Cardiac and cerebral hemodynamics with umbilical cord milking compared with early cord clamping: A randomized cluster crossover trial.

OBJECTIVE: A large, randomized cluster cross-over trial (N = 1730) comparing intact umbilical cord milking (UCM) to early cord clamping (ECC) in non-vigorous near-term/term newborns demonstrated a reduction in cardiorespiratory interventions at birth and less moderate to severe hypoxic ischemic encephalopathy. We evaluated changes in cerebral tissue oxygenation (StO2), pulse oximetry (SpO2), pulse rate and fraction of inspired oxygen (FiO2) during the first 10 min of life in a subset of infants enrolled in the parent trial. STUDY DESIGN: Infants enrolled in the Milking in Non-Vigorous Infants trial that had StO2 monitoring at birth were included in the sub-study conducted at 3 hospitals the US and Canada. A near-infrared spectroscopy sensor, pulse oximeter and electrocardiogram electrodes were placed. Pulse rate, StO2, SpO2, and FiO2 were collected for the first 10 min after birth. Longitudinal models were used to compare effects of UCM and ECC. RESULTS: Thirty-four infants had StO2 data. Fifteen of these infants received UCM and 19 had ECC. Infants receiving UCM had similar heart rates, SpO2, and StO2 values, but were exposed to less FiO2 over the first 10 min of life than infants with ECC (0.26 ± 0.12 vs. 0.81 ± 0.05 at 10 min). CONCLUSION: Non-vigorous term/near term infants who received UCM at birth required lower FiO2 after delivery when compared to infants who umbilical cords were clamped soon after birth while achieving similar peripheral and cerebral oxygenation. Cord milking may be a potential option for placental transfusion in non-vigorous near term/term infants when delayed cord clamping cannot be performed.

Caffeine and Less Invasive Surfactant Administration for Respiratory Distress Syndrome of the Newborn.

BACKGROUND: Management strategies for preterm neonates with respiratory distress syndrome include early initiation of continuous positive airway pressure (CPAP) and titration of fractional inspired oxygen and may include the use of less invasive surfactant administration (LISA) to avoid the need for endotracheal intubation. This randomized trial investigated whether early administration of caffeine and LISA would decrease the need for endotracheal intubation in the first 72 hours of life (HoL) compared with caffeine and CPAP alone. METHODS: Eligible neonates born at 24 weeks 0 days to 29 weeks 6 days of gestational age were randomly assigned to receive intravenous caffeine in the first 2 HoL followed by surfactant administration via the LISA method (intervention) or caffeine followed by CPAP (control). The primary outcome was the frequency of neonates requiring endotracheal intubation or meeting respiratory failure criteria between groups (caffeine and LISA vs. caffeine and CPAP) within the first 72 HoL. Multivariable logistic regression modeling was used to adjust for gestational age strata in normally distributed primary and secondary outcomes. RESULTS: Enrollment occurred between January 2020 and December 2022. Endotracheal intubation or meeting respiratory failure criteria within the first 72 HoL occurred in 21 (23%) of 92 neonates randomly assigned to receive caffeine and LISA compared with 47 (53%) of 88 neonates in the caffeine and CPAP group (odds ratio, 0.258; 95% confidence interval, 0.136 to 0.490; P<0.001), which remained significant after adjusting for gestational age strata (odds ratio, 0.227; 95% confidence interval, 0.112 to 0.460; P<0.001). Adverse events were similar between groups, except bronchopulmonary dysplasia, which occurred in 26% of the LISA group and 39% of the control group (P=0.049). CONCLUSIONS: In preterm neonates supported with CPAP, early caffeine and LISA resulted in a lower frequency of endotracheal intubation within the first 72 HoL. (Funded by Chiesi USA; ClinicalTrials.gov number, NCT04209946.)

Multicentre, randomised trial of preterm infants receiving caffeine and less invasive surfactant administration compared with caffeine and early continuous positive airway pressure (CaLI trial): study protocol.

INTRODUCTION: Respiratory distress syndrome (RDS) or surfactant deficiency occurs primarily in premature infants resulting in composite outcomes of death or bronchopulmonary dysplasia. Initial management strategies for preterm infants with RDS includes early initiation of continuous positive airway pressure (CPAP) and titration of fractional inspired oxygen (FiO2), and may include the use of less invasive surfactant administration (LISA) to avoid the need for mechanical ventilation. In order to optimise success of non-invasive support, the use of early caffeine therapy may be critical to the success of LISA. The objective of our trial is to evaluate whether infants that receive early caffeine, CPAP and surfactant via the LISA method compared with infants that receive caffeine and CPAP alone, have a decreased need for invasive mechanical ventilation in the first 72 hours of life. METHODS AND ANALYSIS: CaLI is an unblinded multicentre, randomised controlled, trial of 180 preterm infants (24+0-29+6 weeks corrected GA). Criteria for intubation/treatment failure will follow guidelines for the management of RDS, including: (1) CPAP level of 6-8 cmH20 and FiO2 >0.40 required to maintain saturations 90%-95% for 2 hours after randomisation; (2) a pH of 7.15 or less or a paCO2 >65 mm Hg on any (2) blood gases (arterial/capillary/or venous) at least 2 hours after randomisation and in the first 72 hours of life; (3) continued apnoea/bradycardia/desaturation events despite nasal intermittent minute ventilation mode of ventilation. Infants will be randomised by 1 hour of life and caffeine/LISA treatments administered by 2 hour of life. Caffeine will be administered prior to surfactant in the LISA arm and before 2 hours of life in the control arm. ETHICS AND DISSEMINATION: Chiesi Farmaceutici, S.p.A is the sponsor of CaLI. Ethical approval has been obtained. Results will be submitted for publication in peer reviewed journals. TRIAL REGISTRATION NUMBER: www.Clinicaltrials.gov: NCT04209946; Pre-results.

Identification of an acetyl disulfide derivative in the synthesis of thiosialosides.

The first report of the formation of an acetyl disulfide sialoside during the synthesis of thioglycosides is described. This compound is a by-product in the synthesis of the 2-thioacetyl sialoside commonly used in thioglycoside preparation. Our investigations into the identification of this novel disulfide are described.