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The incidence of intraventricular hemorrhage (IVH) has overall declined to 15% to 20% of preterm infants with birth weight less than 1500 g. One of the major complications of severe IVH is posthemorrhagic ventricular dilation (PHVD). Nearly 10% of all infants with IVH and 20% of infants with severe IVH will develop progressive PHVD requiring surgical intervention to prevent parenchymal damage in the developing brain. This review focuses on the controversies regarding posthemorrhagic hydrocephalus interventions with a focus on how to interpret recent data from trials that some have seen as heralding a call toward more aggressive intervention.

To examine the frequency of placental abnormalities in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE) and to determine the association between acuity of placental abnormalities and clinical characteristics of HIE.Infants born at ≥36 weeks of gestation (n = 500) with moderate or severe HIE were enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy Trial. A placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute and chronic placental abnormalities using a standard classification system.Complete placental pathologic examination was available for 321 of 500 (64%) trial participants. Placental abnormalities were identified in 273 of 321 (85%) and were more common in infants ≥40 weeks of gestation (93% vs 81%, P = .01). A combination of acute and chronic placental abnormalities (43%) was more common than either acute (20%) or chronic (21%) abnormalities alone. Acute abnormalities included meconium staining of the placenta (41%) and histologic chorioamnionitis (39%). Chronic abnormalities included maternal vascular malperfusion (25%), villitis of unknown etiology (8%), and fetal vascular malperfusion (6%). Infants with chronic placental abnormalities exhibited a greater mean base deficit at birth (-15.9 vs -14.3, P = .049) than those without such abnormalities. Patients with HIE and acute placental lesions had older mean gestational ages (39.1 vs 38.0, P .001) and greater rates of clinically diagnosed chorioamnionitis (25% vs 2%, P .001) than those without acute abnormalities.Combined acute and chronic placental abnormalities were common in this cohort of infants with HIE, underscoring the complex causal pathways of HIE.ClinicalTrials.gov: NCT02811263.

Context The relationship between quality of Goals of Care (GOC) conversations and moral distress among neonatal intensive care unit (NICU) providers is not known. Objectives We sought 1) to explore levels of moral distress in providers, 2) to evaluate how staff moral distress changes in relation to GOC discussions, and 3) to identify elements of GOC discussions associated with change in moral distress. We hypothesized that staff moral distress would change after GOC discussions and that change would vary with presence of key discussion elements. Methods Prospective cohort study in a level IV NICU in an urban teaching hospital. We administered validated instruments at baseline and following GOC discussions including the Moral Distress Thermometer (MDT) and Williams Instrument (a measure of end-of-life care) to physicians, nurses, and social workers. Results We collected data on 79 GOC conversations over a 1-year period from 2018 to 2019. Most providers experienced an increase in moral distress following a GOC discussion. Providers experienced an average increase in moral distress, as measured by the MDT, of 0.84 (+/-3.15; P = 0.002). Physicians experienced an average change in moral distress of 1.1 (+/-3.52; P = 0.01) while nurses experienced an average change of 0.55 (+/-2.66; P = 0.07). Several elements of discussions were associated with the degree of increase in moral distress after the conversation. Conclusion Change in moral distress among providers may be a useful metric of quality of GOC discussions. There are identifiable elements of GOC conversations that are associated with high-quality discussions. These elements warrant further study.

Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown.In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 [normal] to 5 [most impaired]), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition.Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval [CI], 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57).The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT02811263.).

ObjectiveTo characterise the transitional pulmonary physiology of infants with congenital diaphragmatic hernia (CDH) using measures of expiratory tidal volume (TV) and end-tidal carbon dioxide (ETCO2).DesignProspective single-centre observational study.SettingQuaternary neonatal intensive care unit.PatientsInfants with an antenatal diagnosis of CDH born at the Children’s Hospital of Philadelphia.InterventionsTV and ETCO2were simultaneously recorded using a respiratory function monitor (RFM) during invasive positive pressure ventilation immediately after birth.Main outcome measuresTV per birth weight and ETCO2values were summarised for each minute after birth. Subgroups of interest were defined by liver position (thoracic vs abdominal) and extracorporeal membrane oxygenation (ECMO) treatment.ResultsRFM data were available for 50 infants from intubation until a median (IQR) of 9 (7–14) min after birth. TV and ETCO2values increased for the first 10 min after birth, but intersubject values were heterogeneous. TVs were overall lower and ETCO2values higher in infants with an intrathoracic liver and infants who were ultimately treated with ECMO. On hospital discharge, survival was 88% (n=43) and 34% (n=17) of infants were treated with ECMO.ConclusionRespiratory function immediately after birth is heterogeneous for infants with CDH. Lung aeration, as evidenced by expired TV and ETCO2, appears to be ongoing throughout the first 10 min after birth during invasive positive pressure ventilation. Close attention to expired TV and ETCO2levels by 10 min after birth may provide an opportunity to optimise and individualise ventilatory support for this high-risk population.

Background: Clinical measures after birth and studies such as electroencephalogram (EEG) and brain imaging do not fully predict neurodevelopmental outcomes of infants with hypoxic-ischemic encephalopathy. Early detection of adverse neurologic outcomes, and cerebral palsy in particular, in high-risk infants is essential for ensuring timely management. The General Movements Assessment is a tool that can be used in the early detection of cerebral palsy in infants with brain injury. The majority of studies on the General Movements Assessment in the late preterm and term population were performed prior to the introduction of therapeutic hypothermia. Aims: To apply the General Movements Assessment in late preterm and term infants with hypoxic-ischemic encephalopathy (including those who received therapeutic hypothermia), to determine if clinical markers of hypoxic-ischemic encephalopathy predict abnormal General Movements Assessment findings, and to evaluate interrater reliability of the General Movements Assessment in this population. Study design: Pilot prospective cohort study Subjects: We assessed 29 late preterm and full-term infants with mild, moderate, and severe hypoxic-ischemic encephalopathy in Philadelphia, PA. Results: Most infants’ general movements normalized by the fidgety age. Only infants with moderate or severe hypoxic-ischemic encephalopathy had abnormal general movements in both the writhing and the fidgety ages (n = 6). Seizure at any point during the initial hospitalization was the clinical sign most predictive of abnormal general movements in the fidgety age (sensitivity 100%, specificity 55%, positive predictive value 40%, negative predictive value 100%). Interrater reliability was greatest during the fidgety age (κ = 0.67). Conclusions: Seizures were the clinical predictor most closely associated with abnormal findings on the General Movements Assessment. However, clinical markers of hypoxic-ischemic encephalopathy are not fully predictive of abnormal General Movements Assessment findings. Larger future studies are needed to evaluate the associations between the General Movements Assessment and childhood neurologic outcomes in patients with hypoxic-ischemic encephalopathy who received therapeutic hypothermia.

BACKGROUND: Extreme thrombocytosis (EXT, platelet count >1000 × 10(3)/μl) is an uncommon but potentially clinically significant finding. Primary EXT in the setting of myeloproliferative disorders is linked to thrombotic and/or bleeding complications more frequently than secondary EXT, which typically occurs in reaction to infection, inflammation, or iron deficiency. However, comorbidities have been reported in adults with secondary EXT. Clinical implications of EXT in children are not well-defined, as prior studies targeted small and/or specialized pediatric populations. OBJECTIVES: Our objective was to determine etiologies and sequelae of extreme thrombocytosis in a hospitalized general pediatric patient population. PATIENTS AND METHODS: We retrospectively analyzed EXT cases from a single-center pediatric cohort of ~80,000 patients over 8 years. RESULTS: Virtually all cases (99.8%) were secondary in nature, and most were multifactorial. Many cases of EXT occurred in children under 2 years old (47%) and/or during critical illness (55%). No thrombotic or bleeding events directly resulted from EXT, confirming a paucity of clinical complications associated with EXT in pediatric patients. There were indications that neonatal hematopoiesis and individual genetic variation influenced some cases, in addition to certain diagnoses (e.g., sickle cell anemia) and clinical contexts (e.g., asplenia). CONCLUSION: Our findings confirm that thrombotic events related to EXT are rare in pediatric patients, which can inform the use of empiric anti-platelet therapy.

This study aimed to evaluate how parents of former neonatal intensive care unit patients with cerebral palsy perceive prognostic discussions following neuroimaging. Parent members of a cerebral palsy support network described memories of prognostic discussions after neuroimaging in the neonatal intensive care unit. We analyzed responses using Linguistic Inquiry and Word Count, manual content analysis, and thematic analysis. In 2015, a total of 463 parents met eligibility criteria and 266 provided free-text responses. Linguistic Inquiry and Word Count analysis showed that responses following neuroimaging contained negative emotion. The most common components identified through the content analysis included outcome, uncertainty, hope/hopelessness, and weakness in communication. Thematic analysis revealed 3 themes: (1) Information, (2) Communication, and (3) Impact. Parents of children with cerebral palsy report weakness in communication relating to prognosis, which persists in parents’ memories. Prospective work to develop interventions to improve communication between parents and providers in the neonatal intensive care unit is necessary.

To assess the association between opioid exposure during therapeutic hypothermia (TH) for perinatal hypoxic-ischemic encephalopathy (HIE) and in-hospital outcomes.In this retrospective cohort study, linked data were accessed on infants ≥36 weeks gestation, who underwent TH for HIE, born from 2010-2016 in 23 Neonatal Intensive Care Units participating in Children's Hospitals Neonatal Consortium and Pediatric Health Information Systems. We excluded infants who received opioids for5 days.The cohort (n = 1484) was categorized as No opioid [240(16.2%)], Low opioid (1-2 days) [574 (38.7%)] and High opioid group (HOG, 3-5 days) [670 (45.2%)]. After adjusting for HIE severity, opioids were not associated with abnormal MRI, but were associated with decreased likelihood of complete oral feeds at discharge. HOG had increased likelihood of prolonged hospital stay and ventilation.Opioid exposure during TH was not associated with abnormal MRI; its association with adverse short-term outcomes suggests need for cautious empiric use.

OBJECTIVES The objectives of this study are to determine whether abnormalities on neonatal cranial ultrasound (CUS) are associated with minor motor abnormalities at 2 years' corrected age (CA) and to assess functional outcomes and resource utilization among children with minor motor abnormalities. METHODS Infants born at

Background While intercenter variation (ICV) in anti-epileptic drug (AED) use in neonates with seizures has been previously reported, variation in AED practices across regional NICUs has not been specifically and systematically evaluated. This is important as these centers typically have multidisciplinary neonatal neurocritical care teams and protocolized approaches to treating conditions such as hypoxic ischemic encephalopathy (HIE), a population at high risk for neonatal seizures. To identify opportunities for quality improvement (QI), we evaluated ICV in AED utilization for neonates with HIE treated with therapeutic hypothermia (TH) across regional NICUs in the US. Methods Children’s Hospital Neonatal Database and Pediatric Health Information Systems data were linked for 1658 neonates ≥36 weeks’ gestation, > 1800 g birthweight, with HIE treated with TH, from 20 NICUs, between 2010 and 2016. ICV in AED use was evaluated using a mixed-effect regression model. Rates of AED exposure, duration, prescription at discharge and standardized AED costs per patient were calculated as different measures of utilization. Results Ninety-five percent (range: 83–100%) of patients with electrographic seizures, and 26% (0–81%) without electrographic seizures, received AEDs. Phenobarbital was most frequently used (97.6%), followed by levetiracetam (16.9%), phenytoin/fosphenytoin (15.6%) and others (2.4%; oxcarbazepine, topiramate and valproate). There was significant ICV in all measures of AED utilization. Median cost of AEDs per patient was $89.90 (IQR $24.52,$258.58). Conclusions Amongst Children’s Hospitals, there is marked ICV in AED utilization for neonatal HIE. Variation was particularly notable for HIE patients without electrographic seizures, indicating that this population may be an appropriate target for QI processes to harmonize neuromonitoring and AED practices across centers.

Genomic medicine holds promise to revolutionize care for critically ill infants by tailoring treatments for patients and providing additional prognostic information to families. However, measuring the utility of genomic medicine is not straightforward and has important clinical and ethical implications.To review the ways that researchers measure or neglect to measure the utility of genomic medicine for critically ill infants.This systematic review included prospective full-text studies of genomic medicine of both whole exome and genome sequencing in critically ill infants younger than 1 year. PubMed, Embase, Scopus, and Cochrane Library databases, the Cochrane Database of Systematic Reviews, and the ClinicalTrials.gov register were searched with an English language restriction for articles published from the inception of each database through May 2022. Search terms included variations of the following: gene, sequencing, intensive care, critical care, and infant. From the included articles, information on how utility was defined and measured was extracted and synthesized. Information was also extracted from patient cases that authors highlighted by providing additional information. Spearman rank-order correlation was used to evaluate the association between study size and utility.Synthesized data from the 21 included studies reflected results from 1654 patients. A mean of 46% (range, 15%-72%) of patients had a positive genetic test result, and a mean of 37% (range, 13%-61%) met the criteria for experiencing utility. Despite heterogeneity in how studies measured and reported utility, a standardized framework was created with 5 categories of utility: treatment change, redirection of care, prognostic information, reproductive information, and screening or subspecialty referral. Most studies omitted important categories of utility, notably personal utility (patient-reported benefits) (20 studies [95%]), utility of negative or uncertain results (15 [71%]), and disutility (harms) (20 [95%]). Studies disproportionally highlighted patient cases that resulted in treatment change. Larger studies reported substantially lower utility (r = -0.65; P = .002).This systematic review found that genomic medicine offered various categories of utility for a substantial proportion of critically ill infants. Studies measured utility in heterogeneous ways and focused more on documenting change than assessing meaningful benefit. Authors' decisions about which cases to highlight suggest that some categories of utility may be more important than others. A more complete definition of utility that is used consistently may improve understanding of potential benefits and harms of genetic medicine.

Introduction: Ultrasound (US)-based indexes such as fronto-occipital ratio (FOR) can be used to obtain an acceptable estimation of ventricular volume. Patients with colpocephaly present a unique challenge due to the shape of their ventricles. In the present study, we aimed to evaluate the validity and reproducibility of the modified US-FOR index in children with Chiari II-related ventriculomegaly. Methods: In this retrospective study, we evaluated Chiari II patients younger than 1 year who underwent head US and MR or CT scans for ventriculomegaly evaluation. MR/CT-based FOR was measured in the axial plane by identifying the widest diameter of frontal horns, occipital horns, and the interparietal diameter (IPD). US-based FOR (US-FOR) was measured using the largest diameter based on the following landmarks: frontal horn and IPD in the coronal plane at the level of the foramen of Monro, IPD just superior to the Sylvian fissures, and occipital horn posterior to the thalami and inferior to the superior margins of the thalami. Intraclass correlation coefficients (ICCs) were used to evaluate inter-rater reliability, and Pearson correlation coefficients and Bland-Altman plots were applied to assess agreement between US and other two modalities. Results: Sixty-three paired US and MR/CT exams were assessed for agreement between US-FOR and MR/CT-FOR measurements. ICC showed an excellent inter-rater reliability for US-FOR (ICC = 0.99, p < 0.001) and MR/CT-FOR (ICC = 0.99, p < 0.001) measurements. The mean (range) values based on US-FOR showed a slight overestimation in comparison with MR/CT-FOR (0.51 [0.36–0.68] vs. 0.46 [0.34–0.64]). The Pearson correlation coefficient showed high cross-modality agreement for the FOR index (r = 0.83, p < 0.001). The Bland-Altman plot showed excellent concordance between US-FOR and MR/CT-FOR with a bias of 0.05 (95% CI: −0.03 to 0.13). Conclusion: US-FOR in the coronal plane is a comparable tool for evaluating ventriculomegaly in Chiari II patients when compared with MR/CT-FOR, even in the context of colpocephaly.

This study aimed to determine clinical care practices for infants at risk for posthemorrhagic hydrocephalus (PHH) across level IV neonatal intensive care units (NICUs). Cross-sectional survey that addressed center-specific surveillance, neurosurgical intervention, and follow-up practices within the Children's Hospitals Neonatal Consortium. We had a 59% (20/34 sites) response rate, with 10 sites having at least two participants. Respondents included neonatologists (53%) and neurosurgeons (35%). Most participants stated having a standard guideline for PHH (79%). Despite this, 42% of respondents perceive inconsistencies in management. Eight same-center pairs of neonatologists and neurosurgeons were used to determine response agreement. Half of these pairs disagreed on nearly all aspects of care. The greatest agreement pertained to a willingness to adopt a consensus-based protocol. Practice variation in the management of infants at risk of PHH in level IV NICUs exists despite the perception that a common practice is available and used.· Practice variation exists despite the perception that common practices are available/used for PHH.. · Our survey had same-center pairs of neonatologist and neurosurgeons to determine response agreement.. · The greatest agreement pertained to a willingness to adopt a consensus-based protocol..

To describe the parental experience of recruitment and assess differences between parents who participated and those who declined to enroll in a neonatal clinical trial.This was a survey conducted at 12 US neonatal intensive care units of parents of infants who enrolled in the High-dose Erythropoietin for Asphyxia and encephaLopathy (HEAL) trial or who were eligible but declined enrollment. Questions assessed 6 factors of the parental experience of recruitment: (1) interactions with research staff; (2) the consent experience; (3) perceptions of the study; (4) decisional conflict; (5) reasons for/against participation; and (6) timing of making the enrollment decision.In total, 269 of 387 eligible parents, including 183 of 242 (75.6%) of those who enrolled their children in HEAL and 86 of 145 (59.3%) parents who declined to enroll their children in HEAL, were included in analysis. Parents who declined to enroll more preferred to be approached by clinical team members rather than by research team members (72.9% vs 49.2%, P = .005). Enrolled parents more frequently reported positive initial impressions (54.9% vs 10.5%, P .001). Many parents in both groups made their decision early in the recruitment process. Considerations of reasons for/against participation differed by enrollment status.Understanding how parents experience recruitment, and how this differs by enrollment status, may help researchers improve recruitment processes for families and increase enrollment. The parental experience of recruitment varied by enrollment status. These findings can guide future work aiming to inform optimal recruitment strategies for neonatal clinical trials.

OBJECTIVES We developed a tool, Serial Neurologic Assessment in Pediatrics, to screen for neurologic changes in patients, including those who are intubated, are sedated, and/or have developmental disabilities. Our aims were to: 1) determine protocol adherence when performing Serial Neurologic Assessment in Pediatrics, 2) determine the interrater reliability between nurses, and 3) assess the feasibility and acceptability of using Serial Neurologic Assessment in Pediatrics compared with the Glasgow Coma Scale. DESIGN Mixed-methods, observational cohort. SETTING Pediatric and neonatal ICUs. SUBJECTS Critical care nurses and patients. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Serial Neurologic Assessment in Pediatrics assesses Mental Status, Cranial Nerves, Communication, and Motor Function, with scales for children less than 6 months, greater than or equal to 6 months to less than 2 years, and greater than or equal to 2 years old. We assessed protocol adherence with standardized observations. We assessed the interrater reliability of independent Serial Neurologic Assessment in Pediatrics assessments between pairs of trained nurses by percent- and bias- adjusted kappa and percent agreement. Semistructured interviews with nurses evaluated acceptability and feasibility after nurses used Serial Neurologic Assessment in Pediatrics concurrently with Glasgow Coma Scale during routine care. Ninety-eight percent of nurses (43/44) had 100% protocol adherence on the standardized checklist. Forty-three nurses performed 387 paired Serial Neurologic Assessment in Pediatrics assessments (149 < 6 mo; 91 ≥ 6 mo to < 2 yr, and 147 ≥ 2 yr) on 299 patients. Interrater reliability was substantial to near-perfect across all components for each age-based Serial Neurologic Assessment in Pediatrics scale. Percent agreement was independent of developmental disabilities for all Serial Neurologic Assessment in Pediatrics components except Mental Status and lower extremity Motor Function for patients deemed "Able to Participate" with the assessment. Nurses reported that they felt Serial Neurologic Assessment in Pediatrics, compared with Glasgow Coma Scale, was easier to use and clearer in describing the neurologic status of patients who were intubated, were sedated, and/or had developmental disabilities. About 92% of nurses preferred to use Serial Neurologic Assessment in Pediatrics over Glasgow Coma Scale. CONCLUSIONS When used by critical care nurses, Serial Neurologic Assessment in Pediatrics has excellent protocol adherence, substantial to near-perfect interrater reliability, and is feasible to implement. Further work will determine the sensitivity and specificity for detecting clinically meaningful neurologic decline.

Hydrocephalus is a disorder of cerebral spinal fluid (CSF) physiology that results in increased intracranial pressure (ICP). It is commonly treated via surgical placement of a shunt in the ventricles to divert CSF. Diffuse optical measurements of cerebral perfusion and oxygen extraction were acquired before and after surgical shunt placement in neonates with hydrocephalus. An invasive ICP measurement was made at the time of shunt placement. Shunting increased cerebral perfusion and decreased oxygen extraction only in infants with elevated ICP. This suggests abnormally low perfusion in patients with elevated ICP, and normal perfusion in patients without elevated ICP.

OBJECTIVES: To develop predictive models for death or neurodevelopmental impairment (NDI) after neonatal hypoxic-ischemic encephalopathy (HIE) from data readily available at the time of NICU admission (“early”) or discharge (“cumulative”). METHODS: In this retrospective cohort analysis, we used data from the Children’s Hospitals Neonatal Consortium Database (2010–2016). Infants born at ≥35 weeks’ gestation and treated with therapeutic hypothermia for HIE at 11 participating sites were included; infants without Bayley Scales of Infant Development scores documented after 11 months of age were excluded. The primary outcome was death or NDI. Multivariable models were generated with 80% of the cohort; validation was performed in the remaining 20%. RESULTS: The primary outcome occurred in 242 of 486 infants; 180 died and 62 infants surviving to follow-up had NDI. HIE severity, epinephrine administration in the delivery room, and respiratory support and fraction of inspired oxygen of 0.21 at admission were significant in the early model. Severity of EEG findings was combined with HIE severity for the cumulative model, and additional significant variables included the use of steroids for blood pressure management and significant brain injury on MRI. Discovery models revealed areas under the curve of 0.852 for the early model and of 0.861 for the cumulative model, and both models performed well in the validation cohort (goodness-of-fit χ2: P = .24 and .06, respectively). CONCLUSIONS: Establishing reliable predictive models will enable clinicians to more accurately evaluate HIE severity and may allow for more targeted early therapies for those at highest risk of death or NDI.

Introduction: Checklists aid in ensuring consistency and completeness in medical care delivery. However, using an improvement and safety checklist during rounds was variable in our neonatology intensive care unit (NICU), and completion was not tracked sustainably. This quality improvement (QI) initiative’s primary aim was to increase compliance with checklist completion from 31% to >75% within 1 year. Methods: A multidisciplinary QI team identified barriers to checklist completion and implemented a human factors-focused low-technology intervention (redesign of a hard-copy checklist) and later a high-technology clinical decision support tool within the electronic health record. The primary outcome measure was percent compliance with the use of the checklist. Process metrics included the duration of checklist completion. Balancing measures included staff perceptions of work burden and question relevance. Results: Major barriers to checklist utilization were inability to remember, rounding interruptions, and perceived lack of question relevance to patients. Average biweekly checklist compliance improved from 31% before interventions to 80% after interventions. Average checklist completion time decreased from 46 to 11 seconds. Follow-up surveys demonstrated more respondents found questions “completely relevant” (34% pre versus 43% post) but perceived increased work burden (26% pre versus 31% post). Conclusions: Using QI methodology, human factors-based interventions, and a novel clinical decision support tool, we significantly improved efficiency and checklist compliance and created an automated, sustainable method for monitoring completion and responses. This foundational project provides an infrastructure broadly applicable to QI work in other healthcare settings.

Objective This study was aimed to describe utilization of therapeutic hypothermia (TH) in neonates presenting with mild hypoxic-ischemic encephalopathy (HIE) and associated neurological injury on magnetic resonance imaging (MRI) scans in these infants. Study Design Neonates ≥ 36 weeks' gestation with mild HIE and available MRI scans were identified. Mild HIE status was assigned to hyper alert infants with an exaggerated response to arousal and mild HIE as the highest grade of encephalopathy recorded. MRI scans were dichotomized as “injury” versus “no injury.” Results A total of 94.5% (257/272) neonates with mild HIE, referred for evaluation, received TH. MRI injury occurred in 38.2% (104/272) neonates and affected predominantly the white matter (49.0%, n = 51). Injury to the deep nuclear gray matter was identified in (10.1%) 20 infants, and to the cortex in 13.4% (n = 14 infants). In regression analyses (odds ratio [OR]; 95% confidence interval [CI]), history of fetal distress (OR = 0.52; 95% CI: 0.28–0.99) and delivery by caesarian section (OR = 0.54; 95% CI: 0.31–0.92) were associated with lower odds, whereas medical comorbidities during and after cooling were associated with higher odds of brain injury (OR = 2.31; 95% CI: 1.37–3.89). Conclusion Majority of neonates with mild HIE referred for evaluation are being treated with TH. Odds of neurological injury are over two-fold higher in those with comorbidities during and after cooling. Brain injury predominantly involved the white matter. Key Points

Rationale and Objectives: To compare cerebral pulsed arterial spin labeling (PASL) perfusion among controls, hypoxic ischemic encephalopathy (HIE) neonates with normal conventional MRI(HIE/MRI⊕), and HIE neonates with abnormal conventional MRI(HIE/MRI⊖). To create a predictive machine learning model of neurodevelopmental outcomes using cerebral PASL perfusion. Materials and Methods: A total of 73 full-term neonates were evaluated. The cerebral perfusion values were compared by permutation test to identify brain regions with significant perfusion changes among 18 controls, 40 HIE/MRI⊖ patients, and 15 HIE/MRI⊕ patients. A machine learning model was developed to predict neurodevelopmental outcomes using the averaged perfusion in those identified brain regions. Results: Significantly decreased PASL perfusion in HIE/MRI⊖ group, when compared with controls, were found in the anterior corona radiata, caudate, superior frontal gyrus, precentral gyrus. Both significantly increased and decreased cerebral perfusion changes were detected in HIE/MRI⊕ group, when compared with HIE/MRI⊖ group. There were no significant perfusion differences in the cerebellum, brainstem and deep structures of thalamus, putamen, and globus pallidus among the three groups. The machine learning model demonstrated significant correlation (p < 0.05) in predicting language(r = 0.48) and motor(r = 0.57) outcomes in HIE/MRI⊖ patients, and predicting language(r = 0.76), and motor(r = 0.53) outcomes in an additional group combining HIE/MRI⊖ and HIE/MRI⊕. Conclusion: Perfusion MRI can play an essential role in detecting HIE regardless of findings on conventional MRI and predicting language and motor outcomes in HIE survivors. The perfusion changes may also reveal important insights into the reperfusion response and intrinsic autoregulatory mechanisms. Our results suggest that perfusion imaging may be a useful adjunct to conventional MRI in the evaluation of HIE in clinical practice.

Extreme thrombocytosis (ET, platelet count >1000 × 103/ul) is an uncommon clinical finding 1. Primary ET is associated with myeloproliferative disorders, such as essential thrombocythemia 2. Secondary ET is more common and occurs in reaction to infection, inflammation, or iron deficiency. Bleeding and thrombotic complications more frequently arise in primary ET cases 1, but have been reported with secondary ET in adults 3. Etiologies and complications associated with ET in children are less well-defined, as prior pediatric studies have been relatively small or restricted to specialized patient populations 4,5. We aimed to characterize ET in a large, single-center pediatric cohort.

Objectives To describe how parents of neonatal intensive care unit (NICU) graduates with cerebral palsy (CP) perceive both the accuracy of prognoses provided in the NICU and the timing of their child's diagnosis of CP, and to assess the influence of functional outcome on these perceptions. Study design We surveyed parents of NICU graduates with CP about timing and benefit of diagnosis, accuracy of prognosis, and functional abilities of their children. After piloting and validation, CP parent support groups circulated the survey on social media, websites, and email lists. Bivariate relationships between categorical responses to survey questions were assessed with the χ2 test, and multivariable logistic regression was performed to identify independent factors associated with perceptions about the timing of diagnosis. Results Parents of 463 children were included. Two-thirds (67%) of the children were diagnosed with CP before age 2 years, yet 40% of the respondents felt that diagnosis was made late, and only 11% categorized diagnosis as early. More than one-half (59%) perceived a benefit to diagnosis. There was a significant association between earlier age at diagnosis and greater functional limitations; 24% of parents who recalled being given a prognosis reported that their child functioned as predicted, and 46% reported that their child exceeded expectations. Parents were more likely to believe that children with fewer functional limitations had exceeded expectations. Conclusion Parents remember prognostic discussions about children who develop CP as underestimating functional outcome. Diagnosis is rarely seen as early and is associated with benefits. These observations suggest that clinicians should aim to diagnose CP early and to maintain guarded optimism about future outcomes. Tools for improved communication are urgently needed.

Hydrocephalus is one of the most common congenital abnormalities affecting the nervous system, occurring in 0.3 to 2.5 per 1,000 live births. It results from obstruction of cerebrospinal fluid (CSF) pathways by a diverse range of developmental, genetic, and acquired abnormalities and can have negative consequences on the neurodevelopmental outcome of affected neonates. Historically, hydrocephalus was diagnosed after birth and managed with a shunt procedure; however, with the advent of advanced antenatal imaging techniques, it may now be detected and treated before delivery in some individuals. Moreover, surgical options for the treatment of hydrocephalus have increased over the past few decades, and temporary CSF diversion may prevent the need for permanent shunt placement. Posthemorrhagic hydrocephalus is the most common cause of hydrocephalus in the preterm newborn, but the timing of surgical intervention for this condition remains controversial. Recent evidence suggests that earlier, rather than later, intervention may have some benefits, but more data are needed to adequately inform clinical practice. Regardless of etiology or timing of diagnosis, a thorough understanding of the natural history of hydrocephalus and the range of treatment options available is needed for parental counseling, prognostication, and appropriate surgical management.

OBJECTIVE: To demonstrate that a novel non-invasive index of intracranial pressure (ICP) derived from diffuse optics-based techniques is associated with intracranial hypertension. STUDY DESIGN: We compared non-invasive and invasive ICP measurements in infants with hydrocephalus. Infants born term and preterm were eligible for inclusion if clinically determined to require cerebrospinal fluid (CSF) diversion. Ventricular size was assessed preoperatively via ultrasound measurement of the fronto-occipital (FOR) and fronto-temporal (FTHR) horn ratios. Invasive ICP was obtained at the time of surgical intervention with a manometer. Intracranial hypertension was defined as invasive ICP ≥15 mmHg. Diffuse optical measurements of cerebral perfusion, oxygen extraction, and non-invasive ICP were performed preoperatively, intraoperatively, and postoperatively. Optical and ultrasound measures were compared with invasive ICP measurements, and their change in values after CSF diversion were obtained. RESULTS: We included 39 infants; 23 had intracranial hypertension. No group difference in ventricular size was found by FOR (p=0.93) or FTHR (p=0.76). Infants with intracranial hypertension had significantly higher non-invasive ICP (p=0.02) and oxygen extraction fraction (p=0.01) compared with infants without intracranial hypertension. Increased cerebral blood flow (p=0.005) and improved oxygen extraction fraction (P < .001) after CSF diversion were only observed in infants with intracranial hypertension. CONCLUSIONS: Non-invasive diffuse optical measures (including a non-invasive ICP index) were associated with intracranial hypertension. The findings suggest impaired perfusion from intracranial hypertension was independent of ventricular size. Hemodynamic evidence of the benefits of CSF diversion was seen in infants with intracranial hypertension. Non-invasive optical techniques hold promise for aiding the assessment of CSF diversion timing.

A male infant with a prenatal diagnosis of giant omphalocele and left-sided diaphragmatic eventration is noted to have skin peeling 11 days after birth. The infant was admitted to the NICU and maintained on mechanical ventilation. Chest ultrasonography on the day of birth revealed a small left pleural effusion and diaphragmatic eventration. The team placed a peripherally inserted central catheter on the second day after birth to provide parenteral nutrition for a prolonged period. The infant failed a trial of extubation 4 days after birth. On the following day, the team evaluated the infant for sepsis because of clinical instability. A complete blood cell (CBC) count demonstrated a normal white blood cell count, normal platelets, and no …

Preterm infants with post-hemorrhagic hydrocephalus (PHH) are often treated with temporizing measures such as ventricular access devices (VADs) in order to drain cerebrospinal fluid (CSF) prior to permanent diversion with ventriculoperitoneal shunt (VPS) placement. There is little consensus on the timing and management of VADs and VPSs. This leads to marked practice variations among treating services that can adversely affect patient outcomes. This is a quality improvement study evaluating practices from February 2011 to September 2017 including infants with PHH in a single level IV NICU. A multidisciplinary team created a local clinical pathway modified from the Hydrocephalus Clinical Research Network’s Shunting Outcomes in Post-Hemorrhagic Hydrocephalus protocol to manage infants with PHH. Methods of CSF diversion and shunt timing were based on weight. Neonatal care providers performed VAD aspiration; timing was guided by imaging and clinical exam criteria. Surgical procedures were performed in the NICU. There were 78 patients eligible for the study. Prior to pathway implementation, infections occurred in 4% of VAD and 3% of VPS patients. There have been no infections since inception of the pathway. With pathway implementation, treatment compliance improved from 55 to 86% while conversion compliance rate improved from 89 to 100%. Standardization of care for PHH infants leads to improvement in patient outcomes such as a decrease in time to VAD placement. Reservoir aspirations by the neonatology team did not result in an increase in infection rate.

Therapeutic hypothermia (TH) mitigates the long-term effects of neuronal excitotoxicity and cell death seen in hypoxic-ischemic encephalopathy (HIE). It remains the most evidence-based therapy for HIE, but it is not without clinical controversy. The literature abounds with questions, such as “When should we start cooling—as early as the delivery room?” “Given the efficacy of TH for moderate to severe HIE when started within 6 hours of birth, can we expand the therapy to infants with mild HIE?” “What should the target temperature be?” “What is the optimal duration of treatment?” “Is early discontinuation acceptable if the examination findings normalize?” These questions about TH, its incomplete neurologic rescue, and variations in the delivery of this therapy have prompted this review. This article summarizes changing procedural considerations for TH, the level of neuromonitoring available, the use of sedation, and considerations for neuroimaging during and after TH.

We present pilot results on the validation of non-invasive assessment of elevated intracranial pressure with optical measurement of critical closing pressure. A strong correlation (r=0.85) between optical measurements of critical closing pressure and invasive measurements of intracranial pressure was observed in 5 infants with hydrocephalus, and 1 adult patient with diffuse hypoxic ischemic brain injury. By facilitating timely detection of intracranial hypertension, this approach has potential to reduce risk of brain damage in hydrocephalus and other vulnerable patient populations.

Importance It remains poorly understood how parents decide whether to enroll a child in a neonatal clinical trial. This is particularly true for parents from racial or ethnic minority populations. Understanding factors associated with enrollment decisions may improve recruitment processes for families, increase enrollment rates, and decrease disparities in research participation. Objective To assess differences in parental factors between parents who enrolled their infant and those who declined enrollment for a neonatal randomized clinical trial. Design, Setting, and Participants This survey study conducted from July 2017 to October 2019 in 12 US level 3 and 4 neonatal intensive care units included parents of infants who enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial or who were eligible but declined enrollment. Data were analyzed October 2019 through July 2020. Exposure Parental choice of enrollment in neonatal clinical trial. Main Outcomes and Measures Percentages and odds ratios (ORs) of parent participation as categorized by demographic characteristics, self-assessment of child’s medical condition, study comprehension, and trust in medical researchers. Survey questions were based on the hypothesis that parents who enrolled their infant in HEAL differ from those who declined enrollment across 4 categories: (1) infant characteristics and parental demographic characteristics, (2) perception of infant’s illness, (3) study comprehension, and (4) trust in clinicians and researchers. Results Of a total 387 eligible parents, 269 (69.5%) completed the survey and were included in analysis. This included 183 of 242 (75.6%) of HEAL-enrolled and 86 of 145 (59.3%) of HEAL-declined parents. Parents who enrolled their infant had lower rates of Medicaid participation (74 [41.1%] vs 47 [55.3%];P = .04) and higher rates of annual income greater than $55 000 (94 [52.8%] vs 30 [37.5%];P = .03) compared with those who declined. Black parents had lower enrollment rates compared with White parents (OR, 0.35; 95% CI, 0.17-0.73). Parents who reported their infant’s medical condition as more serious had higher enrollment rates (OR, 5.7; 95% CI, 2.0-16.3). Parents who enrolled their infant reported higher trust in medical researchers compared with parents who declined (mean [SD] difference, 5.3 [0.3-10.3]). There was no association between study comprehension and enrollment. Conclusions and Relevance In this study, the following factors were associated with neonatal clinical trial enrollment: demographic characteristics (ie, race/ethnicity, Medicaid status, and reported income), perception of illness, and trust in medical researchers. Future work to confirm these findings and explore the reasons behind them may lead to strategies for better engaging underrepresented groups in neonatal clinical research to reduce enrollment disparities.

Methemoglobinemia occurs when the heme moiety of hemoglobin (Hb) is oxidized from the ferrous to ferric state, leading to impairments in oxygen transport and delivery. Methemoglobinemia is rare in pediatric patients but has been described in the setting of congenital abnormalities in the Hb structure, inherited enzyme deficiencies, oxidative Hb injury in response to illness, and oxidative Hb injury due to toxicants. We present a 1-week-old infant born with a cervical lymphangioma who developed persistent desaturations that were unresponsive to oxygen after sclerotherapy with doxycycline. Arterial blood gas revealed a high Pao2 despite low saturations being found on pulse oximetry and a methemoglobin level that was found to be elevated. Further sclerotherapy was discontinued, the saturations eventually normalized, and the methemoglobin level decreased. This is a novel report of sclerotherapy with doxycycline associated with the development of methemoglobinemia.

OBJECTIVES To investigate whether quantitative contrast-enhanced ultrasound (CEUS) can accurately identify neonates and infants with hypoxic ischemic brain injury. METHODS In this prospective cohort study, 8 neonates and infants with a suspicion of hypoxic ischemic injury were evaluated with CEUS. RESULTS An interesting trend was observed in the central gray nuclei-to-cortex perfusion ratios. The ratios at the peak enhancement, wash-in area under the curve, perfusion index, and maximum wash-in slopes were lower in all of the affected cases compared to the normal group but not statistically significant given the small sample size (P = .0571). Additionally, when the central gray nuclei-to-cortex perfusion ratio was plotted for all time points along the time-intensity curve, it was observed that the affected cases showed a trend that was qualitatively different from that of the normal cases. In the affected cases, the ratio time-intensity curves either stayed below 1.0 for the entire enhancement period or reached 1.0 close to peak wash-in before falling just below 1.0 for the remaining period of enhancement. However, in the unaffected patients, there was a steep wash-in that crossed the 1.0 threshold and remained above 1.0 for most of the enhancement period. CONCLUSIONS Bedside CEUS is an easily obtainable brain-imaging modality that has the potential to effectively identify infants and neonates with evolving brain injury. A larger prospective study evaluating the correlation between CEUS findings and the reference standard of diffusion- and perfusion-weighted magnetic resonance imaging is needed to establish it as a diagnostic tool.

Purpose We describe the frequency and timing of withdrawal of life-support (WLS) in moderate or severe hypoxic-ischemic encephalopathy (HIE) and examine its associations with medical and sociodemographic factors. Procedures We undertook a secondary data analysis of a prospective multicenter data registry of regional level IV Neonatal Intensive Care Units participating in the Children's Hospitals Neonatal Database. Infants ≥36 weeks gestational age with HIE admitted to a Children's Hospitals Neonatal Database Neonatal Intensive Care Unit between 2010 and 2016, who underwent therapeutic hypothermia were categorized as (1) infants who died following WLST and (2) survivors with severe HIE (requiring tube feedings at discharge). Results Death occurred in 267/1,925 (14%) infants with HIE, 87.6% following WLS. Compared to infants with WLS (n = 234), the survived severe group (n = 74) had more public insurance (73% vs 39.3%, P = 0.00001), lower household income ($37,020 vs $41,733, P = 0.006) and fewer [20.3% vs 35.0%, P = 0.0212] were from the South. Among infants with WLS, electroencephalogram was performed within 24 hours in 75% and was severely abnormal in 64% cases; corresponding rates for MRI were 43% and 17%, respectively. Private insurance was independently associated with WLS, after adjustment for HIE severity and center. Conclusions In a multicenter cohort of infants with HIE, WLS occurred frequently and was associated with sociodemographic factors. The rationale for decision-making for WLS in HIE require further exploration.

Utilization of extraocorporeal membrane oxygenation (ECMO) has become increasingly widespread as a bridging therapy for neonates with severe, reversible respiratory or cardiac diseases. While significant risks remain, due to advances in medical and surgical management, overall mortality has decreased. However, short and long-term neurological morbidity has remained high. Therefore, increasing attention has been focused on multimodal neuromonitoring to track and optimally, minimize or prevent intracranial injury. This review will explore the the indications, advantages, disadvantages, timing, frequency, duration, and any known correlation with neurodevelopmental outcomes of common types of neuromonitoring in the neonatal ECMO population. Investigational monitoring techniques such as NIRS will be briefly reviewed.

Objective The objective of this study was to perform a systematic review of all studies that report neurodevelopmental outcomes at 12 months' corrected age or later for preterm infants (< 32 weeks) who are diagnosed with lenticulostriate vasculopathy (LSV) on cranial ultrasound. Study Design This is a systematic review. Results We identified 501 unique publications of which 3 met all prespecified eligibility criteria. Neurodevelopmental outcome data were available for 44 preterm infants with LSV. There were mixed results from the studies: the first reported impairments of mental development; the second reported impairments of motor development only; and finally, the third reported that three of three preterm infants with LSV had mild or moderate developmental delay. Conclusion The available results raise some concern for future impairments in preterm infants with LSV, but they are conflicting and inconclusive. There is insufficient evidence about the neurodevelopmental implications of LSV in preterm infants to inform counseling of parents.

Congenital tuberculosis (CTB) due to maternal genitourinary (GU) TB infection is a rare occurrence, as infection of the genital tract in women generally leads to infertility. Increasing availability of assisted reproductive technology creates the potential for CTB to emerge as a significant problem. We describe five infants (two sets of twins and a singleton birth) conceived by in vitro fertilization who developed CTB. All five infants were born to mothers who had immigrated to the United States from India and none had GU TB diagnosed before the birth of their infected infants.

Background: Warfarin increases mortality of intracerebral hemorrhage (ICH). The authors investigated whether this effect reflects increased baseline ICH volume at presentation or increased ICH expansion.Methods: Subjects were drawn from an ongoing prospective cohort study of ICH outcome. The effect of warfarin on baseline ICH volume was studied in 183 consecutive cases of supratentorial ICH age ≥ 18 years admitted to the emergency department over a 5-year period. Baseline ICH volume was determined using computerized volumetric analysis. The effect of warfarin on ICH expansion (increase in volume ≥ 33% of baseline) was analyzed in 70 consecutive cases in whom ICH volumes were measured on all subsequent CT scans up to 7 days after admission. Multivariable analysis was used to determine warfarin’s influence on baseline ICH, ICH expansion, and whether warfarin’s effect on ICH mortality was dependent on baseline volume or subsequent expansion.Results: There was no effect of warfarin on initial volume. Predictors of larger baseline volume were hyperglycemia (p < 0.0001) and lobar hemorrhage (p < 0.0001). Warfarin patients were at increased risk of death, even when controlling for ICH volume at presentation. Warfarin was the sole predictor of expansion (OR 6.2, 95% CI 1.7 to 22.9) and expansion in warfarin patients was detected later in the hospital course compared with non-warfarin patients (p < 0.001). ICH expansion showed a trend toward increased mortality (OR 3.5, 95% CI 0.7 to 8.9, p = 0.14) and reduced the marginal effect of warfarin on ICH mortality.Conclusions: Warfarin did not increase ICH volume at presentation but did raise the risk of in-hospital hematoma expansion. This expansion appears to mediate part of warfarin’s effect on ICH mortality.

Background: Brain MRI is an important tool in the diagnosis and management of neonates with possible brain injury. In our large quaternary care neonatal intensive care unit (NICU), MRIs are performed for the identification of white matter lesions in preterm infants, prognostication in hypoxic ischemic encephalopathy, peri-operative evaluation of patients with meningomyeloceles and hydrocephalus among other indications. Patients are often sedated in order to obtain high quality images, but sedation carries risks of complications. As part of the development of a Neonatal …

Hypoxic brain injury remains a major source of neurodevelopmental impairment for both term and preterm infants. The perinatal period is a time of rapid transition in oxygen environments and developmental resetting of oxygen sensing. The relationship between neural oxygen sensing ability and hypoxic injury has not been studied. The oxygen sensing circuitry in the model organism C. elegans is well understood. We leveraged this information to investigate the effects of impairments in oxygen sensing on survival after anoxia. There was a significant survival advantage in developing worms specifically unable to sense oxygen shifts below their preferred physiologic range via genetic ablation of BAG neurons, which appear important for conferring sensitivity to anoxia. Oxygen sensing that is mediated through guanylate cyclases (gcy-31, 33, 35) is unlikely to be involved in conferring this sensitivity. Additionally, animals unable to process or elaborate neuropeptides displayed a survival advantage after anoxia. Based on these data, we hypothesized that elaboration of neuropeptides by BAG neurons sensitized animals to anoxia, but further experiments indicate that this is unlikely to be true. Instead, it seems that neuropeptides and signaling from oxygen sensing neurons operate through independent mechanisms, each conferring sensitivity to anoxia in wild type animals.

Introduction: Inconsistencies in the recommendation of prophylactic antibiotics for patients with intracranial pressure monitors compelled us to assess the effect of our standard regimen of continuous antibiotic prophylaxis on cerebrospinal fluid infection. We examined the rate, possible risk factors, causative organisms, and characteristics of infection. Methods: Three hundred eleven patients admitted between September 1998 and February 2001 with an intracranial pressure monitoring device in place were included. Two hundred eleven patients received a ventriculostomy, 95 an intraparenchymal fiber optic intracranial pressure monitor (ICPM), and 5 both an ICPM and a ventriculostomy. Results: The overall infection rate was 5.5% (17/311). No patient with an ICPM developed CSF infection. The infection rate among ventriculostomy patients was 8.1% (17/211). The majority of infections (82%) were caused by Gram-positive species. Younger age (OR=1.04 for each year, 95% CI=1.01–1.08, p=0.03) and increasing duration of ventriculostomy insertion (OR=1.2 for each day of catheter insertion, 95% CI=1.1–1.3, p