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1.
Eur J Pediatr ; 2022 May 17.
Article in English | MEDLINE | ID: mdl-35579708

ABSTRACT

Randomised trials in emergency settings must quickly confirm eligibility and allocate participants to an intervention group without delaying treatment. We report rapid randomisation during two neonatal resuscitation trials using the non-commercial REDCap platform accessed via smartphone. This simple, reliable method has wide applicability for trials in emergency settings. What is Known: • Randomised trials in emergency settings need to rapidly allocate participants to an intervention group. • This process should not delay treatment. What is New: • This non-commercial, smartphone-accessible application enabled rapid, accurate randomisation at the bedside. • This has broad applicability for emergency setting trials.

2.
Front Physiol ; 13: 841229, 2022.
Article in English | MEDLINE | ID: mdl-35309054

ABSTRACT

Background: Preterm newborns commonly experience apnoeas after birth and require respiratory stimulants and support. Antenatal inflammation is a common antecedent of preterm birth and inflammatory mediators, particularly prostaglandin E2 (PGE2), are associated with inhibition of vital brainstem respiratory centers. In this study, we tested the hypothesis that exposure to antenatal inflammation inhibits fetal breathing movements (FBMs) and increases inflammation and PGE2 levels in brainstem respiratory centers, cerebrospinal fluid (CSF) and blood plasma. Methods: Chronically instrumented late preterm fetal sheep at 0.85 of gestation were randomly assigned to receive repeated intravenous saline (n = 8) or lipopolysaccharide (LPS) infusions (experimental day 1 = 300 ng, day 2 = 600 ng, day 3 = 1200 ng, n = 8). Fetal breathing movements were recorded throughout the experimental period. Sheep were euthanized 4 days after starting infusions for assessment of brainstem respiratory center histology. Results: LPS infusions increased circulating and cerebrospinal fluid PGE2 levels, decreased arterial oxygen saturation, increased the partial pressure of carbon dioxide and lactate concentration, and decreased pH (p < 0.05 for all) compared to controls. LPS infusions caused transient reductions in the % of time fetuses spent breathing and the proportion of vigorous fetal breathing movements (P < 0.05 vs. control). LPS-exposure increased PGE2 expression in the RTN/pFRG (P < 0.05 vs. control) but not the pBÖTC (P < 0.07 vs. control) of the brainstem. No significant changes in gene expression were observed for PGE2 enzymes or caspase 3. LPS-exposure reduced the numbers of GFAP-immunoreactive astrocytes in the RTN/pFRG, NTS and XII of the brainstem (P < 0.05 vs. control for all) and increased microglial activation in the RTN/pFRG, preBÖTC, NTS, and XII brainstem respiratory centers (P < 0.05 vs. control for all). Conclusion: Chronic LPS-exposure in late preterm fetal sheep increased PGE2 levels within the brainstem, CSF and plasma, and was associated with inhibition of FBMs, astrocyte loss and microglial activation within the brainstem respiratory centers. Further studies are needed to determine whether the inflammation-induced increase in PGE2 levels plays a key role in depressing respiratory drive in the perinatal period.

3.
Arch Dis Child Fetal Neonatal Ed ; 2022 Jan 20.
Article in English | MEDLINE | ID: mdl-35058279

ABSTRACT

IMPORTANCE: Animal and observational human studies report that delivery of excessive tidal volume (VT) at birth is associated with lung and brain injury. Using a respiratory function monitor (RFM) to guide VT delivery might reduce injury and improve outcomes. OBJECTIVE: To determine whether use of an RFM in addition to clinical assessment versus clinical assessment alone during mask ventilation in the delivery room reduces in-hospital mortality and morbidity of infants <37 weeks' gestation. STUDY SELECTION: Randomised controlled trials (RCTs) comparing RFM in addition to clinical assessment versus clinical assessment alone during mask ventilation in the delivery room of infants born <37 weeks' gestation. DATA ANALYSIS: Risk of bias was assessed using Covidence Collaboration tool and pooled into a meta-analysis using a random-effects model. The primary outcome was death prior to discharge. MAIN OUTCOME: Death before hospital discharge. RESULTS: Three RCTs enrolling 443 infants were combined in a meta-analysis. The pooled analysis showed no difference in rates of death before discharge with an RFM versus no RFM, relative risk (RR) 95% (CI) 0.98 (0.64 to 1.48). The pooled analysis suggested a significant reduction for brain injury (a combination of intraventricular haemorrhage and periventricular leucomalacia) (RR 0.65 (0.48 to 0.89), p=0.006) and for intraventricular haemorrhage (RR 0.69 (0.50 to 0.96), p=0.03) in infants receiving positive pressure ventilation with an RFM versus no RFM. CONCLUSION: In infants <37 weeks, an RFM in addition to clinical assessment compared with clinical assessment during mask ventilation resulted in similar in-hospital mortality, significant reduction for any brain injury and intraventricular haemorrhage. Further trials are required to determine whether RFMs should be routinely available for neonatal resuscitation.

4.
Arch Dis Child Fetal Neonatal Ed ; 2021 Nov 29.
Article in English | MEDLINE | ID: mdl-34844983

ABSTRACT

BACKGROUND: The feasibility and benefits of continuous sustained inflations (SIs) during chest compressions (CCs) during delayed cord clamping (physiological-based cord clamping; PBCC) are not known. We aimed to determine whether continuous SIs during CCs would reduce the time to return of spontaneous circulation (ROSC) and improve post-asphyxial blood pressures and flows in asystolic newborn lambs. METHODS: Fetal sheep were surgically instrumented immediately prior to delivery at ~139 days' gestation and asphyxia induced until lambs reached asystole. Lambs were randomised to either immediate cord clamping (ICC) or PBCC. Lambs then received a single SI (SIsing; 30 s at 30 cmH2O) followed by intermittent positive pressure ventilation, or continuous SIs (SIcont: 30 s duration with 1 s break). We thus examined 4 groups: ICC +SIsing, ICC +SIcont, PBCC +SIsing, and PBCC +SIcont. Chest compressions and epinephrine administration followed international guidelines. PBCC lambs underwent cord clamping 10 min after ROSC. Physiological and oxygenation variables were measured throughout. RESULTS: The time taken to achieve ROSC was not different between groups (mean (SD) 4.3±2.9 min). Mean and diastolic blood pressure was higher during chest compressions in PBCC lambs compared with ICC lambs, but no effect of SIs was observed. SIcont significantly reduced pulmonary blood flow, diastolic blood pressure and oxygenation after ROSC compared with SIsing. CONCLUSION: We found no significant benefit of SIcont over SIsing during CPR on the time to ROSC or on post-ROSC haemodynamics, but did demonstrate the feasibility of continuous SIs during advanced CPR on an intact umbilical cord. Longer-term studies are recommended before this technique is used routinely in clinical practice.

5.
J Cereb Blood Flow Metab ; 42(2): 315-328, 2022 02.
Article in English | MEDLINE | ID: mdl-34551607

ABSTRACT

Neurovascular coupling has been well-defined in the adult brain, but variable and inconsistent responses have been observed in the neonatal brain. The mechanisms that underlie functional haemodynamic responses in the developing brain are unknown. Synchrotron radiation (SR) microangiography enables in vivo high-resolution imaging of the cerebral vasculature. We exploited SR microangiography to investigate the microvascular changes underlying the cerebral haemodynamic response in preterm (n = 7) and 7-10-day old term lambs (n = 4), following median nerve stimulation of 1.8, 4.8 and 7.8 sec durations.Increasing durations of somatosensory stimulation significantly increased the number of cortical microvessels of ≤200 µm diameter in 7-10-day old term lambs (p < 0.05) but not preterm lambs where, in contrast, stimulation increased the diameter of cerebral microvessels with a baseline diameter of ≤200 µm. Preterm lambs demonstrated positive functional responses with increased oxyhaemoglobin measured by near infrared spectroscopy, while 7-10-day old term lambs demonstrated both positive and negative responses. Our findings suggest the vascular mechanisms underlying the functional haemodynamic response differ between the preterm and 7-10-day old term brain. The preterm brain depends on vasodilatation of microvessels without recruitment of additional vessels, suggesting a limited capacity to mount higher cerebral haemodynamic responses when faced with prolonged or stronger neural stimulation.


Subject(s)
Brain , Cerebral Angiography , Cerebrovascular Circulation , Microcirculation , Oxyhemoglobins/metabolism , Synchrotrons , Animals , Animals, Newborn , Brain/blood supply , Brain/diagnostic imaging , Brain/metabolism , Sheep
6.
J Neuroinflammation ; 18(1): 189, 2021 Aug 31.
Article in English | MEDLINE | ID: mdl-34465372

ABSTRACT

BACKGROUND: Increased systemic and tissue levels of interleukin (IL)-1ß are associated with greater risk of impaired neurodevelopment after birth. In this study, we tested the hypothesis that systemic IL-1 receptor antagonist (Ra) administration would attenuate brain inflammation and injury in near-term fetal sheep exposed to lipopolysaccharide (LPS). METHODS: Chronically instrumented near-term fetal sheep at 0.85 of gestation were randomly assigned to saline infusion (control, n = 9), repeated LPS infusions (0 h = 300 ng, 24 h = 600 ng, 48 h = 1200 ng, n = 8) or repeated LPS plus IL-1Ra infusions (13 mg/kg infused over 4 h) started 1 h after each LPS infusion (n = 9). Sheep were euthanized 4 days after starting infusions for histology. RESULTS: LPS infusions increased circulating cytokines and were associated with electroencephalogram (EEG) suppression with transiently reduced mean arterial blood pressure, and increased carotid artery perfusion and fetal heart rate (P < 0.05 vs. control for all). In the periventricular and intragyral white matter, LPS-exposure increased IL-1ß immunoreactivity, numbers of caspase 3+ cells and microglia, reduced astrocyte and olig-2+ oligodendrocyte survival but did not change numbers of mature CC1+ oligodendrocytes, myelin expression or numbers of neurons in the cortex and subcortical regions. IL-1Ra infusions reduced circulating cytokines and improved recovery of EEG activity and carotid artery perfusion. Histologically, IL-1Ra reduced microgliosis, IL-1ß expression and caspase-3+ cells, and improved olig-2+ oligodendrocyte survival. CONCLUSION: IL-1Ra improved EEG activity and markedly attenuated systemic inflammation, microgliosis and oligodendrocyte loss following LPS exposure in near-term fetal sheep. Further studies examining the long-term effects on brain maturation are now needed.


Subject(s)
Brain/drug effects , Encephalitis/drug therapy , Interleukin 1 Receptor Antagonist Protein/pharmacology , Lipopolysaccharides/pharmacology , Oligodendroglia/drug effects , White Matter/drug effects , Animals , Brain/metabolism , Brain/pathology , Encephalitis/metabolism , Encephalitis/pathology , Female , Interleukin 1 Receptor Antagonist Protein/therapeutic use , Oligodendroglia/metabolism , Oligodendroglia/pathology , Pregnancy , Sheep , White Matter/metabolism , White Matter/pathology
7.
Arch Dis Child Fetal Neonatal Ed ; 107(3): 311-316, 2022 May.
Article in English | MEDLINE | ID: mdl-34462318

ABSTRACT

OBJECTIVE: Intraosseous access is recommended as a reasonable alternative for vascular access during newborn resuscitation if umbilical access is unavailable, but there are minimal reported data in newborns. We compared intraosseous with intravenous epinephrine administration during resuscitation of severely asphyxiated lambs at birth. METHODS: Near-term lambs (139 days' gestation) were instrumented antenatally for measurement of carotid and pulmonary blood flow and systemic blood pressure. Intrapartum asphyxia was induced by umbilical cord clamping until asystole. Resuscitation commenced with positive pressure ventilation followed by chest compressions and the lambs received either intraosseous or central intravenous epinephrine (10 µg/kg); epinephrine administration was repeated every 3 min until return of spontaneous circulation (ROSC). The lambs were maintained for 30 min after ROSC. Plasma epinephrine levels were measured before cord clamping, at end asphyxia, and at 3 and 15 min post-ROSC. RESULTS: ROSC was successful in 7 of 9 intraosseous epinephrine lambs and in 10 of 12 intravenous epinephrine lambs. The time and number of epinephrine doses required to achieve ROSC were similar between the groups, as were the achieved plasma epinephrine levels. Lambs in both groups displayed a similar marked overshoot in systemic blood pressure and carotid blood flow after ROSC. Blood gas parameters improved more quickly in the intraosseous lambs in the first 3 min, but were otherwise similar over the 30 min after ROSC. CONCLUSIONS: Intraosseous epinephrine administration results in similar outcomes to intravenous epinephrine during resuscitation of asphyxiated newborn lambs. These findings support the inclusion of intraosseous access as a route for epinephrine administration in current guidelines.


Subject(s)
Cardiopulmonary Resuscitation , Heart Arrest , Hypoxia-Ischemia, Brain , Animals , Animals, Newborn , Asphyxia/therapy , Cardiopulmonary Resuscitation/methods , Epinephrine , Humans , Infant, Newborn , Resuscitation/methods , Sheep
8.
PLoS One ; 16(6): e0253306, 2021.
Article in English | MEDLINE | ID: mdl-34138957

ABSTRACT

BACKGROUND: Delayed umbilical cord clamping (UCC) after birth is thought to cause placental to infant blood transfusion, but the mechanisms are unknown. It has been suggested that uterine contractions force blood out of the placenta and into the infant during delayed cord clamping. We have investigated the effect of uterine contractions, induced by maternal oxytocin administration, on umbilical artery (UA) and venous (UV) blood flows before and after ventilation onset to determine whether uterine contractions cause placental transfusion in preterm lambs. METHODS AND FINDINGS: At ~128 days of gestation, UA and UV blood flows, pulmonary arterial blood flow (PBF) and carotid arterial (CA) pressures and blood flows were measured in three groups of fetal sheep during delayed UCC; maternal oxytocin following mifepristone, mifepristone alone, and saline controls. Each successive uterine contraction significantly (p<0.05) decreased UV (26.2±6.0 to 14.1±4.5 mL.min-1.kg-1) and UA (41.2±6.3 to 20.7 ± 4.0 mL.min-1.kg-1) flows and increased CA pressure and flow (47.1±3.4 to 52.8±3.5 mmHg and 29.4±2.6 to 37.3±3.4 mL.min-1.kg-1). These flows and pressures were partially restored between contractions, but did not return to pre-oxytocin administration levels. Ventilation onset during DCC increased the effects of uterine contractions on UA and UV flows, with retrograde UA flow (away from the placenta) commonly occurring during diastole. CONCLUSIONS: We found no evidence that amplification of uterine contractions with oxytocin increase placental transfusion during DCC. Instead they decreased both UA and UV flow and caused a net loss of blood from the lamb. Uterine contractions did, however, have significant cardiovascular effects and reduced systemic and cerebral oxygenation.


Subject(s)
Oxytocics/administration & dosage , Oxytocin/administration & dosage , Regional Blood Flow/drug effects , Umbilical Arteries/drug effects , Umbilical Veins/drug effects , Uterine Contraction/drug effects , Animals , Animals, Newborn , Female , Mifepristone/pharmacology , Pregnancy , Sheep
9.
Arch Dis Child Fetal Neonatal Ed ; 106(6): 627-634, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34112723

ABSTRACT

OBJECTIVE: To identify risk factors associated with delivery room respiratory support in at-risk infants who are initially vigorous and received delayed cord clamping (DCC). DESIGN: Prospective cohort study. SETTING: Two perinatal centres in Melbourne, Australia. PATIENTS: At-risk infants born at ≥35+0 weeks gestation with a paediatric doctor in attendance who were initially vigorous and received DCC for >60 s. MAIN OUTCOME MEASURES: Delivery room respiratory support defined as facemask positive pressure ventilation, continuous positive airway pressure and/or supplemental oxygen within 10 min of birth. RESULTS: Two hundred and ninety-eight infants born at a median (IQR) gestational age of 39+3 (38+2-40+2) weeks were included. Cord clamping occurred at a median (IQR) of 128 (123-145) s. Forty-four (15%) infants received respiratory support at a median of 214 (IQR 156-326) s after birth. Neonatal unit admission for respiratory distress occurred in 32% of infants receiving delivery room respiratory support vs 1% of infants who did not receive delivery room respiratory support (p<0.001). Risk factors independently associated with delivery room respiratory support were average heart rate (HR) at 90-120 s after birth (determined using three-lead ECG), mode of birth and time to establish regular cries. Decision tree analysis identified that infants at highest risk had an average HR of <165 beats per minute at 90-120 s after birth following caesarean section (risk of 39%). Infants with an average HR of ≥165 beats per minute at 90-120 s after birth were at low risk (5%). CONCLUSIONS: We present a clinical decision pathway for at-risk infants who may benefit from close observation following DCC. Our findings provide a novel perspective of HR beyond the traditional threshold of 100 beats per minute.


Subject(s)
Critical Pathways/standards , Delivery, Obstetric , Electrocardiography/methods , Oxygen Inhalation Therapy , Umbilical Cord , Australia/epidemiology , Cesarean Section/adverse effects , Cesarean Section/methods , Clinical Decision-Making , Constriction , Continuous Positive Airway Pressure/methods , Delivery, Obstetric/adverse effects , Delivery, Obstetric/methods , Delivery, Obstetric/statistics & numerical data , Female , Gestational Age , Heart Rate , Humans , Infant, Newborn , Male , Monitoring, Physiologic/methods , Oxygen Inhalation Therapy/adverse effects , Oxygen Inhalation Therapy/instrumentation , Oxygen Inhalation Therapy/methods , Risk Assessment/methods , Risk Factors , Time-to-Treatment/standards , Time-to-Treatment/statistics & numerical data
10.
Pediatrics ; 147(3)2021 03.
Article in English | MEDLINE | ID: mdl-33622795

ABSTRACT

The transition from intrauterine life to extrauterine existence encompasses significant cardiorespiratory adaptations. These include rapid lung aeration and increase in pulmonary blood flow (PBF). Perinatal asphyxia and fetal growth restriction can severely hamper this transition. Hypoxia is the common denominator in these 2 disease states, with the former characterized by acute insult and the latter by utero-placental insufficiency and a chronic hypoxemic state. Both may manifest as hemodynamic instability. In this review, we emphasize the role of physiologic-based cord clamping in supplementing PBF during transition. The critical role of lung aeration in initiating pulmonary gas exchange and increasing PBF is discussed. Physiologic studies in animal models have enabled greater understanding of the mechanisms and effects of various therapies on transitional circulation. With data from sheep models, we elaborate instrumentation for monitoring of cardiovascular and pulmonary physiology and discuss the combined effect of chest compressions and adrenaline in improving transition at birth. Lastly, physiologic adaptation influencing management in human neonatal cohorts with respect to cardiac and vascular impairments in hypoxic-ischemic encephalopathy and growth restriction is discussed. Impairments in right ventricular function and vascular mechanics hold the key to prognostication and understanding of therapeutic rationale in these critically ill cohorts. The right ventricle and pulmonary circulation seem to be especially affected and may be explored as therapeutic targets. The role of comprehensive assessments using targeted neonatal echocardiography as a longitudinal, reliable, and easily accessible tool, enabling precision medicine facilitating physiologically appropriate treatment choices, is discussed.


Subject(s)
Hypoxia-Ischemia, Brain/physiopathology , Parturition/physiology , Pulmonary Circulation/physiology , Respiration , Acute Disease , Adaptation, Physiological , Animals , Cardiac Output/physiology , Cardiac Output, Low/physiopathology , Chronic Disease , Constriction , Female , Fetal Development/physiology , Fetal Growth Retardation/physiopathology , Fetus/blood supply , Humans , Infant, Newborn , Models, Animal , Placental Insufficiency/physiopathology , Precision Medicine , Pregnancy , Pulmonary Gas Exchange/physiology , Respiratory Therapy/methods , Sheep , Ventricular Dysfunction, Right/physiopathology
11.
Magn Reson Imaging ; 79: 112-120, 2021 06.
Article in English | MEDLINE | ID: mdl-33600894

ABSTRACT

We report the design, construction, and initial tests of a hyperpolariser to produce polarised 129Xe and 3He gas for medical imaging of the lung. The hyperpolariser uses the Spin-Exchange Optical Pumping method to polarise the nuclear spins of the isotopic gas. Batch mode operation was chosen for the design to produce polarised 129Xe and polarised 3He. Two-side pumping, electrical heating and a piston to transfer the polarised gas were some of the implemented techniques that are not commonly used in hyperpolariser designs. We have carried out magnetic resonance imaging experiments demonstrating that the 3He and 129Xe polarisation reached were sufficient for imaging, in particular for in vivo lung imaging using 129Xe. Further improvements to the hyperpolariser have also been discussed.


Subject(s)
Magnetic Resonance Imaging , Xenon Isotopes , Heating , Humans , Lung/diagnostic imaging , Male , Radiography
12.
Front Pediatr ; 8: 584138, 2020.
Article in English | MEDLINE | ID: mdl-33553064

ABSTRACT

Objective: Continuous positive airway pressures (CPAP) used to assist preterm infants at birth are limited to 4-8 cmH2O due to concerns that high-CPAP may cause pulmonary overexpansion and adversely affect the cardiovascular system. We investigated the effects of high-CPAP on pulmonary (PBF) and cerebral (CBF) blood flows and jugular vein pressure (JVP) after birth in preterm lambs. Methods: Preterm lambs instrumented with flow probes and catheters were delivered at 133/146 days gestation. Lambs received low-CPAP (LCPAP: 5 cmH2O), high-CPAP (HCPAP: 15 cmH2O) or dynamic HCPAP (15 decreasing to 8 cmH2O at ~2 cmH2O/min) for up to 30 min after birth. Results: Mean PBF was lower in the LCPAP [median (Q1-Q3); 202 (48-277) mL/min, p = 0.002] compared to HCPAP [315 (221-365) mL/min] and dynamic HCPAP [327 (269-376) mL/min] lambs. CBF was similar in LCPAP [65 (37-78) mL/min], HCPAP [73 (41-106) mL/min], and dynamic HCPAP [66 (52-81) mL/min, p = 0.174] lambs. JVP was similar at CPAPs of 5 [8.0 (5.1-12.4) mmHg], 8 [9.4 (5.3-13.4) mmHg], and 15 cmH2O [8.6 (6.9-10.5) mmHg, p = 0.909]. Heart rate was lower in the LCPAP [134 (101-174) bpm; p = 0.028] compared to the HCPAP [173 (139-205)] and dynamic HCPAP [188 (161-207) bpm] groups. Ventilation or additional caffeine was required in 5/6 LCPAP, 1/6 HCPAP, and 5/7 dynamic HCPAP lambs (p = 0.082), whereas 3/6 LCPAP, but no HCPAP lambs required intubation (p = 0.041), and 1/6 LCPAP, but no HCPAP lambs developed a pneumothorax (p = 0.632). Conclusion: High-CPAP did not impede the increase in PBF at birth and supported preterm lambs without affecting CBF and JVP.

13.
Resuscitation ; 162: 227-235, 2021 05.
Article in English | MEDLINE | ID: mdl-33548362

ABSTRACT

INTRODUCTION: Early identification of infants requiring surfactant therapy improves outcomes. We evaluated the accuracy of delivery room lung ultrasound (LUS) to predict surfactant therapy in very- and extremely preterm infants. METHODS: Infants born at <320/7 weeks were prospectively enrolled at 2 centres. LUS videos of both sides of the chest were obtained 5-10 min, 11-20 min, and 1-3 h after birth. Clinicians were masked to the results of the LUS assessment and surfactant therapy was provided according to local guidelines. LUS videos were graded blinded to clinical data. Presence of unilateral type 1 ('whiteout') LUS or worse was considered test positive. Receiver Operating Characteristic (ROC) analysis compared the accuracy of LUS and an FiO2 threshold of 0.3 to predict subsequent surfactant therapy. RESULTS: Fifty-two infants with a median age of 276/7 weeks (IQR 260/7-286/7) were studied. Thirty infants (58%) received surfactant. Area under the ROC curve (AUC) for LUS at 5-10 min, 11-20 min and 1-3 h was 0.78 (95% CI, 0.66-0.90), 0.76 (95% CI, 0.65-0.88) and 0.86 (95% CI, 0.75-0.97) respectively, outperforming FiO2 at the 5-10 min timepoint (AUC 0.45, 95% CI 0.29-0.62, p = 0.001). At 11-20 min, LUS had a specificity of 95% (95% CI 77-100%) and sensitivity of 59% (95% CI, 39-77%) to predict surfactant therapy. All infants born at 23-276/7 weeks with LUS test positive received surfactant. Twenty-six infants (50%) had worsening of LUS grades on serial assessment. CONCLUSIONS: LUS in the delivery room and accurately predicts surfactant therapy in infants <320/7 weeks.


Subject(s)
Infant, Extremely Premature , Respiratory Distress Syndrome, Newborn , Humans , Infant , Infant, Newborn , Lung/diagnostic imaging , Prospective Studies , Respiratory Distress Syndrome, Newborn/diagnostic imaging , Respiratory Distress Syndrome, Newborn/drug therapy , Surface-Active Agents , Ultrasonography
15.
J Dev Orig Health Dis ; 12(6): 975-981, 2021 12.
Article in English | MEDLINE | ID: mdl-33300490

ABSTRACT

Preterm birth (delivery <37 weeks of gestation) is associated with impaired glomerular capillary growth in neonates; if this persists, it may be a contributing factor in the increased risk of hypertension and chronic kidney disease in people born preterm. Therefore, in this study, we aimed to determine the long-term impact of preterm birth on renal morphology, in adult sheep. Singleton male sheep were delivered moderately preterm at 132 days (~0.9) of gestation (n = 6) or at term (147 days gestation; n = 6) and euthanised at 14.5 months of age (early adulthood). Stereological methods were used to determine mean renal corpuscle and glomerular volumes, and glomerular capillary length and surface area, in the outer, mid and inner regions of the renal cortex. Glomerulosclerosis and interstitial collagen levels were assessed histologically. By 14.5 months of age, there was no difference between the term and preterm sheep in body or kidney weight. Renal corpuscle volume was significantly larger in the preterm sheep than the term sheep, with the preterm sheep exhibiting enlarged Bowman's spaces; however, there was no difference in glomerular volume between groups, with no impact of preterm birth on capillary length or surface area per glomerulus. There was also no difference in interstitial collagen levels or glomerulosclerosis index between groups. Findings suggest that moderate preterm birth does not adversely affect glomerular structure in early adulthood. The enlarged Bowman's space in the renal corpuscles of the preterm sheep kidneys, however, is of concern and merits further research into its cause and functional consequences.


Subject(s)
Kidney/anatomy & histology , Kidney/blood supply , Analysis of Variance , Animals , Australia , Female , Infant, Premature/growth & development , Infant, Premature/metabolism , Kidney Glomerulus/blood supply , Kidney Glomerulus/growth & development , Kidney Glomerulus/pathology , Pregnancy , Sheep/growth & development , Sheep/metabolism
16.
Front Pediatr ; 8: 584983, 2020.
Article in English | MEDLINE | ID: mdl-33194919

ABSTRACT

Background: Physiologic-based cord clamping (PBCC) involves deferring umbilical cord clamping until after lung aeration. It is unclear if infant is at risk of becoming hypothermic during PBCC. Objectives: To test if PBCC would maintain core temperature more effectively than immediate cord clamping (ICC). Design: At 0.93 gestation, fetal lambs were surgically exteriorized and instrumented from pregnant ewes under general anesthesia. Prior to the start of the experiment, lambs were thoroughly dried, placed on hot water bottles, and core temperature was continuously monitored using a rectal thermometer. PBCC lambs (n = 21), received intermittent positive pressure ventilation (iPPV) for ≥5 min prior to umbilical cord clamping. In ICC lambs (n = 23), iPPV commenced within 60 s after umbilical cord clamping. iPPV was provided with heated/humidified gas. Lambs were moved under a radiant warmer after umbilical cord clamping. Additional warmth was provided using a plastic overlay, hairdryer, and extra water bottles, as needed. Two-way mixed and repeated measures one-way ANOVAs were used to compare temperature changes between and within a single group, respectively, over time. Results: Basal fetal parameters including core temperature were similar between groups. ICC lambs had a significant reduction in temperature compared to PBCC lambs (p < 0.001), evident by 1 min (p = 0.002). ICC lambs decreased temperature by 0.51°C (± 0.42) and 0.79°C (± 0.55) at 5 and 10 min respectively (p < 0.001). In PBCC lambs, temperature did not significantly change before or after umbilical cord clamping (p = 0.4 and p = 0.3, respectively). Conclusions: PBCC stabilized core temperature at delivery better than ICC in term lambs. Hypothermia may not be a significant risk during PBCC.

17.
Sci Rep ; 10(1): 16443, 2020 10 05.
Article in English | MEDLINE | ID: mdl-33020561

ABSTRACT

Hypoxic-ischaemia renders the neonatal brain susceptible to early secondary injury from oxidative stress and impaired autoregulation. We aimed to describe cerebral oxygen kinetics and haemodynamics immediately following return of spontaneous circulation (ROSC) and evaluate non-invasive parameters to facilitate bedside monitoring. Near-term sheep fetuses [139 ± 2 (SD) days gestation, n = 16] were instrumented to measure carotid artery (CA) flow, pressure, right brachial arterial and jugular venous saturation (SaO2 and SvO2, respectively). Cerebral oxygenation (crSO2) was measured using near-infrared spectroscopy (NIRS). Following induction of severe asphyxia, lambs received cardiopulmonary resuscitation using 100% oxygen until ROSC, with oxygen subsequently weaned according to saturation nomograms as per current guidelines. We found that oxygen consumption did not rise following ROSC, but oxygen delivery was markedly elevated until 15 min after ROSC. CrSO2 and heart rate each correlated with oxygen delivery. SaO2 remained > 90% and was less useful for identifying trends in oxygen delivery. CrSO2 correlated inversely with cerebral fractional oxygen extraction. In conclusion, ROSC from perinatal asphyxia is characterised by excess oxygen delivery that is driven by rapid increases in cerebrovascular pressure, flow, and oxygen saturation, and may be monitored non-invasively. Further work to describe and limit injury mediated by oxygen toxicity following ROSC is warranted.


Subject(s)
Asphyxia/metabolism , Brain/metabolism , Oxygen/metabolism , Return of Spontaneous Circulation/physiology , Animals , Animals, Newborn , Asphyxia/physiopathology , Asphyxia Neonatorum/metabolism , Asphyxia Neonatorum/physiopathology , Brachial Artery/metabolism , Brachial Artery/physiopathology , Brain/physiopathology , Cardiopulmonary Resuscitation/methods , Carotid Arteries/metabolism , Carotid Arteries/physiopathology , Cerebrovascular Circulation/physiology , Female , Hemodynamics/physiology , Hypoxia/metabolism , Hypoxia/physiopathology , Oxygen Consumption/physiology , Pregnancy , Sheep
18.
Front Neurol ; 11: 862, 2020.
Article in English | MEDLINE | ID: mdl-32922358

ABSTRACT

Many preterm neonates require mechanical ventilation which increases the risk of cerebral inflammation and white matter injury in the immature brain. In this review, we discuss the links between ventilation and brain injury with a focus on the immediate period after birth, incorporating respiratory support in the delivery room and subsequent mechanical ventilation in the neonatal intensive care unit. This review collates insight from large animal models in which acute injurious ventilation and prolonged periods of ventilation have been used to create clinically relevant brain injury patterns. These models are valuable resources in investigating the pathophysiology of ventilation-induced brain injury and have important translational implications. We discuss the challenges of reconciling lung and brain maturation in commonly used large animal models. A comprehensive understanding of ventilation-induced brain injury is necessary to guide the way we care for preterm neonates, with the goal to improve their neurodevelopmental outcomes.

19.
J Appl Physiol (1985) ; 129(5): 1075-1084, 2020 11 01.
Article in English | MEDLINE | ID: mdl-32909920

ABSTRACT

Positive end-expiratory pressure (PEEP) improves oxygenation in mechanically ventilated preterm neonates by preventing lung collapse. However, high PEEP may alter cerebral blood flow secondarily to the increased intrathoracic pressure, predisposing to brain injury. The precise effects of high PEEP on cerebral hemodynamics in the preterm brain are unknown. We aimed to assess the effect of PEEP on microvessels in the preterm brain by using synchrotron radiation (SR) microangiography, which enables in vivo real-time high-resolution imaging of the cerebral vasculature. Preterm lambs (0.8 gestation, n = 4) were delivered via caesarean section, anesthetized, and ventilated. SR microangiography of the right cerebral hemisphere was performed with iodine contrast administered into the right carotid artery during PEEP ventilation of 5 and 10 cmH2O. Carotid blood flow was measured using an ultrasonic flow probe placed around the left carotid artery. An increase of PEEP from 5 to 10 cmH2O increased the diameter of small cerebral vessels (<150 µm) but decreased the diameter of larger cerebral vessels (>500 µm) in all four lambs. Additionally, the higher PEEP increased the cerebral contrast transit time in three of the four lambs. Carotid blood flow increased in two lambs, which also had increased carbon dioxide levels during PEEP 10. Our results suggest that PEEP of 10 cmH2O alters the preterm cerebral hemodynamics, with prolonged cerebral blood flow transit and engorgement of small cerebral microvessels likely due to the increased intrathoracic pressure. These microvascular changes are generally not reflected in global assessment of cerebral blood flow or oxygenation.NEW & NOTEWORTHY An increase of positive end-expiratory pressure (PEEP) from 5 to 10 cmH2O increased the diameter of small cerebral vessels (<150 µm) but decreased the diameter of larger cerebral vessels (>500 µm). This suggests increased intrathoracic pressure due to high PEEP can drive microvessel engorgement in the preterm brain, which may play a role in cerebrovascular injury.


Subject(s)
Brain , Cerebrovascular Circulation , Positive-Pressure Respiration , Synchrotrons , Animals , Brain/radiation effects , Female , Lung , Perfusion , Pregnancy , Sheep
20.
Front Physiol ; 11: 902, 2020.
Article in English | MEDLINE | ID: mdl-32848852

ABSTRACT

Background: Current guidelines recommend immediate umbilical cord clamping (UCC) for newborns requiring chest compressions (CCs). Physiological-based cord clamping (PBCC), defined as delaying UCC until after lung aeration, has advantages over immediate UCC in mildly asphyxiated newborns, but its efficacy in asystolic newborns requiring CC is unknown. The aim of this study was to compare the cardiovascular response to CCs given prior to or after UCC in asystolic near-term lambs. Methods: Umbilical, carotid, pulmonary, and femoral arterial flows and pressures as well as systemic and cerebral oxygenation were measured in near-term sheep fetuses [139 ± 2 (SD) days gestation]. Fetal asphyxia was induced until asystole ensued, whereupon lambs received ventilation and CC before (PBCC; n = 16) or after (n = 12) UCC. Epinephrine was administered 1 min after ventilation onset and in 3-min intervals thereafter. The PBCC group was further separated into UCC at either 1 min (PBCC1, n = 8) or 10 min (PBCC10, n = 8) after return of spontaneous circulation (ROSC). Lambs were maintained for a further 30 min after ROSC. Results: The duration of CCs received and number of epinephrine doses required to obtain ROSC were similar between groups. After ROSC, we found no physiological benefits if UCC was delayed for 1 min compared to immediate cord clamping (ICC). However, if UCC was delayed for 10 min after ROSC, we found significant reductions in post-asphyxial rebound hypertension, cerebral blood flow, and cerebral oxygenation. The prevention of the post-asphyxial rebound hypertension in the PBCC10 group occurred due to the contribution of the placental circulation to a low peripheral resistance. As a result, left and right ventricular outputs continued to perfuse the placenta and were evidenced by reduced mean pulmonary blood flow, persistence of right-to-left shunting across the ductus arteriosus, and persistence of umbilical arterial and venous blood flows. Conclusion: It is possible to obtain ROSC after CC while the umbilical cord remains intact. There were no adverse effects of PBCC compared to ICC; however, the physiological changes observed after ROSC in the ICC and early PBCC groups may result in additional cerebral injury. Prolonging UCC after ROSC may provide significant physiological benefits that may reduce the risk of harm to the cerebral circulation.

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