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.

Transient Tachypnea of Newborns Is Associated With Maternal Spinal Hypotension During Elective Cesarean Delivery: A Retrospective Cohort Study.

BACKGROUND: The risk for transient tachypnea of newborns, a common cause of respiratory distress in the neonatal period, is 2- to 6-fold higher during elective cesarean delivery compared to vaginal delivery. Here, we evaluated the association between transient tachypnea of newborns and the degree and duration of predelivery maternal hypotension during spinal anesthesia for elective cesarean delivery. METHODS: Demographic data, details of anesthetic management, blood pressure measurements, and vasopressor requirement preceding delivery were compared between transient tachypnea newborns (n = 30) and healthy neonates (n = 151) with normal respiratory function born via elective cesarean delivery between July 2015 and February 2016. The degree and duration of hypotension were assessed using area under the curve for systolic blood pressure (SBP) ≤90 mm Hg and area under the curve for mean arterial pressure ≤65 mm Hg. After adjusting for confounders, multivariable logistic regression was used to evaluate the association between area under the curve for SBP and transient tachypnea of newborns. RESULTS: The median area under the curve for SBP was higher in cases of transient tachypnea of newborns (0.94; interquartile range, 0-28.7 mm Hg*min) compared to healthy controls (0; interquartile range, 0-3.30 mm Hg*min; P = .001). Similarly, median area under the curve for mean arterial pressure was also higher in cases of transient tachypnea of newborns (0; interquartile range, 0-18.6 mm Hg*min) compared to controls (0; interquartile range, 0-1.1 mm Hg*min; P = .01). Mothers of transient tachypnea newborns received significantly higher amounts of phenylephrine and ephedrine compared to controls (P = .001 and 0.01, respectively). Hence, the total vasopressor dose given to mothers in the transient tachypnea of newborn group was much higher than for the control group (P = .001). In the multivariable logistic regression, area under the curve for SBP was significantly associated with transient tachypnea of newborns (odds ratio, 1.02; 95% CI, 1.01-1.04, P = .005) after adjusting for gravidity and the type of anesthetic (spinal versus combined spinal epidural). CONCLUSIONS: Our results suggest that the degree and duration of maternal SBP <90 mm Hg after neuraxial anesthesia during elective cesarean delivery are associated with transient tachypnea of newborns. Future prospective studies should further explore the effects of maternal hypotension, its prevention, and treatment for transient tachypnea of newborns.

Increased neointima formation in cysteine-rich protein 2-deficient mice in response to vascular injury.

In response to arterial injury, medial vascular smooth muscle cells (VSMCs) proliferate and migrate into the intima, contributing to the development of occlusive vascular disease. The LIM protein cysteine-rich protein (CRP) 2 associates with the actin cytoskeleton and may maintain the cytoarchitecture. CRP2 also interacts with transcription factors in the nucleus to mediate SMC gene expression. To test the hypothesis that CRP2 may be an important regulator of vascular development or function we generated Csrp2 (gene symbol of the mouse CRP2 gene)-deficient (Csrp2(-/-)) mice by targeted mutation. Csrp2(-/-) mice did not have any gross vascular defects or altered expression levels of SM alpha-actin, SM22alpha, or calponin. Following femoral artery injury, CRP2 expression persisted in the vessel wall at 4 days and then decreased by 14 days. Intimal thickening was enhanced 3.4-fold in Csrp2(-/-) compared with wild-type (WT) mice 14 days following injury. Cellular proliferation was similar between WT and Csrp2(-/-) VSMC both in vivo and in vitro. Interestingly, Csrp2(-/-) VSMC migrated more rapidly in response to PDGF-BB and had increased Rac1 activation. Our data demonstrate that CRP2 is not required for vascular development. However, an absence of CRP2 enhanced VSMC migration and increased neointima formation following arterial injury.