in childhood idiopathic thrombocytopenic purpura.

OBJECTIVE: To increase our understanding of the etiology of idiopathic thrombocytopenic purpura (ITP) some cytokine gene polymorphisms were analyzed for susceptibility to the disease. The aim of this study was to investigate the role of tumor necrosis factor-alpha (TNF-α) -308 G/A and transforming growth factor-beta 1 (TGF-ß1) -915 G/C polymorphisms in the development and clinical progression of childhood ITP. METHODS: In all, 50 pediatric patients with ITP (25 with acute ITP and 25 with chronic ITP) and 48 healthy controls were investigated via LightCycler® PCR analysis for TNF-α -308 G/A and TGF-ß1 -915 G/C polymorphisms. RESULTS: The frequency of TNF-α -308 G/A polymorphism was 20%, 16%, and 22.9% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05). The frequency of TGF-ß1 -915 G/C polymorphism was 16%, 8%, and 8.3% in the acute ITP patients, chronic ITP patients, and controls, respectively (p>0.05). The risk of developing ITP and clinical progression were not associated with TNF-α -308 G/A (OR: 0.738, 95% CI: 0.275-1.981, and OR: 0.762, 95% CI: 0.179-3.249) or TGF-ß1 -915 G/C (OR: 1.5, 95% CI: 0.396-5.685, and OR: 0.457, 95% CI: 0.076-2.755) polymorphisms. CONCLUSION: The frequency of TNF-α -308 G/A and TGF-ß1 -915 G/C polymorphisms did not differ between pediatric ITP patients and healthy controls, and these polymorphisms were not associated with susceptibility to the development and clinical progression of the disease.

Clinical characteristics of recessive and dominant congenital hyperinsulinism due to mutation(s) in the ABCC8/KCNJ11 genes encoding the ATP-sensitive potasium channel in the pancreatic beta cell.

BACKGROUND: Recessive mutations in ABCC8/KCNJ11 of beta-cell K(ATP) channel generally cause severe medically unresponsive hyperinsulinemic hypoglycemia (HH). Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. Rarer dominant mutations in these genes have been described that mostly cause milder, medically responsive congenital hyperinsulinism. To date the phenotype of patients with dominant mutations seems to be different from those with recessive mutations as the majority of patients are responsive to diazoxide therapy. Controversy exists on whether these dominant ABCC8 or KCNJ11 genes mutations predispose to diabetes mellitus in adulthood or not. SUBJECTS: We report the clinical and genetic characteristics of five patients with neonatal HH, three had recessively inherited K(ATP) channel mutations and two with a dominantly acting mutation. As a result of failure to medical therapy, patients with recessive K(ATP) channel mutations underwent a near total pancreatectomy. Two siblings with a novel dominant mutation showed good response to medical treatment. Although the HH remitted in early infancy, they became diabetic at the prepubertal age. Their mother, maternal aunt and maternal grandfather had the same mutation without any medical history of neonatal HH. CONCLUSION: The clinical presentation of our two patients with a dominant ABCC8 mutation was milder than that of patients with the resessive form of the disease as they responded well to medical management.