Neonatal Outcomes of Critical Congenital Heart Defects: A Multicenter Epidemiological Study of Turkish Neonatal Society : Neonatal Outcomes of CCHD.

Critical congenital heart disease (CCHD) is one of the leading causes of neonatal and infant mortality. We aimed to elucidate the epidemiology, spectrum, and outcome of neonatal CCHD in Türkiye. This was a multicenter epidemiological study of neonates with CCHD conducted from October 2021 to November 2022 at national tertiary health centers. Data from 488 neonatal CCHD patients from nine centers were entered into the Trials-Network online registry system during the study period. Transposition of great arteria was the most common neonatal CHD, accounting for 19.5% of all cases. Sixty-three (12.9%) patients had extra-cardiac congenital anomalies. A total of 325 patients underwent cardiac surgery. Aortic arch repair (29.5%), arterial switch (25.5%), and modified Blalock-Taussig shunt (13.2%). Overall, in-hospital mortality was 20.1% with postoperative mortality of 19.6%. Multivariate analysis showed that the need of prostaglandin E1 before intervention, higher VIS (> 17.5), the presence of major postoperative complications, and the need for early postoperative extracorporeal membrane oxygenation were the main risk factors for mortality. The mortality rate of CCHD in our country remains high, although it varies by health center. Further research needs to be conducted to determine long-term outcomes for this vulnerable population.

Two-Year Outcomes After Minimally Invasive Surfactant Therapy in Preterm Infants: Follow-Up of the OPTIMIST-A Randomized Clinical Trial.

Importance: The long-term effects of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome remain to be definitively clarified. Objective: To examine the effect of MIST on death or neurodevelopmental disability (NDD) at 2 years' corrected age. Design, Setting, and Participants: Follow-up study of a randomized clinical trial with blinding of clinicians and outcome assessors conducted in 33 tertiary-level neonatal intensive care units in 11 countries. The trial included 486 infants with a gestational age of 25 to 28 weeks supported with continuous positive airway pressure (CPAP). Collection of follow-up data at 2 years' corrected age was completed on December 9, 2022. Interventions: Infants assigned to MIST (n = 242) received exogenous surfactant (200 mg/kg poractant alfa) via a thin catheter; those assigned to the control group (n = 244) received sham treatment. Main Outcomes and Measures: The key secondary outcome of death or moderate to severe NDD was assessed at 2 years' corrected age. Other secondary outcomes included components of this composite outcome, as well as hospitalizations for respiratory illness and parent-reported wheezing or breathing difficulty in the first 2 years. Results: Among the 486 infants randomized, 453 had follow-up data available (median gestation, 27.3 weeks; 228 females [50.3%]); data on the key secondary outcome were available in 434 infants. Death or NDD occurred in 78 infants (36.3%) in the MIST group and 79 (36.1%) in the control group (risk difference, 0% [95% CI, -7.6% to 7.7%]; relative risk [RR], 1.0 [95% CI, 0.81-1.24]); components of this outcome did not differ significantly between groups. Secondary respiratory outcomes favored the MIST group. Hospitalization with respiratory illness occurred in 49 infants (25.1%) in the MIST group vs 78 (38.2%) in the control group (RR, 0.66 [95% CI, 0.54-0.81]) and parent-reported wheezing or breathing difficulty in 73 (40.6%) vs 104 (53.6%), respectively (RR, 0.76 [95% CI, 0.63-0.90]). Conclusions and Relevance: In this follow-up study of a randomized clinical trial of preterm infants with respiratory distress syndrome supported with CPAP, MIST compared with sham treatment did not reduce the incidence of death or NDD by 2 years of age. However, infants who received MIST had lower rates of adverse respiratory outcomes during their first 2 years of life. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

Factors Predicting Early Major Adverse Events in the Intensive Care Unit After Successful Cardiac Surgery for Congenital Heart Disease in Full-Term Neonates.

OBJECTIVE: In this study, we aimed to evaluate the factors affecting major adverse event (MAE) development after full-term neonatal cardiac surgery. METHODS: This study was conducted retrospectively on newborns who underwent congenital heart surgery between June 1, 2020, and June 1, 2022. MAE was defined as the presence of at least one of the following: cardiac arrest, unplanned reoperation, emergency chest opening, admission to the advanced life support system, and death. The role of blood lactate level, vasoactive inotropic score (VIS), and cerebral near-infrared spectroscopy (NIRS) changes in predicting MAE was investigated. RESULTS: A total of 240 patients (50% male) were operated during the study period. The median age of patients was seven days (interquartile range 3-10 days). MAE was detected in 19.5% of the cases. Peak blood lactate levels >7 mmol/liter (area under the curve [AUC] 0.72, 95% confidence interval [CI] [0.62-0.82], P<0.001, sensitivity 76%, specificity 82%, positive predictive value [PPV] 88%) was an independent risk factor for MAE (odds ratio [OR] 2.7 [95% CI 1.3-6]). More than 30% change in NIRS value during the operative period (AUC 0.84, 95% CI [0.80-0.88], P<0.001, sensitivity 65%, specificity 85%, PPV 90%) was a strong predictor of MAE. VIS > 10 was an independent risk factor (AUC 0.75, 95% CI [0.70-0.84], P<0.001, sensitivity 86%, specificity 80%, PPV 84%) and strongly predicted MAE (OR 1.4 [95% CI 0.9-5]). CONCLUSION: Cerebral NIRS changes > 30%, high blood lactate levels, and VIS score within the 48 hours may help to predict the development of MAE in the postoperative period.

Evaluation of perfusion index and left ventricular output changes in low cardiac output syndrome after arterial switch operation.

INTRODUCTION: Transposition of great arteries is one of newborns' most common cyanotic CHDs, and its treatment is arterial switch operation in the first days of life. Low cardiac output syndrome may develop in the early postoperative period. In this study, we evaluated perfusion index and left ventricular output blood flow changes in patients who underwent arterial switch operation and developed low cardiac output syndrome. METHODS: This study was conducted prospectively in newborns with transposition of great arteries who underwent arterial switch operation between 1st August 2020 and 1st August 2022. Low cardiac output syndrome score and left ventricular output were investigated. Initially, 6th, 12th, 18th, and 24th hour perfusion index and left ventricular output values of patients with and without low cardiac output syndrome were recorded. The results were evaluated statistically. RESULTS: A total of 60 patients were included in the study. Sex distribution was equal. The median age at the time of surgery was 5 days (interquartile range 3-7 days), and the median weight was 3.1 kg (interquartile range 2.9-3. 4). Low cardiac output syndrome was detected in 30% (n = 18) of cases. The median perfusion index of patients who developed low cardiac output syndrome was significantly lower at the 12th, 18th, and 24th hours (p < 0.05) (0.99 versus 1.25, 0.86 versus 1.21, and 0.96 versus 1.33, respectively). Similarly, the median left ventricular output of patients who developed low cardiac output syndrome was significantly lower at 12th, 18th, and 24th hours (p < 0.05) (95 versus 110 ml/kg/min, 89 versus 109 ml/kg/min, and 92 versus 112 ml/kg/min, respectively). There was a significant correlation between perfusion index values and left ventricular output at all measurements (r > 0.500, p < 0.05). CONCLUSION: Perfusion index and left ventricular output measurements decreased in newborns who developed low cardiac output syndrome after arterial switch operation, especially at 12th and 18th hours. Serial perfusion index and left ventricular output measurements can be instructive in predicting low cardiac output syndrome development.

Neonatal Outcomes of Premature Infants Born to Women with the Novel Coronavirus (SARS-CoV-2) Infection: A Case Control Study.

OBJECTIVE: Novel coronavirus disease 2019 (COVID-19) is a disease associated with atypical pneumonia caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The first cases of COVID-19 were reported in Wuhan at the end of 2019. Transmission usually occurs via infected droplets and close personal contact; the possibility of vertical transmission is still under debate. This retrospective study aimed to analyze clinical characteristics of premature infants born to mothers with symptomatic COVID-19 disease. STUDY DESIGN: This case control study compared the clinical and laboratory data of 20 premature infants born to mothers infected with SARS-CoV-2 with sex and gestational age-matched historical controls. RESULTS: The median gestational age and birth weight in both groups were similar. Respiratory distress developed in 11 (55.5%) infants in study group and 19 (47.5%) infants in control group. Mechanical ventilation and endotracheal surfactant administration rates were similar. Median duration of hospitalization was 8.5 (2-76) days in study group and 12 days in historical controls. Real-time reverse-transcription polymerase chain reaction tests (RT-PCR) of nasopharyngeal swab samples for SARS-CoV-2 were found to be negative twice, in the first 24 hours and later at 24 to 48 hours of life. No neutropenia or thrombocytopenia was detected in the study group. Patent ductus arteriosus, bronchopulmonary dysplasia, and necrotizing enterocolitis rates were similar between groups. No mortality was observed in both groups. CONCLUSION: To the best of our knowledge, this is one of the few studies evaluating the clinical outcomes of premature infants born to SARS-CoV-2 infected mothers. There was no evidence of vertical transmission of SARS-CoV-2 from symptomatic SARS-CoV-2-infected women to the neonate in our cohort. The neonatal outcomes also seem to be favorable with no mortality in preterm infants. KEY POINTS: · SARS-CoV-2 pandemic is a challenge for pregnant women.. · Neonatal outcomes of premature infants born to mothers infected with SARS-CoV-2 not well defined.. · SARS-CoV-2 infection seems to have no adverse effect on mortality and morbidity in premature infants..

Effects of Different Onset Times of Early Caffeine Treatment on Mesenteric Tissue Oxygenation and Necrotizing Enterocolitis: A Prospective, Randomized Study.

OBJECTIVE: Caffeine treatment is routinely used in premature infants to prevent development of apnea and bronchopulmonary dysplasia. Although a limited number of studies have reported that early caffeine treatment may cause development of necrotizing enterocolitis (NEC) by reducing mesenteric blood flow, this issue is still under discussion. The aim of this study is to investigate the possible effect of different onset times of early caffeine treatment on mesenteric tissue oxygen saturation and NEC development in premature infants. STUDY DESIGN: A total of 87 preterm infants with ≤1,250-g birth weight (BW) was included in this prospective study. The cases were randomized as group 1 (first 24 hours) and group 2 (72nd hour) caffeine treatment groups and monitored by near-infrared spectroscopy (NIRS) for 72 hours from the time of admission until cerebral, renal, and mesenteric tissue oxygen saturations (rSO2) were recorded. The cases were followed-up to the 40th week in terms of NEC and other neonatal morbidities. RESULTS: A total of 87 infants were included in the study, including 45 in group 1 and 42 in group 2. The groups were similar in terms of demographic characteristics. The incidence of NEC in group 1 (20%) was higher in comparison to group 2 (9%). The mesenteric rSO2 values in the first 72 hours of group 1 were lower than those of group 2. Low gestational week, BW, and late onset of enteral feeding were found to be other significant risk factors for NEC. CONCLUSION: In this study, mesenteric tissue oxygenation was lower, and NEC was higher in group 1. Mesenteric rSO2 measurements may be useful in predicting the development of NEC in patients receiving early caffeine therapy. KEY POINTS: · Onset time of early caffeine treatment may effect on mesenteric tissue oxygen saturation.. · Caffeine treatment that onset in the first 24 hours may be associated with NEC development.. · Mesenteric rSO2 measurements may be useful in patients receiving early caffeine therapy..

Preventive effects of antenatal CDP-choline in a rat model of neonatal hyperoxia-induced lung injury.

Antenatal steroid administration to pregnant women at risk of prematurity provides pulmonary maturation in infants, while it has limited effects on incidence of bronchopulmonary dysplasia (BPD), the clinical expression of hyperoxia-induced lung injury (HILI). Cytidine-5'-diphosphate choline (CDP-choline) was shown to alleviate HILI when administered to newborn rats. Therefore, we investigated effects of maternal administration of CDP-choline, alone or in combination with betamethasone, on lung maturation in neonatal rats subjected to HILI immediately after birth. Pregnant rats were randomly assigned to one of the four treatments: saline (1 mL/kg), CDP-choline (300 mg/kg), betamethasone (0.4 mg/kg), or CDP-choline plus betamethasone (combination therapy). From postnatal day 1 to 11, pups born to mothers in the same treatment group were pooled and randomly assigned to either normoxia or hyperoxia group. Biochemical an d histopathological effects of CDP-choline on neonatal lung tissue were evaluated. Antenatal CDP-choline treatment increased levels of phosphatidylcholine and total lung phospholipids, decreased apoptosis, and improved alveolarization. The outcomes were further improved with combination therapy compared to the administration of CDP-choline or betamethasone alone. These results demonstrate that antenatal CDP-choline treatment provides benefit in experimental HILI either alone or more intensively when administered along with a steroid, suggesting a possible utility for CDP-choline against BPD.

Factors Predicting Early Major Adverse Events in the Intensive Care Unit After Successful Cardiac Surgery for Congenital Heart Disease in Full-Term Neonates

ABSTRACT Objective: In this study, we aimed to evaluate the factors affecting major adverse event (MAE) development after full-term neonatal cardiac surgery. Methods: This study was conducted retrospectively on newborns who underwent congenital heart surgery between June 1, 2020, and June 1, 2022. MAE was defined as the presence of at least one of the following: cardiac arrest, unplanned reoperation, emergency chest opening, admission to the advanced life support system, and death. The role of blood lactate level, vasoactive inotropic score (VIS), and cerebral near-infrared spectroscopy (NIRS) changes in predicting MAE was investigated. Results: A total of 240 patients (50% male) were operated during the study period. The median age of patients was seven days (interquartile range 3-10 days). MAE was detected in 19.5% of the cases. Peak blood lactate levels >7 mmol/liter (area under the curve [AUC] 0.72, 95% confidence interval [CI] [0.62-0.82], P<0.001, sensitivity 76%, specificity 82%, positive predictive value [PPV] 88%) was an independent risk factor for MAE (odds ratio [OR] 2.7 [95% CI 1.3-6]). More than 30% change in NIRS value during the operative period (AUC 0.84, 95% CI [0.80-0.88], P<0.001, sensitivity 65%, specificity 85%, PPV 90%) was a strong predictor of MAE. VIS > 10 was an independent risk factor (AUC 0.75, 95% CI [0.70-0.84], P<0.001, sensitivity 86%, specificity 80%, PPV 84%) and strongly predicted MAE (OR 1.4 [95% CI 0.9-5]). Conclusion: Cerebral NIRS changes > 30%, high blood lactate levels, and VIS score within the 48 hours may help to predict the development of MAE in the postoperative period.

Can we predict risk for cardiac involvement in paediatric inflammatory multi-system syndrome?

INTRODUCTION: Increasing recognition of paediatric inflammatory multi-system syndrome is a cause of concern. This study aimed to evaluate children with paediatric inflammatory multi-system syndrome and compare the clinical and laboratory features of children with and without cardiac involvement. MATERIAL AND METHODS: We conducted a prospective single-centre study including 57 (male 37, 65%) patients with paediatric inflammatory multi-system syndrome at a tertiary care hospital between November, 2020 and March, 2021. The mean age was 8.8 ± 4.5 years (range, 10 months-16.7 years). RESULTS: The most frequent symptoms were fever (100%), abdominal pain (65%) and diarrhoea (42%). SARS-CoV-2 PCR and serology tests were positive in 3 (5%) and 52 (91%) patients, respectively. Eight patients required intensive care support. Nineteen patients (33%) had cardiac involvement (valvular regurgitation in 15, left ventricular systolic dysfunction in 11 and coronary artery dilation in 1). The presence and duration of cough and intensive care admissions were significantly higher in children with cardiac involvement than those without it. The cut-off values of troponin T, pro-brain natriuretic peptide and interleukin 6 for predicting cardiac involvement were 11.65 ng/L (95% confidence interval, 0.63-0.90; sensitivity, 0.63; specificity, 0.84; area under the curve: 0.775, p = 0.009), 849.5 pg/mL (95% CI, 0.54-0.86; sensitivity, 0.63; specificity, 0.63; area under the curve: 0.706, p = 0.009) and 39.8 pg/mL (95% CI, 0.54-0.85; sensitivity, 0.63; specificity, 0.60; area under the curve: 0.698, p = 0.023), respectively. CONCLUSIONS: Cardiac involvement in children with paediatric inflammatory multi-system syndrome is common. The risk of cardiac involvement can be predicted by troponin T, pro-brain natriuretic peptide and interleukin 6 levels.

Bronchopulmonary dysplasia and wnt pathway-associated single nucleotide polymorphisms.

AIM: Genetic variants contribute to the pathogenesis of bronchopulmonary dysplasia (BPD). The aim of this study is to evaluate the association of 45 SNPs with BPD susceptibility in a Turkish premature infant cohort. METHODS: Infants with gestational age <32 weeks were included. Patients were divided into BPD or no-BPD groups according to oxygen need at 28 days of life, and stratified according to the severity of BPD. We genotyped 45 SNPs, previously identified as BPD risk factors, in 192 infants. RESULTS: A total of eight SNPs were associated with BPD risk at allele level, two of which (rs4883955 on KLF12 and rs9953270 on CHST9) were also associated at the genotype level. Functional relationship maps suggested an interaction between five of these genes, converging on WNT5A, a member of the WNT pathway known to be implicated in BPD pathogenesis. Dysfunctional CHST9 and KLF12 variants may contribute to BPD pathogenesis through an interaction with WNT5A. CONCLUSIONS: We suggest investigating the role of SNPs on different genes which are in relation with the Wnt pathway in BPD pathogenesis. We identified eight SNPs as risk factors for BPD in this study. In-silico functional maps show an interaction of the genes harboring these SNPs with the WNT pathway, supporting its role in BPD pathogenesis. TRIAL REGISTRATION: NCT03467828. IMPACT: It is known that genetic factors may contribute to the development of BPD in preterm infants. Further studies are required to identify specific genes that play a role in the BPD pathway to evaluate them as a target for therapeutic interventions. Our study shows an association of BPD predisposition with certain polymorphisms on MBL2, NFKBIA, CEP170, MAGI2, and VEGFA genes at allele level and polymorphisms on CHST9 and KLF12 genes at both allele and genotype level. In-silico functional mapping shows a functional relationship of these five genes with WNT5A, suggesting that Wnt pathway disruption may play a role in BPD pathogenesis.

Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial.

Importance: The benefits of surfactant administration via a thin catheter (minimally invasive surfactant therapy [MIST]) in preterm infants with respiratory distress syndrome are uncertain. Objective: To examine the effect of selective application of MIST at a low fraction of inspired oxygen threshold on survival without bronchopulmonary dysplasia (BPD). Design, Setting, and Participants: Randomized clinical trial including 485 preterm infants with a gestational age of 25 to 28 weeks who were supported with continuous positive airway pressure (CPAP) and required a fraction of inspired oxygen of 0.30 or greater within 6 hours of birth. The trial was conducted at 33 tertiary-level neonatal intensive care units around the world, with blinding of the clinicians and outcome assessors. Enrollment took place between December 16, 2011, and March 26, 2020; follow-up was completed on December 2, 2020. Interventions: Infants were randomized to the MIST group (n = 241) and received exogenous surfactant (200 mg/kg of poractant alfa) via a thin catheter or to the control group (n = 244) and received a sham (control) treatment; CPAP was continued thereafter in both groups unless specified intubation criteria were met. Main Outcomes and Measures: The primary outcome was the composite of death or physiological BPD assessed at 36 weeks' postmenstrual age. The components of the primary outcome (death prior to 36 weeks' postmenstrual age and BPD at 36 weeks' postmenstrual age) also were considered separately. Results: Among the 485 infants randomized (median gestational age, 27.3 weeks; 241 [49.7%] female), all completed follow-up. Death or BPD occurred in 105 infants (43.6%) in the MIST group and 121 (49.6%) in the control group (risk difference [RD], -6.3% [95% CI, -14.2% to 1.6%]; relative risk [RR], 0.87 [95% CI, 0.74 to 1.03]; P = .10). Incidence of death before 36 weeks' postmenstrual age did not differ significantly between groups (24 [10.0%] in MIST vs 19 [7.8%] in control; RD, 2.1% [95% CI, -3.6% to 7.8%]; RR, 1.27 [95% CI, 0.63 to 2.57]; P = .51), but incidence of BPD in survivors to 36 weeks' postmenstrual age was lower in the MIST group (81/217 [37.3%] vs 102/225 [45.3%] in the control group; RD, -7.8% [95% CI, -14.9% to -0.7%]; RR, 0.83 [95% CI, 0.70 to 0.98]; P = .03). Serious adverse events occurred in 10.3% of infants in the MIST group and 11.1% in the control group. Conclusions and Relevance: Among preterm infants with respiratory distress syndrome supported with CPAP, minimally invasive surfactant therapy compared with sham (control) treatment did not significantly reduce the incidence of the composite outcome of death or bronchopulmonary dysplasia at 36 weeks' postmenstrual age. However, given the statistical uncertainty reflected in the 95% CI, a clinically important effect cannot be excluded. Trial Registration: anzctr.org.au Identifier: ACTRN12611000916943.

The possible effect of pentoxifylline on development and severity of retinopathy of prematurity.

BACKGROUND AND AIM: Retinopathy of prematurity (ROP) is the major ocular problem of preterm infants that occurs with abnormal proliferation of immature retinal vessels. Although pentoxifylline (PTX) was reported to inhibit vasculogenesis and neovascularization in experimental studies, there is no clinical data about the effects of PTX treatment on the development and severity of ROP. This clinical study aimed to investigate the possible effects of PTX on the development of ROP. MATERIALS AND METHODS: A single-centre retrospective study was conducted including preterm infants who were hospitalised in the neonatal intensive care unit between 2015-2017 years. Infants were divided into two groups in terms of PTX administration for adjuvant therapy, as PTX and non-PTX groups. RESULTS: A total of 211 infants were included in the study [gestational age 29 (27-31) weeks, birth weight 1140 (960-1340) g]. From these, 97 infants (46%) were given PTX treatment. The two groups were similar in terms of demographic data and baseline clinical characteristics. Any stage of ROP was detected in 47.4% of infants in the PTX group, which was significantly higher than those in the non-PTX group (27.2%) (p = 0.002). The incidence of advanced-stage ROP in the PTX group (10.3%) was also higher than in the non-PTX group (2.6%) (p = 0.021). Repeated usage of PTX was not found to be related to the development of ROP (p = 0.059). The time of PTX administration was similar between the ROP and no-ROP groups (median; one vs one week, p = 0.825). Surfactant therapy, duration of hospital stay, and PTX treatment were found as significant risk factors for ROP in the logistic regression analysis. CONCLUSIONS: In contrast to the experimental studies and also promising results of PTX treatment in some neonatal morbidities, it may be associated with increased incidence and stage of ROP.

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.

Neonatal gastric perforations in very low birth weight infants: a single center experience and review of the literature.

PURPOSE: Gastric perforation is a rare condition with high mortality rates in preterm infants. The aim of this retrospective study was to define the risk factors and prognosis in very low birth weight (VLBW) infants with gastric perforations. METHODS: VLBW infants with a diagnosis of gastric perforation between 2012 and 2016 were included. The data including birth weight, gestational age, gender, risk factors, time and location of the perforation and prognosis were recorded. RESULTS: A total of eight infants were identified. The median gestational age and birth weight of the infants were 26 weeks and 860 g, respectively. Five were male and 6 (75%) had a diagnosis of hemodynamically significant patent ductus arteriosus (PDA), early sepsis, persistent hypotension, and drug administration (paracetamol, ibuprofen). The main clinical finding was abdominal distension and pneumoperitoneum was detected in all infants. The median diagnosis was 6 days of life. The median perforation size was 2.5 cm and curvature major and anterior wall were the most common locations. The mortality rate was 62.5%. CONCLUSION: Male gender, chorioamnionitis, early sepsis, asphyxia, hemodynamic PDA, persistent hypotension, ibuprofen and paracetamol usage, and orogastric catheter administration were the main risk factors for gastric perforations in VLBW infants.

Regression of Cardiac Rhabdomyomas in a Neonate after Everolimus Treatment.

Cardiac rhabdomyoma often shows spontaneous regression and usually requires only close follow-up. However, patients with symptomatic inoperable rhabdomyomas may be candidates for everolimus treatment. Our patient had multiple inoperable cardiac rhabdomyomas causing serious left ventricle outflow-tract obstruction that showed a dramatic reduction in the size after everolimus therapy, a mammalian target of rapamycin (mTOR) inhibitor. After discontinuation of therapy, an increase in the diameter of masses occurred and everolimus was restarted. After 6 months of treatment, rhabdomyomas decreased in size and therapy was stopped. In conclusion, everolimus could be a possible novel therapy for neonates with clinically significant rhabdomyomas.

Evaluation of Etanercept Treatment in Newborn Rat Model with Hyperoxic Lung Injury.

BACKGROUND: Many factors contribute to the development of BPD basically by increasing inflammation in preterm lungs. However, premature neonates have insufficient anti-inflammatory capacity. We aimed to evaluate the effect of etanercept, an anti-TNF agent, on BPD development in newborn rat model with hyperoxia-induced lung injury. METHODS: Thirty-two newborn rats were divided into 3 groups as control group (Group 1, n = 11), hyperoxia + placebo group (Group 2, n = 10), and hyperoxia + etanercept group (Group 3, n = 11). Histopathological and biochemical analysis were performed in order to assess inflammation and oxidative stress. Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, and malondialdehyde (MDA) levels were studied, histopathological scoring and radial alveolar count were applied in lung tissue. Lamellar body membrane protein, vascular endothelial growth factor (VEGF), nuclear factor-kappaB (NF-κB) gene expressions were studied in immunohistochemical evaluation of tissue samples. All three groups were compared with each other in terms of all parameters. RESULTS: SOD and GSH-Px activities were significantly higher, whereas MDA levels were lower in group 3, compared to group 2 (p < 0.001). Histopathological scores were lower, lamellar body membrane protein expression and radial alveolar count were higher in group 3 (p < 0.05). NF-κB expression was higher in group 2, but lower in group 3 in comparison with group 1. Expression of VEGF was decreased in group 2 but came close to group 1 with etanercept treatment in group 3. CONCLUSIONS: We found etanercept treatment to be protective in newborn rats with hyperoxia-induced lung damage.

Endocan and Soluble Triggering Receptor Expressed on Myeloid Cells-1 as Novel Markers for Neonatal Sepsis.

BACKGROUND: Neonatal sepsis is an important cause of neonatal morbidity and mortality in the neonatal intensive care unit. Soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) has been evaluated in sepsis and septic shock, and it was found to be valuable in distinguishing septic cases from nonseptic cases. Endocan is constitutively expressed by endothelial cells, and high levels of endocan may be of relevance for the promotion of systemic inflammation. The aim of this study was to investigate whether the levels of sTREM-1 and endocan were increased in late-onset neonatal sepsis. METHODS: Patients were classified into septic and nonseptic groups. Blood was collected from a peripheral vein of all septic newborns and healthy newborns at the time of initial laboratory evaluation before any treatment, and within 48-72 hours after initiation of treatment. Serum sTREM-1 and endocan measurements were performed when the study was finished. RESULTS: The study population comprised of 50 neonates: 20 nonseptic neonates and 30 septic neonates. The groups were similar with regards to baseline characteristics. The initial measurements of interleukin-6 (IL-6), sTREM-1, endocan, and immature/total neutrophil ratio (I/T ratio) were significantly higher in septic neonates in comparison with nonseptic neonates. Receiver operating characteristic (ROC) curve analyses revealed that IL-6, sTREM-1, endocan, and I/T ratio resulted in significant areas under the curve (AUC) with respect to early identification of septic neonates. Soluble TREM-1 and IL-6 performed best to distinguish septic neonates from nonseptic neonates. Univariate logistic regression analysis showed that increased IL-6 and sTREM-1 were strong predictors of neonatal late-onset sepsis. CONCLUSION: Serum sTREM-1, IL-6, endocan levels, and I/T ratio increased in septic neonates. However, the diagnostic accuracy of circulating sTREM-1 seemed to be better than endocan and I/T ratio, but lower than IL-6.

Protective Effects of Valproic Acid, a Histone Deacetylase Inhibitor, against Hyperoxic Lung Injury in a Neonatal Rat Model.

OBJECTIVE: Histone acetylation and deacetylation may play a role in the pathogenesis of inflammatory lung diseases. We evaluated the preventive effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, on neonatal hyperoxic lung injury. METHODS: Forty newborn rat pups were randomized in normoxia, normoxia+VPA, hyperoxia and hyperoxia+VPA groups. Pups in the normoxia and normoxia+VPA groups were kept in room air and received daily saline and VPA (30 mg/kg) injections, respectively, while those in hyperoxia and hyperoxia+VPA groups were exposed to 95% O2 and received daily saline and VPA (30 mg/kg) injections for 10 days, respectively. Growth, histopathological, biochemical and molecular biological indicators of lung injury, apoptosis, inflammation, fibrosis and histone acetylation were evaluated. RESULTS: VPA treatment during hyperoxia significantly improved weight gain, histopathologic grade, radial alveolar count and lamellar body membrane protein expression, while it decreased number of TUNEL(+) cells and active Caspase-3 expression. Expressions of TGFß3 and phospho-SMAD2 proteins and levels of tissue proinflammatory cytokines as well as lipid peroxidation biomarkers were reduced, while anti-oxidative enzyme activities were enhanced by VPA treatment. VPA administration also reduced HDAC activity while increasing acetylated H3 and H4 protein expressions. CONCLUSIONS: The present study shows for the first time that VPA treatment ameliorates lung damage in a neonatal rat model of hyperoxic lung injury. The preventive effect of VPA involves HDAC inhibition.

Congenital cytomegalovirus infections and glycoprotein B genotypes in live-born infants: a prevalence study in Turkey.

BACKGROUND: Cytomegalovirus (CMV) infections are the leading cause of infectious hearing loss and central nervous system disease among children worldwide. In this study, we aimed to determine the birth prevalence of congenital CMV infection in live-born infants in Turkey. METHODS: In total, 944 consecutive live-born infants born from 926 pregnant women were included in this study. CMV-DNA was investigated in saliva samples of all newborns within the first 3 days after birth using TaqMan-based real-time PCR. RESULTS: The birth prevalence of congenital CMV infection in live-born infants was 1.91% (18/944), and all congenitally infected infants were asymptomatic at birth. The prevalence of congenital CMV infection was 16.7% (3/18) in twin pregnancies and 1.32% (12/908) in single pregnancies (p = 0.002). Genotyping analysis showed glycoprotein B-1 (gB1) to be the most frequently detected genotype at 83.3%. CONCLUSION: The study results suggest that the majority of congenital CMV infection in Turkey occurs following nonprimary maternal infection. We believe that congenital CMV infection and its long-term effects have been underestimated in our country, as infected infants are usually asymptomatic at birth.