Ventilatory Support, Extubation, and Cerebral Perfusion Changes in Pre-Term Neonates: A Near Infrared Spectroscopy Study.

Early extubation is considered to be beneficial for pre-term neonates. On the other hand, premature extubation can cause lung derecruitment, compromised gas exchange, and need for reintubation, which may be associated with severe brain injury caused by sudden cerebral blood flow changes. We used near infrared spectroscopy (NIRS) to investigate changes in cerebral oxygenation (rScO2) and fractional tissue oxygen extraction (+) after extubation in pre-term infants. This is a single-center retrospective study of NIRS data at extubation time of all consecutive pre-term neonates born at our institution over a 1-year period. Comparison between subgroups was performed. Nineteen patients were included; average gestational age (GA) was 29.4 weeks. No significant change was noted in rScO2 and cFTOE after extubation in the whole population. GA and germinal matrix hemorrhage (GMH)-intraventricular hemorrhage (IVH) showed a significant change in rScO2 and cFTOE after extubation. A significant increase in cFTOE was noted in patients with previous GMH-IVH (+0.040; p = 0.05). To conclude, extubation per se was not associated with significant change in cerebral oxygenation and perfusion. Patients with a diagnosed GMH-IVH showed an increase in cFTOE, suggesting perturbation in cerebral perfusion suggesting further understanding during this challenging phenomenon. Larger studies are required to corroborate our findings.

Severe cellulitis from methicillin-resistant Staphylococcus aureus (MRSA) in a couple of preterm twins: a case report.

BACKGROUND: Preterms are at risk of systemic infections as the barrier function of their immature skin is insufficient. The long period of hospitalization and the huge number of invasive procedures represent a risk factor for complications. Among the nosocomial infections of the skin, methicillin-resistant Staphylococcus aureus (MRSA) is associated with significant morbidity and mortality. We report a clinical case of cellulitis and abscess in two preterm twins caused by MRSA in a tertiary level Neonatal Intensive Care Unit (NICU). CASE PRESENTATION: Two preterm female babies developed cellulitis from MRSA within the first month of extrauterine life. The first one (BW 990 g) showed signs of clinical instability 4 days before the detection of a hyperaemic and painful mass on the thorax. The second one (BW 1240 g) showed signs of clinical instability contextually to the detection of an erythematous, oedematous and painful area in the right submandibular space. In both cases the diagnosis of cellulitis was confirmed by ultrasound. A broad spectrum, multidrug antimicrobial therapy was administered till complete resolution. CONCLUSIONS: Due to the characteristic antibiotic resistance of MRSA and the potential complications of those infections in such delicate patients, basic prevention measures still represent the key to avoid the spreading of neonatal MRSA infections in NICUs, which include hand hygiene and strict precautions, as well as screening of patients for MRSA on admission and during hospital stay, routine prophylactic topical antibiotic of patients, enhanced environmental cleaning, cohorting and isolation of positive patients, barrier precautions, avoidance of ward crowding, and, in some units, surveillance, education and decolonization of healthcare workers and visiting parents.

Clinical course and peculiarities of Parechovirus and Enterovirus central nervous system infections in newborns: a single-center experience.

Parechovirus (HpEV) and Enterovirus (EV) infections in children mostly have a mild course but are particularly fearsome in newborns in whom they may cause aseptic meningitis, encephalitis, and myocarditis. Our study aimed to describe the clinical presentations and peculiarities of CNS infection by HpEV and EV in neonates. This is a single-center retrospective study at Istituto Gaslini, Genoa, Italy. Infants aged ≤ 30 days with a CSF RTq-PCR positive for EV or HpEV from January 1, 2022, to December 1, 2023, were enrolled. Each patient's record included demographic data, blood and CSF tests, brain MRI, therapies, length of stay, ICU admission, complications, and mortality. The two groups were compared to identify any differences and similarities. Twenty-five patients (15 EV and 10 HpEV) with a median age of 15 days were included. EV patients had a more frequent history of prematurity/neonatal respiratory distress syndrome (p = 0.021), more respiratory symptoms on admission (p = 0.012), and higher C-reactive protein (CRP) levels (p = 0.027), whereas ferritin values were significantly increased in HpEV patients (p = 0.001). Eight patients had a pathological brain MRI, equally distributed between the two groups. Three EV patients developed myocarditis and one HpEV necrotizing enterocolitis with HLH-like. No deaths occurred.  Conclusion: EV and HpEV CNS infections are not easily distinguishable by clinical features. In both cases, brain MRI abnormalities are not uncommon, and a severe course of the disease is possible. Hyper-ferritinemia may represent an additional diagnostic clue for HpEV infection, and its monitoring is recommended to intercept HLH early and initiate immunomodulatory treatment. Larger studies are needed to confirm our findings. What is Known: • Parechovirus and Enteroviruses are the most common viral pathogens responsible for sepsis and meningoencephalitis in neonates and young infants. • The clinical course and distinguishing features of Parechovirus and Enterovirus central nervous system infections are not well described. What is New: • Severe disease course, brain MRI abnormalities, and complications are not uncommon in newborns with Parechovirus and Enteroviruses central nervous system infections. • Hyper-ferritinemia may represent an additional diagnostic clue for Parechovirus infection and its monitoring is recommended.

Corrigendum: The new Italian registry of infantile thrombosis (RITI): a reflection on its journey, challenges and pitfalls.

[This corrects the article DOI: 10.3389/fped.2023.1094246.].

Early Extra-Uterine Growth Restriction in Very-Low-Birth-Weight Neonates with Normal or Mildly Abnormal Brain MRI: Effects on a 2-3-Year Neurodevelopmental Outcome.

Extra-uterine growth restriction (EUGR) is a common complication and a known risk factor for impaired development in very-low-birth-weight (VLBW) neonates. We report a population of 288 patients with no or with low-grade MRI lesions scanned at a term equivalent age (TEA) born between 2012 and 2018. Griffiths Mental Development Scale II (GMDS II) at 2 and 3 years, preterm complications and weight growth were retrospectively analyzed. EUGR was defined for weight z-score ˂ 10 percentile at TEA, 6 and 12 months of correct age or as z-score decreased by 1-point standard deviation (SDS) from birth to TEA and from TEA to 6 months. Multivariate analysis showed that a higher weight z-score at 6 months is protective for the global developmental quotient (DQ) at 2 years (OR 0.74; CI 95% 0.59-0.93; p = 0.01). EUGR at 6 months was associated with worse locomotor, personal/social, language and performance DQ at 2 years and worse language and practical reasoning DQ at 3 years. In conclusion, a worse weight z-score at 6 months of age seems to be an independent risk factor for significantly reduced GMDS in many areas. These results suggest that we should invest more into post-discharge nutrition, optimizing family nutritional education.

Optimizing haemoglobin measurements in VLBW newborns: Insights from a comparative retrospective study.

INTRODUCTION: Haemoglobin levels assessment is a crucial part of neonatal intensive care practice, the painful experience of repeated heel pricks and venepunctures blood sampling may negatively affect neonatal clinical course. To date the reliability of haemoglobin levels obtained by point-of-care testing (POCT) analysis if compared to standard blood cell count remains controversial. MATERIALS AND METHODS: Retrospective study conducted on all inborn premature infants (gestational age < 32 weeks) admitted to NICU of the IRCCS Giannina Gaslini Institute during the period May 2021-April 2023. We considered blood samplings occurred within the first 28 days of life recording the laboratory haemoglobin levels (Hblab) (reference method), the point-of-care haemoglobin levels (HbPOCT) (alternative method) and the type of puncture (arterial, venous and capillary). A Bland-Altman analysis was performed to evaluate the Hb agreement, it determines the bias (mean difference between the reference and alternative methods) and limits of agreement (LOA; lower, l-LOA; upper, u-LOA) of measures. An acceptable limit of agreement was 1 g/dl according to the existing literature. RESULTS: We considered 845 blood samplings from 189 enrolled patients. The comparison between the reference and the alternative method showed a good agreement for the capillary sampling technique with l-LOA of -0.717 (-0.776; -0.659) and u-LOA of 0.549 (0.490; 0.607), these results were not achievable with the other techniques, with LOAs over ±1 g/dl threshold (venous

Disruption of Cerebellar Granular Layer as a Consequence of Germinal Matrix Intraventricular Hemorrhage in Extreme Prematurity: An Acute Direct Mechanism Too?

Cerebellum is an important brain structure for the future development of motor, cognitive, and behavioral abilities in children. This structure undergoes its most significant growth during the third trimester of pregnancy. Prematurity gathers several risk factors for cerebellar impairment and underdevelopment, and among them is ventricular dilatation following germinal matrix intraventricular hemorrhage (GMH-IVH). In this report, we illustrate how this prevalent complication associated with prematurity may induce secondary cerebellar cortical damage. A premature male born by an emergency Caesarean section displayed massive GMH-IVH at brain ultrasound performed after three hours of extrauterine life and died after 18 hours of life, despite maximized vital support. We report a postmortem histopathological specimen of the cerebellar cortex showing the disruption of the external granular layer (EGL) by hemorrhagic content flowing from the supratentorial ventricles into the fourth ventricle and cisterna magna. The expansion of the ventricular system and the presence of blood in the lateral ventricles can cause inflammation and damage to the cerebellar gyri. Experimental models have shown a thinning of the EGL, suggesting that blood surrounding the cerebellum has a harmful action. Additionally, a sudden influx of cerebrospinal fluid from the lateral ventricles may directly contribute to cerebellar damage, indicating that this may be another way in which the cerebellar gyri are impaired during acute severe GMH-IVH. This is the first histopathologically confirmed case of acute disruption in the cerebellar cortex during a GMH-IVH in a premature baby.

Near-Infrared Spectroscopy and Continuous Glucose Monitoring During Therapeutic Hypothermia.

The relation between glucose homeostasis and cerebral blood flow (CBF) and their correlation to outcome in neonatal hypoxic-ischemic encephalopathy are unclear. In this short communication, we tried to determine whether changes in regional oxygen saturation (rSO2), as measured by near-infrared spectroscopy (NIRS), in asphyxiated neonates during therapeutic hypothermia correlate with the glycemic profile and whether NIRS and continuous glucose monitoring are useful in identifying cooled asphyxiated neonates at high risk of brain injury. Although there was no correlation between blood glucose and CBF in this small cohort of asphyxiated neonates (13 neonates admitted to the IRCCS Giannina Gaslini NICU in Genoa between March and September 2021), after 24 h of life, increased rSO2 and glucose variability with a tendency toward hyperglycemia distinguished neonates who subsequently acquired brain injury from those who did not. As a result of this, it may be possible to monitor cerebral perfusion and metabolic changes as soon as possible after delivery in order to prevent poorer outcomes.

Point-of-care brain ultrasound and transcranial doppler or color-coded doppler in critically ill neonates and children.

Point-of-care brain ultrasound and transcranial doppler or color-coded doppler is being increasingly used as an essential diagnostic and monitoring tool at the bedside of critically ill neonates and children. Brain ultrasound has already established as a cornerstone of daily practice in the management of the critically ill newborn for diagnosis and follow-up of the most common brain diseases, considering the easiness to insonate the brain through transfontanellar window. In critically ill children, doppler based techniques are used to assess cerebral hemodynamics in acute brain injury and recommended for screening patients suffering from sickle cell disease at risk for stroke. However, more evidence is needed regarding the accuracy of doppler based techniques for non-invasive estimation of cerebral perfusion pressure and intracranial pressure, as well as regarding the accuracy of brain ultrasound for diagnosis and monitoring of acute brain parenchyma alterations in children. This review is aimed at providing a comprehensive overview for clinicians of the technical, anatomical, and physiological basics for brain ultrasonography and transcranial doppler or color-coded doppler, and of the current status and future perspectives of their clinical applications in critically ill neonates and children. CONCLUSION: In critically ill neonates, brain ultrasound for diagnosis and follow-up of the most common cerebral pathologies of the neonatal period may be considered the standard of care. Data are needed about the possible role of doppler techniques for the assessment of cerebral perfusion and vasoreactivity of the critically ill neonate with open fontanelles. In pediatric critical care, doppler based techniques should be routinely adopted to assess and monitor cerebral hemodynamics. New technologies and more evidence are needed to improve the accuracy of brain ultrasound for the assessment of brain parenchyma of critically ill children with fibrous fontanelles. WHAT IS KNOWN: • In critically ill neonates, brain ultrasound for early diagnosis and follow-up of the most common cerebral and neurovascular pathologies of the neonatal period is a cornerstone of daily practice. In critically ill children, doppler-based techniques are more routinely used to assess cerebral hemodynamics and autoregulation after acute brain injury and to screen patients at risk for vasospasm or stroke (e.g., sickle cell diseases, right-to-left shunts). WHAT IS NEW: • In critically ill neonates, research is currently focusing on the use of novel high frequency probes, even higher than 10 MHz, especially for extremely preterm babies. Furthermore, data are needed about the role of doppler based techniques for the assessment of cerebral perfusion and vasoreactivity of the critically ill neonate with open fontanelles, also integrated with a non-invasive assessment of brain oxygenation. In pediatric critical care, new technologies should be developed to improve the accuracy of brain ultrasound for the assessment of brain parenchyma of critically ill children with fibrous fontanelles. Furthermore, large multicenter studies are needed to clarify role and accuracy of doppler-based techniques to assess cerebral perfusion pressure and its changes after treatment interventions.

The Transport of Respiratory Distress Syndrome Twin Newborns: The 27-Year-Long Experience of Gaslini Neonatal Emergency Transport Service Using Both Single and Double Ventilators.

OBJECTIVE: Twin pregnancy rates have increased in the past 30 years. We describe the experience of the Neonatal Emergency Transport Service of the Gaslini Hospital, Genoa, Italy, in the transport of twin newborns. METHODS: This was a retrospective study (1996-2021); 7,852 medical charts from the Neonatal Emergency Transport Service were reviewed. We included all twin newborns who were transported with respiratory distress syndrome in the study. We split the included patients into 2 groups (group A and group B) based on if they were simultaneously ventilated by a single ventilator or by 2 different ventilators, and then each group was split by the different types of ventilation (nasal continuous positive airway pressure or intermittent positive pressure ventilation). The pH level, base excess, O2 saturation, Pco2, body temperature, plasma glucose, and Transport Risk Index of Physiologic Stability score were recorded at departure and arrival. RESULTS: One hundred thirty-six patients were included (68 pairs of twins); group A consisted of 92 newborns and group B 44 newborns. Although some significant differences were observed (statistic), none of these had real clinical significance. CONCLUSION: Transporting respiratory distress syndrome twin newborns is challenging. Our study provided a 27-year experience in the field. Transporting twins by a single ventilator is possible, but, in our opinion, using 2 ventilators mounted on the same transport module is the best possible choice in terms of clinical performance, logistics, and cost.

The new Italian registry of infantile thrombosis (RITI): A reflection on its journey, challenges and pitfalls.

Introduction: Thrombotic events in neonates and children represent a rare although severe occurrence in view of the associated risk of mortality and sequelae. Quality evidence is limited in this field, and registry studies provide an essential base for research. The aim of this paper is to present the new Italian Registry of Infantile Thrombosis (RITI), set it into the scene of international thrombosis and stroke registries, and provide some insight on the challenges associated with registry management. Methods: We present the detailed structure and content of the new RITI registry, a brief overview of its main data, and a reflection on its features, pitfalls and the main challenges related to its management. Results: The RITI, initially started in 2007 and officially re-launched in 2017 after structural modifications, is a non-interventional retrospective and prospective registry study collecting data on neonatal and pediatric patients (0-18 years) who experienced a systemic or cerebral thrombotic event in Italy. The RITI is managed by a multidisciplinary team with expertise in pediatric thrombosis, and participation is open to all Italian physicians, on a voluntary basis. The overall aim of the registry is to acquire new evidence to better characterize the population of children with thrombotic events and improve their management and outcome. 48 Italian pediatric and intensive care units are actively involved in the RITI, including 85 medical doctors from 16 Italian regions. A total of 1,001 neonates and children affected by cerebral or systemic thrombosis have been enrolled. Discussion: The RITI is one of the largest available European registries of neonatal and pediatric thrombosis. National registries like the RITI represent a model for the study of rare conditions based on multidisciplinary and multicenter collaboration, aimed at overcoming the limitations due to small populations of patients, and creating a network of experts for patient referral and continuous education. Moreover, registry studies have a pivotal role in the research on pediatric thrombosis, due to the limited feasibility of high-quality studies. In our experience, the main critical stages, pitfalls and challenges in registry management include adequate registry designing, diffusion, data completeness and quality control.

Influence of isolated low-grade intracranial haemorrhages on the neurodevelopmental outcome of infants born very low birthweight.

AIM: To determine whether isolated low-grade germinal matrix-intraventricular haemorrhages (LG-GMH-IVH) and low-grade punctate cerebellar haemorrhages (LG-CBH) contribute to the neurodevelopment of infants born preterm with very low birthweight (VLBW). METHOD: A prospective observational cohort study was conducted on infants born with VLBW hospitalized from January 2012 to July 2017 who had undergone serial cranial ultrasounds since birth and magnetic resonance susceptibility-weighted imaging of the brain at term-corrected age. Only those with VLBW carrying isolated LG-GMH-IVH (grades 1 or 2) or isolated LG-CBH (punctate cerebellar haemorrhages ≤4 mm in diameter) or absence of lesions (no-lesion) were enrolled and followed up to 3 years. The Griffiths Mental Development Scales, Extended and Revised version (GMDS-ER), were used to assess neurodevelopment, considering unsatisfactory scores less than 85. Behaviour, according to the criteria of the International Classification of Diseases, 10th Revision, and rehabilitation data were noted. RESULTS: Two-hundred and forty infants with VLBW were enrolled: 34 with LG-GMH-IVH, 17 with LG-CBH, and 189 as no-lesion. The LG-GMH-IVH and LG-CBH groups scored worse than the no-lesion group on all GMDS-ER scores for 1 year, 2 years, and 3 years. The LG-CBH group scored lower than the LG-GMH-IVH group for total GMDS-ER scores at 1 year and 2 years but not at 3 years. At 3 years, compared with the LG-CBH group, those with LG-GMH-IVH received less and later physical therapy, with more frequent attention problems. The odds ratio for unsatisfactory GMDS-ER scores corrected for gestational age was 5.75 for LG-CBH (95% confidence interval 1.92-17.25; p = 0.002) and 2.67 for LG-GMH-IVH (95% confidence interval 1.16-6.13; p = 0.02). INTERPRETATION: Low-grade haemorrhages affect the neurodevelopment of very-low-birthweight infants. Early rehabilitation might have contributed to their development.

Parent-Administered Oral Stimulation in Preterm Infants: A Randomized, Controlled, Open-Label Pilot Study.

OBJECTIVE: The study aimed to assess whether there was any difference in the transition time to full oral feedings between parent-administered and professional-administered premature infant oral motor intervention (PIOMI). The study also evaluated parental satisfaction with performing the intervention through an open-ended questionnaire. STUDY DESIGN: A single-center, randomized, controlled, open-label pilot study was carried on between March 2017 and May 2019. A total of 39 infants born ≤32 weeks' gestation were randomly assigned to either parent-performed or professionally performed oral stimulation. The oral stimulation was performed once a day for seven consecutive days between 31 and 32 weeks' postmenstrual age. RESULTS: There was no statistically significant difference in transition time, weight gain, or length of hospital stay between the two groups. No adverse events were observed. Parents' satisfaction was high, and their active involvement enhanced their perception of adequacy to care for their infant. CONCLUSION: Following adequate training, a parent-administered PIOMI may be considered in preterm infants to reduce the transition time to full oral feeding and enhance the direct involvement of parents in neonatal care. KEY POINTS: · No difference in transition time between parent-performed and professional-performed PIOMI.. · PIOMI may be delivered by parents following appropriate training.. · Active involvement of parents may improve the parent-infant bonding..

Neurodevelopmental consequences of preterm punctate white matter lesions: a systematic review.

OBJECTIVES: To evaluate punctate white matter lesion (PWML) influence in preterm infants on the long-term neurodevelopmental outcome (NDO). METHODS: PubMed and EMBASE were searched from January 1, 2000, to May 31, 2021. Studies were included in which PWML in preterm infants on MRI around term-equivalent age (TEA) and NDO at ≥12 months were reported. Study and patient characteristics and NDO on motor, cognitive, and behavioral domains were extracted. The quality of studies was assessed using the Cochrane-approved Quality in Prognosis Studies tool. RESULTS: This analysis included nine studies with a total of 1655 patients. Mean incidence of isolated PWML was 22.1%. All studies showed a relationship between PWML and motor delay. Two studies found a significant correlation between cognitive and behavioral outcomes and PWML. Number and PWML location are related to severity and impairment types. LIMITATIONS: PWML were not always separately described from generalized WMI, only studies with imaging around TEA were included, and studies were heterogenic in design and quality. CONCLUSIONS: PWML is common in preterm infants and predictive of adverse NDO, in particular on motor outcomes and less on cognitive and behavioral outcomes. The type and severity of impairments are related to the number and location of PMWL. IMPACT: PWML is common in preterm infants and seems predictive of adverse NDO. DWI and SWI MRI sequences are informative because the different patterns suggest a difference in the underlying pathology. The type and severity of impairments are related to the number and location of PMWL. Our review can inform clinicians and parents about the NDO of preterm infants with a diagnosis of PWML. Prospective neuroimaging case-control cohort studies are recommended.

Intubation Rate Evaluation of Inborn Versus Outborn Premature Newborns Affected by Respiratory Distress Syndrome: Impact of Neonatal Transport.

OBJECTIVE: The aim of this study was to compare the management of preterm newborns with respiratory distress both in the delivery room and during transportation. METHODS: We retrospectively evaluated the intubation rate in preterm newborns (inborn vs. outborn), gestational age (GA) < 34 weeks, admitted to the Gaslini neonatal intensive care unit, Genoa, Italy (January 2019-December 2020). RESULTS: A total of 251 newborns were included (202 inborn and 49 outborn). The intubation rate was significantly higher in outborn newborns (69.4% vs. 42.1%, P = .001) in the GA 30- to 34- week subgroup (63.2% vs 20.6%, P = .001) but not in the GA < 30-week subgroup (90.9% vs. 81.7%, P = .68). CONCLUSION: Although the medical staff members involved in neonatal transport were the same who work both in the neonatal intensive care unit and the delivery room, we found a significantly higher intubation rate in outborn newborns, probably due to the transport itself. It is fundamental to encourage in utero transportation to reduce the risk linked to invasive ventilation due to neonatal transportation.

Proteomic profiling of human amnion for preterm birth biomarker discovery.

Spontaneous preterm birth (PTB) complicates about 12% of pregnancies worldwide, remaining the main cause of neonatal morbidity and mortality. Spontaneous preterm birth PTBs is often caused by microbial-induced preterm labor, mediated by an inflammatory process threatening both maternal and newborn health. In search for novel predictive biomarkers of PTB and preterm prelabor rupture of the membranes (pPROM), and to improve understanding of infection related PTB, we performed an untargeted mass spectrometry discovery study on 51 bioptic mid zone amnion samples from premature babies. A total of 6352 proteins were identified. Bioinformatics analyses revealed a ranked core of 159 proteins maximizing the discrimination between the selected clinical stratification groups allowing to distinguish conditions of absent (FIR 0) from maximal Fetal Inflammatory Response (FIR 3) stratified in function of Maternal Inflammatory Response (MIR) grade. Matrix metallopeptidase-9 (MMP-9) was the top differentially expressed protein. Gene Ontology enrichment analysis of the core proteins showed significant changes in the biological pathways associated to inflammation and regulation of immune and infection response. Data suggest that the conditions determining PTB would be a transversal event, secondary to the maternal inflammatory response causing a breakdown in fetal-maternal tolerance, with fetal inflammation being more severe than maternal one. We also highlight matrix metallopeptidase-9 as a potential predictive biomarker of PTB that can be assayed in the maternal serum, for future investigation.

The Role of Muscle Biopsy in Diagnostic Process of Infant Hypotonia: From Clinical Classification to the Genetic Outcome.

The role of muscle biopsy in the diagnostic workup of floppy infants is controversial. Muscle sampling is invasive, and often, results are not specific. The rapid expansion of genetic approach has made the muscle histopathology analysis less crucial. This study aims to assess the role and efficacy of muscle histopathology in the diagnostic algorithm of hypotonia in early infancy through a retrospective analysis of 197 infants who underwent muscle biopsy in their first 18 months of life. Data analysis revealed that 92/197 (46.7%) of muscle biopsies were non-specific (80) or normal (12), not allowing a specific diagnosis. In 41/197 (20.8%) cases, biopsy suggested a metabolic or mitochondrial myopathy, while in 23/197 cases (11.7%), we found evidence of muscular dystrophy. In 19/197 cases (9.7%), histopathology characteristics of a congenital myopathy were reported. In 22/197 cases (11.7%), the histopathological study indicated presence of a neurogenic damage. Overall, 46 diagnoses were then achieved by oriented genetic tests. Muscle biopsy results were consistent with genetic results in 90% of cases. Diagnostic algorithms for the diagnosis of a floppy infant are largely missing. Muscle biopsy alone can lead to a diagnosis, help the clinician in the choice of a genetic test, or even modify a diagnosis made previously.

Nosological Differences in the Nature of Punctate White Matter Lesions in Preterm Infants.

Background: The pathogenesis of punctuate white matter lesions (PWMLs), a mild form of white matter damage observed in preterm infants, is still a matter of debate. Susceptibility-weighted imaging (SWI) allows to differentiate PWMLs based on the presence (SWI+) or absence (SWI-) of hemosiderin, but little is known about the significance of this distinction. This retrospective study aimed to compare neuroradiological and clinical characteristics of SWI+ and SWI- PWMLs. Materials and Methods: MR images of all VLBW infants scanned consecutively at term-equivalent age between April 2012 and May 2018 were retrospectively reviewed, and infants with PWMLs defined as small areas of high T1 and/or low T2 signal in the periventricular white matter were selected and included in the study. Each lesion was analyzed separately and characterized by localization, organization pattern, and distance from the lateral ventricle. Clinical data were retrieved from the department database. Results: A total of 517 PWMLs were registered in 81 patients, with 93 lesions (18%) visible on SWI (SWI+), revealing the presence of hemosiderin deposits. On univariate analysis, compared to SWI- PWML, SWI+ lesions were closer to the ventricle wall, more frequently organized in linear pattern and associated with lower birth weight, lower gestational age, lower admission temperature, need for intubation, bronchopulmonary dysplasia, retinopathy of prematurity, and presence of GMH-IVH. On multivariate analysis, closer distance to the ventricle wall on axial scan and lower birth weight were associated with visibility of PMWLs on SWI (p = 0.003 and p = 0.0001, respectively). Conclusions: Our results suggest a nosological difference between SWI+ and SWI- PWMLs. Other prospective studies are warranted to corroborate these observations.

Neonatal Hypoglycemia and Brain Vulnerability.

Neonatal hypoglycemia is a common condition. A transient reduction in blood glucose values is part of a transitional metabolic adaptation following birth, which resolves within the first 48 to 72 h of life. In addition, several factors may interfere with glucose homeostasis, especially in case of limited metabolic stores or increased energy expenditure. Although the effect of mild transient asymptomatic hypoglycemia on brain development remains unclear, a correlation between severe and prolonged hypoglycemia and cerebral damage has been proven. A selective vulnerability of some brain regions to hypoglycemia including the second and the third superficial layers of the cerebral cortex, the dentate gyrus, the subiculum, the CA1 regions in the hippocampus, and the caudate-putamen nuclei has been observed. Several mechanisms contribute to neuronal damage during hypoglycemia. Neuronal depolarization induced by hypoglycemia leads to an elevated release of glutamate and aspartate, thus promoting excitotoxicity, and to an increased release of zinc to the extracellular space, causing the extensive activation of poly ADP-ribose polymerase-1 which promotes neuronal death. In this review we discuss the cerebral glucose homeostasis, the mechanisms of brain injury following neonatal hypoglycemia and the possible treatment strategies to reduce its occurrence.