Assessment of hemodynamic dysfunction in septic newborns by functional echocardiography: a systematic review.

BACKGROUND: Neonatal sepsis remains a leading cause of mortality in neonatal units. Neonatologist-performed echocardiography (NPE) offers the potential for early detection of sepsis-associated cardiovascular dysfunction. This review examines available echocardiographic findings in septic neonates. METHODS: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed prospective observational, cross-sectional, case control, and cohort studies on septic newborns with echocardiographic assessments from PubMed, Scopus and Embase. Quality assessment employed the Newcastle-Ottawa Scale, with results analyzed descriptively. RESULTS: From an initial pool of 1663 papers, 12 studies met inclusion criteria after relevance screening and eliminating duplicates/excluded studies. The review encompassed 438 septic newborns and 232 controls. Septic neonates exhibited either increased risk of pulmonary hypertension or left ventricular diastolic dysfunction, and a warm shock physiology characterized by higher cardiac outputs. DISCUSSION: The included studies exhibited heterogeneity in sepsis definitions, sepsis severity scores, echocardiographic evaluations, and demographic data of newborns. Limited sample sizes compromised analytical interpretability. Nonetheless, this work establishes a foundation for future high-quality echocardiographic studies. CONCLUSION: Our review confirms that septic neonates show significant hemodynamic changes that can be identified using NPE. These findings underscore the need for wider NPE use to tailor hemodynamics-based strategies within this population. IMPACT: 1. Our study emphasizes the value of neonatologist-performed echocardiography (NPE) as a feasible tool for identifying significant hemodynamic changes in septic neonates. 2. Our study underscores the importance of standardized echocardiographic protocols and frequent monitoring of cardiac function in septic neonates. 3. The impact of the study lies in its potential to increase researchers' awareness for the need for more high-quality echocardiographic data in future studies. By promoting wider use of NPE, neonatologists can more accurately assess the hemodynamic status of septic newborns and tailor treatment approaches, potentially improving patient outcomes.

The role of point-of-care ultrasound in the management of neonates with congenital diaphragmatic hernia.

In the last few years, current evidence has supported the use of point-of-care ultrasound (POCUS) for a number of diagnostic and procedural applications. Considering the valuable information that POCUS can give, we propose a standardized protocol for the management of neonates with a congenital diaphragmatic hernia (CDH-POCUS protocol) in the neonatal intensive care unit. Indeed, POCUS could be a valid tool for the neonatologist through the evaluation of 1) cardiac function and pulmonary hypertension; 2) lung volumes, postoperative pleural effusion or pneumothorax; 3) splanchnic and renal perfusion, malrotations, and/or signs of necrotizing enterocolitis; 4) cerebral perfusion and eventual brain lesions that could contribute to neurodevelopmental impairment. In this article, we discuss the state-of-the-art in neonatal POCUS for which concerns congenital diaphragmatic hernia (CDH), and we provide suggestions to improve its use. IMPACT: This review shows how point-of-care ultrasound (POCUS) could be a valid tool for managing neonates with congenital diaphragmatic hernia (CDH) after birth. Our manuscript underscores the importance of standardized protocols in neonates with CDH. Beyond the well-known role of echocardiography, ultrasound of lungs, splanchnic organs, and brain can be useful. The use of POCUS should be encouraged to improve ventilation strategies, systemic perfusion, and enteral feeding, and to intercept any early signs related to future neurodevelopmental impairment.

Coagulation profiles and percentiles in neonates with hypoxic-ischemic encephalopathy undergoing therapeutic hypothermia: A step toward more accurate transfusion thresholds.

BACKGROUND: In the literature, there are no studies about the transfusion threshold for neonates with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH). In order to facilitate accurate interpretation of coagulation results in these neonates, we aimed to generate specific reference intervals in this specific population. METHODS: This retrospective study included all HIE neonates admitted from 2014 to 2022 to undergo TH. All infants during TH underwent blood exams, including the coagulation profile. Our primary outcome was to assess the estimates of the 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentiles for each parameter on admission (before transfusion). By the receiver operating characteristic (ROC) analysis, the area under the ROC curve (AUC) and the best cut-off point were used to evaluate the ability of the prothrombin time expressed as international normalized ratio (PT-INR) to predict the risk of any bleeding. RESULTS: A total of 143 infants were included in this study. On admission, the median fibrinogen value was 205 mg/dL, prothrombin time 18.6 seconds, PT-INR 1.50, activated partial thromboplastin time 38.3 seconds, thrombin time 18.6 seconds, antithrombin 57.0%. The optimal cut-off of PT-INR in predicting the risk of any bleeding was greater than 1.84 (AUC .623, p = .024). CONCLUSION: For the first time, we proposed the percentiles of coagulation parameters in our cohort of neonates with HIE. Furthermore, we found that a PT-INR greater than 1.84 can significantly predict the risk of any bleeding. Further studies are needed to determine if a restrictive versus a liberal transfusion approach can be equally safer for these high-risk infants.

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.

Perinatal asphyxia does not influence presepsin levels in neonates: A prospective study.

AIM: To compare Presepsin (presepsin) levels in plasma and urine of uninfected newborn infants with perinatal asphyxia with those of controls. METHODS: In this prospective study, we enrolled 25 uninfected full-term infants with perinatal asphyxia and 19 controls. We measured presepsin levels in whole blood or urine. In neonates with perinatal asphyxia, we compared presepsin levels in blood and urine at four time points. RESULTS: In neonates with perinatal asphyxia, blood and urinary presepsin levels matched each other at any time point. At admission, the median presepsin value in blood was similar in both groups (p = 0.74), while urinary levels were higher in hypoxic neonates (p = 0.05). Perinatal asphyxia seemed to increase serum CRP and procalcitonin levels beyond normal cut-off but not those of presepsin. CONCLUSION: In uninfected neonates with perinatal asphyxia, median blood and urinary presepsin levels matched each other at any point in the first 72 h of life and seemed to be slightly affected by the transient renal impairment associated with perinatal hypoxia in the first 12 h of life. Perinatal asphyxia did not influence presepsin levels within the first 72 h of life, while those of CRP and procalcitonin increased.

Neonatal herpes simplex virus infection: From the maternal infection to the child outcome.

This review examines the recent literature on the management of herpes simplex virus (HSV) infections in neonates. We summarized the three clinical categories of maternal HSV infection during pregnancy (primary first episode, nonprimary first episode, or recurrent episode) and the mechanisms of fetal damage. Considering when the transmission of the infection from the mother to the fetus/newborn occurs, three types of neonatal infection can be distinguished: intrauterine infection (5% of cases), postnatal infection (10% of cases), and perinatal infections (85% of cases). Neonatal presentation could range from a limited disease with skin, eye, and mouth disease to central nervous system disease or disseminated disease: the treatment with acyclovir should be tailored according to symptoms and signs of infection, and virological tests. These children need a multidisciplinary follow-up, to timely intercept any deviation from normal neurodevelopmental milestones. Prevention strategies remain a challenge, in the absence of an available vaccine against HSV.

Decreased incidence of late-onset sepsis during the SARS-CoV-2 pandemic in Italy: a multicentric study on a cohort of infants requiring major surgery.

Changes in the organization of the clinical care wards, requested by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic, have influenced the environmental circulation of other pathogens. The implementation of prevention procedures may have led to a decrease in the incidence of healthcare-associated infections. We aimed to investigate the impact of prevention and control measures for preventing the COVID-19 spread on the incidence of bacterial sepsis and invasive fungal infections in neonates and infants requiring major surgery. We compared the incidence of bacterial and fungal sepsis and their risk factors observed before the SARS-CoV-2 pandemic (from 01/10/2018 to 29/02/2020) with those observed during the pandemic (from 01/03/2020 to 07/05/2021) in 13 level III Neonatal Intensive Care Units in Italy, through a secondary analysis of data, collected during a prospective multicenter study (REF). The patients enrolled were infants within three months of life, hospitalized in the two periods in the participating centers to undergo major surgery. Among 541 enrolled patients, 324 (59.9%) were born in the pre-pandemic period and 217 (40.1%) during the pandemic. The incidence density (ID) of any infection in the pre-pandemic period was 16.0/1000 patient days versus 13.6/1000 patient days in the pandemic period (p < 0.001). One hundred and forty-five (145/324; 44.8%) patients developed at least one episode of bacterial sepsis in the pre-pandemic period, versus 103/217 (31.8%) patients, during the pandemic (p = 0.539). Concerning fungal sepsis, 12 (3.7%) patients had one episode in the pre-pandemic period versus 11 (5.1%) patients during the pandemic (p = 0.516). The most significant differences observed in the use of healthcare procedures were the reduction of CVC days, the reduced use of antibiotics pre-surgery, and that of proton pump inhibitors during the SARS-CoV-2 pandemic compared with the previous period. CONCLUSIONS: In our cohort of patients with major surgical needs, the reduction of CVC days, pre-surgery antibiotics administration, and current use of proton pump inhibitors, during the SARS-CoV-2 pandemic, led to a decrease in the incidence of late-onset sepsis. WHAT IS KNOWN: • Most cases of late-onset sepsis in neonates are referred to as central line-associated bloodstream infections. • In adults, the COVID-19 outbreak negatively influenced healthcare-associated infection rates and infection clusters within hospitals. WHAT IS NEW: • In neonates and infants undergoing major surgery the incidence density of infections was lower in the pandemic period than before. • The most significant differences observed in the use of healthcare procedures were the reduction of CVC days, the reduced use of antibiotics before surgery, and that of proton pump inhibitors during the pandemic compared with previously.

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.

Hemodynamic Assessment of a Large Pulmonary Arteriovenous Malformation in a Neonate: Case Report and Review of Literature.

Herein we report the case of a neonate with a prenatally diagnosed large pulmonary arteriovenous malformation, managed with minimally invasive hemodynamic monitoring in our Neonatal Intensive Care Unit. The combination of Near-Infrared Spectroscopy and Pressure Recording Analytical Method could guide neonatal management of critical cases of vascular anomalies: immediate data are offered to clinicians, from which therapeutic decisions such as timing of surgical resection are made to achieve a positive outcome. We also systemically collected and summarized information on patients' characteristics of previous cases reported in literature to data, and we compared them to our case.

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..

Intrafetal Laser Therapy Is a Feasible Treatment for Different Fetal Conditions: A Systematic Review.

INTRODUCTION: Over the past years, intrafetal laser (IFL) therapy has been increasingly used in the management of various prenatal conditions. The aim of our research was to clarify the effectiveness and safety of this technique. METHODS: A systematic review of the literature was carried out using MEDLINE/PubMed over a period of 20 years (2001-2021). RESULTS: A total of forty-one articles were selected in the literature search, including 194 cases of twin reversed arterial perfusion (TRAP) sequence, 56 cases of bronchopulmonary sequestrations (BPSs), 5 cases of placental chorioangiomas (PCA), 11 cases of sacrococcygeal teratoma (SCT), and 103 cases of embryo reduction (ER) managed using IFL. In TRAP sequence, perfusion of the acardiac twin was successfully disrupted in all cases. However, preterm premature rupture of membranes (P-PROMs) occurred in 6 out of 79 pregnancies (7.5%), and preterm birth (PTB) occurred in 36 out of 122 pregnancies (29.5%). In BPS, IFL was successfully performed in all cases with no significant fetal-maternal complications. The rates of P-PROM and PTB were, respectively, 3.2% and 12.5%. All PCA IFL-treated cases resulted in successful pregnancy outcomes; no cases of P-PROM were reported, but the rate of PTB reached a peak of 60% due to complications such as severe fetal growth restriction and fetal Doppler abnormalities. In SCT cases, complete cessation of blood flow was achieved in 4 patients (36.4%); P-PROM occurred in 2 cases (18.2%), whereas the rate of PTB was 87.5%. In ER, no intraoperative or major maternal complications were described in the literature. Rates of miscarriage and PTB differed between initial trichorionic triamniotic and dichorionic triamniotic triplet pregnancies. CONCLUSION: Our analysis suggests that IFL is a safe and feasible technique for the management of different fetal conditions. However, the overall risk of PTB, and its related morbidity and mortality, ranges from 12.5% in BPS to 87.5% in SCT IFL-treated cases. This information could aid in decision-making during prenatal counseling. However, final perinatal outcome depends on the severity of the disease itself.

Severe herpes virus 6 interstitial pneumonia in an infant with three variants in genes predisposing to lung disease.

Infections due to human herpesvirus 6 (HHV-6) are frequent during early childhood. Usually, they have a favorable clinical course. Conversely, HHV-6 congenital infections occur in about 1% of neonates and may present with more severe clinical pictures. HHV-6 can be found in lung tissues and bronchoalveolar lavage (BAL) samples from patients with pneumonia and in immunocompromised patients can cause mild to severe pneumonia. In neonates, the role of HHV-6 in the genesis of severe pneumonia is poorly defined still now. We describe a healthy infant with a late-onset (15 days of life) severe interstitial pneumonia and heavy HHV-6 genome load, persistently detected in its BAL fluid. The baby underwent high-frequency oscillatory ventilation, hydroxychloroquine, steroids, and ganciclovir for 6 weeks and at 9 months she died. Next-generation sequencing of genes known to cause neonatal respiratory insufficiency revealed the presence of a "probably pathogenetic" heterozygous variant in the autosomal recessive DRC1 gene, a heterozygous variant of unknown significance (VUS) in the autosomal recessive RSPH9 gene, and a heterozygous VUS in the autosomal recessive MUC5B gene. HHV-6 infection should be considered in the differential diagnosis of late-onset severe respiratory distress in neonates and the co-occurrence of genetic predisposing factors or modifiers should be tested by specific molecular techniques. The intensity of HHV-6 genome load in BAL fluid could be an indicator of the response to antiviral therapy.

Expanding the spectrum of congenital myopathies: prenatal onset with extreme hyperextension of the neck.

We describe the case of a male newborn presenting with a prenatal diagnosis of persistent hyperextension of the fetal neck and severe hypotonia and respiratory insufficiency at birth. Facial weakness, increased serum creatine kinase levels, and abnormal feeding, together with other signs, such as severe contractures, also classically associated with congenital myopathies prompted to perform a muscle biopsy showing internal rods suggestive of a possible nemaline myopathy. These findings suggest that a careful neurological examination should be performed in infants with persistent hyperextension of the fetal neck to exclude weakness and a possible underlying muscle disorder.

A novel homozygous variant in JAM3 gene causing hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts (HDBSCC) with neonatal onset.

BACKGROUND: JAM3 gene, located on human chromosome 11q25, encodes a member of the junctional adhesion molecule (JAM) family. Mutations of this gene are associated with hemorrhagic destruction of the brain, subependymal calcification, and congenital cataracts (HDBSCC). CASE REPORT: Herein, we present a newborn male with a prenatal suspicion of bilateral cataracts but without fetal ultrasound findings of cortical malformations. He was postnatally diagnosed with a clinical picture of HDBSCC and Early-onset Developmental and Epileptic Encephalopathy (DEE), associated to a homozygous variant of JAM3 gene. CONCLUSION: Identification of this variant in affected individuals has implications for perinatal and postnatal management and genetic counseling. To the best of our knowledge, this is the first case reported of a child with a JAM3 variant in Italy, from a different ethnic background than the other reported children until now (Saudi Arabian, Turkish, Afghani, and Moroccan origin). JAM3 screening could be requested in prenatal diagnosis of fetal congenital cataracts and included in Next-Generation DNA Sequencing panels.

The Emerging Role of Presepsin (P-SEP) in the Diagnosis of Sepsis in the Critically Ill Infant: A Literature Review.

Sepsis causes high rates of morbidity and mortality in NICUs. The estimated incidence varies between 5 and 170 per 1000 births, depending on the social context. In very low birth-weight neonates, the level of mortality increases with the duration of hospitalization, reaching 36% among infants aged 8-14 days and 52% among infants aged 15-28 days. Early diagnosis is the only tool to improve the poor prognosis of neonatal sepsis. Blood culture, the gold standard for diagnosis, is time-consuming and poorly sensitive. C-reactive protein and procalcitonin, currently used as sepsis biomarkers, are influenced by several maternal and fetal pro-inflammatory conditions in the perinatal age. Presepsin is the N-terminal fragment of soluble CD14 subtype (sCD14-ST): it is released in the bloodstream by monocytes and macrophages, in response to bacterial invasion. Presepsin seems to be a new, promising biomarker for the early diagnosis of sepsis in neonates as it is not modified by perinatal confounding inflammatory factors. The aim of the present review is to collect current knowledge about the role of presepsin in critically ill neonates.

Therapeutic Hypothermia and Leukocytosis in Newborns: An Unusual Association.

Therapeutic hypothermia is a standardized intervention for the treatment of moderate-severe hypoxic-ischemic encephalopathy in newborns with gestational age ≥35 weeks. Several complications have been described. Our aim was to report a case of leukocytosis, for the first time in the literature, in a term newborn who underwent therapeutic hypothermia.

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) in twin sisters with two CD36 frameshift mutations.

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinical radiological syndrome with good prognosis that affects mainly children or young adults. We describe two cases of MERS, associated with echovirus 6 and influenza A infection, in two twin sisters, at the age of 4 years. Genetic analysis was performed; next exome sequencing was performed on twins to disclose the eventual causative gene. Two different frameshift mutations in the CD36 gene [NM_000072] were found in both twins and confirmed by Sanger sequencing. To best of our knowledge, we report an association between CD36 mutation and MERS. We think that this relation between CD36 and inflammation has had a crucial role in the same callosal alteration during viral disease in the twin sister with the same gene mutation.

Vertical Transmission of SARS-CoV-2 (COVID-19): Are Hypotheses More than Evidences?

In spite of the increasing, accumulating knowledge on the novel pandemic coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), questions on the coronavirus disease-2019 (COVID-19) infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending and have not been addressed so far. SARS-CoV-2, a RNA single-stranded virus, has been detected in the amniotic fluid, in the cord blood and in the placentas of the infected women. In the light of these findings, the theoretical risk of intrauterine infection for fetuses, or of peripartum infection occurring during delivery for neonates, has a biological plausibility. The extent of this putative risk might, however, vary during the different stages of pregnancy, owing to several variables (physiological modifications of the placenta, virus receptors' expression, or delivery route). This brief review provides an overview of the current evidence in this area. Further data, based on national and international multicenter registries, are needed not only to clearly assess the extent of the risk for vertical transmission, but also to ultimately establish solid guidelines and consistent recommendations. KEY POINTS: · Questions on the COVID-19 infection transmission from mothers to fetuses or neonates during pregnancy and peripartum period remain pending so far.. · The theoretical risk of intrauterine infection for fetuses, or of neonatal infection during delivery for neonates, has a biological plausibility.. · A caution is recommended in the interpretation of clinical and laboratory data in neonates..

Therapeutic Drug Monitoring Is a Feasible Tool to Personalize Drug Administration in Neonates Using New Techniques: An Overview on the Pharmacokinetics and Pharmacodynamics in Neonatal Age.

Therapeutic drug monitoring (TDM) should be adopted in all neonatal intensive care units (NICUs), where the most preterm and fragile babies are hospitalized and treated with many drugs, considering that organs and metabolic pathways undergo deep and progressive maturation processes after birth. Different developmental changes are involved in interindividual variability in response to drugs. A crucial point of TDM is the choice of the bioanalytical method and of the sample to use. TDM in neonates is primarily used for antibiotics, antifungals, and antiepileptic drugs in clinical practice. TDM appears to be particularly promising in specific populations: neonates who undergo therapeutic hypothermia or extracorporeal life support, preterm infants, infants who need a tailored dose of anticancer drugs. This review provides an overview of the latest advances in this field, showing options for a personalized therapy in newborns and infants.

Long term outcome of eight patients with type 1 Leukocyte Adhesion Deficiency (LAD-1): Not only infections, but high risk of autoimmune complications.

Leukocyte Adhesion Deficiency type 1 (LAD-1) is a rare primary immunodeficiency due to mutations in the gene encoding for the common ß-chain of the ß2 integrin family (CD18). Herein, we describe clinical manifestations and long-term complications of eight LAD-1 patients. Four LAD-1 patients were treated with hematopoietic stem cell transplantation (HSCT), while the remaining four, including two with moderate LAD-1 deficiency, received continuous antibiotic prophylaxis. Untreated patients presented numerous infections and autoimmune manifestations. In particular, two of them developed renal and intestinal autoimmune diseases, despite the expression of Beta-2 integrin was partially conserved. Other two LAD-1 patients developed type 1 diabetes and autoimmune cytopenia after HSCT, suggesting that HSCT is effective for preventing infections in LAD-1, but does not prevent the risk of the autoimmune complications.