High-grade Intraventricular Hemorrhage Research Articles

Preterm Infants on Early Solid Foods and Neurodevelopmental Outcome-A Secondary Outcome Analysis of a Randomized Controlled Trial.

There are no evidence-based recommendations regarding the introduction of solid foods in preterm infants. The objective of this study was to investigate whether age at the introduction of solid foods affects neurodevelopmental outcomes. This study focuses on analyzing secondary outcomes from a prospective trial involving very low birth weight infants who were randomly assigned to either an early (10-12th week corrected age) or a late (16-18th week corrected age) complementary feeding group. The study evaluated neurodevelopmental outcomes at one and two years of corrected age, as well as at three years and four months of uncorrected age by utilizing Bayley scales. In total, 89 infants were assigned to the early and 88 infants to the late group, all with a mean gestational age of 27 + 1 weeks. A linear mixed-effects model was used to compare neurodevelopmental outcomes across the study groups, taking into account variables such as gestational age at birth, sex, nutrition at discharge, parents' highest education level, and high-grade intraventricular hemorrhage. The analysis did not reveal any significant differences between the groups. The timepoint of the introduction of solid foods had no impact on neurodevelopmental outcomes at one and two years of corrected age, and at three years and four months of uncorrected age.

Does perinatal management have the potential to reduce the risk of intraventricular hemorrhage in preterm infants?

Intraventricular hemorrhage (IVH) is an important cause of neurodevelopmental impairment in preterm infants. A number of risk factors for IVH have already been proposed; however, some controversies regarding optimal perinatal management persist. This study aimed to identify perinatal and neonatal attributes associated with IVH in a representative population of preterm infants. Perinatal data on 1,279 very preterm infants (<32 weeks of gestation) admitted to a tertiary neonatal intensive care unit were analyzed. The records were assessed using univariate analysis and logistic regression model to evaluate the risk factors for any and high-grade IVH (grade III-IV according to the classification by Papile) within the first week after birth. The incidence of any IVH was 14.3% (183/1,279); the rate of low-grade (I-II) and high-grade (III-IV) IVH was 9.0% (115/1,279) and 5.3% (68/1,279), respectively. Univariate analysis revealed multiple factors significantly associated with intraventricular hemorrhage: lower gestational age and birth weight, absence of antenatal steroids, vaginal delivery, low Apgar score at 5 min, delivery room intubation, surfactant administration, high frequency oscillation, pulmonary hypertension, pulmonary hemorrhage, tension pneumothorax, persistent ductus arteriosus, hypotension and early onset sepsis. Logistic regression confirmed lower gestational age, vaginal delivery, ductus arteriosus and early onset sepsis to be independent predictors for any IVH. Pulmonary hemorrhage, tension pneumothorax and early onset sepsis were independent risk factors for high-grade IVH. Complete course of antenatal steroids was associated with a lower risk for any (odds ratio 0.58, 95% confidence interval 0.39-0.85; P = .006) and for high-grade intraventricular hemorrhage (odds ratio 0.36, 95% confidence interval 0.20-0.65; P < .001). The use of antenatal steroids and mode of delivery are crucial in the prevention of IVH; however, our study did not confirm the protective effect of placental transfusion. Severe respiratory insufficiency and circulatory instability remain to be powerful contributors to the development of IVH. Early detection and management of perinatal infection may also help to reduce the rate of brain injury and improve neurodevelopment in high-risk newborns.

Weight growth velocity and growth outcomes in very-low-birth-weight infants developing major morbidities

BackgroundExtrauterine growth restriction (EUGR) is common in very-low-birth-weight-infants and may be associated with poor neurodevelopment. The growth velocity of preterm infants is increasing over decades, but the relationship between growth velocity, EUGR, and morbidities of preterm infants remains unknown. MethodsA total of 263 infants born between 2012 and 2020, with birthweight <1500 g and gestational age of 24–33 weeks, were included. Birthweight and weight on day of evaluation point (corrected gestational age 36 weeks or discharged, whenever comes first) were converted to age-specific and gender-specific Z-scores and analyzed by multivariable modeling. The average growth velocity was calculated by the exponential model. ResultsAverage growth velocity from birth to the evaluation point was 11.8 ± 0.3 g/kg/day. The maximum growth velocity from birth to week 8 postnatal occurred at week 4 postnatal (16.4 ± 0.9 g/kg/day). Infants with smaller birth weight, higher gestational age, and indication of intestinal surgery or those who need more days to achieve full enteral feeding were more favorable to have a weight lower than the 10th centile at the evaluation point. By contrast, most comorbidities of prematurity did not affect either lower age-specific weight Z-scores on the evaluation point or larger change in weight Z-score between birth and evaluation point. ConclusionEUGR was associated with gestational age and birth weight. Infants with moderate-to-severe bronchopulmonary dysplasia, high-grade intraventricular hemorrhage, or retinopathy of prematurity tend to have slower growth velocity at 3–5 weeks postnatal, but these did not contribute to EUGR.

Long-Term Video Electroencephalographic Monitoring in

BackgroundDespite recognizing high seizure risk, the current consensus guidelines on evaluating seizures in preterm neonates are based on limited data. We chose to investigate the seizure risk in high-risk preterm (<30 weeks gestation) asymptomatic (without a clinical concern for seizures) infants with high-grade intraventricular hemorrhage who underwent long-term video electroencephalographic monitoring. MethodsWe performed a comprehensive retrospective review on all infants of <30-week gestational age admitted to the University of Alabama at Birmingham Regional Neonatal Intensive Care Unit from June 2018 to October 2022. We selected those patients who underwent electroencephalographic monitoring without a prior clinical concern for seizures. We recorded gender, gestational age, APGAR scores (one and five minutes), intraventricular hemorrhage (grade, age at diagnosis), and electroencephalographic monitoring (timing and duration) data. ResultsAmong 37 premature infants, six had seizures detected on electroencephalographic monitoring. All six infants had subclinical seizures. Only two of six patients had a clinical correlation (although not identified by the providers) with some of their seizures. Patients with seizures were significantly younger in chronological age (median age 6.5 days vs 9 days, P value 0.009) at the time of the electroencephalographic monitoring initiation and were more likely to have subsequent monitoring studies (P value 0.0418). ConclusionsLong-term video electroencephalographic monitoring performed after the diagnosis of high-grade intraventricular hemorrhage captured seizures in ∼16% of asymptomatic premature neonates of <30 weeks’ gestation. Patients identified to have seizures were significantly younger (chronological age) at the time of the electroencephalographic monitoring initiation and were more likely to be remonitored.

Ratios of head circumference to ventricular size vary over time and predict eventual need for CSF diversion in intraventricular hemorrhage of prematurity.

Intraventricular hemorrhage (IVH) of prematurity can lead to hydrocephalus, sometimes necessitating permanent cerebrospinal fluid (CSF) diversion. We sought to characterize the relationship between head circumference (HC) and ventricular size in IVH over time to evaluate the clinical utility of serial HC measurements as a metric in determining the need for CSF diversion. We included preterm infants with IVH born between January 2000 and May 2020. Three measures of ventricular size were obtained: ventricular index (VI), Evan's ratio (ER), and frontal occipital head ratio (FOHR). The Pearson correlations (r) between the initial (at birth) paired measurements of HC and ventricular size were reported. Multivariable longitudinal regression models were fit to examine the HC:ventricle size ratio, adjusting for the age of the infant, IVH grade (I/II vs. III/IV), need for CSF diversion, and sex. A total of 639 patients with an average gestational age of 27.5weeks were included. IVH grade I/II and grade III/IV patients had a positive correlation between initial HC and VI (r = 0.47, p < 0.001 and r = 0.48, p < 0.001, respectively). In our longitudinal models, patients with a low-grade IVH (I/II) had an HC:VI ratio 0.52 higher than those with a high-grade IVH (p-value < 0.001). Patients with low-grade IVH had an HC:ER ratio 12.94 higher than those with high-grade IVH (p-value < 0.001). Patients with low-grade IVH had a HC:FOHR ratio 12.91 higher than those with high-grade IVH (p-value < 0.001). Infants who did not require CSF diversion had an HC:VI ratio 0.47 higher than those who eventually did (p < 0.001). Infants without CSF diversion had an HC:ER ratio 16.53 higher than those who received CSF diversion (p < 0.001). Infants without CSF diversion had an HC:FOHR ratio 15.45 higher than those who received CSF diversion (95% CI (11.34, 19.56), p < 0.001). There is a significant difference in the ratio of HC:VI, HC:ER, and HC:FOHR size between patients with high-grade IVH and low-grade IVH. Likewise, there is a significant difference in HC:VI, HC:ER, and HC:FOHR between those who did and did not have CSF diversion. The routine assessments of both head circumference and ventricle size by ultrasound are important clinical tools in infants with IVH of prematurity.

The Utilization of EEG Monitoring in Premature Infants with High-Grade Intraventricular Hemorrhage (P13-1.004)

<h3>Objective:</h3> We aimed to study the utility of continuous video electroencephalographic (cvEEG) monitoring as a screening tool for seizures in asymptomatic neonates found to have high-grade IVH. <h3>Background:</h3> High-grade intraventricular hemorrhage (IVH) is one of the possible complications of prematurity, and is considered one of the leading causes of seizures in premature infants. Neonatal seizures can be challenging to detect based on clinical symptoms alone and if left untreated, it can be associated with short- and long-term consequences. <h3>Design/Methods:</h3> We performed a comprehensive retrospective review on all premature infants born at the University of Alabama at Birmingham Regional Neonatal Intensive Care Unit from June 2018 to June 2021. We selected asymptomatic infants found to have high-grade (grade 3 and 4) IVH on head ultrasound who underwent cvEEG monitoring. Patient characteristics and comorbidities were then carefully studied and correlated with the screening EEG findings. <h3>Results:</h3> Among 27 premature infants with IVH enrolled in this study, 7 infants (26%) were found to have seizures detected on EEG. Detected seizures were only subclinical in 5 infants, while 2 infants had clinical in addition to subclinical seizures. Infants with seizures were relatively more premature, had a higher degree IVH, and lower APGAR scores at birth when compared to infants with no seizures. <h3>Conclusions:</h3> Our study suggests that EEG monitoring is vital when resources permit to screen for subclinical seizures in infants born with high-grade IVH. EEG screening should start as soon as IVH is suspected or discovered on imaging as early detection of seizures aid in prompt treatment. Since EEG monitoring is resource intensive, we suggest studying additional variables such as the degree of prematurity and APGAR scores to increase the yield of such screening studies. <b>Disclosure:</b> Dr. Al Robaidi has nothing to disclose. Dr. Goyal has nothing to disclose. Dr. Lalor has nothing to disclose. Dr. Shukla has nothing to disclose. Dr. Rashid has nothing to disclose.

Intraventricular Hemorrhage in Very Preterm Children: Mortality and Neurodevelopment at Age 5.

The objectives were to describe mortality and causes of death in children with intraventricular hemorrhage (IVH) and to study neurodevelopmental outcomes. The study was a secondary analysis of the French national prospective and population-based cohort EPIPAGE-2. Children were recruited in 2011. A standardized assessment was conducted at age 5. Children born before 32 weeks' gestation and admitted to a NICU were eligible. Exposure was IVH defined by the Papile classification. Main outcomes were mortality, causes of death, and neurodevelopmental outcomes at age 5. Among the 3468 children included, 578 (16.7%) had grade 1 IVH, 424 (12.2%) grade 2 IVH, and 114 (3.3%) grade 3 IVH; 144 (4.1%) had intraparenchymal hemorrhage (IPH). Mortality was 29.7% (36 of 114) for children with grade 3 IVH and 74.4% (109 of 144) for those with IPH; 67.6% (21 of 31) and 88.7% (86 of 97) of deaths, respectively, were because of withholding and withdrawing of life-sustaining treatment. As compared with no IVH, low-grade IVH was not associated with measured neurodevelopmental disabilities at age 5. High-grade IVH was associated with moderate and severe neurodevelopmental disabilities, reduced full-scale IQ, and cerebral palsy. Rates of neurodevelopmental disabilities at age 5 did not differ between children without IVH and those with low-grade IVH. For high-grade IVH, mortality rate was high, mostly because of withholding and withdrawal of life-sustaining treatment, and we found a strong association with overall neurodevelopmental disabilities in survivors.

Associations between Early Thyroid-Stimulating Hormone Levels and Morbidities in Extremely Preterm Neonates

Introduction: High-end cutoffs of thyroid-stimulating hormone (TSH) have been emphasized for hypothyroidism therapy in extremely preterm infants, but the significance of low TSH levels remains unknown. This study hypothesized that the spectrum of TSH levels by newborn screening after birth signifies specific morbidities in extremely preterm neonates. Methods: The multicenter population cohort analyzed 434 extremely preterm neonates receiving TSH screening at 24–96 h of age in 2008–2019. Neonates were categorized by blood TSH levels into group 1: TSH <0.5 µU/mL, group 2: 0.5 ≤ TSH <2 µU/mL, group 3: 2 ≤ TSH <4 µU/mL, and group 4: TSH ≥4 µU/mL. Neonatal morbidities were categorized using the modified Neonatal Therapeutic Intervention Scoring System. Results: The four groups differed in gestational age, birth weight, and the postnatal age at blood sampling so did the proportions of mechanical ventilation usage (p = 0.01), hypoxic respiratory failure (p = 0.005), high-grade intraventricular hemorrhage (p = 0.007), and periventricular leukomalacia (p = 0.048). Group 1 had higher severity scores for respiratory distress syndrome (RDS; effect size 0.39 [95% confidence interval [CI]: 0.18–0.59]) and brain injury (0.36 [0.15–0.57]) than group 2, which remained significant after adjusting for gestational age, birth weight, dopamine usage, and the postnatal age at TSH screening (RDS: mean + 0.45 points [95% CI: 0.11–0.79]; brain injury: +0.32 [0.11–0.54]). Conclusions: Low TSH levels in extremely preterm neonates are associated with severe RDS and brain injuries. Studies recruiting more neonates with complete thyroid function data are necessary to understand central-peripheral interactions of the hypothalamic-pituitary-thyroid axis.

Impact of low-grade intraventricular hemorrhage on neurodevelopmental outcome in very preterm infants at two years of age

BackgroundHigh-grade intraventricular hemorrhage (IVH) in very preterm infants is a known risk factor for adverse neurodevelopmental outcome. Prognosis is less clear for low-grade (grades I/II) IVH however, with conflicting study results in recent years. ObjectiveTo evaluate the impact of low-grade IVH on neurodevelopmental outcome at 2 years corrected age in preterm infants born below 32 weeks gestation at the University hospital of Zurich between 2009 and 2014. MethodsAmong 843 live-born preterm infants born during the observation period, 509 were included in our study. Exclusion criteria were death, high-grade IVH, cystic periventricular leukomalacia and congenital malformations. Infants were grouped into those with or without low-grade IVH according to cranial ultrasound. Neurodevelopmental impairment (NDI) was defined as cognitive or motor developmental score > 2 standard deviations below the mean and/or CP grades 2–5 and/or moderate/severe vision loss and/or hearing problem corrected with hearing aids. Multivariate linear regression was used to assess effect of low-grade IVH on endpoints while adjusting for other risk factors. Results87 preterm infants had low-grade IVH (42 grade I, 45 grade II) on cranial ultrasound. These were compared to 422 preterm infants without IVH. Follow-up rate was 82.4 %. Preterm infants with low-grade IVH had higher rates of NDI (21.8 vs 13.3 %, p = 0.047). Infants with IVH grade II had significantly higher rates for CP (8.9 % vs 3.6 %, p = 0.003), visual impairment (20.5 % vs 8.3 %, p = 0.009) and NDI (33.3 % vs 13.3 %, p < 0.001). ConclusionIn our study, low-grade IVH – and especially IVH grade II - is associated with adverse neurodevelopmental outcome at 2 years of corrected age.

Neurodevelopmental Outcome at Two Years for Preterm Infants With Intraventricular Hemorrhage: A Case-Control Study

BackgroundHigh-grade intraventricular hemorrhage (IVH), including grade III and grade IV IVH, is known to impact neurodevelopmental outcome of preterm infants, but prognosis remains difficult to establish due to confounding factors and significant variations in the reported outcomes. The aim of this study was to compare the neurodevelopmental outcome of preterm infants with or without severe IVH. MethodsA retrospective case-control study was conducted including preterm infants with gestational age <32 weeks hospitalized between 2009 and 2017 in a level III neonatal intensive care unit. This study included 73 cases with high-grade IVH and 73 controls who were matched to cases, based on the same gestational age, birth weight, sex, and year of birth. The neurodevelopmental outcome was compared at two years of age corrected for prematurity between cases and controls. Neurodevelopmental impairment was defined as cerebral palsy, hearing deficiency, visual impairment, or developmental delay. Multivariate analysis was used to identify whether high-grade IVH was an independent risk factor for neurodevelopmental impairment. ResultsIn univariate analysis, high-grade IVH was associated with death or poor neurodevelopmental outcome at two years of age corrected for prematurity (odds ratio [OR], 16.3; 95% confidence interval [CI], 5.93 to 57.8; P < 0.001), and this association remained significant after adjusting for confounding factors including neonatal infection and bronchopulmonary dysplasia in multivariate analysis (OR, 8.71; 95% CI, 2.48 to 38.09; P = 0.002). ConclusionsThis study highlights the impact of high-grade IVH as an independent risk factor of poor neurodevelopmental outcomes in very preterm infants and suggests that early interventions could improve the prognosis of these infants.

Effects of antenatal corticosteroids on neonatal outcomes in twin and singleton pregnancies: a Korean national cohort study

ObjectiveTo investigate whether effects of antenatal corticosteroids on neonatal outcomes in preterm infants with very low birth weight were different by plurality.DesignNationwide prospective cohort study.PatientsTwins and singletons with very low...

Interobserver reliability between pediatric radiologists and residents in ultrasound evaluation of intraventricular hemorrhage in premature infants.

Germinal matrix intraventricular hemorrhage (IVH) may contribute to significant morbidity and mortality in premature infants. Timely identification and grading of IVH affect decision-making and clinical outcomes. There is possibility of misinterpretation of the ultrasound appearances, and the interobserver variability has not been investigated between radiology resident and board-certified radiologist. To assess interobserver reliability between senior radiology residents performing bedside cranial ultrasound during on-call hours and pediatric radiologists. From June 2018 to June 2020, neonatal cranial ultrasound examinations were performed in neonatal intensive care unit. Ultrasound findings were recorded by the residents performing the ultrasound and the pediatric attending radiologists. In total, 200 neonates were included in the study, with a mean gestational age of 30.9 wk. Interobserver agreement for higher grade (Grade III & IV) IVH was excellent. There was substantial agreement for lower grade (Grade I & II) IVH. There is strong agreement between radiology residents and pediatric radiologists, which is higher for high grade IVHs.

Deferoxamine Prevents Neonatal Posthemorrhagic Hydrocephalus Through Choroid Plexus-Mediated Iron Clearance.

Posthemorrhagic hydrocephalus occurs in up to 30% of infants with high-grade intraventricular hemorrhage and is associated with the worst neurocognitive outcomes in preterm infants. The mechanisms of posthemorrhagic hydrocephalus after intraventricular hemorrhage are unknown; however, CSF levels of iron metabolic pathway proteins including hemoglobin have been implicated in its pathogenesis. Here, we develop an animal model of intraventricular hemorrhage using intraventricular injection of hemoglobin at post-natal day 4 that results in acute and chronichydrocephalus, pathologic choroid plexus iron accumulation, and subsequent choroid plexus injury at post-natal days 5, 7, and 15. This model alsoresults in increased expression ofaquaporin-1, Na+/K+/Cl- cotransporter 1, andNa+/K+/ATPase on the apical surface of the choroid plexus 24h post-intraventricular hemorrhage. We use this model to evaluate a clinically relevant treatment strategy for the prevention of neurological sequelae afterintraventricular hemorrhageusing intraventricular administration of the iron chelator deferoxamine at the time of hemorrhage. Deferoxamine treatment prevented posthemorrhagic hydrocephalus for up to 11days after intraventricular hemorrhage and prevented the development of sensorimotor gating deficits. In addition, deferoxamine treatment facilitated acute iron clearance through the choroid plexus and subsequentlyreduced choroid plexus iron levels at 24hwith reversal of hemoglobin-induced aquaporin-1 upregulation on the apical surface of the choroid plexus. Intraventricular administration of deferoxamine at the time of intraventricular hemorrhage may be a clinically relevant treatment strategy for preventing posthemorrhagic hydrocephalus and likely acts through promoting iron clearance through the choroid plexus to prevent hemoglobin-induced injury.

Cystic Periventricular Leukomalacia Worsens Developmental Outcomes of Very-Low-Birth Weight Infants with Intraventricular Hemorrhage-A Nationwide Cohort Study.

Cystic periventricular leukomalacia (cPVL) is a major brain injury involving periventricular white matter that leads to neurodevelopmental impairment in very-low-birth weight (VLBW) infants. We investigated the neurodevelopmental outcomes (motor, cognition, visual, and hearing) of 5734 VLBW infants born between 2013 and 2019 and enrolled in the Korean Neonatal Network. Cranial ultrasound results were stratified by the presence of cPVL and severity of intraventricular hemorrhage (IVH) (no, low-grade [I/II], high-grade [III]). Neurodevelopmental impairment was evaluated using cerebral palsy for motor and Bayley Scales of Infant Development for cognition. cPVL was associated with motor, cognitive, and visual impairments in those without IVH and with low-grade IVH in pairwise comparisons (Cochran–Mantel–Haenszel p < 0.001). Conversely, cPVL was non-significantly correlated with cognitive impairment in high-grade IVH. In regression models adjusted for neonatal variables, isolated cPVL was strongly associated with motor (22.04; 11.39–42.63) and cognitive (3.10; 1.54–6.22) impairments. This study underlines the overall considerable significance of cPVL on NDI with divergent impacts depending on the severity of IVH and developmental indices.

Clinical determinants of cerebrovascular reactivity in very preterm infants during the transitional period

Preterm infants are at enhanced risk of brain injury due to altered cerebral haemodynamics during postnatal transition. This observational study aimed to assess the clinical determinants of transitional cerebrovascular reactivity and its association with intraventricular haemorrhage (IVH). Preterm infants <32 weeks underwent continuous monitoring of cerebral oxygenation and heart rate over the first 72 h after birth. Serial cranial and cardiac ultrasound assessments were performed to evaluate the ductal status and to diagnose IVH onset. The moving correlation coefficient between cerebral oxygenation and heart rate (TOHRx) was calculated. Linear mixed-effect models were used to analyse the impact of relevant clinical variables on TOHRx. The association between TOHRx and IVH development was also assessed. Seventy-seven infants were included. A haemodynamically significant patent ductus arteriosus (hsPDA) (β = 0.044, 95% CI: 0.007-0.081) and ongoing dopamine treatment (β = 0.096, 95% CI: 0.032-0.159) were associated with increasing TOHRx, indicating impaired cerebrovascular reactivity. A significant association between TOHRx, mean arterial blood pressure (β = -0.004, 95% CI: -0.007, -0.001) and CRIB-II score (β = 0.007, 95% CI: 0.001-0.015) was also observed. TOHRx was significantly higher in infants developing high-grade IVH compared to those without IVH. Dopamine treatment, low blood pressure, hsPDA and high CRIB-II are associated with impaired cerebrovascular reactivity during postnatal transition, with potential implications on IVH development. The correlation coefficient between cerebral oxygenation and heart rate (TOHRx) provides a non-invasive estimation of cerebrovascular reactivity, whose failure has a potential pathogenic role in the development of IVH in preterm infants. This study shows that cerebrovascular reactivity during the transitional period improves over time and is affected by specific clinical and therapeutic factors, whose knowledge could support the development of individualized neuroprotective strategies in at-risk preterm infants. The evidence of increased TOHRx in infants developing high-grade compared to low-grade or no IVH during the transitional period further supports the role of impaired cerebrovascular reactivity in IVH pathophysiology.

Comparison of Surfactant Administration Efficacy in the Treatment of Respiratory Distress Syndrome in Preterm Neonates: Aerosolization Versus INSURE

Background: Respiratory distress syndrome (RDS) is considered one of the most common causes of morbidity in neonates. None of the interventions made in the last three decades to manage this disease has been able to affect the development of RDS as much as surfactant replacement. Objectives: Although the standard approach is intubation during surfactant administration, the development of alternative methods in surfactant administration, such as surfactant administration using nebulizers, has been considered that is the aim of the current study. Methods: This randomized controlled trial was conducted on neonates with a gestational age of 28 - 32 weeks with RDS under nasal continuous positive airway pressure (nCPAP) in Beheshti Medical Center in Isfahan, Iran, within March 2018 to August 2020. The neonates requiring the fraction of inspired oxygen ≥ 0.4 for periods longer than 30 minutes to maintain oxygen saturation in the right hand within the range of 89 - 95% while being supported under continuous distending pressure ≥ 5 cm H2O were randomly divided into a control group and an intervention group. Survanta was administered in the control group through INSURE method and aerosolization using mesh nebulizers in the intervention group. Results: This study showed no significant difference in the arterial/alveolar oxygen ratio gradient after Survanta administration (P-value: 0.10), need for subsequent doses of surfactant (P-value: 0.771) and mechanical ventilation (P-value: 0.145), prevalence of pneumothorax (P-value: 0.50), chronic lung disease (P-value: 0.269), and high-grade intraventricular hemorrhage (P-value: 0.221), duration of nCPAP support (P-value: 0.089), or prevalence of death between the two groups (P-value: 1.00). Conclusions: Since aerosolization is considered to be a noninvasive method, it is required to perform further studies to improve this approach.

Neurodevelopmental outcomes of premature infants with intraventricular hemorrhage across a lifespan

Neurodevelopmental impairment rates remain high among extremely preterm and very low birth weight infants. This review describes the rates of brain injury and neuro-developmental impairment at 2,3 years, early school age, adolescence, and young adulthood for survivors with intraventricular hemorrhage (IVH). Former preterm infants with a history of high-grade IVH are at the greatest risk of adverse neurodevelopmental outcomes. There is variability, however, in definitions of brain injury, methods for assessing brain injury, and definitions of adverse outcomes among multicenter networks. Despite differences in methods described in publications, perinatal grade III-IV intraventricular hemorrhage, post-hemorrhagic hydrocephalus, and white matter injury are consistently associated with increased rates of adverse motor and cognitive outcomes in the first 2,3 years of life, at early school age, in adolescence and early adulthood. Effects of socioeconomic status on outcomes, however, increase with the increasing age of the child. In summary, although preterm survivors of IVH are at an increased risk of adverse outcomes across a lifetime, there is evidence that social and environmental factors contribute to recovery over time.

Prediction of persistent ventricular dilation by initial ventriculomegaly and clot volume in a porcine model.

While intraventricular hemorrhage (IVH) is associated with posthemorrhagic ventricular dilation (PHVD), not all infants affected by high-grade IVH develop PHVD. The authors aimed to determine clot-associated predictors of PHVD in a porcine model by varying the amount and rate of direct intraventricular injection of whole autologous blood. Seven 1-week-old piglets underwent craniectomy and injection of autologous blood into the right lateral ventricle. They survived for a maximum of 28 days. MRI was performed prior to injection, immediately postoperatively, and every 7 days thereafter. T1-weighted, T2-weighted, and susceptibility-weighted imaging (SWI) sequences were used to segment ventricular and clot volumes. Spearman correlations were used to determine the relationship between blood and clot volumes and ventricular volumes over time. The maximum ventricular volume was up to 12 times that of baseline. One animal developed acute hydrocephalus on day 4. All other animals survived until planned endpoints. The interaction between volume of blood injected and duration of injection was significantly associated with clot volume on the postoperative scan (p = 0.003) but not the amount of blood injected alone (p = 0.38). Initial postoperative and day 7 clot volumes, but not volume of blood injected, were correlated with maximum (p = 0.007 and 0.014) and terminal (p = 0.014 and 0.036) ventricular volumes. Initial postoperative ventricular volume was correlated with maximum and terminal ventricular volume (p = 0.007 and p = 0.014). Initial postoperative, maximum, and terminal ventricular dilations were associated with the amount of clot formed, rather than the amount of blood injected. This supports the hypothesis that PHVD is determined by clot burden rather than the presence of blood products and allows further testing of early clot lysis to minimize PHVD risk.

Does ventricle size contribute to cognitive outcomes in posthemorrhagic hydrocephalus? Role of early definitive intervention.

Posthemorrhagic hydrocephalus (PHH) is associated with significant morbidity, smaller hippocampal volumes, and impaired neurodevelopment in preterm infants. The timing of temporary CSF (tCSF) diversion has been studied; however, the optimal time for permanent CSF (pCSF) diversion is unknown. The objective of this study was to determine whether cumulative ventricle size or timing of pCSF diversion is associated with neurodevelopmental outcome and hippocampal size in preterm infants with PHH. Twenty-five very preterm neonates (born at ≤ 32 weeks' gestational age) with high-grade intraventricular hemorrhage (IVH), subsequent PHH, and pCSF diversion with a ventriculoperitoneal shunt (n = 20) or endoscopic third ventriculostomy (n = 5) were followed until 2 years of age. Infants underwent serial cranial ultrasounds from birth until 1 year after pCSF diversion, brain MRI at term-equivalent age, and assessment based on the Bayley Scales of Infant and Toddler Development, Third Edition, at 2 years of age. Frontooccipital horn ratio (FOHR) measurements were derived from cranial ultrasounds and term-equivalent brain MRI. Hippocampal volumes were segmented and calculated from term-equivalent brain MRI. Cumulative ventricle size until the time of pCSF diversion was estimated using FOHR measurements from each cranial ultrasound performed prior to permanent intervention. The average gestational ages at tCSF and pCSF diversion were 28.9 and 39.0 weeks, respectively. An earlier chronological age at the time of pCSF diversion was associated with larger right hippocampal volumes on term-equivalent MRI (Pearson's r = -0.403, p = 0.046) and improved cognitive (r = -0.554, p = 0.047), motor (r = -0.487, p = 0.048), and language (r = -0.414, p = 0.021) outcomes at 2 years of age. Additionally, a smaller cumulative ventricle size from birth to pCSF diversion was associated with larger right hippocampal volumes (r = -0.483, p = 0.014) and improved cognitive (r = -0.711, p = 0.001), motor (r = -0.675, p = 0.003), and language (r = -0.618, p = 0.011) outcomes. There was no relationship between time to tCSF diversion or cumulative ventricle size prior to tCSF diversion and neurodevelopmental outcome or hippocampal size. Finally, a smaller cumulative ventricular size prior to either tCSF diversion or pCSF diversion was associated with a smaller ventricular size 1 year after pCSF diversion (r = 0.422, p = 0.040, R2 = 0.178 and r = 0.519, p = 0.009, R2 = 0.269, respectively). In infants with PHH, a smaller cumulative ventricular size and shorter time to pCSF diversion were associated with larger right hippocampal volumes, improved neurocognitive outcomes, and reduced long-term ventriculomegaly. Future prospective randomized studies are needed to confirm these findings.

Microstructural Periventricular White Matter Injury in Post-hemorrhagic Ventricular Dilatation.

The neurologic deficits of neonatal post-hemorrhagic hydrocephalus (PHH) have been linked to periventricular white matter injury. To improve understanding of PHH-related injury, diffusion basis spectrum imaging (DBSI) was applied in neonates, modeling axonal and myelin integrity, fiber density, and extrafiber pathologies. Objectives included characterizing DBSI measures in periventricular tracts, associating measures with ventricular size, and examining MRI findings in the context of postmortem white matter histology from similar cases. A prospective cohort of infants born very preterm underwent term equivalent MRI, including infants with PHH, high-grade intraventricular hemorrhage without hydrocephalus (IVH), and controls (very preterm [VPT]). DBSI metrics extracted from the corpus callosum, corticospinal tracts, and optic radiations included fiber axial diffusivity, fiber radial diffusivity, fiber fractional anisotropy, fiber fraction (fiber density), restricted fractions (cellular infiltration), and nonrestricted fractions (vasogenic edema). Measures were compared across groups and correlated with ventricular size. Corpus callosum postmortem immunohistochemistry in infants with and without PHH assessed intra- and extrafiber pathologies. Ninety-five infants born very preterm were assessed (68 VPT, 15 IVH, 12 PHH). Infants with PHH had the most severe white matter abnormalities and there were no consistent differences in measures between IVH and VPT groups. Key tract-specific white matter injury patterns in PHH included reduced fiber fraction in the setting of axonal or myelin injury, increased cellular infiltration, vasogenic edema, and inflammation. Specifically, measures of axonal injury were highest in the corpus callosum; both axonal and myelin injury were observed in the corticospinal tracts; and axonal and myelin integrity were preserved in the setting of increased extrafiber cellular infiltration and edema in the optic radiations. Increasing ventricular size correlated with worse DBSI metrics across groups. On histology, infants with PHH had high cellularity, variable cytoplasmic vacuolation, and low synaptophysin marker intensity. PHH was associated with diffuse white matter injury, including tract-specific patterns of axonal and myelin injury, fiber loss, cellular infiltration, and inflammation. Larger ventricular size was associated with greater disruption. Postmortem immunohistochemistry confirmed MRI findings. These results demonstrate DBSI provides an innovative approach extending beyond conventional diffusion MRI for investigating neuropathologic effects of PHH on neonatal brain development.