Neuroendoscopic lavage (NEL) is a time-limited neurosurgical intervention that removes intraventricular blood in post-hemorrhagic hydrocephalus (PHH). Preterm neonates are medically complex and fragile, often precluding neurosurgical procedures due to concerns such as extubation risk and body temperature instability during even routine clinical care. In addition, transportation to the operating room can be difficult and risky. Given these factors, our institution developed and implemented a bedside technique to facilitate safe and timely NEL in the neonatal intensive care unit for the treatment of PHH.

OBJECTIVE The current neurosurgical treatment for intraventricular hemorrhage (IVH) of prematurity resulting in posthemorrhagic hydrocephalus (PHH) seeks to reduce intracranial pressure with temporary and then permanent CSF diversion. In contrast, neuroendoscopic lavage (NEL) directly addresses the intraventricular blood that is hypothesized to damage the ependyma and parenchyma, leading to ventricular dilation and hydrocephalus. The authors sought to determine the feasibility of NEL in PHH. METHODS The records of patients with a diagnosis of grade III or IV IVH were reviewed between September 2022 and February 2024. The Papile grade was determined on cranial ultrasonography. Demographic information collected included gestational age, birth weight, weight at the time of surgical intervention, infection confirmed with CSF, and rehemorrhage. Standard local guidelines for temporary (CSF reservoir) and permanent (shunt or endoscopic third ventriculostomy [ETV]) CSF diversion were implemented. Warmed lactated Ringer’s was utilized for NEL. The primary outcome was the need for permanent CSF diversion (shunt or ETV). RESULTS Twenty consecutive patients with grade III or IV IVH complicated by PHH were identified. Twelve patients underwent CSF reservoir placement and NEL, 4 underwent CSF reservoir placement only, 1 underwent shunt placement only, and 3 did not require neurosurgical intervention. Of the 12 patients who underwent reservoir placement and NEL, 8 (67%) ultimately met criteria for permanent CSF diversion compared with 2 of 4 (50%) who underwent CSF reservoir placement only. The mean gestational age at birth, birth weights, and age/weight at time of temporary CSF diversion were similar across groups. The average time interval between temporary and permanent CSF diversion was longer in patients who underwent NEL (2.5 months for shunt and 6.5 months for ETV) compared with CSF reservoir placement only (1.1 months). CONCLUSIONS NEL is an innovative alternative for the treatment of PHH of prematurity. The authors established an endoscopic lavage program at their institution and herein report the first published account in the United States of the feasibility of NEL for PHH.

ObjectiveTo identify associations between procedural characteristics and success of neonatal tracheal intubation (NTI) using video laryngoscopy (VL).DesignProspective single-centre observational study.SettingQuaternary neonatal intensive care unit.PatientsInfants requiring NTI at the Children’s Hospital of Philadelphia.InterventionsVL NTI recordings were evaluated to assess 11 observable procedural characteristics hypothesised to be associated with VL NTI success. These characteristics included measures of procedural time and performance, glottic exposure and position, and laryngoscope blade tip location.Main outcome measureVL NTI attempt success.ResultsA total of 109 patients underwent 109 intubation encounters with 164 intubation attempts. The first attempt success rate was 65%, and the overall encounter success rate was 100%. Successful VL NTI attempts were associated with shorter procedural duration (36 s vs 60 s, p<0.001) and improved Cormack-Lehane grade (63% grade I vs 49% grade II, p<0.001) compared with unsuccessful NTIs. Other factors more common in successful NTI attempts than unsuccessful attempts were laryngoscope blade placement to lift the epiglottis (45% vs 29%, p=0.002), fewer tracheal tube manoeuvres (3 vs 8, p<0.001) and a left-sided or non-visualised tongue location (76% vs 56%, p=0.009).ConclusionWe identified procedural characteristics visible on the VL screen that are associated with NTI procedural success. Study results may improve how VL is used to teach and perform neonatal intubation.

ObjectiveWe determined the frequency of previously unsuspected genetic or congenital anomalies in infants with HIE, and whether such anomalies are associated with neurodevelopmental outcome.MethodsInfants with moderate or severe HIE enrolled in a phase III randomized controlled trial (HEAL) underwent genetic testing when clinically indicated. Infants with known genetic or congenital anomalies were excluded. The primary outcome, i.e., death or neurodevelopmental impairment (NDI), was determined at two years of age by a standardized neurologic examination, Bayley Scales of Infant Development-III (BSID-III), and the Gross Motor Function Classification Scales. Secondary outcomes included cerebral palsy and BSID-III motor, cognitive and language scores at age 2 years.ResultsOf 500 infants with HIE, 24 (5%, 95% CI 3-7%) were diagnosed with a genetic (n=15) or congenital (n=14) anomaly. Infants with and without genetic or congenital anomalies had similar rates of severe encephalopathy and findings on neonatal EEG and brain MRI. However, infants with genetic or congenital anomalies were more likely to have the primary outcome of death or NDI (75% vs 50%, P= 0.02). Among survivors, those with a genetic or congenital anomaly were more likely to be diagnosed with cerebral palsy (32% vs. 13%, p =0.02), and had lower BSID-III scores in all three domains than HIE survivors without such anomalies.ConclusionAmong infants with HIE, 5% were diagnosed with a genetic or congenital anomaly. Despite similar clinical markers of HIE severity, infants with HIE and a genetic or congenital anomaly had worse neurodevelopmental outcomes than infants with HIE alone.

ObjectiveTo (1) describe differences in types and timing of interventions, (2) report short-term outcomes and (3) describe differences among centres from a large national cohort of preterm infants with post-haemorrhagic hydrocephalus (PHH).DesignCohort study of the Children’s Hospitals Neonatal Database from 2010 to 2022.Setting41 referral neonatal intensive care units (NICUs) in North America.PatientsInfants born before 32 weeks’ gestation with PHH defined as acquired hydrocephalus with intraventricular haemorrhage.Interventions(1) No intervention, (2) temporising device (TD) only, (3) initial permanent shunt (PS) and (4) TD followed by PS (TD-PS).Main outcome measuresMortality and meningitis.ResultsOf 3883 infants with PHH from 41 centres, 36% had no surgical intervention, 16% had a TD only, 19% had a PS only and 30% had a TD-PS. Of the 46% of infants with TDs, 76% were reservoirs; 66% of infants with TDs required PS placement. The percent of infants with PHH receiving ventricular access device placement differed by centre, ranging from 4% to 79% (p<0.001). Median chronological and postmenstrual age at time of TD placement were similar between infants with only TD and those with TD-PS. Infants with TD-PS were older and larger than those with only PS at time of PS placement. Death before NICU discharge occurred in 12% of infants, usually due to redirection of care. Meningitis occurred in 11% of the cohort.ConclusionsThere was significant intercentre variation in rate of intervention, which may reflect variability in care or referral patterns. Rate of PS placement in infants with TDs was 66%.

Sedation and anesthesia are often required in order to facilitate collection of high-quality imaging studies free of significant motion artifact for infants and neonates. Provision of safe sedation and anesthesia requires good communication between the ordering provider, radiologist, and anesthesiologist, careful pre-procedural evaluation of the patient, and availability of appropriate and sufficient equipment, drugs, personnel, and facilities. There are many additional factors to be considered for provision of safe sedation or anesthesia for infants and neonates—it is ideal to involve a fellowship-trained pediatric anesthesiologist in the planning and carry-out of these plans. In this review, we discuss some of the basic definitions of sedation and anesthesia, requirements for safe sedation and anesthesia, and many of the germane risks and additional considerations that factor into the delivery of a safe sedation or anesthesia plan for the imaging of an infant or neonate.

Background Infants at risk for hypoxic ischemic encephalopathy (HIE) require a time sensitive evaluation and decision-making regarding treatment with therapeutic hypothermia (TH). Prior to this project, there was no standardized approach to evaluating these infants locally. Methods Included infants were “at risk for HIE,” defined as meeting the “patient characteristics” and “biochemical criteria” per the institutional HIE pathway. Our primary outcome was documentation of an HIE therapeutic hypothermia evaluation (HIETHE) within the first six hours of life which included: (1) recognition of at-risk status, (2) an encephalopathy exam, and (3) a decision regarding TH. Plan-Do-Study-Act cycles included novel clinical decision support. Results From October 2020 to May 2023, among infants at-risk for HIE, the average percentage with an HIETHE documented improved from 47% to 82%. Conclusions We standardized the approach to infants at risk for HIE and improved the presence of a complete and timely evaluation regarding TH eligibility.

Objective This study aimed to determine clinical care practices for infants at risk for posthemorrhagic hydrocephalus (PHH) across level IV neonatal intensive care units (NICUs). Study Design Cross-sectional survey that addressed center-specific surveillance, neurosurgical intervention, and follow-up practices within the Children's Hospitals Neonatal Consortium. Results 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. Conclusion 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.

Objectives To compare serum ferritin and RET-He values among extremely low gestational age neonates ELGANs with other markers of iron-deficient erythropoiesis. Study Design This is a secondary analysis of the NICHD Darbepoetin Trial. Study data from placebo recipients who had a serum ferritin, a RET-He, and a mean corpuscular volume (MCV) measurement within a 24-hour period were analyzed for correlation. Results Mixed linear regression models showed no association between ferritin and RET-He at both early ( β = 0.0016, p = 0.40) and late ( β = −0.0001, p = 0.96) time points. Positive associations were observed between RET-He and MCV at baseline, early, and late time points ( p < 0.01, =0.01, <0.001, respectively), while ferritin was not associated with MCV at any time point. Conclusions Our study shows that RET-He is better correlated with MCV as a marker of iron-limited erythropoiesis than ferritin. The results suggest that ferritin is limited as a marker of iron sufficiency in premature infants. Study Identification FDA IND Number 100138; ClinicalTrials.gov number NCT03169881; NRN ID number NICHD-NRN-0058 (Darbe).

Key Points Question Is higher resource utilization, quantified by hospital costs, associated with survival without neurodevelopmental impairment among infants with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia? Findings In this cohort study of 381 neonates with hypoxic-ischemic encephalopathy who underwent therapeutic hypothermia in 11 children's hospitals, total hospitalization costs during the first 4 days were not associated with neurodevelopmental outcomes. Higher electroencephalography (EEG) costs were associated with survival without neurodevelopmental impairment, yet higher antiseizure medication or laboratory costs were not. Meaning These findings suggest EEG monitoring may improve outcomes, whereas more intensive laboratory monitoring may not yield similar benefits. This cohort study examines whether there is an association between higher resource utilization during the first 4 days of age, quantified by hospital costs, and survival without neurodevelopmental impairment among infants with hypoxic-ischemic encephalopathy (HIE). Importance Intercenter variation exists in the management of hypoxic-ischemic encephalopathy (HIE). It is unclear whether increased resource utilization translates into improved neurodevelopmental outcomes. Objective To determine if higher resource utilization during the first 4 days of age, quantified by hospital costs, is associated with survival without neurodevelopmental impairment (NDI) among infants with HIE. Design, Setting, and Participants Retrospective cohort analysis of neonates with HIE who underwent therapeutic hypothermia (TH) at US children's hospitals participating in the Children's Hospitals Neonatal Database between 2010 and 2016. Data were analyzed from December 2021 to December 2022. Exposures Infants who survived to 4 days of age and had neurodevelopmental outcomes assessed at greater than 11 months of age were divided into 2 groups: (1) death or NDI and (2) survived without NDI. Resource utilization was defined as costs of hospitalization including neonatal neurocritical care (NNCC). Data were linked with Pediatric Health Information Systems to quantify standardized costs by terciles. Main Outcomes and Measures The main outcome was death or NDI. Characteristics, outcomes, hospitalization, and NNCC costs were compared. Results Among the 381 patients who were included, median (IQR) gestational age was 39 (38-40) weeks; maternal race included 79 (20.7%) Black mothers, 237 (62.2%) White mothers, and 58 (15.2%) mothers with other race; 80 (21%) died, 64 (17%) survived with NDI (combined death or NDI group: 144 patients [38%]), and 237 (62%) survived without NDI. The combined death or NDI group had a higher rate of infants with Apgar score at 10 minutes less than or equal to 5 (65.3% [94 of 144] vs 39.7% [94 of 237]; P<.001) and a lower rate of infants with mild or moderate HIE (36.1% [52 of 144] vs 82.3% [195 of 237]; P<.001) compared with the survived without NDI group. Compared with low-cost centers, there was no association between high- or medium-hospitalization cost centers and death or NDI. High- and medium-EEG cost centers had lower odds of death or NDI compared with low-cost centers (high vs low: OR, 0.30 [95% CI, 0.16-0.57]; medium vs low: OR, 0.29 [95% CI, 0.13-0.62]). High- and medium-laboratory cost centers had higher odds of death or NDI compared with low-cost centers (high vs low: OR, 2.35 [95% CI, 1.19-4.66]; medium vs low: OR, 1.93 [95% CI, 1.07-3.47]). High-antiseizure medication cost centers had higher odds of death or NDI compared with low-cost centers (high vs. low: OR, 3.72 [95% CI, 1.51-9.18]; medium vs low: OR, 1.56 [95% CI, 0.71-3.42]). Conclusions and Relevance Hospitalization costs during the first 4 days of age in neonates with HIE treated with TH were not associated with neurodevelopmental outcomes. Higher EEG costs were associated with lower odds of death or NDI yet higher laboratory and antiseizure medication costs were not. These findings serve as first steps toward identifying aspects of NNCC that are associated with outcomes.

Objective To 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). Design Prospective single-centre observational study. Setting Quaternary neonatal intensive care unit. Patients Infants with an antenatal diagnosis of CDH born at the Children’s Hospital of Philadelphia. Interventions TV and ETCO2 were simultaneously recorded using a respiratory function monitor (RFM) during invasive positive pressure ventilation immediately after birth. Main outcome measures TV per birth weight and ETCO2 values were summarised for each minute after birth. Subgroups of interest were defined by liver position (thoracic vs abdominal) and extracorporeal membrane oxygenation (ECMO) treatment. Results RFM data were available for 50 infants from intubation until a median (IQR) of 9 (7–14) min after birth. TV and ETCO2 values increased for the first 10 min after birth, but intersubject values were heterogeneous. TVs were overall lower and ETCO2 values 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. Conclusion Respiratory 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 ETCO2 levels by 10 min after birth may provide an opportunity to optimise and individualise ventilatory support for this high-risk population.

Few reliable or easily obtainable biomarkers to predict long-term outcome in infants with hypoxic-ischemic encephalopathy (HIE) have been identified. We previously showed that mattress temperature (MT), as proxy for disturbed temperature regulation during therapeutic hypothermia (TH), predicts injury on early MRI and holds promise as physiologic biomarker. To determine whether MT in neonates treated with TH for moderate-severe HIE is associated with long-term outcome at 18–22 months, we performed a secondary analysis of the Optimizing Cooling trial using MT data from 167 infants treated at a core temperature of 33.5°C. Median MTs from four time-epochs (0–6 h, 6–24 h, 24–48 h, and 48–72 h of TH) were used to predict death or moderate-severe neurodevelopmental impairment (NDI), using epoch-specific derived and validated MT cutoffs. Median MT of infants who died or survived with NDI was consistently 1.5–3.0°C higher throughout TH. Infants requiring a median MT above the derived cut-offs had a significantly increased odds of death or NDI, most notably at 0–6 h (aOR 17.0, 95%CI 4.3–67.4). By contrast, infants who remained below cut-offs across all epochs had 100% NDI-free survival. MTs in neonates with moderate-severe HIE during TH are highly predictive of long-term outcome and can be used as physiologic biomarker.

Thrombocytopenia is a common laboratory abnormality encountered in critically ill neonates. The broad differential for thrombocytopenia, and its association with potentially severe neonatal pathology, often presents a diagnostic dilemma prompting extensive evaluation. Hemolysis due to red cell enzymopathies is a rare cause of neonatal thrombocytopenia that is typically brief and self-limiting. Here, we present a case of thrombocytopenia, refractory to transfusion, associated with anemia and hyperbilirubinemia in a neonate with pyruvate kinase deficiency (PKD) arising from compound heterozygous PKLR mutations. The nature of the thrombocytopenia in this patient created considerable diagnostic uncertainty, which was ultimately resolved by whole-exome sequencing. This case emphasizes that inherited red cell defects, such as PKD, are important to consider in cases of neonatal thrombocytopenia.

This systematic review examines how studies of genomic medicine among critically ill infants measure and report the utility of genetic testing.

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.

BACKGROUND AND OBJECTIVES:Genetic testing is expanding among ill neonates, yet the influence of genetic results on medical decision-making is not clear. With this study, we sought to determine how different types of genetic information with uncertain implications for prognosis influence clinicians' decisions to recommend intensive versus palliative care.METHODS:We conducted a national study of neonatologists using a split sample experimental design. The questionnaire contained 4 clinical vignettes. Participants were randomly assigned to see one of 2 versions that varied only regarding whether they included the following genetic findings: (1) a variant of uncertain significance; (2) a genetic diagnosis that affects neurodevelopment but not acute survival; (3) a genetic versus nongenetic etiology of equally severe pathology; (4) a pending genetic testing result. Physicians answered questions about recommendations they would make for the patient described in each vignette.RESULTS:Vignette versions that included a variant of uncertain significance, a diagnosis foreshadowing neurodevelopmental impairment, or a genetic etiology of disease were all associated with an increased likelihood of recommending palliative rather than intensive care. A pending genetic test result did not have a significant effect on care recommendations.CONCLUSIONS:Findings from this study of hypothetical cases suggest neonatologists apply uncertain genetic findings or those that herald neurodevelopmental disability in problematic ways. As genetic testing expands, understanding how it is used in decision-making and educating clinicians regarding appropriate use are paramount.

OBJECTIVE:To assess the association between opioid exposure during therapeutic hypothermia (TH) for perinatal hypoxic-ischemic encephalopathy (HIE) and in-hospital outcomes. STUDY DESIGN: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 for >5 days. RESULTS: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. CONCLUSION:Opioid exposure during TH was not associated with abnormal MRI; its association with adverse short-term outcomes suggests need for cautious empiric use.

BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.).

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.

Determine whether blanket temperatures during therapeutic hypothermia (TH) are associated with 18–22 month outcomes for infants with hypoxic ischemic encephalopathy (HIE). Retrospective cohort study of 181 infants with HIE who received TH in two randomized trials within the Neonatal Research Network. We defined summative blanket temperature constructs and evaluated for association with a primary composite outcome of death or moderate/ severe disability at 18–22 months. Each 0.5 °C above 33.5 °C in the mean of the highest quartile blanket temperature was associated with a 52% increase in the adjusted odds of death/ disability (aOR 1.52, 95% CI 1.09–2.11). Having >8 consecutive blanket temperatures above 33.5 °C rendered an aOR of death/disability of 5.04 in the first 24 h (95% CI 1.54–16.6) and 6.92 in the first 48 h (95% CI 2.20–21.8) of TH. Higher blanket temperature during TH may be an early, clinically useful biomarker of HIE outcome.