Posthemorrhagic Ventricular Dilatation Research Articles

Bedside placement of ventricular access devices under local anaesthesia in neonates with posthaemorrhagic hydrocephalus: preliminary experience

PurposePosthaemorrhagic ventricular dilatation in preterm infants is primarily treated using temporising measures, of which the placement of a ventricular access device (VAD) is one option. Permanent shunt dependency rates are high, though vary widely. In order to improve the treatment burden and lower shunt dependency rates, we implemented several changes over the years. One of these changes involves the setting of the surgery from general anaesthesia in the OR to local anaesthesia in bed at the neonatal intensive care unit (NICU), which may seem counterintuitive to many. In this article, we describe our surgical technique and present the results of this regimen and compare it to our previous techniques.MethodsRetrospective study of a consecutive series of 37 neonates with posthaemorrhagic ventricular dilatation (PHVD) treated using a VAD, with a cohort I (n = 13) treated from 2004 to 2008 under general anaesthesia in the OR, cohort II (n = 11) treated from 2009 to 2013 under general anaesthesia in the NICU and cohort III (n = 13) treated from December 2013 to December 2017 under local anaesthesia on the NICU.ResultsThe overall infection rate was 14%; the VAD revision rate was 22% and did not differ significantly between the cohorts. Procedures under local anaesthesia never required conversion to general anaesthesia and were well tolerated. After an average of 33 tapping days, 38% of the neonates received a permanent ventriculoperitoneal (VP) shunt. The permanent VP shunt rate was 9% with VAD placement under local anaesthesia and 52% when performed under general anaesthesia (p = 0.02).ConclusionBedside placement of VADs for PHVD under local anaesthesia in neonates is a low-risk, well-tolerated procedure that results in at least equal results to surgery performed under general anaesthesia and/or performed in an OR.

Role of beta-2-microglobulin as a biomarker in very preterm and extremely preterm infants with CNS inflammation

BackgroundPremature infants are at risk for severe sepsis and meningitis, both infections associated with high mortality and morbidity. Cerebro-spinal fluid (CSF) culture is the gold standard method for meningitis diagnosis, but interpretation of biochemical parameters of CSF is essential at the moment of the analysis in order to start the appropriate treatment. The main objective of this study was to determine whether levels of CSF beta-2-microglobulin (B2M) were elevated in preterm infants with CNS infections or other inflammatory processes, and to establish if there were differences in B2M concentrations amongst various inflammatory settings (sepsis, meningitis, and progressive post-hemorrhagic ventricular dilatation (PHVD)).MethodsThis is a retrospective study of all very preterm and extremely preterm infants (< 32 weeks of gestation) admitted to our NICU between 2012 and 2017. All those who underwent a lumbar puncture during their stay as part of a sepsis work-up or PHVD were considered for inclusion. CSF biochemical parameters and B2M were tested in all of the patients.ResultsFifty-nine patients were included in the study. In patients with CNS infections, the median value of B2M was 8.69 mg/L (3.92–18.5). B2M levels above 3.92 mg/L showed greater sensitivity and specificity than leukocyte levels in discriminating between patients with CNS infections or other inflammatory processes and those without CNS inflammation.ConclusionsIn this population, CSF B2M proved to be an effective biomarker to discriminate between patients with CNS infections and other inflammatory processes and those without CNS inflammation.

Waiting for ELVIS

Clinicians awaiting the results of randomized trials for preterm infants often have to wait for a very long time to learn the neurodevelopmental outcomes of neonatal interventions. This is highlighted this month in The Journal of Pediatrics as Cizmeci et al report brain magnetic resonance imaging (MRI) outcomes for the Early vs Late Ventricular Intervention Study (ELVIS). In this study, infants with post-hemorrhagic ventricular dilation were randomized to a low vs high threshold for intervention, beginning in 2006 and completing in 2016. No difference was noted for the primary outcome of need for ventriculoperitoneal shunt placement (Arch Dis Child Fetal Neonatal Ed 2019;104:F70-5). Because post-hemorrhagic ventricular dilation is an infrequent complication of prematurity, it took 10 years to accumulate enough patients for the primary outcome. Even now, 13 years after the onset of the trial, clinicians are awaiting the neurodevelopmental outcomes that will be available when all children have been evaluated at 24 months of corrected age. In this interim report, the ELVIS authors demonstrated improved Kidokoro scores at term equivalent age on MRI for the infants who had intervention at a low threshold compared with those who had the intervention at a higher threshold. We would like to know if the improvements in Kidokoro scores will translate to a lower incidence of cerebral palsy, developmental delays, or visual impairments in these infants. Because term equivalent age MRI findings correlate with later outcomes, we would expect this to be true. However, many clinicians will await the 24-month outcomes as the interventions (lumbar puncture, ventricular reservoirs, ventriculoperitoneal shunt) have known complications that require serious consideration and perhaps the highest level of proof that is available. Article page 191▶ Assessment of Brain Injury and Brain Volumes after Posthemorrhagic Ventricular Dilatation: A Nested Substudy of the Randomized Controlled ELVIS TrialThe Journal of PediatricsVol. 208PreviewTo compare the effect of early and late intervention for posthemorrhagic ventricular dilatation on additional brain injury and ventricular volume using term-equivalent age-MRI. Full-Text PDF

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

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

Drainage, Irrigation and Fibrinolytic Therapy (DRIFT) in Premature Infants with Post-Haemorrhagic Ventricular Dilatation: 10-Year Follow-Up of a Randomised Controlled Trial

Background: Progressive ventricular dilatation after intraventricular haemorrhage (IVH) in preterm infants has a very high risk of severe disability and death. Drainage, irrigation and fibrinolytic therapy (DRIFT), in a randomised trial, reduced severe cognitive impairment at two years. No intervention has been shown objectively to improve cognitive outcome at school-age. Methods: Objective: To assess if the cognitive advantage of DRIFT seen at two years persisted until middle school-age. Participants: The randomised controlled trial in four neonatal intensive care units, recruited 77 preterm infants with IVH and progressive ventricular enlargement over specified measurements. Follow up was at a median age of ten years (range 8-12). Intervention: Intraventricular injection of a fibrinolytic followed by continuous ventricular drainage via one catheter and continuous infusion with artificial cerebrospinal fluid via a second catheter. Ventricular lavage was continued until the drainage was clear. Standard care consisted of controlling expansion by lumbar punctures and if expansion persisted via a ventricular access device. Primary outcome: Cognitive Quotient (CQ) derived from the British Ability Scales and Bayley Scales III and survival without severe cognitive disability. Findings: Of the 77 children randomized; 12 died, two could not be traced, ten did not respond and one declined at ten years follow up. 28 in the DRIFT group and 24 in the standard treatment group were assessed by examiners blind to the intervention. Mean CQ was 69·3 (sd=30·1) in the DRIFT group and 53·7 (sd=35·7) in the standard treatment group (unadjusted p=0·1; after adjustment for the pre-specified variables sex, birthweight and grade of IVH, adjusted p=0·01). Survival without severe cognitive disability, over the ten-year period, was 66% in the DRIFT group and 35% in the standard treatment group (unadjusted p=0·019; adjusted p=0·003). Interpretation: DRIFT is the first intervention to objectively demonstrate sustained cognitive improvement. Trial registration: ISRCTN80286058 Funding: NIHR HTA Declaration of Interest: None reported. Ethical Approval: Research ethics approval (14/SW/1078) was granted by the NRES Committee South West-Central Bristol and by the Faculty of Psychology Research Ethics Committee (University of Warsaw).

P93 Randomised controlled trial to determine the role of endoscopic clot lavage after intraventricular haemorrhage in neonates ENLIVEN

ObjectivesClot lavage following intraventricular haemorrhage (IVH) in premature neonates has been shown to reduce rates of hydrocephalus1 and improve neurodevelopmental outcome at 2 years and beyond.2 The aim of the ENLIVEN trial (IRAS: 198936 Rec Ref: 16/LO/1792) is to determine the efficacy of Endoscopic clot lavage after intraventricular haemorrhage in Neonates.DesignSingle centre prospective randomised controlled clinical trial comparing standard treatment with subgaleal shunt (control arm) to endoscopic washout plus standard treatment (intervention arm).SubjectsPower calculation based on published literature1 2: 50 neonates recruited over 4 years – enrolment commenced January 2018 – current recruitment 3 neonates.MethodsNeonates with radiological evidence of IVH (ventricular index &gt;99 th centile +4 mm). Primary outcome is the rate of permanent shunting, secondary outcomes include advanced MRI at term and six months, behavioural assessment at early middle and late infancy, biochemical analysis of CSF and blood.ResultsPreliminary data from the ENLIVEN trial is presented including a full description of the radiological analysis and behavioural assessment.ConclusionsDetermining how endoscopic clot lavage impacts on clinical outcome is of paramount importance in the management of neonatal IVH, the ENLIVEN trial will afford us the possibility of objectively assessing its safety and efficacy.ReferencesSchulz M, Buhrer C, Pohl-Schickinger A, et al. Neuroendoscopic lavage for the treatment of intraventricular hemorrhage and hydrocephalus in neonates. J Neurosurg Pediatr2014;13(6):626–35.Whitelaw A, Jary S, Kmita G, et al. Randomized trial of drainage, irrigation and fibrinolytic therapy for premature infants with posthemorrhagic ventricular dilatation: developmental outcome at 2 years. Pediatrics2010;125(4):e852–e58.

The Relationship Between Clinical Imaging and Neurobehavioral Assessment in Posthemorrhagic Ventricular Dilation of Prematurity.

Introduction: Neonatal intraventricular hemorrhage (IVH) and subsequent posthemorrhagic ventricular dilation and hydrocephalus of prematurity are associated with brain injury and neurodevelopmental impairment in the preterm population. Neuroimaging assesses cerebral injury and guides neurosurgical intervention; however, the relationship of head ultrasound (HUS) and magnetic resonance imaging (MRI) parameters to neonatal exams in this group has not been well described. The NICU Network Neurobehavioral Scale (NNNS) is a reproducible, highly reliable battery with motor and cognitive domain scores.Objective: To evaluate the relationship between neonatal neurobehavioral findings on the NNNS and measures of ventricular dilation and associated brain injury on HUS and MRI.Materials and Methods: Neonates with IVH and ventricular dilatation with and without posthemorrhagic hydrocephalus were enrolled. NNNS exams were performed at approximately term age equivalent. HUS indices were measured on the last HUS before initial neurosurgical procedure or that with worst ventriculomegaly if no intervention. The posterior fossa was assessed with MRI at term. Descriptive statistics including medians, interquartile ranges, means, and percentages were performed. Correlations were estimated using Pearson's method.Results: 28 patients had NNNS and HUS, and 18 patients also had an MRI. Ventricle size measures for the cohort were significantly above normal. Motor and cognitive subscores on the NNNS exam varied from established baseline scores for postmenstrual age. Children who required neurosurgical intervention had higher ventricle/brain ratios and worse NNNS habituation scores. Ventricle sizes were modestly correlated with motor abnormalities (0.24–0.59); larger anterior horn width correlated with nonoptimal reflexes, hypertonicity and hypotonicity. Ventricle sizes were modestly correlated with cognitive scores (−0.44 to 0.27); larger ventricular index correlated with worse attention. Periventricular hemorrhagic infarction correlated with worse habituation.Conclusion: For this cohort of preterm infants with IVH, surgical intervention for posthemorrhagic hydrocephalus correlated with both larger degrees of ventriculomegaly and worse NNNS exams. Findings on both HUS and MRI correlated with motor and cognitive abnormalities on neonatal neurobehavioral exam, suggesting that larger neonatal ventricle sizes and white matter injury have detectable correlates on exam. The NNNS exam provides important additional information when assessing posthemorrhagic ventricular dilation and hydrocephalus of prematurity.

Early inotropes use is associated with higher risk of death and/or severe brain injury in extremely premature infants

Introduction: Extremely premature infants are susceptible to fluctuations in cerebral blood flow due to immaturity of cerebral autoregulation. Inotropes may cause rapid changes to systemic blood pressure and consequently cerebral blood flow, especially within the first 72 hours of life. This period is recognized to carry the greatest risk for cerebral hemorrhage. This study evaluates the incidence of death and/or severe brain injury in extremely preterm infants treated with inotropes in the first 72 hours of life.Methods: Prospective cohort study of infants born ≤29+0 weeks gestational age (GA) between January 2013 and December 2016. Severe brain injury was defined based on head ultrasound as presence of: grade III or IV intraventricular hemorrhage (IVH), moderate to severe post-hemorrhagic ventricular dilatation (PHVD), or cystic periventricular leukomalacia (cPVL). The association between inotrope use and death and/or brain injury was explored via logistic regression controlling for predefined confounding risk factors.Results: Of 497 eligible infants, 97 (19.5%) received inotropes during the first 72 hours. GA at birth, birth weight (BW), and 5-minute Apgar scores were lower among infants who received early inotropes compared to those not treated with inotropes. A stepwise logistic regression of the predefined confounding factors showed GA, exposure for antenatal steroids, and admission hypothermia to be significant confounding factors. Adjusting for those factors, early use of inotropes was associated with increased risk of death and/or severe brain injury (AOR 4.5; 95%CI: 2.4–8.5), severe brain injury (AOR 4.2; 95% CI: 1.9–8.9), and IVH of any grade (AOR 2.9; 95%CI: 1.7–4.9).Conclusion: Early inotropes use was associated with higher risk of death and/or severe brain injury. Strict indications and strategies for minimizing inotrope use while preventing hypotension should be implemented in the early postnatal care of infants at risk for severe brain injury.

Chapter 8 - Preterm brain injury: Germinal matrix–intraventricular hemorrhage and post-hemorrhagic ventricular dilatation

Germinal matrix hemorrhage and intraventricular hemorrhages (GMH-IVH) remain a common and clinically significant problem in preterm infants, particularly extremely preterm infants. A large GMH-IVH is often complicated by posthemorrhagic ventricular dilation (PHVD) or parenchymal hemorrhagic infarction and is associated with an increased risk of adverse neurologic sequelae. The widespread use of cranial ultrasonography since the early 1980s has shown a gradual decrease in the incidence of GMH-IVH and has helped with the identification of antenatal and perinatal risk factors and timing of the lesion. The increased use of magnetic resonance imaging (MRI) has contributed to more detailed visualization of the site and extent of the GMH-IVH. In addition, MRI has contributed to the awareness of associated white matter changes as well as associated cerebellar hemorrhages. Although GMH-IVH and PHVD still cannot be prevented, cerebrospinal fluid drainage initiated in the early stage of PHVD development seems to be associated with a better neurodevelopmental outcome. Further studies are underway to improve treatment strategies for PHVD and to potentially prevent and repair GMH-IVH and PHVD and associated brain injury. This chapter discusses the pathogenesis, incidence, risk factors, and management, including preventive measures, of GHM-IVH and PHVD.

Automatic extraction of the intracranial volume in fetal and neonatal MR scans using convolutional neural networks.

MR images of infants and fetuses allow non-invasive analysis of the brain. Quantitative analysis of brain development requires automatic brain tissue segmentation that is typically preceded by segmentation of the intracranial volume (ICV). Fast changes in the size and morphology of the developing brain, motion artifacts, and large variation in the field of view make ICV segmentation a challenging task. We propose an automatic method for segmentation of the ICV in fetal and neonatal MRI scans. The method was developed and tested with a diverse set of scans regarding image acquisition parameters (i.e. field strength, image acquisition plane, image resolution), infant age (23-45 weeks post menstrual age), and pathology (posthaemorrhagic ventricular dilatation, stroke, asphyxia, and Down syndrome). The results demonstrate that the method achieves accurate segmentation with a Dice coefficient (DC) ranging from 0.98 to 0.99 in neonatal and fetal scans regardless of image acquisition parameters or patient characteristics. Hence, the algorithm provides a generic tool for segmentation of the ICV that may be used as a preprocessing step for brain tissue segmentation in fetal and neonatal brain MR scans.

Editors' note: Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene?

In reference to “Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene?” Dr. Munakomi supports early intervention after intraventricular bleed and reframes the pertinent question to be how to predict early neuronal damage in these patients. He suggests using diffusion tensor imaging (DTI) to assess for anisotropy in the periventricular tracks and near-infrared spectroscopy (NIRS). Authors de Vries and Leijser agree that while predicting neuronal damage would be advantageous, it is not currently possible. NIRS monitoring, they suggest, may be used in combination with other modalities to inform the timing of neurosurgical intervention. Serial DTIs would be technically challenging in most centers, whereas head ultrasounds are more practical and may provide more useful information. In reference to “Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene?” Dr. Munakomi supports early intervention after intraventricular bleed and reframes the pertinent question to be how to predict early neuronal damage in these patients. He suggests using diffusion tensor imaging (DTI) to assess for anisotropy in the periventricular tracks and near-infrared spectroscopy (NIRS).

Reader response: Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene?

I read with interest the article by Leijser et al.1 regarding management algorithm in preterm infants with posthemorrhagic ventricular dilation. The intraventricular hemorrhage indicates neuronal damage owing to its propensity for causing acute hydrocephalus due to clot, chronic hydrocephalus due to fibrosis, and impending neuronal damage due to vasospasm. Early intervention thereby assures early resolution of bleed, maintains patency of the normal CSF pathways, as well as prevents axonal stretch, thereby optimizing neuronal plasticity. So the burning issue is not in when and how to intervene, but how to foresee early neuronal damage following intraventricular bleed. In these aspects, inclusions of diffusion tensor imaging for early visualization of anisotropy within the periventricular tracks and usage of near-infrared spectroscopy may be of immense value in optimizing time of intervention.2 This approach would aid in early intervention, thereby better outcome, as justified by the authors.1

Author response: Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene?

We thank Dr. Munakomi for his interest in our article1 and agree that forseeing early neuronal damage would aid in the decision regarding optimal timing for intervention. However, currently there is no way to foresee this. As described in other studies2,3 and an abstract by our own group,4 near-infrared spectroscopy (NIRS) values decreased in infants with severe ventricular dilatation.

Reader response: Nutrients and bioactives in green leafy vegetables and cognitive decline: Prospective study.

In reference to “Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene?” Dr. Munakomi supports early intervention after intraventricular bleed and reframes the pertinent question to be how to predict early neuronal damage in these patients. He suggests using diffusion tensor imaging (DTI) to assess for anisotropy in the periventricular tracks and near-infrared spectroscopy (NIRS). Authors de Vries and Leijser agree that while predicting neuronal damage would be advantageous, it is not currently possible. NIRS monitoring, they suggest, may be used in combination with other modalities to inform the timing of neurosurgical intervention. Serial DTIs would be technically challenging in most centers, whereas head ultrasounds are more practical and may provide more useful information.

An MR-based quantitative intraventricular hemorrhage porcine model for MR-guided focused ultrasound thrombolysis.

Intraventricular hemorrhage (IVH) affects approximately 50% of premature births where 50% further develop post-hemorrhagic ventricular dilation (PHVD). Patients face significant impact to long-term development if PHVD is not managed. Unfortunately, there is no accepted treatment to remove the thrombus caused by IVH. This paper describes an acute and chronic IVH model for use with magnetic resonance-guided focused ultrasound (MRgFUS) thrombolysis. A total of 12 pigs (~ 1month in age) were used in the model (eight acute and four chronic). A pre-operative brain MRI was obtained for ventricular targeting. 1.25cm3/kg of autologous blood was injected through a burr hole lateral to the midline and anterior of the coronal suture at a rate of 0.6cm3/min. A craniotomy was performed to simulate a "fontanelle". Post-operative MRI was used to calculate the clot volume. Chronic piglets were recovered, monitored daily with a neurological scoring system (NSS), and MRI scanned for 21days. The clot injection was well tolerated. The average clot size was 3987mm3 (median = 4330mm, standard deviation = 739mm3). Postmortem examination validated the presence of the clot. In the chronic animals, there was an increase in ventricular volume of 30%. Transient neurological impairment immediately followed clot injection and with onset of hydrocephalus in the chronic animals. This model establishes a measurable and targetable IVH clot in an MRI-based neonatal porcine model. The progressive post-hemorrhagic ventricular dilation in the chronic model is a potential alterable outcome from MRgFUS thrombolysis.

Treatment thresholds for intervention in posthaemorrhagic ventricular dilation: a randomised controlled trial

ObjectiveTo compare a low versus a higher threshold for intervention in preterm infants with posthaemorrhagic ventricular dilatation.DesignMulticentre randomised controlled trial (ISRCTN43171322).Setting14 neonatal intensive care units in six countries.Patients126 preterm infants...

Posthemorrhagic ventricular dilatation in preterm infants: When best to intervene?

To compare neurodevelopmental outcomes of preterm infants with and without intervention for posthemorrhagic ventricular dilatation (PHVD) managed with an "early approach" (EA), based on ventricular measurements exceeding normal (ventricular index [VI] <+2 SD/anterior horn width <6 mm) with initial temporizing procedures, followed, if needed, by permanent shunt placement, and a "late approach" (LA), based on signs of increased intracranial pressure with mostly immediate permanent intervention. Observational cohort study of 127 preterm infants (gestation <30 weeks) with PHVD managed with EA (n = 78) or LA (n = 49). Ventricular size was measured on cranial ultrasound. Outcome was assessed at 18-24 months. Forty-nine of 78 (63%) EA and 24 of 49 (49%) LA infants received intervention. LA infants were slightly younger at birth, but did not differ from EA infants for other clinical measures. Initial intervention in the EA group occurred at younger age (29.4/33.1 week postmenstrual age; p < 0.001) with smaller ventricles (VI 2.4/14 mm >+2 SD; p < 0.01), and consisted predominantly of lumbar punctures or reservoir taps. Maximum VI in infants with/without intervention was similar in EA (3/1.5 mm >+2 SD; p = 0.3) but differed in the LA group (14/2.1 mm >+2 SD; p < 0.001). Shunt rate (20/92%; p < 0.001) and complications were lower in EA than LA group. Most EA infants had normal outcomes (>-1 SD), despite intervention. LA infants with intervention had poorer outcomes than those without (p < 0.003), with scores <-2 SD in 81%. In preterm infants with PHVD, those with early intervention, even when eventually requiring a shunt, had outcomes indistinguishable from those without intervention, all being within the normal range. In contrast, in infants managed with LA, need for intervention predicted worse outcomes. Benefits of EA appear to outweigh potential risks. This study provides Class III evidence that for preterm infants with PHVD, an EA to management results in better neurodevelopmental outcomes than a LA.

The use of clinical examination and cranial ultrasound in the diagnosis and management of post-hemorrhagic ventricular dilation in extremely premature infants.

The objective of this study is to describe clinical and ultrasound changes in a cohort of premature newborns with post-hemorrhagic ventricular dilation (PHVD), and to correlate these changes with outcome. Premature newborns <29 weeks gestational age (GA) and ≤ 1,500 g birth weight with intraventricular hemorrhage were retrospectively reviewed. Clinical signs and cranial ultrasound (CUS) findings between time after birth and time before first cerebrospinal fluid temporizing intervention were compared with GA-equivalent newborns without interventions. White matter injury was assessed on brain magnetic resonance imaging. Between 2011 and 2014, 64 newborns met inclusion criteria; 23% had PHVD. The growth rates of the ventricles on CUS and the head circumference (HC) were higher in newborns with PHVD (p < 0.01 and p = 0.04, respectively) and correlated inversely with white matter injury (p = 0.006 and p < 0.001, respectively). Progression of PHVD in premature newborns as demonstrated by CUS and the HC correlated with outcome. Consistent measurement of these simple parameters will allow for much needed treatment comparisons, to define optimal protocols that decrease the risk of cerebral palsy in extremely preterm populations.

Monitoring intraventricular vancomycin for ventriculostomy access device infection in preterm infants.

Ventriculitis is a known complication during external CSF drainage in preterm infants with posthaemorrhagic ventricular dilatation. Staphylococci are most frequently isolated in device-associated ventriculitis, and hence, intraventricular vancomycin is a commonly used therapy. Our aim was to study the CSF vancomycin level pattern and drug safety in ventriculostomy access device infection in preterm infants less than 28weeks gestation. This single-centre, retrospective case series included seven infants with a median gestational age of 25+4weeks (range 23+6 to 27+5weeks). Ventriculitis was defined as elevated CSF white cell count of >20/mm3 or positive CSF culture. The CSF vancomycin concentrations following intraventricular vancomycin administration were studied. Forty treatment episodes of intraventricular vancomycin administration were studied in seven preterm infants. Maximum CSF vancomycin concentrations were 24.9mg/L (3mg, n=8, observed concentration-time (OCT), hours (h) =19), 96.3mg/L (5mg, n=17, OCT(h) =14), 94mg/L (10mg, n=14, OCT(h) =24), and 230.7mg/L (15mg, n=1, OCT(h) =24). The threshold for re-dosage is set at CSF vancomycin level of <10mg/L. In all patients, ventriculitis resolution (defined as sterile CSF and CSF WCC of <20/mm3) was achieved in a median of 5.5days (range 2-31days). Individual microbiology data is provided in the online resource. Intraventricular vancomycin is an effective treatment for ventriculostomy access device infection in preterm infants. In doses ranging from 3 to 15mg, sufficient CSF vancomycin level is generated to achieve microbiological cure without any reported adverse effects. Daily CSF drug monitoring is recommended to define dosage interval to maintain drug concentration above breakpoint of minimum inhibitory concentration.

Investigating the effects of cerebrospinal fluid removal on cerebral blood flow and oxidative metabolism in infants with post-hemorrhagic ventricular dilatation.

BackgroundPost-hemorrhagic ventricular dilatation (PHVD) is predictive of mortality and morbidity among very-low-birth-weight preterm infants. Impaired cerebral blood flow (CBF) due to elevated intracranial pressure (ICP) is believed to be a contributing factor.MethodsA hyperspectral near-infrared spectroscopy (NIRS) method of measuring CBF and the cerebral metabolic rate of oxygen (CMRO2) was used to investigate perfusion and metabolism changes in patients receiving a ventricular tap (VT) based on clinical management. To improve measurement accuracy, the spectral analysis was modified to account for compression of the cortical mantle caused by PHVD and the possible presence of blood breakdown products.ResultsFrom nine patients (27 VTs), a significant CBF increase was measured (15.6%) following VT (14.6±4.2 to 16.9±6.6 ml/100 g/min), but with no corresponding change in CMRO2 (1.02±0.41 ml O2/100 g/min). Post-VT CBF was in good agreement with a control group of 13 patients with patent ductus arteriosus but no major cerebral pathology (16.5±7.7 ml/100 g/min), whereas tissue oxygen saturation (StO2) was significantly lower (58.9±12.1% vs. 70.5±9.1% for controls).ConclusionCBF was impeded in PHVD infants requiring a clinical intervention, but the effect is not large enough to alter CMRO2.