Investigating the Impact on Long-Term Outcomes and the Necessity of Hereditary Thrombophilia Screening in Presumed or Perinatal Arterial Ischemic Stroke.

This study aimed to investigate the influence of prothrombotic risk factors on long-term outcomes of patients with perinatal arterial ischemic stroke. The study was conducted through an analysis of monitoring results that were regularly maintained for approximately 20 years at a tertiary stroke-monitoring center. The study assessed prothrombotic risk factors, radiological area of involvement, clinical presentation, treatments, clinical outcomes, and long-term outcomes of the 48 patients included in the study, with a mean monitoring time of 77.6 ± 45.7 months (range: 6-204). Our results showed that the presence of prothrombotic risk factors did not affect long-term outcomes. However, patients with middle cerebral artery infarction had the highest risk of developing cerebral palsy, whereas those with presumed stroke had the highest risk of developing epilepsy. This study suggests that prothrombotic risk factors should not be evaluated during the acute stage unless there is a strong suspicion of the patient's history, and prevention or early diagnosis of presumed stroke patients will positively impact their long-term prognosis.

Effect of Antenatal Magnesium Sulfate Exposure on Patent Ductus Arteriosus in Premature Infants.

OBJECTIVE: Magnesium sulfate (MgSO4) provides effective fetal neuroprotection. However, there is conflicting evidence regarding the association between antenatal MgSO4 exposure and patent ductus arteriosus (PDA). Thus, herein, we aimed to evaluate the association between antenatal MgSO4 exposure and PDA. STUDY DESIGN: Preterm infants born between 240/7 and 316/7 weeks of gestation were included in this retrospective study. Infants who died within the first 72 hours of life and those with significant congenital anomalies were excluded from the study. Echocardiographic and clinical assessment parameters were used to define PDA and hemodynamically significant PDA (hsPDA). Treatments were planned according to the standard protocols of the unit. The following data were collected from hospital medical records: perinatal characteristics, neonatal outcomes, detailed PDA follow-up findings, and maternal characteristics including MgSO4 exposure and doses. RESULTS: Of the 300 included infants, 98 (32.6%) were exposed to antenatal MgSO4. hsPDA rates were similar in the infants exposed and not exposed to antenatal MgSO4, when adjusted for antenatal steroid administration, gestational age, and birth weight (OR: 1.6, 95% CI: 0.849-3.118, p = 0.146). The rates of PDA ligation and open PDA at discharge were similar between the groups. A cumulative MgSO4 dose of >20 g was associated with an increased risk of hsPDA (crude OR: 2.476, 95% CI: 0.893-6.864, p = 0.076; adjusted OR: 3.829, 95% CI: 1.068-13.728, p = 0.039). However, the cumulative dose had no effect on the rates of PDA ligation or open PDA at discharge. Rates of prematurity-related morbidities and mortality were similar between the groups. CONCLUSION: Although antenatal MgSO4 exposure may increase the incidence of hsPDA, it may not affect the rates of PDA ligation or open PDA at discharge. Further studies are required to better evaluate the dose-dependent outcomes and identify the MgSO4 dose that not only provides neuroprotection but also has the lowest risk of adverse effects. KEY POINTS: · Antenatal exposure of MgSO4 may cause PDA.. · Antenatal MgSO4 exposure may not increase the rates of PDA ligation or open PDA at discharge.. · Further studies are required to better evaluate the dose-dependent outcomes and optimal MgSO4 dose..

Evaluation of the "Neonatal Sequential Organ Failure Assessment" to Predict Mortality in Late-Onset Sepsis in Very Preterm Infants.

INTRODUCTION: We aimed to evaluate the use of "Neonatal Sequential Organ Failure Assessment" (nSOFA) scoring in predicting mortality, to compare the accuracy of nSOFA scores at different time points in very preterm infants with late-onset sepsis (LOS), and to investigate other possible parameters that would improve the prediction. METHODS: This single-center, retrospective study included preterm infants born atS<32 weeks' gestation with culture-proven LOS. The nSOFA scores of non-fatal and fatal episodes were compared at nine time points. RESULTS: Of 120 culture-proven LOS episodes in 106 infants, 90 (75%) episodes were non-fatal and 30 (25%) episodes were fatal. The mean birth weight (BW) of the infants who died was lower than that of survivors (p=0.038). In the fatal LOS episodes, median nSOFA scores were higher at all time points measured before sepsis evaluation, at the time of evaluation, and at all time points measured after the evaluation (p<0.001). nSOFA scores before death and at 48 hours were higher in the fatal episodes (p<0.001). At the time of sepsis assessment, nSOFA score>4 was associated with a 7- to 16-fold increased risk of mortality. Adjustment for BW, lymphocyte and monocyte counts increased the risk to 9- to 18-fold. CONCLUSION: This study demonstrated that the use of nSOFA to predict mortality and morbidity in extremely preterm infants seems feasible. The scoring system could be improved by evaluating the other parameters.

Complications of epicutaneo-caval catheters: Pericardial effusion and cardiac tamponade in three preterm infants.

In the neonatal intensive care units (NICU), epicutaneo-caval catheters (ECCs) are common alternative vascular routes. Pericardial effusion (PCE) and cardiac tamponade (CT) are rare but serious complications in infants with ECCs. It may be asymptomatic or present with a variety of significant clinical signs, including dyspnea, bradycardia, sudden asystole, and hypotension. If untreated, PCE can be fatal. This report presents, three cases of ECC-associated PCE/CT during NICU stay. All three patients were born before 30 weeks of gestation and weighed less than 1500 g. Echocardiography was used for diagnosis all patients. PCE/CT was detected incidentally in one patient and after hemodynamic deterioration in the other two. In one patient, CT was developed due to catheter malposition, and the other two patient, the catheter tip was found in the right atrium. PCE did not recur in any of the patients after pericardial fluid was drained and the catheters were removed. No PCE/CT-related deaths were observed. In all three patients, X-ray was used to evaluate the location of the catheter tips. However, after clinical deterioration, echocardiography showed that in the first two cases the tips were actually in the right atrium. Real-time ultrasound was suggested with strong evidence to evaluate the location of the catheter tip and to detect secondary malapposition. PCE/CT should be considered in the presence of unexplained and refractory respiratory distress, abnormal heart rate and blood pressure, and metabolic acidosis in a neonate with ECC. Early diagnosis and prompt pericardiocentesis are essential to reduce mortality and improve prognosis. Prospective studies with educational interventions should be designed to demonstrate that the use of point-of-care ultrasound (POCUS) can be easily acquired and may reduce complications.

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.

Acute Abdomen in an Extremely Low-Birth-Weight Preterm Neonate: A Case of Appendicitis.

INTRODUCTION: Neonatal appendicitis is a very rare surgical entity. Non-specific symptoms such as feeding intolerance, abdominal distension, vomiting, increased gastric residue, lethargy, and fever may be present. The majority of reported cases could not be identified early. In this report, we present an extremely low-birth-weight preterm neonate who has been diagnosed with appendicitis. CASE PRESENTATION: A 980-gram preterm baby girl was born at 31 1/7 weeks of gestation. The physical examination was normal at birth. Her initial clinical course was uneventful. On the 7th day of life, she developed abdominal distention and tenderness. She had an episode of bloody stools and bilious vomiting. An abdominal X-ray suggested localized perforation in the cecum with an air-fluid level in the right lower quadrant. The clinical findings suggested necrotizing enterocolitis and perforation, and a diagnostic laparotomy was performed. The bowel was found to be normal with a necrotic appendix. The appendectomy was performed. She was discharged from the neonatal intensive care unit with no complications. CONCLUSION: Appendicitis is extremely rare in the neonatal period. It is quite challenging to evaluate the presentation accurately, which causes a delay in diagnosis. However, if an atypical NEC or peritonitis is present, appendicitis should be considered. Early diagnosis and timely surgical intervention improve the prognosis of neonatal appendicitis.

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.

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.

Intravenous Immunoglobulin Use in Hemolytic Disease Due to ABO Incompatibility to Prevent Exchange Transfusion.

Introduction: Intravenous immunoglobulin (IVIG) has been widely used to treat the hemolytic disease of the newborn (HDN). Although it has been shown that IVIG treatment reduces the duration of phototherapy and hospitalization, the use of IVIG in hemolytic disease due to ABO incompatibility has been controversial in recent years. This study aimed to investigate the role of IVIG in the prevention of exchange transfusion in infants with ABO HDN who presented with bilirubin levels at or above the level of exchange transfusion. Materials and Methods: This study evaluated the data of infants with ABO HDN in the Turkish Neonatal Jaundice Online Registry. The infants with ABO HDN who met the total serum bilirubin level inclusion criteria (within 2-3 mg/dL of exchange transfusion or even above exchange transfusion level) were included in the study according to the guidelines from the American Academy of Pediatrics and the Turkish Neonatal Society. All patients were managed according to the unit protocols recommended by these guidelines and received light-emitting diode (LED) phototherapy. Infants who only received LED phototherapy, and who received one dose of IVIG with LED phototherapy were compared. Results: During the study period, 531 term infants were included in the study according to inclusion criteria. There were 408 cases in the phototherapy-only group, and 123 cases in the IVIG group. The demographic findings and the mean bilirubin and reticulocyte levels at admission were similar between the groups (p > 0.05), whereas the mean hemoglobin level was slightly lower in the IVIG group (p = 0.037). The mean age at admission was earlier, the need for exchange transfusion was higher, and the duration of phototherapy was longer in the IVIG group (p < 0.001, p = 0.001, and p < 0.001, respectively). The rate of re-hospitalization and acute bilirubin encephalopathy (ABE) was higher in the IVIG group (p < 0.001 and p = 0.01, respectively). Conclusion: In this study, we determined that one dose of IVIG did not prevent an exchange transfusion nor decrease the duration of phototherapy in infants, who had bilirubin levels near or at exchange transfusion level, with hemolytic disease due to ABO incompatibility.

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.

An Update on Patent Ductus Arteriosus and What is Coming Next.

Patent ductus arteriosus is the most common cardiovascular condition in preterm infants. There is a significant uncertainty about when and how to close ductus arteriosus in preterm infants due to a high spontaneous closure rate even in very immature preterm infants. Diagnosis and management of patent ductus arteriosus remain a challenge for both neonatologists and pediatric cardiologists. Researchers have tried to define a balance between an expectant approach and active treatment in selected infants. This review aimed to focus on the pathophysiology and management of patent ductus arteriosus and to make suggestions about approaches that might eliminate the association of morbidities with patent ductus arteriosus.

Inherited metabolic disorders in the neonatal intensive care unit: Red flags to look out for.

BACKGROUND: We aimed to assess symptoms, laboratory findings, and radiological abnormalities in patients diagnosed with inherited metabolic disorders (IMDs) in the neonatal intensive care unit. METHODS: A total of 6,150 newborns treated in a third-level neonatal intensive care unit between 2012 and 2020 in Turkey were screened, of which 195 consulted with a suspicion of metabolic disease based on their clinical, laboratory, or radiological findings were included in the present study. RESULTS: The prevalence of IMDs in the patients was 1:94.6. Those consulted in the department of pediatric metabolism were divided into two groups, with the 65 diagnosed with IMDs assigned as Group I, and the 130 patients who were not diagnosed with IMDs as Group II. The most common IMDs were organic acidemias (29.23%) and urea cycle disorders (UCDs) (26.15%). The rates of consanguinity marriage (75.3% vs 37.6%, P < 0.001), siblings diagnosed with an IMD (27.6% vs 3.8%, P < 0.001), and sibling death (56.9% vs 14.6%, P < 0.001) were higher in Group I than in Group II. Hyperammonemia (61.5% vs 18.4%, P < 0.001) was the most common laboratory finding in Group I, and anemia (Group I 60.0% vs 43.0% P = 0.033), metabolic acidosis (53.8% vs 36.9%, P = 0.028) and respiratory alkalosis (16.9% vs 1.5%, P < 0.001) were all higher in Group I. CONCLUSIONS: This retrospective study found that the results of clinical findings and basic laboratory tests could be strong indicators of IMDs, although extensive newborn screening tests and advanced biochemical and genetic tests should be carried out for the diagnosis of IMDs in newborns.

Exchange transfusion for neonatal hyperbilirubinemia: A multicenter, prospective study of Turkish Neonatal Society.

Objective: The frequency of neonatal exchange transfusion has declined in recent years, but is still performed in many countries. The procedure is associated with complications. The aim of the study was to determine the clinical features and etiologies of infants with hyperbilirubinemia who underwent exchange transfusion and evaluate the adverse events and clinical outcomes. Material and Methods: We performed a secondary analysis of the multicenter Turkish Neonatal Jaundice Online Registry data. Otherwise healthy newborns born ≥35 weeks of gestation who were hospitalized for jaundice and underwent exchange transfusion were included. Results: One-hundred thirty-two patients with a mean serum bilirubin level on admission of 24.9±9.1 mg/dL were enrolled in the study. The most common cause for exchange transfusion was hemolytic jaundice (63.6%), followed by lack of proper feeding (12.9%). It was found that the infants with lack of proper feeding were discharged earlier from the maternity ward (p=0.02), but they were admitted to hospital later (p<0.001) with a higher bilirubin level (p=0.001), and geater weight loss (p=0.04). The reported rate of adverse events associated with exchange transfusion was 11.4%. The most common complication was thrombocytopenia (40%). None of the infants died during the procedure. Acute bilirubin encephalopathy was reported in 13 (9.8%) patients. Conclusion: Severe hyperbilirubinemia requiring exchange transfusion and acute bilirubin encephalopathy are still challenging problems in neonatal periodin our country. The policies including blood group analysis of pregnant women, programs informing parents about breastfeeding and jaundice, and monitoring bilirubin levels of high-risk newborns should be developed to reduce the necessitating for exchange transfusion and to avoid related complications.

Current Controversy on Platelets and Patent Ductus Arteriosus Closure in Preterm Infants.

Platelets are critically involved in murine patent ductus arteriosus (PDA) closure. To date, the clinical significance of these findings in human preterm infants with PDA is still controversial. We discuss the available study data on the role of platelets for PDA closure in preterm infants: Several mostly retrospective studies have yielded conflicting results on whether thrombocytopenia contributes to failed spontaneous ductal closure. The same applies to investigations on the role of thrombocytopenia as a risk factor for unsuccessful ductus arteriosus closure by pharmacological treatment with cyclooxygenase inhibitors. Nonetheless, recent meta-analyses have concluded that thrombocytopenia constitutes an independent risk factor for both failed spontaneous and pharmacological PDA closure in preterm infants. However, the available investigations differ in regard to patient characteristics, diagnostic strategies, and treatment protocols. Several studies suggest that impaired platelet function rather than platelet number is critically involved in failure of ductus arteriosus closure in the preterm infant. A recent randomized-controlled trial on platelet transfusions in preterm infants with PDA failed to show any benefit for liberal vs. restrictive transfusion thresholds on PDA closure rates. Importantly, liberal transfusions were associated with an increased rate of intraventricular hemorrhage, and thus should be avoided. In conclusion, the available evidence suggests that thrombocytopenia and platelet dysfunction contribute to failure of spontaneous and pharmacological PDA closure in preterm infants. However, these platelet effects on PDA seem to be of only moderate clinical significance. Furthermore, platelet transfusions in thrombocytopenic preterm infants in order to facilitate PDA closure appear to cause more harm than good.