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Background: The benefits of facilitating breastmilk feeding and close contact between mother and neonate (family-centred care; FCC) in the perinatal period are well-established. The aim of this study was to determine how the delivery of FCC practices were impacted for neonates born to mothers with perinatal SARS-CoV-2 infection during the COVID-19 pandemic., Methods: Neonates born to mothers with confirmed SARS-CoV-2 infection during pregnancy were identified from the 'EsPnIC Covid paEdiatric NeonaTal REgistry' (EPICENTRE) multinational cohort between 10 March 2020 and 20 October 2021. The EPICENTRE cohort collected prospective data on FCC practices. Rooming-in and breastmilk feeding practice were the main outcomes, and factors influencing each were determined. Other outcomes included mother-baby physical contact prior to separation and the pattern of FCC components relative to time and local site guidelines., Findings: 692 mother-baby dyads (13 sites, 10 countries) were analysed. 27 (5%) neonates were positive for SARS-CoV-2 (14 (52%) asymptomatic). Most sites had policies that encouraged FCC during perinatal SARS-CoV-2 infection for most of the reporting period. 311 (46%) neonates roomed-in with their mother during the admission. Rooming-in increased over time from 23% in March-June 2020 to 74% in January-March 2021 (boreal season). 330 (93%) of the 369 separated neonates had no FCC physical contact with their mother prior, and 319 (86%) were asymptomatic. Maternal breastmilk was used for feeding in 354 (53%) neonates, increasing from 23% to 70% between March-June 2020 and January-March 2021. FCC was most impacted when mothers had symptomatic COVID-19 at birth., Interpretation: This is the largest report of global FCC practice during the COVID-19 pandemic to date. The COVID-19 pandemic may have impacted FCC despite low perinatal transmission rates. Fortunately, clinicians appear to have adapted to allow more FCC delivery as the COVID-19 pandemic progressed., Funding: The National Health and Medical Research Council (Australia): Grant ID 2008212 (DGT), Royal Children's Hospital Foundation: Grant ID 2019-1155 (EJP), Victorian Government Operational Infrastructure Support Program., Competing Interests: AM received an honorarium from Medtronic for one lecture in a symposium related to mechanical ventilation., (© 2023 The Authors.)

Neurally adjusted ventilatory assist (NAVA) ventilation allows patients to determine their peak inspiratory pressure and tidal volume on a breath-by-breath basis. Apprehension exists about premature neonates' ability to self-regulate breath size. This study describes peak pressure and tidal volume distribution of neonates on NAVA and non-invasive NAVA. This is a retrospective study of stored ventilator data with exploratory analysis. Summary statistics were calculated. Distributional assessment of peak pressure and tidal volume were evaluated, overall and per NAVA level. Over 1 million breaths were evaluated from 56 subjects. Mean peak pressure was 16.4 ± 6.4 in the NAVA group, and 15.8 ± 6.4 in the NIV-NAVA group (t test, p < 0.001). Mean tidal volume was 3.5 ± 2.7 ml/kg.Conclusion:In neonates on NAVA, most pressures and volumes were within or lower than recommended ranges with pressure-limited or volume-guarantee ventilation. What is known: • Limiting peak inspiratory pressures or tidal volumes are the main strategies to minimize ventilator-induced lung injury in neonates. Neurally adjusted ventilatory assist allows neonates to regulate their own peak inspiratory pressures and tidal volumes on a breath-to-breath basis using neural feedback. What is new: • When neonates chose the size of their breaths based on neural feedback, the majority of peak inspiratory pressures and tidal volumes were within or lower than the recommended peak inspiratory pressure or tidal volume ranges with pressure-limited or volume guarantee ventilation.

Background: Apnea time allows the clinician to set a minimum spontaneous respiratory frequency when using noninvasive neurally-adjusted ventilatory assist (NIV-NAVA). Short apnea times may provide backup ventilation during periods of physiologic variability causing overventilation and suppression of spontaneous respiratory drive. Longer apnea times may allow more spontaneous ventilation but can result in insufficient respiratory support. The purpose of this study was to evaluate various apnea times in neonates on NIV-NAVA., Methods: This was a 2-center, prospective, 1-factorial, interventional study of neonates <30 weeks gestational age on NIV-NAVA. Clinically important events and ventilator data were recorded for apnea times of 2 s and 5 s for 2 h each., Results: 15 neonates (26 ± 1.6 weeks gestational age, birthweight 893 ± 202 g) were studied. When compared to the 5-s apnea time, the 2-s apnea time showed increased switches into backup ventilation from 0.5 switches/min to 2.5 switches/min ( P < .001), and time spent in backup ventilation increased from 2%/min to 9%/min ( P < .001). However, clinically important events decreased from 7 clinically important events per hour to 2 clinically important events per hour ( P < .001). Measured breathing frequency increased with the 2-s apnea time but spontaneous breathing frequency, F IO 2 , peak and minimum electrical activity of the diaphragm, and peak pressure remained unchanged., Conclusion: Short apnea times resulted in more switches into backup ventilation and longer time in backup ventilation but promoted clinical stability with fewer clinically important events in neonates ventilated with NIV-NAVA., (Copyright © 2019 by Daedalus Enterprises.)

Objective: Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation that delivers ventilatory support in synchrony to the patient's respiratory needs using NAVA level, a proportionality constant that converts the electrical activity of the diaphragm (Edi) into a peak pressure (PIP). Recent published studies suggest that neonates can control the delivered ventilatory support through neural feedback. Systematically increasing the NAVA level initially increases the PIP while maintaining a constant Edi until an inflection point or breakpoint (BrP) is reached, at which time the PIP plateaus and the Edi signal decreases. This study was performed to establish if there is a correlation of pre- and post-extubation BrP in premature neonates., Study Design: NAVA level was increased by 0.5 cm H 2 O mcV -1 every 3 min from 0.1 to 3.0 cm H 2 O mcV -1 . PIP and Edi Peak and Minimum were recorded., Statistics: PIP and phasic Edi (Edi peak-Edi min) were averaged for each NAVA level, plotted on a graph, and the BrP was determined by visual inspection of the inflection point for PIP. The data from the studies were then combined by averaging each variable at the BrP and for each change in NAVA level above and below the BrP., Results: Fifteen infants were studied for paired titration studies. PIP increased until the BrP was reached and then plateaued during both the intubated and extubated titration studies. Edi decreased after the BrP was reached during the titration studies. The BrP increased when patients were extubated from NAVA to noninvasive (NIV) NAVA. As the NAVA level rose above the BrP, PIP plateaued at a higher level and Edi decreased less during the NIV NAVA titration study., Conclusions: Neonates demonstrated an increase in BrP, higher PIP and Edi when extubated from NAVA to NIV NAVA. This is most likely owing to the inefficiencies of NIV ventilation and suggests that neonates require a higher NAVA level when transitioning from NAVA to NIV NAVA.

Background: Neurally adjusted ventilator assist (NAVA) uses electrical activity of the diaphragm (Edi) to provide patient-directed ventilatory support. The NAVA level determines the proportional amount of ventilatory support. Systematically increasing NAVA level initially increases peak inspiratory pressure (PIP) while maintaining a constant Edi until a breakpoint (BrP) is reached. Further increases in NAVA level reduce the Edi, while the PIP plateaus. This study was performed to establish whether premature neonates have intact neural feedback systems allowing them to have a BrP., Method: NAVA level was increased by 0.5 cm H2O μV(-1) every 3 min from 0.5 to 4.0 cm H2O μV(-1). PIP, Edi, mean blood pressure, heart rate, respiratory rate, oxygen saturation and FIO2 were recorded. Statistics: Non-linear regression was done for PIP and Edi. Linear regression was done for the other variables. The data from the trials were combined by normalizing to NAVA levels above and below the BrP., Result: Nine neonates were studied on NAVA and 12 on non-invasive NAVA. PIP increased until the BrP was reached and then remained unchanged. Edi decreased after the BrP was reached. All other variables remained unchanged., Conclusion: Neonates demonstrated a BrP suggesting intact neural feedback mechanisms that may protect lungs from over distention with NAVA ventilation.

Background: Electrical activity of the diaphragm (E(di)) has been proposed as a parameter to evaluate respiratory function. Normative values of electrical activity of the diaphragm in full-term neonates are not known. This is a small case series to establish preliminary values of E(di) in term neonates and to determine how these values vary while awake and asleep and during feeding states., Methods: Three term neonates in room air and nippling feeds at the time of the study were observed for 4 hours. E(di) was measured by electrodes within a nasogastric tube positioned at the level of the diaphragm. Respiratory rate and heart rate were also recorded. Time while awake and asleep were noted. Feeding states included feeding, 30 min pre-prandial, and 30 min post-prandial. Statistics were analysis of variance and t tests, with P < .05., Results: Mean E(di) peak was 11 ± 5 μV. Mean E(di) minimum was 3 ± 2 μV. E(di) peak and minimum were higher while awake. E(di) peak was lower post-prandial. Respiratory rate was higher post-prandial., Conclusions: These are the first preliminary values for E(di) in neonates. Higher E(di) peak while awake may reflect larger tidal volume to meet increased metabolic requirements when awake and active. Post-prandial lower E(di) peak and higher respiratory rate may indicate compensation for decreased tidal volume from increased intra-abdominal pressure. These data may be useful in identifying respiratory pathology in neonates and monitoring progression toward respiratory health., (Copyright 2012 Daedalus Enterprises)

We previously demonstrated that prenatal corticosteroids attenuated the expected exponential increase in circulating catecholamines at birth. The present studies were undertaken to determine if alteration in sulfoconjugation could account for this attenuation. Catheterized fetal lambs received saline (n = 6) or corticosteroids (n = 8) intravenously for 60 h. The lambs were delivered by cesarean section at 130 +/- 1 days gestation. Ventilatory and cardiovascular responses and plasma catecholamine concentrations were measured for 2 h after birth. Although plasma free catecholamines levels were higher in controls than in corticosteroid-treated fetuses, the sulfoconjugated levels were similar in the two groups. Thus the corticosteroid-treated fetuses had a higher proportion of plasma sulfoconjugated catecholamines consistent with the possibility that sulfoconjugation was augmented during intrauterine life. After birth, the corticosteroid-treated animals showed an attenuated increase in plasma free catecholamine levels compared with controls but a similar increase in sulfoconjugated catecholamine levels to the control animals. The proportion of plasma sulfoconjugated catecholamines was higher in the corticosteroid-treated animals; however, the increase in sulfoconjugated catecholamines was insufficient to account for the attenuated overall increase in total catecholamines in the corticosteroid-treated animals.

Objectives: We examined the effect of prenatal corticosteroids and thyrotropin-releasing hormone on postnatal adaptation and sympathoadrenal function in preterm lambs., Study Design: Catheterized fetal lambs received saline solution (n = 6), corticosteroids alone (n = 8), or corticosteroids plus thyrotropin-releasing hormone (n = 6) for 60 hours. The lambs were delivered by cesarean section at a gestational age of 130 +/- 1 days. Ventilatory, cardiovascular, and metabolic responses and plasma catecholamine concentrations were measured for 2 hours after birth. Statistical analysis was performed by use of independent t tests or analysis of variance., Results: Ventilatory function and cardiac contractility were significantly improved in both corticosteroid and corticosteroid plus thyrotropin-releasing hormone animals. Lambs treated with corticosteroid plus thyrotropin-releasing hormone had significantly higher aortic pressure and left ventricular blood pressure than either of the other groups. The postnatal norepinephrine and epinephrine surge was blunted in response to corticosteroid and corticosteroid plus thyrotropin-releasing hormone treatment. There were no differences in metabolic responses among the three groups., Conclusions: In premature lambs prenatal exposure to corticosteroids and thyrotropin-releasing hormone improves postnatal cardiovascular adaptation more than corticosteroids alone.

This study investigates the effects of prenatal corticosteroid administration on newborn sympathoadrenal mechanisms involved in postnatal adaptation. Randomly assigned preterm (122-125 days) fetal sheep were treated with hydrocortisone or saline for 60 h and delivered by cesarean section. We examined postnatal physiological adaptation, sympathoadrenal responses, cardiac beta-receptor density, and the receptor-cyclase system. We observed increased ventilatory, cardiovascular, and metabolic responses function in the corticosteroid-treated animals despite a marked attenuation in the anticipated surge of plasma catecholamine concentrations and a decrease in epinephrine secretion rate, which is normally seen at birth. Myocardial beta-adrenergic receptor density and affinity states were comparable in both groups. Basal and agonist-mediated adenylyl cyclase activity in myocardial tissue was increased in the corticosteroid-treated animals. We speculate that the increase in myocardial adenylyl cyclase activity may be accompanied by similar changes in other organ systems and that this could account for the augmentation in respiratory, cardiovascular, and metabolic responses in the corticosteroid-treated animals.

In adult animals, prolonged beta-agonist exposure leads to down-regulation of beta-adrenergic receptors and desensitization. Prior evidence from our lab suggests that this may not occur in developing animals. To study this, we measured the response to graded epinephrine infusion [2.7, 5.5, 13.6, 27.3 mumol/(kg.min), (0.5, 1.0, 2.5, 5.0 micrograms/(kg.min)], myocardial beta-agonist receptor density, and components of the receptor-cyclase system in newborn lambs before (n = 6) and after (n = 5) 3 d of continuous isoproterenol administration (2 micrograms/kg/min). beta-Adrenergic receptors were measured by radioligand binding. Epinephrine dose-response curves were analyzed for the threshold and slope for changes in mean blood pressure, systolic blood pressure, and heart rate versus plasma epinephrine levels. Despite 3 d of continuous isoproterenol infusion, we observed no desensitization of the hemodynamic response to epinephrine. There was a reduction in receptor density when expressed per membrane protein [155.3 +/- 19.5 (controls) versus 73.2 +/- 3.8 fmol/mg protein (agonist exposed), p less than 0.05], but no alteration in receptor density when expressed per g cardiac wet weight [258.8 +/- 39.9 (controls) versus 406.8 +/- 74.0 fmol/g wet weight (agonist exposed)]. There was no alteration in agonist affinity or in adenylyl cyclase activity after adjustment for membrane protein recovery. Prolonged beta-agonist infusion in newborn lambs does not desensitize hemodynamic responses to infused epinephrine. We propose that receptor regulation in developing animals is fundamentally different than in adult animals.