Composite Scoring and the Natural Course of Post-Hemorrhagic Ventricular Dilation in Neonates with Severe Intraventricular Hemorrhage

Composite Scoring and the Natural Course of Post-Hemorrhagic Ventricular Dilation in Neonates with Severe Intraventricular Hemorrhage | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Composite Scoring and the Natural Course of Post-Hemorrhagic Ventricular Dilation in Neonates with Severe Intraventricular Hemorrhage Garrett Gianneschi, Michael Christian, Hira Arif, Navina Magesh-Kumar, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8613373/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Post-hemorrhagic ventricular dilation (PHVD) is a significant complication in 30–50% of severe intraventricular hemorrhage (SIVH), yet the temporal dynamics of ventricular expansion and late “recoil” remain incompletely characterized. Objective To quantify the rate, magnitude, and temporal pattern of ventricular expansion following SIVH using serial cranial ultrasound measurements, and to explore associations with hemorrhage burden and mortality. Design/Setting Retrospective cohort study of neonates cared for at University Hospital Neonatal Intensive Care Unit (NICU) in Newark, NJ (01/2010–01/2025). Participants 43 neonates with SIVH and PHVD were included. Mortality was 37.2% (16/43); 11.6% (5/43) underwent invasive intervention. Methods Ventricular dilation was quantified on serial head ultrasounds using ventricular index (VI) and anterior horn width (AHW); 347 cranial ultrasounds were analyzed (8 per patient). Growth trajectories were modeled primarily as a function of postmenstrual age (PMA). Results Across the cohort, both VI and AHW increased significantly with PMA, with mean expansion rates of 0.105 mm/day for VI (95% CI 0.092–0.118) and 0.105 mm/day for AHW (95% CI 0.087–0.124) (both p < 0.001). Highest IVH grade (3 vs 4) did not significantly modify growth rate, but a composite bilateral hemorrhage-burden score better stratified outcomes and growth dynamics. When the composite score was grouped into low (3–6) vs high (7–8), high-burden infants demonstrated faster expansion (VI 0.126 vs 0.096 mm/day, p = 0.025; AHW 0.139 vs 0.091 mm/day, p = 0.013). Over time, VI expansion was effectively monotonic, while AHW showed only minor late recoil; overall, late ventricular shrinkage was uncommon. Mortality in the high composite group was 4.79 times higher than the low composite group (p = 0.024). Each 1-point increase in composite IVH severity showed a clinically meaningful association with mortality (OR 1.51 per 1-point increase; p = 0.072) and differed significantly between survivors and non-survivors (Wilcoxon p = 0.034). Conclusions In this retrospective NICU cohort with SIVH-associated PHVD, ventricles enlarged at an approximately linear rate over PMA, with faster expansion in infants with higher composite hemorrhage burden. Composite score was a better predictor of dilation size and mortality. Ventricular “recoil” was minimal, supporting that ventricular size often remains near peak dimensions over the observed course. Health sciences/Diseases/Neurological disorders/Paediatric neurological disorders Health sciences/Biomarkers/Predictive markers Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1. Introduction Severe intraventricular hemorrhage (SIVH), which includes IVH grades 3 and 4 has a reported global incidence range in neonates < 28 weeks gestation of 5–52% (Europe: 5–52%; North America: 8–22%; Asia: 5–36%; Oceania: 8–13%). 1 The California incidence in neonates < 32 weeks gestation was 5.9% in 2015. 2 A 2025 North Carolina study reported an incidence of 9.3% based on a quality improvement study. 3 The total mortality rate in SIVH was 21.3% in grade 3 and 36.1% in grade 4, as shown by a study between 2005 and 2014 using data from the New York and Nebraska State Inpatient Databases. 4 A common complication of SIVH is post-hemorrhagic ventricular dilation (PHVD) in approximately 40–60% of infants with Grade 3 intraventricular hemorrhage (IVH) and 70–80% of those with Grade 4 IVH.5 As the name describes, PHVD is a progressive expansion of the ventricles which can lead to hydrocephalus and require neurosurgical intervention in approximately 30% of all SIVH. 6 Levene first developed growth-charts for ventricular growth in neonates, later refined by Brouwer, and have been used to establish threshold values for neurosurgical intervention. 7 , 8 However, two aspects of PHVD remain under-characterized; 1.) The rate at which ventricles expand in response to SIVH, 2.) characteristics and differences in early vs. late PHVD. These temporal dynamics could aid in earlier prediction of clinical deterioration and guide intervention strategies. It may also be used as a reference to validate effectiveness in emerging PHVD interventions. As such, this study aims to quantify the rate and magnitude of ventricular expansion in neonates with PHVD following SIVH who did not receive neurosurgical intervention. The purpose of this study is to track PHVD anterior horn width and ventricular index throughout the NICU period. This exploratory study may be used to better understand PHVD, and it may be used as a reference historical control for future treatment trials. 2. Methods 2.1 Chart Review This is a retrospective cohort study to generate an average trend for PHVD from SIVH using a chart review of University Hospital NICU patients suffering from SIVH and PHVD between 01/2010 and 01/2025. Flow diagram shown in Fig. 1. We generated a cohort of 43 neonates meeting inclusion criteria using EPIC EMR using ICD10 code P52 or P52.3 and search terms "Intraventricular hemorrhage", "IVH", "germinal matrix hemorrhage", "periventricular hemorrhage". Patients were then screened as shown in Chart 1. Exclusion criteria was a maximum IVH grade of 1 or 2. One patient with IVH grade 3 or 4 was excluded because midline birth defects within the CNS, making measurements difficult. ##### Chart 1: Flow Diagram detailing the chart review process 2.2 Cranial Ultrasound Measurements The 43-patient cohort generated 347 unique Cranial ultrasounds included in analysis​ for an average of 7–8 ultrasounds per patient. IVH was typically monitored for 51 days. GG and NM quantified ventricle dilation using ventricular index (VI), anterior horn width (AHW) and PACS-based measurement tools. Ultrasound methods were taken from AIUM practice parameters and reference values were derived from published norms 9 , 8 , 10 , 7 The radiologist/sonologist physician, HA, reviewed and approved each measurement. A sample of how ventricles were measured and documented is in Fig. 1. Data was then compiled and analyzed by statisticians MLC and EK. In the 5 cases where neurosurgical interventions were performed, we used cranial ultrasounds up until the neonate/infant received the first neurosurgical intervention or lumbar puncture. Cranial ultrasounds post-neurosurgical intervention or post-lumbar puncture were not included in data analysis. ######### Figure 1: Sample patient showing serial cranial ultrasounds measuring ventricular index and anterior horn width from day of life 0 to 5 months of life. Accompanying chart (bottom left) is an example of how patient data was compiled and then plotted on graph (bottom right) 2.3 Data Analysis All analyses were conducted using R (version 4.5.1). The data analysis for this study primarily focuses on understanding the temporal dynamics of ventricular expansion in neonates with severe intraventricular hemorrhage (SIVH), utilizing Postmenstrual Age (PMA) for consistent comparison across patients. PMA is defined as the gestational age (GA) plus the days of life (DOL), which helps normalize comparisons of ventricle sizes, as a lateral ventricle is known to increase by 5.5% for each gestational week. 11 Left and right VI/AHW measurements were averaged at each ultrasound to generate a single bilateral value per time point. We did not use the maximum measurement nor did we use side-specific measures. 3. Results 3.1 Population Demographics Population demographics are shown in Chart 2. Retrospective Cohort N = 43 Gender Female 21 (48.8%) Male 22 (51.2%) Race Black/African American 31 (72.1%) Hispanic 9 (20.9%) Other/Unknown 3 (6.9%) Gestational Age 22 + − 27 36 (83.7%) 28 + − 31 4 (9.3%) >32+ 3 (6.9%) Average Birth Weight (g) 895 Average Maternal Age (years) n = 41 29.12 Average DOL IVH detected 4.8 (+/- 7.3) Average Number of HUS 7.9 (+/- 4.6) Average days monitored with HUS 47.4 (+/- 51.3) Total receiving invasive intervention 5 (11.6%) Total deceased 16 (37.2%) # Grade 3 on Left 19 # Grade 3 on Right 14 # Grade 4 on Left 16 # Grade 4 on Right 16 Chart 2: Population Demographics 3.2 Overall Growth Trends for Severe IVH All 43 patients with SIVH were included to produce a general trend of AHW and VI size in relation to PMA. Both AHW and VI had significant volume growth with increasing PMA as shown in Fig. 2. The average age-related change per day for AHW and VI was 0.105 mm (95% CI: 0.087–0.124, p < 0.001); and 0.105 mm (95% CI: 0.092–0.118, p < 0.001), respectively. ########### N = 43 Rate (mm/day) 95% CI Average VI Expansion 0.105 0.92 − 0.118 Average AHW Expansion 0.105 0.087–0.124 Figure 2: Linear Regression model of post-hemorrhagic ventricular dilatation growth using ventricular index (Top) in relation to postmenstrual days. Approximations of normal ventricular index (green) and p97 + 4mm (red) for context. Linear Regression model of post-hemorrhagic ventricular dilatation growth using anterior horn width (middle) in relation to postmenstrual days with approximations of normal AHW (green) and 10mm (red) for context. Chart (bottom) showing cohort average expansion rate (mm/day). 3.3 Composite Score and Total Hemorrhage Burden vs Classical Scoring A linear regression model was used to examine whether the rate of AHW growth or VI growth correlated with hemorrhage severity (IVH grade 3 vs 4). The interaction between postmenstrual days and highest IVH grade was not statistically significant (p = 0.84 and p = 0.21, respectively) indicating that AHW growth rate and VI growth rate did not differ across IVH severity levels. Although patients were categorized by IVH severity, the extent of hemorrhage within each grade varied substantially. Some patients demonstrated bilateral grade 4 IVH, whereas others had only unilateral involvement. Therefore, IVH grade alone did not fully capture the total hemorrhage burden. To provide a more accurate representation of hemorrhage extent, the right and left IVH grades were combined to create a composite measure of hemorrhage burden. This composite IVH ranged from 3–8 and logistic regression indicated a positive association between this composite IVH and the likelihood of death as described in Mortality Risk Factors section below. Thus, another linear regression model was used to examine the relationship between the rate of AHW growth and VI growth with composite IVH grade. Once the composite IVH grade was binned into two categories: low (composite IVH from 3–6) and high (composite IVH from 7–8), the results were statistically significant (p = 0.013 and p = 0.025 respectively). After stratifying patients by composite scoring and total hemorrhage burden, a pattern emerged indicating that those in higher IVH categories exhibited faster rates of AHW and VI growth compared to patients in lower IVH categories as shown in figure Fig. 3 . While the interaction between PMA and composite IVH grade did not reach conventional statistical significance (p = 0.146 and p = 0.307, respectively), the results suggest a consistent growth trajectory of AHW and VI across different IVH severity levels. ####### Average Ventricular Index Average Anterior Horn Width N = 43 Rate (mm/day) 95% CI Rate (mm/day) 95% CI High Composite IVH 0.126 0.105 - 0.148 0.139 0.109 - 0.169 Low Composite IVH 0.096 0.080 - 0.112 0.091 0.069 - 0.114 Figure 3: Ventricular index and anterior horn width growth trends were divided in high and low composite scoring. High composite score included a total hemorrhage burden of 7-8, and low composite score included total hemorrhage burden of 3-6. 3.4 Ventricular Growth Rate/Velocity Trends This study tracked ventricular growth rate for ventricular index and anterior horn width as shown in Fig. 4. “Growth Rate” can be considered as the “velocity” of ventricular growth and the “change” in size from one cranial ultrasound to the next. “Post-hemorrhage day” was used to standardize growth velocity in relation to when the hemorrhage first occurred in each patient. For example, the day of the first cranial ultrasound showing hemorrhage is labeled post-hemorrhage day 0 for patient #1, and may be postmenstrual age 26 and day of life 3; while for patient #2 post-hemorrhage day 0 may be postmenstrual age 28 and day of life 5. The average VI rate remains approximately stable over time and never goes below zero. Therefore VI is constantly expanding during time of monitoring. Meaning, the ventricles do not recoil or contract over time and the maximum VI is where the ventricles will remain. However, the AHW velocity at approximately post-hemorrhage day 100 shows minor recoil of the ventricles. ######### N = 43 Rate (mm/day 2) 95% CI Average VI Growth Velocity -0.0016 -0.0036–0.0004 Average AHW Growth Velocity -0.0050 -0.0084 - -0.0015 Figure 4: Ventricular Index and Anterior Horn Width growth rate/velocity plotted against post-hemorrhage days. (Number of days after the hemorrhage was first identified.) 3.5 Mortality Risk Factors: VI and AHW growth rate are predictive of mortality. Linear models were used to examine how ventricular growth dynamics changed over time following hemorrhage, using patient status (Alive vs. Deceased) as a grouping factor as shown in Fig. 5 . For the VI, growth rate remained stable over time in patients who survived (β = -0.0003, p = 0.79), whereas patients who ultimately died had a significantly higher baseline growth rate (β = 0.731, p < 0.001) that declined quickly over time (interaction: β = -0.064, p < 0.001). A similar pattern was observed for the anterior horn width (AHW). Survivors showed no significant change in growth rate with time (β = -0.0019, p = 0.235), while deceased patients exhibited a substantially higher initial growth rate (β = 1.62, p < 0.001) that decreased significantly as time progressed (interaction: β = -0.134, p < 0.001). Together, these findings indicate that deceased patients demonstrated accelerated early ventricular expansion—both in overall ventricular size and anterior horn width—that diminished over time, suggesting distinct temporal dynamics of ventricular growth between outcome groups. ####### Average Ventricular Index Average Anterior Horn Width Status Rate (mm/day 2 ) 95% CI Rate (mm/day 2 ) 95% CI Alive -0.0003 -0.0022 - 0.0017 -0.0019 -0.0052 - -0.0013 Deceased -0.064 -0.095 - -0.034 -0.137 -0.186 - -0.087 Figure 5: Growth rate for ventricular index (top) and anterior horn width (middle) for alive and deceased patients compared against days post hemorrhage. Deceased trends (hash marks) show a higher initial growth velocity that drastically trends downward. Alive trends (solid line) show little change in growth rate. Chart (bottom) shows exact figures for each trend. Gestational Age Compared to neonates born 20 + to 25 weeks gestational age; 25 + to 30 weeks had a survival OR of 3.97 (p = 0.06). Weight Compared to neonates 1000g had a survival OR of 5.6 (p = 0.12). IVH Composite Score The association between total IVH severity and survival status was evaluated using logistic regression. The high composite group showed higher odds of mortality compared to the low composite group (OR 4.79; p = 0.024). Furthermore, increasing composite score was associated with higher odds of death (OR 1.51 per point increase; p = 0.07) shown in Fig. 6, considered clinically significant though not reaching conventional statistical significance. In a descriptive comparison, total IVH scores were significantly higher among non-survivors compared with survivors (median 7 [IQR 6–8] vs 6 [IQR 4–7], Wilcoxon rank-sum p = 0.034). These findings are consistent with a trend toward increased IVH burden being associated with decreased survival in this cohort. IVH grade was predictive of survival only when using composite scoring (p = 0.034) as shown in figure below. IVH grade was not predictive of survival when using the "highest grade" approach. This supports the validity of using composite score rather than “highest grade”. ########## Figure 6: Survival percentage compared with Intraventricular Hemorrhage Composite scoring used to produce a total intraventricular hemorrhage burden ranging from 3 to 8. Graph shows a trend of decreasing survival with each additional point of total hemorrhage burden. No statistical significance : APGAR at 1 minute, APGAR at 5 minutes, Maternal Age, Gender, Race 4. Discussion In this retrospective cohort of 43 neonates with severe intraventricular hemorrhage (SIVH) complicated by post-hemorrhagic ventricular dilatation (PHVD), we quantified the temporal course of ventricular enlargement using serial cranial ultrasound measurements of ventricular index (VI) and anterior horn width (AHW). Three findings are most salient. First, ventricular enlargement progressed in an approximately linear fashion over postmenstrual age (PMA), with mean expansion rates of 0.105 mm/day for both VI and AHW across the cohort. Second, conventional categorization by “highest” IVH grade (3 vs 4) did not meaningfully stratify growth trajectories, whereas a simple bilateral composite hemorrhage-burden score did: infants in the high composite group (7–8) demonstrated faster expansion than those in the low composite group (3–6). Third, late ventricular “recoil” was uncommon: VI expansion was effectively monotonic across follow-up, and AHW exhibited only minor late decreases. Together, these findings support the concept that hemorrhage burden (including laterality) and early growth dynamics may capture clinically relevant risk more effectively than the traditional single-grade approach. 4.1 Growth trajectory and implications for monitoring Current PHVD surveillance relies heavily on serial ultrasound metrics (VI, AHW, and often thalamo-occipital distance) anchored to gestational-age–specific normative curves. Large datasets establishing reference values for VI/AHW across gestation (including very preterm infants) have enabled percentile-based monitoring and commonly used thresholds. 8 In that context, a practical contribution of the present work is providing an empiric “average” expansion rate in a real-world NICU cohort with predominantly conservative management. The observed rate (~ 0.105 mm/day) offers a simple way to conceptualize the tempo of progression: a 4 mm increase—on the order of commonly used “higher-threshold” escalation criteria in some protocols—would occur over roughly 38 days at this average pace, acknowledging substantial inter-patient variability. Relatedly, the ELVIS randomized trial operationalized “low” versus “high” intervention thresholds using combinations of VI and AHW cutoffs (e.g., VI > p97 with AHW > 6 mm vs VI > p97 + 4 mm with AHW > 10 mm), reflecting the field’s emphasis on ultrasound-based, standardized triggers. 12 Although our study was not designed to evaluate treatment thresholds, quantifying expected time-dependent change may help clinicians and investigators interpret serial measurements (e.g., distinguishing steady progression from unusually rapid early expansion). It may also serve as a historical control for future study. 4.2 Composite hemorrhage burden versus “highest grade” A recurring limitation of the traditional Papile-style approach in research is that “highest grade” collapses meaningful heterogeneity—particularly laterality and the distribution of hemorrhage—into a single label. In our cohort, summing left and right IVH grades into a composite score (range 3–8) better captured hemorrhage burden and revealed clinically relevant separation in both mortality risk and ventricular growth dynamics. This is directionally consistent with prior literature indicating that bilateral involvement—especially for severe IVH/periventricular hemorrhagic infarction—can carry worse neurodevelopmental prognosis compared with unilateral injury. 13 It also aligns with broader efforts to move beyond a single ordinal grade toward laterality-aware or more granular scoring systems that improve outcome prediction relative to Papile grading alone. 14 Importantly, the composite score you use is intentionally simple: it does not require specialized software or volumetric clot segmentation, and it can be abstracted from routine radiology reporting. In settings where volumetric or MRI-based quantification is impractical, this type of composite measure may provide a feasible bridge between “highest grade” and more complex hemorrhage-burden metrics, and may be a candidate covariate for future PHVD prognostic models and interventional trials. 4.3 Early growth velocity and mortality signal Beyond overall size trajectories, we observed distinct time-dependent patterns when examining growth velocity in relation to survival: non-survivors demonstrated markedly higher early growth velocity that attenuated over time, whereas survivors exhibited comparatively stable, near-flat velocity trends. We interpret this cautiously as an association rather than a causal relationship; accelerated early expansion may be a marker of more extensive hemorrhage, greater inflammatory obstruction to CSF pathways, reduced compliance, systemic illness severity, or unmeasured comorbid factors. Nevertheless, these findings raise the possibility that early post-hemorrhage growth velocity could be an actionable signal for risk stratification alongside absolute VI/AHW values—particularly in the initial weeks when decisions around escalation, temporizing CSF diversion, or transfer may be under consideration. 4.4 Minimal late “recoil” A motivating premise of this study was whether ventricular size meaningfully decreases as intraventricular blood products are resorbed and CSF circulation normalizes. In our cohort, late shrinkage was uncommon: VI remained effectively monotonic and AHW showed only minor late negative velocity. This pattern contrasts with reports that a subset of infants may experience spontaneous resolution of PHVD, underscoring that the “natural history” is heterogeneous and likely depends on case mix, severity, and follow-up duration. 15 Several non-mutually exclusive explanations may account for the limited recoil observed here: persistent impairment of CSF resorption from inflammatory/fibrotic sequelae after IVH, evolving ventricular compliance changes, and the confounding effect of parenchymal injury (e.g., periventricular hemorrhagic infarction) where subsequent encephalomalacia can visually “merge” with ventricular CSF spaces and inflate linear measures. From a practical standpoint, these findings support the clinical intuition that, for many infants with SIVH-associated PHVD, ventricles may remain near peak dimensions over the observed NICU course—reinforcing the value of early monitoring and timely decisions about escalation rather than expecting reliable late spontaneous contraction. 4.5 Limitations This study has several limitations that should temper inference. As stated, left and right VI/AHW measurements were averaged at each ultrasound to generate a single bilateral value per time point. Averaging may reduce sensitivity to asymmetric dilation; however, it reduces measurement noise and supports cohort-level trajectories. Sensitivity analyses using the maximum side should be considered. Furthermore, the cohort size (N = 43) limited power for subgroup analyses and increased susceptibility to residual confounding. Comorbidities were not standardized in this study and there was a wide range of other medical issues present in the neonates. Given the small cohort, we often favored inclusivity despite the wide range of other issues. Measurement was challenging when ventricles were filled with echogenic blood products; in these cases, VI/AHW could be difficult to define and “best estimate” measurements may introduce error. Additionally, late parenchymal cavitation/encephalomalacia may artifactually increase VI/AHW by connecting cystic spaces with the ventricle, complicating interpretation of late measurements and potentially biasing against observing recoil. Comorbidities and illness severity markers were not standardized, and the cohort included infants with a wide range of concurrent medical issues, which may confound associations between ventricular dynamics and outcomes. 4.6 Future directions Future work should (1) validate this laterality-aware composite score against established laterality-based scoring systems and, where feasible, volumetric hemorrhage measures; (2) test whether early growth velocity improves prediction of outcomes beyond absolute VI/AHW thresholds; and (3) extend follow-up beyond the NICU course to determine whether recoil occurs later and how ultrasound-based trajectories relate to MRI injury patterns and longer-term neurodevelopmental endpoints. Contemporary evidence suggests that earlier, ultrasound-guided approaches to PHVD management may be associated with improved developmental outcomes compared with delayed approaches, supporting the clinical relevance of refined early-risk stratification. Conclusion In neonates with SIVH-associated PHVD, ventricular enlargement progressed at an approximately linear rate over PMA with minimal late recoil in this cohort. A simple bilateral composite hemorrhage-burden score better stratified ventricular growth and mortality risk than the traditional “highest grade” approach, supporting the inclusion of laterality-aware hemorrhage metrics in future prognostic models and PHVD trials. Declarations Conflict of Interest Statement : The authors declare that they have no conflicts of interest and no competing financial interests related to this work. Funding: This work received no financial support. References Siffel C, Kistler KD, Sarda SP. Global incidence of intraventricular hemorrhage among extremely preterm infants: a systematic literature review. J Perinat Med 2021;49:1017–26. Handley SC, Passarella M, Lee HC, Lorch SA. Incidence trends and risk factor variation in severe intraventricular hemorrhage across a population based cohort. J Pediatr 2018;200:24-29.e3. Peltola SD, Akpan US, Tumin D, Huffman P. Quality improvement initiative to decrease severe intraventricular hemorrhage rates in preterm infants by implementation of a care bundle. J Perinatol 2025. https://doi.org/10.1038/s41372-025-02274-5. Han RH, McKinnon A, CreveCoeur TS, Baksh BS, Mathur AM, Smyser CD, et al. Predictors of mortality for preterm infants with intraventricular hemorrhage: a population-based study. Childs Nerv Syst 2018;34:2203–13. Volpe, J. J. (2018). Neurology of the Newborn (6th ed.). Philadelphia, PA: Elsevier. Limbrick DD, Mathur A, Johnston JM, Munro R, Sagar J, Inder T, et al. Neurosurgical treatment of progressive posthemorrhagic ventricular dilation in preterm infants: a 10-year single-institution study: Clinical article. J Neurosurg Pediatr 2010;6:224–30. Machado-Rivas, F., Gandhi, J., Choi, J. J., Velasco-Annis, C., Afacan, O., Warfield, S. K., Gholipour, A., & Jaimes, C. (2022). Normal growth, sexual dimorphism, and lateral asymmetries at fetal brain MRI. Radiology, 303(1), 162–170. https://doi.org/10.1148/radiol.211222 Chart 1 Chart 1 is available in the Supplementary Files section. Additional Declarations There is NO conflict of interest to disclose. Supplementary Files IVHFlowChart.jpg Chart 1: Flow Diagram detailing the chart review process Cite Share Download PDF Status: Under Review Version 1 posted Review # 1 received at journal 12 Apr, 2026 Reviewer # 1 agreed at journal 06 Apr, 2026 Reviewers invited by journal 27 Jan, 2026 Submission checks completed at journal 23 Jan, 2026 First submitted to journal 21 Jan, 2026 Unknown event 20 Jan, 2026 Editor assigned by journal 15 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8613373","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":581333491,"identity":"a8b745f6-0d83-46e2-9a43-a4e7318cfc06","order_by":0,"name":"Garrett Gianneschi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA00lEQVRIiWNgGAWjYDACCQbmBwkVCD5jAxFa2Aw+nGFg4CFFC4PkzDZStMhHt18w5p13L3E//+JjH38w2MhuOEBAi+GdMwWPebcVJ/ZIPEuezcOQZkxYy4ycBGPebQlALWeMmRkYDicSpUWadw5Iy/nPjD8Y/hPWIi+RfkByZgNQC38PMzAMDhDWYiBzBhjIxxKMe26wGTPzGCQbzyRoy+z2xw8SahJk2/sPP2b8UWEn20fQlgM8BhCWRAKIS0A52JYG9gcQFj8h00fBKBgFo2DEAgAeSUelHoWz5wAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-3352-1446","institution":"Rutgers New Jersey Medical School","correspondingAuthor":true,"prefix":"","firstName":"Garrett","middleName":"","lastName":"Gianneschi","suffix":""},{"id":581333492,"identity":"08ffe4f4-2232-4890-9ee7-ba7bc9582c13","order_by":1,"name":"Michael Christian","email":"","orcid":"","institution":"Rocky Vista University College of Osteopathic Medicine","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Christian","suffix":""},{"id":581333493,"identity":"78ac4931-fe49-40aa-aea5-45043fb61584","order_by":2,"name":"Hira Arif","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Hira","middleName":"","lastName":"Arif","suffix":""},{"id":581333494,"identity":"7378be8f-6e5a-4106-a433-f0ba2871e562","order_by":3,"name":"Navina Magesh-Kumar","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Navina","middleName":"","lastName":"Magesh-Kumar","suffix":""},{"id":581333495,"identity":"52394efa-f8ce-4680-af1a-20015a70668a","order_by":4,"name":"Onajovwe Fofah","email":"","orcid":"https://orcid.org/0000-0001-8883-5341","institution":"Rutgers-NJMS","correspondingAuthor":false,"prefix":"","firstName":"Onajovwe","middleName":"","lastName":"Fofah","suffix":""}],"badges":[],"createdAt":"2026-01-15 20:00:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8613373/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8613373/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101439003,"identity":"1a966f32-ebc9-40a2-a5d9-52bb83b447ac","added_by":"auto","created_at":"2026-01-29 16:41:41","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":61442,"visible":true,"origin":"","legend":"\u003cp\u003eSample patient showing serial cranial ultrasounds measuring ventricular index and anterior horn width from day of life 0 to 5 months of life. Accompanying chart (bottom left) is an example of how patient data was compiled and then plotted on graph (bottom right)\u003c/p\u003e","description":"","filename":"IVHSamplepatientworkflow.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8613373/v1/835043687c599987625839cf.jpg"},{"id":101439008,"identity":"78c707eb-926a-4864-b5e8-7210371877b1","added_by":"auto","created_at":"2026-01-29 16:41:43","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":484954,"visible":true,"origin":"","legend":"\u003cp\u003eLinear Regression model of post-hemorrhagic ventricular dilatation growth using ventricular index (Top) in relation to postmenstrual days. Approximations of normal ventricular index (green) and p97+4mm (red) for context. Linear Regression model of post-hemorrhagic ventricular dilatation growth using anterior horn width (middle) in relation to postmenstrual days with approximations of normal AHW (green) and 10mm (red) for context. Chart (bottom) showing cohort average expansion rate (mm/day).\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8613373/v1/20efc6e0f0e0f44b1b11f6db.jpg"},{"id":101751236,"identity":"1e9c3a01-5bef-4252-816b-7e7bda99aabe","added_by":"auto","created_at":"2026-02-03 10:18:33","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":460589,"visible":true,"origin":"","legend":"\u003cp\u003eVentricular index and anterior horn width growth trends were divided in high and low composite scoring. High composite score included a total hemorrhage burden of 7-8, and low composite score included total hemorrhage burden of 3-6.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8613373/v1/3fb449ab7bf209e485925cfb.jpg"},{"id":101439004,"identity":"4fe0db82-4258-4130-a8af-836d2b1cf642","added_by":"auto","created_at":"2026-01-29 16:41:41","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":98597,"visible":true,"origin":"","legend":"\u003cp\u003eVentricular growth rate/velocity plotted against post-hemorrhage days. (Number of days after the hemorrhage was first identified.)\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8613373/v1/078cf33ac7152f496f81238b.jpg"},{"id":101439002,"identity":"4555e5ad-3efd-4701-be3a-5cdd6a5f6121","added_by":"auto","created_at":"2026-01-29 16:41:41","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":101180,"visible":true,"origin":"","legend":"\u003cp\u003eGrowth rate for ventricular index (top) and anterior horn width (middle) for alive and deceased patients compared against days post hemorrhage. Deceased trends (hash marks) show a higher initial growth velocity that drastically trends downward. Alive trends (solid line) show little change in growth rate. Chart (bottom) shows exact figures for each trend.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8613373/v1/21eecca307d3b0c2a0b7d886.jpg"},{"id":101439006,"identity":"8f4932a7-78cb-4834-8d2d-f421e9861364","added_by":"auto","created_at":"2026-01-29 16:41:42","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":18859,"visible":true,"origin":"","legend":"\u003cp\u003eSurvival percentage compared with Intraventricular Hemorrhage Composite scoring used to produce a total intraventricular hemorrhage burden ranging from 3 to 8. Graph shows a trend of decreasing survival with each additional point of total hemorrhage burden.\u003c/p\u003e","description":"","filename":"Compositescorewsurvivalpercentage.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8613373/v1/150b14e08772d3e356622a77.jpg"},{"id":102298520,"identity":"be4c94fb-5ad2-4b84-bd32-72da0bef2652","added_by":"auto","created_at":"2026-02-10 10:42:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1967641,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8613373/v1/48f8f964-258b-4192-baed-3a2dadc6b796.pdf"},{"id":101439001,"identity":"43040f1d-2fd1-450e-a783-7daea1328054","added_by":"auto","created_at":"2026-01-29 16:41:41","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":48320,"visible":true,"origin":"","legend":"\u003cp\u003eChart 1: Flow Diagram detailing the chart review process\u003c/p\u003e","description":"","filename":"IVHFlowChart.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8613373/v1/bfc5b42c6c9398dd9914e576.jpg"}],"financialInterests":"There is \u003cb\u003eNO\u003c/b\u003e conflict of interest to disclose.","formattedTitle":"Composite Scoring and the Natural Course of Post-Hemorrhagic Ventricular Dilation in Neonates with Severe Intraventricular Hemorrhage","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eSevere intraventricular hemorrhage (SIVH), which includes IVH grades 3 and 4 has a reported global incidence range in neonates\u0026thinsp;\u0026lt;\u0026thinsp;28 weeks gestation of 5\u0026ndash;52% (Europe: 5\u0026ndash;52%; North America: 8\u0026ndash;22%; Asia: 5\u0026ndash;36%; Oceania: 8\u0026ndash;13%).\u003csup\u003e1\u003c/sup\u003e The California incidence in neonates\u0026thinsp;\u0026lt;\u0026thinsp;32 weeks gestation was 5.9% in 2015.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e A 2025 North Carolina study reported an incidence of 9.3% based on a quality improvement study.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e The total mortality rate in SIVH was 21.3% in grade 3 and 36.1% in grade 4, as shown by a study between 2005 and 2014 using data from the New York and Nebraska State Inpatient Databases.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eA common complication of SIVH is post-hemorrhagic ventricular dilation (PHVD) in approximately 40\u0026ndash;60% of infants with Grade 3 intraventricular hemorrhage (IVH) and 70\u0026ndash;80% of those with Grade 4 IVH.5 As the name describes, PHVD is a progressive expansion of the ventricles which can lead to hydrocephalus and require neurosurgical intervention in approximately 30% of all SIVH.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eLevene first developed growth-charts for ventricular growth in neonates, later refined by Brouwer, and have been used to establish threshold values for neurosurgical intervention.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e However, two aspects of PHVD remain under-characterized; 1.) The rate at which ventricles expand in response to SIVH, 2.) characteristics and differences in early vs. late PHVD. These temporal dynamics could aid in earlier prediction of clinical deterioration and guide intervention strategies. It may also be used as a reference to validate effectiveness in emerging PHVD interventions. As such, this study aims to quantify the rate and magnitude of ventricular expansion in neonates with PHVD following SIVH who did not receive neurosurgical intervention. The purpose of this study is to track PHVD anterior horn width and ventricular index throughout the NICU period. This exploratory study may be used to better understand PHVD, and it may be used as a reference historical control for future treatment trials.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Chart Review\u003c/h2\u003e \u003cp\u003eThis is a retrospective cohort study to generate an average trend for PHVD from SIVH using a chart review of University Hospital NICU patients suffering from SIVH and PHVD between 01/2010 and 01/2025. Flow diagram shown in Fig.\u0026nbsp;1. We generated a cohort of 43 neonates meeting inclusion criteria using EPIC EMR using ICD10 code P52 or P52.3 and search terms \"Intraventricular hemorrhage\", \"IVH\", \"germinal matrix hemorrhage\", \"periventricular hemorrhage\". Patients were then screened as shown in Chart 1. Exclusion criteria was a maximum IVH grade of 1 or 2. One patient with IVH grade 3 or 4 was excluded because midline birth defects within the CNS, making measurements difficult.\u003c/p\u003e \u003cp\u003e#####\u003c/p\u003e \u003cp\u003eChart 1: Flow Diagram detailing the chart review process\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Cranial Ultrasound Measurements\u003c/h2\u003e \u003cp\u003eThe 43-patient cohort generated 347 unique Cranial ultrasounds included in analysis​ for an average of 7\u0026ndash;8 ultrasounds per patient. IVH was typically monitored for 51 days. GG and NM quantified ventricle dilation using ventricular index (VI), anterior horn width (AHW) and PACS-based measurement tools. Ultrasound methods were taken from AIUM practice parameters and reference values were derived from published norms\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e The radiologist/sonologist physician, HA, reviewed and approved each measurement. A sample of how ventricles were measured and documented is in Fig.\u0026nbsp;1. Data was then compiled and analyzed by statisticians MLC and EK.\u003c/p\u003e \u003cp\u003eIn the 5 cases where neurosurgical interventions were performed, we used cranial ultrasounds up until the neonate/infant received the first neurosurgical intervention or lumbar puncture. Cranial ultrasounds post-neurosurgical intervention or post-lumbar puncture were not included in data analysis.\u003c/p\u003e \u003cp\u003e#########\u003c/p\u003e \u003cp\u003eFigure 1: Sample patient showing serial cranial ultrasounds measuring ventricular index and anterior horn width from day of life 0 to 5 months of life. Accompanying chart (bottom left) is an example of how patient data was compiled and then plotted on graph (bottom right)\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Data Analysis\u003c/h2\u003e \u003cp\u003eAll analyses were conducted using R (version 4.5.1). The data analysis for this study primarily focuses on understanding the temporal dynamics of ventricular expansion in neonates with severe intraventricular hemorrhage (SIVH), utilizing Postmenstrual Age (PMA) for consistent comparison across patients. PMA is defined as the gestational age (GA) plus the days of life (DOL), which helps normalize comparisons of ventricle sizes, as a lateral ventricle is known to increase by 5.5% for each gestational week.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eLeft and right VI/AHW measurements were averaged at each ultrasound to generate a single bilateral value per time point. We did not use the maximum measurement nor did we use side-specific measures.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Population Demographics\u003c/h2\u003e \u003cp\u003ePopulation demographics are shown in Chart 2.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetrospective Cohort\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;43\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (48.8%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (51.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eRace\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlack/African American\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (72.1%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (20.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther/Unknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGestational Age\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e22\u0026thinsp;+\u0026thinsp;\u0026minus;\u0026thinsp;27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36 (83.7%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e28\u0026thinsp;+\u0026thinsp;\u0026minus;\u0026thinsp;31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (9.3%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;32+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage Birth Weight (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e895\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage Maternal Age (years) n\u0026thinsp;=\u0026thinsp;41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.12\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage DOL IVH detected\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.8 (+/- 7.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage Number of HUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.9 (+/- 4.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage days monitored with HUS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47.4 (+/- 51.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal receiving invasive intervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (11.6%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal deceased\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (37.2%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e# Grade 3 on Left\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e# Grade 3 on Right\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e# Grade 4 on Left\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e# Grade 4 on Right\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cp\u003eChart 2: Population Demographics\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Overall Growth Trends for Severe IVH\u003c/h2\u003e \u003cp\u003eAll 43 patients with SIVH were included to produce a general trend of AHW and VI size in relation to PMA. Both AHW and VI had significant volume growth with increasing PMA as shown in Fig.\u0026nbsp;2. The average age-related change per day for AHW and VI was 0.105 mm (95% CI: 0.087\u0026ndash;0.124, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001); and 0.105 mm (95% CI: 0.092\u0026ndash;0.118, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), respectively.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e ###########\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;43\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRate (mm/day)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95% CI\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage VI Expansion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.92\u0026thinsp;\u0026minus;\u0026thinsp;0.118\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAverage AHW Expansion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.087\u0026ndash;0.124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFigure 2: Linear Regression model of post-hemorrhagic ventricular dilatation growth using ventricular index (Top) in relation to postmenstrual days. Approximations of normal ventricular index (green) and p97\u0026thinsp;+\u0026thinsp;4mm (red) for context. Linear Regression model of post-hemorrhagic ventricular dilatation growth using anterior horn width (middle) in relation to postmenstrual days with approximations of normal AHW (green) and 10mm (red) for context. Chart (bottom) showing cohort average expansion rate (mm/day).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Composite Score and Total Hemorrhage Burden vs Classical Scoring\u003c/h2\u003e \u003cp\u003eA linear regression model was used to examine whether the rate of AHW growth or VI growth correlated with hemorrhage severity (IVH grade 3 vs 4). The interaction between postmenstrual days and highest IVH grade was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.84 and p\u0026thinsp;=\u0026thinsp;0.21, respectively) indicating that AHW growth rate and VI growth rate did not differ across IVH severity levels.\u003c/p\u003e \u003cp\u003eAlthough patients were categorized by IVH severity, the extent of hemorrhage within each grade varied substantially. Some patients demonstrated bilateral grade 4 IVH, whereas others had only unilateral involvement. Therefore, IVH grade alone did not fully capture the total hemorrhage burden. To provide a more accurate representation of hemorrhage extent, the right and left IVH grades were combined to create a composite measure of hemorrhage burden. This composite IVH ranged from 3\u0026ndash;8 and logistic regression indicated a positive association between this composite IVH and the likelihood of death as described in Mortality Risk Factors section below.\u003c/p\u003e \u003cp\u003eThus, another linear regression model was used to examine the relationship between the rate of AHW growth and VI growth with composite IVH grade. Once the composite IVH grade was binned into two categories: low (composite IVH from 3\u0026ndash;6) and high (composite IVH from 7\u0026ndash;8), the results were statistically significant (p\u0026thinsp;=\u0026thinsp;0.013 and p\u0026thinsp;=\u0026thinsp;0.025 respectively). After stratifying patients by composite scoring and total hemorrhage burden, a pattern emerged indicating that those in higher IVH categories exhibited faster rates of AHW and VI growth compared to patients in lower IVH categories as shown in figure Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e3\u003c/span\u003e. While the interaction between PMA and composite IVH grade did not reach conventional statistical significance (p\u0026thinsp;=\u0026thinsp;0.146 and p\u0026thinsp;=\u0026thinsp;0.307, respectively), the results suggest a consistent growth trajectory of AHW and VI across different IVH severity levels.\u003c/p\u003e\u003cp\u003e#######\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"636\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.4151%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 36.1635%;\"\u003e\n \u003cp\u003eAverage Ventricular Index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 37.4214%;\"\u003e\n \u003cp\u003eAverage Anterior Horn Width\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.4151%;\"\u003e\n \u003cp\u003eN = 43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0252%;\"\u003e\n \u003cp\u003eRate (mm/day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.1384%;\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.8679%;\"\u003e\n \u003cp\u003eRate (mm/day)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.5535%;\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.4151%;\"\u003e\n \u003cp\u003eHigh Composite IVH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0252%;\"\u003e\n \u003cp\u003e0.126\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.1384%;\"\u003e\n \u003cp\u003e0.105 - 0.148\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.8679%;\"\u003e\n \u003cp\u003e0.139\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.5535%;\"\u003e\n \u003cp\u003e0.109 - 0.169\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 26.4151%;\"\u003e\n \u003cp\u003eLow Composite IVH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.0252%;\"\u003e\n \u003cp\u003e0.096\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.1384%;\"\u003e\n \u003cp\u003e0.080 - 0.112\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.8679%;\"\u003e\n \u003cp\u003e0.091\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 18.5535%;\"\u003e\n \u003cp\u003e0.069 - 0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eFigure 3: Ventricular index and anterior horn width growth trends were divided in high and low composite scoring. High composite score included a total hemorrhage burden of 7-8, and low composite score included total hemorrhage burden of 3-6.\u003c/p\u003e\n\u003ch2\u003e3.4 Ventricular Growth Rate/Velocity Trends\u003c/h2\u003e\n\u003cp\u003eThis study tracked ventricular growth rate for ventricular index and anterior horn width as shown in Fig.\u0026nbsp;4. \u0026ldquo;Growth Rate\u0026rdquo; can be considered as the \u0026ldquo;velocity\u0026rdquo; of ventricular growth and the \u0026ldquo;change\u0026rdquo; in size from one cranial ultrasound to the next. \u0026ldquo;Post-hemorrhage day\u0026rdquo; was used to standardize growth velocity in relation to when the hemorrhage first occurred in each patient. For example, the day of the first cranial ultrasound showing hemorrhage is labeled post-hemorrhage day 0 for patient #1, and may be postmenstrual age 26 and day of life 3; while for patient #2 post-hemorrhage day 0 may be postmenstrual age 28 and day of life 5.\u003c/p\u003e\n\u003cp\u003eThe average VI rate remains approximately stable over time and never goes below zero. Therefore VI is constantly expanding during time of monitoring. Meaning, the ventricles do not recoil or contract over time and the maximum VI is where the ventricles will remain. However, the AHW velocity at approximately post-hemorrhage day 100 shows minor recoil of the ventricles.\u003c/p\u003e\n\u003cp\u003e#########\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tabc\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;43\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRate (mm/day\u003csup\u003e2)\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAverage VI Growth Velocity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.0016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.0036\u0026ndash;0.0004\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAverage AHW Growth Velocity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.0050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e-0.0084 - -0.0015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eFigure 4: Ventricular Index and Anterior Horn Width growth rate/velocity plotted against post-hemorrhage days. (Number of days after the hemorrhage was first identified.)\u003c/p\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003e3.5 Mortality Risk Factors:\u003c/h2\u003e\n \u003cp\u003eVI and AHW growth rate are predictive of mortality. Linear models were used to examine how ventricular growth dynamics changed over time following hemorrhage, using patient status (Alive vs. Deceased) as a grouping factor as shown in Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e. For the VI, growth rate remained stable over time in patients who survived (\u0026beta; = -0.0003, p\u0026thinsp;=\u0026thinsp;0.79), whereas patients who ultimately died had a significantly higher baseline growth rate (\u0026beta;\u0026thinsp;=\u0026thinsp;0.731, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) that declined quickly over time (interaction: \u0026beta; = -0.064, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\n \u003cp\u003eA similar pattern was observed for the anterior horn width (AHW). Survivors showed no significant change in growth rate with time (\u0026beta; = -0.0019, p\u0026thinsp;=\u0026thinsp;0.235), while deceased patients exhibited a substantially higher initial growth rate (\u0026beta;\u0026thinsp;=\u0026thinsp;1.62, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) that decreased significantly as time progressed (interaction: \u0026beta; = -0.134, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Together, these findings indicate that deceased patients demonstrated accelerated early ventricular expansion\u0026mdash;both in overall ventricular size and anterior horn width\u0026mdash;that diminished over time, suggesting distinct temporal dynamics of ventricular growth between outcome groups.\u003c/p\u003e\n \u003cp\u003e#######\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"660\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23.7879%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 39.0909%;\"\u003e\n \u003cp\u003eAverage Ventricular Index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 37.1212%;\"\u003e\n \u003cp\u003eAverage Anterior Horn Width\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23.7879%;\"\u003e\n \u003cp\u003eStatus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.697%;\"\u003e\n \u003cp\u003eRate (mm/day\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3939%;\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.4242%;\"\u003e\n \u003cp\u003eRate (mm/day\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.697%;\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23.7879%;\"\u003e\n \u003cp\u003eAlive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.697%;\"\u003e\n \u003cp\u003e-0.0003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3939%;\"\u003e\n \u003cp\u003e-0.0022 - 0.0017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.4242%;\"\u003e\n \u003cp\u003e-0.0019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.697%;\"\u003e\n \u003cp\u003e-0.0052 - -0.0013\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 23.7879%;\"\u003e\n \u003cp\u003eDeceased\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.697%;\"\u003e\n \u003cp\u003e-0.064\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3939%;\"\u003e\n \u003cp\u003e-0.095 - -0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 17.4242%;\"\u003e\n \u003cp\u003e-0.137\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.697%;\"\u003e\n \u003cp\u003e-0.186 - -0.087\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u0026nbsp;Figure 5: Growth rate for ventricular index (top) and anterior horn width (middle) for alive and deceased patients compared against days post hemorrhage. Deceased trends (hash marks) show a higher initial growth velocity that drastically trends downward. Alive trends (solid line) show little change in growth rate. Chart (bottom) shows exact figures for each trend.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eGestational Age\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eCompared to neonates born 20\u0026thinsp;+\u0026thinsp;to 25 weeks gestational age; 25\u0026thinsp;+\u0026thinsp;to 30 weeks had a survival OR of 3.97 (p\u0026thinsp;=\u0026thinsp;0.06).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eWeight\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eCompared to neonates\u0026thinsp;\u0026lt;\u0026thinsp;1000g; neonates born\u0026thinsp;\u0026gt;\u0026thinsp;1000g had a survival OR of 5.6 (p\u0026thinsp;=\u0026thinsp;0.12).\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eIVH Composite Score\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003eThe association between total IVH severity and survival status was evaluated using logistic regression. The high composite group showed higher odds of mortality compared to the low composite group (OR 4.79; p\u0026thinsp;=\u0026thinsp;0.024). Furthermore, increasing composite score was associated with higher odds of death (OR 1.51 per point increase; p\u0026thinsp;=\u0026thinsp;0.07) shown in Fig.\u0026nbsp;6, considered clinically significant though not reaching conventional statistical significance. In a descriptive comparison, total IVH scores were significantly higher among non-survivors compared with survivors (median 7 [IQR 6\u0026ndash;8] vs 6 [IQR 4\u0026ndash;7], Wilcoxon rank-sum p\u0026thinsp;=\u0026thinsp;0.034). These findings are consistent with a trend toward increased IVH burden being associated with decreased survival in this cohort.\u003c/p\u003e\n \u003cp\u003eIVH grade was predictive of survival only when using composite scoring (p\u0026thinsp;=\u0026thinsp;0.034) as shown in figure below. IVH grade was not predictive of survival when using the \u0026quot;highest grade\u0026quot; approach. This supports the validity of using composite score rather than \u0026ldquo;highest grade\u0026rdquo;.\u003c/p\u003e\n \u003cp\u003e##########\u003c/p\u003e\n \u003cp\u003eFigure 6: Survival percentage compared with Intraventricular Hemorrhage Composite scoring used to produce a total intraventricular hemorrhage burden ranging from 3 to 8. Graph shows a trend of decreasing survival with each additional point of total hemorrhage burden.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eNo statistical significance\u003c/strong\u003e: APGAR at 1 minute, APGAR at 5 minutes, Maternal Age, Gender, Race\u003c/p\u003e\n\u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eIn this retrospective cohort of 43 neonates with severe intraventricular hemorrhage (SIVH) complicated by post-hemorrhagic ventricular dilatation (PHVD), we quantified the temporal course of ventricular enlargement using serial cranial ultrasound measurements of ventricular index (VI) and anterior horn width (AHW). Three findings are most salient. First, ventricular enlargement progressed in an approximately linear fashion over postmenstrual age (PMA), with mean expansion rates of 0.105 mm/day for both VI and AHW across the cohort. Second, conventional categorization by “highest” IVH grade (3 vs 4) did not meaningfully stratify growth trajectories, whereas a simple bilateral composite hemorrhage-burden score did: infants in the high composite group (7–8) demonstrated faster expansion than those in the low composite group (3–6). Third, late ventricular “recoil” was uncommon: VI expansion was effectively monotonic across follow-up, and AHW exhibited only minor late decreases. Together, these findings support the concept that hemorrhage burden (including laterality) and early growth dynamics may capture clinically relevant risk more effectively than the traditional single-grade approach.\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Growth trajectory and implications for monitoring\u003c/h2\u003e \u003cp\u003eCurrent PHVD surveillance relies heavily on serial ultrasound metrics (VI, AHW, and often thalamo-occipital distance) anchored to gestational-age–specific normative curves. Large datasets establishing reference values for VI/AHW across gestation (including very preterm infants) have enabled percentile-based monitoring and commonly used thresholds.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e In that context, a practical contribution of the present work is providing an empiric “average” expansion rate in a real-world NICU cohort with predominantly conservative management.\u003c/p\u003e \u003cp\u003eThe observed rate (~ 0.105 mm/day) offers a simple way to conceptualize the tempo of progression: a 4 mm increase—on the order of commonly used “higher-threshold” escalation criteria in some protocols—would occur over roughly 38 days at this average pace, acknowledging substantial inter-patient variability. Relatedly, the ELVIS randomized trial operationalized “low” versus “high” intervention thresholds using combinations of VI and AHW cutoffs (e.g., VI \u0026gt; p97 with AHW \u0026gt; 6 mm vs VI \u0026gt; p97 + 4 mm with AHW \u0026gt; 10 mm), reflecting the field’s emphasis on ultrasound-based, standardized triggers.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Although our study was not designed to evaluate treatment thresholds, quantifying expected time-dependent change may help clinicians and investigators interpret serial measurements (e.g., distinguishing steady progression from unusually rapid early expansion). It may also serve as a historical control for future study.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e4.2 Composite hemorrhage burden versus “highest grade”\u003c/h2\u003e \u003cp\u003eA recurring limitation of the traditional Papile-style approach in research is that “highest grade” collapses meaningful heterogeneity—particularly laterality and the distribution of hemorrhage—into a single label. In our cohort, summing left and right IVH grades into a composite score (range 3–8) better captured hemorrhage burden and revealed clinically relevant separation in both mortality risk and ventricular growth dynamics. This is directionally consistent with prior literature indicating that bilateral involvement—especially for severe IVH/periventricular hemorrhagic infarction—can carry worse neurodevelopmental prognosis compared with unilateral injury.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e It also aligns with broader efforts to move beyond a single ordinal grade toward laterality-aware or more granular scoring systems that improve outcome prediction relative to Papile grading alone.\u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eImportantly, the composite score you use is intentionally simple: it does not require specialized software or volumetric clot segmentation, and it can be abstracted from routine radiology reporting. In settings where volumetric or MRI-based quantification is impractical, this type of composite measure may provide a feasible bridge between “highest grade” and more complex hemorrhage-burden metrics, and may be a candidate covariate for future PHVD prognostic models and interventional trials.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e4.3 Early growth velocity and mortality signal\u003c/h2\u003e \u003cp\u003eBeyond overall size trajectories, we observed distinct time-dependent patterns when examining growth velocity in relation to survival: non-survivors demonstrated markedly higher early growth velocity that attenuated over time, whereas survivors exhibited comparatively stable, near-flat velocity trends. We interpret this cautiously as an association rather than a causal relationship; accelerated early expansion may be a marker of more extensive hemorrhage, greater inflammatory obstruction to CSF pathways, reduced compliance, systemic illness severity, or unmeasured comorbid factors. Nevertheless, these findings raise the possibility that early post-hemorrhage growth velocity could be an actionable signal for risk stratification alongside absolute VI/AHW values—particularly in the initial weeks when decisions around escalation, temporizing CSF diversion, or transfer may be under consideration.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003e4.4 Minimal late “recoil”\u003c/h2\u003e \u003cp\u003eA motivating premise of this study was whether ventricular size meaningfully decreases as intraventricular blood products are resorbed and CSF circulation normalizes. In our cohort, late shrinkage was uncommon: VI remained effectively monotonic and AHW showed only minor late negative velocity. This pattern contrasts with reports that a subset of infants may experience spontaneous resolution of PHVD, underscoring that the “natural history” is heterogeneous and likely depends on case mix, severity, and follow-up duration.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Several non-mutually exclusive explanations may account for the limited recoil observed here: persistent impairment of CSF resorption from inflammatory/fibrotic sequelae after IVH, evolving ventricular compliance changes, and the confounding effect of parenchymal injury (e.g., periventricular hemorrhagic infarction) where subsequent encephalomalacia can visually “merge” with ventricular CSF spaces and inflate linear measures. From a practical standpoint, these findings support the clinical intuition that, for many infants with SIVH-associated PHVD, ventricles may remain near peak dimensions over the observed NICU course—reinforcing the value of early monitoring and timely decisions about escalation rather than expecting reliable late spontaneous contraction.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e4.5 Limitations\u003c/h2\u003e \u003cp\u003eThis study has several limitations that should temper inference. As stated, left and right VI/AHW measurements were averaged at each ultrasound to generate a single bilateral value per time point. Averaging may reduce sensitivity to asymmetric dilation; however, it reduces measurement noise and supports cohort-level trajectories. Sensitivity analyses using the maximum side should be considered. Furthermore, the cohort size (N = 43) limited power for subgroup analyses and increased susceptibility to residual confounding. Comorbidities were not standardized in this study and there was a wide range of other medical issues present in the neonates. Given the small cohort, we often favored inclusivity despite the wide range of other issues. Measurement was challenging when ventricles were filled with echogenic blood products; in these cases, VI/AHW could be difficult to define and “best estimate” measurements may introduce error. Additionally, late parenchymal cavitation/encephalomalacia may artifactually increase VI/AHW by connecting cystic spaces with the ventricle, complicating interpretation of late measurements and potentially biasing against observing recoil. Comorbidities and illness severity markers were not standardized, and the cohort included infants with a wide range of concurrent medical issues, which may confound associations between ventricular dynamics and outcomes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e4.6 Future directions\u003c/h2\u003e \u003cp\u003eFuture work should (1) validate this laterality-aware composite score against established laterality-based scoring systems and, where feasible, volumetric hemorrhage measures; (2) test whether early growth velocity improves prediction of outcomes beyond absolute VI/AHW thresholds; and (3) extend follow-up beyond the NICU course to determine whether recoil occurs later and how ultrasound-based trajectories relate to MRI injury patterns and longer-term neurodevelopmental endpoints. Contemporary evidence suggests that earlier, ultrasound-guided approaches to PHVD management may be associated with improved developmental outcomes compared with delayed approaches, supporting the clinical relevance of refined early-risk stratification.\u003c/p\u003e \u003cp\u003e\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn neonates with SIVH-associated PHVD, ventricular enlargement progressed at an approximately linear rate over PMA with minimal late recoil in this cohort. A simple bilateral composite hemorrhage-burden score better stratified ventricular growth and mortality risk than the traditional “highest grade” approach, supporting the inclusion of laterality-aware hemorrhage metrics in future prognostic models and PHVD trials.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest and no competing financial interests related to this work.\u003c/p\u003e\n\u003cp\u003eFunding:\u003c/p\u003e\n\u003cp\u003eThis work received no financial support.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSiffel C, Kistler KD, Sarda SP. Global incidence of intraventricular hemorrhage among extremely preterm infants: a systematic literature review. J Perinat Med 2021;49:1017\u0026ndash;26. \u003c/li\u003e\n\u003cli\u003eHandley SC, Passarella M, Lee HC, Lorch SA. Incidence trends and risk factor variation in severe intraventricular hemorrhage across a population based cohort. J Pediatr 2018;200:24-29.e3. \u003c/li\u003e\n\u003cli\u003ePeltola SD, Akpan US, Tumin D, Huffman P. Quality improvement initiative to decrease severe intraventricular hemorrhage rates in preterm infants by implementation of a care bundle. J Perinatol 2025. https://doi.org/10.1038/s41372-025-02274-5. \u003c/li\u003e\n\u003cli\u003eHan RH, McKinnon A, CreveCoeur TS, Baksh BS, Mathur AM, Smyser CD, et al. Predictors of mortality for preterm infants with intraventricular hemorrhage: a population-based study. Childs Nerv Syst 2018;34:2203\u0026ndash;13. \u003c/li\u003e\n\u003cli\u003eVolpe, J. J. (2018). \u003cem\u003eNeurology of the Newborn\u003c/em\u003e (6th ed.). Philadelphia, PA: Elsevier.\u003c/li\u003e\n\u003cli\u003eLimbrick DD, Mathur A, Johnston JM, Munro R, Sagar J, Inder T, et al. Neurosurgical treatment of progressive posthemorrhagic ventricular dilation in preterm infants: a 10-year single-institution study: Clinical article. J Neurosurg Pediatr 2010;6:224\u0026ndash;30. \u003c/li\u003e\n\u003cli\u003eMachado-Rivas, F., Gandhi, J., Choi, J. J., Velasco-Annis, C., Afacan, O., Warfield, S. K., Gholipour, A., \u0026amp; Jaimes, C. (2022). Normal growth, sexual dimorphism, and lateral asymmetries at fetal brain MRI. Radiology, 303(1), 162\u0026ndash;170. https://doi.org/10.1148/radiol.211222\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Chart 1","content":"\u003cp\u003eChart 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-perinatology","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"jp","sideBox":"Learn more about [Journal of Perinatology](http://www.nature.com/jp/)","snPcode":"41372","submissionUrl":"https://mts-jper.nature.com/cgi-bin/main.plex","title":"Journal of Perinatology","twitterHandle":"@jperinatology","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8613373/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8613373/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePost-hemorrhagic ventricular dilation (PHVD) is a significant complication in 30–50% of severe intraventricular hemorrhage (SIVH), yet the temporal dynamics of ventricular expansion and late “recoil” remain incompletely characterized.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo quantify the rate, magnitude, and temporal pattern of ventricular expansion following SIVH using serial cranial ultrasound measurements, and to explore associations with hemorrhage burden and mortality.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDesign/Setting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRetrospective cohort study of neonates cared for at University Hospital Neonatal Intensive Care Unit (NICU) in Newark, NJ (01/2010–01/2025).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e43 neonates with SIVH and PHVD were included. Mortality was 37.2% (16/43); 11.6% (5/43) underwent invasive intervention.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eVentricular dilation was quantified on serial head ultrasounds using ventricular index (VI) and anterior horn width (AHW); 347 cranial ultrasounds were analyzed (8 per patient). Growth trajectories were modeled primarily as a function of postmenstrual age (PMA).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAcross the cohort, both VI and AHW increased significantly with PMA, with mean expansion rates of 0.105 mm/day for VI (95% CI 0.092–0.118) and 0.105 mm/day for AHW (95% CI 0.087–0.124) (both p \u0026lt; 0.001). Highest IVH grade (3 vs 4) did not significantly modify growth rate, but a composite bilateral hemorrhage-burden score better stratified outcomes and growth dynamics. When the composite score was grouped into low (3–6) vs high (7–8), high-burden infants demonstrated faster expansion (VI 0.126 vs 0.096 mm/day, p = 0.025; AHW 0.139 vs 0.091 mm/day, p = 0.013). Over time, VI expansion was effectively monotonic, while AHW showed only minor late recoil; overall, late ventricular shrinkage was uncommon. Mortality in the high composite group was 4.79 times higher than the low composite group (p = 0.024). Each 1-point increase in composite IVH severity showed a clinically meaningful association with mortality (OR 1.51 per 1-point increase; p = 0.072) and differed significantly between survivors and non-survivors (Wilcoxon p = 0.034).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this retrospective NICU cohort with SIVH-associated PHVD, ventricles enlarged at an approximately linear rate over PMA, with faster expansion in infants with higher composite hemorrhage burden. Composite score was a better predictor of dilation size and mortality. Ventricular “recoil” was minimal, supporting that ventricular size often remains near peak dimensions over the observed course.\u003c/p\u003e","manuscriptTitle":"Composite Scoring and the Natural Course of Post-Hemorrhagic Ventricular Dilation in Neonates with Severe Intraventricular Hemorrhage","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-29 16:41:36","doi":"10.21203/rs.3.rs-8613373/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"This content is not available.","date":"2026-04-13T03:22:23+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2026-04-07T02:49:34+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2026-01-27T18:04:02+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-23T16:36:25+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Perinatology","date":"2026-01-21T16:15:25+00:00","index":"","fulltext":""},{"type":"checksFailed","content":"","date":"2026-01-20T17:47:51+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-15T19:56:53+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-perinatology","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"jp","sideBox":"Learn more about [Journal of Perinatology](http://www.nature.com/jp/)","snPcode":"41372","submissionUrl":"https://mts-jper.nature.com/cgi-bin/main.plex","title":"Journal of Perinatology","twitterHandle":"@jperinatology","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"11fc65ff-f3fe-43a0-9a0c-7d6de094b8eb","owner":[],"postedDate":"January 29th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":61846928,"name":"Health sciences/Diseases/Neurological disorders/Paediatric neurological disorders"},{"id":61846929,"name":"Health sciences/Biomarkers/Predictive markers"}],"tags":[],"updatedAt":"2026-01-29T16:41:36+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-29 16:41:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8613373","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8613373","identity":"rs-8613373","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}