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Altered cortical processing of somatosensory input in pre-term infants who had high-grade germinal matrix-intraventricular haemorrhage.

ABSTRACT: 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.

SUBMITTER: Whitehead K

PROVIDER: S-EPMC6920135 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Altered cortical processing of somatosensory input in pre-term infants who had high-grade germinal matrix-intraventricular haemorrhage.

Whitehead Kimberley K Jones Laura L Laudiano-Dray Maria Pureza MP Meek Judith J Fabrizi Lorenzo L

NeuroImage. Clinical 20191128

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 whe ...[more]

PMID: 31835239

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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.

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.

Project description:BackgroundGerminal matrix-intraventricular haemorrhage (GMH-IVH) and encephalopathy of prematurity (EoP) remain substantial issues in neonatal intensive care units worldwide. Current therapies to prevent or treat these conditions are limited. Stem cell-based therapies offer a potential therapeutic approach to repair, restore, or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal studies. This is an update of the 2019 review, which did not include EoP.ObjectivesTo evaluate the benefits and harms of stem cell-based interventions for prevention or treatment of GM-IVH and EoP in preterm infants.Search methodsWe used standard, extensive Cochrane search methods. The latest search was April 2022.Selection criteriaWe attempted to include 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 or EoP; for treatment studies, we included preterm infants (less than 37 weeks' gestation), of any postnatal age, with ultrasound diagnosis of GM-IVH or with EoP.Data collection and analysisWe used standard Cochrane methods. Our primary outcomes were 1. all-cause neonatal mortality, 2. major neurodevelopmental disability, 3. GM-IVH, 4. EoP, and 5. extension of pre-existing non-severe GM-IVH or EoP. We planned to use GRADE to assess certainty of evidence for each outcome.Main resultsWe identified no studies that met our inclusion criteria. Three studies are currently registered and ongoing. Phase 1 trials are described in the 'Excluded studies' section.Authors' conclusionsNo evidence is currently available to evaluate the benefits and harms of stem cell-based interventions for treatment or prevention of GM-IVH or EoP in preterm infants. We identified three ongoing studies, with a sample size range from 20 to 200. In two studies, autologous cord blood mononuclear cells will be administered to extremely preterm infants via the intravenous route; in one, intracerebroventricular injection of MSCs will be administered to preterm infants up to 34 weeks' gestational age.

Dataset Information

Altered cortical processing of somatosensory input in pre-term infants who had high-grade germinal matrix-intraventricular haemorrhage.

Publications

Altered cortical processing of somatosensory input in pre-term infants who had high-grade germinal matrix-intraventricular haemorrhage.

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