Integrating Clinical and Neuroimaging Markers to Predict the Onset of Posthemorrhagic Ventricular Dilatation in Preterm Neonates.

BACKGROUND: Posthemorrhagic ventricular dilatation (PHVD) is a major complication of intraventricular hemorrhage (IVH); it is associated with high risks of cerebral palsy and cognitive deficits compared with infants without PHVD. This study aims to explore the early perinatal risk factors-associated with the risk of progressive PHVD. METHODS: Neonates ≤29 weeks gestational age (GA) with Grade II-III IVH and periventricular hemorrhagic infarct (PVHI) between 2015 and 2021 were retrospectively reviewed. All cranial ultrasounds done within 14 days postnatal age (PNA) were assessed for grade of IVH, anterior horn width (AHW), ventricular index (VI), and thalamo-occipital index (TOD). The outcome was defined as death of any cause or VI and/or AHW and/or TOD ≥ moderate-risk zone based on an ultrasound done beyond two weeks PNA. RESULTS: A total of 146 infants with a mean GA of 26 ± 1.8 weeks, birth weight 900 ± 234 g were included, 46% were females. The primary outcome occurred in 56 (39%) infants; among them 17 (30%) and 11 (20%) needed ventricular reservoir and shunt insertion, respectively. The risk factors present within 14 days PNA that significantly increased the odds of developing PHVD were hemodynamically significant patent ductus arteriosus (odds ratio [OR] 6.1, 95% confidence interval [CI] 1.9 to 22), culture-proven sepsis (OR 5.4, 95% CI 1.8 to 18), Grade III IVH (OR 4.6, 95% CI 1.1 to 22), PVHI (OR 3.0, 95% CI 0.9 to 10), and VI (OR 2.1, 95% CI 1.6 to 2.9). CONCLUSIONS: Clinical predictors such as significant ductus arteriosus and bacterial septicemia, along with risk levels of AHW and VI measured with early cranial ultrasounds, are potential predictors of subsequent onset of PHVD.

Associations between diffusion kurtosis imaging metrics and neurodevelopmental outcomes in neonates with low-grade germinal matrix and intraventricular hemorrhage.

Diffusion Kurtosis Imaging (DKI)-derived metrics are recognized as indicators of maturation in neonates with low-grade germinal matrix and intraventricular hemorrhage (GMH-IVH). However, it is not yet known if these factors are associated with neurodevelopmental outcomes. The objective of this study was to acquire DKI-derived metrics in neonates with low-grade GMH-IVH, and to demonstrate their association with later neurodevelopmental outcomes. In this prospective study, neonates with low-grade GMH-IVH and control neonates were recruited, and DKI were performed between January 2020 and March 2021. These neonates underwent the Bayley Scales of Infant Development test at 18 months of age. Mean kurtosis (MK), radial kurtosis (RK) and gray matter values were measured. Spearman correlation analyses were conducted for the measured values and neurodevelopmental outcome scores. Forty controls (18 males, average gestational age (GA) 30 weeks ± 1.3, corrected GA at MRI scan 38 weeks ± 1) and thirty neonates with low-grade GMH-IVH (13 males, average GA 30 weeks ± 1.5, corrected GA at MRI scan 38 weeks ± 1). Neonates with low-grade GMH-IVH exhibited lower MK and RK values in the PLIC and the thalamus (P < 0.05). The MK value in the thalamus was associated with Mental Development Index (MDI) (r = 0.810, 95% CI 0.695-0.13; P < 0.001) and Psychomotor Development Index (PDI) (r = 0.852, 95% CI 0.722-0.912; P < 0.001) scores. RK value in the caudate nucleus significantly and positively correlated with MDI (r = 0.496, 95% CI 0.657-0.933; P < 0.001) and PDI (r = 0.545, 95% CI 0.712-0.942; P < 0.001) scores. The area under the curve (AUC) were used to assess diagnostic performance of MK and RK in thalamus (AUC = 0.866, 0.787) and caudate nucleus (AUC = 0.833, 0.671) for predicting neurodevelopmental outcomes. As quantitative neuroimaging markers, MK in thalamus and RK in caudate nucleus may help predict neurodevelopmental outcomes in neonates with low-grade GMH-IVH.

Premature newborns with intraventricular hemorrhage do not have vasospasm pattern by cranial Doppler ultrasound: A pilot study.

Preterm neonates are at risk for neurodevelopmental impairment, especially those with intraventricular hemorrhage (IVH). Cerebral vasospasm (VSP) is a common complication after subarachnoid hemorrhage (SAH) in adult population, but it is unknown if preterm neonates with IVH may develop it. We prospectively enrolled premature newborns < 32 weeks with IVH and without IVH. All patients received serial transcranial sonography through the temporal window of the middle cerebral artery, anterior cerebral artery, posterior cerebral artery, and the internal carotid artery with transcranial Doppler sonography days 2, 4, and 10 of life. Cerebral blood velocities (CBFVs) were measured including median velocity flow (MV), peak systolic velocity (PSV), and maximum end-diastolic velocity (EDV). Resistance index and pulsatility index were calculated. VSP was defined as an increase of 50% in the baseline velocity per day and/or a Lindegaard ratio higher than 3. Fifty subjects were enrolled. None of the patients with IVH showed elevation of MV or a Lindegaard ratio > 3. There were no differences between IVH and without IVH groups regarding resistance index and pulsatility index.    Conclusion: Preterm infants with IVH do not present a pattern of VSP analyzed by Doppler transcranial ultrasound in this pilot study. What is Known: • In adult population with subarachnoid hemorrhage the most treatable cause of cerebral ischemia is due cerebral vasospasm but is unknown if premature newborn may have vasospasm due the extravasation of blood in the context of intraventricular hemorrhage What is New: •In this pilot study we did not find in premature newborn with intraventricular hemorrhage signs of vasoespam measured by transcranial color doppler ultrasound.

Neurodevelopmental outcome in preterm infants with intraventricular hemorrhages: the potential of quantitative brainstem MRI.

OBJECTIVES: This retrospective study aimed to identify quantitative magnetic resonance imaging markers in the brainstem of preterm neonates with intraventricular hemorrhages. It delves into the intricate associations between quantitative brainstem magnetic resonance imaging metrics and neurodevelopmental outcomes in preterm infants with intraventricular hemorrhage, aiming to elucidate potential relationships and their clinical implications. MATERIALS AND METHODS: Neuroimaging was performed on preterm neonates with intraventricular hemorrhage using a multi-dynamic multi-echo sequence to determine T1 relaxation time, T2 relaxation time, and proton density in specific brainstem regions. Neonatal outcome scores were collected using the Bayley Scales of Infant and Toddler Development. Statistical analysis aimed to explore potential correlations between magnetic resonance imaging metrics and neurodevelopmental outcomes. RESULTS: Sixty preterm neonates (mean gestational age at birth 26.26 ± 2.69 wk; n = 24 [40%] females) were included. The T2 relaxation time of the midbrain exhibited significant positive correlations with cognitive (r = 0.538, P < 0.0001, Pearson's correlation), motor (r = 0.530, P < 0.0001), and language (r = 0.449, P = 0.0008) composite scores at 1 yr of age. CONCLUSION: Quantitative magnetic resonance imaging can provide valuable insights into neurodevelopmental outcomes after intraventricular hemorrhage, potentially aiding in identifying at-risk neonates. Multi-dynamic multi-echo sequence sequences hold promise as an adjunct to conventional sequences, enhancing the sensitivity of neonatal magnetic resonance neuroimaging and supporting clinical decision-making for these vulnerable patients.

Serum Neuron-Specific Enolase as a Biomarker of Neonatal Brain Injury-New Perspectives for the Identification of Preterm Neonates at High Risk for Severe Intraventricular Hemorrhage.

Neonatal brain injury (NBI) is a critical condition for preterm neonates with potential long-term adverse neurodevelopmental outcomes. This prospective longitudinal case-control study aimed at investigating the levels and prognostic value of serum neuron-specific enolase (NSE) during the first 3 days of life in preterm neonates (<34 weeks) that later developed brain injury in the form of either periventricular leukomalacia (PVL) or intraventricular hemorrhage (IVH) during their hospitalization. Participants were recruited from one neonatal intensive care unit, and on the basis of birth weight and gestational age, we matched each case (n = 29) with a neonate who had a normal head ultrasound scan (n = 29). We report that serum NSE levels during the first three days of life do not differ significantly between control and preterm neonates with NBI. Nevertheless, subgroup analysis revealed that neonates with IVH had significantly higher concentrations of serum NSE in comparison to controls and neonates with PVL on the third day of life (p = 0.014 and p = 0.033, respectively). The same pattern on the levels of NSE on the third day of life was also observed between (a) neonates with IVH and all other neonates (PVL and control; p = 0.003), (b) neonates with II-IV degree IVH and all other neonates (p = 0.003), and (c) between control and the five (n = 5) neonates that died from the case group (p = 0.023). We conclude that NSE could be an effective and useful biomarker on the third day of life for the identification of preterm neonates at high risk of developing severe forms of IVH.

Optimal intraventricular hemorrhage volume cutoff for predicting poor outcome in patients with intracerebral hemorrhage.

BACKGROUND AND OBJECTIVES: The prognosis of patients with spontaneous intracerebral hemorrhage (ICH) is often influenced by hematoma volume, a well-established predictor of poor outcome. However, the optimal intraventricular hemorrhage (IVH) volume cutoff for predicting poor outcome remains unknown. METHODS: We analyzed 313 patients with spontaneous ICH not undergoing evacuation, including 7 cases with external ventricular drainage (EVD). These patients underwent a baseline CT scan, followed by a 24-hour CT scan for measurement of both hematoma and IVH volume. We defined hematoma growth as hematoma growth > 33 % or 6 mL at follow-up CT, and poor outcome as modified Rankin Scale score≥3 at three months. Cutoffs with optimal sensitivity and specificity for predicting poor outcome were identified using receiver operating curves. RESULTS: The receiver operating characteristic analysis identified 6 mL as the optimal cutoff for predicting poor outcome. IVH volume> 6 mL was observed in 53 (16.9 %) of 313 patients. Patients with IVH volume>6 mL were more likely to be older and had higher NIHSS score and lower GCS score than those without. IVH volume>6 mL (adjusted OR 2.43, 95 % CI 1.13-5.30; P = 0.026) was found to be an independent predictor of poor clinical outcome at three months in multivariable regression analysis. CONCLUSIONS: Optimal IVH volume cutoff represents a powerful tool for improving the prediction of poor outcome in patients with ICH, particularly in the absence of clot evacuation or common use of EVD. Small amounts of intraventricular blood are not independently associated with poor outcome in patients with intracerebral hemorrhage. The utilization of optimal IVH volume cutoffs may improve the clinical trial design by targeting ICH patients that will obtain maximal benefit from therapies.

Risk factors associated with intraventricular hemorrhage in very-low-birth-weight premature infants.

PURPOSE: To analyze the association between risk factors and severe intraventricular hemorrhage (grade II-IV) in PNB under 1500 g. METHODS: Multicenter, retrospective, analytical, case-control study in PNB under 34 weeks and under 1500 g admitted to the NICU. CASE: PNB with severe intraventricular hemorrhage (grade II-IV). Logistic regression analysis was used to adjust for IVH-associated variables and odds ratios (OR). RESULTS: A total of 90 PNB files were analyzed, 45 cases and 45 controls. The highest risk factors for severe IVH were lower gestational age (OR 1.3, p < 0.001), perinatal asphyxia (OR 12, p < 0.001), Apgar < 6 at minute 1 and 5 (OR 6.3, p < 0.001). CONCLUSION: Lower gestational age, birth asphyxia, Apgar score lower of 6, and respiratory-type factors are associated with increased risk for severe IVH.

Microhemorragias cerebrales. Utilidad de las secuencias de susceptibilidad magnética (SWI) / Cerebral microbleeds. Utility of SWI sequences

Objetivo: Definir el concepto de microhemorragia cerebral y revisar las secuencias de resonancia magnética (RM) utilizadas para su valoración. Revisar cuáles son las patologías que presentan microhemorragias y que pueden beneficiarse del uso de secuencias de susceptibilidad magnética (SWI). Conclusión: Las SWI son útiles en la detección y caracterización de microhemorragias, venas y otras fuentes de susceptibilidad. La secuencia SWI mejora la sensibilidad diagnóstica con respecto a las secuencias convencionales potenciadas en T2* (eco de gradiente T2* [2D-GRE]). Las microhemorragias cerebrales pueden asociarse a diversas enfermedades, aparecer en contextos clínicos menos conocidos o servir como biomarcador tumoral en gliomas (ITTS) y como marcador de actividad inflamatoria en las placas de esclerosis múltiple (EM).(AU)

Objectives: Define the concept of cerebral microbleeds (CMB) and describe the most useful MRI sequences for detecting this finding. Review the entities that most frequently present with CMB and that may benefit from the use of susceptibility-weighted imaging (SWI) sequences. Conclusions: SWI is a useful MRI sequence for the detection and characterization of microhemorrhages, venous structures and other sources of susceptibility in imaging. SWI is particularly sensitive to local magnetic field inhomogeneities generated by certain substances and is superior to T2* GRE sequences for this assessment. CMB may be seen in different neurologic conditions, in certain infrequent clinical contexts and have a key role as a biomarker status in gliomas (ITTS) and as a marker of inflammatory activity in multiple sclerosis.(AU)

Percutaneous Transfontanellar External Ventricular Drainage in an Extremely Low Birth Weight Infant: 2-Dimensional Operative Video.

Intraventricular hemorrhage and the subsequent development of posthemorrhagic hydrocephalus (PHH) is one of the most serious complication of prematurity, especially in extremely low birth weight infants.1 Neurodevelopmental delay, epilepsy, and severe cognitive impairment represent common sequelae of PHH.2,3 A ventriculoperitoneal shunt insertion in such premature infants is associated with higher rates of skin erosion, infection, and shunt failure.4 One therapeutic option is represented by the use of temporary cerebrospinal fluid diversion procedures (such as external ventricular drainage, subcutaneous reservoir, and ventriculosubgaleal shunt) to gain time avoiding the PHH secondary damages.5,6 An extremely low birth weight (birth weight = 653 g) infant at 24 + 4 gestational age weeks presented with a grade III intraventricular hemorrhage and periventricular hemorrhagic infarction 5 days after birth. Serial transfontanellar ultrasound disclosed a progressive PHH. Progressive symptomatic PHH, pulmonary hemodynamic instability, and suboptimal general prematurity conditions were the main factors that led to plan a percutaneous transfontanellar ultrasound-guided external ventricular drainage at the neonatal intensive care unit. The illustrated procedure represents a bedside minimally invasive, effective, reversible, and sparing-time choice alternative to other temporary cerebrospinal fluid diversion techniques. This edited, 2-dimensional operative video highlights the key surgical steps of the proposed procedure (Video 1). All relevant patient identifiers have been removed from the video. Nevertheless, the parent's consent was obtained regarding the procedure, video recording, and redistribution for educational purposes.

Efficiency of a deep learning-based artificial intelligence diagnostic system in spontaneous intracerebral hemorrhage volume measurement.

BACKGROUND: Accurate measurement of hemorrhage volume is critical for both the prediction of prognosis and the selection of appropriate clinical treatment after spontaneous intracerebral hemorrhage (ICH). This study aimed to evaluate the performance and accuracy of a deep learning-based automated segmentation algorithm in segmenting spontaneous intracerebral hemorrhage (ICH) volume either with or without intraventricular hemorrhage (IVH) extension. We compared this automated pipeline with two manual segmentation techniques. METHODS: We retrospectively reviewed 105 patients with acute spontaneous ICH. Depending on the presence of IVH extension, patients were divided into two groups: ICH without (n = 56) and with IVH (n = 49). ICH volume of the two groups were segmented and measured using a deep learning-based artificial intelligence (AI) diagnostic system and computed tomography-based planimetry (CTP), and the ABC/2 score were used to measure hemorrhage volume in the ICH without IVH group. Correlations and agreement analyses were used to analyze the differences in volume and length of processing time among the three segmentation approaches. RESULTS: In the ICH without IVH group, the ICH volumes measured using AI and the ABC/2 score were comparable to CTP segmentation. Strong correlations were observed among the three segmentation methods (r = 0.994, 0.976, 0.974; P < 0.001; concordance correlation coefficient [CCC] = 0.993, 0.968, 0.967). But the absolute error of the ICH volume measured by the ABC/2 score was greater than that of the algorithm (P < 0.05). In the ICH with IVH group, there is no significant differences were found between algorithm and CTP(P = 0.614). The correlation and agreement between CTP and AI were strong (r = 0.996, P < 0.001; CCC = 0.996). The AI segmentation took a significantly shorter amount of time than CTP (P < 0.001), but was slightly longer than ABC/2 score technique (P = 0.002). CONCLUSIONS: The deep learning-based AI diagnostic system accurately quantified volumes of acute spontaneous ICH with high fidelity and greater efficiency compared to the CTP measurement and more accurately than the ABC/2 scores. We believe this is a promising tool to help physicians achieve precise ICH quantification in practice.

Callosal Diffusion-Restriction in Patients with Intracranial Hemorrhage.

OBJECTIVE: We aim to report the incidence and clinical characteristics of patients who were found to have diffusion restricting lesions of the corpus callosum (CC) on Diffusion-weighted imaging (DWI) on magnetic resonance imaging (MRI) following intracranial hemorrhage (ICH). DESIGN/METHODS: A retrospective cross-sectional analysis was performed of medical records of all adult patients admitted to a single tertiary center with a primary diagnosis of ICH and received nicardipine infusion over a 2-year period. Patients without MRI brain available or patients who underwent digital subtraction angiography (DSA) prior to MRI were excluded. ICH and intraventricular hemorrhage (IVH) volumes and scores were calculated. MRI brain scans were evaluated for presence and locations of DWI lesions. RESULTS: Among 162 patients who met inclusion criteria, 6 patients (4%, median age 53, range 37-71, 100% male, 33% white) were found to have DWI lesions in the CC with a median ICH volume of 17ml (range 1-105ml). The ICH locations were lobar (n=3), deep (n=2) and cerebellum (n=1). All patients (100%) had intraventricular hemorrhage (IVH) with median IVH volume of 25ml (range 2.7-55ml). Four patients were on levetiracetam. No identifiable infections or metabolic abnormalities were found among these patients. All but one patient had normal DSA. Follow up MRI was only available in one patient and showed no reversibility at 14 days. CONCLUSION: Although rare, diffusion restricting corpus callosum lesions can be seen in patients with ICH, especially in patients with IVH. The etiology and clinical significance of these lesions remains unknown and warrant further research.

Hematoma Expansion Shift Analysis to Assess Acute Intracerebral Hemorrhage Treatments.

OBJECTIVE: Hematoma expansion (HE) is commonly analyzed as a dichotomous outcome in intracerebral hemorrhage (ICH) trials. In this proof-of-concept study, we propose an HE shift analysis model as a method to improve the evaluation of candidate ICH therapies. METHODS: Using data from the Antihypertensive Treatment of Acute Cerebral Hemorrhage II (ATACH-2) trial, we performed HE shift analysis in response to intensive blood pressure lowering by generating polychotomous strata based on previously established HE definitions, percentile/absolute quartiles of hematoma volume change, and quartiles of 24-hour follow-up hematoma volumes. The relationship between blood pressure treatment and HE shift was explored with proportional odds models. RESULTS: The primary analysis population included 863 patients. In both treatment groups, approximately one-third of patients exhibited no HE. With the use of a trichotomous HE stratification, the highest strata of ≥33% revealed a 5.8% reduction in hematoma growth for those randomized to intensive therapy (adjusted odds ratio [aOR] 0.77, 95% confidence interval [CI] 0.60-0.99). Using percentile quartiles of hematoma volume change, we observed a favorable shift to reduce growth in patients treated with intensive therapy (aOR 0.73, 95% CI 0.57-0.93). Similarly, in a tetrachotomous analysis of 24-hour follow-up hematoma volumes, shifts in the highest stratum (>21.9 mL) were most notable. CONCLUSIONS: Our findings suggest that intensive blood pressure reduction may preferentially mitigate growth in patients at risk of high volume HE. A shift analysis model of HE provides additional insights into the biological effects of a given therapy and may be an additional way to assess hemostatic agents in future studies. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier:NCT01176565.

Neonatal Cranial Ultrasound Findings among Infants Born Extremely Preterm: Associations with Neurodevelopmental Outcomes at 10 Years of Age.

OBJECTIVE: To examine the association between neonatal cranial ultrasound (CUS) abnormalities among infants born extremely preterm and neurodevelopmental outcomes at 10 years of age. STUDY DESIGN: In a multicenter birth cohort of infants born at <28 weeks of gestation, 889 of 1198 survivors were evaluated for neurologic, cognitive, and behavioral outcomes at 10 years of age. Sonographic markers of white matter damage (WMD) included echolucencies in the brain parenchyma and moderate to severe ventricular enlargement. Neonatal CUS findings were classified as intraventricular hemorrhage (IVH) without WMD, IVH with WMD, WMD without IVH, and neither IVH nor WMD. RESULTS: WMD without IVH was associated with an increased risk of cognitive impairment (OR 3.5, 95% CI 1.7, 7.4), cerebral palsy (OR 14.3, 95% CI 6.5, 31.5), and epilepsy (OR 6.9; 95% CI 2.9, 16.8). Similar associations were found for WMD accompanied by IVH. Isolated IVH was not significantly associated these outcomes. CONCLUSIONS: Among children born extremely preterm, CUS abnormalities, particularly those indicative of WMD, are predictive of neurodevelopmental impairments at 10 years of age. The strongest associations were found with cerebral palsy.

Stem cell restores thalamocortical plasticity to rescue cognitive deficit in neonatal intraventricular hemorrhage.

Severe neonatal intraventricular hemorrhage (IVH) patients incur long-term neurologic deficits such as cognitive disabilities. Recently, the intraventricular transplantation of allogeneic human umbilical cord blood-derived mesenchymal stem cells (MSCs) has drawn attention as a therapeutic potential to treat severe IVH. However, its pathological synaptic mechanism is still elusive. We here demonstrated that the integration of the somatosensory input was significantly distorted by suppressing feed-forward inhibition (FFI) at the thalamocortical (TC) inputs in the barrel cortices of neonatal rats with IVH by using BOLD-fMRI signal and brain slice patch-clamp technique. This is induced by the suppression of Hebbian plasticity via an increase in tumor necrosis factor-α expression during the critical period, which can be effectively reversed by the transplantation of MSCs. Furthermore, we showed that MSC transplantation successfully rescued IVH-induced learning deficits in the sensory-guided decision-making in correlation with TC FFI in the layer 4 barrel cortex.

CD47 blocking antibody accelerates hematoma clearance and alleviates hydrocephalus after experimental intraventricular hemorrhage.

Background CD47, a glycoprotein on red blood cell membranes, inhibits phagocytosis via interaction with signal regulatory protein α on phagocytes. Our previous research has demonstrated that blocking CD47 accelerates hematoma clearance and reduces brain injury after intracerebral hemorrhage. The current study investigated whether phagocytosis or erythrocyte CD47 impacts hematoma resolution and hydrocephalus development after intraventricular hemorrhage (IVH). Methods Adult (3-month-old) male Fischer 344 rats were intraventricularly injected with 200 µl autologous blood, mixed with either CD47 blocking antibody or isotype IgG, or 200 µl saline as control. In subgroups of CD47 blocking antibody treated rats, clodronate liposomes (to deplete microglia/monocyte-derived macrophages) or control liposomes were co-injected. Magnetic resonance imaging (MRI) was used to evaluate ventricular volume and intraventricular T2* lesion volume (estimating hematoma volume). The brains were harvested after 4 or 72 h for histology to evaluate phagocytosis. Results In adult male rats, CD47 blocking antibody alleviated hydrocephalus development by day 3. In addition, the CD47 blocking antibody reduced intraventricular T2* lesion and T2* non-hypointense lesion size after IVH through day 1 to day 3. Erythrophagocytosis was observed as soon as 4 h after IVH and was enhanced on day 3. Furthermore, intra-hematoma infiltration of CD68, heme oxygenase-1 and ferritin positive phagocytes were upregulated by CD47 blockade by day 3. Clodronate liposomes co-injection caused more severe hydrocephalus and weight loss. Conclusion Blocking CD47 in the hematoma accelerated hematoma clearance and alleviated hemolysis and hydrocephalus development after IVH, suggesting CD47 might be valuable in the future treatment for IVH.

Post-hemorrhagic ventricular dilatation: inter-observer reliability of ventricular size measurements in extremely preterm infants.

BACKGROUND: Post-hemorrhagic ventricular dilatation (PHVD) in preterm infants can be assessed with ventricular size indices from cranial ultrasound. We explored inter-observer reliability of these indices for prediction of severe PHVD. METHODS: For all 139 infants with IVH, serial neonatal ultrasound at 3 time points (days 4-7, day 14, 36 weeks PMA) were assessed independently by 3 observers with differing levels of training/experience. Ventricular index (VI), anterior horn width (AHW), and fronto-temporal horn ratio (FTHR) were measured and used to diagnose PHVD. For all, inter-observer reliability and predictive values for receipt of surgical intervention were calculated. RESULTS: Inter-observer reliability for all observers varied from poor to excellent, with higher reliability for VI/AHW (ICC 0.49-0.84/0.51-0.81) than FTHR (0.41-0.82), particularly from the second week. Good-excellent inter-expertise reliability was found between observers with ample experience/training (0.65-0.99), particularly for VI and AHW, while poor-moderate when comparing with an inexperienced observer (0.28-0.88). Slightly higher predictive value for PHVD intervention (n = 12) was found for AHW (AUC 0.86-0.96) than for VI and FTHR (0.80-0.96/0.80-0.95). CONCLUSIONS: AHW and VI are highly reproducible in experienced hands compared to FTHR, with AHW from the second week onwards being the strongest predictor for receiving surgical intervention for severe PHVD. AHW may aid in early PHVD diagnosis and decision-making on intervention. IMPACT: While ventricular size indices from serial cUS are superior to clinical signs of increased intracranial pressure to assess PHVD, questions remained on their inter-observer reproducibility and reliability to predict severity of PHVD. AHW and VI are highly reproducible when performed by experienced clinicians. AHW from the second week of birth is the strongest predictor of PHVD onset and severity. AHW, combined with VI, may aid in early PHVD diagnosis and decision-making on need for surgical intervention. Consistent use of these indices has the potential to improve PHVD management and therewith the long-term outcomes in preterm infants.