The effects of cerebral oximetry in mechanically ventilated newborns: a protocol for the SafeBoosC-IIIv randomised clinical trial.

BACKGROUND: The SafeBoosC project aims to test the clinical value of non-invasive cerebral oximetry by near-infrared spectroscopy in newborn infants. The purpose is to establish whether cerebral oximetry can be used to save newborn infants' lives and brains or not. Newborns contribute heavily to total childhood mortality and neonatal brain damage is the cause of a large part of handicaps such as cerebral palsy. The objective of the SafeBoosC-IIIv trial is to evaluate the benefits and harms of cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. METHODS/DESIGN: SafeBoosC-IIIv is an investigator-initiated, multinational, randomised, pragmatic phase-III clinical trial. The inclusion criteria will be newborns with a gestational age more than 28 + 0 weeks, postnatal age less than 28 days, predicted to require mechanical ventilation for at least 24 h, and prior informed consent from the parents or deferred consent or absence of opt-out. The exclusion criteria will be no available cerebral oximeter, suspicion of or confirmed brain injury or disorder, or congenital heart disease likely to require surgery. A total of 3000 participants will be randomised in 60 neonatal intensive care units from 16 countries, in a 1:1 allocation ratio to cerebral oximetry versus usual care. Participants in the cerebral oximetry group will undergo cerebral oximetry monitoring during mechanical ventilation in the neonatal intensive care unit for as long as deemed useful by the treating physician or until 28 days of life. The participants in the cerebral oximetry group will be treated according to the SafeBoosC treatment guideline. Participants in the usual care group will not receive cerebral oximetry and will receive usual care. We use two co-primary outcomes: (1) a composite of death from any cause or moderate to severe neurodevelopmental disability at 2 years of corrected age and (2) the non-verbal cognitive score of the Parent Report of Children's Abilities-Revised (PARCA-R) at 2 years of corrected age. DISCUSSION: There is need for a randomised clinical trial to evaluate cerebral oximetry added to usual care versus usual care in mechanically ventilated newborns. TRIAL REGISTRATION: The protocol is registered at www. CLINICALTRIALS: gov (NCT05907317; registered 18 June 2023).

Multidisciplinary management of a large microcystic congenital pulmonary airway malformation: case report and literature review.

INTRODUCTION: Congenital pulmonary airway malformations (CPAMs) are rare sporadic lesions frequently associated with poor fetal prognosis. Type 3 CPAMs are characterized by small hyperechogenic cysts (<5 mm). Hydrops often develops secondarily, and the fetal survival rate is approximately 5% in this setting. CASE PRESENTATION: We present a case of a large type 3 CPAM complicated by fetal hydrops. The lesion was detected at 19 gestational weeks (GW) and confirmed by fetal MRI at 29 GW. At 22 GW, a course of maternal steroids was given as a possible treatment of type 3 CPAM. Peritoneal-amniotic shunt was placed twice to reduce fetal ascites, with unsatisfactory results. Similarly, polyhydramnios was relieved by two amnioreductions, but redeveloped soon after. A baby girl was delivered spontaneously at 33 GW and received a two-stage partial lobectomy in the first three months of life. Desaturations necessitated challenging invasive oscillatory ventilation between stages. Her outcome is unexpectedly positive and she may expect a good quality of life. She now approaches one year of age, with near-to-normal growth and developmental milestones. DISCUSSION: Type 3 CPAMs complicated by fetal hydrops are associated with high perinatal mortality. While open fetal surgery remains a viable option in select specialist centers, antenatal interventions are typically ineffective. The survival of this infant can be attributed to prenatal management and early postnatal surgical intervention. The lack of guidelines for ventilation in this setting was a significant challenge for neonatal intensivists. Multidisciplinary vigilance and collaboration with frequent specialist follow ups were the key to success for both mother and child.

Cerebral Oximetry Monitoring in Extremely Preterm Infants.

BACKGROUND: The use of cerebral oximetry monitoring in the care of extremely preterm infants is increasing. However, evidence that its use improves clinical outcomes is lacking. METHODS: In this randomized, phase 3 trial conducted at 70 sites in 17 countries, we assigned extremely preterm infants (gestational age, <28 weeks), within 6 hours after birth, to receive treatment guided by cerebral oximetry monitoring for the first 72 hours after birth or to receive usual care. The primary outcome was a composite of death or severe brain injury on cerebral ultrasonography at 36 weeks' postmenstrual age. Serious adverse events that were assessed were death, severe brain injury, bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, and late-onset sepsis. RESULTS: A total of 1601 infants underwent randomization and 1579 (98.6%) were evaluated for the primary outcome. At 36 weeks' postmenstrual age, death or severe brain injury had occurred in 272 of 772 infants (35.2%) in the cerebral oximetry group, as compared with 274 of 807 infants (34.0%) in the usual-care group (relative risk with cerebral oximetry, 1.03; 95% confidence interval, 0.90 to 1.18; P = 0.64). The incidence of serious adverse events did not differ between the two groups. CONCLUSIONS: In extremely preterm infants, treatment guided by cerebral oximetry monitoring for the first 72 hours after birth was not associated with a lower incidence of death or severe brain injury at 36 weeks' postmenstrual age than usual care. (Funded by the Elsass Foundation and others; SafeBoosC-III ClinicalTrials.gov number, NCT03770741.).

Prenatal Detection of a FOXF1 Deletion in a Fetus with ACDMPV and Hydronephrosis.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by the arrest of fetal lung formation, resulting in neonatal death due to acute respiratory failure and pulmonary arterial hypertension. Heterozygous single-nucleotide variants or copy-number variant (CNV) deletions involving the FOXF1 gene and/or its lung-specific enhancer are found in the vast majority of ACDMPV patients. ACDMPV is often accompanied by extrapulmonary malformations, including the gastrointestinal, cardiac, or genitourinary systems. Thus far, most of the described ACDMPV patients have been diagnosed post mortem, based on histologic evaluation of the lung tissue and/or genetic testing. Here, we report a case of a prenatally detected de novo CNV deletion (~0.74 Mb) involving the FOXF1 gene in a fetus with ACDMPV and hydronephrosis. Since ACDMPV is challenging to detect by ultrasound examination, the more widespread implementation of prenatal genetic testing can facilitate early diagnosis, improve appropriate genetic counselling, and further management.

Cerebral regional tissue Oxygen Saturation to Guide Oxygen Delivery in preterm neonates during immediate transition after birth (COSGOD III): multicentre randomised phase 3 clinical trial.

OBJECTIVE: To investigate whether monitoring of cerebral tissue oxygen saturation using near infrared spectroscopy in addition to routine monitoring combined with defined treatment guidelines during immediate transition and resuscitation increases survival without cerebral injury of premature infants compared with standard care alone. DESIGN: Multicentre, multinational, randomised controlled phase 3 trial. SETTING: 11 tertiary neonatal intensive care units in six countries in Europe and in Canada. PARTICIPANTS: 1121 pregnant women (<32 weeks' gestation) were screened prenatally. The primary outcome was analysed in 607 of 655 randomised preterm neonates: 304 neonates in the near infrared spectroscopy group and 303 in the control group. INTERVENTION: Preterm neonates were randomly assigned to either standard care (control group) or standard care plus monitoring of cerebral oxygen saturation with a dedicated treatment guideline (near infrared spectroscopy group) during immediate transition (first 15 minutes after birth) and resuscitation. MAIN OUTCOME MEASURE: The primary outcome, assessed using all cause mortality and serial cerebral ultrasonography, was a composite of survival without cerebral injury. Cerebral injury was defined as any intraventricular haemorrhage or cystic periventricular leukomalacia, or both, at term equivalent age or before discharge. RESULTS: Cerebral tissue oxygen saturation was similar in both groups. 252 (82.9%) out of 304 neonates (median gestational age 28.9 (interquartile range 26.9-30.6) weeks) in the near infrared spectroscopy group survived without cerebral injury compared with 238 (78.5%) out of 303 neonates (28.6 (26.6-30.6) weeks) in the control group (relative risk 1.06, 95% confidence interval 0.98 to 1.14). 28 neonates died (near infrared spectroscopy group 12 (4.0%) v control group 16 (5.3%): relative risk 0.75 (0.33 to 1.70). CONCLUSION: Monitoring of cerebral tissue oxygen saturation in combination with dedicated interventions in preterm neonates (<32 weeks' gestation) during immediate transition and resuscitation after birth did not result in substantially higher survival without cerebral injury compared with standard care alone. Survival without cerebral injury increased by 4.3% but was not statistically significant. TRIAL REGISTRATION: ClinicalTrials.gov NCT03166722.

Multispecialty Approach to a Very Large Congenital Head and Neck Cystic Lymphatic Malformation in an Infant Born by SARS-CoV-2 Positive Mother-A Case Report.

Masses of the head and neck are often diagnosed prenatally and require special care due to the risk of airway obstruction. The EXIT procedure is a preferable mode of delivery. A congenital cystic lymphatic malformation is one of the most common lesions of the cervical region described in neonates. The treatment consists of different strategies and involves the cooperation of multiple specialists. Up to now, no guidelines or protocols are available. We report a case of a congenital cystic lymphatic malformation of the head and neck delivered during the EXIT procedure by a mother who was SARS-CoV-2 positive. We analyzed clinical characteristics, radiologic features, and treatment with injections of sclerotic agents and orally administrated sirolimus. Sirolimus seems a valuable and safe therapeutic option for treating lymphatic malformations, especially with adjunct therapies.

The Influence of Parent Education on the Neurobehavior and Sucking Reflexes of Very Preterm Infants.

The diagnosis of neurobehavioral problems in very preterm neonates helps with planning and applying proper and direct therapeutic interventions. (1) Background: The aim of this study was to determine the direct impact of neurobehavior on the sucking reflex and eating abilities of neonates. (2) Methods: We assessed 18 preterm neonates twice hospitalized at the Gynecology and Obstetrics Clinical Hospital through the use of the Neonatal Behavioral Assessment Scale (NBAS). (3) Results: We found that that a neonate's sucking ability positively correlated with the activity level item from the motor system cluster of the NBAS. (4) Conclusions: Neurobehavior should be closely assessed in very preterm neonates. Firstly, because assessments can detect fundamental problems and help a practitioner plan for early intervention. Secondly, the education of parents regarding the neurobehavior of their child can help in the facilitation of feeding skills and the planning of early rehabilitation.

Maternal serum proteomic profiles of pregnant women with type 1 diabetes.

Despite improvement in the care of diabetes over the years, pregnancy complicated by type 1 diabetes (T1DM) is still associated with adverse maternal and neonatal outcomes. To date, proteomics studies have been conducted to identify T1DM biomarkers in non-pregnant women, however, no studies included T1DM pregnant women. In this study serum proteomic profiling was conducted in pregnant women with T1DM in the late third trimester. Serum samples were collected from 40 women with T1DM and 38 healthy controls within 3 days before delivery at term pregnancy. Significant differences between serum proteomic patterns were revealed, showing discriminative peaks for complement C3 and C4-A, kininogen-1, and fibrinogen alpha chain. Quantification of selected discriminative proteins by ELISA kits was also performed. The serum concentration of kininogen-1 was significantly lower in women with T1DM than in controls. There were no significant differences in serum concentrations of complement C3 and complement C4-A between study groups. These data indicate that pregnant women with T1DM have a distinct proteomic profile involving proteins in the coagulation and inflammatory pathways. However, their utility as biomarkers of pregnancy complications in women with T1DM warrants further investigation.

Long-Term Amnioinfusion through an Intrauterine Catheter in Preterm Premature Rupture of Membranes before 26 Weeks of Gestation: A Retrospective Multicenter Study.

INTRODUCTION: The objective of this study was to elucidate the efficacy of long-term amnioinfusion on perinatal outcomes in patients with preterm premature rupture of membranes (PPROM) before 26 weeks' gestation. MATERIAL: A total of 31 patients with PPROM at a periviable gestational age (21 + 0-25 + 0 weeks) were enrolled. Long-term amnioinfusion was performed in 22 patients, and 9 patients did not receive amnioinfusion. Data were collected retrospectively from 2 clinical sites between January 2017 and March 2019. RESULTS: In the medical management group, there was a significantly higher rate of chorioamnionitis compared to the long-term amnioinfusion group (89 vs. 15%, p = 0.001). The latency period between PPROM and delivery was higher in the amnioinfusion group (median, 5.5 vs. 3 weeks, p = 0.04). The frequency of bronchopulmonary dysplasia was higher in the control group compared to the amnioinfusion group (89 vs. 40%, p = 0.03). The rates of other neonatal complications were similar in both groups. CONCLUSIONS: Long-term amnioinfusion through an intrauterine catheter in PPROM before 26 weeks' gestation may improve pregnancy and newborn outcomes.

Genotype-phenotype correlation in two Polish neonates with alveolar capillary dysplasia.

BACKGROUND: Alveolar capillary dysplasia (ACD) is a rare cause of severe pulmonary hypertension and respiratory failure in neonates. The onset of ACD is usually preceded by a short asymptomatic period. The condition is refractory to all available therapies as it irreversibly affects development of the capillary bed in the lungs. The diagnosis of ACD is based on histopathological evaluation of lung biopsy or autopsy tissue or genetic testing of FOXF1 on chromosome 16q24.1. Here, we describe the first two Polish patients with ACD confirmed by histopathological and genetic examination. CASE PRESENTATION: The patients were term neonates with high Apgar scores in the first minutes of life. They both were diagnosed prenatally with heart defects. Additionally, the first patient presented with omphalocele. The neonate slightly deteriorated around 12th hour of life, but underwent surgical repair of omphalocele followed by mechanical ventilation. Due to further deterioration, therapy included inhaled nitric oxide (iNO), inotropes and surfactant administration. The second patient was treated with prostaglandin E1 since birth due to suspicion of aortic coarctation (CoA). After ruling out CoA in the 3rd day of life, infusion of prostaglandin E1 was discountinued and immediately patient's condition worsened. Subsequent treatment included re-administration of prostaglandin E1, iNO and mechanical ventilation. Both patients presented with transient improvement after application of iNO, but died despite maximized therapy. They were histopathologically diagnosed post-mortem with ACD. Array comparative genomic hybridization in patient one and patient two revealed copy-number variant (CNV) deletions, respectively, ~ 1.45 Mb in size involving FOXF1 and an ~ 0.7 Mb in size involving FOXF1 enhancer and leaving FOXF1 intact. CONCLUSIONS: Both patients presented with a distinct course of ACD, extra-pulmonary manifestations and response to medications. Surgery and ceasing of prostaglandin E1 infusion should be considered as potential causes of this variability. We further highlight the necessity of thorough genetic testing and histopathological examination and propose immunostaining for CD31 and CD34 to facilitate the diagnostic process for better management of infants with ACD.

Fraction of Inspired Oxygen as a Predictor of CPAP Failure in Preterm Infants with Respiratory Distress Syndrome: A Prospective Multicenter Study.

INTRODUCTION: There are limited data available regarding the fraction of inspired oxygen (FiO2) predictive of the failure of continuous positive airway pressure (CPAP) in preterm infants with respiratory distress syndrome (RDS). Therefore, we investigated factors predictive of CPAP failure in the first 72 h of life, with special attention to the prognostic role of FiO2. METHODS: This multicenter, prospective study enrolled infants <30 weeks gestation in whom CPAP was initiated within the first 15 min after birth. In the univariate and multivariate logistic regression models, demographic, perinatal, and respiratory parameters were analyzed. The FiO2 threshold was determined with ROC curve analysis. RESULTS: Of 389 recruited newborns, CPAP failure occurred in 108 infants (27.8%). In the univariate model, each gestational week reduced the odds of CPAP failure by 19%, and each 100 g of birth weight reduced the odds by 16% (both p < 0.05). The risk was increased by 4.2 and 7.5% for each 0.01 increase in FiO2in the first and second hours of life, respectively. In the final multivariate model, birth weight and FiO2 in the second hour of life were the predictive measures. The prognostic threshold was FiO2 = 0.29 in the second hour of life (AUC 0.7; p < 0.0001), with a sensitivity of 73% and a specificity of 57%. CPAP failure implied a more than 20-fold higher risk of death and pneumothorax and a 2- to 5-fold higher risk of typical complications of prematurity, including bronchopulmonary dysplasia and severe intraventricular hemorrhage. CONCLUSION: FiO2 in the second hour of life is a significantpredictor of CPAP failure. The threshold of 0.29 best discriminates the CPAP outcome. Nonresponders to CPAP have a remarkably higher incidence of complications and a higher mortality rate.

Unanticipated difficult airway management in children - the consensus statement of the Paediatric Anaesthesiology and Intensive Care Section and the Airway Management Section of the Polish Society of Anaesthesiology and Intensive Therapy and the Polish So.

Tracheal intubation may be defined as an artificial airway established in order to provide mechanical ventilation of the lungs during surgical procedures under general anaesthesia, treatment in an intensive care unit, as well as in emergency situations. Difficulties encountered during intubation may cause hypoxia, hypoxic brain injury and, in extreme situations, may result in the patient's death. There may be unanticipated and anticipated difficult airway. Children form a specific group of patients as there are significant differences in both anatomy and physiology. There are some limitations in equipment used for the airway management in children. There are only few paediatric difficult airway guidelines available, some of which have significant limitations. The presented algorithm was created by a group of specialists who represent the Polish Society of Anaesthesiology and Intensive Therapy, as well as the Polish Neonatology Society. This algorithm is intended for the unanticipated difficult airway in children and can be used in all age groups. It covers both elective intubation, as well as rescue techniques. A guide forms an integral part of the algorithm. It describes in detail all stages of the algorithm considering some modifications in a specific age group, e.g. neonates. The main aim of Stage I is to optimise conditions for face mask ventilation, laryngoscopy and intubation. Stage IIA focuses on maximising the chances of successful intubation when face mask ventilation is possible. Stage IIB outlines actions aimed at improving face mask ventilation. Stage IIIA describes the use of a SAD (Supraglottic Airway Device) during effective face mask ventilation or in a CICV (Cannot Intubate, Cannot Ventilate) situation. Stage IIIB outlines intubation through a SAD. Stage IV describes rescue techniques and outlines possible options of either proceeding with surgery or postponing it, depending on clinical situation.

Heliox for mechanically ventilated newborns with bronchopulmonary dysplasia.

OBJECTIVE: We assessed the safety and studied the influence of short-term helium-oxygen (heliox) mechanical ventilation (MV) on respiratory function, gas exchange and oxygenation in infants with bronchopulmonary dysplasia (BPD) or at high risk for BPD. DESIGN: A pilot, time-series study. SETTING: Neonatal intensive care unit. PATIENTS: Infants with severe BPD who required MV. INTERVENTIONS: MV with helium-oxygen and air-oxygen mixtures. MAIN OUTCOME MEASURES: Respiratory parameters, acid-base balance, oxygenation and vital signs were recorded at five time points: initially during MV with air-oxygen, after 15 and 60 min of helium-oxygen MV, and 15 and 60 min after return to air-oxygen MV. RESULTS: 15 infants with BPD were enrolled. Helium-oxygen MV was well tolerated and was associated with a statistically significant increase in tidal volume, dynamic compliance and peak expiratory flow rate. An improvement in oxygenation and a decrease in fraction of inspired oxygen was also observed. During helium-oxygen MV there was a significant decrease in the oxygenation index and alveolar-arterial oxygen tension difference. The PaO2/fraction of inspired oxygen (FiO2) ratio increased significantly during helium-oxygen ventilation. A decrease in PaCO2 and an increase in pH were also observed during helium-oxygen administration, however this was not statistically significant. After ventilation with helium-oxygen was discontinued, the infants' respiratory function and oxygenation deteriorated and supplemental oxygen requirements increased accordingly. CONCLUSIONS: Helium-oxygen MV is safe and resulted in improvement of respiratory function and oxygenation in infants with severe BPD requiring MV.

Single dose of green tea extract decreases lipid digestion and absorption from a test meal in humans.

BACKGROUND & AIMS: Green tea is known worldwide for its high content of polyphenolic compounds and multifactorial beneficial effects on human health. The role of green tea as an inhibitor of lipid hydrolysis is widely discussed. The aim of the study was to assess the influence of green tea extract on lipid digestion and absorption. METHODS: The study comprised 32 healthy volunteers aged 23 to 30 years with normal exocrine pancreatic function. In all subjects (13)C-labelled mixed triglyceride breath test was performed twice with and without green tea extract ingestion. Cumulative percentage dose recovery was considered to reflect digestion and absorption of lipids. Values are expressed as medians and 1st-3rd quartile distribution. RESULTS: In all subjects, cumulative percentage dose recovery values were normal in a placebo test (36.8% <30.1-43.3%>). These results were significantly higher (p=0.021) than those obtained in green tea extract test (28.8% <23.1-37.2%>). Results of six tests with GTE were abnormal. CONCLUSIONS: Single dose of green tea extract taken with a test meal decreases lipid digestion and absorption in humans.