A structured programme to promote breastfeeding improved the rates in very preterm infants at discharge.

AIM: We developed the Promotion of Breastfeeding (PROBREAST) programme and evaluated what effect it had on the breastfeeding rate in infants born at less than 32 weeks of gestation or weighing ≤1500 grams. METHODS: We compared the breastfeeding rate in two cohorts of patients who were born before (n = 72; January 2017 to June 2018) and after (n = 80; July 2018 to December 2019) the application of the programme. Moreover, we compared the correlation between type of feeding at discharge and post-discharge breastfeeding rate, between exclusive breastfeeding, postnatal growth and neurodevelopment. RESULTS: Infants in the PROBREAST group had an exclusive breastfeeding rate at discharge higher (42 vs. 16%, p < 0.001) than that in the historical control group. Exclusive breastfeeding was negatively correlated with weight z-score at discharge, but not at 12 and 24 months corrected age, and was positively correlated with cognitive score at 24 months corrected age. CONCLUSION: The application of a structured programme for the promotion of breastfeeding improved the breastfeeding rate in very preterm infants. We demonstrated that exclusive breastfeeding at discharge improved their neurodevelopment without impairing growth.

A Simulation Competition on Neonatal Resuscitation as a New Educational Tool for Pediatric Residents.

BACKGROUND: Training programs on resuscitation have been developed using simulation-based learning to build skills, strengthen cognitive strategies, and improve team performance. This is especially important for residency programs where reduced working hours and high numbers of residents can reduce the educational opportunities during the residency, with lower exposure to practical procedures and prolonged length of training. Within this context, gamification has gained popularity in teaching and learning activities. This report describes the implementation of a competition format in the context of newborn resuscitation and participants' perceptions of the educational experience. METHODS: Thirty-one teams of three Italian pediatric residents participated in a 3-day simulation competition on neonatal resuscitation. The event included an introductory lecture, familiarization time, and competition time in a tournament-like structure using high-fidelity simulation stations. Each match was evaluated by experts in neonatal resuscitation and followed by a debriefing. The scenarios and debriefings of simulation station #1 were live broadcasted in the central auditorium where teams not currently competing could observe. At the end of the event, participants received an online survey regarding their perceptions of the educational experience. RESULTS: 81/93 (87%) participants completed the survey. Training before the event mostly included reviewing protocols and textbooks. Low-fidelity manikins were the most available simulation tools at the residency programs. Overall, the participants were satisfied with the event and appreciated the live broadcast of scenarios and debriefings in the auditorium. Most participants felt that the event improved their knowledge and self-confidence and stimulated them to be more involved in high-fidelity simulations. Suggested areas of improvement included more time for familiarization and improved communication between judges and participants during the debriefing. CONCLUSIONS: Participants appreciated the simulation competition. They self-perceived the educational impact of the event and felt that it improved their knowledge and self-confidence. Our findings suggest areas of improvements for further editions and may serve as an educational model for other institutions.

Carboxyhemoglobin as biomarker of late-onset sepsis in preterm infants.

Carboxyhemoglobin (COHb) is considered a biomarker of oxidative stress and previous studies reported an increase in COHb levels in preterm infants who develop late-onset sepsis (LOS). Our aim was to assess the correlation between COHb levels and the risk for LOS development. We retrospectively studied 100 preterm infants, 50 in the LOS and 50 in the no LOS group. COHb levels were measured on the day of diagnosis of the first episode of LOS, 3, 2, and 1 days before and 1 and 4 days after the onset of LOS. Logistic regression analysis showed that a higher level of COHb 2 days before the diagnosis of LOS increases the risk for LOS development (OR 12.150, 95% Cl 1.311-12.605; P = 0.028). A COHb level of 1.55% measured 2 days before the diagnosis of LOS is the best predictive threshold for LOS with a sensitivity of 70% and a specificity of 70%.    Conclusion: Increased levels of COHb may predict the diagnosis of LOS in very preterm infants with a good accuracy. If further studies confirm our findings, this easy-to-measure biomarker could provide neonatologists with another tool for monitoring and early diagnosis of sepsis in high-risk patients. What is Known: • Carboxyhemoglobin (COHb) is a biomarker of oxidative stress. • Previous studies reported an increase in COHb levels in preterm infants who develop late-onset sepsis (LOS). What is New: • COHb levels increased two days before the diagnosis of LOS and this increase was associated with the risk for developing LOS. • ROC curve analysis for COHb measured two days before the diagnosis of LOS showed that 1.55% is the best predictive threshold for LOS with a sensitivity of 70% and a specificity of 70%.

Neonatal Outcomes of Term Infants Born with Meconium-Stained Amniotic Fluid.

Background Meconium-stained amniotic fluid (MSAF) is considered an alarming sign of possible fetal compromise and it has recently been reported that neonatal outcome correlates with the degree of meconium thickness. Methods We retrospectively studied 400 term infants allocated in clear amniotic fluid and grade 1, 2, and 3 MSAF groups on the basis of color and thickness of AF. Multivariable logistic regression analysis was performed to evaluate the potential independent effect of delivery with MSAF of different severity on the risk of a composite adverse neonatal outcome. Results We found that delivery with grade 2 (OR 16.82, 95% Cl 2.12-33.52; p = 0.008) and 3 (OR 33.79, 95% Cl 4.24-69.33; p < 0.001) MSAF is independently correlated with the risk of adverse neonatal outcome, such as the occurrence of at least one of the following: need of resuscitation in the delivery room, blood cord pH < 7.100, occurrence of meconium aspiration syndrome (MAS), persistent pulmonary hypertension (PPH), transient tachypnea of the newborn (TTN), acute respiratory distress syndrome (ARDS), hypoxic-ischemic encephalopathy (HIE), and sepsis. Conclusions There is a positive correlation between the severity of amniotic fluid meconium staining and thickness and the outcomes of term infants. Therefore, the evaluation and grading of MSAF during labor is useful in order to plan for the presence of a neonatologist at delivery for immediate and proper neonatal care.

Cardiac Hypertrophy Associated with Insulin Therapy in Extremely Preterm Infants.

BACKGROUND: In the neonatal period, cardiac hypertrophy (CH) has been commonly associated with hyperinsulinemic pathologies, and the first case of CH in an extremely preterm infant treated with insulin infusion has recently been reported. To confirm this association, we report a case series of patients who developed CH after insulin therapy. METHODS: Infants with gestational age < 30 weeks and birth weight < 1500 g, born from November 2017 to June 2022, were studied if they developed hyperglycemia requiring treatment with insulin and had echocardiographic diagnosis of CH. RESULTS: We studied 10 extremely preterm infants (24.3 ± 1.4 weeks) who developed CH at a mean age of 124 ± 37 h of life, 98 ± 24 h after the initiation of insulin therapy. All surviving patients had resolution of CH at discharge, while three of four (75%) of the deceased patients had persistent CH. CONCLUSIONS: Our case series supports the association between the development of CH and insulin therapy in extremely preterm infants and suggests further caution and the need for echocardiographic monitoring when treating these fragile patients with insulin.

Carboxyhemoglobin as biomarker of prematurity complications.

BACKGROUND: Carboxyhemoglobin (COHb) is considered a biomarker of oxidative stress and previous studies suggest a correlation between its blood level and prematurity complications. Our aim in this study was to assess the correlation between COHb levels and the risk for bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and retinopathy of prematurity (ROP). METHODS: We retrospectively studied 178 preterm infants with gestational age of 27.0 ± 1.5 weeks, among which 121 (68 %) had BPD, 43 (24 %) IVH, and 33 (19 %) ROP. COHb levels measured during the first seven days of life were recorded. RESULTS: Logistic regression analysis showed that higher levels of COHb on the seventh day of life increases the risk for moderate-to-severe BPD (OR 4.552, 95 % Cl 1.220-16.997; P = 0.024), while higher levels of COHb on the fourth day of life increases the risk for grade 2-4 IVH (OR 5.537, 95 % Cl 1.602-19.134; P = 0.007). CONCLUSIONS: COHb measured in the first week of life can contribute to predicting the risk for BPD and IVH, but not for ROP, in very preterm infants. Since COHb can be readily measured, its assessment can be useful in clinical practice for early identification of preterm infants at high risk for oxidative stress related complications.

Chronic Training Induces Metabolic and Proteomic Response in Male and Female Basketball Players: Salivary Modifications during In-Season Training Programs.

The aim of this study was to characterize the salivary proteome and metabolome of highly trained female and male young basketball players, highlighting common and different traits. A total of 20 male and female basketball players (10 female and 10 male) and 20 sedentary control subjects (10 female and 10 male) were included in the study. The athletes exercised at least five times per week for 2 h per day. Saliva samples were collected mid-season, between 9:00 and 11:00 a.m. and away from sport competition. The proteome and metabolome were analyzed by using 2DE and GC-MS techniques, respectively. A computerized 2DE gel image analysis revealed 43 spots that varied in intensity among groups. Between these spots, 10 (23.2%) were differentially expressed among male athletes and controls, 22 (51.2%) between female basketball players and controls, 11 spots (25.6%) between male and female athletes, and 13 spots (30.2%) between male and female controls. Among the proteins identified were Immunoglobulin, Alpha-Amylase, and Dermcidin, which are inflammation-related proteins. In addition, several amino acids, such as glutamic acid, lysine, ornithine, glycine, tyrosine, threonine, and valine, were increased in trained athletes. In this study, we highlight that saliva is a useful biofluid to assess athlete performance and confirm that the adaptation of men and women to exercise has some common features, but also some different sex-specific behaviors, including differential amino acid utilization and expression of inflammation-related proteins, which need to be further investigated. Moreover, in the future, it will be interesting to examine the influence of sport-type on these differences.

Preliminary results indicate that regular training induces high protection against oxidative stress in basketball players compared to soccer.

In elite athlete several metabolic changes occur during regular training. These modifications are associated with changes in blood metabolic profile and can lead to adaptive mechanisms aimed at establish a new dynamic equilibrium, which guarantees better performance. The goal of this study was to characterize the plasma metabolic profile and redox homeostasis, in athletes practicing two different team sports such as soccer and basketball in order to identify potential metabolic pathways underlying the differences in training programs. A cohort of 30 male, 20 professional players (10 soccer and 10 basketballs) and 10 sedentary males as control were enrolled in the study. Plasma redox balance, metabolites and adiponectin were determined. The results show low levels of oxidative species (25.5%), with both high antioxidant capacity (17.6%) and adiponectin level (64.4%) in plasma from basketball players, in comparison to soccer players. Metabolic analysis indicates in basketball players a significant high plasma level of amino acids Valine and Ornithine both involved in redox homeostasis and anti-inflammatory metabolism.

Effects of a 24-Week Exercise Program on Functional Fitness, Oxidative Stress, and Salivary Cortisol Levels in Elderly Subjects.

Background and Objectives: Aging is a biological and irreversible process characterized by physiological alterations resulting in a progressive decline in biological functions, decreased resistance or adaptability to stress, and increased disease susceptibility. A decline in functional fitness, imbalance between pro- and antioxidant capacity, and/or hormonal dysregulation adversely impact physical capacity, emotional status, and overall quality of life, especially within the elderly population. On the other hand, regular physical activity is considered an effective strategy to prevent and reduce those changes associated with primary aging and concurrent chronic disease, while slowing age-related physical degeneration. However, there is still limited evidence-based information regarding both the intensity and interval of effective interventions on physical functioning in older adults. Thus, the aim of the study was to assess the effects of a 24-week regular multimodal exercise program on functional fitness, oxidative stress, salivary cortisol level, and self-perceived quality of life in a group of eighteen physically active elderly subjects (mean age 72.8 ± 7.5 years). Materials and Methods: A set of anthropometric and physical measurements (grip strength, chair sit to stand, sit and reach and back scratch) assessing the functional fitness performance were evaluated. Moreover, biochemical markers (derived-reactive oxygen metabolites (d-ROMs) and the biological antioxidant potential (BAP) tests, and salivary cortisol levels) and the EuroQoL 5-Dimension 3-Level (EuroQoL 5-D 3-L) self-perceived questionnaire of quality of life were measured before and after the intervention program. All measurements were normally distributed as assessed by D'Agostino and Pearson's omnibus normality test. Student's t-tests were used to evaluate the differences in all the parameters measured at baseline (T0) and after the 24-week physical program (T1). Results: The results showed that an age-tailored structured intervention exercise program (1 h per session, twice per week, for 24 weeks) was effective in improving flexibility and other biomechanical parameters, such as muscle strength and the dynamic balance fitness component, which are key to performing daily tasks independently. Moreover, biochemical analyses demonstrate that the proposed intervention program has beneficial effects on the balance between plasma ROS production and their neutralization. Conclusions: The results confirm the benefits of regular physical activity in older adults resulting in improved physical strength and flexibility in the functional fitness parameters, and in regulating anti- and pro-oxidant activity and cortisol (stress hormone) levels.

Splanchnic oxygenation during phototherapy in preterm infants with hyperbilirubinemia.

BACKGROUND: It has been reported that preterm infants can develop feeding intolerance during phototherapy (PT) and that PT can affect mesenteric perfusion in these patients. AIMS: Our aim was to assess if PT can decrease regional splanchnic oxygenation (rSO2S) measured by near infrared spectroscopy (NIRS). STUDY DESIGN: We prospectively studied infants with gestational age of 25-34 weeks with hyperbilirubinemia requiring PT. Splanchnic regional oxygenation (rSO2S), oxygen extraction fraction (FOES), and cerebrosplanchnic oxygenation ratio (CSOR) were recorded before, during, and after PT discontinuation. RESULTS: During PT rSO2S and CSOR significantly decreased and this effect lasted for some hours after its interruption. FOES contemporary increased, although this effect was not statistically significant. CONCLUSIONS: PT treatment decreases splanchnic oxygenation in preterm infants likely due to peripheral vasodilation which triggers a redistribution of blood flow. These results can help explain the association between PT and the development of feeding intolerance in preterm infants.

Changes of Oxidative Stress-Related Gene Expression in an in vitro Model of Neonatal Hypoxic-Ischemic Encephalopathy.

BACKGROUND: We recently demonstrated that oxygen-glucose deprivation (OGD) and unconjugated bilirubin (UCB) can damage mature and immature organotypic hippocampal slices and induce an oxidative stress similar to what occurs in jaundiced term and preterm infants with hypoxic-ischemic encephalopathy (HIE). OBJECTIVES: To assess the effects of OGD and UCB on the expression of heme-oxygenase 1 (HO-1) and oxidative stress-related enzymes in an in vitro model of HIE. METHODS: Mature and immature organotypic hippocampal slices were exposed to 30-min OGD and to 24 h UCB or UCB plus human serum albumin (HSA). The expression of HO-1, superoxide dismutase 1 (SOD1), catalase (CAT), glutathione peroxidase (GPX), and nuclear factor erythroid-related factor 2 were analyzed by real-time PCR. RESULTS: In mature slices, OGD did not affect the expression of HO-1 and oxidative stress-induced enzymes. The addition of UCB was associated with the upregulation of HO-1 and Nrf2 that is abolished by the presence of equimolar amount of HSA. In immature slices, OGD induced the downregulation of CAT, GPX, and Nrf2 expression and the addition of UCB further decreased GPX. The addition of UCB and HSA reverted the effects of OGD and UCB on gene expression. CONCLUSIONS: In an in vitro model of HIE in term infants, we did not observe neuroprotective changes of the expression of HO-1 and genes involved in antioxidant defenses. Conversely, in an in vitro model of HIE in preterm infants, we observed a harmful decrease of the expression of genes encoding for antioxidant enzymes.

Pharmaceutical strategies for preventing toxicity and promoting antioxidant and anti-inflammatory actions of bilirubin.

Bilirubin (BR) is the final product of haem catabolism. Disruptions along BR metabolic/transport pathways resulting from inherited disorders can increase plasma BR concentration (hyperbilirubinaemia). Unconjugated hyperbilirubinemia may induce BR accumulation in brain, potentially causing irreversible neurological damage, a condition known as BR encephalopathy or kernicterus, to which newborns are especially vulnerable. Numerous pharmaceutical strategies, mostly based on hemoperfusion, have been proposed over the last decades to identify new valid, low-risk alternatives for BR removal from plasma. On the other hand, accumulating evidence indicates that BR produces health benefits due to its potent antioxidant, anti-inflammatory and immunomodulatory action with a significant potential for the treatment of a multitude of diseases. The present manuscript reviews both such aspects of BR pharmacology, gathering literature data on applied pharmaceutical strategies adopted to: (i) reduce the plasma BR concentration for preventing neurotoxicity; (ii) produce a therapeutic effect based on BR efficacy in the treatment of many disorders.

Feeding intolerance during phototherapy in preterm infants.

OBJECTIVE: Many very preterm infants are treated with phototherapy (PT) for hyperbilirubinemia and it has been reported that PT can negatively affect gut perfusion. Thus, our aim was to evaluate the occurrence of feeding intolerance in the course of PT in these patients. METHODS: We retrospectively studied infants born at 25+0-31+6 weeks from November 2017 to April 2020 who required PT during the first two weeks of life. Patients were used as their own controls recording for each one the occurrence of feeding intolerance after starting PT and the resumption of feeding tolerance after its termination. RESULTS: We studied 125 preterm infants of whom 58 (46%) developed a feeding intolerance which disappeared in 47 (81%) of them at the end of PT. Regression analysis showed a trend toward a not significant decrease of risk of feeding intolerance in infants with higher birth weight and age at the start of the first course of PT. CONCLUSION: We found that about half of our patients developed a transient feeding intolerance during PT that ceased in the vast majority of them after termination of the therapy. Further studies are necessary to confirm the correlation between PT and feeding intolerance.

Neurotoxicity of Unconjugated Bilirubin in Neonatal Hypoxic-Ischemic Brain Injury in vitro.

Background: The pathophysiology of bilirubin neurotoxicity in course of hypoxic-ischemic encephalopathy (HIE) in term and preterm infants is still poorly understood. We hypothesized that oxidative stress may be a common mechanism that link hyperbilirubinemia and HIE. Objectives: The objective of the present study was to evaluate whether unconjugated bilirubin (UCB) may enhance the HI brain injury by increasing oxidative stress and to test pioglitazone and allopurinol as new antioxidant therapeutic drugs in vitro. Methods: The effects of UCB were tested on organotypic hippocampal slices subjected to 30 min oxygen-glucose deprivation (OGD), used as in vitro model of HIE. The experiments were performed on mature (14 days in culture) and immature (7 days in culture) slices, to mimic the brains of term and preterm infants, respectively. Mature and immature slices were exposed to UCB, human serum albumin (HSA), pioglitazone, and/or allopurinol for 24 h, immediately after 30 min OGD. Neuronal injury was assessed using propidium iodide (PI) fluorescence. ROS formation was quantified by using the 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA) method. Results: In mature slices, we found that the neurotoxicity, as well as oxidative stress, induced by OGD were enhanced by UCB. HSA significantly prevented UCB-increased neurotoxicity, but had a slight reduction on ROS production. Allopurinol, but not pioglitazone, significantly reduced UCB-increased neurotoxicity induced by OGD. In immature slices exposed to OGD, no increase of neuronal death was observed, whereas oxidative stress was detected after UCB exposure. HSA, pioglitazone and allopurinol have no protective effects on both OGD-induced neuronal death and on UCB-induced oxidative stress. For this reason, UCB, pioglitazone and allopurinol was also tested on ischemic preconditioning protocol. We found that UCB abolished the neuroprotection induced by preconditioning and increased oxidative stress. These effects were restored by allopurinol but not pioglitazone. Conclusions: UCB characterized a different path of neuronal damage and oxidative stress in mature and immature hippocampal slice model of HIE. Management of hyperbilirubinemia in a complex pathological condition, such as HIE and hyperbilirubinemia, should be very careful. Allopurinol could deserve attention as a novel pharmacological intervention for hyperbilirubinemia and HIE.

How to Provide Motherside Neonatal Resuscitation with Intact Placental Circulation?

Immediate clamping and cutting of the umbilical cord have been associated with death and/or neurodisability [...].

Cerebral and splanchnic oxygenation during automated control of inspired oxygen (FiO2 ) in preterm infants.

OBJECTIVES: Our aim in this study was to assess the effect of the Predictive Intelligent Control of Oxygenation (PRICO® ) system on cerebral (rSO2 C) and splanchnic (rSO2 S) oxygenation in a cohort of preterm infants with frequent desaturations. METHODS: Twenty infants with gestational age <32 weeks (n = 20) were assigned in random sequence to 12 h of automated or manual adjustment of FiO2 . Over this period, they were studied continuously by near-infrared spectroscopy (NIRS). RESULTS: We found that rSO2 C [68.0% (60.5%-74.7%) vs. 68.5% (62%-72%); p = .824] and rSO2 S [27.0% (17.3%-45.7%) vs. 27.0% (15%-53%); p = .878] were similar during automatic and manual control of FiO2 . Time spent with SpO2 90%-95% was higher during the automatic than manual control of FiO2 , while time spent with SpO2 <80% or >95% was lower. CONCLUSIONS: Automated control of FiO2 with PRICO® system did not improve brain and splanchnic oxygenation in comparison with manual control in a cohort of preterm infants, but it significantly decreased SpO2 fluctuations and limited the duration of both hypoxemia and hyperoxemia.

Thermal management with and without servo-controlled system in preterm infants immediately after birth: a multicentre, randomised controlled study.

BACKGROUND: The thermal servo-controlled systems are routinely used in neonatal intensive care units (NICUs) to accurately manage patient temperature, but their role during the immediate postnatal phase has not been previously assessed. OBJECTIVE: To compare two modalities of thermal management (with and without the use of a servo-controlled system) immediately after birth. STUDY DESIGN AND SETTING: Multicentre, unblinded, randomised trial conducted 15 Italian tertiary hospitals. PARTICIPANTS: Infants with estimated birth weight <1500 g and/or gestational age <30+6 weeks. INTERVENTION: Thermal management with or without a thermal servo-controlled system during stabilisation in the delivery room. PRIMARY OUTCOME: Proportion of normothermia at NICU admission (axillary temperature 36.5°C-37.5°C). RESULTS: At NICU admission, normothermia was achieved in 89/225 neonates (39.6%) with the thermal servo-controlled system and 95/225 neonates (42.2%) without the thermal servo-controlled system (risk ratio 0.94, 95% CI 0.75 to 1.17). Thermal servo-controlled system was associated with increased mild hypothermia (36°C-36.4°C) (risk ratio 1.48, 95% CI 1.09 to 2.01). CONCLUSIONS: In very low birthweight infants, thermal management with the servo-controlled system conferred no advantage in maintaining normothermia at NICU admission, while it was associated with increased mild hypothermia. Thermal management of preterm infants immediately after birth remains a challenge. TRIAL REGISTRATION NUMBER: NCT03844204.