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.

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.

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.

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.

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.

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.