Olga Romantsik | Lund University (original) (raw)

Papers by Olga Romantsik

Research paper thumbnail of Stem cell-based interventions for the treatment of stroke in newborn infants

Cochrane Database of Systematic Reviews

Research paper thumbnail of Positioning for lumbar puncture in newborn infants

Cochrane Database of Systematic Reviews

Research paper thumbnail of Pharmacological interventions for the management of pain and discomfort during lumbar puncture in newborn infants

The Cochrane library, Dec 14, 2022

This systematic review summarized randomized controlled and cross-over trials evaluating the bene... more This systematic review summarized randomized controlled and cross-over trials evaluating the benefits/harms of pharmacological agents used to reduce high serum potassium levels, as well as to prevent harms of hyperkalaemia such as death and cardiac arrhythmias. This was a focused update of an earlier Cochrane review titled Emergency interventions for hyperkalaemia first published in 2005 and updated in 2013.

Research paper thumbnail of Pathophysiology of extracellular haemoglobin: use of animal models to translate molecular mechanisms into clinical significance

Isbt Science Series, Nov 21, 2016

The blood's major gas-exchange is carried out by haemoglobin, a heme-protein that binds iron and ... more The blood's major gas-exchange is carried out by haemoglobin, a heme-protein that binds iron and oxygen and can have potentially dangerous side effects due to redox reactions. Haemoglobin is a very abundant molecule with a concentration of 150 g/L in whole blood, resulting in almost one kg haemoglobin in an adult human body. Normal turnover of red blood cells results in significant haemoglobin release, and pathological conditions that involve haemolysis can lead to massive haemoglobin levels. To control for the potential threat of extracellular haemoglobin, several protective defence systems have evolved. Many pathological conditions, diseases as well as iatrogenic conditions, such as infusion of haemoglobin-based oxygen carriers, cerebral intraventricular haemorrhage, extracorporeal circulation and the pregnancy complication preeclampsia, involve abnormal levels of haemolysis and extracellular haemoglobin. Although quite different aetiology, the haemoglobin-induced damage often cause similar clinical sequelae and symptoms. Here we will give an overview of the pathophysiological mechanisms of extracellular haemoglobin and its metabolites. Furthermore, we will highlight the use of animal models in advancing the understanding of these mechanisms and discuss how to utilize the knowledge in the development of new and better pharmaceutical therapies.

Research paper thumbnail of Stem cell-based interventions for the prevention and treatment of intraventricular haemorrhage and encephalopathy of prematurity in preterm infants

The Cochrane library, Feb 15, 2023

Stem cell-based interventions for the prevention and treatment of germinal matrix-intraventricula... more Stem cell-based interventions for the prevention and treatment of germinal matrix-intraventricular haemorrhage in preterm infants.

Research paper thumbnail of Mesenchymal stem cell therapy in perinatal arterial ischemic stroke: systematic review of preclinical studies

Pediatric Research, Jul 29, 2022

BACKGROUND: Perinatal arterial ischemic stroke (PAIS) is a neurologic disorder leading to long-te... more BACKGROUND: Perinatal arterial ischemic stroke (PAIS) is a neurologic disorder leading to long-term complications. Mesenchymal stem cells (MSCs) have emerged as a novel therapeutic agent. This systematic review aims to determine the effects of stem cellbased interventions for the treatment of PAIS in preclinical studies. METHODS: We included all controlled studies on MSCs in neonatal animals with PAIS. Functional outcome was the primary outcome. The literature search was performed in February 2021. RESULTS: In the 20 included studies, MSCs were most frequently delivered via intracerebral injection (n = 9), 3 days after the induction of PAIS (n = 8), at a dose ranging from 5 × 10 4 to 5 × 10 6 cells. The meta-analysis showed an improvement on the cylinder rearing test (MD: −10.62; 95% CI: −14.38 to −6.86) and on the water maze test (MD: 1.31 MD; 95% CI: 0.80 to 1.81) in animals treated with MSCs compared to the control group animals. CONCLUSION: MSCs appear to improve sensorimotor and cognitive performance in PAIS-injured animals; however, the certainty of the evidence is low. Registration of the protocol of preclinical studies, appropriate sample size calculation, rigorous randomization, and reporting of the data on animal sex and survival are warranted.PROSPERO registration number: CRD42021239642.

Research paper thumbnail of Stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants

The Cochrane library, Aug 19, 2020

BackgroundHypoxic‐ischaemic encephalopathy (HIE) is a leading cause of mortality and long‐term ne... more BackgroundHypoxic‐ischaemic encephalopathy (HIE) is a leading cause of mortality and long‐term neurological sequelae, affecting thousands of children worldwide. Current therapies to treat HIE are limited to cooling. Stem cell‐based therapies offer a potential therapeutic approach to repair or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal trials.ObjectivesTo determine the efficacy and safety of stem cell‐based interventions for the treatment of hypoxic‐ischaemic encephalopathy (HIE) in newborn infants.Search methodsWe used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 5), MEDLINE via PubMed (1966 to 8 June 2020), Embase (1980 to 8 June 2020), and CINAHL (1982 to 8 June 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi‐randomised trials.Selection criteriaRandomised controlled trials, quasi‐randomised controlled trials and cluster trials comparing 1) stem cell‐based interventions (any type) compared to control (placebo or no treatment); 2) use of mesenchymal stem/stromal cells (MSCs) of type (e.g. number of doses or passages) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus MSCs of other type or source; 3) use of stem cell‐based interventions other than MSCs of type (e.g. mononuclear cells, oligodendrocyte progenitor cells, neural stem cells, hematopoietic stem cells, and inducible pluripotent stem cells) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus stem cell‐based interventions other than MSCs of other type or source; or 4) MSCs versus stem cell‐based interventions other than MSCs.Data collection and analysisFor each of the included trials, two authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, type and source of MSCs or other stem cell‐based interventions) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow‐up). The primary outcomes considered in this review are all‐cause neonatal mortality, major neurodevelopmental disability, death or major neurodevelopmental disability assessed at 18 to 24 months of age. We planned to use the GRADE approach to assess the quality of evidence.Main resultsOur search strategy yielded 616 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion. Fifteen RCTs are currently registered and ongoing. We describe the three studies we excluded.Authors' conclusionsThere is currently no evidence from randomised trials that assesses the benefit or harms of stem cell‐based interventions for the prevention of morbidity and mortality following hypoxic‐ischaemic encephalopathy in newborn infants.

Research paper thumbnail of Intraventricular Hemorrhage and White Matter Injury in Preclinical and Clinical Studies

Neoreviews, Nov 1, 2019

Germinal matrix–intraventricular hemorrhage (IVH) occurs in nearly half of infants born at less t... more Germinal matrix–intraventricular hemorrhage (IVH) occurs in nearly half of infants born at less than 26 weeks’ gestation. Up to 50% of survivors with IVH develop cerebral palsy, cognitive deficits, behavioral disorders, posthemorrhagic ventricular dilatation, or a combination of these sequelae. After the initial bleeding and the primary brain injury, inflammation and secondary brain injury might lead to periventricular leukomalacia or diffuse white matter injury. Potential factors that are involved include microglia and astrocyte activation, degradation of blood components with release of “toxic” products, infiltration of the brain by systemic immune cells, death of neuronal and glial cells, and arrest of preoligodendrocyte maturation. In addition, impairment of the blood-brain barrier may play a major role in the pathophysiology. A wide range of animal models has been used to explore causes and mechanisms leading to IVH-induced brain injury. Preclinical studies have identified potential targets for enhancing brain repair. However, little has been elucidated about the effectiveness of potential interventions in clinical studies. A systematic review of available preclinical and clinical studies might help identify research gaps and which types of interventions may be prioritized. Future trials should report clinically robust and long-term outcomes after IVH.

Research paper thumbnail of Cerebral intraventricular hemorrhage and post-hemorrhagic ventricular dilatation in preterm infants: new mechanistic insights and potential treatment strategies

Cerebral intraventricular hemorrhage and post-hemorrhagic ventricular dilatation in preterm infan... more Cerebral intraventricular hemorrhage and post-hemorrhagic ventricular dilatation in preterm infants: new mechanistic insights and potential treatment strategies Romantsik, Olga 2021 Document Version: Publisher's PDF, also known as Version of record Link to publication Citation for published version (APA): Romantsik, O. (2021). Cerebral intraventricular hemorrhage and post-hemorrhagic ventricular dilatation in preterm infants: new mechanistic insights and potential treatment strategies. [Doctoral Thesis (compilation),

Research paper thumbnail of Severe intraventricular hemorrhage causes long-lasting structural damage in a preterm rabbit pup model

Pediatric Research, May 3, 2022

BACKGROUND: Intraventricular hemorrhage causes significant lifelong mortality and morbidity, espe... more BACKGROUND: Intraventricular hemorrhage causes significant lifelong mortality and morbidity, especially in preterm born infants. Progress in finding an effective therapy is stymied by a lack of preterm animal models with long-term follow-up. This study addresses this unmet need, using an established model of preterm rabbit IVH and analyzing outcomes out to 1 month of age. METHODS: Rabbit pups were delivered preterm and administered intraperitoneal injection of glycerol at 3 h of life and approximately 58% developed IVH. Neurobehavioral assessment was performed at 1 month of age followed by immunohistochemical labeling of epitopes for neurons, synapses, myelination, and interneurons, analyzed by means of digital quantitation and assessed via two-way ANOVA or Student's t test. RESULTS: IVH pups had globally reduced myelin content, an aberrant cortical myelination microstructure, and thinner upper cortical layers (I-III). We also observed a lower number of parvalbumin (PV)-positive interneurons in deeper cortical layers (IV-VI) in IVH animals and reduced numbers of neurons, synapses, and microglia. However, there were no discernable changes in behaviors. CONCLUSIONS: We have established in this preterm pup model that long-term changes after IVH include significant wide-ranging alterations to cortical organization and microstructure. Further work to improve the sensitivity of neurocognitive testing in this species at this age may be required.

Research paper thumbnail of The Effects of Caffeine Following Hypoxic-Ischemic Encephalopathy: A Systematic Review of Preclinical Studies

Social Science Research Network, 2022

Research paper thumbnail of Opioids for newborn infants receiving mechanical ventilation

The Cochrane library, Sep 18, 2020

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To determ... more This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To determine the benefits and harms of opioid analgesics in neonates (term or preterm) receiving mechanical ventilation, compared to placebo, no drug, other opioids, other analgesics or sedatives.

Research paper thumbnail of Stem cell-based interventions for the prevention and treatment of germinal matrix-intraventricular haemorrhage in preterm infants

The Cochrane library, Sep 24, 2019

BackgroundGerminal matrix‐intraventricular haemorrhage (GMH‐IVH) remains a substantial issue in n... more 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.

Research paper thumbnail of The Effects of Caffeine Following Hypoxic-Ischemic Encephalopathy: A Systematic Review of Preclinical Studies

Research paper thumbnail of Intraventricular Hemorrhage and White Matter Injury in the Preterm Infant

Neurology: Neonatology Questions and Controversies, 2012

Abstract This chapter focuses on a brief review of the pathogenesis of periventricular intraventr... more Abstract This chapter focuses on a brief review of the pathogenesis of periventricular intraventricular hemorrhage as well as white matter injury. Various approaches or strategies for the prevention, diagnosis, and treatment as well as outcomes are discussed with gaps in knowledge highlighted.

Research paper thumbnail of The effects of caffeine following hypoxic-ischemic encephalopathy: A systematic review of animal studies

Research paper thumbnail of Clonidine for painful procedures or conditions in infants

Cochrane Database of Systematic Reviews, 2018

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determ... more This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the efficacy and safety of clonidine for the prevention or treatment of procedural or postoperative pain, or pain associated with clinical conditions in neonates. Clonidine will be compared to placebo, no treatment, dexmedetomidine, paracetamol, and opioids. In addition, the safety of clonidine administration will be assessed for potential harms.

Research paper thumbnail of ایمونوتراپی خوراکی و زیرزبانی برای آلرژی به تخممرغ

The Cochrane database of systematic reviews, 2018

BACKGROUND Clinical egg allergy is a common food allergy. Current management relies upon strict a... more BACKGROUND Clinical egg allergy is a common food allergy. Current management relies upon strict allergen avoidance. Oral immunotherapy might be an optional treatment, through desensitization to egg allergen. OBJECTIVES To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with immunoglobulin E (IgE)-mediated egg allergy as compared to a placebo treatment or an avoidance strategy. SEARCH METHODS We searched 13 databases for journal articles, conference proceedings, theses and trials registers using a combination of subject headings and text words (last search 31 March 2017). SELECTION CRITERIA We included randomized controlled trials (RCTs) comparing oral immunotherapy or sublingual immunotherapy administered by any protocol with placebo or an elimination diet. Participants were children or adults with clinical egg allergy. DATA COLLECTION AND ANALYSIS We retrieved 97 studies from the electronic searches. We selected studies, extracted data ...

Research paper thumbnail of SPSS Data for: Behavioral testing and litter effects in the rabbit

Research paper thumbnail of Opioids for newborn infants receiving mechanical ventilation

Cochrane Database of Systematic Reviews, 2021

Study characteristics We collected and analysed all relevant studies to answer the review questio... more Study characteristics We collected and analysed all relevant studies to answer the review question and found 23 studies enrolling 2023 babies. In most studies, babies were born before the due date (before 37 weeks' gestational age). Eight studies compared the use of morphine versus placebo (a substance with no therapeutic value) or no intervention, and seven versus fentanyl. We analysed the other studies separately because researchers compared the use of these two drugs with other opioids or other analgesics. Key results We are uncertain whether opioids have an e ect on pain and neurodevelopmental outcomes at 18 to 24 months; use of morphine or fentanyl probably has little or no e ect in reducing the duration of mechanical ventilation and neonatal mortality. Further research is needed. Certainty of evidence The certainty of evidence is very low to moderate because overall only a small number of studies have looked at this intervention, few babies were included in these studies, and some studies could have been better designed. How up-to-date is this review? We searched for studies that had been published up to

Research paper thumbnail of Stem cell-based interventions for the treatment of stroke in newborn infants

Cochrane Database of Systematic Reviews

Research paper thumbnail of Positioning for lumbar puncture in newborn infants

Cochrane Database of Systematic Reviews

Research paper thumbnail of Pharmacological interventions for the management of pain and discomfort during lumbar puncture in newborn infants

The Cochrane library, Dec 14, 2022

This systematic review summarized randomized controlled and cross-over trials evaluating the bene... more This systematic review summarized randomized controlled and cross-over trials evaluating the benefits/harms of pharmacological agents used to reduce high serum potassium levels, as well as to prevent harms of hyperkalaemia such as death and cardiac arrhythmias. This was a focused update of an earlier Cochrane review titled Emergency interventions for hyperkalaemia first published in 2005 and updated in 2013.

Research paper thumbnail of Pathophysiology of extracellular haemoglobin: use of animal models to translate molecular mechanisms into clinical significance

Isbt Science Series, Nov 21, 2016

The blood's major gas-exchange is carried out by haemoglobin, a heme-protein that binds iron and ... more The blood's major gas-exchange is carried out by haemoglobin, a heme-protein that binds iron and oxygen and can have potentially dangerous side effects due to redox reactions. Haemoglobin is a very abundant molecule with a concentration of 150 g/L in whole blood, resulting in almost one kg haemoglobin in an adult human body. Normal turnover of red blood cells results in significant haemoglobin release, and pathological conditions that involve haemolysis can lead to massive haemoglobin levels. To control for the potential threat of extracellular haemoglobin, several protective defence systems have evolved. Many pathological conditions, diseases as well as iatrogenic conditions, such as infusion of haemoglobin-based oxygen carriers, cerebral intraventricular haemorrhage, extracorporeal circulation and the pregnancy complication preeclampsia, involve abnormal levels of haemolysis and extracellular haemoglobin. Although quite different aetiology, the haemoglobin-induced damage often cause similar clinical sequelae and symptoms. Here we will give an overview of the pathophysiological mechanisms of extracellular haemoglobin and its metabolites. Furthermore, we will highlight the use of animal models in advancing the understanding of these mechanisms and discuss how to utilize the knowledge in the development of new and better pharmaceutical therapies.

Research paper thumbnail of Stem cell-based interventions for the prevention and treatment of intraventricular haemorrhage and encephalopathy of prematurity in preterm infants

The Cochrane library, Feb 15, 2023

Stem cell-based interventions for the prevention and treatment of germinal matrix-intraventricula... more Stem cell-based interventions for the prevention and treatment of germinal matrix-intraventricular haemorrhage in preterm infants.

Research paper thumbnail of Mesenchymal stem cell therapy in perinatal arterial ischemic stroke: systematic review of preclinical studies

Pediatric Research, Jul 29, 2022

BACKGROUND: Perinatal arterial ischemic stroke (PAIS) is a neurologic disorder leading to long-te... more BACKGROUND: Perinatal arterial ischemic stroke (PAIS) is a neurologic disorder leading to long-term complications. Mesenchymal stem cells (MSCs) have emerged as a novel therapeutic agent. This systematic review aims to determine the effects of stem cellbased interventions for the treatment of PAIS in preclinical studies. METHODS: We included all controlled studies on MSCs in neonatal animals with PAIS. Functional outcome was the primary outcome. The literature search was performed in February 2021. RESULTS: In the 20 included studies, MSCs were most frequently delivered via intracerebral injection (n = 9), 3 days after the induction of PAIS (n = 8), at a dose ranging from 5 × 10 4 to 5 × 10 6 cells. The meta-analysis showed an improvement on the cylinder rearing test (MD: −10.62; 95% CI: −14.38 to −6.86) and on the water maze test (MD: 1.31 MD; 95% CI: 0.80 to 1.81) in animals treated with MSCs compared to the control group animals. CONCLUSION: MSCs appear to improve sensorimotor and cognitive performance in PAIS-injured animals; however, the certainty of the evidence is low. Registration of the protocol of preclinical studies, appropriate sample size calculation, rigorous randomization, and reporting of the data on animal sex and survival are warranted.PROSPERO registration number: CRD42021239642.

Research paper thumbnail of Stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants

The Cochrane library, Aug 19, 2020

BackgroundHypoxic‐ischaemic encephalopathy (HIE) is a leading cause of mortality and long‐term ne... more BackgroundHypoxic‐ischaemic encephalopathy (HIE) is a leading cause of mortality and long‐term neurological sequelae, affecting thousands of children worldwide. Current therapies to treat HIE are limited to cooling. Stem cell‐based therapies offer a potential therapeutic approach to repair or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal trials.ObjectivesTo determine the efficacy and safety of stem cell‐based interventions for the treatment of hypoxic‐ischaemic encephalopathy (HIE) in newborn infants.Search methodsWe used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 5), MEDLINE via PubMed (1966 to 8 June 2020), Embase (1980 to 8 June 2020), and CINAHL (1982 to 8 June 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi‐randomised trials.Selection criteriaRandomised controlled trials, quasi‐randomised controlled trials and cluster trials comparing 1) stem cell‐based interventions (any type) compared to control (placebo or no treatment); 2) use of mesenchymal stem/stromal cells (MSCs) of type (e.g. number of doses or passages) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus MSCs of other type or source; 3) use of stem cell‐based interventions other than MSCs of type (e.g. mononuclear cells, oligodendrocyte progenitor cells, neural stem cells, hematopoietic stem cells, and inducible pluripotent stem cells) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus stem cell‐based interventions other than MSCs of other type or source; or 4) MSCs versus stem cell‐based interventions other than MSCs.Data collection and analysisFor each of the included trials, two authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, type and source of MSCs or other stem cell‐based interventions) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow‐up). The primary outcomes considered in this review are all‐cause neonatal mortality, major neurodevelopmental disability, death or major neurodevelopmental disability assessed at 18 to 24 months of age. We planned to use the GRADE approach to assess the quality of evidence.Main resultsOur search strategy yielded 616 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion. Fifteen RCTs are currently registered and ongoing. We describe the three studies we excluded.Authors' conclusionsThere is currently no evidence from randomised trials that assesses the benefit or harms of stem cell‐based interventions for the prevention of morbidity and mortality following hypoxic‐ischaemic encephalopathy in newborn infants.

Research paper thumbnail of Intraventricular Hemorrhage and White Matter Injury in Preclinical and Clinical Studies

Neoreviews, Nov 1, 2019

Germinal matrix–intraventricular hemorrhage (IVH) occurs in nearly half of infants born at less t... more Germinal matrix–intraventricular hemorrhage (IVH) occurs in nearly half of infants born at less than 26 weeks’ gestation. Up to 50% of survivors with IVH develop cerebral palsy, cognitive deficits, behavioral disorders, posthemorrhagic ventricular dilatation, or a combination of these sequelae. After the initial bleeding and the primary brain injury, inflammation and secondary brain injury might lead to periventricular leukomalacia or diffuse white matter injury. Potential factors that are involved include microglia and astrocyte activation, degradation of blood components with release of “toxic” products, infiltration of the brain by systemic immune cells, death of neuronal and glial cells, and arrest of preoligodendrocyte maturation. In addition, impairment of the blood-brain barrier may play a major role in the pathophysiology. A wide range of animal models has been used to explore causes and mechanisms leading to IVH-induced brain injury. Preclinical studies have identified potential targets for enhancing brain repair. However, little has been elucidated about the effectiveness of potential interventions in clinical studies. A systematic review of available preclinical and clinical studies might help identify research gaps and which types of interventions may be prioritized. Future trials should report clinically robust and long-term outcomes after IVH.

Research paper thumbnail of Cerebral intraventricular hemorrhage and post-hemorrhagic ventricular dilatation in preterm infants: new mechanistic insights and potential treatment strategies

Cerebral intraventricular hemorrhage and post-hemorrhagic ventricular dilatation in preterm infan... more Cerebral intraventricular hemorrhage and post-hemorrhagic ventricular dilatation in preterm infants: new mechanistic insights and potential treatment strategies Romantsik, Olga 2021 Document Version: Publisher's PDF, also known as Version of record Link to publication Citation for published version (APA): Romantsik, O. (2021). Cerebral intraventricular hemorrhage and post-hemorrhagic ventricular dilatation in preterm infants: new mechanistic insights and potential treatment strategies. [Doctoral Thesis (compilation),

Research paper thumbnail of Severe intraventricular hemorrhage causes long-lasting structural damage in a preterm rabbit pup model

Pediatric Research, May 3, 2022

BACKGROUND: Intraventricular hemorrhage causes significant lifelong mortality and morbidity, espe... more BACKGROUND: Intraventricular hemorrhage causes significant lifelong mortality and morbidity, especially in preterm born infants. Progress in finding an effective therapy is stymied by a lack of preterm animal models with long-term follow-up. This study addresses this unmet need, using an established model of preterm rabbit IVH and analyzing outcomes out to 1 month of age. METHODS: Rabbit pups were delivered preterm and administered intraperitoneal injection of glycerol at 3 h of life and approximately 58% developed IVH. Neurobehavioral assessment was performed at 1 month of age followed by immunohistochemical labeling of epitopes for neurons, synapses, myelination, and interneurons, analyzed by means of digital quantitation and assessed via two-way ANOVA or Student's t test. RESULTS: IVH pups had globally reduced myelin content, an aberrant cortical myelination microstructure, and thinner upper cortical layers (I-III). We also observed a lower number of parvalbumin (PV)-positive interneurons in deeper cortical layers (IV-VI) in IVH animals and reduced numbers of neurons, synapses, and microglia. However, there were no discernable changes in behaviors. CONCLUSIONS: We have established in this preterm pup model that long-term changes after IVH include significant wide-ranging alterations to cortical organization and microstructure. Further work to improve the sensitivity of neurocognitive testing in this species at this age may be required.

Research paper thumbnail of The Effects of Caffeine Following Hypoxic-Ischemic Encephalopathy: A Systematic Review of Preclinical Studies

Social Science Research Network, 2022

Research paper thumbnail of Opioids for newborn infants receiving mechanical ventilation

The Cochrane library, Sep 18, 2020

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To determ... more This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To determine the benefits and harms of opioid analgesics in neonates (term or preterm) receiving mechanical ventilation, compared to placebo, no drug, other opioids, other analgesics or sedatives.

Research paper thumbnail of Stem cell-based interventions for the prevention and treatment of germinal matrix-intraventricular haemorrhage in preterm infants

The Cochrane library, Sep 24, 2019

BackgroundGerminal matrix‐intraventricular haemorrhage (GMH‐IVH) remains a substantial issue in n... more 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.

Research paper thumbnail of The Effects of Caffeine Following Hypoxic-Ischemic Encephalopathy: A Systematic Review of Preclinical Studies

Research paper thumbnail of Intraventricular Hemorrhage and White Matter Injury in the Preterm Infant

Neurology: Neonatology Questions and Controversies, 2012

Abstract This chapter focuses on a brief review of the pathogenesis of periventricular intraventr... more Abstract This chapter focuses on a brief review of the pathogenesis of periventricular intraventricular hemorrhage as well as white matter injury. Various approaches or strategies for the prevention, diagnosis, and treatment as well as outcomes are discussed with gaps in knowledge highlighted.

Research paper thumbnail of The effects of caffeine following hypoxic-ischemic encephalopathy: A systematic review of animal studies

Research paper thumbnail of Clonidine for painful procedures or conditions in infants

Cochrane Database of Systematic Reviews, 2018

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determ... more This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the efficacy and safety of clonidine for the prevention or treatment of procedural or postoperative pain, or pain associated with clinical conditions in neonates. Clonidine will be compared to placebo, no treatment, dexmedetomidine, paracetamol, and opioids. In addition, the safety of clonidine administration will be assessed for potential harms.

Research paper thumbnail of ایمونوتراپی خوراکی و زیرزبانی برای آلرژی به تخممرغ

The Cochrane database of systematic reviews, 2018

BACKGROUND Clinical egg allergy is a common food allergy. Current management relies upon strict a... more BACKGROUND Clinical egg allergy is a common food allergy. Current management relies upon strict allergen avoidance. Oral immunotherapy might be an optional treatment, through desensitization to egg allergen. OBJECTIVES To determine the efficacy and safety of oral and sublingual immunotherapy in children and adults with immunoglobulin E (IgE)-mediated egg allergy as compared to a placebo treatment or an avoidance strategy. SEARCH METHODS We searched 13 databases for journal articles, conference proceedings, theses and trials registers using a combination of subject headings and text words (last search 31 March 2017). SELECTION CRITERIA We included randomized controlled trials (RCTs) comparing oral immunotherapy or sublingual immunotherapy administered by any protocol with placebo or an elimination diet. Participants were children or adults with clinical egg allergy. DATA COLLECTION AND ANALYSIS We retrieved 97 studies from the electronic searches. We selected studies, extracted data ...

Research paper thumbnail of SPSS Data for: Behavioral testing and litter effects in the rabbit

Research paper thumbnail of Opioids for newborn infants receiving mechanical ventilation

Cochrane Database of Systematic Reviews, 2021

Study characteristics We collected and analysed all relevant studies to answer the review questio... more Study characteristics We collected and analysed all relevant studies to answer the review question and found 23 studies enrolling 2023 babies. In most studies, babies were born before the due date (before 37 weeks' gestational age). Eight studies compared the use of morphine versus placebo (a substance with no therapeutic value) or no intervention, and seven versus fentanyl. We analysed the other studies separately because researchers compared the use of these two drugs with other opioids or other analgesics. Key results We are uncertain whether opioids have an e ect on pain and neurodevelopmental outcomes at 18 to 24 months; use of morphine or fentanyl probably has little or no e ect in reducing the duration of mechanical ventilation and neonatal mortality. Further research is needed. Certainty of evidence The certainty of evidence is very low to moderate because overall only a small number of studies have looked at this intervention, few babies were included in these studies, and some studies could have been better designed. How up-to-date is this review? We searched for studies that had been published up to