Trial of Erythropoietin for Hypoxic-Ischemic Encephalopathy in Newborns.

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.).

Survey of Quaternary Neonatal Management of Posthemorrhagic Hydrocephalus.

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. KEY POINTS: · 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..

Utilization of Therapeutic Hypothermia and Neurological Injury in Neonates with Mild Hypoxic-Ischemic Encephalopathy: A Report from Children's Hospital Neonatal Consortium.

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: · Increasingly, neonates with mild HIE are being referred for consideration for hypothermia therapy.. · Drift in clinical practice shows growing number of neonates treated with hypothermia as having mild HIE.. · MRI data show that 38% of neonates with mild HIE have brain injury, predominantly in the white matter..

Validation of Sonographic Fronto-Occipital Ratio Based on Anatomical Landmarks Compared to MR/CT-Derived Indexes in Children with Chiari II and Ventriculomegaly.

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.

Optical Detection of Intracranial Pressure and Perfusion Changes in Neonates With Hydrocephalus.

OBJECTIVE: To demonstrate that a novel noninvasive index of intracranial pressure (ICP) derived from diffuse optics-based techniques is associated with intracranial hypertension. STUDY DESIGN: We compared noninvasive 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 frontotemporal (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 noninvasive 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 with intracranial hypertension. No group difference in ventricular size was found by FOR (P = .93) or FTHR (P = .76). Infants with intracranial hypertension had significantly higher noninvasive ICP (P = .02) and oxygen extraction fraction (OEF) (P = .01) compared with infants without intracranial hypertension. Increased cerebral blood flow (P = .005) and improved OEF (P < .001) after CSF diversion were observed only in infants with intracranial hypertension. CONCLUSIONS: Noninvasive diffuse optical measures (including a noninvasive ICP index) were associated with intracranial hypertension. The findings suggest that 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. Noninvasive optical techniques hold promise for aiding the assessment of CSF diversion timing.

Parental Enrollment Decision-Making for a Neonatal Clinical Trial.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Acute and Chronic Placental Abnormalities in a Multicenter Cohort of Newborn Infants with Hypoxic-Ischemic Encephalopathy.

OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: Combined acute and chronic placental abnormalities were common in this cohort of infants with HIE, underscoring the complex causal pathways of HIE. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02811263.

Serial Neurologic Assessment in Pediatrics (SNAP): A New Tool for Bedside Neurologic Assessment of Critically Ill Children.

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.

Standardizing treatment of preterm infants with post-hemorrhagic hydrocephalus at a single institution with a multidisciplinary team.

BACKGROUND: 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. LOCAL PROBLEM: 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. METHODS: This is a quality improvement study evaluating practices from February 2011 to September 2017 including infants with PHH in a single level IV NICU. INTERVENTIONS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Practice variation in anti-epileptic drug use for neonatal hypoxic-ischemic encephalopathy among regional NICUs.

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.

Novel Quantitative Contrast-Enhanced Ultrasound Detection of Hypoxic Ischemic Injury in Neonates and Infants: Pilot Study 1.

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.

Parental Perspectives on Diagnosis and Prognosis of Neonatal Intensive Care Unit Graduates with Cerebral Palsy.

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.

Lenticulostriate Vasculopathy and Neurodevelopmental Outcomes in Preterm Infants: A Systematic Review.

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.

Standardizing neonatal hypoxic ischemic encephalopathy evaluation and documentation practices.

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.

Association between video laryngoscopy characteristics and successful neonatal tracheal intubation: a prospective study.

OBJECTIVE: To identify associations between procedural characteristics and success of neonatal tracheal intubation (NTI) using video laryngoscopy (VL). DESIGN: Prospective single-centre observational study. SETTING: Quaternary neonatal intensive care unit. PATIENTS: Infants requiring NTI at the Children's Hospital of Philadelphia. INTERVENTIONS: VL 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 MEASURE: VL NTI attempt success. RESULTS: A 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). CONCLUSION: We 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.

Association between video laryngoscopy characteristics and successful neonatal tracheal intubation: a prospective study.

OBJECTIVE: To identify associations between procedural characteristics and success of neonatal tracheal intubation (NTI) using video laryngoscopy (VL). DESIGN: Prospective single-centre observational study. SETTING: Quaternary neonatal intensive care unit. PATIENTS: Infants requiring NTI at the Children's Hospital of Philadelphia. INTERVENTIONS: VL 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 MEASURE: VL NTI attempt success. RESULTS: A 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). CONCLUSION: We 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.

Surgical interventions and short-term outcomes for preterm infants with post-haemorrhagic hydrocephalus: a multicentre cohort study.

OBJECTIVE: To (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). DESIGN: Cohort study of the Children's Hospitals Neonatal Database from 2010 to 2022. SETTING: 41 referral neonatal intensive care units (NICUs) in North America. PATIENTS: Infants 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 MEASURES: Mortality and meningitis. RESULTS: Of 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. CONCLUSIONS: There 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%.

Genetic and Congenital Anomalies in Infants With Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Infants with hypoxic ischemic encephalopathy (HIE) may have underlying conditions predisposing them to hypoxic-ischemic injury during labor and delivery. It is unclear how genetic and congenital anomalies impact outcomes of HIE. METHODS: Infants with HIE enrolled in a phase III trial 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 age two years by a standardized neurological examination, Bayley Scales of Infant Development, Third Edition (BSID-III), and the Gross Motor Function Classification Scales. Secondary outcomes included cerebral palsy and BSID-III motor, cognitive, and language scores at age two years. RESULTS: Of 500 infants with HIE, 24 (5%, 95% confidence interval 3% to 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 brain magnetic resonance imaging. However, infants with genetic or congenital anomalies were more likely to have 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. CONCLUSIONS: Among 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.

Neonatal Thrombocytopenia as a Presenting Finding in de novo Pyruvate Kinase Deficiency.

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.