Cranial ultrasound findings in preterm germinal matrix haemorrhage, sequelae and outcome.
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ABSTRACT:
SUBMITTER: Parodi A
PROVIDER: S-EPMC7098890 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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Cranial ultrasound findings in preterm germinal matrix haemorrhage, sequelae and outcome.
Parodi Alessandro A Govaert Paul P Horsch Sandra S Bravo Marìa Carmen MC Ramenghi Luca A LA
Pediatric research 20200301 Suppl 1
Germinal matrix-intraventricular haemorrhage (GMH-IVH), periventricular haemorrhagic infarction (PHI) and its complication, post-haemorrhagic ventricular dilatation (PHVD), are still common neonatal morbidities in preterm infants that are highly associated with adverse neurodevelopmental outcome. Typical cranial ultrasound (CUS) findings of GMH-IVH, PHI and PHVD, their anatomical substrates and underlying mechanisms are discussed in this paper. Furthermore, we propose a detailed descriptive clas ...[more]
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Project description:Abstract This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the efficacy and safety of stem cell‐based interventions for the prevention or treatment of germinal matrix‐intraventricular haemorrhage (GM‐IVH) in preterm infants.
| S-EPMC6517067 | biostudies-literature
Project description:BackgroundHead position during care may affect cerebral haemodynamics and contribute to the development of germinal matrix-intraventricular haemorrhage (GM-IVH) in very preterm infants. Turning the head toward one side may occlude jugular venous drainage while increasing intracranial pressure and cerebral blood volume. It is suggested that cerebral venous pressure is reduced and hydrostatic brain drainage improved if the infant is cared for in the supine 'head midline' position.ObjectivesTo assess whether head midline position is more effective than other head positions for preventing (or preventing extension) of GM-IVH in very preterm infants (< 32 weeks' gestation at birth).Search methodsWe used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 9), MEDLINE via PubMed (1966 to 12 September 2019), Embase (1980 to 12 September 2019), and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 12 September 2019). We searched clinical trials databases, conference proceedings, and reference lists of retrieved articles.Selection criteriaRandomised controlled trials (RCTs) comparing caring for very preterm infants in a supine head midline position versus a prone or lateral decubitus position, or undertaking a strategy of regular position change, or having no prespecified position. We included trials enrolling infants with existing GM-IVH and planned to assess extension of haemorrhage in a subgroup of infants. We planned to analyse horizontal (flat) versus head elevated positions separately for all body positions.Data collection and analysisWe used standard methods of Cochrane Neonatal. For each of the included trials, two review authors independently extracted data and assessed risk of bias. The primary outcomes were GM-IVH, severe IVH, and neonatal death. We evaluated treatment effects using a fixed-effect model with risk ratio (RR) for categorical data; and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to assess the certainty of evidence.Main resultsThree RCTs, with a total of 290 infants (either < 30 weeks' gestational age or < 1000 g body weight), met the inclusion criteria. Two trials compared supine midline head position versus head rotated 90° with the cot flat. One trial compared supine midline head position versus head rotated 90° with the bed tilted at 30°. We found no trials that compared supine versus prone midline head position. Meta-analysis of three trials (290 infants) did not show an effect on rates of GM-IVH (RR 1.11, 95% confidence interval (CI) 0.78 to 1.56; I² = 0%) and severe IVH (RR 0.71, 95% CI 0.37 to 1.33; I² = 0%). Neonatal mortality (RR 0.49, 95% CI 0.25 to 0.93; I² = 0%; RD -0.09, 95% CI -0.16 to -0.01) and mortality until hospital discharge (typical RR 0.50, 95% CI 0.28 to 0.90; I² = 0%; RD -0.10, 95% CI -0.18 to -0.02) were lower in the supine midline head position. The certainty of the evidence was very low for all outcomes because of limitations in study design and imprecision of estimates. We identified one ongoing study.Authors' conclusionsWe found few trial data on the effects of head midline position on GM-IVH in very preterm infants. Although meta-analyses suggest that mortality might be reduced, the certainty of the evidence is very low and it is unclear whether any effect is due to cot tilting (a co-intervention in one trial). Further high-quality RCTs would be needed to resolve this uncertainty.
| S-EPMC7389561 | biostudies-literature
Project description:BackgroundGerminal matrix-intraventricular haemorrhage (GMH-IVH) remains a substantial issue in neonatal intensive care units worldwide. Current therapies to prevent or treat GMH-IVH are limited. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, and/or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal studies.ObjectivesTo determine the benefits and harms of stem cell-based interventions for prevention or treatment of germinal matrix-intraventricular haemorrhage (GM-IVH) in preterm infants.Search methodsWe used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 1), in the Cochrane Library; MEDLINE via PubMed (1966 to 7 January 2019); Embase (1980 to 7 January 2019); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to 7 January 2019). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.Selection criteriaWe attempted to identify randomised controlled trials, quasi-randomised controlled trials, and cluster trials comparing (1) stem cell-based interventions versus control; (2) mesenchymal stromal cells (MSCs) of type or source versus MSCs of other type or source; (3) stem cell-based interventions other than MSCs of type or source versus stem cell-based interventions other than MSCs of other type or source; or (4) MSCs versus stem cell-based interventions other than MSCs. For prevention studies, we included extremely preterm infants (less than 28 weeks' gestation), 24 hours of age or less, without ultrasound diagnosis of GM-IVH; for treatment studies, we included preterm infants (less than 37 weeks' gestation), of any postnatal age, with ultrasound diagnosis of GM-IVH.Data collection and analysisFor each of the included trials, two review authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, type and source of MSCs, other stem cell-based interventions) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). Primary outcomes considered in this review are all-cause neonatal mortality, major neurodevelopmental disability, GM-IVH, and extension of pre-existing non-severe GM-IVH. We planned to use the GRADE approach to assess the quality of evidence.Main resultsOur search strategy yielded 769 references. We did not find any completed studies for inclusion. One randomised controlled trial is currently registered and ongoing. Five phase 1 trials are described in the excluded studies.Authors' conclusionsCurrently no evidence is available to show the benefits or harms of stem cell-based interventions for treatment or prevention of GM-IVH in preterm infants.
| S-EPMC6757514 | biostudies-literature
Project description:Germinal matrix hemorrhage (GMH) is a serious complication in extremely preterm infants associated with neurological deficits and mortality. The purpose of the present study was to develop and characterize a grade III and IV GMH model in postnatal day 5 (P5) rats, the equivalent of preterm human brain maturation. P5 Wistar rats were exposed to unilateral GMH through intracranial injection into the striatum close to the germinal matrix with 0.1, 0.2, or 0.3 U of collagenase VII. During 10 days following GMH induction, motor functions and body weight were assessed and brain tissue collected at P16. Animals were tested for anxiety, motor coordination and motor asymmetry on P22-26 and P36-40. Using immunohistochemical staining and neuropathological scoring we found that a collagenase dose of 0.3 U induced GMH. Neuropathological assessment revealed that the brain injury in the collagenase group was characterized by dilation of the ipsilateral ventricle combined with mild to severe cellular necrosis as well as mild to moderate atrophy at the levels of striatum and subcortical white matter, and to a lesser extent, hippocampus and cortex. Within 0.5 h post-collagenase injection there was clear bleeding at the site of injury, with progressive increase in iron and infiltration of neutrophils in the first 24 h, together with focal microglia activation. By P16, blood was no longer observed, although significant gray and white matter brain infarction persisted. Astrogliosis was also detected at this time-point. Animals exposed to GMH performed worse than controls in the negative geotaxis test and also opened their eyes with latency compared to control animals. At P40, GMH rats spent more time in the center of open field box and moved at higher speed compared to the controls, and continued to show ipsilateral injury in striatum and subcortical white matter. We have established a P5 rat model of collagenase-induced GMH for the study of preterm brain injury. Our results show that P5 rat pups exposed to GMH develop moderate brain injury affecting both gray and white matter associated with delayed eye opening and abnormal motor functions. These animals develop hyperactivity and show reduced anxiety in the juvenile stage.
| S-EPMC7744792 | biostudies-literature
Project description:Germinal matrix haemorrhage (GMH), caused by rupturing blood vessels in the germinal matrix, is a prevalent driver of preterm brain injuries and death. Our group recently developed a model simulating GMH using intrastriatal injections of collagenase in 5-day-old rats, which corresponds to the brain development of human preterm infants. This study aimed to define changes to the blood-brain barrier (BBB) and to evaluate BBB proteins as biomarkers in this GMH model. Regional BBB functions were investigated using blood to brain 14C-sucrose uptake as well as using biotinylated BBB tracers. Blood plasma and cerebrospinal fluids were collected at various times after GMH and analysed with ELISA for OCLN and CLDN5. The immunoreactivity of BBB proteins was assessed in brain sections. Tracer experiments showed that GMH produced a defined region surrounding the hematoma where many vessels lost their integrity. This region expanded for at least 6 h following GMH, thereafter resolution of both hematoma and re-establishment of BBB function occurred. The sucrose experiment indicated that regions somewhat more distant to the hematoma also exhibited BBB dysfunction; however, BBB function was normalised within 5 days of GMH. This shows that GMH leads to a temporal dysfunction in the BBB that may be important in pathological processes as well as in connection to therapeutic interventions. We detected an increase of tight-junction proteins in both CSF and plasma after GMH making them potential biomarkers for GMH.
| S-EPMC8303246 | biostudies-literature
Project description:This study investigated if acute and delayed deferoxamine treatment attenuates long-term sequelae after germinal matrix hemorrhage (GMH).Bacterial collagenase (0.3 U) was infused intraparenchymally into the right hemispheric ganglionic eminence in P7 rat pups to induce GMH. GMH animals received either deferoxamine or vehicle twice a day for 7 consecutive days. Deferoxamine administration was initiated at either 1 hour or 72 hours post-GMH. Long-term neurocognitive deficits and motor coordination were assessed using Morris water maze, rotarod, and foot fault tests between day 21 to 28 post-GMH. At 28 days post-GMH, brain morphology was assessed and extracellular matrix protein (fibronectin and vitronectin) expression was determined.Acute and delayed deferoxamine treatment improved long-term motor and cognitive function at 21 to 28 days post-GMH. Attenuated neurofunction was paralleled with improved overall brain morphology at 28 days post-GMH, reducing white matter loss, basal ganglia loss, posthemorrhagic ventricular dilation, and cortical loss. GMH resulted in significantly increased expression of fibronectin and vitronectin, which was reversed by acute and delayed deferoxamine treatment.Acute and delayed deferoxamine administration ameliorated long-term sequelae after GMH.
| S-EPMC4116458 | biostudies-literature
Project description:High-grade (large) germinal matrix-intraventricular haemorrhage (GM-IVH) is one of the most common causes of somatomotor neurodisability in pre-term infants. GM-IVH presents during the first postnatal week and can impinge on somatosensory circuits resulting in aberrant somatosensory cortical events straight after injury. Subsequently, somatosensory circuits undergo significant plastic changes, sometimes allowing the reinstatement of a somatosensory cortical response. However, it is not known whether this restructuring results in a full recovery of somatosensory functions. To investigate this, we compared somatosensory responses to mechanical stimulation measured with 18-channels EEG between infants who had high-grade GM-IVH (with ventricular dilatation and/or intraparenchymal lesion; n = 7 studies from 6 infants; mean corrected gestational age = 33 weeks; mean postnatal age = 56 days) and age-matched controls (n = 9 studies from 8 infants; mean corrected gestational age = 32 weeks; mean postnatal age = 36 days). We showed that infants who had high-grade GM-IVH did not recruit the same cortical source configuration following stimulation of the foot, but their response to stimulation of the hand resembled that of controls. These results show that somatosensory cortical circuits are reinstated in infants who had GM-IVH, during the several weeks after injury, but remain different from those of infants without brain injury. An important next step will be to investigate whether these evidences of neural reorganisation predict neurodevelopmental outcome.
| S-EPMC6920135 | biostudies-literature
Project description:BackgroundAbnormal intracranial findings are often detected at mid-trimester ultrasound (US) in fetuses with myelomeningocele (MMC). It is unclear whether these findings constitute a spectrum of the disease or are an independent finding, which should contraindicate fetal surgery.ObjectiveTo ascertain the spectrum and frequency of US-detected cranial findings in fetuses with MMC.Search strategyMEDLINE, Embase, Web of Science and CENTRAL were searched from January 2000 to June 2020.Selection criteriaStudy reporting incidence of cranial US findings in consecutive cases of second-trimester fetuses with MMC.Data collection and analysisPublication quality was assessed by Newcastle-Ottawa Scale (NOS) and modified NOS. Meta-analysis could not be performed as a result of high clinical diversity and study heterogeneity.Main resultsFourteen cranial US findings were reported in 15 studies. Findings in classic Chiari II malformation (CIIM) spectrum included posterior fossa funnelling (96%), small transcerebellar diameter (82-96%), 'banana' sign (50-100%), beaked tectum (65%) and 'lemon' sign (53-100%). Additional cranial findings were small biparietal diameter (BPD) and head circumference (HC) (<5th centile; 53 and 71%, respectively), ventriculomegaly (45-89%), abnormal pointed shape of the occipital horn (77-78%), thinning of the posterior cerebrum, perinodular heterotopia (11%), abnormal gyration (3%), corpus callosum disorders (60%) and midline interhemispheric cyst (42%).ConclusionsWe identified 14 cranial findings by second-trimester US in fetuses with MMC. The relatively high incidence of these findings and their unclear prognostic significance might not contraindicate fetal surgery in the case of normal fetal genetic testing. Some cranial findings may independently affect postnatal outcome, however. Long-term detailed follow-up is required to investigate this.Tweetable abstractA high rate of cranial abnormalities found on second-trimester ultrasound in fetuses with myelomeningocele.
| S-EPMC8436766 | biostudies-literature
Project description:AimTo create a magnetic resonance imaging (MRI)-based scoring system specific to neonates born preterm with intraventricular haemorrhage (IVH), which could serve as a reliable prognostic indicator for later development and might allow for improved outcome prediction, individually-tailored parental counselling, and clinical decision-making.MethodThis retrospective, two-center observational cohort study included 103 infants born preterm with IVH (61 males, 42 females; median gestational age 26wks 6d), born between 2000 and 2016. Term-equivalent MRI was evaluated using a novel scoring system consisting of 11 items. A total MRI score was calculated and correlated with neurodevelopment between 2 years and 3 years of age. Prediction models for outcome were defined.ResultsThe proposed MRI scoring system showed high correlation and strong predictive ability with regard to later cognitive and motor outcome. The prediction models were translated into easy-to-use tables, allowing developmental risk assessment.InterpretationThe proposed MRI-based scoring system was created especially for infants born preterm with IVH and enables a comprehensive assessment of important brain areas as well as potential additional abnormalities commonly associated with IVH. Thus, it better represents the severity of brain damage when compared with the conventional IVH classification. Our scoring system should provide clinicians with valuable information, to optimize parental counselling and clinical decision-making.
| S-EPMC9299734 | biostudies-literature
Project description:Low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) is the most common complication in extremely premature neonates. The occurrence of GM-IVH is highly associated with hemodynamic instability in the premature brain, yet the long-term impact of low-grade GM-IVH on cerebral blood flow and neuronal health have not been fully investigated. We used an innovative combination of frequency-domain near infrared spectroscopy and diffuse correlation spectroscopy (FDNIRS-DCS) to measure cerebral oxygen saturation (SO2) and an index of cerebral blood flow (CBFi) at the infant's bedside and compute an index of cerebral oxygen metabolism (CMRO2i). We enrolled twenty extremely low gestational age (ELGA) neonates (seven with low-grade GM-IVH) and monitored them weekly until they reached full-term equivalent age. During their hospital stay, we observed consistently lower CBFi and CMRO2i in ELGA neonates with low-grade GM-IVH compared to neonates without hemorrhages. Furthermore, lower CBFi and CMRO2i in the former group persists even after the resolution of the hemorrhage. In contrast, SO2 does not differ between groups. Thus, CBFi and CMRO2i may have better sensitivity than SO2 in detecting GM-IVH-related effects on infant brain development. FDNIRS-DCS methods may have clinical benefit for monitoring the evolution of GM-IVH, evaluating treatment response, and potentially predicting neurodevelopmental outcome.
| S-EPMC4867629 | biostudies-other