|
1
|
Shah EG, Neil JJ, Smyser CD. Advances in Neonatal Neuroimaging. Clin Perinatol 2025; 52:237-269. [PMID: 40350210 DOI: 10.1016/j.clp.2025.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/14/2025]
Abstract
Neuroimaging has a vital role in assessing the neonatal neuroaxis in many different clinical contexts and in stratifying risk for neurodevelopmental differences. Advances in hardware and computational techniques across modalities have burgeoned in the last several decades, contributing to an improved understanding of brain maturation, development, and plasticity in this unique clinical population.
Collapse
Affiliation(s)
- Ekta G Shah
- Division of Neurology, Department of Pediatrics, Emory University School of Medicine, 2174 North Druid Hills Road NE, Atlanta, GA 30329, USA
| | - Jeffrey J Neil
- Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA; Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA; Department of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA
| | - Christopher D Smyser
- Department of Neurology, Washington University School of Medicine, St Louis, MO 63110, USA; Department of Pediatrics, Washington University School of Medicine, St Louis, MO 63110, USA; Department of Radiology, Washington University School of Medicine, St Louis, MO 63110, USA.
| |
Collapse
|
|
2
|
De Palma ST, Hermans EC, Shamorkina TM, Trayford C, van Rijt S, Heck AJR, Nijboer CHA, de Theije CGM. Hypoxic Preconditioning Enhances the Potential of Mesenchymal Stem Cells to Treat Neonatal Hypoxic-Ischemic Brain Injury. Stroke 2025. [PMID: 40248869 DOI: 10.1161/strokeaha.124.048964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Revised: 03/16/2025] [Accepted: 04/04/2025] [Indexed: 04/19/2025]
Abstract
BACKGROUND Neonatal hypoxic-ischemic (HI) brain injury is one of the leading causes of long-term neurological morbidity in newborns. Current treatment options for HI brain injury are limited, but mesenchymal stem cell (MSC) therapy is a promising strategy to boost neuroregeneration after injury. Optimization strategies to further enhance the potential of MSCs are under development. The current study aimed to test the potency of hypoxic preconditioning of MSCs to enhance the therapeutic efficacy in a mouse model of neonatal HI injury. METHODS HI was induced on postnatal day 9 in C57Bl/6 mouse pups. MSCs were cultured under hypoxic (hypoxic-preconditioned MSCs [HP-MSCs], 1% O2) or normoxic-control (normoxic-preconditioned MSCs, 21% O2) conditions for 24 hours before use. At 10 days after HI, HP-MSCs, normoxic-preconditioned MSCs, or vehicle were intranasally administered. Gold nanoparticle-labeled MSCs were used to assess MSC migration 24 hours after intranasal administration. At 28 days post-HI, lesion size, sensorimotor outcome, and neuroinflammation were assessed by hematoxylin and eosin staining, cylinder rearing task, and IBA1 staining, respectively. In vitro, the effect of HP-MSCs was studied on transwell migration, neural stem cell differentiation and microglia activation, and the MSC intracellular proteomic content was profiled using quantitative LC-MS/ms. RESULTS Intranasally administered HP-MSCs were superior to normoxic-preconditioned MSCs in reducing lesion size and sensorimotor impairments post-HI. Moreover, hypoxic preconditioning enhanced MSC migration in an in vitro set-up, and in vivo to the lesioned hemisphere after intranasal application. In addition, HP-MSCs enhanced neural stem cell differentiation into more complex neurons in vitro but had similar anti-inflammatory effects compared with normoxic-preconditioned MSCs. Lastly, hypoxic preconditioning led to elevated abundances of proteins in MSCs related to extracellular matrix remodeling. CONCLUSIONS This study shows for the first time that hypoxic preconditioning enhanced the therapeutic efficacy of MSC therapy in a mouse model of neonatal HI brain injury by increasing the migratory and neuroregenerative capacity of MSCs.
Collapse
Affiliation(s)
- Sara T De Palma
- Department for Developmental Origins of Disease, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital (S.T.D.P., E.C.H., C.H.A.N., C.G.M.d.T.)
| | - Eva C Hermans
- Department for Developmental Origins of Disease, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital (S.T.D.P., E.C.H., C.H.A.N., C.G.M.d.T.)
| | - Tatiana M Shamorkina
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences (T.M.S., A.J.R.H.)
- Utrecht University, the Netherlands. Netherlands Proteomics Center, Utrecht (T.M.S., A.J.R.H.)
| | - Chloe Trayford
- Department of Instructive Biomaterials Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, the Netherlands (C.T., S.v.R.)
| | - Sabine van Rijt
- Department of Instructive Biomaterials Engineering, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, the Netherlands (C.T., S.v.R.)
| | - Albert J R Heck
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences (T.M.S., A.J.R.H.)
- Utrecht University, the Netherlands. Netherlands Proteomics Center, Utrecht (T.M.S., A.J.R.H.)
| | - Cora H A Nijboer
- Department for Developmental Origins of Disease, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital (S.T.D.P., E.C.H., C.H.A.N., C.G.M.d.T.)
| | - Caroline G M de Theije
- Department for Developmental Origins of Disease, University Medical Center Utrecht Brain Center and Wilhelmina Children's Hospital (S.T.D.P., E.C.H., C.H.A.N., C.G.M.d.T.)
| |
Collapse
|
|
3
|
El Shahed AI, Branson HM, Chacko A, Terumalay S, Zheng X, Pang EW, Wilson D, Blaser S, Chau V, Miller SP, Whyte HE, Ly LG. Predictive model of neurodevelopmental outcome in neonatal hypoxic ischemic encephalopathy. Early Hum Dev 2025; 201:106189. [PMID: 39787883 DOI: 10.1016/j.earlhumdev.2024.106189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2024] [Revised: 12/28/2024] [Accepted: 12/29/2024] [Indexed: 01/12/2025]
Abstract
OBJECTIVES To build an early, prognostic model for adverse outcome in infants with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) based on brain magnetic resonance images (MRI), electrophysiological tests and clinical assessments were performed during the first 5 days of life. METHODS Retrospective study of 182 neonates with HIE and managed with TH. The predominant pattern of HIE brain injury on MRI performed following cooling was scored by neuroradiologists. The electroencephalogram (EEG) background and evoked potential (EP) response, were analyzed. Area under the curve (AUC) of these tools for adverse outcome including death and/or moderate disabilities using the Bayley-III at 36 months were calculated. A stepwise model approach was used to reach the final most efficient predictive model. RESULTS Of 182 neonates, 99 were male (54.4 %), with median gestational age of 39 weeks (IQR 38-40) and median weight of 3.3 kg (IQR 2.9-3.7). On admission, 47 (26 %), 104 (57 %) and 31(17 %) neonates presented with mild, moderate and severe encephalopathy respectively. In multivariate analysis of 129 infants who received all prognostic modalities, the predictive value of a model of EEG plus MRI, AUC = 84 %) is equivalent to models of EEG plus MRI with added EP and clinical assessment at discharge (AUC = 84 and 85 % respectively). CONCLUSION In the era of cooling for neonatal HIE, the combination of EEG background and MRI during the first few days of life, provide an objective and highly reliable model for prediction of death and long-term disabilities.
Collapse
Affiliation(s)
- Amr I El Shahed
- Department of Pediatrics, Division of Neonatology, The Hospital for Sick Children and the University of Toronto, Ontario, Canada.
| | - Helen M Branson
- Department of Diagnostic Imaging and Interventional Radiology, The Hospital for Sick Children and the University of Toronto, Ontario, Canada.
| | - Anil Chacko
- Department of Pediatrics (Division of Neonatology), Surrey Memorial Hospital, British Columbia, Canada.
| | | | - Xin Zheng
- Department of Pediatrics, Division of Neonatology, The Hospital for Sick Children and the University of Toronto, Ontario, Canada.
| | - Elizabeth W Pang
- Department of Pediatrics, Division of Neurology, The Hospital for Sick Children and the University of Toronto, Ontario, Canada; Neurosciences and Mental Health Research Institute, Toronto, Ontario, Canada.
| | - Diane Wilson
- Department of Pediatrics, Division of Neonatology, The Hospital for Sick Children and the University of Toronto, Ontario, Canada.
| | - Susan Blaser
- Department of Diagnostic Imaging and Interventional Radiology, The Hospital for Sick Children and the University of Toronto, Ontario, Canada.
| | - Vann Chau
- Department of Pediatrics, Division of Neurology, The Hospital for Sick Children and the University of Toronto, Ontario, Canada; Neurosciences and Mental Health Research Institute, Toronto, Ontario, Canada.
| | - Steven P Miller
- Department of Pediatrics, Division of Neonatology, The Hospital for Sick Children and the University of Toronto, Ontario, Canada; Neurosciences and Mental Health Research Institute, Toronto, Ontario, Canada.
| | - Hilary E Whyte
- Department of Pediatrics, Division of Neonatology, The Hospital for Sick Children and the University of Toronto, Ontario, Canada.
| | - Linh G Ly
- Department of Pediatrics, Division of Neonatology, The Hospital for Sick Children and the University of Toronto, Ontario, Canada.
| |
Collapse
|
|
4
|
Pisani F, Spagnoli C. What are the main challenges in the treatment of neonatal hypoxic ischemic encephalopathy? Expert Rev Neurother 2025; 25:121-124. [PMID: 39656883 DOI: 10.1080/14737175.2024.2438649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2024] [Accepted: 12/03/2024] [Indexed: 12/17/2024]
Affiliation(s)
- Francesco Pisani
- Child Neuropsychiatric Unit, "Policlinico Umberto I" University Hospital, Rome, Italy
- Child Neuropsychiatric Unit, Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy
| | - Carlotta Spagnoli
- Child Neuropsychiatry Unit, Mother and Child Department, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| |
Collapse
|
|
5
|
Rondagh M, de Vries LS, van Steenis A, Meder U, Szakacs L, Jermendy A, Steggerda SJ. Longitudinal Analysis of Amplitude-Integrated Electroencephalography for Outcome Prediction in Infants with Hypoxic-Ischemic Encephalopathy: A Validation Study. J Pediatr 2025; 277:114407. [PMID: 39551094 DOI: 10.1016/j.jpeds.2024.114407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2024] [Revised: 11/07/2024] [Accepted: 11/12/2024] [Indexed: 11/19/2024]
Abstract
OBJECTIVES To validate the prognostic accuracy of a previously published tool (HOPE calculator) using longitudinal analysis of amplitude-integrated electroencephalography (aEEG) background activity and sleep-wake cycling to predict favorable or adverse 2-year neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH), and to evaluate the predictive value for outcome at 5-8 years of age. STUDY DESIGN Single-center retrospective cohort study in 117 infants who underwent TH for HIE between 2008 and 2022. We scored 2-channel aEEG BGPs, sleep-wake cycling, and seizure activity at 6-hour intervals for 84 hours. Neurodevelopmental outcome at 2 years was evaluated using the Bayley Scales of Infant Development-III, defining adverse outcome as death, cerebral palsy, and/or cognitive/motor scores of <85. Adverse outcome at 5-8 years was defined as a total IQ score of <85, a Movement-ABC-2 score of less than p15, cerebral palsy, severe sensory impairment, or death. RESULTS The prediction model showed an area under the curve of 0.90 (95% CI, 0.83-0.95) at 2 years and 0.83 (95% CI, 0.73-0.92) at 5-8 years. Mean predicted probability of favorable outcome was 74.5% (95% CI, 69.4-79.6) in the favorable outcome group compared with 32.8% (95% CI, 23.5-42.2) in the adverse outcome group (P < .001) at 2 years (n = 115) and 76.85% (95% CI, 70.0-83.4) compared with 40.7% (95% CI, 30.0-51.4) at 5-8 years (n = 68). CONCLUSIONS Our study provided external validation of the HOPE calculator, assessing longitudinal aEEG background activity during TH in infants with HIE. The results suggest that this method can predict favorable or adverse outcomes accurately not only at 2 but also at 5-8 years of age.
Collapse
Affiliation(s)
- Mathies Rondagh
- Division of Neonatology, Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center, The Netherlands.
| | - Linda S de Vries
- Division of Neonatology, Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center, The Netherlands
| | - Andrea van Steenis
- Division of Neonatology, Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center, The Netherlands
| | - Unoke Meder
- Division of Neonatology, Department of Pediatrics, Semmelweis University, Budapest, Hungary
| | - Laszlo Szakacs
- Division of Neonatology, Department of Pediatrics, Semmelweis University, Budapest, Hungary
| | - Agnes Jermendy
- Division of Neonatology, Department of Pediatrics, Semmelweis University, Budapest, Hungary
| | - Sylke J Steggerda
- Division of Neonatology, Department of Pediatrics, Willem-Alexander Children's Hospital, Leiden University Medical Center, The Netherlands
| |
Collapse
|
|
6
|
Nabizadeh F. Brain white matter damage biomarkers. Adv Clin Chem 2024; 125:55-91. [PMID: 39988408 DOI: 10.1016/bs.acc.2024.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/25/2025]
Abstract
White matter (WM), constituting nearly half of the human brain's mass, is pivotal for the rapid transmission of neural signals across different brain regions, significantly influencing cognitive processes like learning, memory, and problem-solving. The integrity of WM is essential for brain function, and its damage, which can occur due to conditions such as multiple sclerosis (MS), stroke, and traumatic brain injury, results in severe neurological deficits and cognitive decline. The primary objective of this book chapter is to discuss the clinical significance of fluid biomarkers in assessing WM damage within the central nervous system (CNS). It explores the biological underpinnings and pathological changes in WM due to various neurological conditions and details how alterations can be detected and quantified through fluid biomarkers. By examining biomarkers like Myelin Basic Protein (MBP), Neurofilament light chain (NFL), and others, the chapter highlights their role in enhancing diagnostic precision, monitoring disease progression, and guiding therapeutic interventions, thus providing crucial insights into maintaining WM integrity and preventing cognitive and physical disabilities.
Collapse
Affiliation(s)
- Fardin Nabizadeh
- School of Medicine, Iran University of Medical Sciences, and Alzheimer's Disease Institute, Tehran, Iran.
| |
Collapse
|
|
7
|
Abusaleem MY, Ebrahim MEE, Hamed NF, Eladwy MFM. A Systematic Review of the Relationship Between Neonatal Hypoxic-Ischemic Encephalopathy and Long-Term Cognitive Outcomes: Where Do We Stand? Cureus 2024; 16:e68227. [PMID: 39347282 PMCID: PMC11439448 DOI: 10.7759/cureus.68227] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/29/2024] [Indexed: 10/01/2024] Open
Abstract
This study aims to systematically review the existing literature on long-term cognitive outcomes in neonates with hypoxic-ischemic encephalopathy (HIE). A thorough search of PubMed, MEDLINE, and Embase was conducted to find studies that satisfied the inclusion requirements. Rayyan (Qatar Computing Research Institute, Doha, Qatar) was utilized during the whole operation. Our results included seven studies with a total of 521 patients and 247 (47.4%) were females. All of the included participants were assessed for the incidence of cognitive functions following hypothermia therapy. Newborns with significant HIE are at high risk for neurodevelopmental complications even in the absence of magnetic resonance imagining (MRI) abnormalities, such as poor performance score and hearing-language score, functional status, delayed language skills, emotional processing, sensory movement, learning, and memory. Independent of motor deficits, participants with a history of HIE are susceptible to issues with cognition and executive function during late childhood and adolescence. It is crucial to keep an eye on their intellectual development after infancy since cognitive dysfunction and memory problems might manifest subtly or not at all in the early years of life, but they can cause problems in later childhood and adolescence. Long-term follow-up research is also required to ascertain whether the enhanced cognitive outcomes will continue throughout adolescence. Even in cases where overt neuromotor abnormalities are not evident, children with watershed injuries on brain MRIs should be closely monitored to evaluate cognitive function, particularly language development.
Collapse
Affiliation(s)
| | | | - Nazim F Hamed
- General Pediatrics, Security Forces Hospital Dammam, Dammam, SAU
| | | |
Collapse
|
|
8
|
Christensen R, de Vries LS, Cizmeci MN. Neuroimaging to guide neuroprognostication in the neonatal intensive care unit. Curr Opin Pediatr 2024; 36:190-197. [PMID: 37800448 DOI: 10.1097/mop.0000000000001299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/07/2023]
Abstract
PURPOSE OF REVIEW Neurological problems are common in infants admitted to the neonatal intensive care unit (NICU). Various neuroimaging modalities are available for neonatal brain imaging and are selected based on presenting problem, timing and patient stability. RECENT FINDINGS Neuroimaging findings, taken together with clinical factors and serial neurological examination can be used to predict future neurodevelopmental outcomes. In this narrative review, we discuss neonatal neuroimaging modalities, and how these can be optimally utilized to assess infants in the NICU. We will review common patterns of brain injury and neurodevelopmental outcomes in hypoxic-ischemic encephalopathy, perinatal arterial ischemic stroke and preterm brain injury. SUMMARY Timely and accurate neuroprognostication can identify infants at risk for neurodevelopmental impairment and allow for early intervention and targeted therapies to improve outcomes.
Collapse
Affiliation(s)
- Rhandi Christensen
- Division of Neurology, The Hospital for Sick Children and the University of Toronto, Toronto, Canada
| | - Linda S de Vries
- Division of Neonatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Mehmet N Cizmeci
- Division of Neonatology, The Hospital for Sick Children and the University of Toronto, Toronto, Canada
| |
Collapse
|
|
9
|
Marsia S, Kumar D, Raheel H, Salman A, Aslam B, Ikram A, Kumar P, Aslam A, Shafiq A, Gul A. Evaluating the Safety and Efficacy of Erythropoietin Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Systematic Review and Meta-Analysis. Pediatr Neurol 2024; 152:4-10. [PMID: 38171084 DOI: 10.1016/j.pediatrneurol.2023.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Revised: 12/06/2023] [Accepted: 12/11/2023] [Indexed: 01/05/2024]
Abstract
BACKGROUND Erythropoietin (EPO) is a proposed drug for the treatment of neonatal hypoxic-ischemic encephalopathy (HIE). Multiple studies have linked its use, either as a monotherapy or in conjunction with therapeutic hypothermia (TH), with improved neonatal outcomes including death and neurodisability. However, there is also evidence in the literature that raises concerns about its efficacy and safety for the treatment of neonatal encephalopathy (NE). METHODS We searched MEDLINE, Cochrane CENTRAL, and Embase for both observational studies and randomized controlled trials (RCTs) investigating the effectiveness of EPO in treating NE. Only studies in which at least 300 U/kg of EPO was used and reported any one of the following outcomes: death, death or neurodisability, and cerebral palsy, were included. RESULTS Seven studies with 903 infants with the diagnosis of NE were included in our meta-analysis. EPO did not reduce the risk of death or neurodisability (risk ratio 0.68 [95% confidence interval [CI]: 0.43 to 1.09]) (P = 0.11). Similarly, the risk of cerebral palsy was not reduced by the administration of EPO (risk ratio 0.68 [95% CI: 0.33 to 1.40]) (P = 0.30). The risk of death was also not reduced at any dose of EPO regardless of the use of TH. CONCLUSIONS The results of our meta-analysis do not support the use of EPO for the treatment of neonatal encephalopathy. However, future large-scale RCTs are needed to strengthen these findings.
Collapse
Affiliation(s)
- Shayan Marsia
- Department of Neurology, Spectrum Health/Michigan State University, Grand Rapids, Michigan.
| | - Danisha Kumar
- Dow University of Health Sciences, Karachi, Pakistan
| | - Hamna Raheel
- Dow University of Health Sciences, Karachi, Pakistan
| | - Ali Salman
- Dow University of Health Sciences, Karachi, Pakistan
| | - Baseer Aslam
- Dow University of Health Sciences, Karachi, Pakistan
| | - Armeen Ikram
- Dow University of Health Sciences, Karachi, Pakistan
| | - Piresh Kumar
- Bahria University Of Medical and Dental College, Karachi city, Pakistan
| | - Aimun Aslam
- Jinnah Sindh Medical University, Karachi, Pakistan
| | - Areeba Shafiq
- Dow University of Health Sciences, Karachi, Pakistan
| | - Areeba Gul
- Jinnah Sindh Medical University, Karachi, Pakistan
| |
Collapse
|
|
10
|
Ankar P, Sharath HV, Chavan N. A Case Report of Pediatric Rehabilitation for Hypoxic Ischemic Encephalopathy Associated With Global Developmental Delay. Cureus 2024; 16:e54851. [PMID: 38533149 PMCID: PMC10964207 DOI: 10.7759/cureus.54851] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Accepted: 02/25/2024] [Indexed: 03/28/2024] Open
Abstract
Hypoxic ischemic encephalopathy (HIE) is a critical condition affecting neonates due to oxygen deprivation and insufficient flow of blood to the brain. It is associated with high neonatal mortality and the risk of developmental psychomotor disorders, including cerebral palsy. The global epidemiology of HIE reveals significant disparities, with more advanced healthcare systems reporting lower incidence rates. The aim of the study is to contribute to the understanding of effective rehabilitation strategies for children with HIE and global developmental delay (GDD), with the goal of improving outcomes and quality of life for these individuals. This case report focuses on an 11-month-old male child with a history of perinatal HIE, highlighting the developmental challenges and interventions undertaken. The child showed delayed gross and fine motor development, sensory awareness deficits, and postural coordination issues. A comprehensive physiotherapy intervention plan was implemented, resulting in significant improvements in post-treatment outcome measures. This case highlights the importance of early and holistic physiotherapy interventions in addressing HIE patients' developmental delays and improving their quality of life.
Collapse
Affiliation(s)
- Prajyot Ankar
- Department of Pediatric Physiotherapy, Ravi Nair Physiotherapy College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - H V Sharath
- Department of Pediatric Physiotherapy, Ravi Nair Physiotherapy College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Nitika Chavan
- Department of Neurophysiotherapy, Ravi Nair Physiotherapy College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| |
Collapse
|
|
11
|
Parmentier CEJ, Kropman T, Groenendaal F, Lequin MH, de Vries LS, Benders MJNL, Alderliesten T. Cranial MRI beyond the Neonatal Period and Neurodevelopmental Outcomes in Neonatal Encephalopathy Due to Perinatal Asphyxia: A Systematic Review. J Clin Med 2023; 12:7526. [PMID: 38137594 PMCID: PMC10743759 DOI: 10.3390/jcm12247526] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2023] [Revised: 12/01/2023] [Accepted: 12/03/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND Magnetic resonance imaging (MRI) including diffusion-weighted imaging within seven days after birth is widely used to obtain prognostic information in neonatal encephalopathy (NE) following perinatal asphyxia. Later MRI could be useful for infants without a neonatal MRI or in the case of clinical concerns during follow-up. Therefore, this review evaluates the association between cranial MRI beyond the neonatal period and neurodevelopmental outcomes following NE. METHODS A systematic literature search was performed using PubMed and Embase on cranial MRI between 2 and 24 months after birth and neurodevelopmental outcomes following NE due to perinatal asphyxia. Two independent researchers performed the study selection and risk of bias analysis. Results were separately described for MRI before and after 18 months. RESULTS Twelve studies were included (high-quality n = 2, moderate-quality n = 6, low-quality n = 4). All reported on MRI at 2-18 months: seven studies demonstrated a significant association between the pattern and/or severity of injury and overall neurodevelopmental outcomes and three showed a significant association with motor outcome. There were insufficient data on non-motor outcomes and the association between MRI at 18-24 months and neurodevelopmental outcomes. CONCLUSIONS Cranial MRI performed between 2 and 18 months after birth is associated with neurodevelopmental outcomes in NE following perinatal asphyxia. However, more data on the association with non-motor outcomes are needed.
Collapse
Affiliation(s)
- Corline E. J. Parmentier
- Department of Neonatology, Wilhelmina Children’s Hospital and Utrecht Brain Center, University Medical Center Utrecht and Utrecht University, 3584 EA Utrecht, The Netherlands
| | - Tobias Kropman
- Department of Neonatology, Wilhelmina Children’s Hospital and Utrecht Brain Center, University Medical Center Utrecht and Utrecht University, 3584 EA Utrecht, The Netherlands
| | - Floris Groenendaal
- Department of Neonatology, Wilhelmina Children’s Hospital and Utrecht Brain Center, University Medical Center Utrecht and Utrecht University, 3584 EA Utrecht, The Netherlands
| | - Maarten H. Lequin
- Department of Radiology, Wilhelmina Children’s Hospital and Utrecht Brain Center, University Medical Center Utrecht and Utrecht University, 3584 EA Utrecht, The Netherlands
| | - Linda S. de Vries
- Department of Neonatology, Wilhelmina Children’s Hospital and Utrecht Brain Center, University Medical Center Utrecht and Utrecht University, 3584 EA Utrecht, The Netherlands
| | - Manon J. N. L. Benders
- Department of Neonatology, Wilhelmina Children’s Hospital and Utrecht Brain Center, University Medical Center Utrecht and Utrecht University, 3584 EA Utrecht, The Netherlands
| | - Thomas Alderliesten
- Department of Neonatology, Wilhelmina Children’s Hospital and Utrecht Brain Center, University Medical Center Utrecht and Utrecht University, 3584 EA Utrecht, The Netherlands
| |
Collapse
|
|
12
|
Deng W, Anastasopoulos S, deRegnier RA, Pouppirt N, Barlow AK, Patrick C, O’Brien MK, Babula S, Sukal-Moulton T, Peyton C, Morgan C, Rogers JA, Lieber RL, Jayaraman A. Protocol for a randomized controlled trial to evaluate a year-long (NICU-to-home) evidence-based, high dose physical therapy intervention in infants at risk of neuromotor delay. PLoS One 2023; 18:e0291408. [PMID: 37725613 PMCID: PMC10508609 DOI: 10.1371/journal.pone.0291408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 08/29/2023] [Indexed: 09/21/2023] Open
Abstract
INTRODUCTION Developmental disabilities and neuromotor delay adversely affect long-term neuromuscular function and quality of life. Current evidence suggests that early therapeutic intervention reduces the severity of motor delay by harnessing neuroplastic potential during infancy. To date, most early therapeutic intervention trials are of limited duration and do not begin soon after birth and thus do not take full advantage of early neuroplasticity. The Corbett Ryan-Northwestern-Shirley Ryan AbilityLab-Lurie Children's Infant Early Detection, Intervention and Prevention Project (Project Corbett Ryan) is a multi-site longitudinal randomized controlled trial to evaluate the efficacy of an evidence-based physical therapy intervention initiated in the neonatal intensive care unit (NICU) and continuing to 12 months of age (corrected when applicable). The study integrates five key principles: active learning, environmental enrichment, caregiver engagement, a strengths-based approach, and high dosage (ClinicalTrials.gov identifier NCT05568264). METHODS We will recruit 192 infants at risk for neuromotor delay who were admitted to the NICU. Infants will be randomized to either a standard-of-care group or an intervention group; infants in both groups will have access to standard-of-care services. The intervention is initiated in the NICU and continues in the infant's home until 12 months of age. Participants will receive twice-weekly physical therapy sessions and caregiver-guided daily activities, assigned by the therapist, targeting collaboratively identified goals. We will use various standardized clinical assessments (General Movement Assessment; Bayley Scales of Infant and Toddler Development, 4th Edition (Bayley-4); Test of Infant Motor Performance; Pediatric Quality of Life Inventory Family Impact Module; Alberta Infant Motor Scale; Neurological, Sensory, Motor, Developmental Assessment; Hammersmith Infant Neurological Examination) as well as novel technology-based tools (wearable sensors, video-based pose estimation) to evaluate neuromotor status and development throughout the course of the study. The primary outcome is the Bayley-4 motor score at 12 months; we will compare scores in infants receiving the intervention vs. standard-of-care therapy.
Collapse
Affiliation(s)
- Weiyang Deng
- Shirley Ryan AbilityLab, Chicago, Illinois, United States of America
| | | | - Raye-Ann deRegnier
- Division of Neonatology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, United States of America
- Department of Pediatrics (Neonatology), Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America
| | - Nicole Pouppirt
- Division of Neonatology, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, United States of America
- Department of Pediatrics (Neonatology), Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America
| | - Ann K. Barlow
- Shirley Ryan AbilityLab, Chicago, Illinois, United States of America
| | - Cheryl Patrick
- Division of Rehabilitative Services, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, Illinois, United States of America
| | - Megan K. O’Brien
- Shirley Ryan AbilityLab, Chicago, Illinois, United States of America
- Department of Physical Medicine & Rehabilitation, Feinberg School of Medicine, Northwestern Medicine, Chicago, IL, United States of America
| | - Sarah Babula
- Pathways.org, Shirley Ryan AbilityLab, Chicago, Illinois, United States of America
| | - Theresa Sukal-Moulton
- Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America
- Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America
| | - Colleen Peyton
- Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America
- Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America
| | - Catherine Morgan
- Cerebral Palsy Alliance Research Institute, Discipline of Child and Adolescent Health, The University of Sydney, Sydney, New South Wales, Australia
| | - John A. Rogers
- Department of Biomedical Engineering, Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, Illinois, United States of America
- Departments of Materials Science and Engineering, Chemistry, Mechanical Engineering, Electrical Engineering and Computer Science, Northwestern University, Evanston, Illinois, United States of America
- Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America
| | - Richard L. Lieber
- Shirley Ryan AbilityLab, Chicago, Illinois, United States of America
- Department of Biomedical Engineering, Querrey Simpson Institute for Bioelectronics, Northwestern University, Evanston, Illinois, United States of America
- Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America
- Jessie Brown Jr., Hines V.A. Medical Center, Hines, Illinois, United States of America
| | - Arun Jayaraman
- Shirley Ryan AbilityLab, Chicago, Illinois, United States of America
- Department of Physical Medicine & Rehabilitation, Feinberg School of Medicine, Northwestern Medicine, Chicago, IL, United States of America
- Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United States of America
- Department of Medical Social Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America
| |
Collapse
|
|
13
|
Sutin J, Vyas R, Feldman HA, Ferradal S, Hsiao CH, Zampolli L, Pierce LJ, Nelson CA, Morton SU, Hay S, El-Dib M, Soul JS, Lin PY, Grant PE. Association of cerebral metabolic rate following therapeutic hypothermia with 18-month neurodevelopmental outcomes after neonatal hypoxic ischemic encephalopathy. EBioMedicine 2023; 94:104673. [PMID: 37392599 PMCID: PMC10338207 DOI: 10.1016/j.ebiom.2023.104673] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 06/02/2023] [Accepted: 06/06/2023] [Indexed: 07/03/2023] Open
Abstract
BACKGROUND Therapeutic hypothermia (TH) is standard of care for moderate to severe neonatal hypoxic ischemic encephalopathy (HIE) but many survivors still suffer lifelong disabilities and benefits of TH for mild HIE are under active debate. Development of objective diagnostics, with sensitivity to mild HIE, are needed to select, guide, and assess response to treatment. The objective of this study was to determine if cerebral oxygen metabolism (CMRO2) in the days after TH is associated with 18-month neurodevelopmental outcomes as the first step in evaluating CMRO2's potential as a diagnostic for HIE. Secondary objectives were to compare associations with clinical exams and characterise the relationship between CMRO2 and temperature during TH. METHODS This was a prospective, multicentre, observational, cohort study of neonates clinically diagnosed with HIE and treated with TH recruited from the tertiary neonatal intensive care units (NICUs) of Boston Children's Hospital, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center between December 2015 and October 2019 with follow-up to 18 months. In total, 329 neonates ≥34 weeks gestational age admitted with perinatal asphyxia and suspected HIE were identified. 179 were approached, 103 enrolled, 73 received TH, and 64 were included. CMRO2 was measured at the NICU bedside by frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS-DCS) during the late phases of hypothermia (C), rewarming (RW) and after return to normothermia (NT). Additional variables were body temperature and clinical neonatal encephalopathy (NE) scores, as well as findings from magnetic resonance imaging (MRI) and spectroscopy (MRS). Primary outcome was the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at 18 months, normed (SD) to 100 (15). FINDINGS Data quality for 58 neonates was sufficient for analysis. CMRO2 changed by 14.4% per °C (95% CI, 14.2-14.6) relative to its baseline at NT while cerebral tissue oxygen extraction fraction (cFTOE) changed by only 2.2% per °C (95% CI, 2.1-2.4) for net changes from C to NT of 91% and 8%, respectively. Follow-up data for 2 were incomplete, 33 declined and 1 died, leaving 22 participants (mean [SD] postnatal age, 19.1 [1.2] month; 11 female) with mild to moderate HIE (median [IQR] NE score, 4 [3-6]) and 21 (95%) with BSID-III scores >85 at 18 months. CMRO2 at NT was positively associated with cognitive and motor composite scores (β (SE) = 4.49 (1.55) and 2.77 (1.00) BSID-III points per 10-10 moL/dl × mm2/s, P = 0.009 and P = 0.01 respectively; linear regression); none of the other measures were associated with the neurodevelopmental outcomes. INTERPRETATION Point of care measures of CMRO2 in the NICU during C and RW showed dramatic changes and potential to assess individual response to TH. CMRO2 following TH outperformed conventional clinical evaluations (NE score, cFTOE, and MRI/MRS) at predicting cognitive and motor outcomes at 18 months for mild to moderate HIE, providing a promising objective, physiologically-based diagnostic for HIE. FUNDING This clinical study was funded by an NIH grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (R01HD076258).
Collapse
Affiliation(s)
- Jason Sutin
- Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA; Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA; Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA.
| | - Rutvi Vyas
- Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA; Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA
| | - Henry A Feldman
- Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA; Department of Pediatrics, Institutional Centers for Clinical and Translational Research, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA
| | - Silvina Ferradal
- Department of Intelligent Systems Engineering, Indiana University Bloomington, 107 S Indiana Ave., Bloomington, IN 47405, USA
| | - Chuan-Heng Hsiao
- Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA; Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA
| | - Lucca Zampolli
- Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA; Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA
| | - Lara J Pierce
- Department of Psychology, York University, 198 York Blvd., North York, ON M3J 2S5, Canada
| | - Charles A Nelson
- Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA; Division of Developmental Medicine, Department of Pediatrics, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA
| | - Sarah U Morton
- Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA; Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA; Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA
| | - Susanne Hay
- Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA; Department of Neonatology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, USA
| | - Mohamed El-Dib
- Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA; Division of Newborn Medicine, Department of Pediatrics, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115, USA
| | - Janet S Soul
- Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA; Department of Neurology, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA
| | - Pei-Yi Lin
- Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA; Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA; Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA
| | - Patricia E Grant
- Fetal-Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA; Division of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA; Harvard Medical School, 25 Shattuck St., Boston, MA 02115, USA; Department of Radiology, Boston Children's Hospital, 300 Longwood Ave., Boston, MA 02115, USA
| |
Collapse
|
|
14
|
Dathe AK, Stein A, Bruns N, Craciun ED, Tuda L, Bialas J, Brasseler M, Felderhoff-Mueser U, Huening BM. Early Prediction of Mortality after Birth Asphyxia with the nSOFA. J Clin Med 2023; 12:4322. [PMID: 37445355 DOI: 10.3390/jcm12134322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 06/11/2023] [Accepted: 06/25/2023] [Indexed: 07/15/2023] Open
Abstract
(1) Birth asphyxia is a major cause of delivery room resuscitation. Subsequent organ failure and hypoxic-ischemic encephalopathy (HIE) account for 25% of all early postnatal deaths. The neonatal sequential organ failure assessment (nSOFA) considers platelet count and respiratory and cardiovascular dysfunction in neonates with sepsis. To evaluate whether nSOFA is also a useful predictor for in-hospital mortality in neonates (≥36 + 0 weeks of gestation (GA)) following asphyxia with HIE and therapeutic hypothermia (TH), (2) nSOFA was documented at ≤6 h of life. (3) A total of 65 infants fulfilled inclusion criteria for TH. All but one infant received cardiopulmonary resuscitation and/or respiratory support at birth. nSOFA was lower in survivors (median 0 [IQR 0-2]; n = 56, median GA 39 + 3, female n = 28 (50%)) than in non-survivors (median 10 [4-12], p < 0.001; n = 9, median GA 38 + 6, n = 4 (44.4%)). This was also observed for the respiratory (p < 0.001), cardiovascular (p < 0.001), and hematologic sub-scores (p = 0.003). The odds ratio for mortality was 1.6 [95% CI = 1.2-2.1] per one-point increase in nSOFA. The optimal cut-off value of nSOFA to predict mortality was 3.5 (sensitivity 100.0%, specificity 83.9%). (4) Since early accurate prognosis following asphyxia with HIE and TH is essential to guide decision making, nSOFA (≤6 h of life) offers the possibility of identifying infants at risk of mortality.
Collapse
Affiliation(s)
- Anne-Kathrin Dathe
- Neonatology, Paediatric Intensive Care and Paediatric Neurology, Department of Paediatrics I, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Centre for Translational Neuro- and Behavioural Sciences, C-TNBS, Faculty of Medicine, University of Duisburg-Essen, 45122 Essen, Germany
- Department of Health and Nursing, Occupational Therapy, Ernst-Abbe-University of Applied Sciences, 07745 Jena, Germany
| | - Anja Stein
- Neonatology, Paediatric Intensive Care and Paediatric Neurology, Department of Paediatrics I, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Centre for Translational Neuro- and Behavioural Sciences, C-TNBS, Faculty of Medicine, University of Duisburg-Essen, 45122 Essen, Germany
| | - Nora Bruns
- Neonatology, Paediatric Intensive Care and Paediatric Neurology, Department of Paediatrics I, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Centre for Translational Neuro- and Behavioural Sciences, C-TNBS, Faculty of Medicine, University of Duisburg-Essen, 45122 Essen, Germany
| | - Elena-Diana Craciun
- Neonatology, Paediatric Intensive Care and Paediatric Neurology, Department of Paediatrics I, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Centre for Translational Neuro- and Behavioural Sciences, C-TNBS, Faculty of Medicine, University of Duisburg-Essen, 45122 Essen, Germany
| | - Laura Tuda
- Neonatology, Paediatric Intensive Care and Paediatric Neurology, Department of Paediatrics I, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Centre for Translational Neuro- and Behavioural Sciences, C-TNBS, Faculty of Medicine, University of Duisburg-Essen, 45122 Essen, Germany
| | - Johanna Bialas
- Neonatology, Paediatric Intensive Care and Paediatric Neurology, Department of Paediatrics I, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Centre for Translational Neuro- and Behavioural Sciences, C-TNBS, Faculty of Medicine, University of Duisburg-Essen, 45122 Essen, Germany
| | - Maire Brasseler
- Neonatology, Paediatric Intensive Care and Paediatric Neurology, Department of Paediatrics I, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Centre for Translational Neuro- and Behavioural Sciences, C-TNBS, Faculty of Medicine, University of Duisburg-Essen, 45122 Essen, Germany
| | - Ursula Felderhoff-Mueser
- Neonatology, Paediatric Intensive Care and Paediatric Neurology, Department of Paediatrics I, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Centre for Translational Neuro- and Behavioural Sciences, C-TNBS, Faculty of Medicine, University of Duisburg-Essen, 45122 Essen, Germany
| | - Britta M Huening
- Neonatology, Paediatric Intensive Care and Paediatric Neurology, Department of Paediatrics I, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany
- Centre for Translational Neuro- and Behavioural Sciences, C-TNBS, Faculty of Medicine, University of Duisburg-Essen, 45122 Essen, Germany
| |
Collapse
|
|
15
|
O'Toole JM, Mathieson SR, Raurale SA, Magarelli F, Marnane WP, Lightbody G, Boylan GB. Neonatal EEG graded for severity of background abnormalities in hypoxic-ischaemic encephalopathy. Sci Data 2023; 10:129. [PMID: 36899033 PMCID: PMC10006081 DOI: 10.1038/s41597-023-02002-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 02/03/2023] [Indexed: 03/12/2023] Open
Abstract
This report describes a set of neonatal electroencephalogram (EEG) recordings graded according to the severity of abnormalities in the background pattern. The dataset consists of 169 hours of multichannel EEG from 53 neonates recorded in a neonatal intensive care unit. All neonates received a diagnosis of hypoxic-ischaemic encephalopathy (HIE), the most common cause of brain injury in full term infants. For each neonate, multiple 1-hour epochs of good quality EEG were selected and then graded for background abnormalities. The grading system assesses EEG attributes such as amplitude, continuity, sleep-wake cycling, symmetry and synchrony, and abnormal waveforms. Background severity was then categorised into 4 grades: normal or mildly abnormal EEG, moderately abnormal EEG, majorly abnormal EEG, and inactive EEG. The data can be used as a reference set of multi-channel EEG for neonates with HIE, for EEG training purposes, or for developing and evaluating automated grading algorithms.
Collapse
Affiliation(s)
- John M O'Toole
- INFANT Research Centre, University College Cork, Cork, Ireland.
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland.
| | - Sean R Mathieson
- INFANT Research Centre, University College Cork, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
| | - Sumit A Raurale
- INFANT Research Centre, University College Cork, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
| | - Fabio Magarelli
- INFANT Research Centre, University College Cork, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
| | - William P Marnane
- INFANT Research Centre, University College Cork, Cork, Ireland
- Department of Electronic and Electrical Engineering, University College Cork, Cork, Ireland
| | - Gordon Lightbody
- INFANT Research Centre, University College Cork, Cork, Ireland
- Department of Electronic and Electrical Engineering, University College Cork, Cork, Ireland
| | - Geraldine B Boylan
- INFANT Research Centre, University College Cork, Cork, Ireland
- Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
| |
Collapse
|
|
16
|
Pappas A, Milano G, Chalak LF. Hypoxic-Ischemic Encephalopathy: Changing Outcomes Across the Spectrum. Clin Perinatol 2023; 50:31-52. [PMID: 36868712 DOI: 10.1016/j.clp.2022.11.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/05/2023]
Abstract
Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of death and neurodevelopmental impairment in neonates. Therapeutic hypothermia (TH) is the only established effective therapy and randomized trials affirm that TH reduces death and disability in moderate-to-severe HIE. Traditionally, infants with mild HIE were excluded from these trials due to the perceived low risk for impairment. Recently, multiple studies suggest that infants with untreated mild HIE may be at significant risk of abnormal neurodevelopmental outcomes. This review will focus on the changing landscape of TH, the spectrum of HIE presentations and their neurodevelopmental outcomes.
Collapse
Affiliation(s)
| | - Gina Milano
- University of Texas Southwestern Medical Center, 5323 Harry Hines, Dallas, Texas 75390, USA
| | - Lina F Chalak
- University of Texas Southwestern Medical Center, 5323 Harry Hines, Dallas, Texas 75390, USA.
| |
Collapse
|
|
17
|
Predictive Value of MRI in Hypoxic-Ischemic Encephalopathy Treated with Therapeutic Hypothermia. CHILDREN 2023; 10:children10030446. [PMID: 36980004 PMCID: PMC10047577 DOI: 10.3390/children10030446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 02/16/2023] [Accepted: 02/23/2023] [Indexed: 03/02/2023]
Abstract
Background: Hypoxic-ischemic encephalopathy (HIE) is a severe pathology, and no unique predictive biomarker has been identified. Our aims are to identify associations of perinatal and outcome parameters with morphological anomalies and ADC values from MRI. The secondary aims are to define a predictive ADC threshold value and detect ADC value fluctuations between MRIs acquired within 7 days (MR0) and at 1 year (MR1) of birth in relation to perinatal and outcome parameters. Methods: Fifty-one term children affected by moderate HIE treated with hypothermia and undergoing MRI0 and MRI1 were recruited. Brain MRIs were evaluated through the van Rooij score, while ADC maps were co-registered on a standardized cerebral surface, on which 29 ROIs were drawn. Statistical analysis was performed in Matlab, with the statistical significance value at 0.05. Results: ADC0 < ADC1 in the left and right thalami, left and right frontal white matter, right visual cortex, and the left dentate nucleus of children showing abnormal perinatal and neurodevelopmental parameters. At ROC analysis, the best prognostic ADC cut-off value was 1.535 mm2/s × 10−6 (sensitivity 80%, specificity 86%) in the right frontal white matter. ADC1 > ADC0 in the right visual cortex and left dentate nucleus, positively correlated with multiple abnormal perinatal and neurodevelopmental parameters. The van Rooij score was significantly higher in children presenting with sleep disorders. Conclusions: ADC values could be used as prognostic biomarkers to predict children’s neurodevelopmental outcomes. Further studies are needed to address these crucial topics and validate our results. Early and multidisciplinary perinatal evaluation and the subsequent re-assessment of children are pivotal to identify physical and neuropsychological disorders to guarantee early and tailored therapy.
Collapse
|
|
18
|
Katheria AC, Clark E, Yoder B, Schmölzer GM, Yan Law BH, El-Naggar W, Rittenberg D, Sheth S, Mohamed MA, Martin C, Vora F, Lakshminrusimha S, Underwood M, Mazela J, Kaempf J, Tomlinson M, Gollin Y, Fulford K, Goff Y, Wozniak P, Baker K, Rich W, Morales A, Varner M, Poeltler D, Vaucher Y, Mercer J, Finer N, El Ghormli L, Rice MM. Umbilical cord milking in nonvigorous infants: a cluster-randomized crossover trial. Am J Obstet Gynecol 2023; 228:217.e1-217.e14. [PMID: 35970202 PMCID: PMC9877105 DOI: 10.1016/j.ajog.2022.08.015] [Citation(s) in RCA: 31] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Revised: 07/15/2022] [Accepted: 08/07/2022] [Indexed: 02/02/2023]
Abstract
BACKGROUND Delayed cord clamping and umbilical cord milking provide placental transfusion to vigorous newborns. Delayed cord clamping in nonvigorous newborns may not be provided owing to a perceived need for immediate resuscitation. Umbilical cord milking is an alternative, as it can be performed more quickly than delayed cord clamping and may confer similar benefits. OBJECTIVE We hypothesized that umbilical cord milking would reduce admission to the neonatal intensive care unit compared with early cord clamping in nonvigorous newborns born between 35 and 42 weeks' gestation. STUDY DESIGN This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks' gestation in 10 medical centers in 3 countries between January 2019 and May 2021. The centers were randomized to umbilical cord milking or early cord clamping for approximately 1 year and then crossed over for an additional year or until the required number of consented subjects was reached. Waiver of consent as obtained in all centers to implement the intervention. Infants were eligible if nonvigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to umbilical cord milking or early cord clamping according to their birth hospital randomization assignment. The baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the neonatal intensive care unit for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy. Data were analyzed by the intention-to-treat concept. RESULTS Among 16,234 screened newborns, 1780 were eligible (905 umbilical cord milking, 875 early cord clamping), and 1730 had primary outcome data for analysis (97% of eligible; 872 umbilical cord milking, 858 early cord clamping) either via informed consent (606 umbilical cord milking, 601 early cord clamping) or waiver of informed consent (266 umbilical cord milking, 257 early cord clamping). The difference in the frequency of neonatal intensive care unit admission using predefined criteria between the umbilical cord milking (23%) and early cord clamping (28%) groups did not reach statistical significance (modeled odds ratio, 0.69; 95% confidence interval, 0.41-1.14). Umbilical cord milking was associated with predefined secondary outcomes, including higher hemoglobin (modeled mean difference between umbilical cord milking and early cord clamping groups 0.68 g/dL, 95% confidence interval, 0.31-1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude odds ratio, 0.72; 95% confidence interval, 0.56-0.92); cardiorespiratory support at delivery (61% vs 71%, modeled odds ratio, 0.57; 95% confidence interval, 0.33-0.99), and therapeutic hypothermia (3% vs 4%, crude odds ratio, 0.57; 95% confidence interval, 0.33-0.99). Moderate-to-severe hypoxic-ischemic encephalopathy was significantly less common with umbilical cord milking (1% vs 3%, crude odds ratio, 0.48; 95% confidence interval, 0.24-0.96). No significant differences were observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude odds ratio, 0.81; 95% confidence interval, 0.62-1.06), or a serious adverse event composite of death before discharge. CONCLUSION Among nonvigorous infants born at 35 to 42 weeks' gestation, umbilical cord milking did not reduce neonatal intensive care unit admission for predefined criteria. However, infants in the umbilical cord milking arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate-to-severe hypoxic-ischemic encephalopathy, and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that umbilical cord milking in nonvigorous infants is feasible, safe and, superior to early cord clamping.
Collapse
MESH Headings
- Female
- Humans
- Infant, Newborn
- Pregnancy
- Blood Transfusion
- Constriction
- Cross-Over Studies
- Hemoglobins
- Hypoxia-Ischemia, Brain/etiology
- Infant, Premature
- Placenta
- Umbilical Cord/surgery
- Umbilical Cord Clamping/methods
- Infant, Premature, Diseases/surgery
- Infant, Premature, Diseases/therapy
- Infant, Newborn, Diseases/surgery
- Infant, Newborn, Diseases/therapy
Collapse
Affiliation(s)
- Anup C Katheria
- Neonatal Research Institute, Sharp Mary Birch Hospital for Women & Newborns, San Diego, CA.
| | - Erin Clark
- Division of Maternal-Fetal Medicine, The University of Utah School of Medicine, Salt Lake City, UT
| | - Bradley Yoder
- Division of Neonatology, The University of Utah School of Medicine, Salt Lake City, UT
| | - Georg M Schmölzer
- Division of Neonatal-Perinatal Care, University of Alberta, Alberta, Canada
| | - Brenda Hiu Yan Law
- Division of Neonatal-Perinatal Care, University of Alberta, Alberta, Canada
| | - Walid El-Naggar
- Division of Neonatal-Perinatal Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
| | - David Rittenberg
- Department of Obstetrics and Gynaecology, Dalhousie University, Halifax, Nova Scotia, Canada
| | - Sheetal Sheth
- Department of Obstetrics and Gynecology, The GW Medical Faculty Associates, Washington, DC
| | - Mohamed A Mohamed
- Department of Neonatology, Cleveland Clinic Children's, Cleveland, OH
| | | | - Farha Vora
- Loma Linda Health University, Loma Linda, CA
| | | | - Mark Underwood
- University of California Davis Children's Hospital, Sacramento, CA
| | - Jan Mazela
- Poznan University of Medical Science, Poznan, Poland
| | - Joseph Kaempf
- Providence St. Vincent Medical Center, Providence Health System, Oregon, United States of America
| | - Mark Tomlinson
- Providence St. Vincent Medical Center, Providence Health System, Oregon, United States of America
| | - Yvonne Gollin
- Neonatal Research Institute, Sharp Mary Birch Hospital for Women & Newborns, San Diego, CA
| | | | | | - Paul Wozniak
- Neonatal Research Institute, Sharp Mary Birch Hospital for Women & Newborns, San Diego, CA; Sharp Grossmont Hospital, La Mesa, CA
| | - Katherine Baker
- Neonatal Research Institute, Sharp Mary Birch Hospital for Women & Newborns, San Diego, CA
| | - Wade Rich
- Neonatal Research Institute, Sharp Mary Birch Hospital for Women & Newborns, San Diego, CA
| | - Ana Morales
- Neonatal Research Institute, Sharp Mary Birch Hospital for Women & Newborns, San Diego, CA
| | - Michael Varner
- Division of Maternal-Fetal Medicine, The University of Utah School of Medicine, Salt Lake City, UT
| | - Debra Poeltler
- Neonatal Research Institute, Sharp Mary Birch Hospital for Women & Newborns, San Diego, CA
| | | | - Judith Mercer
- Neonatal Research Institute, Sharp Mary Birch Hospital for Women & Newborns, San Diego, CA
| | - Neil Finer
- Neonatal Research Institute, Sharp Mary Birch Hospital for Women & Newborns, San Diego, CA
| | - Laure El Ghormli
- The George Washington University Biostatistics Center, Washington, DC
| | | |
Collapse
|
|
19
|
Korğalı EÜ, Tunç G. The levels of postpartum depression, anxiety, and hopelessness of the mothers of infants receiving therapeutic hypothermia in NICU. CHILDRENS HEALTH CARE 2023. [DOI: 10.1080/02739615.2022.2160331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Affiliation(s)
- Elif Ünver Korğalı
- Department of Pediatrics, Sivas Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| | - Gaffari Tunç
- Department of Pediatrics, Department of Neonatology, Sivas Cumhuriyet University Faculty of Medicine, Sivas, Turkey
| |
Collapse
|
|
20
|
Ji X, Zhou Y, Gao Q, He H, Wu Z, Feng B, Mei Y, Cheng Y, Zhou W, Chen Y, Xiong M. Functional reconstruction of the basal ganglia neural circuit by human striatal neurons in hypoxic-ischaemic injured brain. Brain 2022; 146:612-628. [PMID: 36516880 PMCID: PMC9924911 DOI: 10.1093/brain/awac358] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 08/16/2022] [Accepted: 09/09/2022] [Indexed: 12/16/2022] Open
Abstract
Perinatal hypoxic-ischaemic encephalopathy is the leading cause of neonatal death and permanent neurological deficits, while the basal ganglia is one of the major nuclei that is selectively and greatly affected in the brains of hypoxic-ischaemic encephalopathy patients, especially in severe cases. Human embryonic stem cell-derived neurons have shown great potential in different types of brain disorders in adults. However, it remains unknown whether and how grafted human embryonic stem cell-derived neurons can repair immature brains with hypoxic-ischaemic encephalopathy. Here, by administrating genetically labelled human embryonic stem cell-derived striatal neural progenitors into the ipsilateral striatum of hypoxic-ischaemic encephalopathy-injured mice, we found that the grafted cells gradually matured into GABA spiny projection neurons morphologically and electrophysiologically, and significantly rescued the area loss of hypoxic-ischaemic encephalopathy-injured brains. Intriguingly, using immunohistochemical staining combined with enhanced ascorbate peroxidase-based immunoelectron microscopy and rabies virus-mediated trans-synaptic tracing, we show that the grafts start to extend axonal projections to the endogenous target areas (globus pallidus externa, globus pallidus internus, substantia nigra), form synapses with host striatal, globus pallidus and nigra neurons, and receive extensive and stable synaptic inputs as early as 2 months post-transplantation. Importantly, we further demonstrated functional neural circuits re-established between the grafted neurons and host cortical, striatal and substantial nigra neurons at 3-6 months post-transplantation in the hypoxic-ischaemic encephalopathy-injured brain by optogenetics combined with electrophysiological recording. Finally, the transplanted striatal spiny projection neurons but not spinal GABA neurons restored the motor defects of hypoxic-ischaemic encephalopathy, which were reversed by clozapine-N-oxide-based inhibition of graft function. These findings demonstrate anatomical and functional reconstruction of the basal ganglia neural circuit including multiple loops by striatal spiny projection neurons in hypoxic-ischaemic encephalopathy-injured immature brains, which raises the possibility of such a cell replacement therapeutic strategy for hypoxic-ischaemic encephalopathy in neonates.
Collapse
Affiliation(s)
| | | | - Qinqin Gao
- Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
| | - Hui He
- Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China,University of Chinese Academy of Sciences, Beijing, China
| | - Ziyan Wu
- Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
| | - Ban Feng
- Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
| | - Yuting Mei
- Stem Cell Center, Children’s Hospital of Fudan University, Shanghai 201102, China
| | - Yan Cheng
- Stem Cell Center, Children’s Hospital of Fudan University, Shanghai 201102, China
| | - Wenhao Zhou
- Wenhao Zhou 399 Wanyuan Road, Children’s Hospital of Fudan University, Shanghai, China E-mail:
| | - Yuejun Chen
- Correspondence may also be addressed to: Yuejun Chen 320 Yueyang Road, Chinese Academy of Sciences, Shanghai, China E-mail:
| | - Man Xiong
- Correspondence to: Man Xiong 138 Medical College Road, Shanghai, Fudan University, China E-mail:
| |
Collapse
|
|
21
|
Back to School: Academic Functioning and Educational Needs among Youth with Acquired Brain Injury. CHILDREN 2022; 9:children9091321. [PMID: 36138630 PMCID: PMC9497748 DOI: 10.3390/children9091321] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/19/2022] [Accepted: 08/24/2022] [Indexed: 11/17/2022]
Abstract
Youth with a history of traumatic or non-traumatic acquired brain injury are at increased risk for long-lasting cognitive, emotional, behavioral, social, and physical sequelae post-injury. Such sequelae have great potential to negatively impact this population’s academic functioning. Consistently, poorer academic achievement and elevated need for educational supports have been well-documented among youth with a history of acquired brain injury. The current paper reviews the literature on neuropsychological, psychiatric, and academic outcomes of pediatric acquired brain injury. A discussion of special education law as it applies to this patient population, ongoing limitations within the field, and a proposal of solutions are also included.
Collapse
|
|
22
|
The Alpha 7 Nicotinic Acetylcholine Receptor Does Not Affect Neonatal Brain Injury. Biomedicines 2022; 10:biomedicines10082023. [PMID: 36009570 PMCID: PMC9405910 DOI: 10.3390/biomedicines10082023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 08/11/2022] [Accepted: 08/15/2022] [Indexed: 11/16/2022] Open
Abstract
Inflammation plays a central role in the development of neonatal brain injury. The alpha 7 nicotinic acetylcholine receptor (α7nAChR) can modulate inflammation and has shown promising results as a treatment target in rodent models of adult brain injury. However, little is known about the role of the α7nAChR in neonatal brain injury. Hypoxic-ischemic (HI) brain injury was induced in male and female C57BL/6 mice, α7nAChR knock-out (KO) mice and their littermate controls on postnatal day (PND) 9–10. C57BL/6 pups received i.p. injections of α7nAChR agonist PHA 568487 (8 mg/kg) or saline once daily, with the first dose given directly after HI. Caspase-3 activity and cytokine mRNA expression in the brain was analyzed 24 h after HI. Motor function was assessed 24 and 48 h after HI, and immunohistochemistry was used to assess tissue loss at 24 h and 7 days after HI and microglial activation 7 days after HI. Activation of α7nAChR with the agonist PHA 568487 significantly decreased CCL2/MCP-1, CCL5/RANTES and IL-6 gene expression in the injured brain hemisphere 24 h after HI compared with saline controls in male, but not female, pups. However, α7nAChR activation did not alter caspase-3 activity and TNFα, IL-1β and CD68 mRNA expression. Furthermore, agonist treatment did not affect motor function (24 or 48 h), neuronal tissue loss (24 h or 7 days) or microglia activation (7 days) after HI in either sex. Knock-out of α7nAChR did not influence neuronal tissue loss 7 days after HI. In conclusion, targeting the α7nAChR in neonatal brain injury shows some effect on dampening acute inflammatory responses in male pups. However, this does not lead to an effect on overall injury outcome.
Collapse
|
|
23
|
Biomarker und Neuromonitoring zur Entwicklungsprognose nach perinataler Hirnschädigung. Monatsschr Kinderheilkd 2022; 170:688-703. [PMID: 35909417 PMCID: PMC9309449 DOI: 10.1007/s00112-022-01542-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/30/2022] [Indexed: 11/02/2022]
Abstract
Das sich entwickelnde Gehirn ist in der Perinatalperiode besonders empfindlich für eine Vielzahl von Insulten, wie z. B. Extremfrühgeburtlichkeit und perinatale Asphyxie. Ihre Komplikationen können zu lebenslangen neurokognitiven, sensorischen und psychosozialen Einschränkungen führen; deren Vorhersage bleibt eine Herausforderung. Eine Schlüsselfunktion kommt der möglichst exakten Identifikation von Hirnläsionen und funktionellen Störungen zu. Die Prädiktion stützt sich auf frühe diagnostische Verfahren und die klinische Erfassung der Meilensteine der Entwicklung. Zur klinischen Diagnostik und zum Neuromonitoring in der Neonatal- und frühen Säuglingsperiode stehen bildgebende Verfahren zur Verfügung. Hierzu zählen zerebrale Sonographie, MRT am errechneten Termin, amplitudenintegriertes (a)EEG und/oder klassisches EEG, Nah-Infrarot-Spektroskopie, General Movements Assessment und die frühe klinische Nachuntersuchung z. B. mithilfe der Hammersmith Neonatal/Infant Neurological Examination. Innovative Biomarker und -muster (Omics) sowie (epi)genetische Prädispositionen sind Gegenstand wissenschaftlicher Untersuchungen. Neben der Erfassung klinischer Risiken kommt psychosozialen Faktoren im Umfeld des Kindes eine entscheidende Rolle zu. Eine möglichst akkurate Prognose ist mit hohem Aufwand verbunden, jedoch zur gezielten Beratung der Familien und der Einleitung von frühen Interventionen, insbesondere vor dem Hintergrund der hohen Plastizität des sich entwickelnden Gehirns, von großer Bedeutung. Diese Übersichtsarbeit fokussiert die Charakterisierung der oben genannten Verfahren und ihrer Kombinationsmöglichkeiten. Zudem wird ein Ausblick gegeben, wie innovative Techniken in Zukunft die Prädiktion der Entwicklung und Nachsorge dieser Kinder vereinfachen können.
Collapse
|
|
24
|
Parmentier CEJ, Steggerda SJ, Weeke LC, Rijken M, De Vries LS, Groenendaal F. Outcome of non-cooled asphyxiated infants with under-recognised or delayed-onset encephalopathy. Arch Dis Child Fetal Neonatal Ed 2022; 107:364-370. [PMID: 34916259 DOI: 10.1136/archdischild-2020-321331] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 09/15/2021] [Indexed: 11/04/2022]
Abstract
OBJECTIVE To describe the clinical characteristics, MRI findings and neurodevelopmental outcome of infants with documented perinatal asphyxia and seizure onset within 24 hours after birth who were not selected for therapeutic hypothermia (TH). DESIGN Retrospective cohort study. SETTING AND PATIENTS (Near-)term infants with documented perinatal asphyxia referred to two Dutch level III neonatal units with neonatal encephalopathy (NE) and seizures <24 hours after birth not treated with TH. Infants with a diagnosis other than NE following perinatal asphyxia causing the seizures were excluded. MAIN OUTCOME MEASURES Clinical characteristics, findings on cranial MRI performed within 8 days after birth and neurodevelopmental outcome assessed using the Griffiths Mental Development Scales at 18 months or Bayley Scales of Infant and Toddler Development-Third Edition at 2 years of age. RESULTS 39 infants were included. All had abnormalities on MRI. Predominant white matter/watershed injury was the most common pattern of injury, 23 (59%). 7 (18%) infants had predominant basal ganglia/thalamus injury, 3 (8%) near total brain injury, 5 (13%) arterial ischaemic stroke, 1 (3%) an intraventricular haemorrhage. Adverse outcome was seen in 51%: 6 died, 11 developed cerebral palsy (spastic n=8, dyskinetic n=3), 2 had neurodevelopmental delay, 1 had severe hearing impairment. CONCLUSIONS All infants with documented perinatal asphyxia and seizure onset within 24 hours after birth who did not receive TH had abnormalities on MRI. 51% had an adverse outcome. Better methods for recognition of infants who might benefit from TH and careful neurodevelopmental follow-up are urgently needed.
Collapse
Affiliation(s)
| | - Sylke J Steggerda
- Department of Neonatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Lauren C Weeke
- Department of Neonatology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Monique Rijken
- Department of Neonatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Linda S De Vries
- Department of Neonatology, University Medical Center Utrecht, Utrecht, The Netherlands.,Department of Neonatology, Leiden University Medical Center, Leiden, The Netherlands
| | - Floris Groenendaal
- Department of Neonatology, University Medical Center Utrecht, Utrecht, The Netherlands
| |
Collapse
|
|
25
|
Zhou L, McDonald C, Yawno T, Jenkin G, Miller S, Malhotra A. Umbilical Cord Blood and Cord Tissue-Derived Cell Therapies for Neonatal Morbidities: Current Status and Future Challenges. Stem Cells Transl Med 2022; 11:135-145. [PMID: 35259278 PMCID: PMC8929446 DOI: 10.1093/stcltm/szab024] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 10/31/2021] [Indexed: 11/30/2022] Open
Abstract
Cell therapies are an emerging focus for neonatal research, with benefits documented for neonatal respiratory, neurological, and cardiac conditions in pre-clinical studies. Umbilical cord blood (UCB) and umbilical cord (UC) tissue-derived cell therapy is particularly appealing for preventative or regenerative treatment of neonatal morbidities; they are a resource that can be collected at birth and used as an autologous or allogeneic therapy. Moreover, UCB contains a diverse mix of stem and progenitor cells that demonstrate paracrine actions to mitigate damaging inflammatory, immune, oxidative stress, and cell death pathways in several organ systems. In the past decade, published results from early-phase clinical studies have explored the use of these cells as a therapeutic intervention in neonates. We present a systematic review of published and registered clinical trials of UCB and cord tissue-derived cell therapies for neonatal morbidities. This search yielded 12 completed clinical studies: 7 were open-label phase I and II safety and feasibility trials, 3 were open-label dose-escalation trials, 1 was a open-label placebo-controlled trial, and 1 was a phase II randomized controlled trial. Participants totaled 206 infants worldwide; 123 (60%) were full-term infants and 83 (40%) were preterm. A majority (64.5%) received cells via an intravenous route; however, 54 (26.2%) received cells via intratracheal administration, 10 (4.8%) intraoperative cardiac injection, and 9 (4.3%) by direct intraventricular (brain) injection. Assessment of efficacy to date is limited given completed studies have principally been phase I and II safety studies. A further 24 trials investigating UCB and UC-derived cell therapies in neonates are currently registered.
Collapse
Affiliation(s)
- Lindsay Zhou
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
- Department of Paediatrics, Monash University, Clayton, VIC, Australia
- Monash Children’s Hospital, Monash Health, Clayton, VIC, Australia
| | - Courtney McDonald
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
- Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia
| | - Tamara Yawno
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
- Department of Paediatrics, Monash University, Clayton, VIC, Australia
- Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia
| | - Graham Jenkin
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
- Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia
| | - Suzanne Miller
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
- Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia
| | - Atul Malhotra
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
- Department of Paediatrics, Monash University, Clayton, VIC, Australia
- Monash Children’s Hospital, Monash Health, Clayton, VIC, Australia
| |
Collapse
|
|
26
|
Parmentier CEJ, de Vries LS, Groenendaal F. Magnetic Resonance Imaging in (Near-)Term Infants with Hypoxic-Ischemic Encephalopathy. Diagnostics (Basel) 2022; 12:diagnostics12030645. [PMID: 35328199 PMCID: PMC8947468 DOI: 10.3390/diagnostics12030645] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Revised: 03/03/2022] [Accepted: 03/04/2022] [Indexed: 01/14/2023] Open
Abstract
Hypoxic-ischemic encephalopathy (HIE) is a major cause of neurological sequelae in (near-)term newborns. Despite the use of therapeutic hypothermia, a significant number of newborns still experience impaired neurodevelopment. Neuroimaging is the standard of care in infants with HIE to determine the timing and nature of the injury, guide further treatment decisions, and predict neurodevelopmental outcomes. Cranial ultrasonography is a helpful noninvasive tool to assess the brain before initiation of hypothermia to look for abnormalities suggestive of HIE mimics or antenatal onset of injury. Magnetic resonance imaging (MRI) which includes diffusion-weighted imaging has, however, become the gold standard to assess brain injury in infants with HIE, and has an excellent prognostic utility. Magnetic resonance spectroscopy provides complementary metabolic information and has also been shown to be a reliable prognostic biomarker. Advanced imaging modalities, including diffusion tensor imaging and arterial spin labeling, are increasingly being used to gain further information about the etiology and prognosis of brain injury. Over the past decades, tremendous progress has been made in the field of neonatal neuroimaging. In this review, the main brain injury patterns of infants with HIE, the application of conventional and advanced MRI techniques in these newborns, and HIE mimics, will be described.
Collapse
Affiliation(s)
- Corline E. J. Parmentier
- Department of Neonatology, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands; (C.E.J.P.); (L.S.d.V.)
| | - Linda S. de Vries
- Department of Neonatology, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands; (C.E.J.P.); (L.S.d.V.)
- Department of Neonatology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Floris Groenendaal
- Department of Neonatology, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands; (C.E.J.P.); (L.S.d.V.)
- Correspondence:
| |
Collapse
|
|
27
|
Atkinson J, Braddick O, Montague-Johnson C, Baker B, Parr JR, Sullivan P, Andrew MJ. Visual attention and dietary supplementation in children with perinatal brain injury. Dev Med Child Neurol 2022; 64:340-346. [PMID: 34449080 DOI: 10.1111/dmcn.15017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Revised: 07/11/2021] [Accepted: 07/12/2021] [Indexed: 11/27/2022]
Abstract
AIM To investigate whether children with perinatal brain injury have impairments in specific components of visual attention, and whether early dietary supplementation can reduce any deficits. METHOD Children participating in the Dolphin neonatal trial of dietary supplementation were tested at age 6 months with the Infant Fixation Shift Attention Test, and at 4 to 5 years with four subtests of the Early Childhood Attention Battery (ECAB) assessing different components of attention (selective, sustained, and executive function), and the Fluid Crystallized Intelligence Index of the Kaufman Assessment Battery for Children, Second Edition (KABC-II). From 59 children originally assigned to trial groups, 33 were available for testing at 4 to 5 years (18 treatment group of whom seven, six, and five showed mild, moderate, or severe neonatal brain injury; 15 controls with one, seven, and seven in the neonatal brain injury categories respectively). Given the imbalance in numbers with mild brain injury, analysis of trial group differences is restricted to moderate and severe brain injury severities (n=25). RESULTS Children with perinatal brain injury showed poorer attention across all components relative to age norms (mean standard scores 75-87; p<0.001 for three of the four subtests), with the greatest impairment in sustained attention. These impairments remained when compared with cognitive age assessed using the Fluid Crystallized Intelligence Index. Impairment was reduced in the treatment compared to the control group (p=0.04 for flanker test, p=0.002 for counterpointing, and p=0.027 for the overall ECAB score). INTERPRETATION Perinatal brain injury is associated with later impaired attention, beyond that predicted from any general cognitive disability. Impairment varies across attention components, being most severe for sustained attention. The effects on flanker and counterpointing suggest that dietary supplementation from 0 to 2 years of age may reduce attention problems. Measuring the different components of attention is important when considering assessment and interventions for children with perinatal brain injury.
Collapse
Affiliation(s)
- Janette Atkinson
- Faculty of Brain Sciences, University College London, London, UK
| | - Oliver Braddick
- Department of Experimental Psychology, University of Oxford, Oxford, UK
| | | | - Bonny Baker
- Department of Paediatrics, University of Oxford, Oxford, UK
| | - Jeremy R Parr
- Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
| | - Peter Sullivan
- Department of Paediatrics, University of Oxford, Oxford, UK
| | - Morag J Andrew
- Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK
| |
Collapse
|
|
28
|
Jiang L, El-Metwally D, Sours Rhodes C, Zhuo J, Almardawi R, Medina AE, Wang L, Gullapalli RP, Raghavan P. Alterations in motor functional connectivity in Neonatal Hypoxic Ischemic Encephalopathy. Brain Inj 2022; 36:287-294. [PMID: 35113755 DOI: 10.1080/02699052.2022.2034041] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
BACKGROUND Neonatal hypoxic-ischemic encephalopathy (HIE) is the result of global hypoxic-ischemic brain injury in neonates due to asphyxia during birth and is one of the most common causes of severe, long-term neurologic deficits in children. Methods: Resting state fMRI (rs-fMRI) was used to assess potential functional disruptions in the primary and association motor areas in HIE neonates (n = 16) compared to healthy controls (n = 11). RESULTS Results demonstrate reduced intra-hemispheric resting state functional connectivity (rs-FC) between primary motor regions (upper extremity and facial motor regions) as well as reduced inter-hemispheric rs-FC in the HIE group. In addition, HIE neonates demonstrated increased rs-FC between motor regions and frontal, temporal and parietal cortices but decreased rs-FC with the cerebellum. DISCUSSION These preliminary results provide initial evidence for the disruption of functional communication with the motor network in neonates with HIE. Further studies are necessary to both validate these findings in a larger dataset as well as to determine if rs-fMRI measurements collected at birth may have the potential to serve as a prognostic marker in addition to the traditional combination of clinical measurements and conventional MRI.
Collapse
Affiliation(s)
- Li Jiang
- Center for Advanced Imaging Research (Cair), 670 W Baltimore St, University of Maryland School of Medicine, Baltimore, USA.,Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, USA
| | - Dina El-Metwally
- Department of Pediatrics, University of Maryland School of Medicine, Baltimore, USA
| | - Chandler Sours Rhodes
- Center for Advanced Imaging Research (Cair), 670 W Baltimore St, University of Maryland School of Medicine, Baltimore, USA.,Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, USA.,National Intrepid Center of Excellence, Walter Reed National Military Medical Center, Bethesda, USA
| | - Jiachen Zhuo
- Center for Advanced Imaging Research (Cair), 670 W Baltimore St, University of Maryland School of Medicine, Baltimore, USA.,Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, USA
| | - Ranyah Almardawi
- Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, USA
| | - Alexandre E Medina
- Department of Pediatrics, University of Maryland School of Medicine, Baltimore, USA
| | - Li Wang
- Department of Radiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA
| | - Rao P Gullapalli
- Center for Advanced Imaging Research (Cair), 670 W Baltimore St, University of Maryland School of Medicine, Baltimore, USA.,Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, USA
| | - Prashant Raghavan
- Department of Diagnostic Radiology & Nuclear Medicine, University of Maryland School of Medicine, Baltimore, USA
| |
Collapse
|
|
29
|
Mota-Rojas D, Villanueva-García D, Solimano A, Muns R, Ibarra-Ríos D, Mota-Reyes A. Pathophysiology of Perinatal Asphyxia in Humans and Animal Models. Biomedicines 2022; 10:347. [PMID: 35203556 PMCID: PMC8961792 DOI: 10.3390/biomedicines10020347] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 01/28/2022] [Accepted: 01/28/2022] [Indexed: 12/16/2022] Open
Abstract
Perinatal asphyxia is caused by lack of oxygen delivery (hypoxia) to end organs due to an hypoxemic or ischemic insult occurring in temporal proximity to labor (peripartum) or delivery (intrapartum). Hypoxic-ischemic encephalopathy is the clinical manifestation of hypoxic injury to the brain and is usually graded as mild, moderate, or severe. The search for useful biomarkers to precisely predict the severity of lesions in perinatal asphyxia and hypoxic-ischemic encephalopathy (HIE) is a field of increasing interest. As pathophysiology is not fully comprehended, the gold standard for treatment remains an active area of research. Hypothermia has proven to be an effective neuroprotective strategy and has been implemented in clinical routine. Current studies are exploring various add-on therapies, including erythropoietin, xenon, topiramate, melatonin, and stem cells. This review aims to perform an updated integration of the pathophysiological processes after perinatal asphyxia in humans and animal models to allow us to answer some questions and provide an interim update on progress in this field.
Collapse
Affiliation(s)
- Daniel Mota-Rojas
- Neurophysiology, Behavior and Animal Welfare Assessment, Universidad Autónoma Metropolitana (UAM), Mexico City 04960, Mexico
| | - Dina Villanueva-García
- Division of Neonatology, National Institute of Health Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico;
| | - Alfonso Solimano
- Department of Pediatrics, University of British Columbia, Vancouver, BC V6H 3V4, Canada;
| | - Ramon Muns
- Livestock Production Sciences Unit, Agri-Food and Biosciences Institute, Hillsborough BT26 6DR, UK;
| | - Daniel Ibarra-Ríos
- Division of Neonatology, National Institute of Health Hospital Infantil de México Federico Gómez, Mexico City 06720, Mexico;
| | - Andrea Mota-Reyes
- School of Medicine and Health Sciences, TecSalud, Instituto Tecnológico y de Estudios Superiores de Monterrey (ITESM), Monterrey 64849, Mexico;
| |
Collapse
|
|
30
|
Tuiskula A, Metsäranta M, Toiviainen‐Salo S, Vanhatalo S, Haataja L. Profile of minor neurological findings after perinatal asphyxia. Acta Paediatr 2022; 111:291-299. [PMID: 34599610 PMCID: PMC9299470 DOI: 10.1111/apa.16133] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 09/20/2021] [Accepted: 09/30/2021] [Indexed: 12/29/2022]
Abstract
Aim To characterise the spectrum of findings in sequential neurological examinations, general movements (GM) assessment and magnetic resonance imaging (MRI) of infants with perinatal asphyxia. Methods The prospective cohort study of term infants with perinatal asphyxia treated at Helsinki University Hospital's neonatal units in 2016–2020 used Hammersmith Neonatal Neurological Examination (HNNE) and brain MRI at 2 weeks and Hammersmith Infant Neurological Examination (HINE) and GM assessment at 3 months of age. Results Analysis included 50 infants: 33 displaying perinatal asphyxia without hypoxic‐ischaemic encephalopathy (HIE), seven with HIE1 and 10 with HIE2. Of the infants with atypical HNNE findings, 24/25 perinatal asphyxia without HIE cases, 5/6 HIE1 cases and all 10 HIE2 cases showed atypical findings in the HINE. The HINE identified atypical spontaneous movements significantly more often in infants with white matter T2 hyperintensity. Conclusion In this cohort, most infants with perinatal asphyxia, with or without HIE, presented atypical neurological findings in sequential examinations. The profile of neurological findings for children with perinatal asphyxia without HIE resembled that of children with HIE. White matter T2 hyperintensity was associated with atypical spontaneous movements in the HINE and was a frequent MRI finding also in perinatal asphyxia without HIE.
Collapse
Affiliation(s)
- Anna Tuiskula
- BABA Center Pediatric Research Center Department of Pediatrics, Children's Hospital Helsinki University Hospital and University of Helsinki Helsinki Finland
| | - Marjo Metsäranta
- Department of Neonatology, Children's Hospital BABA Center Pediatric Research Center Helsinki University Hospital and University of Helsinki Helsinki Finland
| | - Sanna Toiviainen‐Salo
- Department of Pediatric Radiology, Radiology, HUS Diagnostic Center BABA Center Pediatric Research Center Helsinki University Hospital and University of Helsinki Helsinki Finland
| | - Sampsa Vanhatalo
- Department of Clinical Neurophysiology, Children's Hospital BABA Center Pediatric Research Center Neuroscience Center, Helsinki Institute of Life Science Helsinki University Hospital and University of Helsinki Helsinki Finland
| | - Leena Haataja
- Department of Pediatric Neurology, Children's Hospital BABA Center Pediatric Research Center Helsinki University Hospital and University of Helsinki Helsinki Finland
| |
Collapse
|
|
31
|
Long-term cognitive outcomes in term newborns with watershed injury caused by neonatal encephalopathy. Pediatr Res 2022; 92:505-512. [PMID: 34702974 PMCID: PMC9038956 DOI: 10.1038/s41390-021-01526-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Revised: 03/10/2021] [Accepted: 03/29/2021] [Indexed: 11/08/2022]
Abstract
BACKGROUND We previously reported that increasing severity of watershed (WS) injury in neonatal magnetic resonance imaging (MRI) is associated with worse language outcomes in early childhood. In the present study, we investigated the relationship between neonatal injury patterns and cognitive profile in adolescents with neonatal encephalopathy. METHODS Term neonates with encephalopathy were prospectively enrolled and imaged using brain MRI from 1999 to 2008. Neonatal brain injury was scored according to the degree of injury in WS and basal ganglia/thalamus (BG/T) areas. The children underwent a neurocognitive assessment and follow-up brain MRI at the age of 10-16 years. The relationship between neonatal brain injury patterns and adolescent cognitive outcomes was assessed. RESULTS In a cohort of 16 children, neonatal MRI showed WS injury in 7, BG/T injury in 2, and normal imaging in 7. Children with WS injury had lower estimated overall cognitive ability than those with normal imaging. Increasing WS injury score was associated with decreasing estimated overall cognitive ability, Perceptual Reasoning Index, and digit span score. CONCLUSIONS Children with the WS injury are at an increased risk of having problems in long-term intellectual ability. These cognitive outcomes may underlie early language difficulties seen in children with neonatal WS injury. IMPACT Adolescents with a history of neonatal encephalopathy and watershed pattern of injury on neonatal brain magnetic resonance imaging (MRI) had lower overall cognitive ability, perceptual reasoning skills, and auditory working memory than those with normal neonatal imaging. Children with post-neonatal epilepsy and cerebral palsy had the worst cognitive outcomes. Watershed pattern of injury confers high long-term differences in intellectual ability.
Collapse
|
|
32
|
Lee BL, Glass HC. Cognitive outcomes in late childhood and adolescence of neonatal hypoxic-ischemic encephalopathy. Clin Exp Pediatr 2021; 64:608-618. [PMID: 34044480 PMCID: PMC8650814 DOI: 10.3345/cep.2021.00164] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2021] [Accepted: 05/18/2021] [Indexed: 12/04/2022] Open
Abstract
Hypoxic-ischemic encephalopathy (HIE) is the most common cause of neonatal encephalopathy with a global incidence of approximately 1 to 8 per 1,000 live births. Neonatal encephalopathy can cause neurodevelopmental and cognitive impairments in survivors of hypoxic-ischemic insults with and without functional motor deficits. Normal neurodevelopmental outcomes in early childhood do not preclude cognitive and behavioral difficulties in late childhood and adolescence because cognitive functions are not yet fully developed at this early age. Therapeutic hypothermia has been shown to significantly reduced death and severe disabilities in term newborns with HIE. However, children treated with hypothermia therapy remain at risk for cognitive impairments and follow-up is necessary throughout late childhood and adolescence. Novel adjunctive neuroprotective therapies combined with therapeutic hypothermia may enhance the survival and neurodevelopmental outcomes of infants with HIE. The extent and severity of brain injury on magnetic resonance imaging might predict neurodevelopmental outcomes and lead to targeted interven tions in children with a history of neonatal encephalopathy. We provide a summary of the long-term cognitive outcomes in late childhood and adolescence in children with a history of HIE and the association between pattern of brain injury and neurodevelopmental outcomes.
Collapse
Affiliation(s)
- Bo Lyun Lee
- Department of Pediatrics, Inje University Busan Paik Hospital, Inje University College of Medicine, Busan, Korea
| | - Hannah C Glass
- Department of Neurology and Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.,Department of Pediatrics, Benioff Children's Hospital, University of California San Francisco, San Francisco, CA, USA.,Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA
| |
Collapse
|
|
33
|
Erdi-Krausz G, Rocha R, Brown A, Myneni A, Lennartsson F, Romsauerova A, Cianfaglione R, Edmonds CJ, Vollmer B. Neonatal hypoxic-ischaemic encephalopathy: Motor impairment beyond cerebral palsy. Eur J Paediatr Neurol 2021; 35:74-81. [PMID: 34666231 DOI: 10.1016/j.ejpn.2021.10.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 08/21/2021] [Accepted: 10/09/2021] [Indexed: 11/30/2022]
Abstract
BACKGROUND Research investigating neuromotor function in the absence of cerebral palsy (CP) for children who had neonatal HIE is limited. AIMS To investigate school-age neurological and neuromotor function, and correlations with attention, neonatal Magnetic Resonance Imaging (MRI), and neuromotor assessments at toddler age. METHODS Twenty-seven children with neonatal HIE without CP who underwent hypothermia treatment and a comparison group of 20 children were assessed at age 5-7 years for Minor Neurological Dysfunction (MND; simplified Touwen), motor skills (Movement Assessment Battery for Children-2; MABC-2), parental concern over motor function (MABC Checklist), general cognition (Wechsler Preschool and Primary Scale of Intelligence-IV, WPPSI), and attention (DuPaul ADHD Rating Scale). Neurological examination and motor development, using Bayley-3 scales, at age 24-months was extracted from the clinical database. Clinical neonatal MRI was assessed for hypoxic-ischaemic injury. RESULTS In the HIE group, MND was more prevalent (p = 0.026) and M-ABC performance (total score p = 0.006; balance subtest p = 0.008) was worse; parents were more concerned about children's motor function (p = 0.011). HIE group inattention scores were higher (p = 0.032), which correlated with lower MABC-2 scores (rs = -0.590, p = 0.004). Neurological examination at 24-months correlated with MND (rs = 0.437, p = 0.033); Bayley-3 motor scores did not correlate with M-ABC-2 scores (rs = 368, p = 0.133). Neonatal MRI findings were not associated with school-age MND (rs = 0.140, p = 0.523) or MABC-2 (rs = 0.300, p = 0.165). CONCLUSIONS Children with neonatal HIE, without CP, treated with hypothermia may be more likely to develop MND and motor difficulties than typically developing peers. Inattention may contribute to motor performance. In the absence of CP, neonatal MRI and toddler age assessment of motor development have limited predictive value for school-age outcome. Since this was an exploratory study with a small sample size, findings should be confirmed by a definite larger study.
Collapse
Affiliation(s)
- Gergo Erdi-Krausz
- Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK
| | - Ruben Rocha
- Centro Materno Infantil do Norte, Centro Hospitalar Universitário do Porto, Portugal
| | - Alice Brown
- Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK
| | - Archana Myneni
- Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK
| | - Finn Lennartsson
- Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK; Department of Clinical Sciences Lund, Diagnostic Radiology, Lund University, Lund, Sweden
| | - Andrea Romsauerova
- Neuroradiology Department, University Hospital of Southampton NHS Foundation Trust, UK
| | - Rina Cianfaglione
- Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK
| | - Caroline J Edmonds
- Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK; School of Psychology, University of East London, London, UK
| | - Brigitte Vollmer
- Clinical Neurosciences, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, UK; Neonatal and Paediatric Neurology, Southampton Children's Hospital, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
| |
Collapse
|
|
34
|
Long-Term Outcomes of Perinatal Hypoxia and Asphyxia at an Early School Age. MEDICINA-LITHUANIA 2021; 57:medicina57090988. [PMID: 34577911 PMCID: PMC8466311 DOI: 10.3390/medicina57090988] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 09/12/2021] [Accepted: 09/16/2021] [Indexed: 11/29/2022]
Abstract
Background and Objectives: Late long-term outcomes of perinatal asphyxia (PA) in school-age are often unclear. To assess long-term outcomes at an early school age in children who had experienced perinatal hypoxia or asphyxia, where therapeutic hypothermia was not applied. Materials and Methods: The case group children were 8–9-year-old children (n = 32) who were born at full term and experienced hypoxia or asphyxia at birth, where therapeutic hypothermia (TH) was not applied. The control group consisted of 8–9-year-old children (n = 16) born without hypoxia. A structured neurological examination was performed at an early school age. The neuromotor function was assessed using the Gross Motor Function Classification System (GMFCS). Health-related quality-of-life was assessed using the Health Utilities Index (HUI) questionnaire. Intellectual abilities were assessed using the Wechsler Intelligence Scale for Children (WISC). Results: The case group, compared with controls, had significantly (p = 0.002) lower mean [SD] full-scale IQ (87(16.86) vs. 107(12.15)), verbal-scale IQ (89(17.45) vs. 105(11.55)), verbal comprehension index (89(17.36) vs. 105(10.74)), working memory index (89(15.68) vs. 104(11.84)), performance IQ (87(16.51) vs. 108(15.48)) and perceptual organization index (85(15.71) vs. 105(15.93)). We did not find any significant differences in the incidence of disorders of neurological examination, movement abilities and health-related quality of life at an early school age between the case and the control group children. Conclusion: In children who experienced perinatal asphyxia but did not have cerebral paralysis (CP), where therapeutic hypothermia was not applied, cognitive assessment scores at an early school age were significantly lower compared to those in the group of healthy children, and were at a low average level.
Collapse
|
|
35
|
Jiang Z, Hu X, Zeng H, Wang X, Tan C, Ni C, Dai L, Liu S. Nomogram for perinatal prediction of intrapartum fever: a retrospective case-control study. BMC Pregnancy Childbirth 2021; 21:445. [PMID: 34172031 PMCID: PMC8228904 DOI: 10.1186/s12884-021-03891-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Accepted: 05/17/2021] [Indexed: 01/19/2023] Open
Abstract
Objective To explore the risk factors for intrapartum fever and to develop a nomogram to predict the incidence of intrapartum fever. Methods The general demographic characteristics and perinatal factors of 696 parturients who underwent vaginal birth at the Affiliated Hospital of Xuzhou Medical University from May 2019 to April 2020 were retrospectively analysed. Data was collected from May 2019 to October 2019 on 487 pregnant women who formed a training cohort. A multivariate logistic regression model was used to identify the independent risk factors associated with intrapartum fever during vaginal birth, and a nomogram was developed to predict the occurrence. To verify the nomogram, data was collected from January 2020 to April in 2020 from 209 pregnant women who formed a validation cohort. Results The incidence of intrapartum fever in the training cohort was found in 72 of the 487 parturients (14.8%), and the incidence of intrapartum fever in the validation cohort was 31 of the 209 parturients (14.8%). Multivariate logistic regression analysis showed that the following factors were significantly related to intrapartum fever: primiparas (odds ratio [OR] 2.43; 95% confidence interval [CI] 1.15–5.15), epidural labour analgesia (OR 2.89; 95% CI 1.23–6.82), premature rupture of membranes (OR 2.37; 95% CI 1.13–4.95), second stage of labour ≥ 120 min (OR 4.36; 95% CI 1.42–13.41), amniotic fluid pollution degree III (OR 10.39; 95% CI 3.30–32.73), and foetal weight ≥ 4000 g (OR 7.49; 95% CI 2.12–26.54). Based on clinical experience and previous studies, the duration of epidural labour analgesia also appeared to be a meaningful factor for intrapartum fever; therefore, these seven variables were used to develop a nomogram to predict intrapartum fever in parturients. The nomogram achieved a good area under the ROC curve of 0.86 and 0.81 in the training and in the validation cohorts, respectively. Additionally, the nomogram had a well-fitted calibration curve, which also showed excellent diagnostic performance. Conclusion We constructed a model to predict the occurrence of fever during childbirth and developed an accessible nomogram to help doctors assess the risk of fever during childbirth. Such assessment may be helpful in implementing reasonable treatment measures. Trial registration Clinical Trial Registration: (www.chictr.org.cnChiCTR2000035593)
Collapse
Affiliation(s)
- Zhenfei Jiang
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China.,Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China
| | - Xiaoyi Hu
- Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China
| | - Huabei Zeng
- Department of Anesthesiology, Obstetrics and Gynecology Hospital, Suqian, Jiangsu, China
| | - Xinghe Wang
- Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China
| | - Cheng Tan
- Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China
| | - Chunyan Ni
- Department of Anesthesiology, Obstetrics and Gynecology Hospital, Suqian, Jiangsu, China
| | - Lingyun Dai
- Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China. .,Department of Anesthesiology, Suqian First People's Hospital, Jiangsu, China.
| | - Su Liu
- Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu, China. .,Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China.
| |
Collapse
|
|
36
|
Factors associated with follow-up of infants with hypoxic-ischemic encephalopathy in a high-risk infant clinic in California. J Perinatol 2021; 41:1347-1354. [PMID: 33311530 DOI: 10.1038/s41372-020-00898-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 10/23/2020] [Accepted: 11/20/2020] [Indexed: 11/08/2022]
Abstract
OBJECTIVE To determine the rates of high-risk infant follow-up (HRIF) attendance and the characteristics associated with follow-up among infants with hypoxic-ischemic encephalopathy (HIE) in California. STUDY DESIGN Using population-based datasets, 1314 infants with HIE born in 2010-2016 were evaluated. The characteristics associated with follow-up were identified through multivariable logistic regression. RESULTS 73.9% of infants attended HRIF by age 1. Follow-up rates increased and variation in follow-up by clinic decreased over time. Female infants; those born to African-American, single, less than college-educated, or publicly insured caregivers; and those referred to high-volume or regional programs had lower follow-up rates. In multivariable analysis, Asian and Pacific Islander race/ethnicity had lower odds of follow-up; infants with college- or graduate school-educated caregivers or referred to mid-volume HRIF programs had greater odds. CONCLUSION Sociodemographic and program-level characteristics were associated with lack of follow-up among HIE infants. Understanding these characteristics may improve the post-discharge care of HIE infants.
Collapse
|
|
37
|
Zhang T, Brander G, Mantel Ä, Kuja-Halkola R, Stephansson O, Chang Z, Larsson H, Mataix-Cols D, Fernández de la Cruz L. Assessment of Cesarean Delivery and Neurodevelopmental and Psychiatric Disorders in the Children of a Population-Based Swedish Birth Cohort. JAMA Netw Open 2021; 4:e210837. [PMID: 33666663 PMCID: PMC7936261 DOI: 10.1001/jamanetworkopen.2021.0837] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
IMPORTANCE Recent studies suggest that cesarean delivery (CD) is associated with increased risk of neurodevelopmental disorders in children, although they were unable to control for indications for CD or familial confounding beyond full siblings. OBJECTIVE To examine the association between CD and neurodevelopmental and psychiatric disorders in children. DESIGN, SETTING, AND PARTICIPANTS This Swedish register-based cohort study included 1 179 341 term-birth singletons born between January 1, 1990, and December 31, 2003, and followed up through December 31, 2013. All individuals were linked to their full siblings, maternal and paternal half siblings, and maternal full cousins. Statistical analyses were performed from September 26, 2019, to January 16, 2021. EXPOSURES Birth by CD recorded at birth, stratified into planned and intrapartum CD. MAIN OUTCOMES AND MEASURES Registered diagnoses of neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), intellectual disability, tic disorders, communication disorders, learning disorders, and any neurodevelopmental disorder; and psychiatric disorders, including anxiety disorders, obsessive-compulsive disorder, depressive disorders, eating disorders, bipolar disorders, psychotic disorders, and any psychiatric disorder. RESULTS Of 1 179 341 individuals, 1 048 838 (533 140 boys [50.8%]) were delivered vaginally, 59 514 (30 138 boys [50.6%]) were delived via planned CD, and 70 989 (39 191 boys [55.2%]) were delivered via intrapartum CD. Mean (SD) age at follow-up was 17.7 (4.1) years for vaginal delivery, 16.6 (4.2) years for planned CD, and 16.8 (4.1) years for intrapartum CD. Compared with vaginal delivery, and after controlling for measured covariates (parental and neonatal characteristics, maternal comorbidities, and pregnancy complications), CD was associated with higher risk in children of any neurodevelopmental disorder (planned CD, hazard ratio [HR], 1.17; 95% CI, 1.13-1.22; intrapartum CD, HR, 1.10; 95% CI, 1.05-1.14), ADHD (planned CD, HR, 1.17; 95% CI, 1.12-1.23; intrapartum CD, HR, 1.10; 95% CI, 1.05-1.15), and intellectual disability (planned CD, HR, 1.26; 95% CI, 1.14-1.39; intrapartum CD, HR, 1.17; 95% CI, 1.06-1.28). Only planned CD was associated with a higher risk of ASD (HR, 1.20; 95% CI, 1.10-1.31), communication disorders (HR, 1.14; 95% CI, 1.02-1.28), and learning disorders (HR, 1.15; 95% CI, 1.01-1.30). Cesarean delivery was not associated with the remaining disorders. The associations between CD and any neurodevelopmental disorder, ADHD, ASD, and intellectual disability attenuated in full cousins and paternal half siblings, and further attenuated (became nonsignificant) in maternal half siblings and full siblings (risk of any neurodevelopmental disorder in full siblings, planned CD, HR, 0.93; 95% CI, 0.81-1.06; intrapartum CD, HR, 1.07; 95% CI, 0.96-1.21). CONCLUSIONS AND RELEVANCE The findings of this study suggest that the association between CD and increased risk of neurodevelopmental disorders in the children was most likely explained by unmeasured familial confounding.
Collapse
Affiliation(s)
- Tianyang Zhang
- Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden
- Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Gustaf Brander
- Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden
- Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
- Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
| | - Ängla Mantel
- Department of Women’s Health, Karolinska University Hospital, Stockholm, Sweden
- Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Ralf Kuja-Halkola
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Olof Stephansson
- Department of Women’s Health, Karolinska University Hospital, Stockholm, Sweden
- Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Zheng Chang
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Henrik Larsson
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- School of Medical Sciences, Örebro University, Örebro, Sweden
| | - David Mataix-Cols
- Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden
- Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
| | - Lorena Fernández de la Cruz
- Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden
- Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
| |
Collapse
|
|
38
|
Placental origins of neonatal diseases: toward a precision medicine approach. Pediatr Res 2021; 89:377-383. [PMID: 33288874 DOI: 10.1038/s41390-020-01293-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 10/05/2020] [Accepted: 10/20/2020] [Indexed: 01/30/2023]
Abstract
The placenta is the single most reliable source for precise information on intrauterine environment, as well as maternal and fetal health. It mediates the physiology of two distinct yet highly interconnected individuals. The pathology that develops in the placenta, and the adaptations the placenta undergoes to mitigate this pathology, may influence the later life health of the mother and baby. Pathological placental examination provides a unique opportunity to explore and understand the intrauterine environment, as well as providing a record of events that may be associated with adverse pregnancy outcomes. A number of placental lesions have been described in association with various neonatal morbidities. The purpose of this review is to summarize the evidence for the association of placental pathologic lesions with neurodevelopmental outcomes infants with specific neonatal morbidities, including (1) neonatal encephalopathy, (2) bronchopulmonary dysplasia, (3) congenital heart diseases, and (4) autism spectrum disorders. For each of these disease processes, we will also propose specific research priorities in future studies. We conclude with a hospital-specific protocol for triaging which placentas should receive histological evaluation as a fundamental first step for the field of neuroplacentology to guide precision-based therapeutic approaches in the affected newborns. IMPACT: The purpose of this review is to summarize the evidence for placental origins of neonatal diseases. We propose specific research priorities in the field of neuroplacentology in future studies. We also present a targeted hospital-based approach for triaging which placentas should receive histological evaluation.
Collapse
|
|
39
|
Powell JM, Hersh AR, Greiner KS, Frank ZC, Pilliod RA, Caughey AB. Obstetric management for stillbirth complicated by a prior cesarean delivery: a cost-effectiveness analysis. J Matern Fetal Neonatal Med 2020; 35:3684-3693. [PMID: 33103519 DOI: 10.1080/14767058.2020.1837770] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
BACKGROUND The primary concern for a trial of labor after cesarean (TOLAC) is a uterine rupture leading to neonatal injury or mortality and maternal mortality. In individuals who have a term stillbirth, the neonatal concern is absent, yet repeat cesarean delivery remains common in this setting. Given the increased maternal risks from cesarean, it is important to evaluate obstetric management options in the population of women who have a term stillbirth and prior cesarean delivery (CD). OBJECTIVES To examine the outcomes and costs of a TOLAC via induction of labor verses a repeat CD for cases of stillbirth occurring near term. STUDY DESIGN A decision-analytic model incorporating the current and a subsequent delivery using TreeAge software was designed to compare outcomes in women induced for a TOLAC to those undergoing repeat CD in the setting of stillbirth at 34-41 weeks' gestation. We used a theoretical cohort of 6000 women, the estimated annual number of women a prior cesarean who experience a stillbirth in the United States. Outcomes included quality-adjusted life years (QALY) for both modes of delivery with consideration of future pregnancy risks. Future pregnancy risks included uterine rupture, hysterectomy, placenta accreta, maternal death, neonatal death, and neonatal neurological deficits. Probabilities were derived from the literature, and a cost-effectiveness threshold was set at $100,000/QALY. RESULTS In our theoretical cohort of 6000 women with a prior CD and current stillbirth, induction of labor resulted in 4836 fewer cesarean deliveries during stillbirth management, 1040 fewer cesarean deliveries in the subsequent pregnancy, and 14 fewer cases of placenta accreta in the subsequent pregnancy, despite 29 additional uterine ruptures across both pregnancies. Induction of labor was found to be the dominant strategy, resulting in decreased costs and increased QALYs. Univariate sensitivity analyses demonstrated that induction of labor was cost effective until the risk of uterine rupture in the first delivery exceeded 0.83% (baseline estimate: 0.38%). Additional univariate sensitivity analyses found that induction of labor was cost effective until the risk of IOL failure in the first delivery exceeded 64% (baseline estimate: 19%). CONCLUSION In our theoretical cohort, induction of labor for TOLAC in the setting of a stillbirth with a history of prior CD is cost effective compared to a repeat CD. The results of this analysis demonstrate the benefit of induction of labor among women in this scenario who desire a future pregnancy.
Collapse
Affiliation(s)
- Jacqueline M Powell
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, USA
| | - Alyssa R Hersh
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, USA
| | - Karen S Greiner
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, USA
| | - Zoe C Frank
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, USA
| | - Rachel A Pilliod
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, USA
| | - Aaron B Caughey
- Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, OR, USA
| |
Collapse
|
|
40
|
Kuiper MJ, Meiners LC, Chandler ES, Brandsma R, Bos AF, Horst HT, Sival DA, Brouwer O, Elema A, Heineman K, Hitzert M, vd Hoeven J, Lunsing R. Dyskinesia Impairment Scale scores in Dutch pre-school children after neonatal therapeutic hypothermia. Eur J Paediatr Neurol 2020; 28:70-76. [PMID: 32950367 DOI: 10.1016/j.ejpn.2020.07.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2020] [Revised: 07/18/2020] [Accepted: 07/28/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND Neonatal therapeutic hypothermia (TH) can ameliorate or prevent the development of dyskinetic cerebral palsy (CP) after hypoxic-ischemic encephalopathy (HIE). The Dyskinesia Impairment Scale (DIS) was recently launched to quantify dyskinetic (dystonic and choreatic) motor features in patients with CP. In TH treated children, who are at risk of developing dyskinetic CP, we aimed to determine DIS-scores at pre-school age. METHOD In 21 Dutch pre-school children (3-6 years of age) who had received TH according to the Dutch-Flemish treatment protocol, we determined DIS-scores. We associated DIS-scores with 1. age-matched control values (Kuiper et al., 2018) [1], and 2. previously reported DIS-score range in dyskinetic CP (Monbaliu E et al., 2015). RESULTS The motor phenotype was determined as: normal (n = 18/21), mildly impaired (reduced coordination (n = 2/21)) and abnormal (dyskinetic CP; n = 1/21). In absence of CP (n = 20/21), DIS-scores were lower (more favorable) than in dyskinetic CP, without any overlapping group scores (mean difference: 71 points; p < .05). However, the obtained DIS-scores were still higher than previously reported in healthy age-matched controls (mean difference: 14 points; p < .05). There was an association between DIS-scores and retrospective neonatal MRI (basal ganglia and thalamus injury on diffusion weighted imaging (DWI)) and (a)EEG parameters (p < .05). CONCLUSION In the vast majority (95%) of Dutch TH-HIE treated pre-school children, the phenotypic motor outcome was favorable. However, DIS-scores were moderately increased compared with healthy age-matched controls. Future studies may elucidate the significance of moderately increased DIS-scores should to further extent.
Collapse
Affiliation(s)
- M J Kuiper
- Department of Neurology, University Medical Center Groningen, University of Groningen, the Netherlands
| | - L C Meiners
- Department of Radiology, University Medical Center Groningen, University of Groningen, the Netherlands
| | - E S Chandler
- Department of Neurology, University Medical Center Groningen, University of Groningen, the Netherlands
| | - R Brandsma
- Department of Neurology, University Medical Center Groningen, University of Groningen, the Netherlands
| | - A F Bos
- Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, the Netherlands
| | - Hj Ter Horst
- Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, the Netherlands
| | - D A Sival
- Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, the Netherlands.
| | | | | | | | | | | | | | | |
Collapse
|
|
41
|
Zhang S, Li B, Zhang X, Zhu C, Wang X. Birth Asphyxia Is Associated With Increased Risk of Cerebral Palsy: A Meta-Analysis. Front Neurol 2020; 11:704. [PMID: 32765409 PMCID: PMC7381116 DOI: 10.3389/fneur.2020.00704] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Accepted: 06/09/2020] [Indexed: 01/04/2023] Open
Abstract
Objective: To assess the association between birth asphyxia—as defined by the pH of umbilical cord blood—and cerebral palsy in asphyxiated neonates ≥35 weeks' gestation. Methods: Two reviewers independently selected English-language studies that included data on the incidence of cerebral palsy in asphyxiated neonates ≥35 weeks' gestation. Studies were searched from the Embase, Google Scholar, PubMed, and Cochrane Library databases up to 31 December 2019, and the references in the retrieved articles were screened. Results: We identified 10 studies that met the inclusion criteria for our meta-analysis, including 8 randomized controlled trials and 2 observational studies. According to a random effects model, the pooled rate of cerebral palsy in the randomized controlled trials was 20.3% (95% CI: 16.0–24.5) and the incidence of cerebral palsy in the observational studies was 22.2% (95% CI: 8.5–35.8). Subgroup analysis by treatment for hypoxic ischemic encephalopathy in asphyxiated neonates showed that the pooled rates of cerebral palsy were 17.3% (95% CI: 13.3–21.2) and 23.9% (95% CI: 18.1–29.7) for the intervention group and non-intervention group, respectively. Conclusion: Our findings suggest that the incidence of cerebral palsy in neonates (≥35 weeks' gestation) with perinatal asphyxia is significantly higher compared to that in the healthy neonate population. With the growing emphasis on improving neonatal neurodevelopment and reducing neurological sequelae, we conclude that the prevention and treatment of perinatal asphyxia is essential for preventing the development of cerebral palsy.
Collapse
Affiliation(s)
- Shan Zhang
- Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Bingbing Li
- Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Xiaoli Zhang
- Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China
| | - Changlian Zhu
- Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China.,Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.,Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
| | - Xiaoyang Wang
- Henan Key Laboratory of Child Brain Injury, Third Affiliated Hospital and Institute of Neuroscience of Zhengzhou University, Zhengzhou, China.,Center of Perinatal Medicine and Health, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| |
Collapse
|
|
42
|
Minor neurological signs and behavioural function at age 2 years in neonatal hypoxic ischaemic encephalopathy (HIE). Eur J Paediatr Neurol 2020; 27:78-85. [PMID: 32327390 DOI: 10.1016/j.ejpn.2020.04.003] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2019] [Revised: 03/15/2020] [Accepted: 04/07/2020] [Indexed: 11/20/2022]
Abstract
BACKGROUND Neurodevelopmental follow-up in Neonatal Hypoxic Ischaemic Encephalopathy (HIE) typically focusses on major neuromotor (cerebral palsy, CP) and severe cognitive impairment. Outcomes in those without major neuromotor impairment are less well explored. OBJECTIVES To examine behavioural, cognitive and neurological outcomes after neonatal HIE, in a clinical cohort of children without CP, at age 2 years. METHODS Clinical routine outcome data from children admitted to a tertiary centre with neonatal HIE for hypothermia treatment between 05/08/09-30/05/2016. Children were assessed for neuromotor status - particularly minor neurological signs (MNS), with Bayley Scales of Infant and Toddler Development III (Bayley III) or Ages and Stages Questionnaire-3 (ASQ), Child Behavior Checklist 1.5-5 (CBCL), Quantitative Checklist for Autism in Toddlers (Q-CHAT). RESULTS Of 107 children, 75.5% had normal neurology, 12.1% CP, 12.1% MNS. Children with CP were excluded from analyses. For those without CP, Bayley-III scores were in the average range for the majority; mild cognitive delay observed in 5%, 4.2% language, 1.3% motor development; severe delay in 1.3% for cognitive, 4.2% for language. More than in the normative population scored in clinical ranges for CBCL externalising, sleep, and other problems. No significant difference was seen for Q-CHAT. Children with MNS were significantly more likely to have impaired Bayley-III scores, parent-reported internalising, sleep, and other problems. CONCLUSIONS In this clinical cohort, the majority of children had favourable outcome at 2 years. However, children with MNS were at risk for cognitive and behavioural difficulties and will benefit from enhanced clinical follow-up and support.
Collapse
|
|
43
|
Dekkers L, Janssen A, Steiner K, Schaijk NMV, Akkermans R, de Swart B, Nijhuis-van der Sanden M. Individual longitudinal neurodevelopmental trajectories of children treated with hypothermia for perinatal asphyxia from 3 months to 5 years of age. RESEARCH IN DEVELOPMENTAL DISABILITIES 2020; 102:103659. [PMID: 32438308 DOI: 10.1016/j.ridd.2020.103659] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 03/30/2020] [Accepted: 04/08/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND Hypothermia for perinatal asphyxia is a common treatment to decrease morbidity. This study aims to describe a) individual longitudinal neurodevelopmental trajectories over 5 years in children with perinatal asphyxia treated with hypothermia and b) the correlation between movement quality at 3 months and motor developmental outcomes at 5 years of age. METHODS In this longitudinal cohort study, 18 children (12 male) were assessed at 3 (t1), 6 (t2), 12 (t3), and 24 (t4) months, and at the age of 5 (t5) years, with standardized norm-referenced tests. RESULTS Six children showed abnormal movement quality assessed with General Movements (t1) and all showed severe neurodevelopmental disabilities at t5. The 12 children without severe disabilities, showed a significant normalization of z-scores over the five assessment points (linear mixed model analysis). At t5, four of these children scored mildly delayed motor or cognitive development. CONCLUSION AND IMPLICATIONS Children without anomalies on the MRI before hospital discharge and normal movement quality at 3 months of age showed normal neurodevelopment at the age of 5, however, individual motor trajectories showed variability over time. Presents of abnormal GMs tend to detect CP and developmental problems, advocating a developmental surveillance to determine need for early intervention.
Collapse
Affiliation(s)
- Lieke Dekkers
- HAN University of Applied Sciences, Department of Allied Health Studies, PO Box 6960, 6503 GL, Nijmegen, the Netherlands; Radboud University Medical Center, Amalia Children's Hospital, Radboud Institute for Health Sciences, Department of Rehabilitation, Pediatric Physical Therapy.
| | - Anjo Janssen
- Radboud University Medical Center, Amalia Children's Hospital, Radboud Institute for Health Sciences, Department of Rehabilitation, Pediatric Physical Therapy
| | | | | | - Reinier Akkermans
- Radboud University Medical Center, Department of Primary and Community Care
| | - Bert de Swart
- HAN University of Applied Sciences, Department of Allied Health Studies, PO Box 6960, 6503 GL, Nijmegen, the Netherlands; Radboud University Medical Center, Amalia Children's Hospital, Radboud Institute for Health Sciences, Department of Rehabilitation, Pediatric Physical Therapy
| | - Maria Nijhuis-van der Sanden
- Radboud University Medical Center, Amalia Children's Hospital, Radboud Institute for Health Sciences, Department of Rehabilitation, Pediatric Physical Therapy; Radboud University Medical Center, Scientific Institute for Quality of Health Care, PO Box 9101, 6500 HB Nijmegen, the Netherlands
| |
Collapse
|
|
44
|
Turlova E, Wong R, Xu B, Li F, Du L, Habbous S, Horgen FD, Fleig A, Feng ZP, Sun HS. TRPM7 Mediates Neuronal Cell Death Upstream of Calcium/Calmodulin-Dependent Protein Kinase II and Calcineurin Mechanism in Neonatal Hypoxic-Ischemic Brain Injury. Transl Stroke Res 2020; 12:164-184. [PMID: 32430797 DOI: 10.1007/s12975-020-00810-3] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 03/12/2020] [Accepted: 03/18/2020] [Indexed: 11/25/2022]
Abstract
Transient receptor potential melastatin 7 (TRPM7), a calcium-permeable, ubiquitously expressed ion channel, is critical for axonal development, and mediates hypoxic and ischemic neuronal cell death in vitro and in vivo. However, the downstream mechanisms underlying the TRPM7-mediated processes in physiology and pathophysiology remain unclear. In this study, we employed a mouse model of hypoxic-ischemic brain cell death which mimics the pathophysiology of hypoxic-ischemic encephalopathy (HIE). HIE is a major public health issue and an important cause of neonatal deaths worldwide; however, the available treatments for HIE remain limited. Its survivors face life-long neurological challenges including mental retardation, cerebral palsy, epilepsy and seizure disorders, motor impairments, and visual and auditory impairments. Through a proteomic analysis, we identified calcium/calmodulin-dependent protein kinase II (CaMKII) and phosphatase calcineurin as potential mediators of cell death downstream from TRPM7 activation. Further analysis revealed that TRPM7 mediates cell death through CaMKII, calmodulin, calcineurin, p38, and cofilin cascade. In vivo, we found a significant reduction of brain injury and improvement of short- and long-term functional outcomes after HI after administration of specific TRPM7 blocker waixenicin A. Our data demonstrate a molecular mechanism of TRPM7-mediated cell death and identifies TRPM7 as a promising therapeutic and drug development target for HIE.
Collapse
Affiliation(s)
- Ekaterina Turlova
- Department of Surgery, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
- Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
| | - Raymond Wong
- Department of Surgery, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
- Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
| | - Baofeng Xu
- Department of Surgery, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
- Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
| | - Feiya Li
- Department of Surgery, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
- Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
| | - Lida Du
- Department of Surgery, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
- Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
| | - Steven Habbous
- Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada
| | - F David Horgen
- Department of Natural Sciences, Hawaii Pacific University, Kaneohe, HI, 96744, USA
| | - Andrea Fleig
- Center for Biomedical Research at The Queen's Medical Center and John A. Burns School of Medicine, University of Hawaii, Honolulu, HI, 96720, USA
| | - Zhong-Ping Feng
- Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
| | - Hong-Shuo Sun
- Department of Surgery, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
- Department of Physiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.
- Department of Pharmacology, University of Toronto, 1 King's College Circle, Toronto, M5S 1A8, Canada.
- Leslie Dan Faculty of Pharmacy, University of Toronto, University of Toronto, Toronto, Canada.
| |
Collapse
|
|
45
|
Chacko A, Andronikou S, Mian A, Gonçalves FG, Vedajallam S, Thai NJ. Cortical ischaemic patterns in term partial-prolonged hypoxic-ischaemic injury-the inter-arterial watershed demonstrated through atrophy, ulegyria and signal change on delayed MRI scans in children with cerebral palsy. Insights Imaging 2020; 11:53. [PMID: 32232679 PMCID: PMC7105592 DOI: 10.1186/s13244-020-00857-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Accepted: 03/05/2020] [Indexed: 12/24/2022] Open
Abstract
The inter-arterial watershed zone in neonates is a geographic area without discernible anatomic boundaries and difficult to demarcate and usually not featured in atlases. Schematics currently used to depict the areas are not based on any prior anatomic mapping, compared to adults.Magnetic resonance imaging (MRI) of neonates in the acute to subacute phase with suspected hypoxic-ischaemic injury (HII) can demonstrate signal abnormality and restricted diffusion in the cortical and subcortical parenchyma of the watershed regions.In the chronic stage of partial-prolonged hypoxic-ischaemic injury, atrophy and ulegyria can make the watershed zone more conspicuous as a region. Our aim is to use images extracted from a sizable medicolegal database (approximately 2000 cases), of delayed MRI scans in children with cerebral palsy, to demonstrate the watershed region.To achieve this, we have selected cases diagnosed on imaging as having sustained a term pattern of partial-prolonged HII affecting the hemispheric cortex, based on the presence of bilateral, symmetric atrophy with ulegyria. From these, we have identified those patients demonstrating injury along the whole watershed continuum as well as those demonstrating selective anterior or posterior watershed predominant injury for demonstration.Recognition of this zone is essential for diagnosing partial-prolonged hypoxic-ischaemic injury sustained in term neonates. The images presented in this pictorial review provide a template for identifying the cortical watershed distribution when there is milder regional (anterior, parasagittal, peri-Sylvian and posterior) watershed injury and for more severe injury where multiple regions are injured in combination or as a continuum.
Collapse
Affiliation(s)
- Anith Chacko
- Clinical Research & Imaging Centre, Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, UK.
| | - Savvas Andronikou
- Clinical Research & Imaging Centre, Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, UK
- Department of Radiology, Division of Neuroradiology, Children's Hospital of Philadelphia, Philadelphia, USA
| | - Ali Mian
- Department of Radiology, Division of Neuroradiology, Children's Hospital of Philadelphia, Philadelphia, USA
| | | | - Schadie Vedajallam
- Clinical Research & Imaging Centre, Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, UK
| | - Ngoc Jade Thai
- Clinical Research & Imaging Centre, Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, UK
| |
Collapse
|
|
46
|
Magai DN, Newton CR, Mwangi P, Koot HM, Abubakar A. Patterns of neurobehavioral functioning in school-aged survivors of neonatal jaundice and hypoxic-ischemic encephalopathy in Kilifi, Kenya: A cross-sectional study. Wellcome Open Res 2020. [DOI: 10.12688/wellcomeopenres.15200.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Background: Studies in high-income countries have reported that school-aged children who survive neonatal jaundice (NNJ) and hypoxic-ischemic encephalopathy (HIE) develop long-term neurocognitive problems. However, less is known about the patterns of functioning in school-aged survivors of NNJ and HIE in sub-Saharan Africa. This study examined patterns of functioning in school-aged children who survived NNJ and HIE in Kilifi, Kenya. Methods: This is a cross-sectional study that included 107 survivors of NNJ/HIE (64 with NNJ, 43 with HIE), aged 6-12 years, admitted to Kilifi County Hospital on the Kenyan Coast. The Gross Motor Function Classification System (GMFCS), Adapted Communication Profile, Raven’s Coloured Progressive Matrices (RCPM) and an epilepsy screening tool were used to assess gross motor function, communication function, intellectual functioning, and epilepsy, respectively. Results: Most of the survivors of NNJ (95.2%) and HIE (95.3%) had no impairments in gross motor functioning. A small percentage of the children in the NNJ and HIE groups had profound problems in their communication (4.7% and 4.7%); expressive communication function (4.7% and 4.7%); social functions (3.1% and 2.3%); receptive communication (4.7% and 2.3%); and communicative effectiveness (4.7% and 2.3%). Cognitive impairment was reported in 10.9% and 11.9% for NNJ and HIE survivors, respectively. Active epilepsy was detected in 1.6% of survivors of NNJ and 2.3% of survivors of HIE. All children had normal hearing and visual functioning except one participant who presented with mild visual acuity problems. Conclusions: Most school-aged children who survive with NNJ and HIE have normal motor and communication function; however, one in ten are likely to present with lowered intellectual functioning compared to the normative sample.
Collapse
|
|
47
|
Farquhar CM, Armstrong S, Masson V, Thompson JMD, Sadler L. Clinician Identification of Birth Asphyxia Using Intrapartum Cardiotocography Among Neonates With and Without Encephalopathy in New Zealand. JAMA Netw Open 2020; 3:e1921363. [PMID: 32074288 DOI: 10.1001/jamanetworkopen.2019.21363] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
IMPORTANCE Despite improvements in antenatal care and increasing cesarean delivery rates, birth asphyxia leading to neonatal encephalopathy (NE) continues to contribute to neonatal death and long-term neurodevelopmental disability. Cardiotocography (CTG) has been used in labor for several decades to detect a stressed fetus so that delivery can be expedited and NE avoided. OBJECTIVE To investigate whether experienced clinicians can detect and respond to abnormal readings from CTGs during the penultimate hour before birth in infants with moderate to severe NE but no acute peripartum event. DESIGN, SETTING, AND PARTICIPANTS This case-control study included 10 practicing obstetricians and midwives at maternity hospitals in New Zealand. Participants, who were masked to the perinatal outcome, were asked to assess CTG tracings from 35 neonates with NE and evidence of birth hypoxia (ie, cases) and 105 neonates without NE or birth hypoxia (ie, controls), all of whom were born in 2010 to 2011. Data analysis was conducted from May to December 2017. EXPOSURES Brief clinical details and 1 hour of CTG tracings from the penultimate hour before birth were provided for each baby. Clinicians assessed the CTG tracings and recommended a plan. MAIN OUTCOMES AND MEASURES Intra-assessor and interassessor agreement on CTG findings and action plans as well as sensitivity (ie, detection of NE) and specificity (ie, ruling out those without NE) for the assessment of abnormal CTG readings leading to immediate action (ie, fetal blood sample or immediate delivery) were reported. RESULTS A total of 35 infants (mean [SD] gestational age, 40 [1.4] weeks; 16 [45.7%] cesarean deliveries) were designated cases, and 105 infants (mean [SD] gestational age, 39.4 [1.2] weeks; 22 [21.0%] cesarean deliveries) were designated controls. No infants had congenital anomalies. The mean (range) sensitivity for detection of abnormal CTG results and for recommending immediate action for all assessors was 75% (63%-91%) and 41% (23%-57%), respectively, with a mean (range) specificity of 67% (53%-77%) and 87% (65%-99%), respectively. A sensitivity analysis including only assessors with 80% or more interassessor agreement only differed from the main analysis by 6% or less (mean [range] sensitivity for detection, 76% [63%-91%]; sensitivity for action plan, 36% [25%-49%]; specificity for detection, 71% [53%-77%]; and specificity for action plan, 93% [88%-99%]). CONCLUSIONS AND RELEVANCE Experienced clinicians detected 3 of 4 infants who were subsequently diagnosed with NE. Action to expedite delivery was recommended for more than 40% of infants with NE. These results indicate that CTG does not identify all infants at risk of NE, and that there is a need for further investment in new approaches to fetal surveillance in labor.
Collapse
Affiliation(s)
- Cynthia M Farquhar
- Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand
- Auckland District Health Board, Auckland, New Zealand
| | - Sarah Armstrong
- Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand
| | - Vicki Masson
- Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand
| | - John M D Thompson
- Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand
| | - Lynn Sadler
- Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand
- Auckland District Health Board, Auckland, New Zealand
| |
Collapse
|
|
48
|
Mohammad K. Assessing pupil reaction to light using ultrasound in a sick neonate with Hypoxic Ischemic Encephalopathy. J Neonatal Perinatal Med 2020; 13:459-461. [PMID: 32176661 DOI: 10.3233/npm-190394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Examining pupil reaction to light is an important component of the neurological examination in infants with hypoxic ischemic encephalopathy (HIE) to determine eligibility for therapeutic hypothermia (TH) and as part of serial neurological assessment for prognostication. Pupil examination can be challenging in critically ill infants with generalized edema. In this paper I report a simple technique using bedside point of care ultrasound to examine the pupil reaction to light in an infant with moderate HIE undergoing therapeutic hypothermia.
Collapse
Affiliation(s)
- K Mohammad
- Department of Pediatrics, Section of Neonatology, University of Calgary, AB, Canada
| |
Collapse
|
|
49
|
Schreglmann M, Ground A, Vollmer B, Johnson MJ. Systematic review: long-term cognitive and behavioural outcomes of neonatal hypoxic-ischaemic encephalopathy in children without cerebral palsy. Acta Paediatr 2020; 109:20-30. [PMID: 31002422 DOI: 10.1111/apa.14821] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 04/11/2019] [Accepted: 04/15/2019] [Indexed: 01/20/2023]
Abstract
AIM To evaluate long-term cognitive and behavioural outcomes of children with neonatal hypoxic-ischaemic encephalopathy (HIE) in the absence of cerebral palsy (CP). METHODS A systematic search was performed on five databases (EMBASE, Medline, PubMed, Web of Science, PsycInfo). Randomised controlled trials, non-randomised controlled trials, or observational studies, published between 1990 and 2017, that reported long-term (age greater than or equal to four years) cognitive and/or behavioural outcomes of neonatal HIE without CP were included. RESULTS Seven articles met the inclusion criteria (n = 352 total participants, n = 53 treated with therapeutic hypothermia). Studies reporting cognitive outcome demonstrate impairment of general cognitive abilities in 25-63% of participants with HIE without CP. Specific cognitive difficulties were reported in two studies for attention, executive functioning, memory function and language. Results regarding behavioural outcome possibly indicate a higher risk of difficulties. CONCLUSION A substantial proportion of children with neonatal HIE who survive without CP are at increased risk of general and/or specific cognitive impairments. Behavioural problems may be more common, but evidence is limited. Results highlight the importance of comprehensive long-term follow-up to identity difficulties and enable intervention to optimise educational achievement and behavioural adjustment.
Collapse
Affiliation(s)
- Magdalena Schreglmann
- Department of Neonatal Medicine Southampton Children's Hospital University Hospital Southampton NHS Foundation Trust Southampton UK
- Clinical and Experimental Sciences Faculty of Medicine University of Southampton Southampton UK
| | - Amy Ground
- Clinical and Experimental Sciences Faculty of Medicine University of Southampton Southampton UK
| | - Brigitte Vollmer
- Clinical and Experimental Sciences Faculty of Medicine University of Southampton Southampton UK
- Paediatric and Neonatal Neurology Southampton Children's Hospital University Hospital Southampton NHS Foundation Trust Southampton UK
| | - Mark J. Johnson
- Department of Neonatal Medicine Southampton Children's Hospital University Hospital Southampton NHS Foundation Trust Southampton UK
- National Institute for Health Research Southampton Biomedical Research Centre University Hospital Southampton NHS Foundation Trust and University of Southampton Southampton UK
| |
Collapse
|
|
50
|
The development and validation of a cerebral ultrasound scoring system for infants with hypoxic-ischaemic encephalopathy. Pediatr Res 2020; 87:59-66. [PMID: 32218538 PMCID: PMC7098882 DOI: 10.1038/s41390-020-0782-0] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Hypoxic-ischaemic encephalopathy (HIE) is an important cause of morbidity and mortality in neonates. When the gold standard MRI is not feasible, cerebral ultrasound (CUS) might offer an alternative. In this study, the association between a novel CUS scoring system and neurodevelopmental outcome in neonates with HIE was assessed. METHODS (Near-)term infants with HIE and therapeutic hypothermia, a CUS on day 1 and day 3-7 after birth and available outcome data were retrospectively included in cohort I. CUS findings on day 1 and day 3-7 were related to adverse outcome in univariate and the CUS of day 3-7 also in multivariable logistic regression analyses. The resistance index, the sum of deep grey matter and of white matter involvement were included in multivariable logistic regression analyses. A comparable cohort from another hospital was used for validation (cohort II). RESULTS Eighty-three infants were included in cohort I and 35 in cohort II. The final CUS scoring system contained the sum of white matter (OR = 2.6, 95% CI 1.5-4.7) and deep grey matter involvement (OR = 2.7, 95% CI 1.7-4.4). The CUS scoring system performed well in cohort I (AUC = 0.90) and II (AUC = 0.89). CONCLUSION This validated CUS scoring system is associated with neurodevelopmental outcome in neonates with HIE.
Collapse
|