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.

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.

Lung Ultrasound Score in Neonates with Congenital Diaphragmatic Hernia (CDH-LUS): A Cross-Sectional Study.

Introduction: The use of a lung ultrasound (LUS) score has been described in the early phases of neonatal respiratory distress syndrome; however, there is still no data regarding the application of the LUS score to neonates with a congenital diaphragmatic hernia (CDH). The objective of this observational cross-sectional study was to explore, for the first time, the postnatal changes in LUS score patterns in neonates with CDH, with the creation of a new specific CDH-LUS score. Methods: We included all consecutive neonates with a prenatal diagnosis of CDH admitted to our Neonatal Intensive Care Unit (NICU) from June 2022 to December 2022 who underwent lung ultrasonography. Lung ultrasonography (LUS) was determined at scheduled time points: (T0) during the first 24 h of life; (T1) at 24-48 h of life; (T2) within 12 h of surgical repair; (T3) a week after the surgical repair. We used a modified LUS score (CDH-LUS), starting from the original 0-3 score. We assigned 4 as a score in the presence of herniated viscera in the hemithorax (liver, small bowel, stomach, or heart in the case of a mediastinal shift) in the preoperative scans or pleural effusions in the postoperative scans. Results: We included in this observational cross-sectional study 13 infants: twelve/13 had a left-sided hernia (2 severe, 3 moderate, and 7 mild cases), while one patient had a right-sided severe hernia. The median CDH-LUS score was 22 (IQR 16-28) during the first 24 h of life (T0), 21 (IQR 15-22) at 24-48 h of life (T1), 14 (IQR 12-18) within 12 h of surgical repair (T2) and 4 (IQR 2-15) a week after the surgical repair (T3). The CDH-LUS significantly dropped over time from the first 24 h of life (T0) to a week after the surgical repair (T3), according to ANOVA for repeated measures. Conclusion: We showed a significant improvement in CDH-LUS scores from the immediate postoperative period, with normal ultrasonographic evaluations a week after surgery in most patients.

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.

Post-operative ventilation strategies after surgical repair in neonates with esophageal atresia: A retrospective cohort study.

BACKGROUND: Infants affected by Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) may require non-invasive ventilation (NIV) in the post-operative period after elective extubation, especially if born preterm. The aim of the paper is to evaluate the role of different ventilation strategies on anastomotic complications, specifically on anastomotic leak (AL). MATERIALS AND METHODS: Retrospective single Institution study, including all consecutive neonates affected by EA with or without TEF in a 5-year period study (from 2014 to 2018). Only infants with a primary anastomosis were included in the study. All infants were mechanically ventilated after surgery and electively extubated after 6-7 days. The duration of invasive ventilation was decided on a case-by-case basis after surgery, based on the pre-operative esophageal gap and intraoperative findings. The need for non-invasive ventilation (NCPAP, NIPPV, and HHHFNC) after extubation and extubation failure with the need for mechanical ventilation in the post-operative period were assessed. The primary outcome evaluated was the rate of anastomotic leak. RESULTS: 102 EA/TEF infants were managed in the study period. Sixty-seven underwent primary anastomosis. Of these, 29 (43.3%) were born preterm. Patients who required ventilation (n = 32) had a significantly lower gestational age as well as birthweight (respectively p = 0.007 and p = 0.041). 4/67 patients had an AL after surgical repair, with no statistical differences among post-operative ventilation strategies. CONCLUSION: We found no significant differences in the rate of anastomotic leak (AL) according to post-operative ventilation strategies in neonates operated on for EA/TEF.

Defective Leukocyte ß2 Integrin Expression and Reactive Oxygen Species Production in Neonates.

Neonates are highly susceptible to bacterial infections, which represent a major source of mortality and morbidity in this age category. It is recognized that ß2 integrins play a critical role in innate immunity by mediating leukocyte vascular adhesion, transmigration and bacterial phagocytosis. Therefore, we aimed to assess if the impaired immune functions seen in newborns may derive, in part, from a transient insufficient ß2 integrin expression. In the present study we measured baseline lymphocyte function-associated antigen-1 (LFA-1 or CD11a/CD18), macrophage-1 antigen (MAC-1 or CD11b/CD18) and leukocyte integrin p150-95 (CD11c/CD18) expression on cord blood, and on the third day of life in a cohort of 35 healthy neonates, compared with a control group of 12 healthy adults. For any of the three ß2 integrins, the expression on polymorphonuclear cells was significantly lower on cord blood than in adults and increased from birth to day 3. We also compared superoxide radical (SR) production in these neonates with 28 non-smoking adults. SR production in response to integrin stimulation by Zymosan was significantly lower at birth than in adults, and it decreased further in the third day of life. These findings suggest that innate immune impairment in newborns may be, in part, accounted for by a lower ß2 integrin expression on phagocytes in the neonatal period, but also by a functional impairment of free radical production.

Growth and morbidity in infants with Congenital Diaphragmatic Hernia according to initial lung volume: A pilot study.

Background In congenital diaphragmatic hernia (CDH) survivors, failure to thrive is a well-known complication, ascribed to several factors. The impact of lung volume on growth of CDH survivors is poorly explored. Our aim was to evaluate if, in CDH survivors, lung volume (LV) after extubation correlates with growth at 12 and 24 months of life. Methods LV (measured as functional residual capacity-FRC) was evaluated by multibreath washout traces with an ultrasonic flowmeter and helium gas dilution technique, shortly after extubation. All CDH survivors are enrolled in a dedicated follow-up program. For the purpose of this study, we analyzed the correlation between FRC obtained shortly after extubation and anthropometric measurements at 12 and 24 months of age. We also compared growth between infants with normal lungs and those with hypoplasic lungs according to FRC values. A p < 0.05 was considered as statistically significant. Results We included in the study 22 CDH survivors who had FRC analyzed after extubation and auxological follow-up at 12 and 24 months of age. We found a significant correlation between FRC and weight Z-score at 12 months, weight Z-score at 24 months and height Z-score at 24 months. We also demonstrated that CDH infants with hypoplasic lungs had a significantly lower weight at 12 months and at 24 months and a significantly lower height at 24 months, when compared to infants with normal lungs. Conclusion We analyzed the predictive value of bedside measured lung volumes in a homogeneous cohort of CDH infants and demonstrated a significant correlation between FRC and growth at 12 and 24 months of age. An earlier identification of patients that will require an aggressive nutritional support (such as those with pulmonary hypoplasia) may help reducing the burden of failure to thrive.

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.

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 Role of Lung Function Testing in Newborn Infants With Congenital Thoracic Arterial Anomalies.

Introduction: Congenital thoracic arterial anomalies (CTAAs), such as complete or incomplete vascular rings, pulmonary artery sling, and innominate artery compression syndrome, may cause severe tracheomalacia and upper airway obstruction. An obstructive ventilatory pattern at lung function testing (LFT) has been suggested in the presence of CTAA. The severity of obstruction may be evaluated by LFT. Little is known about the use of LFT in newborn infants with CTAA. The aim of our study is to evaluate the role of LFT in CTAA diagnosis. Methods: This is a retrospective study, conducted between February 2016 and July 2020. All CTAA cases for whom LFT was performed preoperatively were considered for inclusion. Tidal volume (Vt), respiratory rate, and the ratio of time to reach the peak tidal expiratory flow over total expiratory time (tPTEF/tE) were assessed and compared to existing normative data. Demographics and CTAA characteristics were also collected. Results: Thirty cases were included. All infants with CTAA showed a significantly reduced Vt and tPTEF/tE, compared to existing normative data suggesting an obstructive pattern. No significant differences were found for LFT between cases with a tracheal obstruction <50% compared to those with tracheal obstruction ≥50%, or between cases with and without symptoms. Sixteen infants (53.3%) had respiratory symptoms related to CTAA. Of these, only two cases had also dysphagia. Conclusion: LFT values were significantly reduced in cases with CTAA before surgery. LFT represents a potential feasible and non-invasive useful tool to guide diagnosis in the suspect of CTAA.

Invasive Candida Infections in Neonates after Major Surgery: Current Evidence and New Directions.

Infections represent a serious health problem in neonates. Invasive Candida infections (ICIs) are still a leading cause of mortality and morbidity in neonatal intensive care units (NICUs). Infants hospitalized in NICUs are at high risk of ICIs, because of several risk factors: broad spectrum antibiotic treatments, central catheters and other invasive devices, fungal colonization, and impaired immune responses. In this review we summarize 19 published studies which provide the prevalence of previous surgery in neonates with invasive Candida infections. We also provide an overview of risk factors for ICIs after major surgery, fungal colonization, and innate defense mechanisms against fungi, as well as the roles of different Candida spp., the epidemiology and costs of ICIs, diagnosis of ICIs, and antifungal prophylaxis and treatment.

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.

Neurodevelopmental outcomes in very preterm infants: The role of severity of Bronchopulmonary Dysplasia.

OBJECTIVE: Bronchopulmonary dysplasia is a chronic respiratory disease that still affects preterm neonates; its association with neurodevelopmental (ND) impairment is already known. Different studies investigated neurodevelopmental outcomes in infants with BPD, often using the old dichotomous definition (BPD vs Non-BPD). This retrospective study aims to evaluate the role of different BPD severity grades on ND outcomes at 24 months of corrected age (CA). METHODS: All preterm infants born between 2011 and 2015 in the study hospital with a gestational age (GA) ≤ 30 weeks and discharged from our NICU were included and were divided in infants with and without BPD. Infants with BPD were divided into three severity groups as defined by NICHD/NHLBI Workshop in 2001, and were compared to their Non-BPD peers, matching them according to the same GA and year of birth. At 24 months postmenstrual age, we assessed general outcomes (growth and hospital readmissions) and neurodevelopmental outcomes (motor, developmental and sensory outcomes) with a standardized assessment. RESULTS: We enrolled 89 patients affected by BPD of different grades of severity and a control group of 89 preterm infants without BPD. Infants with Moderate and Severe BPD showed a significantly higher corrected odds ratio (OR) for cognitive impairment compared to controls. Within the group of infants without severe disability (regarding Griffiths' scales), infants with Moderate and Severe BPD as well as infants with Mild BPD showed a significantly higher risk of a lower total Developmental Quotient (DQ) score, even after correction for confounding factors. CONCLUSIONS: Our study evidenced that not only Severe BPD infants, but also Moderate ones showed a higher risk of overall cognitive impairment at 24 months CA. Within the group of infants without severe disability, also those with Mild BPD had lower Griffiths DQ scores than those without. This would suggest that infants with BPD, regardless of severity, warrant neurodevelopmental follow-up.

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.

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.

Should isolated Pseudo-Bartter syndrome be considered a CFTR-related disorder of infancy?

BACKGROUND: Infants that are negative to cystic fibrosis (CF) newborn screening (NBS) programs, or in countries without NBS, may present with metabolic alkalosis and severe salt depletion, a well-known clinical manifestation of CF termed Pseudo-Bartter syndrome (PBS). Here, we report the cases of three CF-negative children, who carry rare mutations in the CF transmembrane conductance regulator (CFTR) gene, and, for whom, PBS was the only manifestation of CFTR protein dysfunction. There is no diagnostic label for these cases. METHODS: Medical records of patients followed at our Cystic Fibrosis Centre were revised and data were collected for all patients who presented with an isolated PBS. The syndrome was defined as an episode of dehydration with low levels of serum sodium (<134mmol/L), potassium ( <3.4mmol/L), and chloride ( <100mmol/L), with metabolic alkalosis (bicarbonatemia >27mmol/L) in the absence of renal tubulopathy. RESULTS: Three out of 73 (4%) CF infants presented with a severe metabolic alkalosis with salt depletion; two of these required admission to the intensive care unit. Two infants had a negative NBS, and one was identified as a CF carrier. Sweat test was repeatedly in the negative/borderline ranges for all patients. Less than two CF causing mutations were identified (F508del/R1070W, F508del; L467F/P5L, R1066H/P5L). During a mean follow-up of 9 years, the children had no other CF manifestations. CONCLUSION: We suggest that PBS as the sole manifestation of CFTR dysfunction might be considered a CFTR-related disorder of infancy.

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.