Physiologic-Based Cord Clamping Maintains Core Temperature vs. Immediate Cord Clamping in Near-Term Lambs

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 <

High-CPAP does not impede cardiovascular changes at birth in preterm sheep

Objective: Continuous positive airway pressures (CPAP) used to assist preterm infants at birth are limited to 4-8 cmH(2)O 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 cmH(2)O), high-CPAP (HCPAP: 15 cmH(2)O) or dynamic HCPAP (15 decreasing to 8 cmH(2)O at similar to 2 cmH(2)O/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 cmH(2)O [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.Developmen

Physiological-based cord clamping in very preterm infants — Randomised controlled trial on effectiveness of stabilisation

Aim: To test whether stabilising very preterm infants while performing physiological-based cord clamping (PBCC) is at least as effective as the standard approach of time-based delayed cord clamping (DCC). Methods: A randomised contr

Effects of intra-amniotic lipopolysaccharide and maternal betamethasone on brain inflammation in fetal sheep

Rationale: Chorioamnionitis and antenatal glucocorticoids are common exposures for preterm infants and can affect the fetal brain, contributing to cognitive and motor deficits in preterm infants. The effects of antenatal glucocorticoids on the brain in the setting of chorioamnionitis are unknown. We hypothesized that antenatal glucocorticoids would modulate inflammation in the brain and prevent hippocampal and white matter injury after intra-amniotic lipopolysaccharide (LPS) exposure. Methods: Time-mated ewes received saline (control), an intra-amniotic injection of 10 mg LPS at 106d GA or 113d GA, maternal intra-muscular betamethasone (0.5 mg/kg maternal weight) alone at 113d GA, betamethasone at 106d GA before LPS or betamethasone at 113d GA after LPS. Animals were delivered at 120d GA (term=150d). Brain structure volumes were measured on T2-weighted MRI images. The subcortical white matter (SCWM), periventricular white matter (PVWM) and hippocampus were analyzed for microglia, astrocytes, apoptosis, proliferation, myelin and pre-synaptic vesicles. Results: LPS and/or betamethasone exposure at different time-points during gestation did not alter brain structure volumes on MRI. Betamethasone alone did not alter any of the measurements. Intra-amniotic LPS at 106d or 113d GA induced inflammation as indicated by increased microglial and astrocyte recruitment which was paralleled by increased apoptosis and hypomyelination in the SCWM and decreased synaptophysin density in the hippocampus. Betamethasone before the LPS exposure at 113d GA prevented microglial activation and the decrease in synaptophysin. Betamethasone after LPS exposure increased microglial infiltration and apoptosis. Conclusion: Intra-uterine LPS exposure for 7d or 14d before delivery induced inflammation and injury in the fetal white matter and hippocampus. Antenatal glucocorticoids aggravated the inflammatory changes in the brain caused by pre-existing intra-amniotic inflammation. Antenatal glucocorticoids prior to LPS reduced the effects of intra-uterine inflammation on the brain. The timing of glucocorticoid administration in the setting of chorioamnionitis can alter outcomes for the fetal brain

Effect of maternal oxytocin on umbilical venous and arterial blood flows during physiological-based cord clamping in preterm lambs

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 findingsAt similar to 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 (pDevelopmen

A comparison of high-frequency jet ventilation and synchronised intermittent mandatory ventilation in preterm lambs

Purpose: Synchronised intermittent mandatory ventilation (SIMV) and high-frequency jet ventilation (HFJV) are accepted ventilatory strategies for treatment of respiratory distress syndrome (RDS) in preterm babies. We hypothesised that SIMV and HFJV both facilitate adequate oxygenation and ventilation but that HFJV is associated with less lung injury. Results: There were no differences in arterial oxygenation or partial pressure of carbon dioxide despite lower mean airway pressure during SIMV for most of the study. There were no consistent significant differences in end systolic and end diastolic PBF, lung injury data and static lung compliance. Methods: Preterm lambs of anaesthetised ewes were instrumented, intubated and delivered by caesarean section after intratracheal suction and instillation of surfactant. Each lamb was managed for 3 hr according to a predetermined algorithm for ventilatory support consistent with open lung ventilation. Pulmonary blood flow (PBF) was measured continuously and pulsatility index was calculated. Ventilatory parameters were recorded and arterial blood gases were measured at intervals. At postmortem, in situ pressure-volume deflation curves were recorded, and bronchoalveolar lavage fluid and lung tissue were obtained to assess inflammation. Conclusions: SIMV and HFJV have comparable clinical efficacy and ventilator pressure requirements when applied with a targeted lung volume recruitment strategy

A physiological approach to the timing of umbilical cord clamping at birth

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Impact of conventional breath inspiratory time during high-frequency jet ventilation in preterm lambs

Background: Conventional mechanical ventilator (CMV) breaths during high-frequency jet ventilation (HFJV) are advocated to recruit and stabilize alveoli. Objectives: To establish if CMV breath duration delivered during HFJV influences gas exchange, lung mechanics and lung injury. Methods: Preterm lambs at 128 days gestational age were studied. HFJV (7 Hz, PEEP 8 cm H2O, PIPHFJV 40 cm H2O, FiO2 0.4) with superimposed CMV breaths (PIPCMV 25 cm H2O, rate 5 breaths/min) was commenced after delivery and continued for 2 h. CMV breath inspiratory time (tI) was either 0.5 s (HFJV+CMV0.5; n = 8) or 2.0 s (HFJV+CMV2.0; n = 8). Age-matched unventilated controls (UVC) were included for comparison. Results: Serial arterial blood gas analyses were performed. PIPHFJV was adjusted to target a PaCO2 of 45–55 mm Hg. FiO2 was adjusted to target SpO2 90–95%. Pressure-volume curves, broncho-alveolar lavage (BAL) and lung tissue samples were obtained postmortem. Gas exchange, ventilation parameters, static lung compliance and BAL inflammatory markers were not different between HFJV+CMV0.5 and HFJV+CMV2.0. Both ventilation groups had higher BAL inflammatory markers and increased iNOS-positive cells on histology compared to UVC, whilst lung tissue IL-1β and IL-6 mRNA expression was higher in the HFJV+CMV2.0 group compared to the UVC group. Conclusions: Preterm lambs were ventilated effectively with HFJV and 5 CMV breaths/min. CMV breath duration did not alter blood gas exchange, ventilation parameters, ex vivo static lung mechanics or markers of lung injury over a 2-hour study, although consistent trends towards increased inflammatory markers with the longer tI suggest greater risk of injury

Animal models in neonatal resuscitation research: What can they teach us?0

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The physiology of delayed umbilical cord clamping at birth: let's not add to the confusion

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