Direct-to-participant recruitment of mothers and infants: A strategic approach during challenging pandemic times.

Under traditional circumstances, most clinical trials rely on in-person operations to identify, recruit, and enroll study participants and to complete study-related visits. During unusual circumstances, such as the COVID-19 pandemic, the typical clinical trial model is challenged and forced to explore alternative approaches to implementing study recruitment, participant enrollment, and data collection strategies. One such alternative is a direct-to-participant approach which leverages electronic resources and relevant technological devices (e.g., smart phones) available to researchers and patients. This approach functions under the assumption that a participant has access to a device that connects to the internet such as a smart phone, tablet, or computer. Researchers are then able to transition a typical paper-based, in-person model to an electronic-based, siteless, remote study. This article describes the challenges clinicians and researchers faced when implementing a direct-to-participant study approach during the COVID-19 pandemic. The lessons learned during this study of infant populations could help increase efficiency of future trials, specifically, by lessening the burden on participants and clinicians as well as streamlining the process for enrollment and data collection. While direct-to-adult participant recruitment is not a novel approach, our findings suggest that studies attempting to recruit the infant population may benefit from such a direct-to-participant approach.

Placental Transfusion, Timing of Plastic Wrap or Bag Placement, and Preterm Neonates.

OBJECTIVE: Compare delivery room practices and outcomes of infants born at less than 32 weeks' gestation or less than 1,500 g who have plastic wrap/bag placement simultaneously during placental transfusion to those receiving plastic wrap/bag placement sequentially following placental transfusion. STUDY DESIGN: Retrospective analysis of data from a multisite quality improvement initiative to refine stabilization procedures pertaining to placental transfusion and thermoregulation using a plastic wrap/bag. Delivery room practices and outcome data in 590 total cases receiving placental transfusion were controlled for propensity score matching and hospital of birth. RESULTS: The simultaneous and sequential groups were similar in demographic and most outcome metrics. The simultaneous group had longer duration of delayed cord clamping compared with the sequential group (42.3 ± 14.8 vs. 34.1 ± 10.3 seconds, p < 0.001), and fewer number of times cord milking was performed (0.41 ± 1.26 vs. 0.86 ± 1.92 seconds, p < 0.001). The time to initiate respiratory support was also significantly shorter in the simultaneous group (97.2 ± 100.6 vs. 125.2 ± 177.6 seconds, p = 0.02). The combined outcome of death or necrotizing enterocolitis in the simultaneous group was more frequent than in the sequential group (15.3 vs. 9.3%, p = 0.038); all other outcomes measured were similar. CONCLUSION: Timing of plastic wrap/bag placement during placental transfusion did affect duration of delayed cord clamping, number of times cord milking was performed, and time to initiate respiratory support in the delivery room but did not alter birth hospital outcomes or respiratory care practices other than the combined outcome of death or necrotizing enterocolitis. KEY POINTS: · Plastic bag placement during placental transfusion is effective in stabilization of preterms.. · Plastic bag placement after placental transfusion is effective in stabilization of preterms.. · Plastic bag placement during placental transfusion and risk of death or necrotizing enterocolitis needs additional study..

Low Rate of Spontaneous Closure in Premature Infants Discharged with a Patent Ductus Arteriosus: A Multicenter Prospective Study.

OBJECTIVES: To assess the rate of spontaneous closure and the incidence of adverse events in infants discharged home with a patent ductus arteriosus. STUDY DESIGN: In a prospective multicenter study, we enrolled 201 premature infants (gestational age of 23-32 weeks at birth) discharged home with a persistently patent ductus arteriosus (PDA) and followed their PDA status at 6-month intervals through 18 months of age. The primary study outcome was the rate and timing of spontaneous ductal closure. Secondary outcomes included rate of assisted closure and the incidence of serious adverse events. RESULTS: Spontaneous ductal closure occurred in 95 infants (47%) at 12 months and 117 infants (58%) by 18 months. Seventeen infants (8.4%) received assisted closure with surgical ligation or device assisted occlusion. Three infants died (1.5%). Although infants with spontaneous closure had a higher mean birth weight and gestational age compared with infants with a persistent PDA or assisted closure, we did not identify other factors predictive of spontaneous closure. CONCLUSIONS: Spontaneous closure of the PDA occurred in slightly less than one-half of premature infants discharged with a patent ductus by 1 year, lower than prior published reports. The high rate of assisted closure and/or adverse events in this population warrants close surveillance following discharge. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02750228.

The pediatric airway: Historical concepts, new findings, and what matters.

New observations from novel imaging techniques regarding the anatomy, dimensions, and shape of the pediatric airway have emerged and provide insight for potential changes in the clinical management of the airway in infants and children. These new findings are challenging the historical concepts of a funnel-shaped upper airway with the cricoid ring as the narrowest dimension. Although these tenets have been accepted and used to guide clinical practice in airway management, there are limited clinical investigations in children to support the validity of these concepts. Imaging modalities such as magnetic resonance imaging, computed tomography (CT) scanning, multi-detector CT imaging, and videobronchoscopy suggest the need to revisit the historical view of the pediatric airway. This manuscript reviews the historical evolution of pediatric airway studies, summarizes important scientific observations from recent investigations relevant to our clinical understanding of pediatric airway anatomy, and discusses the importance of these findings for pediatric airway management.

Tracheobronchial angles in children: Three-dimensional computed tomography-based measurements.

BACKGROUND: Studies have shown significant variation in the tracheobronchial angles in pediatric-aged patients. The current study revisits tracheobronchial angle measurements in children using accurate computed tomography-based 3-dimensional images to add clarity to the understanding of tracheobronchial angles. The primary objective of the current study was to measure the right and left bronchial angle take off from the trachea using 3-dimensional computed tomography-based images of the air column in the tracheobronchial tree. METHODS: Computed tomography-based images of 45 children younger than 8 years were reviewed. The children were evaluated during spontaneous ventilation either during natural sleep or with sedation. The right and left bronchial angles were computed between the central axes of the respective main bronchi and a vertical line passing through the central axis of the longitudinal tracheal air column. The right and left bronchial angles were compared using paired t tests, and the age dependence of the right bronchial angle and left bronchial angle difference was evaluated using Pearson's correlation coefficient. RESULTS: The study cohort included 18 males and 27 females with an average age of 49 ± 25 months. The right bronchial angle ranged from 23° to 56° (mean 42 ± 7°), whereas left bronchial angle varied between 25° and 68° (mean 43 ± 9°). The difference in means of 1 degree was not statistically significant (95% confidence interval of difference: -1°, 4°; P = .282). No association was found between left and right bronchial angle difference and patient age (r = -.019). CONCLUSION: According to computed tomography-based 3-dimensional imaging, right and left bronchial angles are virtually identical in children up to 8 years of age, and the difference between right and left bronchial angles does not vary with age in this population.

Increased indomethacin dosing for persistent patent ductus arteriosus in preterm infants: a multicenter, randomized, controlled trial.

OBJECTIVE: We conducted a multicenter, randomized, controlled trial to determine whether higher doses of indomethacin would improve the rate of patent ductus arteriosus (PDA) closure. STUDY DESIGN: Infants (<28 weeks gestation) who received a conventional, prophylactic 3-dose course of indomethacin were eligible if they had continued evidence of persistent ductus patency on an echocardiogram obtained before the third prophylactic indomethacin dose. Infants (n = 105) were randomized to receive an extended 3-day course of either low-dose (0.1 mg/kg/d) or higher-dose (0.2 or 0.5 mg/kg/d) indomethacin. An echocardiogram was obtained 24 hours after the last dose of study drug. RESULTS: Despite increasing serum indomethacin concentrations by 2.9-fold in the higher-dose group, we failed to detect a significant decrease in the rate of persistent PDA (low = 52%; higher = 45%, P = .50). The higher-dose group had a significantly higher occurrence of serum creatinine >2 mg/100 mL (low = 6%, higher = 19%, P < .05) and moderate/severe retinopathy of prematurity (ROP) (low = 15%, higher = 36%, P < .025). The incidence of moderate/severe ROP was directly related to the poststudy indomethacin concentrations (odds ratio = 1.75, confidence interval: 1.15-2.68, P < .01). CONCLUSION: Increasing indomethacin concentrations above the levels achieved with a conventional dosing regimen had little effect on the rate of PDA closure but was associated with higher rates of moderate/severe ROP and renal compromise.

Neonatology has always been a bargain--even when we weren't very good at it!

OBJECTIVE: We wondered whether Neonatal Intensive Care Unit resources for Extremely Low Birth Weight infants have always been disproportionately devoted to survivors, even when ELBW infants were very likely to die. METHODS: We documented survival and length of stay (LOS) for 2354 ELBW infants (BW 450-1000 g) admitted to the NICU at the University of Chicago between 1978 and 2003. NICU bed-days were a proxy for medical expenses. RESULTS: Over the past 25 years, ELBW admissions have risen four-fold from 25 to 100/year, and ELBW bed-days have risen ten-fold, from 700 to 7000/year. In 1978, when ELBW mortality was 80%, only 30% of ELBW bed-days were expended on non-survivors. Currently, the percentage of ELBW non-survivor bed days (NSBD) is below 10%. Even more striking, as soon as there were any survivors with BW 450-750 g, the NSBD index fell below 30%, and settled quickly around 10%. CONCLUSIONS: It is almost self-evident that there are no credible distributive justice arguments to deflect NICU care for ELBW infants now, when survival is so good. But, surprisingly, even when NICU survival was much worse, there have never been credible distributive justice arguments against NICU care for infants with BW <1000 g, whether dollars spent on survivors or 'intact survivors' is the outcome measure.

New variability in cerebrovascular anatomy determines severity of hippocampal injury following forebrain ischemia in the Mongolian gerbil.

Transient bilateral carotid artery occlusion in the Mongolian gerbil is a widely used model of forebrain ischemia due to species-specific absence of communicating arteries between the middle and posterior cerebral arteries. We have found that transient carotid occlusion induces a wide variation in histological injury of the hippocampus, suggesting that Mongolian gerbils currently available in the US have anomalous connections between the vertebral and carotid circulations. We subjected Mongolian gerbils from Harlan Sprague-Dawley and Charles River Laboratories to 5 min of bilateral carotid occlusion under continuous striatal temperature control and assessed hippocampal injury histologically 5 or 14 days later. The severity of occlusion-induced hippocampal injury depended on the presence and size of posterior cerebral communicating arteries. Injury was markedly attenuated in hippocampi having ipsilateral communicating arteries >50 microm in diameter. In contrast, severe ischemic injury occurred when either no posterior communicating artery was present, or when communicating arteries were smaller than 50 microm in diameter. Ischemic injury was independent of any communicating arteries on the contralateral side. Communicating arteries were present in 90% of gerbils from each vendor, ranging from 19 microm to 125 microm in diameter. The high prevalence of posterior communicating arteries and their profound effect on attenuating hippocampal injury indicates that an understanding of the presence and size of posterior communicating cerebral arteries in each animal is now required to interpret the extent of hippocampal injury following bilateral carotid artery occlusion in this species.