Periventricular Hemorrhagic Infarction Research Articles

Size and Location of Preterm Brain Injury and Associations With Neurodevelopmental Outcomes.

We examined associations of white matter injury (WMI) and periventricular hemorrhagic infarction (PVHI) volume and location with 18-month neurodevelopment in very preterm infants. A total of 254 infants born <32 weeks' gestational age were prospectively recruited across 3 tertiary neonatal intensive care units (NICUs). Infants underwent early-life (median 33.1 weeks) and/or term-equivalent-age (median 41.9 weeks) MRI. WMI and PVHI were manually segmented for quantification in 92 infants. Highest maternal education level was included as a marker of socioeconomic status and was defined as group 1 = primary/secondary school; group 2 = undergraduate degree; and group 3 = postgraduate degree. Eighteen-month neurodevelopmental assessments were completed with Bayley Scales of Infant and Toddler Development, Third Edition. Adverse outcomes were defined as a score of less than 85 points. Multivariable linear regression models were used to examine associations of brain injury (WMI and PVHI) volume with neurodevelopmental outcomes. Voxel-wise lesion symptom maps were developed to assess relationships between brain injury location and neurodevelopmental outcomes. Greater brain injury volume was associated with lower 18-month Motor scores (β = -5.7, 95% CI -9.2 to -2.2, p = 0.002) while higher maternal education level was significantly associated with higher Cognitive scores (group 3 compared 1: β = 14.5, 95% CI -2.1 to 26.9, p = 0.03). In voxel-wise lesion symptom maps, brain injury involving the central and parietal white matter was associated with an increased risk of poorer motor outcomes. We found that brain injury volume and location were significant predictors of motor, but not cognitive outcomes, suggesting that different pathways may mediate outcomes across domains of neurodevelopment in preterm infants. Specifically, assessing lesion size and location may allow for more accurate identification of infants with brain injury at highest risk of poorer motor outcomes. These data also highlight the importance of socioeconomic status in cognitive outcomes, even in preterm infants with brain injury.

Periventricular hemorrhagic infarction in preterm neonates: Etiology and time of development.

To find the obstetrical and delivery associated risk factors of antenatal and postnatal grade III intraventricular hemorrhage (IVH) or periventricular hemorrhagic infarction (PVHI) in preterm neonates. A retrospective study of obstetric and delivery associated risk factors included neonates (<35 gestational weeks) with severe IVH/PVHI (n = 120) and a prospectively collected control group (n = 50). The children were divided into: (1) antenatal onset group (n = 27) with insult visible on cerebral ultrasonography within the first 12 hours of birth or periventricular cystic changes visible in PVHI within the first 3 days; (2) neonatal onset group (n = 70) with insult diagnosed after initial normal findings or I-II grade IVH, and (3) unknown time-onset group (n = 23) with insult visible at > 12 h of age. The mothers of the antenatal onset group had significantly more bacterial infections before delivery compared to the neonatal onset group: 20/27 (74.1%) versus 23/69 (33.3%), (odds ratio (OR) 5.7 [95% confidence interval 2.1-16]; p = 0.0008) or compared to the control group (11/50 (22%); OR 11 [2.8-42]; p = 0.0005). Placental histology revealed chorioamnionitis more often in the antenatal compared to the neonatal onset group (14/21 (66.7%) versus 16/42 (38.1%), respectively; OR 3.7 [1.18-11]; p = 0.025). Neonates with neonatal development of severe IVH/PVHI had significantly more complications during delivery or intensive care. Bacterial infection during pregnancy is an important risk factor for development of antenatal onset severe IVH or PVHI. In neonates born to mothers with severe bacterial infection during pregnancy, cerebral ultrasonography is indicated for early detection of severe IVH or PVHI.

Fetal intraventricular hemorrhage and periventricular hemorrhagic venous infarction: time for dedicated classification system.

Fetal intraventricular hemorrhage and periventricular hemorrhagic venous infarction: time for dedicated classification system.

Incidence of brain injuries in a large cohort of very preterm and extremely preterm infants at term-equivalent age: results of a single tertiary neonatal care center over 10years.

Cerebral magnetic resonance imaging (cMRI) at term-equivalent age (TEA) can detect brain injury (BI) associated with adverse neurological outcomes in preterm infants. This study aimed to assess BI incidences in a large, consecutive cohort of preterm infants born < 32weeks of gestation, the comparison between very (VPT, ≥ 28 + 0 to < 32 + 0weeks of gestation) and extremely preterm infants (EPT, < 28 + 0weeks of gestation) and across weeks of gestation. We retrospectively analyzed cMRIs at TEA of VPT and EPT infants born at a large tertiary center (2009-2018). We recorded and compared the incidences of BI, severe BI, intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction (PVHI), cerebellar hemorrhage (CBH), cystic periventricular leukomalacia (cPVL), and punctate white matter lesions (PWML) between VPTs, EPTs, and across weeks of gestation. We included 507 preterm infants (VPT, 335/507 (66.1%); EPT, 172/507 (33.9%); mean gestational age (GA), 28 + 2weeks (SD 2 + 2weeks); male, 52.1%). BIs were found in 48.3% of the preterm infants (severe BI, 12.0%) and increased with decreasing GA. IVH, PVHI, CBH, cPVL, and PWML were seen in 16.8%, 0.8%, 10.5%, 3.4%, and 18.1%, respectively. EPT vs. VPT infants suffered more frequently from BI (59.3% vs. 42.7%, p < 0.001), severe BI (18.6% vs. 8.7%, p = 0.001), IVH (31.9% vs. 9.0%, p < 0.001), and CBH (18.0% vs. 6.6%, p < 0.001). Brain injuries are common cMRI findings among preterm infants with a higher incidence of EPT compared to VPT infants. These results may serve as reference values for clinical management and research. Our results with regard to gestational age might provide valuable clinical insights, serving as a key reference for parental advice, structured follow-up planning, and enhancing research and management within the Neonatal Intensive Care Unit. • Brain injury is a common cMRI finding in preterm infants seen in 48.3% individuals. • Extremely preterm compared to very preterm infants have higher brain injury incidences driven by brain injuries such as intraventricular and cerebellar hemorrhage. • Reference incidence values are crucial for parental advice and structured follow-up planning.

EP07.04: Fetal intraventricular hemorrhage and periventricular hemorrhagic venous infarction: time for a new classification

EP07.04: Fetal intraventricular hemorrhage and periventricular hemorrhagic venous infarction: time for a new classification

66 Association of Low Hemoglobin at Birth and Neurodevelopmental Outcomes in Preterm Neonates &amp;lt; 29 Weeks’ Gestation: A Retrospective Cohort Study

Abstract Background Low hemoglobin (Hb) at birth is not an uncommon presentation for infants born preterm. The association of early anemia and neurodevelopmental outcomes in extremely preterm infants is not well studied. Objectives The objective of this study was to assess neurodevelopmental outcomes at 18-24 months corrected age (CA) of preterm infants with Hb &amp;lt;120 gm/l compared to those with Hb ≥120 gm/l at birth. Design/Methods In this retrospective cohort study, infants of &amp;lt;29 weeks’ gestational age (GA) with an Hb result at birth and admitted to one of two Canadian tertiary care NICUs between January 2009 and June 2018, were included. Baseline sociodemographic, antenatal, and neonatal data were compared between groups. The primary outcome was neurodevelopmental impairment (NDI), defined as the presence of one or more of: cerebral palsy; motor, cognitive, or language impairments on standardized testing; or visual or hearing impairment, at 18-24 months. Secondary outcomes included significant NDI (sNDI), death, severe retinopathy of prematurity (ROP) (≥ stage 3), grade III intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction, bronchopulmonary dysplasia (BPD), and composite outcomes of death or NDI. Multivariable logistic regression adjusting for GA, small for GA (SGA), sex, birth centre, and antenatal steroids, was used to determine the association between early anemia and outcomes. Results Of the 2351 eligible neonates, 351 (14.9%) had Hb levels &amp;lt;120 gm/L at birth. Baseline characteristics for groups are summarized in Table 1. Of the infants who survived, 1534 (72.5%) had developmental follow-up at 18 to 24 months CA. Low Hb was associated with significantly higher odds of NDI among survivors in univariate analyses but not in multivariable logistic regression (Table 2). The composite outcome of death or NDI was significantly higher in the low Hb group, primarily driven by the higher incidence of mortality. Neonatal death, IVH, ROP, and BPD were significantly higher in the low Hb group. Conclusion In preterm infants of &amp;lt;29 weeks’ GA, low Hb at birth was not associated with significant NDI outcomes at 18-24 months. However, low Hb was associated with higher odds of death, severe IVH, severe ROP, and BPD.

Trends in Outcomes of Major Intracerebral Haemorrhage in a National Cohort of Very Preterm Born Infants in Switzerland.

Major brain lesions, such as grade 3 intraventricular haemorrhage (G3-IVH) and periventricular haemorrhagic infarction (PVHI) are among the main predictors for poor neurodevelopment in preterm infants. In the last decades advancements in neonatal care have led to a general decrease in adverse outcomes. To assess trends of mortality and neurodevelopmental impairment (NDI) in a recent Swiss cohort of very preterm infants with grade 3 intraventricular haemorrhage (G3-IVH) and periventricular haemorrhagic infarction (PVHI). In this retrospective population-based cohort study, rates of mortality, and NDI at 2 years corrected age were reported in infants born at 24-29 weeks gestational age (GA) in Switzerland in 2002-2014, with G3-IVH and/or PVHI. Out of 4956 eligible infants, 462 (9%) developed G3-IVH (n = 172) or PVHI (n = 290). The average mortality rates for the two pathologies were 33% (56/172) and 60% (175/290), respectively. In 2002-2014, no change in rates of mortality (G3-IVH, p = 0.845; PVHI, p = 0.386) or NDI in survivors (G3-IVH, p = 0.756; PVHI, p = 0.588) were observed, while mean GA decreased (G3-IVH, p = 0.020; PVHI, p = 0.004). Multivariable regression analysis showed a strong association of G3-IVH and PVHI for both mortality and NDI. Death occurred after withdrawal of care in 81% of cases. In 2002-2014, rates of mortality and NDI in very preterm born infants with major brain lesions did not change. The significant decrease in mean GA and changing hospital policies over this time span may factor into the interpretation of these results.

High Prevalence of Collagenopathies in Preterm- and Term-Born Children With Periventricular Venous Hemorrhagic Infarction.

The aim of this study was to evaluate genetic risk factors in term-born children with antenatal periventricular hemorrhagic infarction (PVHI), presumed antenatal periventricular venous infarction and periventricular hemorrhagic infarction in preterm neonates. Genetic analysis and magnetic resonance imaging were performed in 85 children: term-born children (≥36 gestational weeks) with antenatal periventricular hemorrhagic infarction (n = 6) or presumed antenatal (n = 40) periventricular venous infarction and preterm children (<36 gestational weeks) with periventricular hemorrhagic infarction (n = 39). Genetic testing was performed using exome or large gene panel (n = 6700 genes) sequencing. Pathogenic variants associated with stroke were found in 11 of 85 (12.9%) children with periventricular hemorrhagic infarction/periventricular venous infarction. Among the pathogenic variants, COL4A1/A2 and COL5A1 variants were found in 7 of 11 (63%) children. Additionally, 2 children had pathogenic variants associated with coagulopathy, whereas 2 other children had other variants associated with stroke. Children with collagenopathies had significantly more often bilateral multifocal stroke with severe white matter loss and diffuse hyperintensities in the white matter, moderate to severe hydrocephalus, moderate to severe decrease in size of the ipsilesional basal ganglia and thalamus compared to children with periventricular hemorrhagic infarction/periventricular venous infarction without genetic changes in the studied genes (P ≤ .01). Severe motor deficit and epilepsy developed more often in children with collagenopathies compared to children without genetic variants (P = .0013, odds ratio [OR] = 233, 95% confidence interval [CI]: 2.8-531; and P = .025, OR = 7.3, 95% CI: 1.3-41, respectively). Children with periventricular hemorrhagic infarction/periventricular venous infarction have high prevalence of pathogenic variants in collagene genes (COL4A1/A2 and COL5A1). Genetic testing should be considered for all children with periventricular hemorrhagic infarction/periventricular venous infarction; COL4A1/A2 and COL5A1/A2 genes should be investigated first.

Imaging the Cerebral Veins in Pediatric Patients: Beyond Dural Venous Sinus Thrombosis.

The range of intracranial venous anomalies in children differs from that in adults. As a commonly encountered highly morbid disease, sinovenous thrombosis has been discussed extensively in the literature, and the associated imaging considerations are similar in pediatric and adult patients. The authors shift the focus to less frequently discussed cerebral venous diseases in pediatric patients. First, the practical embryology pertinent to malformations, syndromes, and variants such as vein of Galen aneurysmal malformation, Sturge-Weber syndrome, and developmental venous anomalies are discussed. Second, anatomic considerations that are applicable to neuroimaging in pediatric patients with cerebral venous anomalies are reviewed. In the discussion of anatomy, special attention is given to the medullary venous system that serves the cerebral white matter, superficial cortical veins (tributaries of the dural venous sinuses), and bridging veins, which carry blood from the superficial cortical veins through the potential subdural space into the dural venous sinuses. Third, the selection of imaging modalities (US, CT and CT venography, and MRI) is addressed, and various MR venographic pulse sequences (time-of-flight, phase-contrast, and contrast-enhanced sequences) are compared. Finally, a broad variety of congenital and acquired superficial and deep venous diseases in children are reviewed, with emphasis on less frequently discussed entities involving the medullary (eg, deep medullary venous engorgement and thrombosis, periventricular hemorrhagic venous infarction due to germinal matrix hemorrhage), cortical (eg, cortical venous thrombosis), and bridging (eg, acute and chronic manifestations of injury in abusive head trauma) veins, as well as the deep veins and dural venous sinuses (eg, varix). © RSNA, 2023 Quiz questions for this article are available through the Online Learning Center. Online supplemental material and the slide presentation from the RSNA Annual Meeting are available for this article.

Corpus callosum injury after neurosurgical intervention for posthemorrhagic ventricular dilatation and association with neurodevelopmental outcome at 2 years.

Direct injury to the corpus callosum (CC) due to neurosurgical interventions in infants with posthemorrhagic ventricular dilatation (PHVD) has not been reported in the literature. The authors observed a subset of infants who had suffered penetrating CC injury after neurosurgical interventions for PHVD and hypothesized that this pattern of injury may result in suboptimal CC maturation and neurodevelopmental impairment. In this multicenter, retrospective, observational study, 100 preterm and 17 full-term infants with PHVD were included and compared with 23 preterm controls. Both neonatal and postneonatal brain MRI scans were assessed for injury, and measurements were performed on postneonatal MRI scans at 2 years' corrected age. Neurodevelopmental outcome was assessed at 2 years' corrected age. A total of 269 brain MRI scans of 140 infants were included. Of infants with PHVD, 48 (41%) had penetrating CC injury following neurosurgical interventions. The median (IQR) CC midsagittal surface area was smaller in infants with CC injury when compared with infants with PHVD who had intact CC and controls (190 mm2 [149-262 mm2] vs 268 mm2 [206-318 mm2] vs 289 mm2 [246-320 mm2], respectively; p < 0.001). In the univariate analysis, the area of the CC was associated with cognitive Z score (coefficient 0.009 [95% CI 0.005-0.012], p < 0.001) and motor Z score (coefficient 0.009 [95% CI 0.006-0.012], p < 0.001). In the multivariable model, CC injury was not independently associated with cognitive and motor Z score after adjusting for gestational age and presence of periventricular hemorrhagic infarction (coefficient 0.04 [95% CI -0.36 to 0.46] and -0.37 [95% CI -0.83 to 0.09], p = 0.7 and 0.1, respectively). CC injury was not uncommon following neurosurgical interventions for PHVD in both preterm and full-term infants. At the age of 2 years, the CC midsagittal surface area was smaller in infants with injury, but CC injury was not independently associated with cognitive and motor outcomes at 2 years' corrected age.

Delivery Mode and Neurological Complications in Very Low Birth Weight Infants.

The risk of intraventricular hemorrhage (IVH) and periventricular leukomalacia is associated with low birth weight and gestational age. Caesarean section (CS) may reduce the risk of IVH, although it has been a matter of debate. The aim of this study was to evaluate the influence of the mode of delivery (MOD) on the development of IVH and cystic periventricular leukomalacia (cPVL). We analyzed an initial cohort of 11,023 very low birth weight (VLBW) infants born between January 2010 and December 2019. Infants with major malformations and gestational age <23 weeks and ≥32 weeks were excluded. A final cohort of 8,251 newborns was analyzed. Data was collected from Portuguese National very low birth weight registry. Cases were classified as vaginal delivery (VD) or CS. Outcome was assessed in univariate and logistic regression analyses. The median gestational age was 29 weeks (IQR 3.3) and the median weight was 1,100 g (IQR 555). The prevalence of IVH was significantly higher in the VD group versus the CS group, across all grading levels:1,144 newborns had grade I IVH (16% VD vs. 14% CS, p <0.01), 706 had grade II IVH (12% VD vs. 7.6% CS, p <0.01), and 777 had grade III IVH (14% VD vs. 7.9% CS, p <0.01). Post-hemorrhagic ventricular dilatation occurred in 457 newborns (8.3% VD vs. 4.6% CS, p <0.01) and 456 newborns had periventricular hemorrhagic infarction (8.4% VD vs. 4.5% CS, p <0.01). There was no association between MOD and cPVL. After applying a logistic regression analysis, including known risk factors for IVH and cPVL, VD was independently associated with an increased risk of IVH (odds ratio [OR] 1.600[1.423-1.799], p <0.001) and its complications (OR 1.440[1.195-1.735], p <0.001). MOD was not associated with an increased risk of cPVL. Our study suggests that CS is associated with a reduced risk of IVH and its complications in preterm VLBW infants < 32 weeks of gestational age. A CS should be considered in this group of infants to prevent the development of IVH and its complications. · IVH and cPVL are risk factors for neurological disabilities.. · CS may decrease the risk of IVH in preterms <32 weeks GA.. · There is no association between the MOD and cPVL..

Sodium supply from administered blood products was associated with severe intraventricular haemorrhage in extremely preterm infants.

AimThe aim of this study was to investigate the associations between sodium supply, fluid volume, sodium imbalances and severe intraventricular haemorrhage (IVH) in extremely preterm (EPT) infants.MethodsWe used data from the EXtremely PREterm infants in Sweden Study (EXPRESS) cohort consisting of all infants born at 22 to 26 gestational weeks from 2004 to 2007 and conducted a nested case–control study. For every infant with severe IVH (grade 3 or peri‐ventricular haemorrhagic infarction), one IVH‐free control infant with the birthday closest to the case infant and matched for hospital, sex, gestational age and birth weight was selected (n = 70 case–control pairs).ResultsTotal sodium supply and fluid volume were higher in infants with severe IVH compared with controls [daily total sodium supply until postnatal Day 2: mean ± SD (mmol/kg/day): 5.49 ± 2.53 vs. 3.95 ± 1.91, p = 0.009]. These differences were accounted for by sodium and fluid from transfused blood products. High plasma sodium concentrations or large sodium fluctuations were not associated with severe IVH.ConclusionOur results suggest a relationship between sodium‐rich transfusions of blood products and severe IVH in EPT infants. It is unclear whether this is an effect of sodium load, volume load or some other transfusion‐related factor.

Bimanual performance in children with unilateral perinatal arterial ischaemic stroke or periventricular haemorrhagic infarction.

Long term outcome data on bimanual performance in children with perinatal arterial ischaemic stroke (PAIS) and periventricular haemorrhagic infarction (PVHI) with and without unilateral spastic cerebral palsy (USCP) is sparse. To assess bimanual performance in children with PAIS or PVHI with and without USCP and to explore the relationship with unilateral hand function and full-scale IQ (FSIQ) in a cross-sectional study. Fifty-two children with PAIS (n=27) or PVHI (n=25) participated at a median age of 12 years and 1 month (range 6-20 years). The Bruininks Oseretsky Test of Motor Proficiency-2 (bimanual precision and dexterity subtest), Assisting Hand Assessment, Purdue Pegboard Test and Wechsler Intelligence scale were administered. Bimanual dexterity was worse in children with USCP (p<0.02) without a difference for the pathology groups. In children without USCP (n=21), those with PAIS showed a better bimanual precision compared to children with PVHI (p<0.04). The AHA score and the Purdue Pegboard score of the dominant hand explained 51% of the variance in bimanual precision and dexterity in children with USCP. In absence of USCP, FSIQ together with AHA scores explained 66% of the variance in bimanual precision and FSIQ together with the Purdue Pegboard Test score of the dominant hand, 71% of the variance in bimanual dexterity. Children with PAIS without USCP have a more favourable bimanual hand function compared to children with PVHI. This difference appears to be associated with a preserved FSIQ.

Epidemiology and pathogenesis of stroke in preterm infants: A systematic review.

BACKGROUND:Perinatal stroke is one of the principal causes of cerebral palsy (CP) in preterm infants. Stroke in preterm infants is different from stroke in term infants, given the differences in brain maturation and the mechanisms of injury exclusive to the immature brain. We conducted a systematic review to explore the epidemiology and pathogenesis of periventricular hemorrhagic infarction (PVHI), perinatal arterial ischemic stroke (PAIS) and cerebral sinovenous thrombosis (CSVT) in preterm infants.METHODS:Studies were identified based on predefined study criteria from MEDLINE, EMBASE, SCOPUS and WEB OF SCIENCE electronic databases from 2000 –2019. Results were combined using descriptive statistics.RESULTS:Fourteen studies encompassed 546 stroke cases in preterm infants between 23 –36 weeks gestational ages and birth weights between 450 –3500 grams. Eighty percent (436/546) of the stroke cases were PVHI, 17%(93/546) were PAIS and 3%(17/546) were CSVT. Parietal PVHI was more common than temporal and frontal lobe PVHI. For PAIS, left middle cerebral artery (MCA) was more common than right MCA or cerebellar stroke. For CSVT partial or complete thrombosis in the transverse sinus was universal. All cases included multiple possible risk factors, but the data were discordant precluding aggregation within a meta-analysis.CONCLUSION:This systematic review confirms paucity of data regarding the etiology and the precise causal pathway of stroke in preterm infants. Moreover, the preterm infants unlike the term infants do not typically present with seizures. Hence high index of clinical suspicion and routine cUS will assist in the timely diagnosis and understanding of stroke in this population.

Post-hemorrhagic ventricular dilatation affects white matter maturation in extremely preterm infants.

Data on microstructural white matter integrity in preterm infants with post-hemorrhagic ventricular dilatation (PHVD) using diffusion tensor imaging (DTI) are limited. Also, to date, no study has focused on the DTI changes in extremely preterm (EP) infants with PHVD. A case-control study of EP infants <28 weeks' gestation with PHVD was conducted. Diffusivity and fractional anisotropy (FA) values of corticospinal tracts (CST) and corpus callosum (CC) were measured using DTI at term-equivalent age. Outcomes were assessed at 2-years-corrected age. Twenty-one infants with PHVD and 21 matched-controls were assessed. FA values in the CC were lower in infants with PHVD compared with controls (mean difference, 0.05 [95% confidence interval (CI), 0.02-0.08], p < 0.001). In infants with periventricular hemorrhagic infarction, FA values in the CC were lower than in controls (mean difference, 0.05 [95% CI, 0.02-0.09], p = 0.005). The composite cognitive and motor scores were associated with the FA value of the CC (coefficient 114, p = 0.01 and coefficient 147, p = 0.004; respectively). Extremely preterm infants with PHVD showed lower FA values in CC. A positive correlation was also shown between the composite cognitive and motor scores and FA value of the CC at 2-years-corrected age. Extremely preterm infants with post-hemorrhagic ventricular dilatation showed lower fractional anisotropy values in their corpus callosum compared with controls reflecting the impaired microstructure of these commissural nerve fibers that are adjacent to the dilated ventricles. Impaired microstructure of the corpus callosum was shown to be associated with cognitive and motor scores at 2-years-corrected age.

Risk Factors for Mortality and Neurodevelopmental Impairment among Neonates Born at 22–23 Weeks’ Gestation

Introduction: We aimed to evaluate the risk factors for mortality and neurodevelopmental impairment (NDI) among infants of 22–23 weeks’ gestational age, which currently remain unclear. Methods: This retrospective case-control study included 104 infants delivered at 22–23 weeks’ gestation at Kagoshima City Hospital from 2006 to 2015. We compared 65 and 34 cases of survival to discharge and postnatal in-hospital death (5 excluded), respectively, and 26 and 35 cases with and without NDI, respectively, using maternal, prenatal, and postnatal records. A high rate of survivors’ follow-up (61/65) was achieved in this study. Results: The survival rate was 75.0% (21/28) and 62.0% (44/71) among infants born at 22 and 23 weeks’ gestation, respectively. Infants who died weighed less (525.5 vs. 578 g, p = 0.04) and their intrauterine growth retardation (IUGR) rate (<5th percentile) was higher (14.7 vs. 1.5%, p = 0.02). Mortality was associated with an increased incidence of bradycardia on fetal heart rate monitoring (11.8 vs. 1.5%, p = 0.046), periventricular hemorrhagic infarction (PVHI; 32.4 vs. 6.2%, p = 0.001), necrotizing enterocolitis (NEC, surgery or drain tube; 14.7 vs. 0.0%, p = 0.004), and tension pneumothorax (29.4 vs. 6.2%, p = 0.004). There were significant differences in the proportion of PVHI (15.4 vs. 0%, p = 0.03) between infants with and without NDI. Conclusions: IUGR, bradycardia, PVHI, NEC, and tension pneumothorax were associated with neonatal mortality among infants born at 22–23 weeks’ gestation. NDI at 36–42 months’ chronological age was associated with PVHI.

Consensus Approach for Standardizing the Screening and Classification of Preterm Brain Injury Diagnosed With Cranial Ultrasound: A Canadian Perspective.

Acquired brain injury remains common in very preterm infants and is associated with significant risks for short- and long-term morbidities. Cranial ultrasound has been widely adopted as the first-line neuroimaging modality to study the neonatal brain. It can reliably detect clinically significant abnormalities that include germinal matrix and intraventricular hemorrhage, periventricular hemorrhagic infarction, post-hemorrhagic ventricular dilatation, cerebellar hemorrhage, and white matter injury. The purpose of this article is to provide a consensus approach for detecting and classifying preterm brain injury to reduce variability in diagnosis and classification between neonatologists and radiologists. Our overarching goal with this work was to achieve homogeneity between different neonatal intensive care units across a large country (Canada) with regards to classification, timing of brain injury screening and frequency of follow up imaging. We propose an algorithmic approach that can help stratify different grades of germinal matrix-intraventricular hemorrhage, white matter injury, and ventricular dilatation in very preterm infants.

Recovery of the brain after intraventricular hemorrhage

Intraventricular hemorrhage (IVH) remains a major complication of prematurity, worldwide. The severity of IVH is variable, ranging from a tiny germinal matrix bleed to a moderate-to-large ventricular hemorrhage or periventricular hemorrhagic infarction. Survivors with IVH often suffer from hydrocephalus and white matter injury. There is no tangible treatment to prevent post-hemorrhagic cerebral palsy, cognitive deficits, or hydrocephalus in these infants. White matter injury is attributed to blood-induced damage to axons and maturing oligodendrocyte precursors, resulting in reduced myelination and axonal loss. Hydrocephalus results from obstructed CSF circulation by blood clots, increased CSF production, and reduced CSF absorption by lymphatics and arachnoid villi. Several strategies to promote neurological recovery have shown promise in animal models, including the elimination of blood and blood products, alleviating cerebral inflammation and oxidative stress, as well as promoting survival and maturation of oligodendrocyte precursors. The present review integrates novel mechanisms of brain injury in IVH and the imminent therapies to alleviate post-hemorrhagic white matter injury and hydrocephalus in the survivors with IVH.

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.

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

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. 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. 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. 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. 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.