Potential pathogenetic role of a novel ABCC8 missense variant on both transient neonatal diabetes mellitus and fetal growth restriction: a case report.

BACKGROUND: The diagnosis of neonatal diabetes can be problematic in preterm infants with fetal growth restriction (FGR). Growth restricted fetuses may have impaired insulin production and secretion; low birthweight infants may have a reduced response to insulin. We report a novel missense ABCC8 variant associated with a clinical phenotype compatible with transient neonatal diabetes mellitus (TNDM) in a fetal growth restricted preterm infant. METHODS AND RESULTS: A preterm growth restricted infant experienced hyperglycemia from the first day of life, requiring insulin therapy on the 13th and 15th day of life and leading to the diagnosis of TNDM. Glycemic values normalized from the 35th day of life onwards. Genetic screening was performed by next generation sequencing, using a Clinical Exon panel of 4800 genes, filtered for those associated with the clinical presentation and by means of methylation-specific multiplex ligation-dependent probe amplification analysis to identify chromosomal aberrations at 6q24. Genetic tests excluded defects at 6q24 and were negative for KCNJ11, SLC2A2 (GLUT-2) and HNF1B, but revealed the presence of the heterozygous missense variant c.2959T > C (p.Ser987Pro) in ABCC8 gene. The presence of the variant was excluded in parents' DNA and the proband variant was then considered de novo. CONCLUSIONS: In our infant, the persistence of hyperglycemia beyond 3 weeks of life led us to the diagnosis of TNDM and to hypothesize a possible genetic cause. The genetic variant we found could be, most likely, the main cause of both FGR and TNDM.

Neonatal hypoglycemia and neurodevelopmental outcomes: Yesterday, today, tomorrow.

Neonatal hypoglycemia is a major source of concern for pediatricians since it has commonly been related to poor neurodevelopmental outcomes. Diagnosis is challenging, considering the different operational thresholds provided by each guideline. Screening of infants at risk plays a crucial role, considering that most hypoglycemic infants show no clinical signs. New opportunities for prevention and treatment are provided by the use of oral dextrose gel. Continuous glucose monitoring systems could be a feasible tool in the next future. Furthermore, there is still limited evidence to underpin the current clinical practice of administering, in case of hypoglycemia, an intravenous "mini-bolus" of 10% dextrose before starting a continuous dextrose infusion. This brief review provides an overview of the latest advances in this field and neurodevelopmental outcomes according to different approaches.   Conclusion: To adequately define if a more permissive approach is risk-free for neurodevelopmental outcomes, more research on continuous glucose monitoring and long-term follow-up is still needed. What is Known: • Neonatal hypoglycemia (NH) is a well-known cause of brain injury that could be prevented to avoid neurodevelopmental impairment. • Diagnosis is challenging, considering the different suggested operational thresholds for NH (<36, <40, <45, <47 or <50 mg/dl). What is New: • A 36 mg/dl threshold seems to be not associated with a worse psychomotor development at 18 months of life when compared to the "traditional" threshold (47 mg/dl). • Further studies on long-term neurodevelopmental outcomes are required before suggesting a more permissive management of NH.

Presepsin levels in neonatal cord blood are not influenced by maternal SARS-CoV-2 infection.

OBJECTIVES: Coronavirus disease (COVID-19) can present with various symptoms and can involve multiple organs. Women infected during pregnancy have a higher incidence of obstetrical complications and infants born to "positive" mothers may get the infection with different manifestations. Presepsin seems to be a promising sepsis biomarker in adults and neonates. The aim of this study was to assess if presepsin levels in neonatal cord blood could be influenced by maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: A total of 119 neonates born from women with a confirmed diagnosis of SARS-CoV-2 infection were enrolled and presepsin levels of cord blood samples were collected. All neonates were tested for SARS-CoV-2 infection at birth and after 48-72 h. RESULTS: The median presepsin value in umbilical cord blood samples collected after birth was 455 pg/mL. Presepsin levels were not influenced by maternal symptoms of COVID-19, weight for gestational age, or delivery mode, and did not significantly differ between infants with and without adverse neonatal outcomes. Infants hospitalized for more than 5 days had a significantly higher presepsin level at birth rather than those discharged up to 4 days of life. Three infants with positive nasopharyngeal swab at birth had higher Presepsin levels than two infants tested positive at 48 h. CONCLUSIONS: This is the first study reporting cord presepsin levels in term and preterm infants born to mothers with COVID-19, that appeared to be not influenced by maternal clinical presentation. However, further studies are needed to explain the mechanisms of P-SEP increase in neonates exposed to perinatal maternal SARS-CoV-2 infection or with an indeterminate/possible SARS-CoV-2 infection in the same neonates.

Brain Growth Evaluation Assessed with Transfontanellar (B-GREAT) Ultrasound. Old and New Bedside Markers to Estimate Cerebral Growth in Preterm Infants: a Pilot Study.

OBJECTIVE: We aimed to investigate the feasibility of evaluating overall preterm brain growth using a gathered set of measurements of brain structures in standard cranial ultrasound planes. We called this method of assessment Brain Growth Evaluation Assessed with Transfontanellar ultrasound (B-GREAT). STUDY DESIGN: In this prospective observational cohort study, cranial ultrasound was regularly performed (on day 1, 2, 3, and 7 of life, and then weekly until discharge, and at term) in preterm infants born with gestational age (GA) less than 32 weeks. We evaluated corpus callosum length, corpus callosum-fastigium length, anterior horn width, frontal white matter height, total brain surface, deep grey matter height, hemisphere height, transverse cerebellar diameter in the axial view, and transverse cerebellar diameter coronal view. Measurements obtained were used to develop growth charts for B-GREAT markers as a function of postmenstrual age. Reproducibility of B-GREAT markers was studied. RESULTS: A total of 528 cranial ultrasounds were performed in 80 neonates (median birth GA: 28+5 weeks and interquartile range: 27+3-30+5). The intraclass correlation coefficients for intra-observer and inter-observer analyses showed substantial agreement for all B-GREAT markers. Growth curves for B-GREAT markers were developed. CONCLUSION: B-GREAT is a feasible and reproducible method for bedside monitoring of the growth of the main brain structures in preterm neonates. KEY POINTS: · Overall neonatal brain growth is not routinely monitored using ultrasound.. · Old and new markers were used to build a standardized and non-invasive tool to monitor brain growth.. · All B-GREAT measurements had a good intra-observer and inter-observer agreement..

Diagnostic accuracy of an automated chemiluminescent immunoassay for anti-SARS-CoV-2 IgM and IgG antibodies: an Italian experience.

A pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading throughout the world. Though molecular diagnostic tests are the gold standard for COVID-19, serological testing is emerging as a potential surveillance tool, in addition to its complementary role in COVID-19 diagnostics. Indubitably quantitative serological testing provides greater advantages than qualitative tests but today there is still little known about serological diagnostics and what the most appropriate role quantitative tests might play. Sixty-one COVID-19 patients and 64 patients from a control group were tested by iFlash1800 CLIA analyzer for anti-SARS CoV-2 antibodies IgM and IgG. All COVID-19 patients were hospitalized in San Giovanni di Dio Hospital (Florence, Italy) and had a positive oro/nasopharyngeal swab reverse-transcription polymerase chain reaction result. The highest sensitivity with a very good specificity performance was reached at a cutoff value of 10.0 AU/mL for IgM and of 7.1 for IgG antibodies, hence near to the manufacturer's cutoff values of 10 AU/mL for both isotypes. The receiver operating characteristic curves showed area under the curve values of 0.918 and 0.980 for anti-SARS CoV-2 antibodies IgM and IgG, respectively. iFlash1800 CLIA analyzer has shown highly accurate results for the anti-SARS-CoV-2 antibodies profile and can be considered an excellent tool for COVID-19 diagnostics.

Maturation of the Middle Phalanx of the Third Finger: A Comparative Study between Right and Left Hand.

OBJECTIVES: Recently a classification of patient's skeletal age based on the phalanx maturation, The Middle Phalanx Maturation of the third finger (MPM) method, was suggested. The aim of this study is to evaluate if there is a difference in MPM between the right and left hand. STUDY DESIGN: Two hundred fifty-four patients were obtained from the Complex Operating Unit of Orthodontics of Padua University Hospital. The total sample size has been selected by appropriate statistical calculations resulting in 130 patients. It was decided to further double the sample size of a previous study to ensure a robust statistical analysis. Radiographs of the right and left were obtained using the MPM method. Stages were compared using the right hand as a reference. The statistical analysis (Fisher exact test) was performed for the entire sample and related to gender in order to compare the right and the left hand stages. RESULTS: In MPS2, 6 out 49 (12.2%) males and 7 out 27 females (25.9%) showed MPS3 in the left hand (p-value < 0.05). In all other stages, a total agreement (100%) was found. CONCLUSION: The authors confirm the use of the right hand as reference. In patients with MPS2 an additional radiograph on the left hand can be taken in order to increase the diagnostic accuracy. In all other stages other radiographs are not needed as a total agreement between the right and left hand was found.

Customized orthodontics: The Insignia System.

Customized treatment systems offer both patient and clinician numerous advantages, first and foremost the possibility of viewing a computerized rendering of the dentition in three dimensions. This allows the orthodontist to perform accurate measurements, analyses and simulations, and for both to be able to view the end result on screen. Thus, computerized technology consents optimization of not only the diagnostic phase, by means of extremely accurate three-dimensional imaging systems, but also the operative phase, by supplying individualized appliances with little or no correction while the treatment is in progress. In this article we present a customized orthodontic system called Insignia and how it works through two different clinical cases.

Secondary Hirata Syndrome in a Neonate: Practical Approach and Management.

Hirata disease, also known as insulin autoimmune syndrome (IAS), is a rare cause of hypoglycemia, due to the presence of insulin autoantibodies (IAA) in the circulating blood. These antibodies are immunoglobulin G (IgG), making placental transfer to the fetus possible. To our knowledge, no reports of IAS have been previously described in the neonatal population. We present a case report of hypoglycemia due to a secondary IAS in a neonate and discuss the management and treatment of the disease.

Real-Time Ultrasound Tip Location Reduces Malposition and Radiation Exposure during Umbilical Venous Catheter Placement in Neonates: A Retrospective, Observational Study.

INTRODUCTION: The umbilical venous catheter is a vital access device in neonatal intensive care units for preterm and critically ill infants. Correct positioning is crucial, as malpositioning can lead to severe complications. According to international guidelines, the position of the umbilical venous catheter tip must be assessed in real time; traditionally, the catheter is visualized with a thoracoabdominal X-ray, but one of the most effective and safest methods is therefore real-time ultrasound. METHODS: This study compares real-time ultrasound and traditional X-ray methods for assessing umbilical venous catheter tip location in 461 cases. The rate of tip malposition was analyzed retrospectively. The secondary aim was to assess indwelling time of umbilical venous catheters and reasons of removal. RESULTS: Real-time ultrasound tip location, found to be more reliable and efficient, demonstrated a significantly lower incidence of primary malpositioning compared to X-ray assessments (9.6 vs. 75.9%). The study also highlighted the association of real-time ultrasound with reduced catheter manipulation, fewer radiographs, and higher indwelling times of umbilical venous catheter. The multiple logistic regression showed a high probability of the central safe position of the umbilical venous catheter tip using real-time ultrasound tip location (odds ratio 29.5, 95% confidence interval: 17.4-49.4). CONCLUSION: The findings support the adoption of real-time ultrasound in clinical settings to enhance umbilical venous catheter placement accuracy and minimize associated risks. A minimal training investment is needed to attain the proficiency to visualize the umbilical venous catheters, offering a substantial advantage in terms of both cost-effectiveness for the procedure and enhanced patient safety.

Diagnostic Accuracy of Lung Ultrasound in Neonatal Diseases: A Systematized Review.

Background: Respiratory problems are frequent in newborns, and are mainly studied with chest X-rays, whereas CT scans are usually needed for the evaluation of rare malformations and diseases. Lung ultrasound (LUS] has been proposed as an alternative method of diagnosing a variety of respiratory conditions. In recent years, there has been a rapid increase in LUS studies, thanks to the ability of LUS to rapidly exclude complications and significantly reduce radiation exposure in this fragile population. We aimed to summarize the current knowledge about LUS. Methods: A literature search was conducted on the Medline and Cochrane databases using appropriate terms. The inclusion criteria were: English language and human species. Exclusion criteria were: non-English language, animal species, case reports, case series, non-systematic reviews, and editorials. Results: The search returned 360 results. No Cochrane reviews were found. Titles and abstracts were screened, and 37 were finally considered. Studies concerning the use of lung ultrasound for the following conditions were presented: neonatal respiratory distress syndrome, transient tachypnea of the newborn, pneumothorax, pulmonary hemorrhage, pneumonia, bronchopulmonary dysplasia, and prediction of extubation success. Conclusions: We discussed the utility of LUS for the diagnosis and treatment of neonatal diseases according to the most recent literature.

Diaphragm atrophy during invasive mechanical ventilation is related to extubation failure in preterm infants: An ultrasound study.

BACKGROUND: Diaphragm dysfunction is associated with poor outcomes in critically ill patients. Ventilator-induced diaphragmatic dysfunction (VIDD), including diaphragm atrophy (DA), is poorly studied in newborns. We aimed to assess VIDD and its associations in newborns. METHODS: Single-center prospective study. Diaphragm thickness was measured at end-inspiration (TDI) and end-expiration (TDE) on the right midaxillary line. DA was defined as decrease in TDE ≥ 10%. Daily measurements were recorded in preterm newborns on invasive mechanical ventilation (IMV) for ≥2 days. Clinical characteristics of patients and extubation failure were recorded. Univariate analysis, logistic regression, and mixed models were performed to describe VIDD and associated factors. RESULTS: We studied 17 patients (median gestational age 270/7 weeks) and 22 IMV cycles (median duration 9 days). Median TDE decreased from 0.118 cm (interquartile range [IQR] 0.094-0.165) on the first IMV day to 0.104 cm (IQR 0.083-0.120) on the last IMV day (p = .092). DA occurred in 11 IMV cycles (50%) from 10 infants early during IMV (median: second IMV day). Mean airway pressure (MAP) and lung ultrasound score (LUS) on the first IMV day were significantly higher in patients who developed DA. DA was more frequent in patients with extubation failure than in those with extubation success within 7 days (83.3 vs. 33.3%, p = .038). CONCLUSIONS: DA, significantly associated with extubation failure, occurred in 58.8% of the study infants on IMV. Higher MAP and LUS at IMV start were associated with DA. Our results suggest a potential role of diaphragm ultrasound to assess DA and predict extubation failure in clinical practice.

The Utility and Safety of a Continuous Glucose Monitoring System (CGMS) in Asphyxiated Neonates during Therapeutic Hypothermia.

BACKGROUND: The present study was designed to assess the feasibility and reliability of a Continuous Glucose Monitoring System (CGMS) in a population of asphyxiated neonates during therapeutic hypothermia. METHODS: This non-randomized feasibility study was conducted in the Neonatal Intensive Care Unit (NICU) facilities of Fondazione Policlinico A. Gemelli IRCSS. Infants matching the criteria for hypothermic treatment were included in this study and were connected to the CGMS (Medtronic, Northridge, CA, USA) within the first 12 h of life. Hypoglycemia was defined as a glucose value ≤ 47 mg/dL, and hyperglycemia was defined as a glucose value ≥ 180 mg/dL. Data obtained via the CGMS were compared with those obtained via a point-of-care blood glucometer (GTX). RESULTS: The two measuring techniques were compared using the Modified Clarke Error Grid (MCEG). Sixteen infants were enrolled. The sensor had an average (standard deviation) duration of 93 (38) h. We collected 119 pairs of glycemia values (CGMVs) from the CGMS vs. GTX measurements. The CGMS detected twenty-five episodes of hypoglycemia and three episodes of hyperglycemia. All the CGMVs indicating hyperglycemia matched with the blood sample taken via the point-of-care glucometer. CONCLUSIONS: The use of a CGMS would be useful as it could detect more episodes of disglycemia than standard care. Our data show poor results in terms of the accuracy of the CGMS in this particular setting.

Lung Ultrasound in the Early Diagnosis and Management of the Mild Form of Meconium Aspiration Syndrome: A Case Report.

MAS is a common cause of neonatal respiratory distress in term and post-term neonates. Meconium staining of the amniotic fluid occurs in about 10-13% of normal pregnancies, and about 4% of these infants develop respiratory distress. In the past, MAS was diagnosed mainly on the basis of history, clinical symptoms, and chest radiography. Several authors have addressed the ultrasonographic assessment of the most common respiratory patterns in neonates. In particular, MAS is characterised by a heterogeneous alveolointerstitial syndrome, subpleural abnormalities with multiple lung consolidations, characterised by a hepatisation aspect. We present six cases of infants with a clinical history of meconium-stained fluid who presented with respiratory distress at birth. Lung ultrasound allowed the diagnosis of MAS in all the studied cases, despite the mild clinical picture. All children had the same ultrasound pattern with diffuse and coalescing B-lines, pleural line anomalies, air bronchograms, and subpleural consolidations with irregular shapes. These patterns were distributed in different areas of the lungs. These signs are specific enough to distinguish between MAS and other causes of neonatal respiratory distress, allowing the clinician to optimise therapeutic management.

The Role of Ultrasound in Epicutaneo-Caval Catheter Insertion in Neonates: Systematic Review, Meta-Analysis and Future Perspectives.

Chest and abdominal X-rays after the insertion of an epicutaneo-caval catheter in infants are the standard method of checking the tip location in many neonatal intensive care units. The role of ultrasound in the tip location of the epicutaneo-caval catheter in neonates has been the subject of many recent studies. This systematic review investigates the accuracy of epicutaneo-caval catheter tip location by comparing ultrasound and conventional radiology. We performed a systematic literature search in multiple databases. The selection of studies yielded nineteen articles. The systematic review and meta-analysis were performed according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analysis). The analyses showed that ultrasound is a better imaging technique for epicutaneo-caval catheter tip location in the neonatal intensive care unit than conventional radiology. By improving operator training and selecting a standardized echography protocol, ultrasound could become the gold standard for visualizing the epicutaneo-caval catheter tip in the neonatal intensive care unit. This would have some important benefits: (1) increased accuracy in tip location (2); a more rapid use of the central venous access (3); and a significant reduction in radiation exposure.

Bile Acids Pneumonia: A Respiratory Distress Syndrome in Early-Term Neonates.

Intrahepatic cholestasis of pregnancy (ICP) complicates among 0.2-2% of pregnancies and has been associated with adverse perinatal outcomes, including sudden stillbirth, meconium strained fluid, preterm birth, perinatal asphyxia, and transient tachypnea of the newborn. The diagnosis of "bile acids pneumonia" was previously proposed and a causative role of bile acids (BA) was supposed with a possible mechanism of action including surfactant dysfunction, inflammation, and chemical pneumonia. In the last few years, the role of lung ultrasound (LUS) in the diagnosis and management of neonatal respiratory distress syndrome has grown, and LUS scores have been introduced in the literature, as an effective predictor of the need for surfactant treatment among neonates with respiratory distress syndrome. We present four cases of infants born from pregnancies complicated by ICP, who developed respiratory distress syndrome early after birth. Lung ultrasound showed the same pattern for all infants, corresponding to a homogeneous alveolar-interstitial syndrome characterized by a diffuse coalescing B-line pattern (white lung). All infants evaluated require non-invasive respiratory support and in three cases surfactant administration, despite the near-term gestational age, with rapid improvement of respiratory disease and a good clinical outcome.

The future of neonatal lung ultrasound: Validation of an artificial intelligence model for interpreting lung scans. A multicentre prospective diagnostic study.

BACKGROUND: Artificial intelligence (AI) is a promising field in the neonatal field. We focused on lung ultrasound (LU), a useful tool for the neonatologist. Our aim was to train a neural network to create a model able to interpret LU. METHODS: Our multicentric, prospective study included newborns with gestational age (GA) ≥ 33 + 0 weeks with early tachypnea/dyspnea/oxygen requirements. For each baby, three LU were performed: within 3 h of life (T0), at 4-6 h of life (T1), and in the absence of respiratory support (T2). Each scan was processed to extract the region of interest used to train a neural network to classify it according to the LU score (LUS). We assessed sensitivity, specificity, positive and negative predictive value of the AI model's scores in predicting the need for respiratory assistance with nasal continuous positive airway pressure and for surfactant, compared to an already studied and established LUS. RESULTS: We enrolled 62 newborns (GA = 36 ± 2 weeks). In the prediction of the need for CPAP, we found a cutoff of 6 (at T0) and 5 (at T1) for both the neonatal lung ultrasound score (nLUS) and AI score (AUROC 0.88 for T0 AI model, 0.80 for T1 AI model). For the outcome "need for surfactant therapy", results in terms of area under receiver operator characteristic (AUROC) are 0.84 for T0 AI model and 0.89 for T1 AI model. In the prediction of surfactant therapy, we found a cutoff of 9 for both scores at T0, at T1 the nLUS cutoff was 6, while the AI's one was 5. Classification accuracy was good both at the image and class levels. CONCLUSIONS: This is, to our knowledge, the first attempt to use an AI model to interpret early neonatal LUS and can be extremely useful for neonatologists in the clinical setting.

Cord blood presepsin as a predictor of early-onset neonatal sepsis in term and preterm newborns.

BACKGROUND: To date, no studies on presepsin values in cord blood of term infants with risk factors for early-onset sepsis (EOS) are available, whereas only one study reported presepsin values in cord blood of preterm infants at risk. In this study, we investigated the presepsin values in cord blood of term and preterm infants with documented risk factors for EOS. METHODS: In this single-center prospective pilot study, we enrolled neonates presenting with documented risk factors for EOS. P-SEP levels were assessed in a blood sample collected from the clamped umbilical cord after the delivery in 93 neonates, using a point-of-care device. The primary outcome of our study was to evaluate the role of cord blood P-SEP in predicting clinical EOS in term and preterm infants. RESULTS: During the study period, we enrolled 93 neonates with risk factors for EOS with a gestational age ranging between 24.6 and 41.6 weeks (median 38.0). The median P-SEP value in all infants was 491 pg/ml (IQR 377 - 729). Median cord P-SEP values were significantly higher in infants with clinical sepsis (909 pg/ml, IQR 586 - 1307) rather than in infants without (467 pg/ml, IQR 369 - 635) (p = 0.010). We found a statistically significant correlation between cord P-SEP value at birth and the later diagnosis of clinical sepsis (Kendall's τ coefficient 0.222, p = 0.002). We identified the maximum Youden's Index (best cut-off point) at 579 pg/ml, corresponding to a sensitivity of 87.5% and a specificity of 71.8% in predicting clinical sepsis. CONCLUSIONS: Maximum Youden's index was 579 pg/ml for clinical EOS using cord P-SEP values. This could be the starting point to realize multicenter studies, confirming the feasibility of dosing P-SEP in cord blood of infants with risk factors of EOS to discriminate those who could develop clinical sepsis and spare the inappropriate use of antibiotics.

Early Respiratory Physiotherapy versus an Individualized Postural Care Program for Reducing Mechanical Ventilation in Preterm Infants: A Randomised Controlled Trial.

BACKGROUND: Tactile stimulation manoeuvres stimulate spontaneous breathing in preterm newborns. The aim of this study is to evaluate the effect of early respiratory physiotherapy on the need for mechanical ventilation during the first week of life in preterm infants with respiratory failure. METHODS: This is a monocentric, randomised controlled trial. Preterm infants (gestational age ≤ 30 weeks) not intubated in the delivery room and requiring non-invasive respiratory support at birth were eligible for the study. The intervention group received early respiratory physiotherapy, while the control group received only a daily physiotherapy program (i.e., modifying the infant's posture in accordance with the patient's needs). RESULTS: between October 2019 and March 2021, 133 preterm infants were studied, 68 infants in the study group and 65 in routine care. The study group showed a reduction in the need for mechanical ventilation (not statistically significant) and a statistically significant reduction in hemodynamically significant patent ductus arteriosus with respect to the control group (19/68 (28%) vs. 35/65 (54%), respectively, p = 0.03). CONCLUSIONS: early respiratory physiotherapy in preterm infants requiring non-invasive respiratory support at birth is safe and has proven to be protective against haemodynamically significant PDA.