Current Status and Associated Factors of Post-Hemorrhagic Hydrocephalus in Infants of 22 to 28 Weeks Gestation With Severe Intraventricular Hemorrhage in Korea: A Nationwide Cohort Study.

BACKGROUND: Post-hemorrhagic hydrocephalus (PHH), a common complication of severe intraventricular hemorrhage (IVH) in very low birth weight (BW) infants, is associated with significant morbidity and poor neurological outcomes. The objective of this study was to assess the current status of PHH and analyze the risk factors associated with the necessity of treatment for PHH in infants born between 22 and 28 weeks of gestation, specifically those with severe IVH (grade 3 or 4). METHODS: The analysis was conducted on 1,097 infants who were born between 22-28 gestational weeks and diagnosed with severe IVH, using data from the Korean Neonatal Network. We observed that the prevalence of PHH requiring treatment was 46.3% in infants with severe IVH. RESULTS: Higher rates of mortality, transfer during admission, cerebral palsy, and ventriculoperitoneal shunt after discharge were higher in infants with PHH than in those without PHH. PHH in severe IVH was associated with a higher rate of pulmonary hemorrhage, seizures, and IVH grade 4 in the entire cohort. In addition, it was associated with a lower rate of small for gestational age and chorioamnionitis. In the subgroup analysis, high BW, outborn status, pulmonary hemorrhage, seizure, sepsis, and IVH grade 4 were associated with a higher incidence of PHH between 22 and 25 gestational weeks (GW). In infants born between 26 and 28 GW, a higher incidence of PHH was associated with seizures and IVH grade 4. CONCLUSION: It is necessary to maintain meticulous monitoring and neurological intervention for infants with PHH not only during admission but also after discharge. In addition, identifying the clinical factors that increase the likelihood of developing PHH from severe IVH is crucial.

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

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

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

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

C3/C3aR inhibition alleviates GMH-IVH-induced hydrocephalus by preventing microglia-astrocyte interactions in neonatal rats.

Activation of microglia and astrocytes following germinal matrix hemorrhage and intraventricular hemorrhage (GMH-IVH) plays a detrimental role in posthemorrhagic hydrocephalus (PHH). It is still unclear whether or how an interaction occurs between microglia and astrocytes in PHH. Here, we investigated the role of the C3/C3aR pathway in microglia and astrocyte interactions and whether C3/C3aR-targeted inhibition could alleviate PHH following GMH-IVH. A total of 152 Sprague-Dawley rats at postnatal day seven (P7) were enrolled in the study, and collagenase VII was used to induce GMH-IVH. Minocycline (45 mg/kg) was administered to inhibit microglial activation. Complement C3a peptide and C3aR antagonist (SB 290157, 10 mg/kg) were used to regulate the C3/C3aR pathway. As a result, the data demonstrated that periventricular C3aR+/Iba-1+ microglia and C3+/GFAP+ astrocytes were significantly increased in GMH-IVH pups at 28 days after surgery. Intranasal C3a peptide upregulated C3aR expression in microglia. Inhibition of microglia by minocycline decreased both C3+/GFAP+ astrocytes and the colocalization volume of Iba-1 and GFAP. In addition, intraperitoneally injected C3aRA alleviated the periventricular colocalization volume of microglia and astrocytes. Compared with vehicle-treated pups, the protein level of IL-1ß, IL-6 and TNF-α in cerebral spinal fluid and brain tissue at 28 days following GMH-IVH were reduced in C3aRA-treated pups. Moreover, hydrocephalus was alleviated, and long-term cognitive ability were improved in the C3aRA-treated group. Our data presented simultaneous periventricular astrogliosis and microgliosis of pups following GMH-IVH and proved their potential interaction through the C3/C3aR pathway, indicating C3aRA as a potential pharmacological treatment of PHH in neonates.

Biochemical profile of human infant cerebrospinal fluid in intraventricular hemorrhage and post-hemorrhagic hydrocephalus of prematurity.

BACKGROUND: Intraventricular hemorrhage (IVH) and post-hemorrhagic hydrocephalus (PHH) have a complex pathophysiology involving inflammatory response, ventricular zone and cell-cell junction disruption, and choroid-plexus (ChP) hypersecretion. Increased cerebrospinal fluid (CSF) cytokines, extracellular matrix proteins, and blood metabolites have been noted in IVH/PHH, but osmolality and electrolyte disturbances have not been evaluated in human infants with these conditions. We hypothesized that CSF total protein, osmolality, electrolytes, and immune cells increase in PHH. METHODS: CSF samples were obtained from lumbar punctures of control infants and infants with IVH prior to the development of PHH and any neurosurgical intervention. Osmolality, total protein, and electrolytes were measured in 52 infants (18 controls, 10 low grade (LG) IVH, 13 high grade (HG) IVH, and 11 PHH). Serum electrolyte concentrations, and CSF and serum cell counts within 1-day of clinical sampling were obtained from clinical charts. Frontal occipital horn ratio (FOR) was measured for estimating the degree of ventriculomegaly. Dunn or Tukey's post-test ANOVA analysis were used for pair-wise comparisons. RESULTS: CSF osmolality, sodium, potassium, and chloride were elevated in PHH compared to control (p = 0.012 - < 0.0001), LGIVH (p = 0.023 - < 0.0001), and HGIVH (p = 0.015 - 0.0003), while magnesium and calcium levels were higher compared to control (p = 0.031) and LGIVH (p = 0.041). CSF total protein was higher in both HGIVH and PHH compared to control (p = 0.0009 and 0.0006 respectively) and LGIVH (p = 0.034 and 0.028 respectively). These differences were not reflected in serum electrolyte concentrations nor calculated osmolality across the groups. However, quantitatively, CSF sodium and chloride contributed 86% of CSF osmolality change between control and PHH; and CSF osmolality positively correlated with CSF sodium (r, p = 0.55,0.0015), potassium (r, p = 0.51,0.0041), chloride (r, p = 0.60,0.0004), but not total protein across the entire patient cohort. CSF total cells (p = 0.012), total nucleated cells (p = 0.0005), and percent monocyte (p = 0.016) were elevated in PHH compared to control. Serum white blood cell count increased in PHH compared to control (p = 0.042) but there were no differences in serum cell differential across groups. CSF total nucleated cells also positively correlated with CSF osmolality, sodium, potassium, and total protein (p = 0.025 - 0.0008) in the whole cohort. CONCLUSIONS: CSF osmolality increased in PHH, largely driven by electrolyte changes rather than protein levels. However, serum electrolytes levels were unchanged across groups. CSF osmolality and electrolyte changes were correlated with CSF total nucleated cells which were also increased in PHH, further suggesting PHH is a neuro-inflammatory condition.

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

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

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

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

Complicaciones en la hemorragia intraventricular del recién nacido, a propósito de un caso / Complications in the intraventricular hemorrhage of the newborn, a propos of a case

RESUMEN La hemorragia interventricular es una complicación frecuente en el recién nacido prematuro. Se presentó el caso con el objetivo de describir las complicaciones en la hemorragia intraventricular en el recién nacido. Se trató de una recién nacida, producto de un embarazo de 30 semanas de gestación, con peso al nacer de 1 600 g. Desarrolló una hemorragia intraventricular e hidrocefalia que requirió diferentes intervenciones neuroquirúrgicas y desarrolló complicaciones sépticas graves. La ventriculitis y los abscesos cerebrales fueron las complicaciones más peligrosas. Se realizaron lavados ventriculares. Se utilizó antibióticos intraventriculares y también antibioticoterapia sistémica, cambios frecuentes de catéter de derivación al exterior y permanencia de una derivación ventricular externa por 102 días. Después de seis meses de evolución, de más de veinte intervenciones quirúrgicas, y de haber sufrido severas complicaciones sépticas, se logró realizar la derivación ventrículo-peritoneal definitiva, lográndose su egreso. Al año de vida, la paciente mantiene un desarrollo psicomotor adecuado (AU).

ABSTRACT The interventricular hemorrhage is a frequent complication in the premature newborn baby. The case was presente with the aim of describing the complications of intraventricular hemorrhage in the newborn baby. It dealed with a female newborn baby, product of a 30 weeks pregnancy, with weight at birth of 1 600 g. She developed intraventricular hemorrhage and hydrocephalus that required different neurosurgical interventions and developed serious septic complications. Ventriculitis and brain abscesses were the most dangerous complications. Ventricular lavages were performed. Intraventricular antibiotics were used as well as systemic antibiotic therapy, frequent changes of bypass catheter to the exterior and permanence of an external ventricular bypass for 102 days. And permanence of an external ventricular shunt for 102 days. After six months of evolution, more than twenty surgical interventions, and having suffered severe septic complications, it was possible to perform the definitive ventricular-peritoneal bypass, achieving her discharge. At a year of life, the patient maintains adequate psychomotor development (AU).

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

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

Relationship between intraventricular hemorrhage and acute kidney injury in premature infants and its effect on neonatal mortality.

Intraventricular hemorrhage (IVH) and acute kidney injury (AKI) are important neonatal morbidities in premature infants. This study aimed to investigate the relationship between IVH and AKI in premature infants and whether this association affects the incidence of neonatal mortality. Infants [gestational age (GA) ≤ 32 weeks; birth weight (BW) < 1500 g] were retrospectively evaluated in a large tertiary neonatal intensive care unit. Of 710 premature infants, 268 (37.7%) developed AKI. Infants with IVH were more likely to have AKI than those without IVH. Infants with severe IVH had a higher incidence of AKI than infants with mild IVH. Infants younger than 28 weeks with IVH were more likely to have AKI than those without IVH. An association between IVH grades and AKI stages was observed in the overall study population, in infants with GA < 28 weeks, and in infants with GA between 28 and 32 weeks. Mortality was increased 1.5 times in infants with IVH and AKI compared with that in infants with IVH but without AKI. Furthermore, mortality was increased in infants with IVH and AKI compared with infants without IVH or AKI. This study shows a direct relationship between the severity of IVH and the degree of AKI; both IVH and AKI increase the incidence of neonatal mortality.

Predicting intraventricular hemorrhage growth with a machine learning-based, radiomics-clinical model.

We constructed a radiomics-clinical model to predict intraventricular hemorrhage (IVH) growth after spontaneous intracerebral hematoma. The model was developed using a training cohort (N=626) and validated with an independent testing cohort (N=270). Radiomics features and clinical predictors were selected using the least absolute shrinkage and selection operator (LASSO) method and multivariate analysis. The radiomics score (Rad-score) was calculated through linear combination of selected features multiplied by their respective LASSO coefficients. The support vector machine (SVM) method was used to construct the model. IVH growth was experienced by 13.4% and 13.7% of patients in the training and testing cohorts, respectively. The Rad-score was associated with severe IVH and poor outcome. Independent predictors of IVH growth included hypercholesterolemia (odds ratio [OR], 0.12 [95%CI, 0.02-0.90]; p=0.039), baseline Graeb score (OR, 1.26 [95%CI, 1.16-1.36]; p<0.001), time to initial CT (OR, 0.70 [95%CI, 0.58-0.86]; p<0.001), international normalized ratio (OR, 4.27 [95%CI, 1.40, 13.0]; p=0.011), and Rad-score (OR, 2.3 [95%CI, 1.6-3.3]; p<0.001). In the training cohort, the model achieved an AUC of 0.78, sensitivity of 0.83, and specificity of 0.66. In the testing cohort, AUC, sensitivity, and specificity were 0.71, 0.81, and 0.64, respectively. This radiomics-clinical model thus has the potential to predict IVH growth.

Novel Score for Stratifying Risk of Critical Care Needs in Patients With Intracerebral Hemorrhage.

OBJECTIVE: To develop a risk prediction score identifying patients with intracerebral hemorrhage (ICH) at low risk for critical care. METHODS: We retrospectively analyzed data of 451 patients with ICH between 2010 and 2018. The sample was randomly divided into a development and a validation cohort. Logistic regression was used to develop a risk score by weighting independent predictors of intensive care unit (ICU) needs according to strength of association. The risk score was tested in the validation cohort and externally validated in a dataset from another institution. RESULTS: The rate of ICU interventions was 80.3%. Systolic blood pressure (SBP), Glasgow Coma Scale (GCS) score, intraventricular hemorrhage (IVH), and ICH volume were independent predictors of critical care, resulting in the following point assignments for the Intensive Care Triaging in Spontaneous Intracerebral Hemorrhage (INTRINSIC) score: SBP 160 to 190 mm Hg (1 point), SBP >190 mm Hg (3 points); GCS 8 to 13 (1 point), GCS <8 (3 points); ICH volume 16 to 40 cm3 (1 point), ICH volume >40 cm3 (2 points); and presence of IVH (1 point), with values ranging between 0 and 9. Among patients with a score of 0 and no ICU needs during their emergency department stay, 93.6% remained without critical care needs. In an external validation cohort of patients with ICH, the INTRINSIC score achieved an area under the receiver operating characteristic curve of 0.823 (95% confidence interval 0.782-0.863). A score <2 predicted the absence of critical care needs with 48.5% sensitivity and 88.5% specificity, and a score <3 predicted the absence of critical care needs with 61.7% sensitivity and 83.0% specificity. CONCLUSION: The INTRINSIC score identifies patients with ICH who are at low risk for critical care interventions. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the INTRINSIC score identifies patients with ICH at low risk for critical care interventions.

Tailor-Made Endoscopic Surgical Strategy for Severe Intraventricular Hemorrhage with Obstructive Hydrocephalus.

BACKGROUND: Severe intraventricular hemorrhage (IVH) is associated with a high mortality rate and poor functional outcome, even with recent neurosurgical developments. IVH requires emergent surgery to save the patient's life, but the optimal surgical strategy remains controversial. We assessed the results obtained with our tailor-made endoscopic surgical strategy for severe IVH with obstructive hydrocephalus. METHODS: Consecutive patients with severe IVH owing to intracerebral hemorrhage who were treated with endoscopic surgery in the acute phase were retrospectively reviewed. Both rigid and flexible endoscopes were used for removal of hematoma in the whole ventricular system. Endoscopic third ventriculostomy and septostomy were performed as appropriate in each individual case. RESULTS: Eight patients met the inclusion criteria and were included in the analysis. Sufficient IVH removal without neglecting the fourth ventricle was achieved with our technique in 6 of 8 cases (75.0%). Endoscopic third ventriculostomy and septostomy were added in 4 cases each (50.0%). Four patients (50.0%) had a marked recovery and a good outcome (modified Rankin Scale score ≤2) despite disease severity at onset. The procedure was completed successfully in all cases, and there were no surgery-related complications. CONCLUSIONS: This study showed that our tailor-made endoscopic surgical strategy for severe IVH with obstructive hydrocephalus may be beneficial.

Face mask versus nasal prong or nasopharyngeal tube for neonatal resuscitation in the delivery room: a systematic review and meta-analysis.

IMPORTANCE: The current neonatal resuscitation guidelines recommend positive pressure ventilation via face mask or nasal prongs at birth. Using a nasal interface may have the potential to improve outcomes for newborn infants. OBJECTIVE: To determine whether nasal prong/nasopharyngeal tube versus face mask during positive pressure ventilation of infants born <37 weeks' gestation in the delivery room reduces in-hospital mortality and morbidity. DATA SOURCES: MEDLINE (through PubMed), Google Scholar and EMBASE, Clinical Trials.gov and the Cochrane Central Register of Controlled Trials through August 2019. STUDY SELECTION: Randomised controlled trials comparing nasal prong/nasopharyngeal tube versus face mask during positive pressure ventilation of infants born <37 weeks' gestation in the delivery room. DATA ANALYSIS: Risk of bias was assessed using the Covidence Collaboration Tool, results were pooled into a meta-analysis using a random effects model. MAIN OUTCOME: In-hospital mortality. RESULTS: Five RCTs enrolling 873 infants were combined into a meta-analysis. There was no statistical difference in in-hospital mortality (risk ratio (RR 0.98, 95% CI 0.63 to 1.52, p=0.92, I2=11%), rate of chest compressions in the delivery room (RR 0.37, 95% CI 0.10 to 1.33, p=0.13, I2=28%), rate of intraventricular haemorrhage (RR 1.54, 95% CI 0.88 to 2.70, p=0.13, I2=0%) or delivery room intubations in infants ventilated with a nasal prong/tube (RR 0.63, 95% CI 0.39,1.02, p=0.06, I2=52%). CONCLUSION: In infants born <37 weeks' gestation, in-hospital mortality and morbidity were similar following positive pressure ventilation during initial stabilisation with a nasal prong/tube or a face mask.

White matter injury in infants with intraventricular haemorrhage: mechanisms and therapies.

Intraventricular haemorrhage (IVH) continues to be a major complication of prematurity that can result in cerebral palsy and cognitive impairment in survivors. No optimal therapy exists to prevent IVH or to treat its consequences. IVH varies in severity and can present as a bleed confined to the germinal matrix, small-to-large IVH or periventricular haemorrhagic infarction. Moderate-to-severe haemorrhage dilates the ventricle and damages the periventricular white matter. This white matter injury results from a constellation of blood-induced pathological reactions, including oxidative stress, glutamate excitotoxicity, inflammation, perturbed signalling pathways and remodelling of the extracellular matrix. Potential therapies for IVH are currently undergoing investigation in preclinical models and evidence from clinical trials suggests that stem cell treatment and/or endoscopic removal of clots from the cerebral ventricles could transform the outcome of infants with IVH. This Review presents an integrated view of new insights into the mechanisms underlying white matter injury in premature infants with IVH and highlights the importance of early detection of disability and immediate intervention in optimizing the outcomes of IVH survivors.

Comparative Analysis of the Patients with Spontaneous Thalamic Hemorrhage with Concurrent Intraventricular Hemorrhage and Those without Intraventricular Hemorrhage.

BACKGROUND: This study aimed to compare the characteristics of patients with spontaneous thalamic hemorrhage (STH) accompanied by intraventricular hemorrhage (IVH) with those of patients without IVH. METHODS: The medical records of consecutive patients with STH admitted to our institute between January 2000 and December 2018 were reviewed retrospectively. The laboratory and radiological results, mortality, and functional recovery were compared between the STH patients with IVH and those without IVH. RESULTS: Among 2,389 patients with spontaneous intracerebral hemorrhage, 233 (9.8%) patients were included in this study. Concurrent IVH was detected in 159 (68.2%) patients with STH, and more frequently in those with body mass index ≥ 25, Glasgow Coma Scale score of 3-8, underlying disease, family history of stoke, posterior/medial/global location of hematoma, ventriculomegaly, large volume of hemorrhage, and midline shift ≥ 5 mm. The 3-month mortality was 25.8% and 8.1% (P = 0.039), the rate of good functional recovery at 6 months was 52.2% and 31.0% (P = 0.040), and incidence of delayed normal pressure hydrocephalus (NPH) at 12 months was 10.8% and 24.5% (P = 0.062) in the STH patients with IVH and those without IVH, respectively. At 12 months, delayed NPH developed in 28 of 47 (59.6%) patients who received external ventricular drainage (EVD)-based treatment, 5 of 45 (11.1%) patients who underwent endoscopic evacuation-based treatment, and 8 of 45 (17.8%) patients who underwent other surgeries. CONCLUSION: Concurrent IVH is strongly associated with mortality in patients with STH. Delayed NPH may develop more frequently in STH patients with IVH who were treated with EVD.

Neonatal Antiepileptic Medication Treatment Patterns: A Decade of Change.

OBJECTIVE: This study aims to describe the frequency and characteristics of anticonvulsant medication treatments initiated in the neonatal period. STUDY DESIGN: We analyzed a cohort of neonates with a seizure diagnosis who were discharged from institutions in the Pediatric Health Information System between 2007 and 2016. Adjusted risk ratios and 95% confidence intervals for characteristics associated with neonatal (≤ 28 days postnatal) anticonvulsant initiation were calculated via modified Poisson regression. RESULTS: A total of 6,245 infants from 47 institutions were included. There was a decrease in both phenobarbital initiation within the neonatal period (96.9 to 91.3%, p = 0.015) and continuation at discharge (90.6 to 68.6%, p <0.001). Levetiracetam (7.9 to 39.6%, p < 0.001) initiation within the neonatal period and continuation at discharge (9.4 to 49.8%, p < 0.001) increased. Neonates born at ≥ 37 weeks' gestation and those diagnosed with intraventricular hemorrhage, ischemic/thrombotic stroke, other hemorrhagic stroke, and hypoxic ischemic encephalopathy (HIE) had a higher probability of anticonvulsant administration. The most prevalent diagnosis was HIE (n = 2,223, 44.4%). CONCLUSION: Phenobarbital remains the most widely used neonatal seizure treatment. Levetiracetam is increasingly used as a second line therapy. Increasing levetiracetam use indicates a need for additional study to determine its effectiveness in reducing seizure burden and improving long-term outcomes.

Antenatal diagnosis of fetal intraventricular hemorrhage: systematic review and meta-analysis.

AIM: To determine how the severity of antenatally diagnosed germinal matrix-intraventricular hemorrhage (GMH-IVH) relates to morbidity and mortality, and to explore potential risk factors. METHOD: We conducted a systematic review and individual patient data meta-analysis of antenatally diagnosed fetal GMH-IVH. The primary outcomes were mortality and morbidity. Potential associations with clinical factors during pregnancy were explored. Analysis employed Fisher's exact test and logistic regression. RESULTS: We included 240 cases from 80 studies. Presence of venous infarction was associated with mortality (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.4-13.25), motor impairment (OR 103.2, 95% CI 8.6-1238), epilepsy (OR 6.46, 95% CI 2.64-16.06), and developmental delay (OR 8.55, 95% CI 2.12-48.79). Shunt placement was associated with gestational age at GMH-IVH diagnosis and in utero progression. Many cases had uncomplicated pregnancies but possible co-occurring conditions included twin gestation, small for gestational age, and congenital anomalies. INTERPRETATION: Severity of fetal GMH-IVH, specifically venous infarction, is associated with overall mortality and morbidity. Risk factors for fetal GMH-IVH are poorly understood and controlled studies are required. WHAT THIS PAPER ADDS: Preterm germinal matrix-intraventricular hemorrhage (GMH-IVH) grading can be applied to fetuses. Many fetal germinal matrix hemorrhages occur in otherwise typical pregnancies. Half of fetuses with post-hemorrhagic ventricular dilatation receive a shunt after delivery. Fetuses with grade I or II GMH-IVH have few sequelae. Fetuses with periventricular hemorrhagic infarction have a high burden of motor impairment.

School-age outcomes following intraventricular haemorrhage in infants born extremely preterm.

OBJECTIVE: To determine the associations of different grades of intraventricular haemorrhage (IVH), particularly grades 1 and 2, with neurodevelopmental outcomes at 8 years of age in children born extremely preterm. DESIGN: Population-based cohort study. SETTING: State of Victoria, Australia. PATIENTS: Survivors born at <28 weeks' gestational age (n=546) and matched term-born controls (n=679) from three distinct eras, namely, those born in 1991-1992, 1997 and 2005. EXPOSURE: Worst grade of IVH detected on serial neonatal cranial ultrasound. OUTCOME MEASURES: Intellectual ability, executive function, academic skills, cerebral palsy and motor function at 8 years. RESULTS: There was a trend for increased motor dysfunction with increasing severity of all grades of IVH, from 24% with no IVH, rising to 92% with grade 4 IVH. Children with grade 1 or 2 IVH were at higher risk of developing cerebral palsy than those without IVH (OR 2.24, 95% CI 1.21 to 4.16). Increased rates of impairment in intellectual ability and academic skills were observed with higher grades of IVH, but not for grade 1 and 2 IVH. Parent-rated executive functioning was not related to IVH. CONCLUSION: While low-grade IVH is generally considered benign, it was associated with higher rates of cerebral palsy in school-aged children born EP, but not with intellectual ability, executive function, academic skills or overall motor function. Higher grades of IVH were associated with higher rates and risks of impairment in motor function, intellectual ability and some academic skills, but not parental ratings of executive function.

Mechanical injury and blood are drivers of spatial memory deficits after rapid intraventricular hemorrhage.

Aneurysmal intraventricular hemorrhage (IVH) survivors may recover with significant deficits in learning and memory. The goal of this study was to investigate the mechanism of memory decline after intraventricular aneurysm rupture. We developed an aneurysmal IVH rat model by injecting autologous, arterial blood over the period of two minutes into the right lateral ventricle. We also evaluated the effects of a volume-matched artificial cerebrospinal fluid (CSF) control, thrombin and the mode of delivery (pulsed hand injection versus continuous pump infusion). We performed magnetic resonance brain imaging after 1 and 5 weeks to evaluate for hydrocephalus and histological analysis of the dentate gyrus after 6 weeks. Only animals which underwent a whole blood pulsed hand injection had a spatial memory acquisition and retention deficit 5 weeks later. These animals had larger ventricles at 1 and 5 weeks than animals which underwent a continuous pump infusion of whole blood. We did not find a decline in dentate gyrus granule cell neurons or an impairment in dentate gyrus neurogenesis or differentiation 6 weeks after IVH. Rapid injections of blood or volume resulted in microglial activation in the dentate gyrus. In conclusion, our results point to mechanical injury as the predominant mechanism of memory decline after intraventricular aneurysmal rupture. However, volume-matched pulsed injections of artificial CSF did not create a spatial memory deficit at 5 weeks. Therefore, whole blood itself must play a role in the mechanism. Further research is required to evaluate whether the viscosity of blood causes additional mechanical disruption and hydrocephalus through a primary injury mechanism or whether the toxicity of blood causes a secondary injury mechanism that leads to the observed spatial memory deficit after 5 weeks.