Monitoring lung and cerebral oxygenation using near-infrared spectroscopy in preterm infants during kangaroo mother care.

Lung function has never been assessed during kangaroo mother care (KMC) in preterm infants. We measured lung (rSO2L) and cerebral (rSO2C) oxygenation by near-infrared spectroscopy (NIRS) in infants born at less than 32 weeks of gestation or weighing ≤ 1500 g during KMC. rSO2L, rSO2C, and pulmonary (FOEL) and cerebral (FOEC) tissue oxygen extraction fraction were measured in 20 preterm infants before, during, and after a 2-h period of KMC at a mean postnatal age of 36 ± 21 days of life. We found that rSO2L, rSO2C, FOEL, and FOEC did not change in our patients. After 120 min of KMC, rSO2L was lower (71.3 ± 1.4 vs. 76.7 ± 4.6%; P = 0.012) in infants with BPD (n = 6; 30%) than in infants without BPD (n = 14 = 60%), while FOEL was higher (0.26 ± 0.02 vs. 0.20 ± 0.05; P = 0.012).Conclusion: Cerebral and lung oxygenation did not change in preterm infants during KMC. A transient decrease in lung oxygenation was offset by the increase in oxygen extraction, but these changes were clinically insignificant. These results confirm the safety of KMC in preterm infants who are in stable clinical conditions. What is Known • Kangaroo mother care (KMC) is widely used to improve the care of preterm newborns since it improves their outcome. • KMC is safe as patients' vital parameters, are not negatively affected, but lung function has never been directly assessed. What is New • Cerebral and lung oxygenation measured by near-infrared spectroscopy did not change during KMC. • A transient decrease in lung oxygenation compensated for by the increase in oxygen extraction occurred only in infants with BPD, but these changes were clinically insignificant.

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.

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%.

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.

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.

Midwife-to-newborn ratio and neonatal outcome in healthy term infants.

AIM: To assess the effect of midwife-to-infant ratio on healthy term infant outcome. METHODS: Infants were enrolled in an inhospital midwife-led centre and an obstetrician-led centre with different midwife-to-infant ratios (1:2.5-1:5 vs 1:7-1:15). The primary endpoint was exclusive breastfeeding rate; secondary endpoints were neonatal admission in neonatal care unit rate and length of hospital stay. RESULTS: One hundred and ten infants were enrolled in both midwife- and obstetrician-led centre. Exclusive breastfeeding rate at discharge was higher (88% vs 78%, P = .048) in infants born in the midwife- than in the obstetrician-led centre. Admission rate in neonatal care units (9% vs 2%, P = .017) and stay in hospital duration (3.1 ± 1.8 vs 2.6 ± 0.8 days, P = .008) were higher in the obstetrician- than in the midwife-led centre. Birth in the midwife-led centre increased the likelihood of exclusive breastfeeding (OR: 2.04, 1.07-3.92), while newborns' admission in neonatal care units decreased it (OR : 0.17, 0.07-0.43). CONCLUSION: Healthy term infants' neonatal outcome is negatively associated with a low midwife-to-infant ratio which decreases exclusive breastfeeding rate and is associated with a higher likelihood of admission in neonatal care units and longer stay in hospital.

Changes in bilirubin in infants with hypoxic-ischemic encephalopathy.

Antioxidant properties of bilirubin have been reported in many studies. We hypothesized that bilirubin might be involved in neuroprotection mechanisms against oxidative stress in infants with hypoxic-ischemic encephalopathy (HIE) and that total serum bilirubin (TSB) might increase in these patients. We retrospectively studied infants with gestational age ≥ 35 weeks and birth weight ≥ 1800 g who were admitted to the neonatal intensive care unit (NICU) with a diagnosis of moderate-to-severe HIE and received or did not receive therapeutic hypothermia. We evaluated peak TSB and changes of mean TSB in these patients in comparison with a control group of infants admitted to the NICU with diagnoses other than HIE. Peak and mean TSB values were lower in the no hypothermia and hypothermia groups in comparison with the control group, while differences were not noted between infants who received hypothermia or did not. Regression analysis showed that HIE and hypothermia significantly reduced the risk of developing TSB values higher than median value (> 8.4 mg/dL) in our population.Conclusion: Peak and mean TSB values were lower in infants with moderate-to-severe HIE than in control infants. HIE and hypothermia independently decreased TSB. These results exclude a TSB increase as a neuroprotective mechanism in infants with HIE. We speculated that low TSB values in infants with HIE could be due to hypoxic repression of HO expression and represent a defensive strategy for limiting brain injuries in these patients. What is Known: • The role of oxidative stress in the pathophysiology of hypoxic-ischemic encephalopathy (HIE) has been elucidated in many studies, and other studies have demonstrated the antioxidant properties of bilirubin. • The potential neuroprotective role of bilirubin as antioxidant agent has never been evaluated in infants with HIE. What is New: • Mean total serum bilirubin (TSB) values are lower in infants with moderate-to-severe HIE than in control infants, since HIE and hypothermia independently decreased TSB. • An increase in bilirubin was not a neuroprotective mechanism in infants with HIE possibly because of hypoxic repression of HO expression as defensive strategy for limiting brain injuries.

Effect on cerebral oxygenation of paracetamol for patent ductus arteriosus in preterm infants.

Paracetamol seems to have similar success rates compared with indomethacin and ibuprofen in closing patent ductus arteriosus (PDA) in preterm infants, but with a better safety profile. The aim of our study was to evaluate the possible effects of paracetamol on cerebral oxygenation and cerebral blood flow velocity (CBFV). Infants with gestational age < 32 weeks with hemodynamically significant PDA (hsPDA) were prospectively studied by near infrared spectroscopy (NIRS) after the first dose of paracetamol (15 mg/kg) or ibuprofen (10 mg/kg). Cerebral regional oxygenation (rSO2C) and fractional oxygen extraction ratio (FOEC) were recorded 30 min before (T0) and 60 ± 20 min (T1), 180 ± 30 min (T2), and 360 ± 30 min (T3) after the beginning of drug infusion. Moreover, mean flow velocity (Vmean) and resistance index (RI = PSV-DV/PSV) measured with Doppler ultrasound in pericallosal artery were recorded at the same times. Significant changes in rSO2C and FOEC were not found during the study period within and between the groups. Similarly, Vmean did not vary in infants treated with paracetamol or ibuprofen, while RI decreased in the ibuprofen group. CONCLUSION: The treatment of hsPDA with paracetamol does not affect cerebral oxygenation in very preterm infants; there were no differences in cerebral oxygenation in infants treated with paracetamol or ibuprofen, although in the ibuprofen group, the possible closure progression of PDA was associated to changes of RI. What is Known: • Paracetamol has similar success rates to indomethacin and ibuprofen in closing PDA with a better safety profile since previous studies did not report adverse effects. What is New: • Paracetamol does not affect cerebral oxygenation and perfusion in very preterm infants with PDA and this confirms its good safety profile.

Painful procedures can affect post-natal growth and neurodevelopment in preterm infants.

AIM: This Italian study evaluated whether painful procedures during the first four weeks of life were related to subsequent weight gain, head circumference (HC) and neurodevelopmental outcomes in preterm infants, METHODS: We evaluated the number of invasive procedures that infants born at less than 32 weeks of gestational age (GA) underwent in the Neonatal Intensive Care Unit of Careggi Hospital, Florence, from January to December 2015. Weight and HC were recorded at birth, 36 weeks of PMA and six and 12 months of CA. Neurological outcomes were assessed at six and 12 months of CA using the Bayley Scales of Infant and Toddler Development - Third Edition. RESULTS: We studied 83 preterm infants with a GA of 28 ± 2 weeks and birth weight of 1098 ± 340 g. A higher number of invasive painful procedures were related to a lower HC standard deviation score at 36 weeks of PMA and six and 12 months of CA and with lower cognitive scores at six months. At 12 months, the relationship only remained significant for infants born at less than 28 weeks (p < 0.001). CONCLUSION: Invasive painful procedures affected regular HC growth and short-term cognitive scores in preterm infants in the first year of life.

Area-based study identifies risk factors associated with missed antenatal corticosteroid prophylaxis in women delivering preterm infants.

AIM: All women delivering a preterm infant should receive antenatal corticosteroid prophylaxis, but many miss this opportunity. We determined the risk factors associated with missed prophylaxis in a geographically defined area of Italy. METHODS: We prospectively studied all mothers who delivered babies between 24 and 31 completed weeks of gestation, from 2009 to 2013, in all maternity units in Tuscany. RESULTS: Of 1232 mothers, 186 (15.1%) did not receive prophylaxis. The risk was higher in migrant mothers, with an adjusted risk ratio (RR) of 1.28 and 95% confidence interval (95% CI) of 1.04-1.56, and in mothers hospitalised for less than 24 hours (RR 4.09, 95% CI: 2.90-5.78). Preterm prelabour rupture of membranes (RR 0.63, 95% CI: 0.41-0.96) and maternal antepartum transfer (RR 0.24, 95% CI: 0.18-0.32) were protective. Hospital level at birth and gestational age did not influence the prophylaxis rate. The population-attributable fractions were 50.4% for late hospital admissions and 10.2% for migrant status. CONCLUSION: In a highly organised network of hospitals, neither level of care nor gestational age influenced prophylaxis. Timely arrival of women in hospital, better recognition of the imminence of delivery and tighter steroids administration guidelines are the most relevant targets to further increase prophylaxis.