Neonatal Hypoxic-Ischemic Encephalopathy Spectrum: Severity-Stratified Analysis of Neuroimaging Modalities and Association with Neurodevelopmental Outcomes.

OBJECTIVE: To compare hypoxic-ischemic injury on early cranial ultrasonography (cUS) and post-rewarming brain magnetic resonance imaging (MRI) in newborn infants with hypoxic-ischemic encephalopathy (HIE) and to correlate that neuroimaging with neurodevelopmental outcomes. STUDY DESIGN: This was a retrospective cohort study of infants with mild, moderate, and severe HIE treated with therapeutic hypothermia and evaluated with early cUS and postrewarming MRI. Validated scoring systems were used to compare the severity of brain injury on cUS and MRI. Neurodevelopmental outcomes were assessed at 18 months of age. RESULTS: Among the 149 included infants, abnormal white matter (WM) and deep gray matter (DGM) hyperechogenicity on cUS in the first 48 hours after birth were more common in the severe HIE group than the mild HIE group (81% vs 39% and 50% vs 0%, respectively; P < .001). In infants with a normal cUS, 95% had normal or mildly abnormal brain MRIs. In infants with severely abnormal cUS, none had normal and 83% had severely abnormal brain MRIs. Total abnormality scores on cUS were higher in neonates with near-total brain injury on MRI than in neonates with normal MRI or WM-predominant injury pattern (adjusted P < .001 for both). In the multivariable model, a severely abnormal MRI was the only independent risk factor for adverse outcomes (OR: 19.9, 95% CI: 4.0-98.1; P < .001). CONCLUSION: The present study shows the complementary utility of cUS in the first 48 hours after birth as a predictive tool for the presence of hypoxic-ischemic injury on brain MRI.

Prognostic Indicators of Reorientation of Care in Perinatal Hypoxic-Ischemic Encephalopathy Spectrum.

OBJECTIVE: To investigate the clinical, electrographic, and neuroimaging characteristics in neonates with perinatal hypoxic-ischemic encephalopathy who underwent reorientation of care using standardized scoring systems. STUDY DESIGN: A nested observational substudy within a prospective hypoxic-ischemic encephalopathy cohort was conducted. Group 1 comprised infants whose parents received the medical recommendation for reorientation of care, while group 2 continued to receive standard care. Encephalopathy scores were monitored daily. Amplitude-integrated and continuous-video-integrated electroencephalogram during therapeutic hypothermia were analyzed. Standardized scoring systems for cranial ultrasonography and postrewarming brain magnetic resonance imaging were deployed. RESULTS: The study included 165 infants, with 35 in group 1 and 130 in Group 2. By day 3, all infants in group 1 were encephalopathic with higher Thompson scores (median 13 [IQR 10-19] vs 0 [IQR 0-3], P < .001). Electrographic background normalization within 48 hours occurred in 3% of group 1 compared with 46% of group 2 (P < .001). Sleep-wake cycling was not observed in group 1 and emerged in 63% of group 2 within the first 72 hours (P < .001). The number of antiseizure medications received was higher in group 1 (median 3 [IQR, 2-4] vs 0 [IQR, 0-1], respectively; P < .001). Group 1 had higher cranial ultrasound injury scores (median 4 [IQR 2-7] vs 1 [IQR 0-1], P < .001) within 48 hours and postrewarming brain magnetic resonance imaging injury scores (median 33 [range 20-51] vs 4 [range 0-28], P < .001). CONCLUSIONS: Neonates with perinatal hypoxic-ischemic encephalopathy who underwent reorientation of care presented with and maintained significantly more pronounced clinical manifestations, electrographic findings, and near-total brain injury as scored objectively on all modalities. TRIAL REGISTRATION: Registration of the study cohort: NCT04913324.

Remote ischemic post-conditioning for neonatal encephalopathy: a safety and feasibility trial.

BACKGROUND: Despite implementation of therapeutic hypothermia (TH) for infants with neonatal encephalopathy (NE), a significant proportion of infants suffer neurodevelopmental impairment (NDI). Remote ischemic conditioning (RIC) is a proposed neuroprotective maneuver that has been studied in adults with brain injury, but it has not been previously investigated in infants with NE. METHODS: We performed a prospective, randomized, safety and dose escalation study in 32 neonates with NE. Four cohorts of consecutive patients were randomized to RIC therapy, including four cycles of limb ischemia and reperfusion on progressive days of TH, or sham. Clinical, biochemical, and safety outcomes were monitored in both groups. RESULTS: All patients received the designated RIC therapy without interruption or delay. RIC was not associated with increased pain, vascular, cutaneous, muscular, or neural safety events. There was no difference in the incidence of seizures, brain injury, or mortality between the two groups with the escalation of RIC dose and frequency. CONCLUSIONS: We found that RIC is a safe and feasible adjunctive therapy for neonates with NE undergoing TH. IMPACT: This pilot study establishes critical safety and feasibility data that are necessary for the design of future studies to investigate the potential efficacy of RIC to reduce NDI. IMPACT: Remote ischemic conditioning (RIC) is a possible neuroprotective intervention in infants with hypoxic-ischemic encephalopathy (HIE). RIC can be administered concurrently with therapeutic hypothermia without any notable adverse events. Future studies will need to address potential efficacy of RIC to improve neurodevelopmental outcomes, as well as consider the ideal temporal window and dose for RIC in this patient population.

Neuroimaging to guide neuroprognostication in the neonatal intensive care unit.

PURPOSE OF REVIEW: Neurological problems are common in infants admitted to the neonatal intensive care unit (NICU). Various neuroimaging modalities are available for neonatal brain imaging and are selected based on presenting problem, timing and patient stability. RECENT FINDINGS: Neuroimaging findings, taken together with clinical factors and serial neurological examination can be used to predict future neurodevelopmental outcomes. In this narrative review, we discuss neonatal neuroimaging modalities, and how these can be optimally utilized to assess infants in the NICU. We will review common patterns of brain injury and neurodevelopmental outcomes in hypoxic-ischemic encephalopathy, perinatal arterial ischemic stroke and preterm brain injury. SUMMARY: Timely and accurate neuroprognostication can identify infants at risk for neurodevelopmental impairment and allow for early intervention and targeted therapies to improve outcomes.

The Current State of Neonatal Neurodevelopmental Follow-up Programs in North America: A Children's Hospitals Neonatal Consortium Report.

OBJECTIVE: This study aimed to determine neonatal neurodevelopmental follow-up (NDFU) practices across academic centers. STUDY DESIGN: This study was a cross-sectional survey that addressed center-specific neonatal NDFU practices within the Children's Hospitals Neonatal Consortium (CHNC). RESULTS: Survey response rate was 76%, and 97% of respondents had a formal NDFU program. Programs were commonly staffed by neonatologists (80%), physical therapists (77%), and nurse practitioners (74%). Median gestational age at birth identified for follow-up was ≤32 weeks (range 26-36). Median duration was 3 years (range 2-18). Ninety-seven percent of sites used Bayley Scales of Infant and Toddler Development, but instruments used varied across ages. Scores were recorded in discrete electronic data fields at 43% of sites. Social determinants of health data were collected by 63%. Care coordination and telehealth services were not universally available. CONCLUSION: NDFU clinics are almost universal within CHNC centers. Commonalities and variances in practice highlight opportunities for data sharing and development of best practices. KEY POINTS: · Neonatal NDFU clinics help transition high-risk infants home.. · Interdisciplinary neonatal intensive care unit follow-up brings together previously separated outpatient service lines.. · This study reviews the current state of neonatal NDFU in North America..

The effect of non-invasive high-frequency oscillatory ventilation on the duration of non-invasive respiratory support in late preterm and term infants with transient tachypnea of the newborn: a randomized controlled trial.

Nasal continuous positive airway pressure (nCPAP) is one of the most commonly used non-invasive respiratory support modes in neonates with transient tachypnea of the newborn (TTN). Non-invasive high-frequency oscillatory ventilation (nHFOV) is a non-invasive respiratory support mode that has been increasingly used in neonatal respiratory disorders. This prospective randomized controlled study compared the efficacy of nHFOV and nCPAP in reducing the duration of non-invasive respiratory support. Late preterm and term infants > 34 weeks' gestation were included in the study. The infants were randomly assigned to receive either nHFOV or nCPAP. Treatment was started with standard settings in both groups. Infants who met treatment failure criteria were switched to nasal intermittent mandatory ventilation for further positive-pressure support. A total of 60 infants were included in the study. Thirty of these infants were included in the nHFOV group and 30 were included in the nCPAP group. The median duration of non-invasive respiratory support was not significantly different between the two groups (21 h [IQR: 16-68] for nHFOV vs 15 h [IQR: 11-33] for nCPAP; p = 0.09). However, after adjusting for potential confounders, nHFOV was associated with a shorter duration of non-invasive respiratory support than nCPAP (adjusted mean difference: 16.3 h; 95% CI: 0.7 to 31.9; p = 0.04). nHFOV was well tolerated and did not increase the risk of complications.    Conclusion: Our findings suggest that nHFOV is an effective and safe ventilation mode for late preterm and term neonates with TTN.   Trial registry: Clinicaltrials.gov (NCT03006354). Date of registration: December 30, 2016. What is Known: • nHFOV is a ventilation model that has been increasingly used for the management of RDS. • TTN is one of the most common causes of neonatal respiratory distress. What is New: • nHFOV is associated with shorter duration of non-invasive respiratory support and duration of oxygen support. • nHFOV may be a safe and effective alternative to nCPAP for neonates with TTN.

Post-hemorrhagic ventricular dilatation affects white matter maturation in extremely preterm infants.

BACKGROUND: Data on microstructural white matter integrity in preterm infants with post-hemorrhagic ventricular dilatation (PHVD) using diffusion tensor imaging (DTI) are limited. Also, to date, no study has focused on the DTI changes in extremely preterm (EP) infants with PHVD. METHODS: A case-control study of EP infants <28 weeks' gestation with PHVD was conducted. Diffusivity and fractional anisotropy (FA) values of corticospinal tracts (CST) and corpus callosum (CC) were measured using DTI at term-equivalent age. Outcomes were assessed at 2-years-corrected age. RESULTS: Twenty-one infants with PHVD and 21 matched-controls were assessed. FA values in the CC were lower in infants with PHVD compared with controls (mean difference, 0.05 [95% confidence interval (CI), 0.02-0.08], p < 0.001). In infants with periventricular hemorrhagic infarction, FA values in the CC were lower than in controls (mean difference, 0.05 [95% CI, 0.02-0.09], p = 0.005). The composite cognitive and motor scores were associated with the FA value of the CC (coefficient 114, p = 0.01 and coefficient 147, p = 0.004; respectively). CONCLUSIONS: Extremely preterm infants with PHVD showed lower FA values in CC. A positive correlation was also shown between the composite cognitive and motor scores and FA value of the CC at 2-years-corrected age. IMPACT: Extremely preterm infants with post-hemorrhagic ventricular dilatation showed lower fractional anisotropy values in their corpus callosum compared with controls reflecting the impaired microstructure of these commissural nerve fibers that are adjacent to the dilated ventricles. Impaired microstructure of the corpus callosum was shown to be associated with cognitive and motor scores at 2-years-corrected age.

Periventricular Hemorrhagic Infarction in Very Preterm Infants: Characteristic Sonographic Findings and Association with Neurodevelopmental Outcome at Age 2 Years.

OBJECTIVE: To describe the sonographic characteristics of periventricular hemorrhagic infarction (PVHI) and their association with mortality and neurodevelopmental disability in very preterm infants born in 2008-2013. STUDY DESIGN: Retrospective multicenter observational cohort study. Diagonal PVHI size was measured and severity score assessed. PVHI characteristics were scored and temporal trends were assessed. Neurodevelopmental outcome at 2 years of corrected age was assessed using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales. Multigroup analyses were applied as appropriate. RESULTS: We enrolled 160 infants with median gestational age of 26.6 weeks. PVHI was mostly unilateral (90%), associated with an ipsilateral grade III intraventricular hemorrhage (84%), and located in the parietal lobe (51%). Sixty-four (40%) infants with PVHI died in the neonatal period. Of the survivors assessed at 2 years of corrected age, 65% had normal cognitive and 69% had normal motor outcomes. The cerebral palsy rate was 42%. The composite outcome of death or severe neurodevelopmental disability was observed in 58%, with no trends over the study period (P = .6). Increasing PVHI severity score was associated with death (P < .001). Increasing PVHI size and severity score were negatively associated with gross motor scores (P = .01 and .03, respectively). Trigone involvement was associated with cerebral palsy (41% vs 14%; P = .004). Associated posthemorrhagic ventricular dilation (36%) was an independent risk factor for poorer cognitive and motor outcomes (P < .001 for both). CONCLUSIONS: Increasing PVHI size and severity score were predictive of less optimal gross motor outcome and death in very preterm infants.

Randomized Controlled Early versus Late Ventricular Intervention Study in Posthemorrhagic Ventricular Dilatation: Outcome at 2 Years.

OBJECTIVE: To compare the effect of intervention at low vs high threshold of ventriculomegaly in preterm infants with posthemorrhagic ventricular dilatation on death or severe neurodevelopmental disability. STUDY DESIGN: This multicenter randomized controlled trial reviewed lumbar punctures initiated after either a low threshold (ventricular index of >p97 and anterior horn width of >6 mm) or high threshold (ventricular index of >p97 + 4 mm and anterior horn width of >10 mm). The composite adverse outcome was defined as death or cerebral palsy or Bayley composite cognitive/motor scores <-2 SDs at 24 months corrected age. RESULTS: Outcomes were assessed in 113 of 126 infants. The composite adverse outcome was seen in 20 of 58 infants (35%) in the low threshold group and 28 of 55 (51%) in the high threshold (P = .07). The low threshold intervention was associated with a decreased risk of an adverse outcome after correcting for gestational age, severity of intraventricular hemorrhage, and cerebellar hemorrhage (aOR, 0.24; 95% CI, 0.07-0.87; P = .03). Infants with a favorable outcome had a smaller fronto-occipital horn ratio (crude mean difference, -0.06; 95% CI, -0.09 to -0.03; P < .001) at term-equivalent age. Infants in the low threshold group with a ventriculoperitoneal shunt, had cognitive and motor scores similar to those without (P = .3 for both), whereas in the high threshold group those with a ventriculoperitoneal shunt had significantly lower scores than those without a ventriculoperitoneal shunt (P = .01 and P = .004, respectively). CONCLUSIONS: In a post hoc analysis, earlier intervention was associated with a lower odds of death or severe neurodevelopmental disability in preterm infants with progressive posthemorrhagic ventricular dilatation. TRIAL REGISTRATION: ISRCTN43171322.

Assessment of Brain Injury and Brain Volumes after Posthemorrhagic Ventricular Dilatation: A Nested Substudy of the Randomized Controlled ELVIS Trial.

OBJECTIVE: To compare the effect of early and late intervention for posthemorrhagic ventricular dilatation on additional brain injury and ventricular volume using term-equivalent age-MRI. STUDY DESIGN: In the Early vs Late Ventricular Intervention Study (ELVIS) trial, 126 preterm infants ≤34 weeks of gestation with posthemorrhagic ventricular dilatation were randomized to low-threshold (ventricular index >p97 and anterior horn width >6 mm) or high-threshold (ventricular index >p97 + 4 mm and anterior horn width >10 mm) groups. In 88 of those (80%) with a term-equivalent age-MRI, the Kidokoro Global Brain Abnormality Score and the frontal and occipital horn ratio were measured. Automatic segmentation was used for volumetric analysis. RESULTS: The total Kidokoro score of the infants in the low-threshold group (n = 44) was lower than in the high-threshold group (n = 44; median, 8 [IQR, 5-12] vs median 12 [IQR, 9-17], respectively; P < .001). More infants in the low-threshold group had a normal or mildly increased score vs more infants in the high-threshold group with a moderately or severely increased score (46% vs 11% and 89% vs 54%, respectively; P = .002). The frontal and occipital horn ratio was lower in the low-threshold group (median, 0.42 [IQR, 0.34-0.63]) than the high-threshold group (median 0.48 [IQR, 0.37-0.68], respectively; P = .001). Ventricular cerebrospinal fluid volumes could be calculated in 47 infants and were smaller in the low-threshold group (P = .03). CONCLUSIONS: More brain injury and larger ventricular volumes were demonstrated in the high vs the low-threshold group. These results support the positive effects of early intervention for posthemorrhagic ventricular dilatation. TRIAL REGISTRATION: ISRCTN43171322.

Bedside Ultrasound-Guided Percutaneous Needle Aspiration of Intra- and Extra-Axial Intracranial Hemorrhage in Neonates.

Intracranial hemorrhage is an important cause of brain injury in the neonatal population and bedside percutaneous needle aspiration has emerged as an alternative due to the major risks that can be caused by standard neurosurgical decompression. We aimed to assess the effectiveness of this minimally invasive bedside technique and conducted a retrospective analysis of all newborn infants with a large extra-axial hemorrhage associated with a parenchymal hemorrhage causing a midline shift, managed at three academic centers over a 15-year period. Collected data included clinical history, laboratory results, review of all imaging studies performed, and neurodevelopmental follow-up. Eight infants (3 preterm and 5 full-term) presented on day 1 to 2 with seizures (n = 6) and apneas (n = 5), signs of increased intracranial pressure (n = 4), and coning (n = 1). Risk factors were present in six. Cranial ultrasound and computed tomography showed a midline shift in all; two infants showed status epilepticus on amplitude-integrated electroencephalography with complete resolution after the procedure. Between 7 and 34 mL could be aspirated associated with a decrease in the midline shift as seen by ultrasonography performed during the puncture. No complications were seen related to the procedure and none of the infants required further acute neurosurgical intervention. On follow-up, three had mild sequelae, including motor coordination problems (n = 1) and hemianopia (n = 2); none developed cerebral palsy or postneonatal epilepsy. Neonates, presenting with severe symptoms, can be managed successfully using ultrasound-guided needle aspiration and this minimally invasive bedside method should be kept in mind before performing neurosurgical decompression.

Harlequin color change after abdominal paracentesis in a newborn with neonatal hemochromatosis.

Harlequin color change is a distinctive cutaneous phenomenon presenting as a well-demarcated color change, with half of the body displaying erythema and the other half pallor. Only a few cases have been reported, possibly because of under-recognition. Recognition of this benign, self-limited condition may enable physicians to avoid unnecessary interventions. Herein we describe a neonate with nonimmune hydrops fetalis due to neonatal hemochromatosis who developed Harlequin color change after abdominal paracentesis.

Epidemiology and Outcomes of Neonatal Meningitis: Results of the Turkish Neo-Meningitis Nationwide Study.

OBJECTIVE: To investigate the incidence and etiology of neonatal meningitis and to assess the associated risk factors, complications and outcomes in a nationwide multicenter retrospective descriptive study. METHOD: Twenty-seven centers from 7 geographical regions participated in the study. Newborns with a positive cerebrospinal fluid culture and/or cerebrospinal fluid polymerase chain reaction were included in the study. Demographic characteristics, clinical, laboratory and neuroimaging findings and mortality characteristics were analyzed. RESULTS: A total of 634 confirmed cases of neonatal meningitis were included in the final analysis. The incidence was 2.51 per 1000 intensive care unit hospitalizations and mortality was observed in 149 (23.5%). Gram-positive bacteria were the predominant pathogens (54.5%), with coagulase-negative Staphylococci accounting for 45.3% of the cases, followed by Gram-negative organisms (37.3%). Viral and fungal organisms were isolated in 3.2% and 1.7% of the infants, respectively. Gram-negative culture growth was more common in infants who died (51% vs. 34.6%; P < 0.001). In the multivariable model, the odds of mortality was higher in those with respiratory distress requiring invasive ventilatory support [odds ratio (OR): 10.3; 95% confidence interval (CI): 4.9-21.7; P < 0.01], hypotension requiring inotropes (OR: 4.4; 95% CI: 2.7-7.1; P < 0.001), low birth weight status (OR: 2.5; 95% CI: 1.4-4.6; P = 0.002), lack of exposure to antenatal steroids (OR: 2.4; 95% CI: 1.3-4.4; P = 0.005) and the presence of concomitant sepsis (OR: 1.9; 95% CI: 1.1-3.2; P = 0.017). CONCLUSIONS: In this nationwide study, neonatal meningitis was found to be associated with high mortality. Coagulase-negative Staphylococci was the most common causative microorganism followed by Gram-negative bacteria. Severe clinical presentation with invasive mechanical ventilation and inotrope requirement, as well as concomitant sepsis, low birth weight status and lack of exposure to antenatal steroids, were found to be independent risk factors for mortality.

Human Studies of Transcranial Ultrasound neuromodulation: A systematic review of effectiveness and safety.

BACKGROUND: Transcranial ultrasound stimulation (TUS) is gaining traction as a safe and non-invasive technique in human studies. There has been a rapid increase in TUS human studies in recent years, with more than half of studies to date published after 2020. This rapid growth in the relevant body of literature necessitates comprehensive reviews to update clinicians and researchers. OBJECTIVE: The aim of this work is to review human studies with an emphasis on TUS devices, sonication parameters, outcome measures, results, and adverse effects, as well as highlight future directions of investigation. METHODS: A systematic review was conducted by searching the Web of Science and PubMed databases on January 12, 2022. Human studies of TUS were included. RESULTS: A total of 35 studies were identified using focused/unfocused ultrasound devices. A total of 677 subjects belonging to diverse cohorts (i.e., healthy, chronic pain, dementia, epilepsy, traumatic brain injury, depression) were enrolled. The stimulation effects vary in a sonication parameter-dependant fashion. Clinical, neurophysiological, radiological and histological outcome measures were assessed. No severe adverse effects were reported in any of the studies surveyed. Mild symptoms were observed in 3.4% (14/425) of the subjects, including headache, mood deterioration, scalp heating, cognitive problems, neck pain, muscle twitches, anxiety, sleepiness and pruritis. CONCLUSIONS: Although increasingly being used, TUS is still in its early phases. TUS can change short-term brain excitability and connectivity, induce long-term plasticity, and modulate behavior. New techniques should be used to further elucidate its underlying mechanisms and identify its application in novel populations.

Corpus callosum injury after neurosurgical intervention for posthemorrhagic ventricular dilatation and association with neurodevelopmental outcome at 2 years.

OBJECTIVE: Direct injury to the corpus callosum (CC) due to neurosurgical interventions in infants with posthemorrhagic ventricular dilatation (PHVD) has not been reported in the literature. The authors observed a subset of infants who had suffered penetrating CC injury after neurosurgical interventions for PHVD and hypothesized that this pattern of injury may result in suboptimal CC maturation and neurodevelopmental impairment. METHODS: In this multicenter, retrospective, observational study, 100 preterm and 17 full-term infants with PHVD were included and compared with 23 preterm controls. Both neonatal and postneonatal brain MRI scans were assessed for injury, and measurements were performed on postneonatal MRI scans at 2 years' corrected age. Neurodevelopmental outcome was assessed at 2 years' corrected age. RESULTS: A total of 269 brain MRI scans of 140 infants were included. Of infants with PHVD, 48 (41%) had penetrating CC injury following neurosurgical interventions. The median (IQR) CC midsagittal surface area was smaller in infants with CC injury when compared with infants with PHVD who had intact CC and controls (190 mm2 [149-262 mm2] vs 268 mm2 [206-318 mm2] vs 289 mm2 [246-320 mm2], respectively; p < 0.001). In the univariate analysis, the area of the CC was associated with cognitive Z score (coefficient 0.009 [95% CI 0.005-0.012], p < 0.001) and motor Z score (coefficient 0.009 [95% CI 0.006-0.012], p < 0.001). In the multivariable model, CC injury was not independently associated with cognitive and motor Z score after adjusting for gestational age and presence of periventricular hemorrhagic infarction (coefficient 0.04 [95% CI -0.36 to 0.46] and -0.37 [95% CI -0.83 to 0.09], p = 0.7 and 0.1, respectively). CONCLUSIONS: CC injury was not uncommon following neurosurgical interventions for PHVD in both preterm and full-term infants. At the age of 2 years, the CC midsagittal surface area was smaller in infants with injury, but CC injury was not independently associated with cognitive and motor outcomes at 2 years' corrected age.

Intraparenchymal hemorrhage after serial ventricular reservoir taps in neonates with hydrocephalus and association with neurodevelopmental outcome at 2 years of age.

OBJECTIVE: Decompressing the ventricles with a temporary device is often the initial neurosurgical intervention for preterm infants with hydrocephalus. The authors observed a subgroup of infants who developed intraparenchymal hemorrhage (IPH) after serial ventricular reservoir taps and sought to describe the characteristics of IPH and its association with neurodevelopmental outcome. METHODS: In this multicenter, case-control study, for each neonate with periventricular and/or subcortical IPH, a gestational age-matched control with reservoir who did not develop IPH was selected. Digital cranial ultrasound (cUS) scans and term-equivalent age (TEA)-MRI (TEA-MRI) studies were assessed. Ventricular measurements were recorded prior to and 3 days and 7 days after reservoir insertion. Changes in ventricular volumes were calculated. Neurodevelopmental outcome was assessed at 2 years corrected age using standardized tests. RESULTS: Eighteen infants with IPH (mean gestational age 30.0 ± 4.3 weeks) and 18 matched controls were included. Reduction of the ventricular volumes relative to occipitofrontal head circumference after 7 days of reservoir taps was greater in infants with IPH (mean difference -0.19 [95% CI -0.37 to -0.004], p = 0.04). Cognitive and motor Z-scores were similar in infants with and those without IPH (mean difference 0.42 [95% CI -0.17 to 1.01] and 0.58 [95% CI -0.03 to 1.2]; p = 0.2 and 0.06, respectively). Multifocal IPH was negatively associated with cognitive score (coefficient -0.51 [95% CI -0.88 to -0.14], p = 0.009) and ventriculoperitoneal shunt with motor score (coefficient -0.50 [95% CI -1.6 to -0.14], p = 0.02) after adjusting for age at the time of assessment. CONCLUSIONS: This study reports for the first time that IPH can occur after a rapid reduction of the ventricular volume during the 1st week after the initiation of serial reservoir taps in neonates with hydrocephalus. Further studies on the use of cUS to guide the amount of cerebrospinal fluid removal are warranted.

Elevated blood carboxyhemoglobin levels as an early predictor of phototherapy requirement in moderate and late preterm infants.

Objective: Preterm infants are prone to increased bilirubin burden and display adverse outcomes if left unmonitored; therefore, predicting an increased bilirubin production is of paramount importance.Methods: We aimed to evaluate carboxyhemoglobin (COHb) levels in moderate (GA: 320/7-336/7) and late preterm (GA: 340/7-366/7) infants to assess whether this molecule could be used as an early predictor of phototherapy requirement.Results: A total of 221 infants were enrolled in the study. On admission, carboxyhemoglobin levels of infants who received phototherapy were significantly higher than that of infants who did not require this treatment, and this difference persisted in the consecutive hours (median (min-max): 1.2% (0.3-1.7) versus 0.8% (0.4-1.1); p < .001). The initial and consecutive COHb levels showed positive correlation (r = 0.77, p < .001). In the post-hoc analysis, direct antiglobulin test positivity significantly affected phototherapy requirement (p < .001). Receiver operating characteristics analysis showed that a COHb level of ≥0.95% was found to have a sensitivity of 90% and a specificity of 88%. Multinomial logistic regression analysis demonstrated that high COHb levels on admission significantly increased the likelihood of phototherapy requirement when adjusted for covariants (adjusted odds ratio: 2.2; 95% confidence interval: 1.4-3.5; p < .001).Conclusion: Carboxyhemoglobin measurement can be simply used to predict preterm infants who will require phototherapy.