Pub Date : 2024-10-09DOI: 10.1016/j.semperi.2024.151990
Summer Elshenawy, Monique R Radman-Harrison, Philip T Levy, Satyan Lakshminrusimha, Taylor L Sawyer, Brenda H Law
Severe bronchopulmonary dysplasia (sBPD) requiring invasive mechanical ventilation is a heterogeneous disease process that contributes to morbidity and mortality in infants. As the most common lung disease of prematurity, sBPD has a multitude of overlapping cardiac, airway, pulmonary vascular, and infectious phenotypic presentations that progress through four different phases of care. Premature infants with sBPD are at a high risk of acute decompensation and subsequent cardiopulmonary arrest. A comprehensive determination of the complex phenotypes that contribute to the clinical presentation will help clinicians decipher the phase of care, identify cardiopulmonary compromise earlier and guide targeted therapeutic intervention during acute episodes of deterioration. The approach to resuscitation of premature infants with sBPD undergoing an acute decompensation differs from general neonatal and pediatric resuscitation practices. This review summarizes the phenotypes of sBPD, the phases of care, the common triggers of acute exacerbations, and the principles of resuscitation of a deteriorating infant with sBPD. We offer a framework for sBPD resuscitation with a focus on prevention, assessment, and post-resuscitative care.
{"title":"Principles of resuscitation for infants with severe bronchopulmonary dysplasia.","authors":"Summer Elshenawy, Monique R Radman-Harrison, Philip T Levy, Satyan Lakshminrusimha, Taylor L Sawyer, Brenda H Law","doi":"10.1016/j.semperi.2024.151990","DOIUrl":"https://doi.org/10.1016/j.semperi.2024.151990","url":null,"abstract":"<p><p>Severe bronchopulmonary dysplasia (sBPD) requiring invasive mechanical ventilation is a heterogeneous disease process that contributes to morbidity and mortality in infants. As the most common lung disease of prematurity, sBPD has a multitude of overlapping cardiac, airway, pulmonary vascular, and infectious phenotypic presentations that progress through four different phases of care. Premature infants with sBPD are at a high risk of acute decompensation and subsequent cardiopulmonary arrest. A comprehensive determination of the complex phenotypes that contribute to the clinical presentation will help clinicians decipher the phase of care, identify cardiopulmonary compromise earlier and guide targeted therapeutic intervention during acute episodes of deterioration. The approach to resuscitation of premature infants with sBPD undergoing an acute decompensation differs from general neonatal and pediatric resuscitation practices. This review summarizes the phenotypes of sBPD, the phases of care, the common triggers of acute exacerbations, and the principles of resuscitation of a deteriorating infant with sBPD. We offer a framework for sBPD resuscitation with a focus on prevention, assessment, and post-resuscitative care.</p>","PeriodicalId":21761,"journal":{"name":"Seminars in perinatology","volume":" ","pages":"151990"},"PeriodicalIF":3.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-09DOI: 10.1016/j.semperi.2024.151991
Elizabeth Schierholz, Elizabeth A Wetzel, Alyssa R Thomas, Beena D Kamath-Rayne, Danielle J W Reed
The Neonatal Resuscitation Program (NRP) is the most used resuscitation algorithm for infants requiring resuscitation in the neonatal intensive care unit (NICU). The population of infants cared for in the NICU is varied and complex with resuscitation needs that may extend beyond the NRP algorithm. To provide resuscitation care that addresses these needs, institutions may choose to incorporate algorithms from the Pediatric Advanced Life Support or a "hybrid" approach that includes NRP. Limited evidence exists to support one algorithm or approach over another. In this article, we identify potential gaps in the application of using NRP or PALS in the NICU population, present select patient decompensations and discuss the resuscitation management approach using the NRP or PALS algorithms. Challenges associated with NICU resuscitation education will be explored as well as approaches to overcome some of the identified resuscitation education obstacles.
{"title":"Resuscitation education for NICU providers: Current practice and recommendations for NRP and PALS in the NICU.","authors":"Elizabeth Schierholz, Elizabeth A Wetzel, Alyssa R Thomas, Beena D Kamath-Rayne, Danielle J W Reed","doi":"10.1016/j.semperi.2024.151991","DOIUrl":"https://doi.org/10.1016/j.semperi.2024.151991","url":null,"abstract":"<p><p>The Neonatal Resuscitation Program (NRP) is the most used resuscitation algorithm for infants requiring resuscitation in the neonatal intensive care unit (NICU). The population of infants cared for in the NICU is varied and complex with resuscitation needs that may extend beyond the NRP algorithm. To provide resuscitation care that addresses these needs, institutions may choose to incorporate algorithms from the Pediatric Advanced Life Support or a \"hybrid\" approach that includes NRP. Limited evidence exists to support one algorithm or approach over another. In this article, we identify potential gaps in the application of using NRP or PALS in the NICU population, present select patient decompensations and discuss the resuscitation management approach using the NRP or PALS algorithms. Challenges associated with NICU resuscitation education will be explored as well as approaches to overcome some of the identified resuscitation education obstacles.</p>","PeriodicalId":21761,"journal":{"name":"Seminars in perinatology","volume":" ","pages":"151991"},"PeriodicalIF":3.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142474245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-08DOI: 10.1016/j.semperi.2024.151989
Beth Ann Johnson, Jennifer Shepherd, Shazia Bhombal, Noorjahan Ali, Chloe Joynt
Effective resuscitation of neonates with congenital heart disease (CHD) depends on comprehensive planning, thorough understanding of physiology, vigilant monitoring, and interdisciplinary collaboration to achieve the best outcomes. Neonatal heart disease can affect cardiac structure, rhythm, or ventricular function, and may be either congenital or acquired. Critical congenital heart disease (CCHD) can result in inadequate pulmonary blood flow, impaired intracardiac mixing, airway obstruction, or insufficient cardiac output. Tailored resuscitation strategies are important as early as the delivery room, where some CHD lesions may cause immediate cardiovascular instability during the transition from fetal to postnatal circulation. Premature infants with CHD are at higher risk due to their small size and the complications associated with prematurity, affecting both CHD management and overall clinical stability. Addressing both cardiac and non-cardiac causes of decompensation requires a precise understanding of each patient's unique physiology and trajectory from delivery through postintervention intensive care.
{"title":"Special considerations for the stabilization and resuscitation of patients with cardiac disease in the Neonatal Intensive Care Unit.","authors":"Beth Ann Johnson, Jennifer Shepherd, Shazia Bhombal, Noorjahan Ali, Chloe Joynt","doi":"10.1016/j.semperi.2024.151989","DOIUrl":"https://doi.org/10.1016/j.semperi.2024.151989","url":null,"abstract":"<p><p>Effective resuscitation of neonates with congenital heart disease (CHD) depends on comprehensive planning, thorough understanding of physiology, vigilant monitoring, and interdisciplinary collaboration to achieve the best outcomes. Neonatal heart disease can affect cardiac structure, rhythm, or ventricular function, and may be either congenital or acquired. Critical congenital heart disease (CCHD) can result in inadequate pulmonary blood flow, impaired intracardiac mixing, airway obstruction, or insufficient cardiac output. Tailored resuscitation strategies are important as early as the delivery room, where some CHD lesions may cause immediate cardiovascular instability during the transition from fetal to postnatal circulation. Premature infants with CHD are at higher risk due to their small size and the complications associated with prematurity, affecting both CHD management and overall clinical stability. Addressing both cardiac and non-cardiac causes of decompensation requires a precise understanding of each patient's unique physiology and trajectory from delivery through postintervention intensive care.</p>","PeriodicalId":21761,"journal":{"name":"Seminars in perinatology","volume":" ","pages":"151989"},"PeriodicalIF":3.2,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.semperi.2024.151928
Critically ill newborns experience numerous painful procedures as part of lifesaving care in the Neonatal Intensive Care Unit. However, painful exposures in the neonatal period have been associated with alterations in brain maturation and poorer neurodevelopmental outcomes in childhood. The most frequently used medications for pain and sedation in the NICU are opioids, benzodiazepines and sucrose; these have also been associated with abnormalities in brain maturation and neurodevelopment making it challenging to know what the best approach is to treat neonatal pain. This article provides clinicians with an overview of how neonatal exposure to pain as well as analgesic and sedative medications impact brain maturation and neurodevelopmental outcomes in critically ill infants. We also highlight areas in need of future research to develop standardized neonatal pain monitoring and management strategies.
{"title":"Effects of pain, sedation and analgesia on neonatal brain injury and brain development","authors":"","doi":"10.1016/j.semperi.2024.151928","DOIUrl":"10.1016/j.semperi.2024.151928","url":null,"abstract":"<div><p>Critically ill newborns experience numerous painful procedures as part of lifesaving care in the Neonatal Intensive Care Unit. However, painful exposures in the neonatal period have been associated with alterations in brain maturation and poorer neurodevelopmental outcomes in childhood. The most frequently used medications for pain and sedation in the NICU are opioids, benzodiazepines and sucrose; these have also been associated with abnormalities in brain maturation and neurodevelopment making it challenging to know what the best approach is to treat neonatal pain. This article provides clinicians with an overview of how neonatal exposure to pain as well as analgesic and sedative medications impact brain maturation and neurodevelopmental outcomes in critically ill infants. We also highlight areas in need of future research to develop standardized neonatal pain monitoring and management strategies.</p></div>","PeriodicalId":21761,"journal":{"name":"Seminars in perinatology","volume":"48 5","pages":"Article 151928"},"PeriodicalIF":3.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0146000524000624/pdfft?md5=d710888fa8c40a2ddbb5249b10529286&pid=1-s2.0-S0146000524000624-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141394217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.semperi.2024.151926
Parents play a pivotal role in neurodevelopmental outcomes of their children in the neonatal intensive care unit (NICU) and beyond. Integration of parents in clinical care and research is synergistic. Engaged parents yield more comprehensive clinical care and more robust and meaningful research products. Subsequently, successful clinical and research efforts improve outcomes for children. We review strategies for parental integration into NICU clinical care and research, including parental involvement in therapeutic interventions and neurodevelopmental care, and effective communication strategies for clinicians and researchers. We discuss challenges in neonatal trials and emphasize the need for building a culture of research, collaborative partnerships with patient advocacy organizations, and ongoing support beyond the NICU. Overall, we call for recognizing and fostering the impactful role of parents as teammates with clinicians and researchers in optimizing neurodevelopmental outcomes in the NICU and beyond.
{"title":"Parental impact during and after neonatal intensive care admission","authors":"","doi":"10.1016/j.semperi.2024.151926","DOIUrl":"10.1016/j.semperi.2024.151926","url":null,"abstract":"<div><p><span>Parents play a pivotal role in neurodevelopmental outcomes of their children in the neonatal intensive care unit (NICU) and beyond. Integration of parents in clinical care and research is synergistic. Engaged parents yield more comprehensive clinical care and more robust and meaningful research products. Subsequently, successful clinical and research efforts improve outcomes for children. We review strategies for parental integration into NICU clinical care and research, including parental involvement in therapeutic interventions and neurodevelopmental care, and effective communication strategies for clinicians and researchers. We discuss challenges in neonatal trials and emphasize the need for building a culture of research, collaborative partnerships with </span>patient advocacy organizations, and ongoing support beyond the NICU. Overall, we call for recognizing and fostering the impactful role of parents as teammates with clinicians and researchers in optimizing neurodevelopmental outcomes in the NICU and beyond.</p></div>","PeriodicalId":21761,"journal":{"name":"Seminars in perinatology","volume":"48 5","pages":"Article 151926"},"PeriodicalIF":3.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141393235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.semperi.2024.151925
In this review, we explore race-based disparities in neonatology and their impact on brain injury and neurodevelopmental outcomes. We discuss the historical context of healthcare discrimination, focusing on the post-Civil War era and the segregation of healthcare facilities. We highlight the increasing disparity in infant mortality rates between Black and White infants, with premature birth being a major contributing factor, and emphasize the role of prenatal factors such as metabolic syndrome and toxic stress in affecting neonatal health. Furthermore, we examine the geographic and historical aspects of racial disparities, including the consequences of redlining and limited access to healthcare facilities or nutritious food options in Black communities. Finally, we delve into the higher incidence of brain injuries in Black neonates, as well as disparities in adverse neurodevelopmental outcome. This evidence underscores the need for comprehensive efforts to address systemic racism and provide equitable access to healthcare resources.
{"title":"Racial and geographic disparities in neonatal brain care","authors":"","doi":"10.1016/j.semperi.2024.151925","DOIUrl":"10.1016/j.semperi.2024.151925","url":null,"abstract":"<div><p>In this review, we explore race-based disparities in neonatology and their impact on brain injury and neurodevelopmental outcomes. We discuss the historical context of healthcare discrimination, focusing on the post-Civil War era and the segregation of healthcare facilities. We highlight the increasing disparity in infant mortality rates between Black and White infants, with premature birth being a major contributing factor, and emphasize the role of prenatal factors such as metabolic syndrome and toxic stress in affecting neonatal health. Furthermore, we examine the geographic and historical aspects of racial disparities, including the consequences of redlining and limited access to healthcare facilities or nutritious food options in Black communities. Finally, we delve into the higher incidence of brain injuries in Black neonates, as well as disparities in adverse neurodevelopmental outcome. This evidence underscores the need for comprehensive efforts to address systemic racism and provide equitable access to healthcare resources.</p></div>","PeriodicalId":21761,"journal":{"name":"Seminars in perinatology","volume":"48 5","pages":"Article 151925"},"PeriodicalIF":3.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0146000524000594/pdfft?md5=22f404a6ca4e469dd12b81fe680a8f89&pid=1-s2.0-S0146000524000594-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141407722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.semperi.2024.151931
{"title":"Protecting and healing the newborn brain through non-pharmacologic and pharmacologic measures","authors":"","doi":"10.1016/j.semperi.2024.151931","DOIUrl":"10.1016/j.semperi.2024.151931","url":null,"abstract":"","PeriodicalId":21761,"journal":{"name":"Seminars in perinatology","volume":"48 5","pages":"Article 151931"},"PeriodicalIF":3.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141408686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.semperi.2024.151930
Therapeutic hypothermia is now standard of care for neonates with hypoxic-ischemic encephalopathy (HIE) in high income countries (HIC). Conversely, compelling trial evidence suggests that hypothermia is ineffective, and may be deleterious, in low- and middle-income countries (LMIC), likely reflecting the lower proportion of infants who had sentinel events at birth, suggesting that injury had advanced to a stage when hypothermia is no longer effective. Although hypothermia significantly reduced the risk of death and disability in HICs, many infants survived with disability and in principle may benefit from targeted add-on neuroprotective or neurorestorative therapies. The present review will assess biomarkers that could be used to personalize treatment for babies with HIE – to determine first whether an individual infant is likely to respond to hypothermia, and second, whether additional treatments may be beneficial.
目前,治疗性低温疗法已成为高收入国家(HIC)治疗新生儿缺氧缺血性脑病(HIE)的标准疗法。相反,令人信服的试验证据表明,低体温疗法在中低收入国家(LMIC)是无效的,而且可能是有害的,这可能反映了出生时发生哨点事件的婴儿比例较低,表明损伤已发展到低体温疗法不再有效的阶段。虽然低体温疗法能大大降低高收入国家的死亡和残疾风险,但许多婴儿存活下来时仍有残疾,原则上可能会受益于有针对性的附加神经保护或神经恢复疗法。本综述将评估可用于对 HIE 婴儿进行个性化治疗的生物标志物--首先确定婴儿个体是否可能对低体温有反应,其次确定额外的治疗是否可能有益。
{"title":"How do we reach the goal of personalized medicine for neuroprotection in neonatal hypoxic-ischemic encephalopathy?","authors":"","doi":"10.1016/j.semperi.2024.151930","DOIUrl":"10.1016/j.semperi.2024.151930","url":null,"abstract":"<div><p>Therapeutic hypothermia is now standard of care for neonates with hypoxic-ischemic encephalopathy (HIE) in high income countries (HIC). Conversely, compelling trial evidence suggests that hypothermia is ineffective, and may be deleterious, in low- and middle-income countries (LMIC), likely reflecting the lower proportion of infants who had sentinel events at birth, suggesting that injury had advanced to a stage when hypothermia is no longer effective. Although hypothermia significantly reduced the risk of death and disability in HICs, many infants survived with disability and in principle may benefit from targeted add-on neuroprotective or neurorestorative therapies. The present review will assess biomarkers that could be used to personalize treatment for babies with HIE – to determine first whether an individual infant is likely to respond to hypothermia, and second, whether additional treatments may be beneficial.</p></div>","PeriodicalId":21761,"journal":{"name":"Seminars in perinatology","volume":"48 5","pages":"Article 151930"},"PeriodicalIF":3.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0146000524000648/pdfft?md5=ead39b4a98d93ad966f805f4f2126896&pid=1-s2.0-S0146000524000648-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.semperi.2024.151927
Early nutritional exposures, including during embryogenesis and the immediate postnatal period, affect offspring outcomes in both the short- and long-term. Alterations of these modifiable exposures shape the developing gut microbiome, intestinal development, and even neurodevelopmental outcomes. A gut-brain axis exists, and it is intricately connected to early life feeding and nutritional exposures. Here, we seek to discuss the (1) origins of the gut-brain access and relationship with neurodevelopment, (2) components of human milk (HM) beyond nutrition and their role in the developing newborn, and (3) clinical application of nutritional practices, including fluid management and feeding on the development of the gut-brain axis, and long-term neurodevelopmental outcomes. We conclude with a discussion on future directions and unanswered questions that are critical to provide further understanding and insight into how clinicians and healthcare providers can optimize early nutritional practices to ensure children not only survive, but thrive, free of neurodevelopmental impairment.
{"title":"Nutrition and the gut-brain axis in neonatal brain injury and development","authors":"","doi":"10.1016/j.semperi.2024.151927","DOIUrl":"10.1016/j.semperi.2024.151927","url":null,"abstract":"<div><p><span>Early nutritional exposures, including during embryogenesis and the immediate postnatal period, affect offspring outcomes in both the short- and long-term. Alterations of these modifiable exposures shape the developing </span>gut microbiome<span><span>, intestinal development, and even neurodevelopmental outcomes. A gut-brain axis exists, and it is intricately connected to early life feeding and nutritional exposures. Here, we seek to discuss the (1) origins of the gut-brain access and relationship with neurodevelopment, (2) components of human milk (HM) beyond nutrition and their role in the developing </span>newborn, and (3) clinical application of nutritional practices, including fluid management and feeding on the development of the gut-brain axis, and long-term neurodevelopmental outcomes. We conclude with a discussion on future directions and unanswered questions that are critical to provide further understanding and insight into how clinicians and healthcare providers can optimize early nutritional practices to ensure children not only survive, but thrive, free of neurodevelopmental impairment.</span></p></div>","PeriodicalId":21761,"journal":{"name":"Seminars in perinatology","volume":"48 5","pages":"Article 151927"},"PeriodicalIF":3.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-01DOI: 10.1016/j.semperi.2024.151929
Hypoxic ischemic encephalopathy (HIE) remains a leading cause of neonatal mortality and lifelong disability across the world. While therapeutic hypothermia (HT) is beneficial, it is only partially protective and adjuvant treatments that further improve outcomes are urgently needed. In high-income countries where HT is standard care, novel treatments are tested in conjunction with HT. Mesenchymal stromal cells (MSC) represent a paradigm shift in brain protection, uniquely adapting to the host cellular microenvironment. MSC have low immunogenicity and potent paracrine effects stimulating the host tissue repair and regeneration and reducing inflammation and apoptosis. Preclinical studies in perinatal brain injury suggest that MSC are beneficial after hypoxia-ischemia (HI) and most preclinical studies of MSC with HT show protection. Preclinical and early phase clinical trials have shown that allogenic administration of MSC to neonates with perinatal stroke and HIE is safe and feasible but further safety and efficacy studies of HT with MSC in these populations are needed. Combination therapies that target all stages of the evolution of injury after HI (eg HT, melatonin and MSC) show promise for improving outcomes in HIE.
缺氧缺血性脑病(HIE)仍然是全球新生儿死亡和终身残疾的主要原因。治疗性低温(HT)虽然有益,但只能起到部分保护作用,因此迫切需要能进一步改善预后的辅助治疗方法。在将低体温疗法作为标准治疗方法的高收入国家,新型疗法与低体温疗法一起进行了测试。间充质基质细胞(MSC)能独特地适应宿主细胞微环境,代表了脑保护领域的范式转变。间充质干细胞免疫原性低,具有强大的旁分泌效应,可刺激宿主组织修复和再生,减少炎症和细胞凋亡。围产期脑损伤的临床前研究表明,间充质干细胞对缺氧缺血(HI)后的脑损伤有益。临床前和早期临床试验表明,对患有围产期中风和缺氧缺血性脑损伤的新生儿进行异基因间充质干细胞给药是安全可行的,但还需要对这些人群使用间充质干细胞进行缺氧缺血性脑损伤的安全性和有效性进行进一步研究。针对 HIE 后损伤演变各阶段的联合疗法(如 HT、褪黑激素和间充质干细胞)有望改善 HIE 的预后。
{"title":"Mesenchymal Stromal Cell therapy for Hypoxic Ischemic Encephalopathy: Future directions for combination therapy with hypothermia and/or melatonin","authors":"","doi":"10.1016/j.semperi.2024.151929","DOIUrl":"10.1016/j.semperi.2024.151929","url":null,"abstract":"<div><p>Hypoxic ischemic encephalopathy (HIE) remains a leading cause of neonatal mortality and lifelong disability across the world. While therapeutic hypothermia (HT) is beneficial, it is only partially protective and adjuvant treatments that further improve outcomes are urgently needed. In high-income countries where HT is standard care, novel treatments are tested in conjunction with HT. Mesenchymal stromal cells (MSC) represent a paradigm shift in brain protection, uniquely adapting to the host cellular microenvironment. MSC have low immunogenicity and potent paracrine effects stimulating the host tissue repair and regeneration and reducing inflammation and apoptosis. Preclinical studies in perinatal brain injury suggest that MSC are beneficial after hypoxia-ischemia (HI) and most preclinical studies of MSC with HT show protection. Preclinical and early phase clinical trials have shown that allogenic administration of MSC to neonates with perinatal stroke and HIE is safe and feasible but further safety and efficacy studies of HT with MSC in these populations are needed. Combination therapies that target all stages of the evolution of injury after HI (eg HT, melatonin and MSC) show promise for improving outcomes in HIE.</p></div>","PeriodicalId":21761,"journal":{"name":"Seminars in perinatology","volume":"48 5","pages":"Article 151929"},"PeriodicalIF":3.2,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0146000524000636/pdfft?md5=faa9a0b7c827fc4ff65b4e16d146e535&pid=1-s2.0-S0146000524000636-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141403138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}