Incidence and Management of Neonatal Pneumothorax in a 10-Hospital Regional Perinatal Network in Switzerland: A Retrospective Observational Study.

OBJECTIVE: Pneumothorax (PTX) is a potentially life-threatening condition that affects neonates, with an incidence of 0.05 to 2%. Its management includes conservative treatment, chest tube (CT) drainage, and needle aspiration (NA). Aims were to evaluate the incidence of PTX in a 10-hospital perinatal network, its clinical characteristics and risk factors, and to compare the different treatment options. STUDY DESIGN: All neonates diagnosed with PTX and hospitalized in the network were included in this retrospective observational trial over a period of 30 months. Primary outcome was the incidence of PTX. Secondary outcomes were the treatment modality, the length of stay (LOS), and the number of chest X-rays. RESULTS: Among the 173 neonates included, the overall incidence of PTX was 0.56 per 100 births with a large range among the hospitals (0.12-1.24). Thirty-nine percent of pneumothoraces were treated conservatively, 41% by CT drainage, 13% by NA, and 7% by combined treatment. Failure rate was higher for NA (37%) than for CT drainage (9%). However, the number of X-rays was lower for patients treated by NA, with a median of 6 (interquartile range [IQR] 4-6.25), than by CT drainage, with a median of 9 (IQR 7-12). LOS was shorter for NA than for CT drainage, with a median of 2 (IQR 1-4.25) and 6 days (IQR 3-15), respectively. Complications, including apnea and urinary retention, occurred in 28% of patients managed with CT drainage, whereas none was observed with NA. CONCLUSION: High variability of PTX incidence was observed among the hospitals within the network, but these values correspond to the literature. NA showed to reduce the number of X-rays, the LOS, and complications compared with CT drainage, but it carries a high failure rate. This study helped provide a new decisional management algorithm to harmonize and improve PTX treatment within our network. KEY POINTS: · Neonatal PTX is a frequent pathology with a high incidence requiring urgent management.. · We report a large variability of PTX incidence between different hospitals of the same network.. · Needle aspiration carries higher failure rate, shorter hospital stay duration without complications reported..

Bronchopulmonary dysplasia: a predictive scoring system for very low birth weight infants. A diagnostic accuracy study with prospective data collection.

Our aim was to develop and validate a predictive risk score for bronchopulmonary dysplasia (BPD), according to two clinically used definitions: 1. Need for supplementary oxygen during ≥ 28 cumulative days, BPD28, 2. Need for supplementary oxygen at 36 weeks postmenstrual age (PMA), BPD36. Logistic regression was performed in a national cohort (infants born in Switzerland with a birth weight < 1501 g and/or between 23 0/7 and 31 6/7 weeks PMA in 2009 and 2010), to identify predictors of BPD. We built the score as the sum of predicting factors, weighted according to their ORs, and analysed its discriminative properties by calculating the area under the ROC (receiver operating characteristic) curves (AUCs). This score was then applied to the Swiss national cohort from the years 2014-2015 to perform external validation. The incidence of BPD28 was 21.6% in the derivation cohort (n = 1488) and 25.2% in the validation cohort (n = 2006). The corresponding numbers for BPD36 were 11.3% and 11.1%, respectively. We identified gestational age, birth weight, antenatal corticosteroids, surfactant administration, proven infection, patent ductus arteriosus and duration of mechanical ventilation as independent predictors of BPD28. The AUCs of the BPD risk scores in the derivation cohort were 0.90 and 0.89 for the BPD28 and BPD36 definitions, respectively. The corresponding AUCs in the validation cohort were 0.92 and 0.88, respectively.Conclusion: This score allows for predicting the risk of a very low birth weight infant to develop BPD early in life and may be a useful tool in clinical practice and neonatal research. What is Known: • Many studies have proposed scoring systems to predict bronchopulmonary dysplasia (BPD). • Such a risk prediction may be important to identify high-risk patients for counselling parents, research purposes and to identify candidates for specific treatment. What is New: • A predictive risk score for BPD was developed and validated in a large national multicentre cohort and its performance assessed by two indices of accuracy. • The developed scoring system allows to predict the risk of BPD development early but also at any day of life with high validity.

[Perinatal care for extremely preterm labor between 23 and 26 weeks : management in CHUV]. / Menace sévère d'accouchement entre 23 et 26 SA†: algorithme de prise en charge obstétrico-néonatale au CHUV.

Management of patients at high risk of extreme premature birth between 23 and 26 weeks should be performed by an experienced multidisciplinary team. In order to optimize guidance for couples with regard to this complex decision, we developed joint guidelines between obstetricians and neonatologists, in order to standardize practices and insure individualized care plans. Fetal outcome is not solely associated with gestational age but is multifactorial, and this should be considered when counseling parents. Thus, enhancement of fetal lung maturation, a major prognostic factor, should be promptly acted upon when delivery is anticipated. Antenatal corticosteroids should not be withheld while awaiting the parents' ultimate decision on neonatal care.

La prise en charge des patientes à haut risque d'accouchement prématuré entre 23 et 26 semaines d'aménorrhée (SA) doit être faite par une équipe périnatale expérimentée. Afin d'améliorer la prise en charge des couples dans cette situation particulièrement difficile, nous avons élaboré un protocole commun entre obstétriciens et néonatologues. Cette réflexion vise à uniformiser les pratiques au sein du CHUV et à assurer aux couples des soins personnalisés. Le pronostic fœtal ne dépend pas uniquement de l'âge gestationnel mais d'un ensemble de facteurs dont il est important de tenir compte dans la discussion avec les parents. Ainsi la corticothérapie, facteur pronostique majeur, doit être réalisée le plus rapidement possible en cas de menace sévère. L'injection ne doit pas être différée par la réflexion des couples sur les soins néonataux.

Measurement of stress in stable neonates during ambulance transportation: A feasibility study.

BACKGROUND: Stress during ambulance transportation has been described in adult healthy volunteers where indicators of stress such as heart rate, blood pressure, and cortisol increased significantly. In neonates, a few studies have described stress in ambulance with behavioural scales. However, there is no study in neonates assessing both behavioural and physiological indicators of stress simultaneously during ambulance transportation. OBJECTIVE: To assess the feasibility of a study aiming at identifying stress in clinically stable neonates during ambulance transportation in non-emergency situations. METHODS: Stable neonates transported by ambulance from September 2015 to January 2016 were eligible. Physiological and behavioural parameters of stress were measured during the entire transfer procedure, starting on the ward of departure until hospitalisation at destination. Physiological parameters included salivary cortisol concentration, heart rate, respiratory rate, and oxygen saturation. Behavioural parameters were measured with the Comfort Behavior and the Premature Infant Pain Profile-Revised scales. RESULTS: Twenty neonates were included. The study proved to be feasible, but collection of saliva for cortisol measurement was problematic. To reach a sufficient amount of saliva, the collection time had to be extended from 90 to 300 s. Physiological parameters demonstrated heterogeneous patterns of stress. Behavioural scores increased during the entire transfer procedure and did not return to baseline values, indicating discomfort, specifically during transfer from the cot into the transport incubator. CONCLUSIONS: Salivary cortisol values were variable. Behavioural measurement of stress provided a more sensitive measure to detect low level of stress, as shown in our sample of stable neonates, during non-emergency transportation.

Prediction of ROP Treatment and Evaluation of Screening Criteria in VLBW Infants-a Population Based Analysis.

BACKGROUND: The incidence of retinopathy of prematurity (ROP) and ROP screening criteria differ between countries. We assessed whether ROP screening could be reduced based on the local ROP incidence. METHODS: Observational cohort study of infants born in Switzerland between 2006 and 2015 <32 0/7 weeks. Chronological and postmenstrual ages at ROP treatment were analyzed. A model to identify ROP treatment on patients born between 2006 and 2012 (training set) was developed and tested on patients born between 2013 and 2015 (validation set). RESULTS: Of 7817 live-born infants, 1098 died within the first 5 weeks of life. The remaining 6719 infants were included into analysis. All patients requiring ROP treatment would have been identified if screening had been performed before reaching 60 days of life or 37 3/7 weeks postmenstrual age, whichever came first. The training and validation sets included 4522 and 2197 preterm infants encompassing 56 and 20 patients receiving ROP treatment, respectively. All patients would have required screening to reach 100% sensitivity. To reach a sensitivity of 95.0% and a specificity of 87.6%, we predicted a reduction in 13.2% of patients requiring screening (c-statistic = 0.916). CONCLUSIONS: A substantial reduction of infants requiring screening seems possible, but necessitates prospective testing of new screening criteria.

Gene expression profile in newborn rat lungs after two days of recovery of mechanical ventilation.

BACKGROUND: Preterm infants having immature lungs often require respiratory support, potentially leading to bronchopulmonary dysplasia (BPD). Conventional BPD rodent models based on mechanical ventilation (MV) present outcome measured at the end of the ventilation period. A reversible intubation and ventilation model in newborn rats recently allowed discovering that different sets of genes modified their expression related to time after MV. In a newborn rat model, the expression profile 48 h after MV was analyzed with gene arrays to detect potentially interesting candidates with an impact on BPD development. METHODS: Rat pups were injected P4-5 with 2 mg/kg lipopolysaccharide (LPS). One day later, MV with 21 or 60% oxygen was applied during 6 h. Animals were sacrified 48 h after end of ventilation. Affymetrix gene arrays assessed the total gene expression profile in lung tissue. RESULTS: In fully treated animals (LPS + MV + 60% O(2)) vs. controls, 271 genes changed expression significantly. All modified genes could be classified in six pathways: tissue remodeling/wound repair, immune system and inflammatory response, hematopoiesis, vasodilatation, and oxidative stress. Major alterations were found in the MMP and complement system. CONCLUSION: MMPs and complement factors play a central role in several of the pathways identified and may represent interesting targets for BPD treatment/prevention.Bronchopulmonary dysplasia (BPD) is a chronic lung disease occurring in ~30% of preterm infants born less than 30 wk of gestation (1). Its main risk factors include lung immaturity due to preterm delivery, mechanical ventilation (MV), oxygen toxicity, chorioamnionitis, and sepsis. The main feature is an arrest of alveolar and capillary formation (2). Models trying to decipher genes involved in the pathophysiology of BPD are mainly based on MV and oxygen application to young mammals with immature lungs of different species (3). In newborn rodent models, analyses of lung structure and gene and protein expression are performed for practical reasons directly at the end of MV (4,5,6). However, later appearing changes of gene expression might also have an impact on lung development and the evolution towards BPD and cannot be discovered by such models. Recently, we developed a newborn rat model of MV using an atraumatic (orotracheal) intubation technique that allows the weaning of the newborn animal off anesthesia and MV, the extubation to spontaneous breathing, and therefore allows the evaluation of effects of MV after a ventilation-free period of recovery (7). Indeed, applying this concept of atraumatic intubation by direct laryngoscopy, we recently were able to show significant differences between gene expression changes appearing directly after MV compared to those measured after a ventilation-free interval of 48 h. Immediately after MV, inflammation-related genes showed a transitory modified expression, while another set of more structurally related genes changed their expression only after a delay of 2 d (7). Lung structure, analyzed by conventional 2D histology and also by 3D reconstruction using synchrotron x-ray tomographic microscopy revealed, 48 h after end of MV, a reduced complexity of lung architecture compared to the nonventilated rat lungs, similar to the typical findings in BPD. To extend these observations about late gene expression modifications, we performed with a similar model a full gene expression profile of lung tissue 48 h after the end of MV with either room air or 60% oxygen. Essentially, we measured changes in the expression of genes related to the MMPs and complement system which played a role in many of the six identified mostly affected pathways.

Swiss medical centres vary significantly when it comes to outcomes of neonates with a very low gestational age.

AIM: This study quantified the impact of perinatal predictors and medical centre on the outcome of very low-gestational-age neonates (VLGANs) born at <32 completed weeks in Switzerland. METHODS: Using prospectively collected data from a 10-year cohort of VLGANs, we developed logistic regression models for three different time points: delivery, NICU admission and seven days of age. The data predicted survival to discharge without severe neonatal morbidity, such as major brain injury, moderate or severe bronchopulmonary dysplasia, retinopathy of prematurity (≥stage three) or necrotising enterocolitis (≥stage three). RESULTS: From 2002 to 2011, 6892 VLGANs were identified: 5854 (85%) of the live-born infants survived and 84% of the survivors did not have severe neonatal complications. Predictors for adverse outcome at delivery and on NICU admission were low gestational age, low birthweight, male sex, multiple birth, birth defects and lack of antenatal corticosteroids. Proven sepsis was an additional risk factor on day seven of life. The medical centre remained a statistically significant factor at all three time points after adjusting for perinatal predictors. CONCLUSION: After adjusting for perinatal factors, the survival of Swiss VLGANs without severe neonatal morbidity was strongly influenced by the medical centre that treated them.

Surgical complications due to postnatal cytomegalovirus infection in a preterm infant with malrotation.

We report a case of an extremely preterm infant with intestinal malrotation who contracted postnatal systemic cytomegalovirus (CMV) infection with a complicated intestinal evolution requiring repeated surgical interventions and antiviral treatment. This report is to emphasize that prolonged gastrointestinal symptoms in extremely preterm infants fed with non-pasteurized breast milk should lead to suspicion of CMV infection. The importance of preventive measures when feeding very preterm infants with breast milk needs to be considered. Furthermore, the indications for antiviral treatment, in particular in preterm infants, need to be clarified.

Neonatal steroids induce a down-regulation of tenascin-C and elastin and cause a deceleration of the first phase and an acceleration of the second phase of lung alveolarization.

Pre- and postnatal corticosteroids are often used in perinatal medicine to improve pulmonary function in preterm infants. To mimic this clinical situation, newborn rats were treated systemically with dexamethasone (Dex), 0.1-0.01 mg/kg/day on days P1-P4. We hypothesized that postnatal Dex may have an impact on alveolarization by interfering with extracellular matrix proteins and cellular differentiation. Morphological alterations were observed on 3D images obtained by high-resolution synchrotron radiation X-ray tomographic microscopy. Alveolarization was quantified stereologically by estimating the formation of new septa between days P4 and P60. The parenchymal expression of tenascin-C (TNC), smooth muscle actin (SMA), and elastin was measured by immunofluorescence and gene expression for TNC by qRT-PCR. After Dex treatment, the first phase of alveolarization was significantly delayed between days P6 and P10, whereas the second phase was accelerated. Elastin and SMA expressions were delayed by Dex treatment, whereas TNC expression was delayed and prolonged. A short course of neonatal steroids impairs the first phase of alveolarization, most likely by altering the TNC and elastin expression. Due to an overshooting catch-up during the second phase of alveolarization, the differences disappear when the animals reach adulthood.

Day Admission Surgery Program in a Prospective Payment System: What Are the Financial Incentives?

Background: Day admission surgery (DAS) is meant to provide a better in-hospital experience for patients and to save costs by reducing the length of stay. However, in a prospective payment system, it may also reduce the reimbursement amount, leading to unintended incentives for hospitals. Methods: Over a 4-month period in 2021 and based on predefined clinical and logistic criteria, patients from different surgical sub-specialties were identified to follow the institutional DAS program. Revenue-analysis was performed, considering the Swiss diagnosis-related group (SwissDRG) prospective payment policy. Revenue with DAS program was compared to revenue if patients were admitted the day prior surgery (No DAS) using nonparametric pooled bootstrap t-test. All other costs considered identical, an estimation of the average cost spared due to the avoidance of pre-operative hospitalization in the DAS setting was carried out using a micro-costing approach. Results: Overall, 105 inpatients underwent DAS over the study period, totaling a revenue of CHF 1 209 840. Among them, 25 patients (24%) were low outliers due to the day spared from the DAS program and triggering a mean (SD) financial discount of Swiss Francs (CHF) 4192 (2835), yielding a total amount of CHF 105 435. DAS revealed a mean revenue of CHF 7320 (656), compared to CHF 11 510 (1108) if patients were admitted the day before surgery (No DAS, P = .007). Conclusion: In a PPS, anticipation of financial penalties when implementing a DAS for all-comers is key to prevent an imbalance of the hospital equation if no financial criteria are used to select eligible patients. Promptly revising workflow to maintain constant fixed costs for a greater number of patients may be a valuable hedging strategy.

Ending Neonatal Deaths From Hypothermia in Sub-Saharan Africa: Call for Essential Technologies Tailored to the Context.

Neonatal death represents a major burden in Sub-Saharan Africa (SSA), where the main conditions triggering mortality, such as prematurity, labor complications, infections, and respiratory distress syndrome, are frequently worsened by hypothermia, which dramatically scales up the risk of death. In SSA, the lack of awareness on the procedures to prevent hypothermia and the shortage of essential infant devices to treat it are hampering the reduction of neonatal deaths associated to hypothermia. Here, we offer a snapshot on the current available medical solutions to prevent and treat hypothermia in SSA, with a focus on Kenya. We aim to provide a picture that underlines the essential need for infant incubators in SSA. Specifically, given the inappropriateness of the incubators currently on the market, we point out the need for reinterpretation of research in the field, calling for technology-based solutions tailored to the SSA context, the need, and the end-user.

Estradiol and progesterone strongly inhibit the innate immune response of mononuclear cells in newborns.

Newborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, and Escherichia coli and group B Streptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-κB pathway but not the mitogen-activated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period.

Respiratory distress in newborn infants in Western Switzerland.

AIM: To assess epidemiological data about respiratory distress (RD) in newborn infants hospitalized in Western Switzerland. METHODS: During 1 year, two questionnaires were sent out to the seven neonatal and pediatric units of a well-defined geographic region in Switzerland. Data about their obstetrical activity and details about all newborn infants hospitalized with RD were collected, asking for pre-, peri-, and postnatal clinical data in association with RD. RESULTS: Almost 6% of all newborn infants born in the Canton of Vaud had to be hospitalized for RD. All newborn infants below 32 weeks of gestational age (GA) had developed RD, accounting for 14.6% of all neonates, hospitalized with RD, whereas the moderate to late preterm infants contributed with 36.8% much more to the RD hospitalizations. Associated factors to hospitalizations with RD were prematurity, cesarean delivery, and multiple births. CONCLUSIONS: Efforts should be made to reduce avoidable RD by reconsidering the management of pregnancies with premature rupture of the membranes around 34 weeks of GA and by delaying elective cesarean sections after 39 completed weeks of gestation.

Clinical presentation and improvised management of neonatal pneumothorax in the setting of a low-resource country: Conakry, Guinea.

Two neonates were presented at the Neonatology Department of the Institute of Child Nutrition and Health in Conakry, Guinea, with tension pneumothoraces as confirmed by chest X-ray. They were initially managed with needle thoracentesis but required continuous thoracic drainage. Due to scarce resources in the public health sector, no prepacked and dedicated pleural drainage systems were available as is the case in many developing countries. Therefore, we fabricated an improvised underwater seal drain out of a plastic infusion bottle and a Heimlich valve out of a vicryl fingerstall. Both devices have shown to be effective. Pneumothorax is a common and potentially life-threatening disease in neonates that often requires prompt treatment. This case series demonstrates how tension pneumothorax in two newborns was successfully managed by improvising different chest drainage systems. The depicted techniques shall serve as an instruction manual to healthcare professionals working in low-resource settings and facing similar challenges.

Tenascin-C: Friend or Foe in Lung Aging?

Lung aging is characterized by lung function impairment, ECM remodeling and airspace enlargement. Tenascin-C (TNC) is a large extracellular matrix (ECM) protein with paracrine and autocrine regulatory functions on cell migration, proliferation and differentiation. This matricellular protein is highly expressed during organogenesis and morphogenetic events like injury repair, inflammation or cancer. We previously showed that TNC deficiency affected lung development and pulmonary function, but little is known about its role during pulmonary aging. In order to answer this question, we characterized lung structure and physiology in 18 months old TNC-deficient and wild-type (WT) mice. Mice were mechanically ventilated with a basal and high tidal volume (HTV) ventilation protocol for functional analyses. Additional animals were used for histological, stereological and molecular biological analyses. We observed that old TNC-deficient mice exhibited larger lung volume, parenchymal volume, total airspace volume and septal surface area than WT, but similar mean linear intercept. This was accompanied by an increase in proliferation, but not apoptosis or autophagy markers expression throughout the lung parenchyma. Senescent cells were observed in epithelial cells of the conducting airways and in alveolar macrophages, but equally in both genotypes. Total collagen content was doubled in TNC KO lungs. However, basal and HTV ventilation revealed similar respiratory physiological parameters in both genotypes. Smooth muscle actin (α-SMA) analysis showed a faint increase in α-SMA positive cells in TNC-deficient lungs, but a marked increase in non-proliferative α-SMA + desmin + cells. Major TNC-related molecular pathways were not up- or down-regulated in TNC-deficient lungs as compared to WT; only minor changes in TLR4 and TGFßR3 mRNA expression were observed. In conclusion, TNC-deficient lungs at 18 months of age showed exaggerated features of the normal structural lung aging described to occur in mice between 12 and 18 months of age. Correlated to the increased pulmonary function parameters previously observed in young adult TNC-deficient lungs and described to occur in normal lung aging between 3 and 6 months of age, TNC might be an advantage in lung aging.

"Assessing Today for a Better Tomorrow": An observational cohort study about quality of care, mortality and morbidity among newborn infants admitted to neonatal intensive care in Guinea.

BACKGROUND: Neonatal mortality in Guinea accounts for about 30% of all fatalities in children younger than five years. Countrywide, specialized neonatal intensive care is provided in one single clinic with markedly limited resources. To implement targeted measures, prospective data on patient characteristics and factors of neonatal death are needed. OBJECTIVE: To determine the rates of morbidity and mortality, to describe clinical characteristics of admitted newborns requiring intensive care, to assess the quality of disease management, and to identify factors contributing to neonatal mortality. METHODS: Prospective observational cohort study of newborns admitted to the hospital between mid-February and mid-March 2019 after birth in other institutions. Data were collected on maternal/prenatal history, delivery, and in-hospital care via convenience sampling. Associations of patient characteristics with in-hospital death were assessed using cause-specific Cox proportional-hazards models. RESULTS: Half of the 168 admitted newborns underwent postnatal cardiopulmonary resuscitation. Reasons for admission included respiratory distress (49.4%), poor postnatal adaptation (45.8%), prematurity (46.2%), and infections (37.1%). 101 newborns (61.2%) arrived in serious/critical general condition; 90 children (53.9%) showed clinical signs of neurological damage. Quality of care was poor: Only 59.4% of the 64 newborns admitted with hypothermia were externally heated; likewise, 57.1% of 45 jaundiced infants did not receive phototherapy. Death occurred in 56 children (33.3%) due to birth asphyxia (42.9%), prematurity (33.9%), and sepsis (12.5%). Newborns in serious/critical general condition at admission had about a fivefold higher hazard to die than those admitted in good condition (HR 5.21 95%-CI 2.42-11.25, p = <0.0001). Hypothermia at admission was also associated with a higher hazard of death (HR 2.00, 95%-CI 1.10-3.65, p = 0.023). CONCLUSION: Neonatal mortality was strikingly high. Birth asphyxia, prematurity, and infection accounted for 89.3% of death, aggravated by poor quality of in-hospital care. Children with serious general condition at admission had poor chances of survival. The whole concept of perinatal care in Guinea requires reconsideration.

Congenital hyperinsulinism: 2 case reports with different rare variants in ABCC8.

Congenital hyperinsulinism (CHI) is a rare glucose metabolism disorder characterized by unregulated secretion of insulin that leads to hyperinsulinemic hypoglycemia (HH). Most cases are caused by mutations in the KATP-channel genes ABCC8 and KCNJ11. We report 2 patients that experienced severe HH from the first day of life. Patient 1 developed midgut volvulus after initiating diazoxide and required intestinal resection. He was subsequently managed with a high-dose octreotide and glucose-enriched diet. Consistent with diffuse type CHI by 18F-dihydroxyphenylalanine positron emission tomography-computed tomography, genetic testing revealed a homozygous ABCC8 variant, c.1801G>A, p.(Val601Ile). The rare variant was previously reported to be diazoxide-responsive, and the patient responded well to diazoxide monotherapy, with clinical remission at 2 years of age. Patient 2 responded to diazoxide with spontaneous clinical remission at 15 months of age. However, an oral glucose tolerance test at 7 years of age revealed hyperinsulinism. Genetic testing revealed that the proband and several seemingly healthy family members harbored a novel, heterozygous ABCC8 variant, c.1780T>C, p.(Ser594Pro). Genetic findings identified previously unrecognized HH in the proband's mother. The proband's uncle had been diagnosed with monogenic ABCC8-diabetes and was successfully transitioned from insulin to glibenclamide therapy. We report findings of intestinal malrotation and volvulus occurring 2 days after initiation of diazoxide treatment. We also report a novel, heterozygous ABCC8 variant in a family that exhibited cases of CHI in infancy and HH and monogenic diabetes in adult members. The cases demonstrate the importance and clinical utility of genetic analyses for informing and guiding treatment and care.

Evaluation of different POCT devices for glucose measurement in a clinical neonatal setting.

Hypoglycaemia is a major cause of neonatal morbidity and may induce long-term developmental sequelae. Clinical signs of hypoglycaemia in neonatal infants are unspecific or even absent, and therefore, precise and accurate methods for the assessment of glycaemia are needed. Glycaemia measurement in newborns has some particularities like a very low limit of normal glucose concentration compared to adults and a large range of normal haematocrit values. Many bedside point-of-care testing (POCT) systems are available, but literature about their accuracy in newborn infants is scarce and not very convincing. In this retrospective study, we identified over a 1-year study period 1,324 paired glycaemia results, one obtained at bedside with one of three different POCT systems (Elite™ XL, Ascensia™ Contour™ and ABL 735) and the other in the central laboratory of the hospital with the hexokinase reference method. All three POCT systems tended to overestimate glycaemia values, and none of them fulfilled the ISO 15197 accuracy criteria. The Elite XL appeared to be more appropriate than Contour to detect hypoglycaemia, however with a low specificity. Contour additionally showed an important inaccuracy with increasing haematocrit. The bench analyzer ABL 735 was the most accurate of the three tested POCT systems. Both of the tested handheld glucometers have important drawbacks in their use as screening tools for hypoglycaemia in newborn infants. ABL 735 could be a valuable alternative, but the blood volume needed is more than 15 times higher than for handheld glucometers. Before daily use in the newborn population, careful clinical evaluation of each new POCT system for glucose measurement is of utmost importance.

Tenascin-C inactivation impacts lung structure and function beyond lung development.

Tenascin-C (TNC) is an extracellular matrix protein expressed at high levels during lung organogenesis. Later, TNC is only transiently de novo expressed to orchestrate tissue repair in pathological situations. We previously showed that TNC inactivation affects lung development and thus evaluated here the implications on lung function in newborn/adult mice. Respiratory function parameters were measured in anesthetized and mechanically ventilated wild-type (WT) and TNC-deficient mice at 5 (P5) and 90 (P90) days of age under basal conditions, as well as following high tidal volume (HTV) ventilation. At P5, TNC-deficient mice showed an increased static compliance (Cst) and inspiratory capacity (IC) relative to WT at baseline and throughout HTV. At P90, however, Cst and IC were only elevated at baseline. Control non-ventilated newborn and adult TNC-deficient mice showed similar lung morphology, but less alpha smooth muscle actin (α-SMA) around small airways. SMA + cells were decreased by 50% in adult TNC-deficient lungs and collagen layer thickened around small airways. Increased surfactant protein C (SP-C) and altered TGFß and TLR4 signaling pathways were also detected. Thus, TNC inactivation-related defects during organogenesis led to persisting functional impairment in adulthood. This might be of interest in the context of pulmonary diseases with thickened airway smooth muscle layer or ventilation heterogeneity, like asthma and COPD.