The Impact of Antenatal Corticosteroids on the Metabolome of Preterm Newborns: An Untargeted Approach.

We analyzed and compared variations in the urinary metabolome, as well as postnatal clinical outcomes among preterm infants, based on the timing of antenatal corticosteroid (ACS) administration in response to preterm labor onset in their mothers. This was a prospective observational study held in the Neonatal Intensive Care Unit, Department of Woman's and Child's Health, Padova University Hospital (Italy). A urine sample was obtained from each patient within 24 h of birth; Mass Spectrometry-based untargeted metabolomics analysis was then conducted. We searched for any significant disparities in the metabolomic profile of preterm newborns subjected to antenatal corticosteroid (ACS) treatment at varying timings; their correlation with clinical outcomes were also evaluated. The group receiving ACS within the optimal time window (1-7 days before delivery) exhibited elevated levels of cysteine, N-acetylglutamine, propionyl carnitine and 5-hydroxyindolacetic acid, coupled with a decrease in pipecolic acid. Clinically, this group demonstrated a reduced need for invasive ventilation (p = 0.04). In conclusion, metabolomics analysis identified several metabolites that discriminated preterm infants whose mothers received ACS within the recommended time window. Elevated levels of cysteine and 5-Hydroxyindoleacetic acid, metabolites characterized by antioxidant and anti-inflammatory properties, were observed in these infants. This metabolic profile correlated with improved respiratory outcomes, as evidenced by a reduced necessity for invasive ventilation at birth.

Neonatal Enterovirus-Associated Myocarditis in Dizygotic Twins: Myocardial Longitudinal Strain Pattern Analysis.

Enteroviruses (EVs) are the most common causes of viral myocarditis in neonates. Neonatal enterovirus myocarditis manifestations range from nonspecific febrile illness to congestive heart failure and cardiogenic shock with high risk of in-hospital mortality and long-term cardiac sequelae. Early recognition is essential to undertake appropriate therapy and predict outcomes. Echocardiography and echo-derived left ventricular strain measures seem promising for these purposes. We herein report two cases of neonatal enterovirus-associated myocarditis in dichorionic diamniotic twins, with different presentation, clinical course, and intensity of treatments.

Neurosteroid pathway derangement in asphyctic infants treated with hypothermia: an untargeted metabolomic approach.

BACKGROUND: The pathobiological mechanisms associated with perinatal asphyxia and hypoxic-ischemic encephalopathy are complex and poorly understood. The metabolic effects of therapeutic hypothermia have been partially explored. METHODS: We conducted a single-center longitudinal study to investigate the metabolic effects of perinatal asphyxia and hypoxic-ischemic encephalopathy on the urinary metabolome of a group of 12 asphyctic infants over time compared to 22 matched healthy newborns, using untargeted metabolomics based on mass spectrometry. FINDINGS: Over-representation pathway analysis identified the steroidogenesis pathway as being significantly disrupted, with reduced steroid levels in the first three days of life despite treatment with hypothermia. Comparison with matched healthy newborns showed that the urinary steroid content was lower in asphyctic infants before hypothermia. The lysine degradation and carnitine synthesis pathways were also significantly affected. INTERPRETATION: Steroidogenesis is significantly disrupted in asphyctic infants compared to healthy newborns. Given how neurosteroids are involved in neuromodulation and neuroprotection, translational research is warranted on the potential role of neurosteroid-based intervention in asphyctic infants. FUNDING: None.

Early Biomarkers of Bronchopulmonary Dysplasia: A Quick Look to the State of the Art.

Bronchopulmonary dysplasia (BPD) is one of the most common pulmonary sequelae of extreme preterm birth, with long-lasting respiratory symptoms and reduced lung function. A reliable predictive tool of BPD development is urgent and its search remains one of the major challenges for neonatologists approaching the upcoming arrival of possible new preventive therapies. Biomarkers, identifying an ongoing pathogenetic pathway, could allow both the selection of preterm infants with an evolving disease and potentially the therapeutic targets of the indicted pathogenesis. The "omic" sciences represent well-known promising tools for this objective. In this review, we resume the current laboratoristic, metabolomic, proteomic, and microbiomic evidence in the prediction of BPD. KEY POINTS: · The early prediction of BPD development would allow the targeted implementation of new preventive therapies.. · BPD is a multifactorial disease consequently it is unlikely to find a single disease biomarker.. · "Omic" sciences offer a promising insight in BPD pathogenesis and its development's fingerprints..

Urinary metabotypes of newborns with perinatal asphyxia undergoing therapeutic hypothermia.

Perinatal asphyxia (PA) still occurs in about three to five per 1,000 deliveries in developed countries; 20% of these infants show hypoxic-ischemic encephalopathy (HIE) on brain magnetic resonance imaging (MRI). The aim of our study was to apply metabolomic analysis to newborns undergoing therapeutic hypothermia (TH) after PA to identify a distinct metabotype associated with the development of HIE on brain MRI. We enrolled 53 infants born at >35 weeks of gestation with PA: 21 of them showed HIE on brain MRI (the "HIE" group), and 32 did not (the "no HIE" group). Urine samples were collected at 24, 48 and 72 hours of TH. Metabolomic data were acquired using high-resolution mass spectrometry and analyzed with univariate and multivariate methods. Considering the first urines collected during TH, untargeted analysis found 111 relevant predictors capable of discriminating between the two groups. Of 35 metabolites showing independent discriminatory power, four have been well characterized: L-alanine, Creatine, L-3-methylhistidine, and L-lysine. The first three relate to cellular energy metabolism; their involvement suggests a multimodal derangement of cellular energy metabolism during PA/HIE. In addition, seven other metabolites with a lower annotation level (proline betaine, L-prolyl-L-phenylalanine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E, 2,6 dimethylheptanoyl carnitine, Octanoylglucuronide, 19-hydroxyandrost-4-ene-3,17-dione) showed biological consistency with the clinical picture of PA. Moreover, 4 annotated metabolites (L-lysine, L-3-methylhistidine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E) retained a significant difference between the "HIE" and "no HIE" groups during all the TH treatment. Our analysis identified a distinct urinary metabotype associated with pathological findings on MRI, and discovered 2 putative markers (L-lysine, L-3-methylhistidine) which may be useful for identifying neonates at risk of developing HIE after PA.

Surgical management of large scalp infantile hemangioma in 30-month-old infant.

Infantile Hemangiomas (IH) are the most common benign tumor of infancy, occurring in over 10% of newborns. The head and neck is the most frequently affected area (60%), and the scalp is a typical site for such large lesions. Scalp-IHs are usually focal lesions that can be both disfiguring and may lead to complications such as ulceration and bleeding. We describe a case of a 30-months old female who presented a large scalp-IH at birth that rapidly grew in the first year of life. Topical and systemic treatments (with timolol ointment and oral propranolol, respectively) were not effective in reducing dimensions of the hemangioma. After vascular imaging study, the patient underwent surgical resection of the IH and primary closure with excellent cosmetic outcome. When medical therapy is ineffective or cosmetic and functional integrity is threatened, early surgery allows to completely removing large scalp-IHs, with good cosmetic results.

Trends in respiratory management of transferred very preterm infants in the last two decades.

BACKGROUND: Among infants needing urgent transfer after birth, very preterm infants are a high-risk sub-group requiring special attention. This study aimed to assess trends in early respiratory management in a large series of very preterm infants undergoing postnatal transfer. METHODS: Trends in patient characteristics and early respiratory management were assessed in 798 very preterm infants who were transferred by the Eastern Veneto Neonatal Emergency Transport Service in 2000-2019. Trends were analyzed using joinpoint regression analysis and summarized as annual percentage changes (APCs). RESULTS: Proportion of neonates with birth weight less than 1 kg decreased from 33% to 16% (APC -3.82%). Use of nasal-continuous-positive-airway pressure increased (at call: APC 15.39%; during transfer: APC 15.60%), while use of self-inflating bag (at call: APC -12.09%), oxygen therapy (at call: APC -13.00%; during transfer: APC -23.77%) and mechanical ventilation (at call: APC -2.71%; during transfer: APC -2.99%) decreased. Use of oxygen concentrations at 21% increased (at call: APC 6.26%; during transfer: APC 7.14%), while oxygen concentrations above 40% decreased (at call: APC -5.73%; at transfer APC -8.89%). Surfactant administration at call increased (APC 3%-10%), while surfactant administration when arriving at referring hospital remained around 7-11% (APC 2.55%). CONCLUSION: Relevant trends toward "gentle" approaches in early respiratory management of very preterm infants undergoing postnatal transfer occurred during the last twenty years. In addition, the proportion of transferred extremely low birth weight infants halved. Clinicians and stakeholders should consider such information when allocating assets to both hospitals and transfer services and planning regional perinatal programs.

Influenza-associated hemolytic uremic syndrome: The pathogenic role of the virus.

A 3-year-old girl came to our attention for fever and upper respiratory tract infection associated with thrombocytopenia, non-immune hemolytic anemia, and acute kidney injury (AKI). Complete blood count and renal function slowly normalized, with no need for dialysis. She was always normotensive with valid diuresis; her neurological status also rapidly improved. Nasal swab turned out positive for influenza A H1N1; stool test was negative for Shiga toxin-producing Escherichia coli (STEC). The patient was treated with oseltamivir for 5 days with a favorable outcome. Association between hemolytic uremic syndrome (HUS) and H1N1 influenza is poorly reported in literature [1, 2, 3, 4]. The pathogenic role of the virus in causing HUS is still controversial and debated [1, 2, 3, 4]. In our patient, complement activity markers (serum C3 and C5b-9) alteration suggested a transient, virus-mediated complement activation.

Tissue Doppler Imaging in the evaluation of abdominal aortic pulsatility: a useful tool for the neonatologist.

Sonographic cardiac evaluation of newborns with suspected aortic coarctation (AoC) should tend to demonstrate a good phasic and pulsatile flow and the absence of pressure gradient along a normally conformed aortic arch from the modified left parasternal and suprasternal echocardiographic views; these findings, however, may not necessarily rule out a more distal coarctation in the descending aorta. For this reason, the sonographic exam of newborns with suspected AoC should always include a Doppler evaluation of abdominal aortic blood flow from the subcostal view. Occasionally, however, a clearly pulsatile Doppler flow trace in abdominal aorta may be difficult to obtain due to the bad insonation angle existing between the probe and the vessel. In such suboptimal ultrasonic alignment situation, the use of Tissue Doppler Imaging instead of classic Doppler flow imaging may reveal a preserved aortic pulsatility by sampling the aortic wall motion induced by normal flow. We propose to take advantage of the TDI pattern as a surrogate of a normal pulsatile Doppler flow trace in abdominal aorta when the latter is difficult to obtain due to malalignment with the insonated vessel.

Intravenous paracetamol for PDA closure in the preterm: a single-center experience.

UNLABELLED: Increasing recent evidence favors paracetamol use for patent ductus arteriosus (PDA) closure in preterms. Our study aims were (1) to assess efficacy and safety of intravenous (i.v.) paracetamol for PDA closure in a 23-32-week preterm population, as "first-line" (when traditional ibuprofen treatment was contraindicated) or "rescue" treatment (after ibuprofen failed), and (2) to identify predictors of PDA closure. The cumulative efficacy of consecutive cycles of i.v. paracetamol on PDA closure was confirmed after both "first-line" and "rescue" treatment, the overall PDA closure rates being, respectively, 56.7 and 61.1 % (p = 0.7624) after two cycles and 63.3 and 77.8 % (p = 0.2959) after three cycles. No toxicity was apparent after either "first-line" or "rescue" i.v. paracetamol treatment. On multivariate analysis, gestational age (GA) emerged as an independent predictor of PDA closure in the "first-line" i.v. paracetamol treatment group, while clinical risk index for babies (CRIB) score (a patient risk index based on birth weight, GA at birth, sex, patient's temperature on admission, and maximum base excess in first 12 h of life) was an independent predictor of PDA closure failure in the "rescue" group. CONCLUSION: I.V. paracetamol proved effective in our study population. Randomized control trials (RCTs) are warranted to further investigate the efficacy and safety of i.v. paracetamol for PDA closure in preterms. WHAT IS KNOWN: • Oral paracetamol has been judged as effective as oral ibuprofen for PDA closure in the preterm. • To date, only a handful of non-randomized studies exist to support the effectiveness of i.v. paracetamol in PDA closure. What is New: • Our observations confirm the clinical efficacy of i.v. paracetamol for PDA closure in a very low birth weight (VLBW)/extremely low birth weight (ELBW) preterm population. • Gestational age and CRIB score emerge as independent predictors of PDA closure.