Randomized Study of Delayed Cord Clamping of 30 to 60 Seconds in the Larger Infant Born Preterm.

In a randomized study of infants born preterm (gestational age 28-34 6/7 weeks), we evaluated delayed cord clamping for 30 (n = 50) vs 60 (n = 55) seconds. The primary outcome of initial hematocrit differed by 2.8% (P = .006), being greater with 60 seconds. There were no differences in secondary outcomes and no adverse consequences between groups. These findings should serve as a stimulus to many centers that are reluctant to implement delayed cord clamping in this targeted larger premature population.

A quality improvement initiative to reduce antibiotic use in transient tachypnea of the newborn.

OBJECTIVE: Evidence suggests that antibiotics are unnecessary in infants with transient tachypnea of the newborn (TTN) that are low-risk for early-onset sepsis. The aim was to reduce ampicillin and gentamicin days of therapy (DOT) in infants with suspected TTN by 10% within 12 months. STUDY DESIGN: We used the Model for Improvement to test interventions from August 2019 to September 2021 to decrease antibiotic utilization in low-risk infants with TTN. Interventions included the creation of an evidence-based clinical pathway, admission huddles, and prescriber audit and feedback. RESULTS: We reduced ampicillin and gentamicin use by 26% and 23%, respectively. In 123 infants with suspected TTN, we sequentially decreased starting antibiotics in this group from 71% to 41%, 13% and 0%. There were no cases of missed bacteremia. CONCLUSION: Creation of a multidisciplinary antimicrobial stewardship QI team and subsequent interventions were successful in safely reducing antibiotic use in infants with TTN.

Assessment and management of retinopathy of prematurity in the era of anti-vascular endothelial growth factor (VEGF).

The incidence of retinopathy of prematurity (ROP) continues to rise due to the improved survival of very low birth weight infants in developed countries. This epidemic is also fueled by increased survival of preterm babies with variable use of oxygen and a lack of ROP awareness and screening services in resource-limited regions. Improvements in technology and a basic understanding of the disease pathophysiology have changed the way we screen and manage ROP, educate providers and patients, and improve ROP awareness. Advancements in imaging techniques, expansion of telemedicine services, and the potential for artificial intelligence-assisted ROP screening programs have created opportunities to improve ROP care in areas with a shortage of ophthalmologists trained in ROP. To address the gap in provider knowledge regarding ROP, the Global Education Network for Retinopathy of Prematurity (GEN-ROP) created a web-based tele-education training module that can be used to educate all providers involved in ROP, including non-physician ROP screeners. Over the past 50 years, the treatment of severe ROP has evolved from limited treatment modalities to cryotherapy and laser photocoagulation. More recently, there has been growing evidence to support the use of anti-vascular endothelial growth factor (VEGF) agents for the treatment of severe ROP. However, VEGF is known to be important in organogenesis and microvascular maintenance, and given that intravitreal anti-VEGF treatment can result in systemic VEGF suppression over a period of at least 1-12 weeks, there are concerns regarding adverse effects and long-term ocular and systemic developmental consequences of anti-VEGF therapy. Future research in ophthalmology to address the growing burden of ROP should focus on cost-effective fundus imaging devices, implementation of artificial intelligence platforms, updated treatment algorithms with optimal use of anti-VEGF and careful investigation of its long-term effects, and surgical options in advanced ROP. Addressing these unmet needs will aid the global effort against the ROP epidemic and optimize our understanding and treatment of this blinding disease.

Evaluation of an Artificial Intelligence System for Retinopathy of Prematurity Screening in Nepal and Mongolia.

Purpose: To evaluate the performance of a deep learning (DL) algorithm for retinopathy of prematurity (ROP) screening in Nepal and Mongolia. Design: Retrospective analysis of prospectively collected clinical data. Participants: Clinical information and fundus images were obtained from infants in 2 ROP screening programs in Nepal and Mongolia. Methods: Fundus images were obtained using the Forus 3nethra neo (Forus Health) in Nepal and the RetCam Portable (Natus Medical, Inc.) in Mongolia. The overall severity of ROP was determined from the medical record using the International Classification of ROP (ICROP). The presence of plus disease was determined independently in each image using a reference standard diagnosis. The Imaging and Informatics for ROP (i-ROP) DL algorithm was trained on images from the RetCam to classify plus disease and to assign a vascular severity score (VSS) from 1 through 9. Main Outcome Measures: Area under the receiver operating characteristic curve and area under the precision-recall curve for the presence of plus disease or type 1 ROP and association between VSS and ICROP disease category. Results: The prevalence of type 1 ROP was found to be higher in Mongolia (14.0%) than in Nepal (2.2%; P < 0.001) in these data sets. In Mongolia (RetCam images), the area under the receiver operating characteristic curve for examination-level plus disease detection was 0.968, and the area under the precision-recall curve was 0.823. In Nepal (Forus images), these values were 0.999 and 0.993, respectively. The ROP VSS was associated with ICROP classification in both datasets (P < 0.001). At the population level, the median VSS was found to be higher in Mongolia (2.7; interquartile range [IQR], 1.3-5.4]) as compared with Nepal (1.9; IQR, 1.2-3.4; P < 0.001). Conclusions: These data provide preliminary evidence of the effectiveness of the i-ROP DL algorithm for ROP screening in neonatal populations in Nepal and Mongolia using multiple camera systems and are useful for consideration in future clinical implementation of artificial intelligence-based ROP screening in low- and middle-income countries.

Delayed onset of sleep-wake cycling with favorable outcome in hypothermic-treated neonates with encephalopathy.

OBJECTIVE: To determine whether hypothermia modulates acquisition of sleep-wake cycling in term neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE) and the relationship to outcome. STUDY DESIGN: Twenty-nine term infants with moderate to severe HIE treated with selective head cooling were evaluated. All were monitored with amplitude-integrated electroencephalography during and video electroencephalography immediately after hypothermia for ≥72 hours. Electroencephalograpic data were analyzed for background and sleep-wake cycling. Abnormal outcome included death or severe global neurodevelopmental disability ≥18 months. RESULTS: Acquisition of sleep-wake cycling was noted in nine infants by 72 hours, in 13 by 96 hours, 19 by 120 hours, and 22 by 144 hours. Presence of sleep-wake cycling was associated with normal outcome, that is, 14 of 22 (64%), versus abnormal outcome, that is, none of seven without sleep-wake cycling (P = .006). The presence of sleep-wake cycling by 120 hours had a positive predictive value of 68% and negative predictive value of 90%. Magnetic resonance imaging abnormalities were related to onset of sleep-wake cycling. CONCLUSIONS: Although onset of sleep-wake cycling is markedly delayed in term neonates with moderate to severe HIE treated with hypothermia, approximately 65% with acquisition of cycling have a normal outcome. Sleep-wake cycling is an important additional tool for assessing recovery in term infants with moderate to severe HIE treated with hypothermia.

Oxygen management among infants in neonatal units in sub-Saharan Africa: a cross-sectional survey.

OBJECTIVES: To provide more comprehensive data on the management of oxygen supplementation in neonates in sub-Saharan Africa. STUDY DESIGN: An online survey on the management of oxygen supplementation for infants in neonatal units was sent to 278 healthcare personnel in sub-Saharan Africa. RESULTS: One hundred and nine responses from 82 neonatal care units in 54% (26/48) sub-Saharan African countries were received. All units had the capacity to provide oxygen supplementation. However, only 50% (38/76) had access to blend oxygen with medical air and 1% (1/75) had the capacity to blend oxygen/air for every infant. Although 96% (72/75) of units could monitor oxygen saturation, monitoring was mostly intermittent and only 32% (24/75) were able to monitor oxygen saturation in every infant receiving oxygen supplementation. CONCLUSIONS: Findings indicate that oxygen supplementation is inadequately managed in neonatal units in sub-Saharan Africa, which may put infants at risk of developing severe ROP.

Stimulus-induced seizure in sick neonates--novel observations with potential clinical implications.

Stimulus-induced seizure is a well-described entity in children and adults and is often associated with severe epilepsy and neurologic impairment. The occurrence and clinical expression of stimulus-induced seizure in three sick neonates is described. The cohort comprised 26 neonates undergoing continuous video-electroencephalography (vEEG) monitoring between July and December 2007. Three cases (11.5%) of stimulus-induced seizure were identified. The underlying injury included stroke (n = 2) and intraventricular hemorrhage (n = 1). Seizures were induced by physical stimuli such as stroking the forehead, movements, (i.e., starting to feed), and one during endotracheal suctioning. Stimulus-evoked electrographic patterns have been reported in neonates with brain injury; however, these events appear to be more common than previously thought, especially with the abundance of subclinical seizures observed in these patients. These observations stress the usefulness of vEEG monitoring and importance of care to avoid unnecessary stimuli in at-risk neonates.

Mechanisms of brain injury in newborn infants associated with the fetal inflammatory response syndrome.

The fetal inflammatory response syndrome (FIRS) is characterized by umbilical cord inflammation and elevated fetal pro-inflammatory cytokines. Surviving neonates, especially very preterm infants, have increased rates of neonatal morbidity including neurodevelopmental impairment. The mechanism of brain injury in FIRS is complex and may involve "multiple hits." Exposure to in utero inflammation initiates a cascade of the fetal immune response, where pro-inflammatory cytokines can cause direct injury to oligodendrocytes and neurons. Activation of microglia results in further injury to vulnerable pre-myelinating oligodendrocytes and influences the integrity of the fetal and newborn's blood-brain barrier, resulting in further exposure of the brain to developmental insults. Newborns exposed to FIRS are frequently exposed to additional perinatal and postnatal insults that can result in further brain injury. Future directions should include evaluations for new therapeutic interventions aimed at reducing brain injury by dampening FIRS, inhibition of microglial activation, and regeneration of immature oligodendrocytes.

Evaluation of Potential Systemic Adverse Events Related to Fluorescein Angiography in Pediatric Patients.

PURPOSE: To evaluate adverse events of fluorescein angiography (FA) in pediatric patients. DESIGN: Single-institution retrospective chart review. PARTICIPANTS: Patients 0 to 18 years of age who underwent FA between January 2010 and December 2015 at a single institution in the United States. METHODS: Pediatric patients who underwent FA by 3 surgeons were included in the study. Patients with fewer than 24 hours of documented follow-up were excluded. Significant adverse events within 24 hours of FA were evaluated. Detailed intraoperative and perioperative physiological parameters, including heart rate, blood pressure, oxygen saturation, and ventilation parameters, in inpatients undergoing simultaneous examination under anesthesia were reviewed. Peri-injection effects of FA were evaluated by 2-tailed paired t test comparison of mean 5-minute preinjection and 5-minute postinjection physiological data. MAIN OUTCOME MEASURES: Significant adverse events associated with FA. RESULTS: One hundred fifteen patients with a total of 214 FA examinations were included. No significant adverse events were associated directly with FA. Comparison of mean 5-minute preinjection and postinjection physiologic parameters in 27 patients who underwent intravenous FA during EUA did not reveal significant changes associated with FA. A significant difference was found in average patient age between inpatient (2.5 years) and outpatient (10.7 years) FA (P < 0.00001). The youngest patients who underwent successful FA were 3.8 years old in the outpatient setting and 32 weeks' postmenstrual age in the inpatient setting. Patients younger than 3.8 years accounted for most (77.6%; n = 85) inpatient FA examinations. Excluding patients with a need or likely need for laser or surgery, the reasons for inpatient FA in patients older than 3.8 years included the lack of availability of outpatient ultra-widefield FA (UWFA) and more challenging situations in patients with developmental delay. CONCLUSIONS: Fluorescein angiography was not found to be associated directly with systemic adverse events in pediatric patients in this study. Younger patients more commonly were found to require an inpatient FA, whereas older patients older than 4 years underwent outpatient UWFA.

Development of Screening Criteria for Retinopathy of Prematurity in Ulaanbaatar, Mongolia, Using a Web-based Data Management System.

PURPOSE: To describe a process for identifying birth weight (BW) and gestational age (GA) screening guidelines in Mongolia. METHODS: This was a prospective cohort study in a tertiary care hospital in Ulaanbataar, Mongolia, of 193 premature infants with GA of 36 weeks or younger and/or BW of 2,000 g or less) with regression analysis to determine associations between BW and GA and the development of retinopathy of prematurity (ROP). RESULTS: As BW and GA decreased, the relative risk of developing ROP increased. The relative risk of developing any stage of ROP in infants born at 29 weeks or younger was 2.91 (95% CI: 1.55 to 5.44; P < .001] compared to older infants. The relative risk of developing any type of ROP in infants with BW of less than 1,200 g was 2.41 (95% CI: 1.35 to 4.29; P = .003] and developing type 2 or worse ROP was 2.05 (95% CI: 0.99 to 4.25; P = .05). CONCLUSIONS: Infants in Mongolia with heavier BW and older GA who fall outside of current United States screening guidelines of GA of 30 weeks or younger and/or BW of 1,500 g or less developed clinically relevant ROP. [J Pediatr Ophthalmol Strabismus. 2020;57(5):333-339.].

The Relationship Between Motor Delays and Language Development in Very Low Birthweight Premature Children at 18 Months Corrected Age.

Purpose: The aim of this study is to determine if there is a specific association between motor delays and receptive and expressive language function, respectively, in prematurely born children. Method: Retrospective data review: 126 premature children ≤ 1,250-g birthweight from English-speaking families were evaluated on motor development (normal, mild delay, and moderate-severe delay) and the cognitive and language scales of the Bayley Scales of Infant and Toddler Development-Third Edition (Bayley, 2006) at 18 months corrected age. Cognitive scores were categorized as normal, suspect, and abnormal. Gender, demographic, and perinatal variables were recorded and analyzed with respect to motor category. Results: Lower birthweight, chronic need for oxygen, severe intraventricular hemorrhage, and intestinal infection/inflammation were related to poorer motor development. On receptive language, the normal motor group attained significantly higher scores than the moderate-severe motor group but did not differ significantly from the mild delay motor group. On expressive language, the normal motor group had significantly higher scores than both the mild and moderate-severe groups. Girls performed better than boys on receptive and expressive language, but there was no significant interaction between gender and motor category on any of the Bayley scores. Cognitive, but not motor, category significantly contributed to variance of receptive language scores; cognitive and motor category each independently contributed to the variance in expressive language. Conclusion: Findings suggest that motor control areas of the brain may be implicated in expressive language development of premature children. Further research is needed to determine the underlying factors for the association between motor and expressive language function.

Amplitude-integrated EEG in newborns with critical congenital heart disease predicts preoperative brain magnetic resonance imaging findings.

OBJECTIVE: The study aims are to evaluate cerebral background patterns using amplitude-integrated electroencephalography in newborns with critical congenital heart disease, determine if amplitude-integrated electroencephalography is predictive of preoperative brain injury, and assess the incidence of preoperative seizures. We hypothesize that amplitude-integrated electroencephalography will show abnormal background patterns in the early preoperative period in infants with congenital heart disease that have preoperative brain injury on magnetic resonance imaging. METHODS: Twenty-four newborns with congenital heart disease requiring surgery at younger than 30 days of age were prospectively enrolled within the first 3 days of age at a tertiary care pediatric hospital. Infants had amplitude-integrated electroencephalography for 24 hours beginning close to birth and preoperative brain magnetic resonance imaging. The amplitude-integrated electroencephalographies were read to determine if the background pattern was normal, mildly abnormal, or severely abnormal. The presence of seizures and sleep-wake cycling were noted. The preoperative brain magnetic resonance imaging scans were used for brain injury and brain atrophy assessment. RESULTS: Fifteen of 24 infants had abnormal amplitude-integrated electroencephalography at 0.71 (0-2) (mean [range]) days of age. In five infants, the background pattern was severely abnormal. (burst suppression and/or continuous low voltage). Of the 15 infants with abnormal amplitude-integrated electroencephalography, 9 (60%) had brain injury. One infant with brain injury had a seizure on amplitude-integrated electroencephalography. A severely abnormal background pattern on amplitude-integrated electroencephalography was associated with brain atrophy (P = 0.03) and absent sleep-wake cycling (P = 0.022). CONCLUSION: Background cerebral activity is abnormal on amplitude-integrated electroencephalography following birth in newborns with congenital heart disease who have findings of brain injury and/or brain atrophy on preoperative brain magnetic resonance imaging.

White matter injury in newborns with congenital heart disease: a diffusion tensor imaging study.

BACKGROUND: Brain injury is observed on cranial magnetic resonance imaging preoperatively in up to 50% of newborns with congenital heart disease. Newer imaging techniques such as diffusion tensor imaging provide sensitive measures of the white matter integrity. The objective of this study was to evaluate the diffusion tensor imaging analysis technique of tract-based spatial statistics in newborns with congenital heart disease. METHODS: Term newborns with congenital heart disease who would require surgery at less than 1 month of age were prospectively enrolled (n = 19). Infants underwent preoperative and postoperative brain magnetic resonance imaging with diffusion tensor imaging. Tract-based spatial statistics, an objective whole-brain diffusion tensor imaging analysis technique, was used to determine differences in white matter fractional anisotropy between infant groups. Term control infants were also compared with congenital heart disease infants. Postmenstrual age was equivalent between congenital heart disease infant groups and between congenital heart disease and control infants. RESULTS: Ten infants had preoperative brain injury, either infarct or white matter injury, by conventional brain magnetic resonance imaging. The technique of tract-based spatial statistics showed significantly lower fractional anisotropy (P < 0.05, corrected) in multiple major white matter tracts in the infants with preoperative brain injury compared with infants without preoperative brain injury. Fractional anisotropy values increased in the white matter tracts from the preoperative to the postoperative brain magnetic resonance imaging correlating with brain maturation. Control infants had higher fractional anisotropy in multiple white matter tracts compared with infants with congenital heart disease. CONCLUSION: Tract-based spatial statistics is a valuable diffusion tensor imaging analysis technique that may have better sensitivity in detecting white matter injury compared with conventional brain magnetic resonance imaging in term newborns with congenital heart disease.

Quantitative cranial magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy.

The volume of acute injury detected by diffusion-weighted imaging and quantitative brain growth on serial cranial magnetic resonance imaging was not previously used to predict neurodevelopmental outcomes in infants with neonatal hypoxic-ischemic encephalopathy treated with head cooling. Our longitudinal study involved 16 head-cooled term infants with hypoxic-ischemic encephalopathy who underwent early and follow-up cranial magnetic resonance imaging and follow-up neurologic evaluations, out of 105 infants who received therapeutic hypothermia. The volume of acute injury was measured on initial cranial magnetic resonance imaging, using diffusion-weighted images. Total brain volumes were measured in both early and follow-up magnetic resonance imaging studies. Acute injury volume in the corpus callosum >0.5 cm(3) was associated with developing epilepsy (odds ratio, 20; 95% confidence interval, 1.01-1059.6; P = 0.013). Follow-up whole brain volume was reduced in those with unfavorable outcomes (i.e., epilepsy, cerebral palsy, and delayed developmental milestones), compared with infants without all three outcomes. Although acute brain injury volume and brain growth measurements may be useful predictors of outcomes in neonatal hypoxic-ischemic encephalopathy, the evolution of brain injury in these infants has yet to be fully understood and should be studied prospectively.

Therapeutic hypothermia in a neonate with perinatal asphyxia and transposition of the great arteries.

Despite advances in surgical techniques and perioperative management, many newborns with complex congenital heart disease (CCHD) continue to have adverse neurodevelopmental outcomes. With increasing survival of these infants, neuroprotective therapies at various time points, should be considered as an important area of investigation. As some brain injury has been shown to precede surgery, the preoperative period may be a key time to direct protective therapy. Selective hypothermia is used as a neuroprotective therapy for neonates with moderate-to-severe hypoxic-ischemic encephalopathy. We report a case of an asphyxiated term newborn with severe neonatal encephalopathy following neonatal resuscitation and subsequently found to have transposition of the great arteries with a relatively intact atrial septum, who underwent CoolCap(®) therapy following emergent balloon atrial septostomy. Brain injury observed on magnetic resonance imaging preoperatively after cooling was focal and did not extend following neonatal arterial switch operation. The patient's neurologic outcome appeared to be favorable at hospital discharge and at age 6 months. This case presents a therapeutic intervention which may represent a valuable neuroprotective strategy to limit brain injury, and therefore, improve neurodevelopmental outcomes in neonates with CCHD with perinatal asphyxia.

Seizures are common in term infants undergoing head cooling.

Selective head cooling was used to treat infants at risk of developing encephalopathy within 6 hours as part of a practice plan. Amplitude-integrated electroencephalography and raw, single-channel electroencephalography tracings were performed continuously during cooling. Routine electroencephalography was performed intermittently during, and video electroencephalography immediately after, selective head cooling. Magnetic resonance imaging was performed at the end of week 1. We sought a better delineation of the occurrence and timing of clinical and electrographic seizures during selective head cooling. Twenty term infants are described. Eleven received chest compressions, all at pH <7. Upon admission, encephalopathy was characterized clinically as moderate (n = 13) or severe (n = 7), and by amplitude-integrated electroencephalography as moderate (n = 8), severe (n = 6), or indeterminate (n = 6). Clinical seizures (n = 18) were most prominent on day 1. Amplitude-integrated electroencephalography seizures (n = 9) were evident upon admission and on day 1 (n = 19), and were continuous between 24-36 hours (n = 9). Amplitude-integrated electroencephalography seizures were confirmed by routine electroencephalography. Magnetic resonance imaging was abnormal in nine infants, with predominantly bilateral involvement of the basal ganglia (n = 8). Magnesium was at