Respiratory Support Effects over Time on Regional Lung Ventilation Assessed by Electrical Impedance Tomography in Premature Infants.

Background and objectives: Respiratory distress syndrome (RDS) frequently necessitates respiratory support. While non-invasive methods are typically the preferred approach, mechanical ventilation becomes necessary for patients with insufficient response. Our study aimed to compare two common respiratory support modes, volume-targeted mechanical ventilation and non-invasive ventilation continuous positive airway pressure (CPAP) and high-flow nasal cannula (HFNC), using electrical impedance tomography. Materials and Methods: Infants with very low birth weight and gestational ages of less than 32 weeks were eligible for inclusion in the study. All enrolled infants were beyond the transitional period (>72 h of age). The infants were divided into two groups: infants receiving invasive respiratory support through an endotracheal tube and infants receiving non-invasive respiratory support. We used electrical impedance tomography to assess end-expiratory lung impedance (EELZ), DeltaZ, heterogeneity, and regional ventilation distribution. Patients were evaluated at 0, 30, and 60 min after assuming the supine position to examine potential time-related effects. Results: Our study initially enrolled 97 infants, and the final analysis included a cohort of 72 infants. Ventilated infants exhibited significantly larger EELZ compared to their non-invasive counterparts (p = 0.026). DeltaZ was also greater in the invasive respiratory support group (p < 0.001). Heterogeneity was higher in the non-invasive group and did not change significantly over time. The non-invasive group demonstrated significantly greater ventilation in the dependent lung areas compared to intubated patients (p = 0.005). Regional distribution in the left lung was lower than in the right lung in both groups; however, this difference was significantly more pronounced in intubated patients (p < 0.001). Conclusions: Our study revealed that volume-targeted mechanical ventilation results in higher EELZ and DeltaZ compared to spontaneously breathing infants receiving non-invasive respiratory support. However, lung heterogeneity was lower during mechanical ventilation. Our study also reaffirmed that spontaneous breathing promotes greater involvement of the dependent lung compared to mechanical ventilation.

Noninvasive Respiratory Support Effects on Sighs in Preterm Infants by Electrical Impedance Tomography.

OBJECTIVE: To evaluate differences regarding sigh frequency between noninvasive respiratory support types and to assess regional ventilation distribution, delta Z, and end-expiratory lung impedance differences before and after sighs. METHODS: Very low-birth-weight infants with gestational ages less than 32 wk were included in the study. Participants were split into two groups: those receiving continuous positive airway pressure and infants receiving high-flow nasal cannula therapy. RESULTS: The study enrolled 30 infants. The high-flow nasal cannula therapy group had more sighs per 10-min period than infants receiving continuous positive airway pressure (p = 0.016). Ventilation distribution was similar in the anterior and right ventilation distribution compartments pre- and post-sigh (46.30% vs. 45.68% and 54.27% vs. 55.26%, respectively). No statistically significant increase in end-expiratory lung impedance or delta Z was observed in global or separate lung regions (p > 0.05). CONCLUSION: The study has demonstrated that sighs are more frequent in infants receiving high-flow nasal cannula respiratory support compared to continuous positive airway pressure. Spontaneously occurring sighs on noninvasive respiratory support due to respiratory distress syndrome (RDS) do not increase end-expiratory lung impedance or alter delta Z, and appear to have limited clinical significance. TRIAL REGISTRATION: Prospectively registered at www. CLINICALTRIALS: gov , reg. No. NCT04542096, reg. date 01/09/2020.

Appendicitis in a Newborn: Case Report and Review of the Literature.

Background: Acute appendicitis in a newborn is rare and may be fatal. The reported incidence is 0,04 % to 0,2 %. Diagnosis remains challenging as the symptoms are undefined. Case presentation: Here we present a full-term newborn boy of 9 days presenting with malaise, reluctance to feed and subfebrile fever. Over the course of 6 days his condition became worse. The newborn was febrile, passed no stool and his stomach became distended. Perforation due to necrotizing enterocolitis was highly suspected. The diagnosis of acute appendicitis was finalized perioperatively after the perforation and worsening condition made the emergency surgery inevitable. After 16 days of admission the patient was discharged in good condition. Conclusion: Appendicitis in neonates is a dangerous yet manageable condition. While rare it should be included in differential diagnosis when presented with atypical necrotizing enterocolitis or unexplained peritonitis. Quick and accurate diagnosis may increase survival rates.

Impact of Medical Treatment of Hemodynamically Significant Patent Ductus Arteriosus on Cerebral and Renal Tissue Oxygenation Measured by Near-Infrared Spectroscopy in Very Low-Birth-Weight Infants.

Background and objective: Hemodynamically significant patent ductus arteriosus (hsPDA) can cause ductal steal and contribute to poor outcomes in preterm infants. Near-infrared spectroscopy (NIRS) allows us to continuously evaluate regional tissue oxygenation (rSpO2) and perfusion changes in underlying organs. The aim of this study was to evaluate the effect of medical treatment for hsPDA on cerebral and renal rSpO2 in infants less than 32 weeks of gestational age, and older than 72 h of life. Materials and methods: Infants with a gestational age of <32 weeks with hsPDA were prospectively studied before and during medical treatment. Two-site (cerebral and renal) rSpO2 monitoring by NIRS was performed 1 h before treatment (T0) and 24 h (T1), 24−48 h (T2), 48−72 h (T3) after the infusion of the first drug dose. Results: A total of 21 infants were studied. The mean day of life at treatment initiation was 8.2 (SD, 2.75). The DA diameter, LA/Ao ratio, and resistive index in the anterior cerebral artery (RI ACA) were significantly lower after treatment (p < 0.05). There were no significant differences in cerebral rSpO2, cerebral fractional tissue oxygen extraction (FTOE), and SpO2 comparing different time points. A significantly higher renal SpO2 value was recorded at T2 as compared with T0 (75.0%, SD 4.9%, vs. 69.4%, SD 7.6%; p < 0.013), while for renal FTOE, a tendency to lower values at T2 was observed (0.18, SD 0.05, vs. 0.24, SD 0.09; p = 0.068). Conclusions: Late (later than 7 days postpartum) hsPDA medical treatment with paracetamol or ibuprofen completely closed the duct only in a small proportion of preterm infants, despite a statistically significant reduction in the DA diameter, LA/Ao ratio, and RI ACA. Continuous renal, not cerebral, NIRS measurements can help to anticipate the efficacy of medical treatment of hsPDA in preterm infants. Large-scale prospective studies are needed to ascertain that renal and cerebral NIRS can be used as a reliable tool for evaluating the effectiveness of medical treatment for hsPDA.

Ultrasonic cardiac output monitor provides effective non-invasive bedside measurements of neonatal cardiac output.

This study determined the accuracy and validity for the haemodynamic parameters of haemodynamically stable neonates after postnatal circulatory adaptation using the ultrasonic cardiac output monitor (USCOM) in comparison with echocardiography. We conducted a prospective, observational study of neonates born at 23-41 weeks of gestation. They all underwent both echocardiography and USCOM assessments for comparison purposes. The 127 neonates were examined at the median of postmenstrual age of 35 weeks and there was a very high correlation between the cardiac output measurements provided by both methods. The mean difference in cardiac output was - 12 ± 25 ml/kg/min, with percentage error of 8.3 ± 6.9%. A larger bias was observed in cases with higher left ventricular output. Bland-Altman analysis confirmed no significant bias, with acceptable limits of agreement between these two methods. There was a very good correlation between the USCOM and echocardiographic methods when we used them to measure cardiac output in neonates.

Brain and renal oxygenation measured by NIRS related to patent ductus arteriosus in preterm infants: a prospective observational study.

BACKGROUND: Patent ductus arteriosus (PDA) is common among preterm neonates. Haemodynamically significant ductus arteriosus (hsPDA) can cause ductal steal and contribute to poor outcomes. Our aim was to evaluate ductus arteriosus patency and significance using two-site near-infrared spectroscopy (NIRS) measurements in preterm infants older than 72 h as a supplemental tool to echocardiography. METHODS: In this prospective observational study, 123 preterm infants (gestational age (GA) < 32 weeks, birth weight < 1500 g) were enrolled. Sixty-four newborns had closed ductus arteriosus (noPDA), and 41 and 18 patients were assigned to the PDA and hsPDA groups, respectively, per predefined echocardiographic criteria. Cerebral and renal oxygenation were assessed during NIRS monitoring. RESULTS: A higher renal mean (±SD) regional tissue oxygen saturation (rSpO2) (76.7 (±7.64)) was detected in the noPDA group than in the PDA (71.7 (±9.02)) and hsPDA (67.4 (±13.48)) groups (p < 0.001). Renal fractional tissue oxygen extraction (FTOE) (0.18 (±0.079)) was lower in the noPDA group than in the PDA (0.23 (±0.092)) and hsPDA (0.24 (±0.117))0.117 groups (p = 0.002). Cerebral oxygenation was significantly lower in the hsPDA group (77.0 (±5.16)) than in the noPDA (79.3 (±2.45)) and PDA (79.7 (±2.27)) groups (p = 0.004). There was no significant difference in cerebral fractional tissue oxygen extraction (FTOE) between any of the groups. CONCLUSIONS: Our results suggest that renal oxygenation is affected by ductus patency in preterm infants older than 72 h. Significant differences in cerebral oxygenation were observed between the hsPDA group and the PDA and noPDA groups. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04295395. Registration date: 4 March 2020. This study was retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04295395 .

Pharmacokinetics and Safety of Ceftobiprole in Pediatric Patients.

BACKGROUND: Ceftobiprole, the active moiety of the prodrug ceftobiprole medocaril, is an advanced-generation, broad-spectrum, intravenous cephalosporin, which is currently approved for the treatment of adults with hospital-acquired or community-acquired pneumonia. METHODS: Noncompartmental pharmacokinetics and safety were analyzed from 2 recently completed pediatric studies, a single-dose, phase 1 study in neonates and infants up to 3 months of age (7.5 mg/kg) and a phase 3 study in patients 3 months to 17 years of age with pneumonia (10-20 mg/kg with a maximum of 500 mg per dose every 8 hours for up to 14 days). RESULTS: Total ceftobiprole plasma concentrations peaked at the end of infusion. Half life (median ranging from 1.9 to 2.9 hours) and overall exposure (median AUC ranging from 66.6 to 173 µg•h/mL) were similar to those in adults (mean ± SD, 3.3 ± 0.3 hours and 102 ± 11.9 µg•h/mL, respectively). Calculated free-ceftobiprole concentrations in the single-dose study remained above a minimum inhibitory concentration (MIC) of 4 mg/L (fT > MIC of 4 mg/L) for a mean of 5.29 hours after dosing. In the pneumonia study, mean fT > MIC of 4 mg/L was ≥5.28 hours in all dose groups. Ceftobiprole was well tolerated in both studies. CONCLUSIONS: Pharmacokinetic parameters of ceftobiprole characterized in the pediatric population were within the range of those observed in adults. In the pneumonia study, the lowest percentage of the dosing interval with fT > MIC of 4 mg/L was 50.8%, which suggests that pharmacokinetic-pharmacodynamic target attainment can be sufficient in pediatric patients. Ceftobiprole was well tolerated.

The Effect of Prolonged Freezing and Holder Pasteurization on the Macronutrient and Bioactive Protein Compositions of Human Milk.

Introduction: Human donor milk is widely used to feed premature and sick newborns when the milk of their own mothers is insufficient. All treatment processes involving human milk affect its composition. The aim of this study was to assess changes in the macronutrients and bioactive protein (lactoferrin and lysozyme) content in human milk caused by freezing and Holder pasteurization. Materials and Methods: Milk samples were collected from 42 mothers 14-16 days after delivery. Each sample was divided into two parts and tested twice for macronutrient content, once upon being freshly collected and again after freezing at -40°C, thawing and Holder pasteurization. The lysozyme and lactoferrin concentrations were first determined in the unpasteurized thawed human milk after it was stored frozen at -80°C for up to 10 months and again after Holder pasteurization. The macronutrient concentrations were determined by midinfrared spectrophotometry, and enzyme-linked immunosorbent assay was used to measure the lysozyme and lactoferrin concentrations. Results: Freezing and Holder pasteurization had no significant effects on the macronutrient concentrations. The mean lactoferrin content before and after pasteurization was 2.5 ± 1.07 and 0.03 ± 0.03 mg/mL, respectively (p < 0.001), and the lysozyme content was 19.57 ± 20.11 and 12.62 ± 14.14 µg/mL, respectively (p = 0.007). Conclusions: Freezing and Holder pasteurization did not decrease the nutritional value of human milk but caused considerable loss of lactoferrin and lysozyme. New methods for treating human milk are needed that ensure the destruction of pathogenic microorganisms while retaining the biological and nutritional value of the milk. The Clinical Trial Registration number: NCT04382989.

Circadian changes in the composition of human milk macronutrients depending on pregnancy duration: a cross-sectional study.

BACKGROUND: The purpose of this study was to evaluate the circadian variation of human milk macronutrients and energy content depending upon pregnancy duration. METHODS: One hundred eighty fresh human milk samples from 45 mothers (27 of preterm and 18 of full-term newborns) were collected on a single day chosen between the 14th to 16th day after delivery. The samples were taken four times per day at 12 PM, 6 PM, 12 AM and 6 AM. Only lactating women, who could not breastfeed their hospitalized newborns and expressed milk by breast pump, were enrolled in the study. Human milk macronutrient composition and energy count were evaluated by mid-infrared spectrophotometry. RESULTS: Significant differences in macronutrient content were observed between 6 AM and 12 PM for mean protein content (t = - 4.62, df = 44, p < 0.001), for mean fat content (t = - 2.10, df = 44, p = 0.04) and for mean energy content (t = - 2.24, df = 44, p = 0.03); between 6 AM and 6 PM for mean protein content (t = - 2.41, df = 43, p = 0.02), for mean fat content (t = - 3.76, df = 43, p = 0.001) and for mean energy content (t = - 3.85, df = 43, p < 0.001); between 12 PM and 12 AM for mean protein content (Wilcoxon test V = 75.5, p = 0.001), for mean fat content (t = 2.50, df = 44, p = 0.02) and for mean energy content (t = 2.74, df = 44, p = 0.01); between 6 PM and 12 AM for mean protein content (V = 229, p = 0.02), for mean fat content (t = 4.39, df = 43, p < 0.001) and for mean energy content (t = - 4.57, df = 43, p < 0.001). The average content of carbohydrates did not change significantly during the 24 h. The samples of preterm newborns' mothers had more apparent diurnal fluctuations in macronutrient content. CONCLUSIONS: Our study revealed significant diurnal variations in protein and fat in human milk, and these circadian fluctuations were more apparent in the milk of mothers of preterm infants.

Congenital methemoglobinemia: Rare presentation of cyanosis in newborns.

Methemoglobin (MetHb) is an oxidized form on hemoglobin, which is unable to bind oxygen and consequently carry it to the tissues. Normally present in small quantities (<1%) without detrimental effects, its elevation produces hypoxemia which can be profound and even lethal. Methemoglobinemia is an abnormal increase of MetHb (>3%) of total hemoglobin. It can be classified in two types: hereditary and acquired. Acquired form is caused by exogenous oxidizing agents, such as nitrites or certain medications, while hereditary types of disease are the result of genetic deficiency in cytochrome B5 reductase, an enzyme responsible for MetHb reduction to hemoglobin. Little data is available on the epidemiology of methemoglobinemia. In general population only sporadic cases are described, while some isolated ethnic populations have increased incidence, possibly inherited from a common ancestor. We present a case of congenital methemoglobinemia in which detection of MetHb was hampered by faulty initial blood gas spectrometry results. A short literature review is also included.

Challenges in the diagnosis and management of isolated congenital complete atrioventricular block in premature newborns.

Diagnostic and treatment challenges of congenital complete atrioventricular block in two premature newborn babies are presented. Timely recognition of this fetal condition, appropriate antenatal care, and treatment at a tertiary level care hospital as well as prompt postnatal management of the newborn baby are the key factors for good outcome. Prematurity is also associated with an additional risk of poor outcome and complications.

Nasal high-frequency oscillatory ventilation and CO2 removal: A randomized controlled crossover trial.

OBJECTIVE: To compare short-term application of nasal high-frequency oscillatory ventilation (nHFOV) with nasal continuous positive airway pressure (nCPAP). WORKING HYPOTHESIS: nHFOV improves CO2 removal with respect to nCPAP in preterm infants needing noninvasive respiratory support and persistent oxygen supply after the first 72 h of life. STUDY DESIGN: Multicenter non-blinded prospective randomized crossover study. PATIENT SELECTION: Thirty premature infants from eight tertiary neonatal intensive care units, of mean ± SD 26.4 ± 1.8 weeks of gestational age and 921 ± 177 g of birth weight. METHODOLOGY: Infants were randomly allocated in a 1:1 ratio to receive a starting treatment mode of either nCPAP or nHFOV delivered by the ventilator CNO (Medin, Germany), using short binasal prongs of appropriate size. A crossover design with four 1-h treatment periods was used, such that each infant received both treatments twice. The primary outcome was the mean transcutaneous partial pressure of CO2 (TcCO2 ) value during the 2-h cumulative period of nHFOV compared with the 2-h cumulative period of nCPAP. RESULTS: Significantly lower TcCO2 values were observed during nHFOV compared with nCPAP: 47.5 ± 7.6 versus 49.9 ± 7.2 mmHg, respectively, P = 0.0007. A different TcCO2 behavior was found according to the random sequence: in patients starting on nCPAP, TcCO2 significantly decreased from 50.0 ± 8.0 to 46.6 ± 7.5 mmHg during nHFOV (P = 0.001). In patients starting on nHFOV, TcCO2 slightly increased from 48.5 ± 7.8 to 49.9 ± 6.7 mmHg during nCPAP (P = 0.13). CONCLUSIONS: nHFOV delivered through nasal prongs is more effective than nCPAP in improving the elimination of CO2 .

Perinatal manifestation of mevalonate kinase deficiency and efficacy of anakinra.

BACKGROUND: Mevalonate kinase deficiency is a metabolic autoinflammatory syndrome caused by mutations in the MVK gene, mevalonate kinase, the key enzyme in the non-sterol isoprenoid biosynthesis pathway. Two phenotypes of mevalonate kinase deficiency are known based on the level of enzymatic deficiency, mevalonic aciduria and hyperimmunoglobulinemia D syndrome, but a wide spectrum of intermediate phenotypes has been reported. Currently one of the most effective treatments is biological therapy (with interleukin-1 antagonist anakinra or tumour necrosis factor-α inhibitor etanercept). CASE PRESENTATION: The patient in this case has a phenotype contributing to a severe disease that caused the symptoms to manifest very early, in the prenatal period. Mevalonate kinase deficiency was suspected on the basis of clinical (hydrops fetalis, hepatosplenomegaly, hypotonia) and laboratory signs (anaemia, intense acute phase reaction, increased urinary excretion of mevalonic acid). Mutation analysis of the MVK gene confirmed the biochemical diagnosis. Treatment with the interleukin-1 antagonist anakinra was started (minimal dose of 1 mg/kg/day) and revealed its efficacy after three days. CONCLUSIONS: Our case highlights the need for a very detailed clinical and laboratory assessment in new-borns with any suggestion of autoinflammatory disorders. It is important that patients are diagnosed as early as possible to provide better multidisciplinary follow-up and therapy when needed.