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.

Routine Supplementation of Lactobacillus rhamnosus GG and Risk of Necrotizing Enterocolitis in Very Low Birth Weight Infants.

OBJECTIVE: To evaluate if routine supplementation of Lactobacillus rhamnosus GG ATCC 53103 (LGG) is associated with a decreased risk of necrotizing enterocolitis in very low birth weight (VLBW) infants. STUDY DESIGN: Retrospective observational cohort study of VLBW (<1500 g) infants at a single center from 2008 to 2016. LGG supplementation with Culturelle at a dose of 2.5 to 5 × 109 CFU/day began in 2014. We used multivariable logistic regression to evaluate the association between LGG supplementation and necrotizing enterocolitis (modified Bell stage IIA or greater), after adjusting for potential confounders. We also compared changes in necrotizing enterocolitis incidence before and after implementation of LGG using a statistical process control chart. RESULTS: We evaluated 640 VLBW infants with a median gestational age of 28.7 weeks (IQR 26.3-30.6); 78 (12%) developed necrotizing enterocolitis. The median age at first dose of LGG was 6 days (IQR 3-10), and duration of supplementation was 32 days (IQR 18-45). The incidence of necrotizing enterocolitis in the epoch before LGG implementation was 10.2% compared with 16.8% after implementation. In multivariable analysis, LGG supplementation was associated with a higher risk of necrotizing enterocolitis (aOR 2.10, 95 % CI 1.25-3.54, P = .005). We found no special cause variation in necrotizing enterocolitis after implementation of LGG supplementation. There were no episodes of Lactobacillus sepsis during 5558 infant days of LGG supplementation. CONCLUSIONS: In this study, routine LGG supplementation was not associated with a decreased risk of necrotizing enterocolitis. Our findings do not support the use of the most common probiotic preparation currently supplemented to VLBW infants in the US.

Pathogenesis of NEC: Role of the innate and adaptive immune response.

Necrotizing enterocolitis (NEC) is a devastating disease in premature infants with high case fatality and significant morbidity among survivors. Immaturity of intestinal host defenses predisposes the premature infant gut to injury. An abnormal bacterial colonization pattern with a deficiency of commensal bacteria may lead to a further breakdown of these host defense mechanisms, predisposing the infant to NEC. Here, we review the role of the innate and adaptive immune system in the pathophysiology of NEC.