Combining artificial intelligence and conventional statistics to predict bronchopulmonary dysplasia in very preterm infants using routinely collected clinical variables.

BACKGROUND: Prematurity is the strongest predictor of bronchopulmonary dysplasia (BPD). Most previous studies investigated additional risk factors by conventional statistics, while the few studies applying artificial intelligence, and specifically machine learning (ML), for this purpose were mainly targeted to the predictive ability of specific interventions. This study aimed to apply ML to identify, among routinely collected data, variables predictive of BPD, and to compare these variables with those identified through conventional statistics. METHODS: Very preterm infants were recruited; antenatal, perinatal, and postnatal clinical data were collected. A BPD prediction model was built using conventional statistics, and nine supervised ML algorithms were applied for the same purpose: the results of the best-performing model were described and compared with those of conventional statistics. RESULTS: Both conventional statistics and ML identified the degree of immaturity (low gestational age and/or birth weight), need for mechanical ventilation, and absent or reversed end diastolic flow (AREDF) in the umbilical arteries as risk factors for BPD. Each of the two approaches also identified additional potentially predictive clinical variables. CONCLUSION: ML algorithms might be useful to integrate conventional statistics in identifying novel risk factors, in addition to prematurity, for the development of BPD in very preterm infants. Specifically, the identification of AREDF status as an independent risk factor for BPD by both conventional statistics and ML highlights the opportunity to include detailed antenatal information in clinical predictive models for neonatal diseases.

Identification of the core competencies of pediatric hematology-oncology nurses: A Delphi study.

PURPOSE: To identify the core competencies of the pediatric hematology-oncology nurse. METHODS: A Delphi study was conducted. After identifying the competencies of the pediatric hematology-oncology nurse through a literature review, a questionnaire was created to be administered to a panel of experts to obtain consensus. The panel of experts consisted of 19 nurses. For each competence identified, it was necessary to evaluate the competence in terms of "understanding" and "relevance", assigning a score from 0 (not at all) to 4 (completely), according to a Likert scale. Then, the experts identified what could be the necessary "level of work experience" within which a nurse should become autonomous in every competency choosing among the levels: beginner, intermediate, expert. Consensus among the experts was reached in two rounds. RESULTS: After submitting the document to two rounds, a final document was obtained with a total of 126 competencies, divided into nine areas. Fifty-eight competencies fall into the "beginner" level, 46 competencies into the "intermediate" level and 22 competencies into the "expert" level. CONCLUSIONS: The document produced by this study could be a starting point for organizing specific training courses for nurses in the pediatric hematology-oncology department. A clear description of specific competencies for pediatric hematology-oncology nurses would help ensure the best care for the child.

Neurodevelopmental Correlates of Brain Magnetic Resonance Imaging Abnormalities in Extremely Low-birth-weight Infants.

OBJECTIVE: To evaluate the relationship between impaired brain growth and structural brain abnormalities at term-equivalent age (TEA) and neurodevelopment in extremely low-birth-weight (ELBW) infants over the first 2 years. METHODS: ELBW infants born from 2009 through 2018 and undergoing brain magnetic resonance imaging (MRI) at TEA were enrolled in this retrospective cohort study. MRI scans were reviewed using a validated quali-quantitative score, including several white and gray matter items. Neurodevelopment was assessed at 6, 12, 18, and 24 months using the Griffiths scales. The independent associations between MRI subscores and the trajectories of general and specific neurodevelopmental functions were analyzed by generalized estimating equations. RESULTS: One hundred-nine ELBW infants were included. White matter volume reduction and delayed myelination were associated with worse general development (b = -2.33, P = .040; b = -6.88, P = .049 respectively), social skills (b = -3.13, P = .019; b = -4.79, P = .049), and eye-hand coordination (b = -3.48, P = .009; b = -7.21, P = .045). Cystic white matter lesions were associated with poorer motor outcomes (b = -4.99, P = .027), while white matter signal abnormalities and corpus callosum thinning were associated with worse nonverbal cognitive performances (b = -6.42, P = .010; b = -6.72, P = .021, respectively). Deep gray matter volume reduction correlated with worse developmental trajectories. CONCLUSIONS: Distinctive MRI abnormalities correlate with specific later developmental skills. This finding may suggest that TEA brain MRI may assist with neurodevelopmental prediction, counseling of families, and development of targeted supportive interventions to improve neurodevelopment in ELBW neonates.

Antenatal and Postnatal Sequelae of Oxidative Stress in Preterm Infants: A Narrative Review Targeting Pathophysiological Mechanisms.

The detrimental effects of oxidative stress (OS) can start as early as after conception. A growing body of evidence has shown the pivotal role of OS in the development of several pathological conditions during the neonatal period, which have been therefore defined as OS-related neonatal diseases. Due to the physiological immaturity of their antioxidant defenses and to the enhanced antenatal and postnatal exposure to free radicals, preterm infants are particularly susceptible to oxidative damage, and several pathophysiological cascades involved in the development of prematurity-related complications are tightly related to OS. This narrative review aims to provide a detailed overview of the OS-related pathophysiological mechanisms that contribute to the main OS-related diseases during pregnancy and in the early postnatal period in the preterm population. Particularly, focus has been placed on pregnancy disorders typically associated with iatrogenic or spontaneous preterm birth, such as intrauterine growth restriction, pre-eclampsia, gestational diabetes, chorioamnionitis, and on specific postnatal complications for which the role of OS has been largely ascertained (e.g., respiratory distress, bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, necrotizing enterocolitis, neonatal sepsis). Knowledge of the underlying pathophysiological mechanisms may increase awareness on potential strategies aimed at preventing the development of these conditions or at reducing the ensuing clinical burden.

Atypical Findings of Shwachman-Diamond Syndrome in Early Infancy: A Diagnostic Challenge.

Shwachman-Diamond syndrome (SDS) is a rare autosomal recessive disorder characterized by hematological abnormalities, exocrine pancreatic insufficiency, and skeletal dysplasia. We describe a 2-month-old girl with intrauterine and extrauterine growth restriction who presented with an isolated severe anemia requiring red blood cell transfusion, without gastrointestinal symptoms, history of infection, or congenital abnormalities. An abdominal ultrasound revealed a reduced pancreatic thickness and abnormal echogenicity without fat infiltration, further confirmed by MRI. Because of this peculiar pancreatic appearance, pancreatic function was investigated and revealed exocrine insufficiency. Genetic testing confirmed SDS diagnosis. The typical clinical, laboratory, and imaging features of SDS are often lacking in the first months of life, and this may delay diagnosis. In early infancy, low birth weight and lack of catch-up growth, isolated hematological abnormalities other than neutropenia and atypical pancreatic imaging may lead to SDS diagnosis even when the most common diagnostic criteria are not fulfilled.

Resting respiratory lung volumes are "healthier" than exercise respiratory volumes in different types of palliated or corrected congenital heart disease.

AIMS: Cardiac surgery has improved life expectancy of patients with congenital heart diseases (CHDs). Exercise capacity is an important determinant of survival in patients with CHDs. There is a lack of studies focusing on the role of resting respiratory performance in reducing exercise tolerance in these patients. OBJECTIVES: To determine the prevalence and severity of respiratory functional impairment in different types of corrected/palliated CHDs, and its impact on an exercise test. MATERIALS AND METHODS: Retrospective single-center study involving 168 corrected/palliated patients with CHD and 52 controls. Patients CHD were divided into subgroups according to the presence of native pulmonary blood flow or total cavopulmonary connection (TCPC). All subjects performed complete pulmonary function tests and gas diffusion; patients with CHD also performed cardiopulmonary exercise test (CPX). RESULTS: Mean values of lung volumes were within the normal range in all CHD groups. Comparing to controls, patients with the reduced pulmonary flow and with TCPC had the highest reduction in lung volumes. CPX was reduced in all groups, most severely in TCPC, and it was correlated to decreased dynamic volumes in all CHD groups except in TCPC. Younger age at intervention and number of surgical operations negatively affected lung volumes. CONCLUSIONS: Respiratory function is within the normal range in our patients with different CHDs at rest but altered in all CHDs during exercise when cardiorespiratory balance is likely to be inadequate. Comparing the different groups, patients with reduced pulmonary flow and TCPC are the most impaired.

Free radicals and neonatal encephalopathy: mechanisms of injury, biomarkers, and antioxidant treatment perspectives.

Neonatal encephalopathy (NE), most commonly a result of the disruption of cerebral oxygen delivery, is the leading cause of neurologic disability in term neonates. Given the key role of free radicals in brain injury development following hypoxia-ischemia-reperfusion, several oxidative biomarkers have been explored in preclinical and clinical models of NE. Among these, antioxidant enzyme activity, uric acid excretion, nitric oxide, malondialdehyde, and non-protein-bound iron have shown promising results as possible predictors of NE severity and outcome. Owing to high costs and technical complexity, however, their routine use in clinical practice is still limited. Several strategies aimed at reducing free radical production or upregulating physiological scavengers have been proposed for NE. Room-air resuscitation has proved to reduce oxidative stress following perinatal asphyxia and is now universally adopted. A number of medications endowed with antioxidant properties, such as melatonin, erythropoietin, allopurinol, or N-acetylcysteine, have also shown potential neuroprotective effects in perinatal asphyxia; nevertheless, further evidence is needed before these antioxidant approaches could be implemented as standard care.

Effect of Different Tube Feeding Methods on the Delivery of Docosahexaenoic and Arachidonic Acid: An In Vitro Pilot Study.

BACKGROUND: Arachidonic acid (AA) and docosahexaenoic acid (DHA) are crucial for neural and visual development after premature birth. Preterm infants usually require tube feeding (TF) until the achievement of adequate oral feeding skills; the impact of TF on DHA and AA delivery has not been investigated yet. This study aimed to evaluate the effect of different TF techniques on the delivery of AA and DHA contained in human milk (HM). METHODS: HM samples (65 mL each) were collected and divided into three 20-mL aliquots. The remaining 5 mL served as baseline. Three TF techniques were simulated (1 for each aliquot): gravity bolus feeding (BF), 3-hour continuous feeding using a horizontal feeding pump, and 3-hour continuous feeding with the feeding pump angled at 45°. For horizontal continuous feeding (HCF) and 45° angled continuous feeding (ACF), aliquots delivered between 0 and 90 minutes (T1) and 91 and 180 minutes (T2) were collected separately. AA and DHA concentration was analyzed by gas chromatography/mass spectrometry and compared among the TF methods. DHA and AA delivery at T1 and T2 was also evaluated. RESULTS: Fifty-one simulated feeds were performed. DHA and AA amounts after BF and ACF did not differ significantly compared with baseline, whereas HCF resulted in significantly lower DHA and AA concentration. During T2, ACF delivered almost twice the DHA and AA amounts compared with T1. CONCLUSION: The delivery of HM AA and DHA is significantly affected by TF, with potential clinical implications. When BF is not tolerated, ACF might represent a feasible alternative to reduce TF-related DHA and AA loss.

Maternal Supplementation With Krill Oil During Breastfeeding and Long-Chain Polyunsaturated Fatty Acids (LCPUFAs) Composition of Human Milk: A Feasibility Study.

Background: Docosahexaenoic acid (DHA) is a major constituent of neuronal and retinal membranes and plays a crucial role in brain and visual development within the first months of life. Dietary intakes are fundamental to provide neonates with adequate DHA supply; hence, maternal supplementation might represent a useful strategy to implement DHA contents in breast milk (BM), with possible benefits on neonatal neurodevelopment. Antarctic krill is a small crustacean rich in highly available phospholipid-bound DHA. This pilot study aimed to evaluate whether maternal supplementation with krill oil during breastfeeding increases long-chain polyunsaturated fatty acids (LCPUFAs) BM contents. Methods: Mothers of infants admitted to the Neonatal Intensive Care Unit were enrolled in this open, randomized-controlled study between 4 and 6 weeks after delivery and randomly allocated in 2 groups. Group 1 received an oral krill oil-based supplement providing 250 mg/day of DHA and 70 mg/day of eicosapentaenoic acid (EPA) for 30 days; group 2 served as control. BM samples from both groups were collected at baseline (T0) and day 30 (T1) and underwent a qualitative analysis of LCPUFAs composition by gas chromatography/mass spectrometry. Results: Sixteen breastfeeding women were included. Of these, 8 received krill-oil supplementation and 8 were randomized to the control group. Baseline percentage values of DHA (%DHA), arachidonic acid (%AA), and EPA (%EPA) did not differ between groups. A significant increase in %DHA (T0: median 0.23% [IQR 0.19;0.38], T1:0.42% [0.32;0.49], p 0.012) and %EPA (T0: median 0.10% [IQR 0.04;0.11], T1:0.11% [0.04;0.15], p 0.036) and a significant reduction in %AA (T0: median 0.48% [IQR 0.42;0.75], T1:0.43% [0.38;0.61], p 0.017) between T0 and T1 occurred in Group 1, whereas no difference was seen in Group 2. Consistently, a significant between-group difference was observed in percentage changes from baseline of DHA (Δ%DHA, group 1: median 64.2% [IQR 27.5;134.6], group 2: -7.8% [-12.1;-3.13], p 0.025) and EPA (Δ%EPA, group 1: median 39% [IQR 15.7;73.4]; group 2: -25.62% [-32.7;-3.4], p 0.035). Conclusions: Oral krill oil supplementation effectively increases DHA and EPA contents in BM. Potential benefits of this strategy on brain and visual development in breastfed preterm neonates deserve further evaluation in targeted studies. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03583502.

Octreotide in a Critically Ill Extremely Preterm Infant With Perforated Necrotizing Enterocolitis.

Necrotizing enterocolitis (NEC) is the most severe gastrointestinal complication of prematurity. Surgery, either peritoneal drainage placement or laparotomy with resection of the intestinal necrotic tracts, is the definitive treatment of perforated NEC; however, when clinical conditions contraindicate surgical approaches, little is known about medical treatments adjuvant or alternative to surgery. Octreotide is a synthetic somatostatin analog that inhibits pancreatic secretion and leads to splanchnic vasoconstriction. In preterm neonates, it is mainly used off-label for chylothorax and congenital hyperinsulinism, whereas gastrointestinal indications are limited. We describe the case of a critically ill extremely low birth weight infant with perforated NEC, who had unsuccessfully undergone peritoneal drainage placement and laparotomy. Her unstable condition contraindicated a further laparotomy, thus off-label treatment with octreotide was attempted. No adverse events occurred. The infant's condition gradually improved and progressive reduction of peritoneal outputs and successful resolution of pneumoperitoneum were achieved, with no relapse after octreotide discontinuation.

Altered Intracellular ATP Production by Activated CD4+ T-Cells in Very Preterm Infants.

Background. The neonatal immune system is not fully developed at birth; newborns have adequate lymphocytes counts but these cells lack function. Objective. To assess the activity of T-cells and the influence of the main perinatal factors in very preterm infants (birth weight < 1500 g). Design. Blood samples from 59 preterm infants (21/59 were dizygotic twins) were collected at birth and at 30 days of life to measure CD4+ T-cell activity using the ImmuKnow™ assay. Fifteen healthy adults were included as a control group. Results. CD4+ T-cell activity was lower in VLBW infants compared with adults (p < 0.001). Twins showed lower immune activity compared to singletons (p = 0.005). Infants born vaginally showed higher CD4+ T-cell activity compared to those born by C-section (p = 0.031); infants born after prolonged Premature Rupture of Membranes (pPROM) showed higher CD4+ T-cell activity at birth (p = 0.002) compared to infants born without pPROM. Low CD4+ T-cell activity at birth is associated with necrotizing enterocolitis (NEC) in the first week of life (p = 0.049). Conclusions. Preterm infants show a lack in CD4+ T-cell activity at birth. Perinatal factors such as intrauterine inflammation, mode of delivery, and zygosity can influence the adaptive immune activation capacity at birth and can contribute to exposing these infants to serious complications such as NEC.

Renal involvement in hypocomplementaemic urticarial vasculitis syndrome: a report of three paediatric cases.

OBJECTIVE: To describe the diagnosis and management of renal disease in three paediatric cases of hypocomplementaemic urticarial vasculitis syndrome (HUVS). METHODS: Three children who were diagnosed with HUVS and developed abnormalities of renal function during the disease course are described. RESULTS: Urinary findings were heterogeneous: all the patients developed persistent microhaematuria, which was isolated in patient 1, associated with mild proteinuria in patient 2 and with nephrotic syndrome in patient 3. Renal biopsies were performed in all the patients: patients 1 and 2, who had normal levels of serum autoantibodies, shared a full-house IF (C3, C1q and Ig deposits), compatible with an SLE-like disease; patient 3 showed negative staining for IgG and IgM, but developed positive anti-dsDNA without fulfilling criteria for the diagnosis of SLE. CONCLUSION: Renal involvement in HUVS is probably more frequent and more severe than in adults and may appear later. Isolated microhaematuria can be the only sign of subclinical renal involvement: its role should not be underestimated and a renal biopsy should be considered. Previous observations of rapidly progressive nephritis and consequent end-stage renal disease in children suggest the need for prompt diagnosis and treatment of renal involvement.

Adapting a Vacuum Assisted Closure dressing to challenging wounds: negative pressure treatment for perineal necrotizing fasciitis with rectal prolapse in a newborn affected by acute myeloid leukaemia.

We report the case of a newborn with acute myeloid leukaemia, who developed perineal necrotizing fasciitis due to Pseudomonas Aeruginosa, after twenty days of life. Following surgical debridement, she was effectively treated with topical negative pressure therapy (V.A.C.(R) device) with silver foam dressings, this achieved complete closure in thirteen days. Negative pressure therapy should be considered when conventional wound care fails to achieve complete wound closure, even in neonates.