Ventilatory Assistance Before Umbilical Cord Clamping in Extremely Preterm Infants: A Randomized Clinical Trial.

Importance: Providing assisted ventilation during delayed umbilical cord clamping may improve outcomes for extremely preterm infants. Objective: To determine whether assisted ventilation in extremely preterm infants (23 0/7 to 28 6/7 weeks' gestational age [GA]) followed by cord clamping reduces intraventricular hemorrhage (IVH) or early death. Design, Setting, and Participants: This phase 3, 1:1, parallel-stratified randomized clinical trial conducted at 12 perinatal centers across the US and Canada from September 2, 2016, through February 21, 2023, assessed IVH and early death outcomes of extremely preterm infants randomized to receive 120 seconds of assisted ventilation followed by cord clamping vs delayed cord clamping for 30 to 60 seconds with ventilatory assistance afterward. Two analysis cohorts, not breathing well and breathing well, were specified a priori based on assessment of breathing 30 seconds after birth. Intervention: After birth, all infants received stimulation and suctioning if needed. From 30 to 120 seconds, infants randomized to the intervention received continuous positive airway pressure if breathing well or positive-pressure ventilation if not, with cord clamping at 120 seconds. Control infants received 30 to 60 seconds of delayed cord clamping followed by standard resuscitation. Main Outcomes and Measures: The primary outcome was any grade IVH on head ultrasonography or death before day 7. Interpretation by site radiologists was confirmed by independent radiologists, all masked to study group. To estimate the association between study group and outcome, data were analyzed using the stratified Cochran-Mantel-Haenszel test for relative risk (RR), with associations summarized by point estimates and 95% CIs. Results: Of 1110 women who consented to participate, 548 were randomized and delivered infants at GA less than 29 weeks. A total of 570 eligible infants were enrolled (median [IQR] GA, 26.6 [24.9-27.7] weeks; 297 male [52.1%]). Intraventricular hemorrhage or death occurred in 34.9% (97 of 278) of infants in the intervention group and 32.5% (95 of 292) in the control group (adjusted RR, 1.02; 95% CI, 0.81-1.27). In the prespecified not-breathing-well cohort (47.5% [271 of 570]; median [IQR] GA, 26.0 [24.7-27.4] weeks; 152 male [56.1%]), IVH or death occurred in 38.7% (58 of 150) of infants in the intervention group and 43.0% (52 of 121) in the control group (RR, 0.91; 95% CI, 0.68-1.21). There was no evidence of differences in death, severe brain injury, or major morbidities between the intervention and control groups in either breathing cohort. Conclusions and Relevance: This study did not show that providing assisted ventilation before cord clamping in extremely preterm infants reduces IVH or early death. Additional study around the feasibility, safety, and efficacy of assisted ventilation before cord clamping may provide additional insight. Trial Registration: ClinicalTrials.gov Identifier: NCT02742454.

Post-hemorrhagic ventricular dilatation: inter-observer reliability of ventricular size measurements in extremely preterm infants.

BACKGROUND: Post-hemorrhagic ventricular dilatation (PHVD) in preterm infants can be assessed with ventricular size indices from cranial ultrasound. We explored inter-observer reliability of these indices for prediction of severe PHVD. METHODS: For all 139 infants with IVH, serial neonatal ultrasound at 3 time points (days 4-7, day 14, 36 weeks PMA) were assessed independently by 3 observers with differing levels of training/experience. Ventricular index (VI), anterior horn width (AHW), and fronto-temporal horn ratio (FTHR) were measured and used to diagnose PHVD. For all, inter-observer reliability and predictive values for receipt of surgical intervention were calculated. RESULTS: Inter-observer reliability for all observers varied from poor to excellent, with higher reliability for VI/AHW (ICC 0.49-0.84/0.51-0.81) than FTHR (0.41-0.82), particularly from the second week. Good-excellent inter-expertise reliability was found between observers with ample experience/training (0.65-0.99), particularly for VI and AHW, while poor-moderate when comparing with an inexperienced observer (0.28-0.88). Slightly higher predictive value for PHVD intervention (n = 12) was found for AHW (AUC 0.86-0.96) than for VI and FTHR (0.80-0.96/0.80-0.95). CONCLUSIONS: AHW and VI are highly reproducible in experienced hands compared to FTHR, with AHW from the second week onwards being the strongest predictor for receiving surgical intervention for severe PHVD. AHW may aid in early PHVD diagnosis and decision-making on intervention. IMPACT: While ventricular size indices from serial cUS are superior to clinical signs of increased intracranial pressure to assess PHVD, questions remained on their inter-observer reproducibility and reliability to predict severity of PHVD. AHW and VI are highly reproducible when performed by experienced clinicians. AHW from the second week of birth is the strongest predictor of PHVD onset and severity. AHW, combined with VI, may aid in early PHVD diagnosis and decision-making on need for surgical intervention. Consistent use of these indices has the potential to improve PHVD management and therewith the long-term outcomes in preterm infants.