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Seber T, Uylar Seber T, Özdemir A, Baştuğ O, Keskin Ş, Aktaş E. Volumetric apparent diffusion coefficient histogram analysis in term neonatal asphyxia treated with hypothermia. Br J Radiol 2024; 97:1302-1310. [PMID: 38775658 PMCID: PMC11186576 DOI: 10.1093/bjr/tqae105] [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] [Received: 07/04/2023] [Revised: 11/07/2023] [Accepted: 05/16/2024] [Indexed: 06/21/2024] Open
Abstract
OBJECTIVES Our aim is to estimate the long-term neurological sequelae and prognosis in term neonatal asphyxia treated with hypothermia via volumetric apparent diffusion coefficient (ADC) map histogram analysis (HA). METHODS Brain MRI studies of 83 term neonates with asphyxia who received whole-body hypothermia treatment and examined between postnatal (PN) fourth and sixth days were retrospectively re-evaluated by 2 radiologists. Volumetric HA was performed for the areas frequently affected in deep and superficial asphyxia (thalamus, lentiform nucleus, posterior limb of internal capsule, corpus callosum forceps major, and perirolandic cortex-subcortical white matter) on ADC map. The quantitative ADC values were obtained separately for each region. Qualitative-visual (conventional) MRI findings were also re-evaluated. Neonates were examined neurodevelopmentally according to the Revised Brunet-Lezine scale. The distinguishability of long-term neurodevelopmental outcomes was statistically investigated. RESULTS With HA, the adverse neurodevelopmental outcomes could only be distinguished from mild-moderated impairment and normal development at the thalamus with 10th percentile ADC (P = .02 and P = .03, respectively) and ADCmin (P = .03 and P = .04, respectively). Also with the conventional MRI findings, adverse outcome could be distinguished from mild-moderated impairment (P = .04) and normal development (P = .04) via cytotoxic oedema of the thalamus, corpus striatum, and diffuse cerebral cortical. CONCLUSION The long-term adverse neurodevelopmental outcomes in newborns with asphyxia who received whole-body hypothermia treatment can be estimated similarly with volumetric ADC-HA and the conventional assessment of the ADC map. ADVANCES IN KNOWLEDGE This study compares early MRI ADC-HA with neurological sequelae in term newborns with asphyxia who received whole-body hypothermia treatment. We could not find any significant difference in predicting adverse neurological sequelae between the visual-qualitative evaluation of the ADC map and HA.
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Affiliation(s)
- Turgut Seber
- Department of Radiology, Kayseri City Education and Research Hospital, Kayseri 38080, Turkey
| | - Tuğba Uylar Seber
- Department of Radiology, Kayseri City Education and Research Hospital, Kayseri 38080, Turkey
| | - Ahmet Özdemir
- Department of Neonatology, Kayseri City Education and Research Hospital, Kayseri 38080, Turkey
| | - Osman Baştuğ
- Department of Neonatology, Kayseri City Education and Research Hospital, Kayseri 38080, Turkey
| | - Şuayip Keskin
- Department of Child Health and Diseases, Kayseri City Education and Research Hospital, Kayseri 38080, Turkey
| | - Elif Aktaş
- Department of Radiology, Kayseri City Education and Research Hospital, Kayseri 38080, Turkey
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Kromm GH, Patankar H, Nagalotimath S, Wong H, Austin T. Socioemotional and Psychological Outcomes of Hypoxic-Ischemic Encephalopathy: A Systematic Review. Pediatrics 2024; 153:e2023063399. [PMID: 38440801 PMCID: PMC10979301 DOI: 10.1542/peds.2023-063399] [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] [Accepted: 01/05/2024] [Indexed: 03/06/2024] Open
Abstract
BACKGROUND AND OBJECTIVES Therapeutic hypothermia has reduced the risk of death or major disability following perinatal hypoxic-ischemic encephalopathy (HIE); however, many children who experience perinatal HIE still go on to develop personal and behavioral challenges, which can be difficult for caregivers and a public health burden for society. Our objective with this review is to systematically identify and synthesize studies that evaluate associations between perinatal HIE and socioemotional or psychological outcomes. METHODS We screened all search-returned journal articles from Cochrane Library, Embase, Medline, PsycINFO, Scopus, and Web of Science from data inception through February 1, 2023. Keywords related to HIE (eg, neonatal encephalopathy, neonatal brain injury) and outcomes (eg, social*, emotion*, behav* problem, psycholog*, psychiatr*) were searched with a predefined search string. We included all observational human studies reporting socioemotional or psychological sequelae of term HIE. Study data were recorded on standardized sheets, and the Newcastle-Ottawa Scale was adapted to assess study quality. RESULTS We included 43 studies documenting 3244 HIE participants and 2132 comparison participants. We found statistically significant associations between HIE and social and emotional, behavioral, and psychological and psychiatric deficits throughout infancy, childhood, and adolescence (19 studies). The authors of the included studies also report nonsignificant findings (11 studies) and outcomes without statistical comparison (25 studies). CONCLUSIONS Perinatal HIE may be a risk factor for a range of socioemotional and psychological challenges in the short- and long-term. Routine screening, early intervention, and follow-up support may be particularly beneficial to this population.
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Affiliation(s)
| | | | | | - Hilary Wong
- Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom
- NICU, Rosie Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
| | - Topun Austin
- Department of Paediatrics, University of Cambridge, Cambridge, United Kingdom
- NICU, Rosie Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
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Tran HTT, Le HT, Tran DM, Nguyen GTH, Hellström-Westas L, Alfven T, Olson L. Therapeutic hypothermia after perinatal asphyxia in Vietnam: medium-term outcomes at 18 months - a prospective cohort study. BMJ Paediatr Open 2024; 8:e002208. [PMID: 38388007 PMCID: PMC10882320 DOI: 10.1136/bmjpo-2023-002208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 01/31/2024] [Indexed: 02/24/2024] Open
Abstract
AIM To determine neurodevelopmental outcome at 18 months after therapeutic hypothermia for hypoxic-ischaemic encephalopathy (HIE) infants in Vietnam, a low-middle-income country. METHOD Prospective cohort study investigating outcomes at 18 months in severely asphyxiated outborn infants who underwent therapeutic hypothermia for HIE in Hanoi, Vietnam, during the time period 2016-2019. Survivors were examined at discharge and at 6 and 18 months by a neonatologist, a neurologist and a rehabilitation physician, who were blinded to the infants' clinical severity during hospitalisation using two assessment tools: the Ages and Stages Questionnaire (ASQ) and the Hammersmith Infant Neurological Examination (HINE), to detect impairments and promote early interventions for those who require it. RESULTS In total, 130 neonates, 85 (65%) with moderate and 45 (35%) with severe HIE, underwent therapeutic hypothermia treatment using phase change material. Forty-three infants (33%) died during hospitalisation and in infancy. Among the 87 survivors, 69 (79%) completed follow-up until 18 months. Nineteen children developed cerebral palsy (8 diplegia, 3 hemiplegia, 8 dyskinetic), and 11 had delayed neurodevelopment. At each time point, infants with a normal or delayed neurodevelopment had significantly higher ASQ and HINE scores (p<0.05) than those with cerebral palsy. CONCLUSION The rates of mortality and adverse neurodevelopment rate were high and comparable to recently published data from other low-middle-income settings. The ASQ and HINE were useful tools for screening and evaluation of neurodevelopment and neurological function.
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Affiliation(s)
- Hang Thi Thanh Tran
- Department of Global Public Health, Karolinska Institute, Stockholm, Sweden
- Neonatal Care Center, Vietnam National Children's Hospital, Ha Noi, Viet Nam
| | - Ha Thi Le
- Neonatal Care Center, Vietnam National Children's Hospital, Ha Noi, Viet Nam
| | | | | | | | - Tobias Alfven
- Department of Global Public Health, Karolinska Institute, Stockholm, Sweden
- Sachs' Children and Youth Hospital, Stockholm, Sweden
| | - Linus Olson
- Department of Global Public Health, Karolinska Institute, Stockholm, Sweden
- Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
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Arnautovic T, Sinha S, Laptook AR. Neonatal Hypoxic-Ischemic Encephalopathy and Hypothermia Treatment. Obstet Gynecol 2024; 143:67-81. [PMID: 37797337 PMCID: PMC10841232 DOI: 10.1097/aog.0000000000005392] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 07/27/2023] [Indexed: 10/07/2023]
Abstract
Neonatal hypoxic-ischemic encephalopathy (HIE) is an important clinical entity because it is associated with death and long-term disability, including cognitive impairment, cerebral palsy, seizures, and neurosensory deficits. Over the past 40 years, there has been an intensive search to identify therapies to improve the prognosis of neonates with HIE. Hypothermia treatment represents the culmination of laboratory investigations including small and large animal studies, followed by pilot human studies, and, finally, randomized controlled trials to establish efficacy and safety. Clinical trials have demonstrated that hypothermia treatment reduces mortality and improves early childhood outcome among survivors. Hypoxic-ischemic encephalopathy is a multi-system disease process that requires intensive medical support for brain monitoring and monitoring of non-central nervous system organ dysfunction. Treatment must be conducted in a level III or IV neonatal intensive care unit with infrastructure for an integrated approach to care for critically ill neonates. Hypothermia treatment is the first and currently the only therapy to improve outcomes for neonates with HIE and indicates that HIE is modifiable. However, outcomes likely can be improved further. Hypothermia treatment has accelerated investigation of other therapies to combine with hypothermia. It has also stimulated a more intensive approach to brain monitoring, which allows earlier intervention for complications. Finally, HIE and hypothermia treatment negatively influences the psychological state of affected families, and there is growing recognition of the importance of trauma-informed principles to guide medical professionals.
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Affiliation(s)
- Tamara Arnautovic
- Department of Pediatrics, Women & Infants Hospital of Rhode Island, and Warren Alpert Medical School of Brown University, Providence, Rhode Island
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Leith WM, Zeegers MP, Freeman MD. A predictive model for perinatal hypoxic ischemic encephalopathy using linked maternal and neonatal hospital data. Ann Epidemiol 2024; 89:29-36. [PMID: 38042440 DOI: 10.1016/j.annepidem.2023.11.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 11/26/2023] [Accepted: 11/29/2023] [Indexed: 12/04/2023]
Abstract
PURPOSE To build an evidence-based model to estimate case-specific risk of perinatal hypoxic ischemic encephalopathy. METHODS A retrospective, cross-sectional study of all births in Hawaii, Michigan, and New Jersey between 2010 and 2015, using linked maternal labor/delivery and neonatal birth records. Stepwise logistic regression and competitive Akaike information criterion were used to identify the most parsimonious model. Predictive ability of the model was measured with bootstrapped optimism-adjusted area under the ROC curve. RESULTS Among 836,216 births there were 376 (0.45 per 1000) cases of hypoxic ischemic encephalopathy. The final model included 28 variables, 24 associated with increased risk, and 4 that were protective. The optimism-adjusted area under the ROC curve was 0.84. Estimated risk in the study population ranged from 1 in ∼323,000 to 1 in 2.5. The final model confirmed known risk factors (e.g., sentinel events and shoulder dystocia) and identified novel risk factors, such as maternal race and insurance status. CONCLUSION Our study shows that risk of perinatal hypoxic ischemic encephalopathy injury can be estimated with high confidence. Our model fills a notable gap in the study of hypoxic ischemic encephalopathy prevention: the estimation of risk, particularly in the United States population which is unique with respect to racial and socioeconomic disparities.
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Affiliation(s)
- Wendy M Leith
- Maastricht University, Care and Primary Healthcare Research Institute, Faculty of Health, Medicine, and Life Sciences, P.O. Box 616 6200 MD, Maastricht, the Netherlands.
| | - Maurice P Zeegers
- Maastricht University, Care and Primary Healthcare Research Institute, Faculty of Health, Medicine, and Life Sciences, P.O. Box 616 6200 MD, Maastricht, the Netherlands
| | - Michael D Freeman
- Maastricht University, Care and Primary Healthcare Research Institute, Faculty of Health, Medicine, and Life Sciences, P.O. Box 616 6200 MD, Maastricht, the Netherlands
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Malan R, Van der Linde J, Kritzinger A, Graham MA, Krüger E. Evolution of Feeding and Developmental Outcomes in Infants With Moderate Hypoxic-Ischemic Encephalopathy: A Pilot Study. Neonatal Netw 2023; 42:264-275. [PMID: 37657810 DOI: 10.1891/nn-2023-0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/20/2023] [Indexed: 09/03/2023]
Abstract
The purpose of the study was to describe the evolution of outcomes among full-term infants with moderate hypoxic-ischemic encephalopathy (HIE); from their early swallowing and feeding abilities during hospitalization, to their later developmental outcomes at 6 and 12 months. Four participants with moderate HIE were recruited. Early feeding and swallowing were assessed using the Neonatal Feeding Assessment Scale and video fluoroscopic swallow studies. Developmental assessments were conducted at 6 and 12 months using the Rossetti Infant-Toddler Language Scale and Vineland-3 Scale. All participants displayed atypical outcomes throughout the study, including oropharyngeal dysphagia initially during hospitalization. All participants were discharged on oral feeds but some breastfeeding difficulties persisted. Variable but pervasive developmental delays were found among all participants at 6 and 12 months. This study emphasizes the need for consistent early intervention from the neonatal period onward, for all infants with moderate HIE. Future studies should use larger cohorts, longer follow-up, and correlational designs.
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Chebet M, Musaba MW, Mukunya D, Makoko B, Napyo A, Nantale R, Auma P, Atim K, Nahurira D, Lee S, Okello D, Ssegawa L, Bromley K, Burgoine K, Ndeezi G, Tumwine JK, Wandabwa J, Kiguli S. High Burden of Neurodevelopmental Delay among Children Born to Women with Obstructed Labour in Eastern Uganda: A Cohort Study. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:3470. [PMID: 36834165 PMCID: PMC9963417 DOI: 10.3390/ijerph20043470] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Revised: 02/12/2023] [Accepted: 02/14/2023] [Indexed: 05/11/2023]
Abstract
Over 250 million infants in low and middle-income countries do not fulfill their neurodevelopment potential. In this study, we assessed the incidence and risk factors for neurodevelopmental delay (NDD) among children born following obstructed labor in Eastern Uganda. Between October 2021 and April 2022, we conducted a cohort study of 155 children (aged 25 to 44 months), born at term and assessed their neurodevelopment using the Malawi Developmental Assessment Tool. We assessed the gross motor, fine motor, language and social domains of neurodevelopment. The incidence of neurodevelopmental delay by 25 to 44 months was 67.7% (105/155) (95% CI: 59.8-75.0). Children belonging to the poorest wealth quintile had 83% higher risk of NDD compared to children belonging to the richest quintile (ARR (Adjusted Risk Ratio): 1.83; 95% CI (Confidence Interval): [1.13, 2.94]). Children fed the recommended meal diversity had 25% lower risk of neurodevelopmental delay compared to children who did not (ARR: 0.75; 95% CI: [0.60, 0.94]). Children who were exclusively breastfed for the first 6 months had 27% lower risk of neurodevelopmental delay compared to children who were not (ARR: 0.73; 95% CI: [0.56, 0.96]). We recommend that infants born following obstructed labor undergo neurodevelopmental delay screening.
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Affiliation(s)
- Martin Chebet
- Department of Pediatrics and Child Health, Busitema University, Mbale P.O. Box 1460, Uganda
- Department of Global Public Health and Primary Health Care, Centre for International Health, University of Bergen, 5007 Bergen, Norway
| | - Milton W. Musaba
- Department of Obstetrics and Gynecology, Busitema University, Mbale P.O. Box 1460, Uganda
| | - David Mukunya
- Department of Community and Public Health, Busitema University, Mbale P.O. Box 1460, Uganda
- Department of Research, Nikao Medical Center, Kampala P.O. Box 10005, Uganda
| | - Brian Makoko
- Department of Community and Public Health, Busitema University, Mbale P.O. Box 1460, Uganda
| | - Agnes Napyo
- Department of Community and Public Health, Busitema University, Mbale P.O. Box 1460, Uganda
| | - Ritah Nantale
- Department of Community and Public Health, Busitema University, Mbale P.O. Box 1460, Uganda
| | - Proscovia Auma
- Department of Obstetrics and Gynecology, Mbale Regional Referral Hospital, Mbale P.O. Box 921, Uganda
| | - Ketty Atim
- Department of Obstetrics and Gynecology, Mbale Regional Referral Hospital, Mbale P.O. Box 921, Uganda
| | - Doreck Nahurira
- Department of Obstetrics and Gynecology, Busitema University, Mbale P.O. Box 1460, Uganda
| | - Seungwon Lee
- Department of Neuroscience, University of Pennsylvania, Philadelphia, PA 19104, USA
| | - Dedan Okello
- Department of Pediatrics and Child Health, Busitema University, Mbale P.O. Box 1460, Uganda
| | - Lawrence Ssegawa
- Department of Research, Sanyu Africa Research Institute, Mbale P.O. Box 2190, Uganda
| | - Kieran Bromley
- Research Institute for Primary Care and Health Sciences, School of Medicine, Keele University, Newcastle ST5 5BG, UK
| | - Kathy Burgoine
- Neonatal Unit, Mbale Regional Referral Hospital, Mbale P.O. Box 921, Uganda
| | - Grace Ndeezi
- Department of Pediatrics and Child Health, Makerere University, Kampala P.O. Box 7062, Uganda
| | - James K. Tumwine
- Department of Pediatrics and Child Health, Makerere University, Kampala P.O. Box 7062, Uganda
- Department of Pediatrics and Child Health, Kabale University, Kabale P.O. Box 317, Uganda
| | - Julius Wandabwa
- Department of Obstetrics and Gynecology, Busitema University, Mbale P.O. Box 1460, Uganda
| | - Sarah Kiguli
- Department of Pediatrics and Child Health, Makerere University, Kampala P.O. Box 7062, Uganda
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Durán-Carabali LE, Da Silva JL, Colucci ACM, Netto CA, De Fraga LS. Protective effect of sex steroid hormones on morphological and cellular outcomes after neonatal hypoxia-ischemia: A meta-analysis of preclinical studies. Neurosci Biobehav Rev 2023; 145:105018. [PMID: 36572200 DOI: 10.1016/j.neubiorev.2022.105018] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 12/20/2022] [Accepted: 12/21/2022] [Indexed: 12/24/2022]
Abstract
Sex steroid hormones play an important role in fetal development, brain functioning and neuronal protection. Growing evidence highlights the positive effects of these hormones against brain damage induced by neonatal hypoxia-ischemia (HI). This systematic review with meta-analysis aims to verify the efficacy of sex steroid hormones in preventing HI-induced brain damage in rodent models. The protocol was registered at PROSPERO and a total of 22 articles were included. Moderate to large effects were observed in HI animals treated with sex steroid hormones in reducing cerebral infarction size and cell death, increasing neuronal survival, and mitigating neuroinflammatory responses and astrocyte reactivity. A small effect was evidenced for cognitive function, but no significant effect for motor function; moreover, a high degree of heterogeneity was observed. In summary, data suggest that sex steroid hormones, such as progesterone and 17β estradiol, improve morphological and cellular outcomes following neonatal HI. Further research is paramount to examine neurological function during HI recovery and standardization of methodological aspects is imperative to reduce the risk of spurious findings.
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Affiliation(s)
- L E Durán-Carabali
- Graduate Program in Biological Sciences: Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
| | - J L Da Silva
- Department of Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - A C M Colucci
- Graduate Program in Biological Sciences: Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - C A Netto
- Graduate Program in Biological Sciences: Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - L S De Fraga
- Graduate Program in Biological Sciences: Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil; Department of Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
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Zironi I, Aicardi G. Hypoxia Depresses Synaptic Transmission in the Primary Motor Cortex of the Infant Rat-Role of Adenosine A 1 Receptors and Nitric Oxide. Biomedicines 2022; 10:2875. [PMID: 36359395 PMCID: PMC9687150 DOI: 10.3390/biomedicines10112875] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 11/02/2022] [Accepted: 11/04/2022] [Indexed: 09/08/2024] Open
Abstract
The acute and long-term consequences of perinatal asphyxia have been extensively investigated, but only a few studies have focused on postnatal asphyxia. In particular, electrophysiological changes induced in the motor cortex by postnatal asphyxia have not been examined so far, despite the critical involvement of this cortical area in epilepsy. In this study, we exposed primary motor cortex slices obtained from infant rats in an age window (16-18 day-old) characterized by high incidence of hypoxia-induced seizures associated with epileptiform motor behavior to 10 min of hypoxia. Extracellular field potentials evoked by horizontal pathway stimulation were recorded in layers II/III of the primary motor cortex before, during, and after the hypoxic event. The results show that hypoxia reversibly depressed glutamatergic synaptic transmission and neuronal excitability. Data obtained in the presence of specific blockers suggest that synaptic depression was mediated by adenosine acting on pre-synaptic A1 receptors to decrease glutamate release, and by a nitric oxide (NO)/cGMP postsynaptic pathway. These effects are neuroprotective because they limit energy failure. The present findings may be helpful in the preclinical search for therapeutic strategies aimed at preventing acute and long-term neurological consequences of postnatal asphyxia.
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Affiliation(s)
- Isabella Zironi
- Department of Physics and Astronomy, University of Bologna, 40127 Bologna, Italy
| | - Giorgio Aicardi
- Department for Life Quality Studies, University of Bologna, 40127 Bologna, Italy
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Pang R, Mujuni BM, Martinello KA, Webb EL, Nalwoga A, Ssekyewa J, Musoke M, Kurinczuk JJ, Sewegaba M, Cowan FM, Cose S, Nakakeeto M, Elliott AM, Sebire NJ, Klein N, Robertson NJ, Tann CJ. Elevated serum IL-10 is associated with severity of neonatal encephalopathy and adverse early childhood outcomes. Pediatr Res 2022; 92:180-189. [PMID: 33674741 PMCID: PMC9411052 DOI: 10.1038/s41390-021-01438-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 01/27/2021] [Accepted: 02/01/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Neonatal encephalopathy (NE) contributes substantially to child mortality and disability globally. We compared cytokine profiles in term Ugandan neonates with and without NE, with and without perinatal infection or inflammation and identified biomarkers predicting neonatal and early childhood outcomes. METHODS In this exploratory biomarker study, serum IL-1α, IL-6, IL-8, IL-10, TNFα, and VEGF (<12 h) were compared between NE and non-NE infants with and without perinatal infection/inflammation. Neonatal (severity of NE, mortality) and early childhood (death or neurodevelopmental impairment to 2.5 years) outcomes were assessed. Predictors of outcomes were explored with multivariable linear and logistic regression and receiver-operating characteristic analyses. RESULTS Cytokine assays on 159 NE and 157 non-NE infants were performed; data on early childhood outcomes were available for 150 and 129, respectively. NE infants had higher IL-10 (p < 0.001), higher IL-6 (p < 0.017), and lower VEGF (p < 0.001) levels. Moderate and severe NE was associated with higher IL-10 levels compared to non-NE infants (p < 0.001). Elevated IL-1α was associated with perinatal infection/inflammation (p = 0.013). Among NE infants, IL-10 predicted neonatal mortality (p = 0.01) and adverse early childhood outcome (adjusted OR 2.28, 95% CI 1.35-3.86, p = 0.002). CONCLUSIONS Our findings support a potential role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy. IMPACT Neonatal encephalopathy is a common cause of child death and disability globally. Inflammatory cytokines are potential biomarkers of encephalopathy severity and outcome. In this Ugandan health facility-based cohort, neonatal encephalopathy was associated with elevated serum IL-10 and IL-6, and reduced VEGF at birth. Elevated serum IL-10 within 12 h after birth predicted severity of neonatal encephalopathy, neonatal mortality, and adverse early childhood developmental outcomes, independent of perinatal infection or inflammation, and provides evidence to the contribution of the inflammatory processes. Our findings support a role for IL-10 as a biomarker for adverse outcomes after neonatal encephalopathy in a sub-Saharan African cohort.
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Affiliation(s)
- Raymand Pang
- Institute for Women's Health, University College London, London, UK
| | - Brian M Mujuni
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | | | - Emily L Webb
- MRC International Statistics and Epidemiology Group, London School of Hygiene and Tropical Medicine, London, UK
| | - Angela Nalwoga
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - Julius Ssekyewa
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - Margaret Musoke
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | | | - Margaret Sewegaba
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - Frances M Cowan
- Department of Pediatrics, Imperial College London, London, UK
| | - Stephen Cose
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK
| | - Margaret Nakakeeto
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - Alison M Elliott
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK
| | - Neil J Sebire
- UCL Institute of Child Health and GOSH BRC, UCL, London, UK
| | - Nigel Klein
- UCL Institute of Child Health and GOSH BRC, UCL, London, UK
| | - Nicola J Robertson
- Institute for Women's Health, University College London, London, UK
- Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
| | - Cally J Tann
- Institute for Women's Health, University College London, London, UK.
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda.
- Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK.
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11
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Durán-Carabali LE, Odorcyk FK, Sanches EF, de Mattos MM, Anschau F, Netto CA. Effect of environmental enrichment on behavioral and morphological outcomes following neonatal hypoxia-ischemia in rodent models: A systematic review and meta-analysis. Mol Neurobiol 2022; 59:1970-1991. [PMID: 35040041 DOI: 10.1007/s12035-022-02730-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 01/02/2022] [Indexed: 02/06/2023]
Abstract
Neonatal hypoxia-ischemia (HI) is a major cause of mortality and morbidity in newborns and, despite recent advances in neonatal intensive care, there is no definitive treatment for this pathology. Once preclinical studies have shown that environmental enrichment (EE) seems to be a promising therapy for children with HI, the present study conducts a systematic review and meta-analysis of articles with EE in HI rodent models focusing on neurodevelopmental reflexes, motor and cognitive function as well as brain damage. The protocol was registered a priori at PROSPERO. The search was conducted in PubMed, Embase and PsycINFO databases, resulting in the inclusion of 22 articles. Interestingly, EE showed a beneficial impact on neurodevelopmental reflexes (SMD= -0.73, CI= [-0.98; -0.47], p< 0.001, I2= 0.0%), motor function (SMD= -0.55, CI= [-0.81; -0.28], p< 0.001, I2= 62.6%), cognitive function (SMD= -0.93, CI= [-1.14; -0.72], p< 0.001, I2= 27.8%) and brain damage (SMD= -0.80, CI= [-1.03; -0.58], p< 0.001, I2= 10.7%). The main factors that potentiate EE positive effects were enhanced study quality, earlier age at injury as well as earlier start and longer duration of EE exposure. Overall, EE was able to counteract the behavioral and histological damage induced by the lesion, being a promising therapeutic strategy for HI.
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Affiliation(s)
- L E Durán-Carabali
- Graduate Program in Biological Sciences: Physiology, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
| | - F K Odorcyk
- Graduate Program in Biological Sciences: Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - E F Sanches
- Division of Child Development and Growth, Department of Pediatrics, Gynecology and Obstetrics, School of Medicine, University of Geneva, Geneva, Switzerland
| | - M M de Mattos
- Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600, anexo, Porto Alegre, RS, CEP 90035-003, Brazil
| | - F Anschau
- Medicine school, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.,Graduation Program on Evaluation and Production of Technologies for the Brazilian National Health System, Porto Alegre, Brazil
| | - C A Netto
- Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600, anexo, Porto Alegre, RS, CEP 90035-003, Brazil. .,Department of Physiology, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
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12
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Kumar P, Hair P, Cunnion K, Krishna N, Bass T. Classical complement pathway inhibition reduces brain damage in a hypoxic ischemic encephalopathy animal model. PLoS One 2021; 16:e0257960. [PMID: 34591905 PMCID: PMC8483388 DOI: 10.1371/journal.pone.0257960] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Accepted: 09/15/2021] [Indexed: 11/19/2022] Open
Abstract
Perinatal hypoxic ischemic encephalopathy (HIE) remains a major contributor of infant death and long-term disability worldwide. The role played by the complement system in this ischemia-reperfusion injury remains poorly understood. In order to better understand the role of complement activation and other modifiable mechanisms of injury in HIE, we tested the dual-targeting anti-inflammatory peptide, RLS-0071 in an animal model of HIE. Using the well-established HIE rat pup model we measured the effects of RLS-0071 during the acute stages of the brain injury and on long-term neurocognitive outcomes. Rat pups subject to hypoxia-ischemia insult received one of 4 interventions including normothermia, hypothermia and RLS-0071 with and without hypothermia. We measured histopathological effects, brain C1q levels and neuroimaging at day 1 and 21 after the injury. A subset of animals was followed into adolescence and evaluated for neurocognitive function. On histological evaluation, RLS-0071 showed neuronal protection in combination with hypothermia (P = 0.048) in addition to reducing C1q levels in the brain at 1hr (P = 0.01) and at 8 hr in combination with hypothermia (P = 0.005). MRI neuroimaging demonstrated that RLS-0071 in combination with hypothermia reduced lesion volume at 24 hours (P<0.05) as well as decreased T2 signal at day 21 in combination with hypothermia (P<0.01). RLS-0071 alone or in combination with hypothermia improved both short-term and long-term memory. These findings suggest that modulation by RLS-0071 can potentially decrease brain damage resulting from HIE.
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Affiliation(s)
- Parvathi Kumar
- ReAlta Life Sciences, Norfolk, VA, United States of America
- Department of Pediatrics, Children’s Hospital of The King’s Daughters, Norfolk, VA, United States of America
- * E-mail:
| | - Pamela Hair
- ReAlta Life Sciences, Norfolk, VA, United States of America
| | - Kenji Cunnion
- ReAlta Life Sciences, Norfolk, VA, United States of America
- Department of Pediatrics, Children’s Hospital of The King’s Daughters, Norfolk, VA, United States of America
- Eastern Virginia Medical School, Norfolk, VA, United States of America
| | - Neel Krishna
- ReAlta Life Sciences, Norfolk, VA, United States of America
- Department of Pediatrics, Children’s Hospital of The King’s Daughters, Norfolk, VA, United States of America
- Eastern Virginia Medical School, Norfolk, VA, United States of America
| | - Thomas Bass
- Department of Pediatrics, Children’s Hospital of The King’s Daughters, Norfolk, VA, United States of America
- Eastern Virginia Medical School, Norfolk, VA, United States of America
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13
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Iqbal N, Younus J, Malik M, Fatima B, Imran A, Maqbool S, Irfan Waheed KA, Haque K. The Neuroprotective Efficacy of Postnatal Magnesium Sulfate in Term or Near-Term Infants With Moderate-to-Severe Birth Asphyxia. Cureus 2021; 13:e16826. [PMID: 34513419 PMCID: PMC8407416 DOI: 10.7759/cureus.16826] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/02/2021] [Indexed: 11/05/2022] Open
Abstract
Background In Pakistan, the neonatal mortality rate is 41 per 1,000 live births and birth asphyxia is one of the leading causes of neonatal mortality and morbidity. The goal of this study was to determine whether postnatal magnesium sulfate therapy can improve short- and long-term neurological outcomes in term or near-term neonates with moderate-to-severe birth asphyxia. Methodology This prospective double-blind randomized controlled trial was conducted in the Neonatology Department of the Children's Hospital & The Institute of Child Health, Lahore. A total of 62 neonates (31 in each group) were randomized to receive either three doses of magnesium sulfate infusion at 250 mg/kg per dose, 24 hours apart (treatment group), or three doses of injection 10% distilled water infusion at 3 mL/kg, 24 hours apart (placebo group). Both groups received similar supportive care. The neurodevelopmental assessment was done at six months of age using the ShaMaq Developmental Inventory. Results Demographic data such as gestational age, mean weight, age at presentation, gender, hypoxic-ischemic encephalopathy grade, mode of delivery, and the presence of seizures at presentation were comparable between both groups. In the magnesium sulfate group, statistically significant results were seen in terms of early seizure control (p = 0.001), early initiation of feed (p = 0.002), and shorter duration of hospital stay (p = 0.003). Moreover, the magnesium sulfate group had lower mortality compared to the control group, though it was not statistically significant (p = 0.390). There was no significant difference in terms of cranial ultrasound findings between the two groups (p = 0.783) at the time of discharge. Regarding the neurodevelopmental delay, there was no significant difference between the magnesium sulfate and control groups (p = 0.535). Conclusions Postnatal magnesium sulfate treatment improves short-term neurologic outcomes at discharge in term or near-term neonates with moderate-to-severe perinatal asphyxia. However, no difference was noted in the neurodevelopmental outcome at six months.
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Affiliation(s)
- Nadeem Iqbal
- Neonatology, The Children's Hospital & The Institute of Child Health, Lahore, PAK
| | - Javaria Younus
- Neonatology, The Children's Hospital & The Institute of Child Health, Lahore, PAK
| | - Muneeba Malik
- Developmental and Behavioural Pediatrics, The Children's Hospital & The Institute of Child Health, Lahore, PAK
| | - Bushra Fatima
- Neonatology, The Children's Hospital & The Institute of Child Health, Lahore, PAK
| | - Ahmed Imran
- Pediatric Radiology, The Children's Hospital & The Institute of Child Health, Lahore, PAK
| | - Shazia Maqbool
- Developmental and Behavioural Pediatrics, The Children's Hospital & The Institute of Child Health, Lahore, PAK
| | | | - Khalid Haque
- Neonatology, The Children's Hospital & The Institute of Child Health, Lahore, PAK
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14
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Nagy E, Self J, Williams C, Vollmer B. Disorders of vision in neonatal hypoxic-ischaemic encephalopathy: a systematic review. Arch Dis Child Fetal Neonatal Ed 2021; 106:357-362. [PMID: 33246969 DOI: 10.1136/archdischild-2020-318998] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 10/15/2020] [Accepted: 10/30/2020] [Indexed: 11/04/2022]
Abstract
OBJECTIVE Neonatal hypoxic-ischaemic encephalopathy (HIE) following perinatal asphyxia in term infants is associated with neonatal mortality and a high risk of neurodevelopmental impairment later in life. Visual disorders are an accepted complication of HIE and the association has been cited in the literature many times. This review aims to study the evidence for this association and assess the quality of the data on which this is based. DESIGN A systematic literature review was conducted and 922 citations were assessed using standard methods outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. RESULTS The results demonstrate that the majority of studies have reported on various neurodevelopmental outcomes but rarely specifically vision. Based on limited currently available data, extracted from a number of small studies, an association of neonatal HIE with visual impairments seems to exist but detail is lacking. Notably, in the existing studies, there is a striking lack of consistency in the methods used to diagnose HIE and, similarly, a wide variation in the methods employed to measure visual function. CONCLUSIONS To explore the observed association further in terms of prognosis and the effects of HIE treatments on visual outcomes, future studies will need to address the issues of standardised diagnostic criteria, severity grading and robust, age-appropriate visual assessment.
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Affiliation(s)
- Eva Nagy
- Faculty of Medicine, University of Southampton, Southampton, UK .,Neonatal and Paediatric Neurology, Southampton General Hospital, Southampton, UK
| | - Jay Self
- Southampton Eye Unit, Southampton General Hospital, Southampton, UK
| | - Cathy Williams
- Ophthalmology, Bristol Eye Hospital, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.,Bristol Medical School, University of Bristol, Bristol, UK
| | - Brigitte Vollmer
- Paediatric Neurosciences, University of Southampton/University Hospitals Southampton, Southampton, UK
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15
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Tann CJ, Kohli-Lynch M, Nalugya R, Sadoo S, Martin K, Lassman R, Nanyunja C, Musoke M, Sewagaba M, Nampijja M, Seeley J, Webb EL. Surviving and Thriving: Early Intervention for Neonatal Survivors With Developmental Disability in Uganda. INFANTS AND YOUNG CHILDREN 2021; 34:17-32. [PMID: 33790497 PMCID: PMC7983078 DOI: 10.1097/iyc.0000000000000182] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Global attention on early child development, inclusive of those with disability, has the potential to translate into improved action for the millions of children with developmental disability living in low- and middle-income countries. Nurturing care is crucial for all children, arguably even more so for children with developmental disability. A high proportion of survivors of neonatal conditions such as prematurity and neonatal encephalopathy are affected by early child developmental disability. The first thousand days of life is a critical period for neuroplasticity and an important window of opportunity for interventions, which maximize developmental potential and other outcomes. Since 2010, our group has been examining predictors, outcomes, and experiences of neonatal encephalopathy in Uganda. The need for an early child intervention program to maximize participation and improve the quality of life for children and families became apparent. In response, the "ABAaNA early intervention program," (now re-branding as 'Baby Ubuntu') a group participatory early intervention program for young children with developmental disability and their families, was developed and piloted. Piloting has provided early evidence of feasibility, acceptability, and impact and a feasibility trial is underway. Future research aims to develop programmatic capacity across diverse settings and evaluate its impact at scale.
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Affiliation(s)
- Cally J. Tann
- Department of Infectious Disease Epidemiology, School of Hygiene and Tropical Medicine, London, England (Dr Tann and Dr Sadoo); Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda (Drs Tann, Nampijja, and Professor Seeley and Mss Nalugya, Nanyunja, Musoke, and Sewagaba); Institute for Women's Health, University College London, London, England (Dr Tann and Dr Martin); Centre for Academic Child Health, University of Bristol, Bristol, England (Dr Kohli-Lynch); Alder Hey Children's NHS Foundation Trust, Liverpool, England (Dr Martin); Kyaninga Child Development Centre, Fort Portal, Uganda (Ms Lassman); African Population and Health Research Center, Nairobi, Kenya (Dr Nampijja); Department of Global Health & Development, London School of Hygiene & Tropical Medicine, London, England (Dr Seeley); and MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, England (Dr Webb)
| | - Maya Kohli-Lynch
- Department of Infectious Disease Epidemiology, School of Hygiene and Tropical Medicine, London, England (Dr Tann and Dr Sadoo); Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda (Drs Tann, Nampijja, and Professor Seeley and Mss Nalugya, Nanyunja, Musoke, and Sewagaba); Institute for Women's Health, University College London, London, England (Dr Tann and Dr Martin); Centre for Academic Child Health, University of Bristol, Bristol, England (Dr Kohli-Lynch); Alder Hey Children's NHS Foundation Trust, Liverpool, England (Dr Martin); Kyaninga Child Development Centre, Fort Portal, Uganda (Ms Lassman); African Population and Health Research Center, Nairobi, Kenya (Dr Nampijja); Department of Global Health & Development, London School of Hygiene & Tropical Medicine, London, England (Dr Seeley); and MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, England (Dr Webb)
| | - Ruth Nalugya
- Department of Infectious Disease Epidemiology, School of Hygiene and Tropical Medicine, London, England (Dr Tann and Dr Sadoo); Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda (Drs Tann, Nampijja, and Professor Seeley and Mss Nalugya, Nanyunja, Musoke, and Sewagaba); Institute for Women's Health, University College London, London, England (Dr Tann and Dr Martin); Centre for Academic Child Health, University of Bristol, Bristol, England (Dr Kohli-Lynch); Alder Hey Children's NHS Foundation Trust, Liverpool, England (Dr Martin); Kyaninga Child Development Centre, Fort Portal, Uganda (Ms Lassman); African Population and Health Research Center, Nairobi, Kenya (Dr Nampijja); Department of Global Health & Development, London School of Hygiene & Tropical Medicine, London, England (Dr Seeley); and MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, England (Dr Webb)
| | - Samantha Sadoo
- Department of Infectious Disease Epidemiology, School of Hygiene and Tropical Medicine, London, England (Dr Tann and Dr Sadoo); Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda (Drs Tann, Nampijja, and Professor Seeley and Mss Nalugya, Nanyunja, Musoke, and Sewagaba); Institute for Women's Health, University College London, London, England (Dr Tann and Dr Martin); Centre for Academic Child Health, University of Bristol, Bristol, England (Dr Kohli-Lynch); Alder Hey Children's NHS Foundation Trust, Liverpool, England (Dr Martin); Kyaninga Child Development Centre, Fort Portal, Uganda (Ms Lassman); African Population and Health Research Center, Nairobi, Kenya (Dr Nampijja); Department of Global Health & Development, London School of Hygiene & Tropical Medicine, London, England (Dr Seeley); and MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, England (Dr Webb)
| | - Karen Martin
- Department of Infectious Disease Epidemiology, School of Hygiene and Tropical Medicine, London, England (Dr Tann and Dr Sadoo); Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda (Drs Tann, Nampijja, and Professor Seeley and Mss Nalugya, Nanyunja, Musoke, and Sewagaba); Institute for Women's Health, University College London, London, England (Dr Tann and Dr Martin); Centre for Academic Child Health, University of Bristol, Bristol, England (Dr Kohli-Lynch); Alder Hey Children's NHS Foundation Trust, Liverpool, England (Dr Martin); Kyaninga Child Development Centre, Fort Portal, Uganda (Ms Lassman); African Population and Health Research Center, Nairobi, Kenya (Dr Nampijja); Department of Global Health & Development, London School of Hygiene & Tropical Medicine, London, England (Dr Seeley); and MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, England (Dr Webb)
| | - Rachel Lassman
- Department of Infectious Disease Epidemiology, School of Hygiene and Tropical Medicine, London, England (Dr Tann and Dr Sadoo); Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda (Drs Tann, Nampijja, and Professor Seeley and Mss Nalugya, Nanyunja, Musoke, and Sewagaba); Institute for Women's Health, University College London, London, England (Dr Tann and Dr Martin); Centre for Academic Child Health, University of Bristol, Bristol, England (Dr Kohli-Lynch); Alder Hey Children's NHS Foundation Trust, Liverpool, England (Dr Martin); Kyaninga Child Development Centre, Fort Portal, Uganda (Ms Lassman); African Population and Health Research Center, Nairobi, Kenya (Dr Nampijja); Department of Global Health & Development, London School of Hygiene & Tropical Medicine, London, England (Dr Seeley); and MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, England (Dr Webb)
| | - Carol Nanyunja
- Department of Infectious Disease Epidemiology, School of Hygiene and Tropical Medicine, London, England (Dr Tann and Dr Sadoo); Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda (Drs Tann, Nampijja, and Professor Seeley and Mss Nalugya, Nanyunja, Musoke, and Sewagaba); Institute for Women's Health, University College London, London, England (Dr Tann and Dr Martin); Centre for Academic Child Health, University of Bristol, Bristol, England (Dr Kohli-Lynch); Alder Hey Children's NHS Foundation Trust, Liverpool, England (Dr Martin); Kyaninga Child Development Centre, Fort Portal, Uganda (Ms Lassman); African Population and Health Research Center, Nairobi, Kenya (Dr Nampijja); Department of Global Health & Development, London School of Hygiene & Tropical Medicine, London, England (Dr Seeley); and MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, England (Dr Webb)
| | - Margaret Musoke
- Department of Infectious Disease Epidemiology, School of Hygiene and Tropical Medicine, London, England (Dr Tann and Dr Sadoo); Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda (Drs Tann, Nampijja, and Professor Seeley and Mss Nalugya, Nanyunja, Musoke, and Sewagaba); Institute for Women's Health, University College London, London, England (Dr Tann and Dr Martin); Centre for Academic Child Health, University of Bristol, Bristol, England (Dr Kohli-Lynch); Alder Hey Children's NHS Foundation Trust, Liverpool, England (Dr Martin); Kyaninga Child Development Centre, Fort Portal, Uganda (Ms Lassman); African Population and Health Research Center, Nairobi, Kenya (Dr Nampijja); Department of Global Health & Development, London School of Hygiene & Tropical Medicine, London, England (Dr Seeley); and MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, England (Dr Webb)
| | - Margaret Sewagaba
- Department of Infectious Disease Epidemiology, School of Hygiene and Tropical Medicine, London, England (Dr Tann and Dr Sadoo); Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda (Drs Tann, Nampijja, and Professor Seeley and Mss Nalugya, Nanyunja, Musoke, and Sewagaba); Institute for Women's Health, University College London, London, England (Dr Tann and Dr Martin); Centre for Academic Child Health, University of Bristol, Bristol, England (Dr Kohli-Lynch); Alder Hey Children's NHS Foundation Trust, Liverpool, England (Dr Martin); Kyaninga Child Development Centre, Fort Portal, Uganda (Ms Lassman); African Population and Health Research Center, Nairobi, Kenya (Dr Nampijja); Department of Global Health & Development, London School of Hygiene & Tropical Medicine, London, England (Dr Seeley); and MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, England (Dr Webb)
| | - Margaret Nampijja
- Department of Infectious Disease Epidemiology, School of Hygiene and Tropical Medicine, London, England (Dr Tann and Dr Sadoo); Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda (Drs Tann, Nampijja, and Professor Seeley and Mss Nalugya, Nanyunja, Musoke, and Sewagaba); Institute for Women's Health, University College London, London, England (Dr Tann and Dr Martin); Centre for Academic Child Health, University of Bristol, Bristol, England (Dr Kohli-Lynch); Alder Hey Children's NHS Foundation Trust, Liverpool, England (Dr Martin); Kyaninga Child Development Centre, Fort Portal, Uganda (Ms Lassman); African Population and Health Research Center, Nairobi, Kenya (Dr Nampijja); Department of Global Health & Development, London School of Hygiene & Tropical Medicine, London, England (Dr Seeley); and MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, England (Dr Webb)
| | - Janet Seeley
- Department of Infectious Disease Epidemiology, School of Hygiene and Tropical Medicine, London, England (Dr Tann and Dr Sadoo); Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda (Drs Tann, Nampijja, and Professor Seeley and Mss Nalugya, Nanyunja, Musoke, and Sewagaba); Institute for Women's Health, University College London, London, England (Dr Tann and Dr Martin); Centre for Academic Child Health, University of Bristol, Bristol, England (Dr Kohli-Lynch); Alder Hey Children's NHS Foundation Trust, Liverpool, England (Dr Martin); Kyaninga Child Development Centre, Fort Portal, Uganda (Ms Lassman); African Population and Health Research Center, Nairobi, Kenya (Dr Nampijja); Department of Global Health & Development, London School of Hygiene & Tropical Medicine, London, England (Dr Seeley); and MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, England (Dr Webb)
| | - Emily L. Webb
- Department of Infectious Disease Epidemiology, School of Hygiene and Tropical Medicine, London, England (Dr Tann and Dr Sadoo); Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda (Drs Tann, Nampijja, and Professor Seeley and Mss Nalugya, Nanyunja, Musoke, and Sewagaba); Institute for Women's Health, University College London, London, England (Dr Tann and Dr Martin); Centre for Academic Child Health, University of Bristol, Bristol, England (Dr Kohli-Lynch); Alder Hey Children's NHS Foundation Trust, Liverpool, England (Dr Martin); Kyaninga Child Development Centre, Fort Portal, Uganda (Ms Lassman); African Population and Health Research Center, Nairobi, Kenya (Dr Nampijja); Department of Global Health & Development, London School of Hygiene & Tropical Medicine, London, England (Dr Seeley); and MRC Tropical Epidemiology Group, London School of Hygiene & Tropical Medicine, London, England (Dr Webb)
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16
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Seo YM, Im SA, Sung IK, Youn YA. The prognosis of brain magnetic resonance imaging injury pattern for outcomes of hypothermia-treated infants. Medicine (Baltimore) 2020; 99:e23176. [PMID: 33235078 PMCID: PMC7710188 DOI: 10.1097/md.0000000000023176] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022] Open
Abstract
Magnetic resonance imaging (MRI) can be a tool that allows the observation of structural injury patterns after cooling. The aim of this study was to determine the early pattern of brain injury in the MRIs of infants with hypoxic ischemic encephalopathy (HIE) after cooling and to search for any clinical factors related to abnormal MRI findings.The study retrospectively recruited 118 infants who were treated with therapeutic hypothermia (TH) between 2013 and 2016.Forty-three patients had normal brain MRI, and 75 had abnormal brain MRI findings. The TH-treated infants with abnormal brain MRI readings showed significantly more clinical seizures and the use of additional antiepileptic drugs (AEDs) than the normal MRI group. As a long-term outcome, more lesions in the basal ganglia and thalamus, posterior limb of internal capsule, or severe white matter lesions were associated with abnormal neurodevelopmental outcomes at 18 to 24 months of age.A higher frequency of clinical seizures and AED use were related to abnormal brain injury on MRI. A significant risk for poor long-term outcomes was found in the abnormal brain MRI group.
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Affiliation(s)
| | - Soo-Ah Im
- Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
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17
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Ezenwa B, Ezeaka C, Fajolu I, Ogbenna A, Olowoyeye O, Nwaiwu O, Opoola Z, Olorunfemi G. Impact of Erythropoietin in the management of Hypoxic Ischaemic Encephalopathy in resource-constrained settings: protocol for a randomized control trial. BMC Neurol 2020; 20:171. [PMID: 32366288 PMCID: PMC7199320 DOI: 10.1186/s12883-020-01751-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Accepted: 04/27/2020] [Indexed: 11/11/2022] Open
Abstract
Background Perinatal asphyxia, more appropriately known as hypoxic-ischemic encephalopathy (HIE), is a condition characterized by clinical and laboratory evidence of acute or sub-acute brain injury resulting from systemic hypoxemia and/or reduced cerebral blood flow. HIE is a common and devastating clinical condition in resource-poor countries with poor treatment outcome. This paper describes the protocol for an ongoing study that aims to evaluate the neuroprotective effects of Erythropoietin (EPO) as compared to routine care in the management of moderate to severe HIE among term infants. Methods This study is a double-blind randomized controlled trial that will be conducted in the neonatal wards of the Lagos University Teaching Hospital (LUTH), Lagos, Nigeria, over a two-year period after ethical approvals and consents. One hundred and twenty-eight term newborns (≥ 37 weeks gestation) diagnosed with moderate/ severe HIE at admission will be allocated by randomization to receive either EPO or normal saline. All the participants will be offered standard care according to the unit protocol for HIE. Baseline investigations and close monitoring of the babies are done until discharge. Participants are followed up for 2 years to monitor their outcome (death or neurological development) using standard instruments. Discussion Previous trials had shown that EPO confers neuroprotective benefits and improve neurological and behavioral outcome in infants with HIE both singly or as an adjuvant to therapeutic hypothermia. This study hypothesized that administering EPO to newborns with moderate /severe HIE can positively influence their clinical and neurological outcomes and will provide evidence to either support or disprove the usefulness of Erythropoietin as a sole agent in the treatment of HIE, especially in resource-limited environment with the highest burden of the disease. Trial registration The study has been registered with the Pan African Clinical trials registry on the 2nd of December 2018, with registration number PACTR201812814507775.
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Affiliation(s)
- Beatrice Ezenwa
- Neonatology unit, Department of Paediatrics, College of Medicine University of Lagos, Lagos, Nigeria. .,Department of Paediatrics, Lagos University Teaching Hospital, Lagos, Nigeria.
| | - Chinyere Ezeaka
- Neonatology unit, Department of Paediatrics, College of Medicine University of Lagos, Lagos, Nigeria.,Department of Paediatrics, Lagos University Teaching Hospital, Lagos, Nigeria
| | - Iretiola Fajolu
- Neonatology unit, Department of Paediatrics, College of Medicine University of Lagos, Lagos, Nigeria.,Department of Paediatrics, Lagos University Teaching Hospital, Lagos, Nigeria
| | - Anne Ogbenna
- Department of Haematology & Blood transfusion, College of Medicine University of Lagos, Lagos, Nigeria
| | - Omodele Olowoyeye
- Department of Radiodiagnosis, College of Medicine University of Lagos, Lagos, Nigeria
| | - Obiyo Nwaiwu
- Department of Pharmacology, Therapeutics &Toxicology, College of Medicine University of Lagos, Lagos, Nigeria
| | - Zainab Opoola
- Department of Paediatrics, Lagos University Teaching Hospital, Lagos, Nigeria
| | - Gbenga Olorunfemi
- Division of Epidemiology and Biostatistics, School of Public Health, University of Witwatersrand, Johannesburg, South Africa
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O'Connor A, Seeber C, Harris E, Hamilton D, Sachmann M, Fisher C. Developmental outcomes following prenatal exposure to methamphetamine: A Western Australian perspective. J Paediatr Child Health 2020; 56:372-378. [PMID: 31479558 DOI: 10.1111/jpc.14618] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 08/02/2019] [Accepted: 08/16/2019] [Indexed: 11/28/2022]
Abstract
AIM To describe neurodevelopmental outcomes among a cohort of Western Australian infants exposed to maternal methamphetamine use during pregnancy and to determine whether the Ages and Stages Questionnaire is a reliable screening tool for this population. METHODS Methamphetamine-using women were approached for participation when referred to the state-wide perinatal specialist drug and alcohol service for pregnancy care. Drug use during pregnancy was self-reported in each trimester using a standardised questionnaire. Ages and Stages Questionnaires were completed by infant care givers at 4 and 12 months, and development was formally assessed at 12 months using the Griffiths Mental Development Scales. Griffiths results for term-born infants in our cohort were compared to a Western Australian historical cohort of 443 healthy 1-2-year-olds. RESULTS A total of 112 methamphetamine-using pregnant women participated in the study, who gave birth to 110 live-born infants. Ages and Stages Questionnaires were completed for 89 (81%) and 78 (71%) of the infants at 4 and 12 months, respectively. The Ages and Stages assessment identified 30 infants (33.7%) as having a potential developmental delay at 4 months and 29 infants (38.7%) as having a potential developmental delay at 12 months. Griffiths assessments were performed on 64 (58%) of the infants, with a mean general quotient of 92.7. This was significantly lower in term-born babies compared to the historical cohort (who had a median general quotient of 113.0). There was a weak correlation between 12-month Ages and Stages scores and Griffiths general quotients (r = 0.322) and no correlation between 4-month Ages and Stages Questionnaire scores and later Griffiths results. CONCLUSIONS Infants born to women reporting methamphetamine use during pregnancy are at increased risk of developmental delay and may warrant enhanced developmental follow-up. However, they are a challenging group to follow due to complex psychosocial factors. Ages and Stages Questionnaires at 4 and 12 months were not helpful in screening for infants who had a developmental delay at 12 months.
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Affiliation(s)
- Angela O'Connor
- Women and Newborn Drug and Alcohol Service, King Edward Memorial Hospital, Perth, Western Australia, Australia.,Australian College of Midwifery, Canberra, Australian Capital Territory, Australia
| | - Carly Seeber
- Neonatology Clinical Care Unit, King Edward Memorial Hospital, Perth, Western Australia, Australia
| | - Emma Harris
- Neonatology Clinical Care Unit, King Edward Memorial Hospital, Perth, Western Australia, Australia.,Centre for Newborn Research and Education, University of Western Australia, Perth, Western Australia, Australia
| | - Dale Hamilton
- Department of Obstetrics, King Edward Memorial Hospital, Perth, Western Australia, Australia
| | - Mark Sachmann
- School of Allied Health, University of Western Australia, Perth, Western Australia, Australia
| | - Colleen Fisher
- School of Population and Public Health, University of Western Australia, Perth, Western Australia, Australia
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19
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Mynarek M, Bjellmo S, Lydersen S, Strand KM, Afset JE, Andersen GL, Vik T. Prelabor rupture of membranes and the association with cerebral palsy in term born children: a national registry-based cohort study. BMC Pregnancy Childbirth 2020; 20:67. [PMID: 32005186 PMCID: PMC6995227 DOI: 10.1186/s12884-020-2751-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 01/17/2020] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Guidelines regarding management of prelabor rupture of membranes (PROM) at term vary between immediate induction and expectant management. A long interval between PROM and delivery increases the risk for perinatal infections. Severe perinatal infections are associated with excess risk for cerebral palsy (CP) and perinatal death. We investigated if increasing intervals between PROM and delivery were associated with perinatal death or CP. METHODS Eligible to participate in this population-based cohort-study were term born singletons without congenital malformations born in Norway during 1999-2009. Data was retrieved from the Medical Birth Registry of Norway (MBRN) and the Cerebral Palsy Register of Norway. In line with the registration in the MBRN, intervals between PROM and delivery of more than 24 h was defined as 'prolonged' and intervals between 12 and 24 h as 'intermediate'. Outcomes were stillbirth, death during delivery, neonatal mortality and CP. Logistic regression was used to calculate odds ratio (OR) with 95% confidence intervals (CI) for adverse outcomes in children born after prolonged and intermediate intervals, compared with a reference group comprising all children born less than 12 h after PROM or without PROM. RESULTS Among 559,972 births, 34,759 children were born after intermediate and 30,332 were born after prolonged intervals. There was no association between increasing intervals and death during delivery or in the neonatal period, while the prevalence of stillbirths decreased with increasing intervals. Among children born after intermediate intervals 38 (0.11%) had CP, while among those born after prolonged intervals 46 (0.15%) had CP. Compared with the reference group, the OR for CP was 1.16 (CI; 0.83 to 1.61) after intermediate and 1.61 (CI; 1.19 to 2.18) after prolonged intervals. Adjusting for antenatal factors did not affect these associations. Among children with CP the proportion with diffuse cortical injury and basal ganglia pathology on cerebral MRI, consistent with hypoxic-ischemic injuries, increased with increasing intervals. CONCLUSION Intervals between PROM and delivery of more than 24 h were associated with CP, but not with neonatal mortality or death during delivery. The inverse association with stillbirth is probably due to reverse causality.
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Affiliation(s)
- Maren Mynarek
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Faculty of Medicine and Health Sciences, PO Box 8905, NO-7491, Trondheim, Norway.
| | - Solveig Bjellmo
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Faculty of Medicine and Health Sciences, PO Box 8905, NO-7491, Trondheim, Norway.,Department of Obstetrics and Gynecology, Helse More og Romsdal HF, Alesund, Norway
| | - Stian Lydersen
- Department of Mental Health, Regional Centre for Child and Youth Health and Child Welfare, PB 8905, MTFS, 7491, Trondheim, Norway
| | - Kristin Melheim Strand
- Department of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Jan Egil Afset
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Faculty of Medicine and Health Sciences, PO Box 8905, NO-7491, Trondheim, Norway.,Department of Medical Microbiology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Guro L Andersen
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Faculty of Medicine and Health Sciences, PO Box 8905, NO-7491, Trondheim, Norway.,Vestfold Hospital Trust, The Cerebral Palsy Register of Norway, PB 2168, 3103, Tønsberg, Norway
| | - Torstein Vik
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Faculty of Medicine and Health Sciences, PO Box 8905, NO-7491, Trondheim, Norway
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20
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Tann CJ, Webb EL, Lassman R, Ssekyewa J, Sewegaba M, Musoke M, Burgoine K, Hagmann C, Deane-Bowers E, Norman K, Milln J, Kurinczuk JJ, Elliott AM, Martinez-Biarge M, Nakakeeto M, Robertson NJ, Cowan FM. Early Childhood Outcomes After Neonatal Encephalopathy in Uganda: A Cohort Study. EClinicalMedicine 2018; 6:26-35. [PMID: 30740596 PMCID: PMC6358042 DOI: 10.1016/j.eclinm.2018.12.001] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2018] [Revised: 11/12/2018] [Accepted: 12/03/2018] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Neonatal encephalopathy (NE) is a leading cause of global child mortality. Survivor outcomes in low-resource settings are poorly described. We present early childhood outcomes after NE in Uganda. METHODS We conducted a prospective cohort study of term-born infants with NE (n = 210) and a comparison group of term non-encephalopathic (non-NE) infants (n = 409), assessing neurodevelopmental impairment (NDI) and growth at 27-30 months. Relationships between early clinical parameters and later outcomes were summarised using risk ratios (RR). FINDINGS Mortality by 27-30 months was 40·3% after NE and 3·8% in non-NE infants. Impairment-free survival occurred in 41·6% after NE and 98·7% of non-NE infants. Amongst NE survivors, 29·3% had NDI including 19·0% with cerebral palsy (CP), commonly bilateral spastic CP (64%); 10·3% had global developmental delay (GDD) without CP. CP was frequently associated with childhood seizures, vision and hearing loss and mortality. NDI was commonly associated with undernutrition (44·1% Z-score < - 2) and microcephaly (32·4% Z-score < - 2). Motor function scores were reduced in NE survivors without CP/GDD compared to non-NE infants (median difference - 8·2 (95% confidence interval; - 13·0, - 3·7)). Neonatal clinical seizures (RR 4.1(2.0-8.7)), abnormalities on cranial ultrasound, (RR 7.0(3.8-16.3), nasogastric feeding at discharge (RR 3·6(2·1-6·1)), and small head circumference at one year (Z-score < - 2, RR 4·9(2·9-5·6)) increased the risk of NDI. INTERPRETATION In this sub-Saharan African population, death and neurodevelopmental disability after NE were common. CP was associated with sensorineural impairment, malnutrition, seizures and high mortality by 2 years. Early clinical parameters predicted impairment outcomes.
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Affiliation(s)
- Cally J Tann
- Department of Infectious Disease Epidemiology, School of Hygiene and Tropical Medicine, London, UK
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- Institute for Women's Health, University College London, London, UK
| | - Emily L Webb
- MRC Tropical Epidemiology Group, London School of Hygiene and Tropical Medicine, London, UK
| | | | - Julius Ssekyewa
- Mulago National Referral and Teaching Hospital, Kampala, Uganda
| | - Margaret Sewegaba
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - Margaret Musoke
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - Kathy Burgoine
- Department of Paediatrics and Child Health, Mbale Regional Referral Hospital, and Mbale Clinical Research Institute, Mbale, Uganda
| | - Cornelia Hagmann
- University Children Hospital of Zurich and Children's Research Center, Zurich, Switzerland
| | | | - Kerstin Norman
- Uganda Maternal and Newborn Hub, Knowledge for Change, UK
| | - Jack Milln
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
| | - Jennifer J Kurinczuk
- National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Alison M Elliott
- Medical Research Council/Uganda Virus Research Institute and London School of Hygiene and Tropical Medicine Uganda Research Unit, Entebbe, Uganda
- Clinical Research Department, Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, UK
| | | | | | | | - Frances M Cowan
- Department of Paediatrics, Imperial College London, London, UK
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21
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Shepherd E, Salam RA, Middleton P, Han S, Makrides M, McIntyre S, Badawi N, Crowther CA, Cochrane Neonatal Group. Neonatal interventions for preventing cerebral palsy: an overview of Cochrane Systematic Reviews. Cochrane Database Syst Rev 2018; 6:CD012409. [PMID: 29926474 PMCID: PMC6513209 DOI: 10.1002/14651858.cd012409.pub2] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
BACKGROUND Cerebral palsy is an umbrella term that encompasses disorders of movement and posture attributed to non-progressive disturbances occurring in the developing foetal or infant brain. As there are diverse risk factors and aetiologies, no one strategy will prevent cerebral palsy. Therefore, there is a need to systematically consider all potentially relevant interventions for prevention. OBJECTIVES PrimaryTo summarise the evidence from Cochrane Systematic Reviews regarding effects of neonatal interventions for preventing cerebral palsy (reducing cerebral palsy risk).SecondaryTo summarise the evidence from Cochrane Systematic Reviews regarding effects of neonatal interventions that may increase cerebral palsy risk. METHODS We searched the Cochrane Database of Systematic Reviews (27 November 2016) for reviews of neonatal interventions reporting on cerebral palsy. Two review authors assessed reviews for inclusion, extracted data, and assessed review quality (using AMSTAR and ROBIS) and quality of the evidence (using the GRADE approach). Reviews were organised by topic; findings were summarised in text and were tabulated. Interventions were categorised as effective (high-quality evidence of effectiveness); possibly effective (moderate-quality evidence of effectiveness); ineffective (high-quality evidence of harm); probably ineffective (moderate-quality evidence of harm or lack of effectiveness); and no conclusions possible (low- to very low-quality evidence). MAIN RESULTS Forty-three Cochrane Reviews were included. A further 102 reviews pre-specified the outcome cerebral palsy, but none of the included randomised controlled trials (RCTs) reported this outcome. Included reviews were generally of high quality and had low risk of bias, as determined by AMSTAR and ROBIS. These reviews involved 454 RCTs; data for cerebral palsy were available from 96 (21%) RCTs involving 15,885 children. Review authors considered interventions for neonates with perinatal asphyxia or with evidence of neonatal encephalopathy (3); interventions for neonates born preterm and/or at low or very low birthweight (33); and interventions for other specific groups of 'at risk' neonates (7). Quality of evidence (GRADE) ranged from very low to high.Interventions for neonates with perinatal asphyxia or with evidence of neonatal encephalopathyEffective interventions: high-quality evidence of effectivenessResearchers found a reduction in cerebral palsy following therapeutic hypothermia versus standard care for newborns with hypoxic ischaemic encephalopathy (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.54 to 0.82; seven trials; 881 children).No conclusions possible: very low-quality evidenceOne review observed no clear differences in cerebral palsy following therapeutic hypothermia versus standard care.Interventions for neonates born preterm and/or at low or very low birthweightPossibly effective interventions: moderate-quality evidence of effectivenessResearchers found a reduction in cerebral palsy with prophylactic methylxanthines (caffeine) versus placebo for endotracheal extubation in preterm infants (RR 0.54, 95% CI 0.32 to 0.92; one trial; 644 children).Probably ineffective interventions: moderate-quality evidence of harmResearchers reported an increase in cerebral palsy (RR 1.45, 95% CI 1.06 to 1.98; 12 trials; 1452 children) and cerebral palsy in assessed survivors (RR 1.50, 95% CI 1.13 to 2.00; 12 trials; 959 children) following early (at less than eight days of age) postnatal corticosteroids versus placebo or no treatment for preventing chronic lung disease in preterm infants.Probably ineffective interventions: moderate-quality evidence of lack of effectivenessTrial results showed no clear differences in cerebral palsy following ethamsylate versus placebo for prevention of morbidity and mortality in preterm or very low birthweight infants (RR 1.13, 95% CI 0.64 to 2.00; three trials, 532 children); volume expansion versus no treatment (RR 0.76, 95% CI 0.48 to 1.20; one trial; 604 children); gelatin versus fresh frozen plasma (RR 0.94, 95% CI 0.52 to 1.69; one trial, 399 children) for prevention of morbidity and mortality in very preterm infants; prophylactic indomethacin versus placebo for preventing mortality and morbidity in preterm infants (RR 1.04, 95% CI 0.77 to 1.40; four trials; 1372 children); synthetic surfactant versus placebo for respiratory distress syndrome in preterm infants (RR 0.76, 95% CI 0.55 to 1.05; five trials; 1557 children); or prophylactic phototherapy versus standard care (starting phototherapy when serum bilirubin reached a pre-specified level) for preventing jaundice in preterm or low birthweight infants (RR 0.96, 95% CI 0.50 to 1.85; two trials; 756 children).No conclusions possible: low- to very low-quality evidenceNo clear differences in cerebral palsy were observed with interventions assessed in 21 reviews.Interventions for other specific groups of 'at risk' neonatesNo conclusions possible: low- to very low-quality evidenceReview authors observed no clear differences in cerebral palsy with interventions assessed in five reviews. AUTHORS' CONCLUSIONS This overview summarises evidence from Cochrane Systematic Reviews regarding effects of neonatal interventions on cerebral palsy, and can be used by researchers, funding bodies, policy makers, clinicians, and consumers to aid decision-making and evidence translation. To formally assess other benefits and/or harms of included interventions, including impact on risk factors for cerebral palsy, review of the included Reviews is recommended.Therapeutic hypothermia versus standard care for newborns with hypoxic ischaemic encephalopathy can prevent cerebral palsy, and prophylactic methylxanthines (caffeine) versus placebo for endotracheal extubation in preterm infants may reduce cerebral palsy risk. Early (at less than eight days of age) postnatal corticosteroids versus placebo or no treatment for preventing chronic lung disease in preterm infants may increase cerebral palsy risk.Cerebral palsy is rarely identified at birth, has diverse risk factors and aetiologies, and is diagnosed in approximately one in 500 children. To date, only a small proportion of Cochrane Systematic Reviews assessing neonatal interventions have been able to report on this outcome. There is an urgent need for long-term follow-up of RCTs of such interventions addressing risk factors for cerebral palsy (through strategies such as data linkage with registries) and for consideration of the use of relatively new interim assessments (including the General Movements Assessment). Such RCTs must be rigorous in their design and must aim for consistency in cerebral palsy outcome measurement and reporting to facilitate pooling of data and thus to maximise research efforts focused on prevention.
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Affiliation(s)
- Emily Shepherd
- The University of AdelaideARCH: Australian Research Centre for Health of Women and Babies, Robinson Research Institute, Discipline of Obstetrics and GynaecologyAdelaideSouth AustraliaAustralia5006
| | - Rehana A Salam
- Aga Khan University HospitalDivision of Women and Child HealthStadium RoadPO Box 3500KarachiSindPakistan74800
| | - Philippa Middleton
- Healthy Mothers, Babies and Children, South Australian Health and Medical Research InstituteWomen's and Children's Hospital72 King William RoadAdelaideSouth AustraliaAustralia5006
| | - Shanshan Han
- The University of AdelaideARCH: Australian Research Centre for Health of Women and Babies, Robinson Research Institute, Discipline of Obstetrics and GynaecologyAdelaideSouth AustraliaAustralia5006
| | - Maria Makrides
- Healthy Mothers, Babies and Children, South Australian Health and Medical Research InstituteWomen's and Children's Hospital72 King William RoadAdelaideSouth AustraliaAustralia5006
| | - Sarah McIntyre
- University of SydneyResearch Institute, Cerebral Palsy Alliance187 Allambie Road, Allambie HeightsSydneyAustralia2100
| | - Nadia Badawi
- University of SydneyResearch Institute, Cerebral Palsy Alliance187 Allambie Road, Allambie HeightsSydneyAustralia2100
- The Children's Hospital at WestmeadGrace Centre for Newborn CareSydneyAustralia
| | - Caroline A Crowther
- The University of AucklandLiggins InstitutePrivate Bag 9201985 Park RoadAucklandNew Zealand
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22
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Boskabadi H, Moradi A, Zakerihamidi M. Interleukins in diagnosis of perinatal asphyxia: A systematic review. Int J Reprod Biomed 2018; 17. [PMID: 31435616 PMCID: PMC6653496 DOI: 10.18502/ijrm.v17i5.4598] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Revised: 03/25/2018] [Accepted: 09/12/2018] [Indexed: 11/24/2022] Open
Abstract
Background Biochemical markers including interleukins (ILs) has been proposed for early diagnosis of asphyxia. Objective This study has aimed to systematically review the significance of IL measurements in the diagnosis of perinatal asphyxia. Materials and Methods PubMed, Cochrane Library, Web of Science, Embase, and Scopus databases before 2017 were searched for the following keywords: asphyxia, neonatal, interleukin, and diagnosis. A total of 13 out of 300 searched papers were finally selected for evaluation. Interleukins under study were IL6 and interleukin 1 β (IL-1 β ). Interleukins had been measured in 10 studies by serum samples, 2 studies by samples of Cerebro Spinal Fluid (CSF), and 1 study by sample of umbilical cord blood. The inclusion criteria were: studies on neonates, with adequate information from the test results and studies using markers other than ILs to detect asphyxia; however, studies with only abstracts available were excluded. Results Research on the issue suggests that IL6 > 41 Pg/dl has the sensitivity of 84.88% and the specificity of 85.43%, whereas IL-1 β > 4.7 Pg/dl has the sensitivity of 78% and specificity of 83% in the diagnosis of neonatal asphyxia. Among diagnostic ILs for neonatal asphyxia, combination of IL6 and IL-1 β had the highest sensitivity, that is, 92.9%. Conclusion IL6 and IL-1 β of serum samples were used in the early diagnosis of perinatal asphyxia and are useful predictors for the outcomes of perinatal asphyxia and its intensity. In addition, simultaneous evaluation of IL-1 β and IL6 can improve the sensitivity of the early diagnosis of perinatal asphyxia.
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Affiliation(s)
- Hassan Boskabadi
- Department of Pediatrics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Moradi
- Orthopedic Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Maryam Zakerihamidi
- Department of Midwifery, Faculty of Medical Sciences, Islamic Azad University, Tonekabon Branch, Tonekabon, Iran
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23
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Youngstrom M, Tita A, Grant J, Szychowski JM, Harper LM. Perinatal Outcomes in Women With a History of Chronic Hypertension but Normal Blood Pressures Before 20 Weeks of Gestation. Obstet Gynecol 2018; 131:827-834. [PMID: 29630010 DOI: 10.1097/aog.0000000000002574] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To compare the perinatal outcomes of normotensive women with those of women with a history of chronic hypertension with normal blood pressures before 20 weeks of gestation, stratifying the latter by whether they were receiving antihypertensive medication. METHODS We conducted a retrospective cohort study of all singletons with a history of chronic hypertension from 2000 to 2014. Exclusions were blood pressure greater than 140/90 mm Hg before 20 weeks of gestation, fetal anomalies, major medical problems other than hypertension, and diabetes. For the same time period, a randomly selected group without a diagnosis of chronic hypertension was chosen using the same exclusion criteria. Outcomes were compared among women without chronic hypertension, women with chronic hypertension on no antihypertensive medication but with blood pressures less than 140/90 mm Hg before 20 weeks of gestation, and women with chronic hypertension on antihypertensive medication with blood pressures less than 140/90 mm Hg before 20 weeks of gestation. The primary outcome was a perinatal composite of stillbirth, neonatal death, respiratory support at birth, arterial cord pH less than 7, 5-minute Apgar score 3 or less, and seizures. Secondary outcomes assessed were preterm birth before 37 and 34 weeks of gestation, small for gestational age, and preeclampsia. RESULTS Of 830 women with chronic hypertension and blood pressures less than 140/90 mm Hg before 20 weeks of gestation, 212 (26%) were not taking antihypertensive medication and 618 (74%) were. These groups were compared with 476 women without chronic hypertension. Women with hypertension were more likely to be older and have baseline renal disease and diabetes compared with women in the no hypertension group. The perinatal composite was more common in both hypertensive groups: no antihypertensive medication (9.9%) and antihypertensive medication (14.6%) compared with women in the control group (2.9%) (adjusted odds ratio [OR] 2.9, 95% CI 1.21-6.85 no antihypertensive medications compared with no chronic hypertension; adjusted OR 5.0, 95% CI 2.38-10.54 antihypertensive medications vs no chronic hypertension). The risk of early preterm birth, small for gestational age, and preeclampsia was not significantly increased in women with chronic hypertension and no antihypertensive medications compared with women without chronic hypertension. CONCLUSION Despite normal baseline blood pressures without medications before 20 weeks of gestation, women with chronic hypertension are at an increased risk of adverse perinatal outcomes compared with women without.
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Affiliation(s)
- Mallory Youngstrom
- Department of Gynecology and Obstetrics, Emory University, Atlanta, Georgia; and the Department of Obstetrics and Gynecology, the University of Alabama at Birmingham, Birmingham, Alabama
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24
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Frey HA, Liu X, Lynch CD, Musindi W, Samuels P, Rood KM, Thung SF, Bakk JM, Cheng W, Landon MB. An evaluation of fetal heart rate characteristics associated with neonatal encephalopathy: a case-control study. BJOG 2018; 125:1480-1487. [DOI: 10.1111/1471-0528.15222] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/07/2018] [Indexed: 11/30/2022]
Affiliation(s)
- HA Frey
- Department of Obstetrics and Gynecology; The Ohio State University College of Medicine; Columbus OH USA
| | - X Liu
- Department of Obstetrics; International Peace Maternity & Child Health Hospital; Shanghai Jiao Tong University; Shanghai China
| | - CD Lynch
- Department of Obstetrics and Gynecology; The Ohio State University College of Medicine; Columbus OH USA
| | - W Musindi
- Department of Obstetrics and Gynecology; The Ohio State University College of Medicine; Columbus OH USA
| | - P Samuels
- Department of Obstetrics and Gynecology; The Ohio State University College of Medicine; Columbus OH USA
| | - KM Rood
- Department of Obstetrics and Gynecology; The Ohio State University College of Medicine; Columbus OH USA
| | - SF Thung
- Department of Obstetrics and Gynecology; The Ohio State University College of Medicine; Columbus OH USA
| | - JM Bakk
- Department of Obstetrics and Gynecology; The Ohio State University College of Medicine; Columbus OH USA
| | - W Cheng
- Department of Obstetrics; International Peace Maternity & Child Health Hospital; Shanghai Jiao Tong University; Shanghai China
| | - MB Landon
- Department of Obstetrics and Gynecology; The Ohio State University College of Medicine; Columbus OH USA
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25
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Procianoy RS, Corso AL, Longo MG, Vedolin L, Silveira RC. Therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy: magnetic resonance imaging findings and neurological outcomes in a Brazilian cohort. J Matern Fetal Neonatal Med 2018; 32:2727-2734. [DOI: 10.1080/14767058.2018.1448773] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Affiliation(s)
- Renato S. Procianoy
- Newborn Section, Department of Pediatrics, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Andrea Lucia Corso
- Newborn Section, Department of Pediatrics, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
| | - Maria Gabriela Longo
- Radiology Section, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
- Hospital Moinhos de Vento, Porto Alegre, Brazil
| | | | - Rita C. Silveira
- Newborn Section, Department of Pediatrics, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
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26
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Sánchez Fernández I, Morales-Quezada JL, Law S, Kim P. Prognostic Value of Brain Magnetic Resonance Imaging in Neonatal Hypoxic-Ischemic Encephalopathy: A Meta-analysis. J Child Neurol 2017; 32:1065-1073. [PMID: 28925315 DOI: 10.1177/0883073817726681] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
OBJECTIVE To quantify the prognostic value of neonatal brain magnetic resonance imaging (MRI) in neonatal hypoxic-ischemic encephalopathy. METHODS Meta-analysis of studies with ≥35-week neonates with hypoxic-ischemic encephalopathy who underwent brain MRI within age 4 weeks and had neurodevelopmental follow-up for at least 12 months. RESULTS An abnormal neonatal brain MRI was more frequent among patients with unfavorable neurodevelopmental outcome: odds ratio = 18.2 (95% confidence interval: 9.4-34.9), P <.0001. The prognostic value of neonatal brain MRI in moderate hypoxic-ischemic encephalopathy had an odds ratio of 17.7 (95% confidence interval: 5.3-59.3) and in severe hypoxic-ischemic encephalopathy, the odds ratio was 125.0 (95% confidence interval: 2.0-7917.1). Therapeutic hypothermia did not change the prognostic value of neonatal brain MRI (odds ratio for hypothermia, 14.0 [95% confidence interval: 3.1-63.6], vs no hypothermia, 18.1 [95% confidence interval: 10.0-33.1], P = .7525). CONCLUSION Neonatal brain MRI provides prognostic information on outcome beyond early infancy in hypoxic-ischemic encephalopathy and therapeutic hypothermia does not change its prognostic value.
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Affiliation(s)
- Iván Sánchez Fernández
- 1 Division of Epilepsy and Clinical Neurophysiology, Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.,2 Department of Child Neurology, Hospital Sant Joan de Déu, Universidad de Barcelona, Barcelona, Spain
| | - J Leon Morales-Quezada
- 3 Spaulding Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA
| | - Samuel Law
- 4 Department of Psychiatry, St. Michael's Hospital, University of Toronto, Toronto, Canada
| | - Paggie Kim
- 5 Division of Neuroradiology and Pediatric Radiology, Department of Radiology, Loma Linda University School of Medicine, Loma Linda, CA, USA
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Maoulainine FMR, Elbaz M, Elfaiq S, Boufrioua G, Elalouani FZ, Barkane M, El Idrissi Slitine N. Therapeutic Hypothermia in Asphyxiated Neonates: Experience from Neonatal Intensive Care Unit of University Hospital of Marrakech. Int J Pediatr 2017; 2017:3674140. [PMID: 28567061 PMCID: PMC5439062 DOI: 10.1155/2017/3674140] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2016] [Revised: 03/02/2017] [Accepted: 03/16/2017] [Indexed: 11/18/2022] Open
Abstract
INTRODUCTION Therapeutic hypothermia (TH) is now recommended for the treatment neonates with hypoxic-ischemic encephalopathy (HIE). This treatment protocol is applied in our department since June 2012. The aim of this study is to report the first experience with head cooling in asphyxiated neonates in Morocco. PATIENTS AND METHODS Prospective study of newborns admitted for HIE from July 18, 2012, to May 15, 2014, in Neonatal Intensive Care Unit (NICU) of Mohamed VI University Hospital. The results were studied by comparing a newborn group who received hypothermia to a control group. RESULTS Seventy-two cases of neonates with perinatal asphyxia were admitted in the unit. According to inclusion criteria thirty-eight cases were eligible for the study. Only 19 cases have received the hypothermia protocol for different reason; the arrival beyond six hours of life was the main cause accounting for 41%. Complications of asphyxia were comparable in both groups with greater pulmonary hypertension recorded in the control group. The long-term follow-up of protocol group was normal in almost half of cases. CONCLUSION Our first experience with the controlled TH supports its beneficial effect in newborns with HIE. This treatment must be available in all the centers involved in the neonatal care in Morocco.
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Affiliation(s)
- F. M. R. Maoulainine
- Neonatal Intensive Care Unit, Mohamed VI University Hospital, Marrakech, Morocco
- Research Unit of Childhood Health and Development, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech, Morocco
| | - M. Elbaz
- Neonatal Intensive Care Unit, Mohamed VI University Hospital, Marrakech, Morocco
| | - S. Elfaiq
- Neonatal Intensive Care Unit, Mohamed VI University Hospital, Marrakech, Morocco
| | - G. Boufrioua
- Neonatal Intensive Care Unit, Mohamed VI University Hospital, Marrakech, Morocco
| | - F. Z. Elalouani
- Neonatal Intensive Care Unit, Mohamed VI University Hospital, Marrakech, Morocco
| | - M. Barkane
- Neonatal Intensive Care Unit, Mohamed VI University Hospital, Marrakech, Morocco
| | - Nadia El Idrissi Slitine
- Neonatal Intensive Care Unit, Mohamed VI University Hospital, Marrakech, Morocco
- Research Unit of Childhood Health and Development, Faculty of Medicine and Pharmacy, Cadi Ayyad University, Marrakech, Morocco
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Shepherd E, Middleton P, Makrides M, McIntyre S, Badawi N, Crowther CA. Neonatal interventions for preventing cerebral palsy: an overview of Cochrane systematic reviews. Hippokratia 2016. [DOI: 10.1002/14651858.cd012409] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Emily Shepherd
- The University of Adelaide; ARCH: Australian Research Centre for Health of Women and Babies, Robinson Research Institute, Discipline of Obstetrics and Gynaecology; Adelaide South Australia Australia 5006
| | - Philippa Middleton
- Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute; Women's and Children's Hospital 72 King William Road Adelaide South Australia Australia 5006
| | - Maria Makrides
- Healthy Mothers, Babies and Children, South Australian Health and Medical Research Institute; Women's and Children's Hospital 72 King William Road Adelaide South Australia Australia 5006
| | - Sarah McIntyre
- University of Sydney; Research Institute, Cerebral Palsy Alliance; 187 Allambie Road, Allambie Heights Sydney Australia 2100
| | - Nadia Badawi
- University of Sydney; Research Institute, Cerebral Palsy Alliance; 187 Allambie Road, Allambie Heights Sydney Australia 2100
- The Children's Hospital at Westmead; Grace Centre for Newborn Care; Sydney Australia
| | - Caroline A Crowther
- The University of Auckland; Liggins Institute; Private Bag 92019 85 Park Road Auckland New Zealand
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Early MRI in neonatal hypoxic-ischaemic encephalopathy treated with hypothermia: Prognostic role at 2-year follow-up. Eur J Radiol 2016; 85:1366-74. [DOI: 10.1016/j.ejrad.2016.05.005] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2016] [Revised: 05/05/2016] [Accepted: 05/10/2016] [Indexed: 11/23/2022]
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Birca A, Lortie A, Birca V, Decarie JC, Veilleux A, Gallagher A, Dehaes M, Lodygensky GA, Carmant L. Rewarming affects EEG background in term newborns with hypoxic–ischemic encephalopathy undergoing therapeutic hypothermia. Clin Neurophysiol 2016; 127:2087-94. [DOI: 10.1016/j.clinph.2015.12.013] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2015] [Revised: 12/09/2015] [Accepted: 12/12/2015] [Indexed: 11/15/2022]
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Ahearne CE, Boylan GB, Murray DM. Short and long term prognosis in perinatal asphyxia: An update. World J Clin Pediatr 2016; 5:67-74. [PMID: 26862504 PMCID: PMC4737695 DOI: 10.5409/wjcp.v5.i1.67] [Citation(s) in RCA: 161] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Revised: 11/18/2015] [Accepted: 12/18/2015] [Indexed: 02/06/2023] Open
Abstract
Interruption of blood flow and gas exchange to the fetus in the perinatal period, known as perinatal asphyxia, can, if significant, trigger a cascade of neuronal injury, leading on to neonatal encephalopathy (NE) and resultant long-term damage. While the majority of infants who are exposed to perinatal hypoxia-ischaemia will recover quickly and go on to have a completely normal survival, a proportion will suffer from an evolving clinical encephalopathy termed hypoxic-ischaemic encephalopathy (HIE) or NE if the diagnosis is unclear. Resultant complications of HIE/NE are wide-ranging and may affect the motor, sensory, cognitive and behavioural outcome of the child. The advent of therapeutic hypothermia as a neuroprotective treatment for those with moderate and severe encephalopathy has improved prognosis. Outcome prediction in these infants has changed, but is more important than ever, as hypothermia is a time sensitive intervention, with a very narrow therapeutic window. To identify those who will benefit from current and emerging neuroprotective therapies we must be able to establish the severity of their injury soon after birth. Currently available indicators such as blood biochemistry, clinical examination and electrophysiology are limited. Emerging biological and physiological markers have the potential to improve our ability to select those infants who will benefit most from intervention. Biomarkers identified from work in proteomics, metabolomics and transcriptomics as well as physiological markers such as heart rate variability, EEG analysis and radiological imaging when combined with neuroprotective measures have the potential to improve outcome in HIE/NE. The aim of this review is to give an overview of the literature in regards to short and long-term outcome following perinatal asphyxia, and to discuss the prediction of this outcome in the early hours after birth when intervention is most crucial; looking at both currently available tools and introducing novel markers.
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Is fetal manipulation during shoulder dystocia management associated with severe maternal and neonatal morbidities? Arch Gynecol Obstet 2016; 294:505-9. [DOI: 10.1007/s00404-016-4013-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Accepted: 01/05/2016] [Indexed: 10/22/2022]
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McKenna MC, Scafidi S, Robertson CL. Metabolic Alterations in Developing Brain After Injury: Knowns and Unknowns. Neurochem Res 2015; 40:2527-43. [PMID: 26148530 PMCID: PMC4961252 DOI: 10.1007/s11064-015-1600-7] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2015] [Revised: 04/10/2015] [Accepted: 05/02/2015] [Indexed: 12/21/2022]
Abstract
Brain development is a highly orchestrated complex process. The developing brain utilizes many substrates including glucose, ketone bodies, lactate, fatty acids and amino acids for energy, cell division and the biosynthesis of nucleotides, proteins and lipids. Metabolism is crucial to provide energy for all cellular processes required for brain development and function including ATP formation, synaptogenesis, synthesis, release and uptake of neurotransmitters, maintaining ionic gradients and redox status, and myelination. The rapidly growing population of infants and children with neurodevelopmental and cognitive impairments and life-long disability resulting from developmental brain injury is a significant public health concern. Brain injury in infants and children can have devastating effects because the injury is superimposed on the high metabolic demands of the developing brain. Acute injury in the pediatric brain can derail, halt or lead to dysregulation of the complex and highly regulated normal developmental processes. This paper provides a brief review of metabolism in developing brain and alterations found clinically and in animal models of developmental brain injury. The metabolic changes observed in three major categories of injury that can result in life-long cognitive and neurological disabilities, including neonatal hypoxia-ischemia, pediatric traumatic brain injury, and brain injury secondary to prematurity are reviewed.
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Affiliation(s)
- Mary C McKenna
- Department of Pediatrics and Program in Neuroscience, University of Maryland School of Medicine, 655 W. Baltimore St., Room 13-019, Baltimore, MD, 21201, USA.
| | - Susanna Scafidi
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Courtney L Robertson
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
- Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Lopez E, de Courtivron B, Saliba E. [Neonatal complications related to shoulder dystocia]. ACTA ACUST UNITED AC 2015; 44:1294-302. [PMID: 26527013 DOI: 10.1016/j.jgyn.2015.09.049] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2015] [Accepted: 09/18/2015] [Indexed: 11/18/2022]
Abstract
OBJECTIVE To describe neonatal complications related to shoulder dystocia. METHODS This systematic evidence review is based on PubMed search, Cochrane library and experts' recommendations. RESULTS The risks of brachial plexus birth injury, clavicle and humeral fracture, perinatal asphyxia, hypoxic-ischemic encephalopathy and perinatal mortality are increased after shoulder dystocia. The medical team should be able to provide neonatal resuscitation in the delivery room in case of perinatal asphyxia following shoulder dystocia, according to national and international guidelines. The initial clinical examination should search for complications such as brachial plexus birth injury or clavicle fracture. CONCLUSION The risk of perinatal complications is increased in newborn after shoulder dystocia. The medical team should be able to manage these complications.
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Affiliation(s)
- E Lopez
- Réanimation néonatale, hôpital Clocheville, CHU de Tours, 49, boulevard Béranger, 37044 Tours cedex 9, France.
| | - B de Courtivron
- Chirurgie orthopédique pédiatrique, hôpital Clocheville, CHU de Tours, 49, boulevard Béranger, 37044 Tours cedex 9, France
| | - E Saliba
- Réanimation néonatale, hôpital Clocheville, CHU de Tours, 49, boulevard Béranger, 37044 Tours cedex 9, France
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McKenna MC, Scafidi S, Robertson CL. Metabolic Alterations in Developing Brain After Injury: Knowns and Unknowns. Neurochem Res 2015. [PMID: 26148530 DOI: 10.1007/s11064‐015‐1600‐7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Brain development is a highly orchestrated complex process. The developing brain utilizes many substrates including glucose, ketone bodies, lactate, fatty acids and amino acids for energy, cell division and the biosynthesis of nucleotides, proteins and lipids. Metabolism is crucial to provide energy for all cellular processes required for brain development and function including ATP formation, synaptogenesis, synthesis, release and uptake of neurotransmitters, maintaining ionic gradients and redox status, and myelination. The rapidly growing population of infants and children with neurodevelopmental and cognitive impairments and life-long disability resulting from developmental brain injury is a significant public health concern. Brain injury in infants and children can have devastating effects because the injury is superimposed on the high metabolic demands of the developing brain. Acute injury in the pediatric brain can derail, halt or lead to dysregulation of the complex and highly regulated normal developmental processes. This paper provides a brief review of metabolism in developing brain and alterations found clinically and in animal models of developmental brain injury. The metabolic changes observed in three major categories of injury that can result in life-long cognitive and neurological disabilities, including neonatal hypoxia-ischemia, pediatric traumatic brain injury, and brain injury secondary to prematurity are reviewed.
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Affiliation(s)
- Mary C McKenna
- Department of Pediatrics and Program in Neuroscience, University of Maryland School of Medicine, 655 W. Baltimore St., Room 13-019, Baltimore, MD, 21201, USA.
| | - Susanna Scafidi
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Courtney L Robertson
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.,Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Pappas A, Shankaran S, McDonald SA, Vohr BR, Hintz SR, Ehrenkranz RA, Tyson JE, Yolton K, Das A, Bara R, Hammond J, Higgins RD, for the Hypothermia Extended Follow-up Subcommittee of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Cognitive outcomes after neonatal encephalopathy. Pediatrics 2015; 135:e624-34. [PMID: 25713280 PMCID: PMC4338321 DOI: 10.1542/peds.2014-1566] [Citation(s) in RCA: 116] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
OBJECTIVES To describe the spectrum of cognitive outcomes of children with and without cerebral palsy (CP) after neonatal encephalopathy, evaluate the prognostic value of early developmental testing and report on school services and additional therapies. METHODS The participants of this study are the school-aged survivors of the National Institute of Child Health and Human Development Neonatal Research Network randomized controlled trial of whole-body hypothermia. Children underwent neurologic examinations and neurodevelopmental and cognitive testing with the Bayley Scales of Infant Development-II at 18 to 22 months and the Wechsler intelligence scales and the Neuropsychological Assessment-Developmental Neuropsychological Assessment at 6 to 7 years. Parents were interviewed about functional status and receipt of school and support services. We explored predictors of cognitive outcome by using multiple regression models. RESULTS Subnormal IQ scores were identified in more than a quarter of the children: 96% of survivors with CP had an IQ <70, 9% of children without CP had an IQ <70, and 31% had an IQ of 70 to 84. Children with a mental developmental index <70 at 18 months had, on average, an adjusted IQ at 6 to 7 years that was 42 points lower than that of those with a mental developmental index >84 (95% confidence interval, -49.3 to -35.0; P < .001). Twenty percent of children with normal IQ and 28% of those with IQ scores of 70 to 84 received special educational support services or were held back ≥1 grade level. CONCLUSIONS Cognitive impairment remains an important concern for all children with neonatal encephalopathy.
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Affiliation(s)
- Athina Pappas
- Department of Pediatrics, Wayne State University, Detroit, Michigan;
| | - Seetha Shankaran
- Department of Pediatrics, Wayne State University, Detroit, Michigan
| | - Scott A. McDonald
- Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, North Carolina
| | - Betty R. Vohr
- Department of Pediatrics, Women & Infant’s Hospital, Brown University, Providence, Rhode Island
| | - Susan R. Hintz
- Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California
| | | | - Jon E. Tyson
- Department of Pediatrics, University of Texas Medical School at Houston, Houston, Texas
| | - Kimberly Yolton
- Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
| | - Abhik Das
- Social, Statistical and Environmental Sciences Unit, RTI International, Rockville, Maryland; and
| | - Rebecca Bara
- Department of Pediatrics, Wayne State University, Detroit, Michigan
| | - Jane Hammond
- Social, Statistical and Environmental Sciences Unit, RTI International, Rockville, Maryland; and
| | - Rosemary D. Higgins
- Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland
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Jadas V, Brasseur-Daudruy M, Chollat C, Pellerin L, Devaux AM, Marret S. [The contribution of the clinical examination, electroencephalogram, and brain MRI in assessing the prognosis in term newborns with neonatal encephalopathy. A cohort of 30 newborns before the introduction of treatment with hypothermia]. Arch Pediatr 2013; 21:125-33. [PMID: 24374026 DOI: 10.1016/j.arcped.2013.11.007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2012] [Revised: 09/16/2013] [Accepted: 11/19/2013] [Indexed: 10/25/2022]
Abstract
OBJECTIVES Perinatal asphyxia complicated by hypoxic ischemic brain injury remains a source of neurological lesions. A major aim of neonatologists is to evaluate the severity of neonatal encephalopathy (NE) and to evaluate prognosis. The purpose of this study was to determine the contribution of brain MRI compared to electroencephalogram (EEG) and clinical data in assessing patients' prognosis. MATERIALS AND METHODS Thirty newborns from the pediatric resuscitation unit at Rouen university hospital were enrolled in a retrospective study between January 2006 and December 2008, prior to introduction of hypothermia treatment. All 30 newborns had at least two anamnestic criteria of perinatal asphyxia, one brain MRI in the first 5 days of life and another after 7 days of life as well as an early EEG in the first 2 days of life. Then, the infants were seen in consultation to assess neurodevelopment. RESULTS This study showed a relation between NE stage and prognosis. During stage 1, prognosis was good, whereas stage 3 was associated with poor neurodevelopment outcome. Normal clinical examination before the 8th day of life was a good prognostic factor in this study. There was a relationship between severity of EEG after the 5th day of life and poor outcome. During stage 2, EEG patterns varied in severity, and brain MRI provided a better prognosis. Lesions of the basal ganglia and a decreased or absent signal of the posterior limb of the internal capsule were poor prognostic factors during brain MRI. These lesions were underestimated during standard MRI in the first days of life but were visible with diffusion sequences. Cognitive impairment affected 40% of surviving children, justifying extended pediatric follow-up. CONCLUSION This study confirms the usefulness of brain MRI as a diagnostic tool in hypoxic ischemic encephalopathy in association with clinical data and EEG tracings.
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Affiliation(s)
- V Jadas
- Service de pédiatrie néonatale et réanimation, centre d'éducation fonctionnelle de l'enfant, CHU de Rouen, 1, rue de Germont, 76031 Rouen cedex, France; Équipe région-Inserm EA 4309 Neovasc handicap neurologique périnatal, IRIB, faculté de médecine et pharmacie, université de Rouen, 76000 Rouen, France.
| | - M Brasseur-Daudruy
- Service de radiologie pédiatrique, CHU de Rouen, 1, rue de Germont, 76031 Rouen cedex, France
| | - C Chollat
- Service de pédiatrie néonatale et réanimation, centre d'éducation fonctionnelle de l'enfant, CHU de Rouen, 1, rue de Germont, 76031 Rouen cedex, France; Équipe région-Inserm EA 4309 Neovasc handicap neurologique périnatal, IRIB, faculté de médecine et pharmacie, université de Rouen, 76000 Rouen, France
| | - L Pellerin
- Service de pédiatrie générale, CHU de Caen, 14200 Caen, France
| | - A M Devaux
- Service de pédiatrie néonatale et réanimation, centre d'éducation fonctionnelle de l'enfant, CHU de Rouen, 1, rue de Germont, 76031 Rouen cedex, France; Équipe région-Inserm EA 4309 Neovasc handicap neurologique périnatal, IRIB, faculté de médecine et pharmacie, université de Rouen, 76000 Rouen, France
| | - S Marret
- Service de pédiatrie néonatale et réanimation, centre d'éducation fonctionnelle de l'enfant, CHU de Rouen, 1, rue de Germont, 76031 Rouen cedex, France; Équipe région-Inserm EA 4309 Neovasc handicap neurologique périnatal, IRIB, faculté de médecine et pharmacie, université de Rouen, 76000 Rouen, France
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Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr Res 2013; 74 Suppl 1:50-72. [PMID: 24366463 PMCID: PMC3873711 DOI: 10.1038/pr.2013.206] [Citation(s) in RCA: 451] [Impact Index Per Article: 37.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Intrapartum hypoxic events ("birth asphyxia") may result in stillbirth, neonatal or postneonatal mortality, and impairment. Systematic morbidity estimates for the burden of impairment outcomes are currently limited. Neonatal encephalopathy (NE) following an intrapartum hypoxic event is a strong predictor of long-term impairment. METHODS Linear regression modeling was conducted on data identified through systematic reviews to estimate NE incidence and time trends for 184 countries. Meta-analyses were undertaken to estimate the risk of NE by sex of the newborn, neonatal case fatality rate, and impairment risk. A compartmental model estimated postneonatal survivors of NE, depending on access to care, and then the proportion of survivors with impairment. Separate modeling for the Global Burden of Disease 2010 (GBD2010) study estimated disability adjusted life years (DALYs), years of life with disability (YLDs), and years of life lost (YLLs) attributed to intrapartum-related events. RESULTS In 2010, 1.15 million babies (uncertainty range: 0.89-1.60 million; 8.5 cases per 1,000 live births) were estimated to have developed NE associated with intrapartum events, with 96% born in low- and middle-income countries, as compared with 1.60 million in 1990 (11.7 cases per 1,000 live births). An estimated 287,000 (181,000-440,000) neonates with NE died in 2010; 233,000 (163,000-342,000) survived with moderate or severe neurodevelopmental impairment; and 181,000 (82,000-319,000) had mild impairment. In GBD2010, intrapartum-related conditions comprised 50.2 million DALYs (2.4% of total) and 6.1 million YLDs. CONCLUSION Intrapartum-related conditions are a large global burden, mostly due to high mortality in low-income countries. Universal coverage of obstetric care and neonatal resuscitation would prevent most of these deaths and disabilities. Rates of impairment are highest in middle-income countries where neonatal intensive care was more recently introduced, but quality may be poor. In settings without neonatal intensive care, the impairment rate is low due to high mortality, which is relevant for the scale-up of basic neonatal resuscitation.
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Abstract
OBJECTIVE Hypothermia improves clinical outcomes and brain magnetic resonance imaging (MRI) findings in infants with hypoxic-ischemic encephalopathy. We hypothesized that clinical status following hypothermia predicts brain MRI abnormalities, and helps determine which infants need an early MRI evaluation before discharge. The objective of this study was to determine whether the clinical evaluation 1 week after completion of 72 h of hypothermia treatment predicts the presence of brain MRI abnormalities related to hypoxia-ischemia. STUDY DESIGN The medical records of 83 consecutively cooled infants who underwent brain MRI were reviewed. Clinical evaluation by day 10 of life consisted of assessment of oral feeding ability, spontaneous activity, need for mechanical ventilation and a history of clinical seizures. Logistic regression analysis was performed using all four covariates, with an abnormal MRI as the primary outcome. Brain MRI with lesions in both the basal nuclei and the cortex was considered to be severely abnormal. RESULT MRI was abnormal in 46 (55%) infants. Univariate analysis identified all of the criteria as being significantly associated with an abnormal MRI. On multivariate analysis, only feeding difficulty (P<0.001, OR 9.5, 95% confidence interval (CI) 3 to 29.8) and a history of clinical seizures (P<0.001, OR 12, 95% CI 3 to 46.5) were significantly associated with an abnormal MRI. The areas under the receiver operating characteristic curve for feeding ability and seizure activity combined (0.86, 95% CI 0.77 to 0.94) indicated good accuracy with respect to the primary outcome. The negative predictive values of feeding difficulty and seizure activity for a severely abnormal MRI were 91% and 96%, respectively. CONCLUSION Infants who do not have a history of clinical seizures and who attained full oral feeding by 1 week after hypothermia are unlikely to have an abnormal brain MRI. This simple assessment provides significant prognostic information that can be useful in parental counseling, and may allow selective use of pre-discharge MRI.
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Kyriakopoulos P, Oskoui M, Dagenais L, Shevell MI. Term neonatal encephalopathy antecedent cerebral palsy: a retrospective population-based study. Eur J Paediatr Neurol 2013. [PMID: 23195237 DOI: 10.1016/j.ejpn.2012.11.001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
OBJECTIVE To compare the clinical profile of term-born cerebral palsy children with or without antecedent moderate to severe neonatal encephalopathy. We hypothesized that antecedent neonatal encephalopathy is associated with a spastic quadriparesis cerebral palsy clinical profile, a higher severity of functional motor impairment, and a greater number of associated comorbidities. METHODS Using the Quebec Cerebral Palsy Registry, neurologic subtype, Gross Motor Function Classification System stratification, and comorbidities were compared in children with cerebral palsy with and without antecedent neonatal encephalopathy. Differences between groups were evaluated using chi square analysis for categorical variables and student t test for continuous variables. RESULTS We identified 132 children with cerebral palsy born full term over a 4 year-interval (1999-2002 inclusive) within the Quebec Cerebral Palsy Registry, of which 44 (33%) had an antecedent neonatal encephalopathy. Spastic quadriplegia subtype of cerebral palsy and Gross Motor Function Classification System Level III-V (non-independent ambulation) were significantly associated with antecedent neonatal encephalopathy. The mean number of comorbidities experienced was not different in the two groups. Of five documented comorbidities, only severe communication difficulties were found to be associated (p < 0.05) with antecedent neonatal encephalopathy. CONCLUSION A pattern of increased neuromotor impairment, functional gross motor severity and possible communication difficulties was found in the 33% of children with cerebral palsy born at term and with a history of neonatal encephalopathy.
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Affiliation(s)
- Paulina Kyriakopoulos
- Division of Pediatric Neurology, Montreal Children's Hospital-McGill University Health Center, Montreal, Quebec, Canada
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Hypothermie thérapeutique contrôlée pour asphyxie périnatale : intérêt de l’électroencéphalogramme d’amplitude pour évaluer l’indication. Arch Pediatr 2013; 20:181-5. [DOI: 10.1016/j.arcped.2012.11.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2012] [Revised: 05/14/2012] [Accepted: 11/05/2012] [Indexed: 11/22/2022]
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Dynamic Changes of Cerebral-Specific Proteins in Full-Term Newborns with Hypoxic–Ischemic Encephalopathy. Cell Biochem Biophys 2012. [DOI: 10.1007/s12013-012-9478-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Potential of diffusion tensor MR imaging in the assessment of cognitive impairments in children with periventricular leukomalacia born preterm. Eur J Radiol 2012; 82:158-64. [PMID: 23084875 DOI: 10.1016/j.ejrad.2012.06.032] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2012] [Revised: 06/07/2012] [Accepted: 06/11/2012] [Indexed: 11/21/2022]
Abstract
PURPOSE To investigate MR diffusion tensor imaging (DTI) and fiber tractography (FT) in the assessment of altered major white matter fibers correlated with cognitive functions in preterm infants with periventricular leukomalacia (PVL), to explore the neural foundation for PVL children's cognitive impairments. MATERIALS AND METHODS Forty six preterm infants (16 ± 4.7 months) suffered from PVL and 16 age-matched normal controls were recruited. Developmental quotient (DQ) was recorded to evaluate PVL children's cognitive functions. According to the DQ scores, patients were divided into three groups: mild, moderate and severe cognitive impairment groups. DTI scan was performed. Fractional anisotropy (FA) values of major white matter fibers were measured and their correlation with cognitive levels was evaluated. RESULTS Compared with the control group, the PVL group showed a significant mean FA reduction in bilateral corticospinal tract (CST), anterior/posterior limb of internal capsule (ICAL/ICPL), arcuate fasciculus (AF), corona radiate (CR), superior longitudinal fasciculus (SLF), splenium of corpus callosum (SCC) (p<0.05) and bilateral posterior thalamic radiation (PTR) (p<0.01). The FA values of left CST, bilateral AF, anterior cingulum (ACG), SLF, ICAL, ICPL, PTR, CR, genu of corpus callosum (GCC), SCC and middle cerebellar peduncle showed significant negative correlations with the cognitive levels. CONCLUSIONS DTI can provide more information for understanding the pathophysiology of cognitive impairment in preterm infants with PVL.
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Bharadwaj SK, Bhat BV. Therapeutic hypothermia using gel packs for term neonates with hypoxic ischaemic encephalopathy in resource-limited settings: a randomized controlled trial. J Trop Pediatr 2012; 58:382-8. [PMID: 22396230 DOI: 10.1093/tropej/fms005] [Citation(s) in RCA: 55] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
OBJECTIVE To evaluate the efficacy of therapeutic hypothermia (TH) using gel packs in reducing mortality and morbidity in term neonates with HIE and study the associated problems with TH. METHODS Hypoxic ischaemic encephalopathy babies were randomized into TH and control group. Babies in TH group were cooled for first 72 h of birth using cloth covered cooling gel packs to maintain target rectal temperature of 33-34°C. Infants were followed up to 6 months and were assessed using Baroda Developmental Screening Test. RESULTS There were no significant differences in baseline parameters. TH group showed significant reduction in the combined rate of death or developmental delay at 6 months of age by 21% (8.1% in the TH group vs. 29% in the control, RR 0.28, 95% CI: 0.11-0.70; p = 0.003). CONCLUSIONS TH using gel packs reduces the risk of death or developmental delay at 6 months of age in infants with HIE.
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Affiliation(s)
- Shruthi K Bharadwaj
- Department of Paediatrics, Division of Neonatology, JIPMER, Puducherry, 605 006, India.
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Khurshid F, Lee KS, McNamara PJ, Whyte H, Mak W. Lessons learned during implementation of therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy in a regional transport program in Ontario. Paediatr Child Health 2012; 16:153-6. [PMID: 22379379 DOI: 10.1093/pch/16.3.153] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/18/2010] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Therapeutic hypothermia (TH) is the first intervention to consistently show improved neurological outcomes in neonates with hypoxic ischemic encephalopathy (HIE). Since the recent introduction of TH for HIE in many centres, reviews of practices during the implementation of TH in Canada have not been published. OBJECTIVE To determine if eligible neonates are being offered TH and to identify any barriers to the effective implementation of TH. METHODS A retrospective review of neonates referred to a regional tertiary centre at a gestational age of 35 weeks or more with HIE was conducted. RESULTS Among 41 neonates referred, 29 (71%) were eligible for TH; among eligible patients, five were moribund and excluded, and TH was initiated in 16 (67%) of the remaining 24. Reasons for not cooling in eight eligible patients included a delay in referral (n=5, median age at referral was 14 h) and a failure to recognize the severity of HIE (n=3). Among cooled patients, median times were the following: 116 min for age at referral; 80 min for time from referral to transport team arrival; and 358 min for age at initiation of cooling. Seven (44%) patients had cooling initiated after 6 h of age. CONCLUSION A significant proportion of eligible patients were not offered TH, and in many cooled patients, initiation of cooling was delayed beyond the recommended 6 h. For eligible patients to benefit from TH, it is imperative that all birthing centres be made aware that TH is now widely available as an important treatment option, but also that TH is a time-sensitive therapy requiring rapid identification and referral. In the region studied, for eligible patients, referring hospitals should initiate passive cooling before arrival of the transport team. Referring hospitals should be prepared to provide early, yet safe initiation of passive cooling by having the appropriate equipment, and having staff trained in the use and monitoring of rectal temperatures.
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Yang ZJ, Carter EL, Kibler KK, Kwansa H, Crafa DA, Martin LJ, Roman RJ, Harder DR, Koehler RC. Attenuation of neonatal ischemic brain damage using a 20-HETE synthesis inhibitor. J Neurochem 2012; 121:168-79. [PMID: 22251169 PMCID: PMC3303996 DOI: 10.1111/j.1471-4159.2012.07666.x] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
20-Hydroxyeicosatetraenoic acid (20-HETE) is a cytochrome P450 metabolite of arachidonic acid that that contributes to infarct size following focal cerebral ischemia. However, little is known about the role of 20-HETE in global cerebral ischemia or neonatal hypoxia-ischemia (H-I). The present study examined the effects of blockade of the synthesis of 20-HETE with N-hydroxy-N'-(4-n-butyl-2-methylphenyl) formamidine (HET0016) in neonatal piglets after H-I to determine if it protects highly vulnerable striatal neurons. Administration of HET0016 after H-I improved early neurological recovery and protected neurons in putamen after 4 days of recovery. HET0016 had no significant effect on cerebral blood flow. cytochrome P450 4A immunoreactivity was detected in putamen neurons, and direct infusion of 20-HETE in the putamen increased phosphorylation of Na(+), K(+) -ATPase and NMDA receptor NR1 subunit selectively at protein kinase C-sensitive sites but not at protein kinase A-sensitive sites. HET0016 selectively inhibited the H-I induced phosphorylation at these same sites at 3 h of recovery and improved Na(+), K(+) -ATPase activity. At 3 h, HET0016 also suppressed H-I induced extracellular signal-regulated kinase 1/2 activation and protein markers of nitrosative and oxidative stress. Thus, 20-HETE can exert direct effects on key proteins involved in neuronal excitotoxicity in vivo and contributes to neurodegeneration after global cerebral ischemia in immature brain.
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Affiliation(s)
- Zeng-Jin Yang
- Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
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Abstract
OBJECTIVE To estimate the modalities of management of post-term neonates. METHODS This study is based on PubMed search, Cochrane library and HAS recommendations. RESULTS Medical team should be able to provide neonatal resuscitation in delivery room in case of meconium-stained fluid or perinatal asphyxia according to the international guidelines ILCOR 2010. The glycaemia of the post-term newborn with macrosomia should be evaluated. The initial clinical examination should search complications such as shoulder dystocia or clavicular fracture. Full blood count should be performed in symptomatic newborn post-term. Developmental assessment should be performed in post-term newborn in case of associated pathology. CONCLUSIONS The risk of perinatal complications is increased in newborn post-term in delivery room and during hospitalization. Medical team should be able to manage these complications.
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Affiliation(s)
- E Lopez
- Service de médecine néonatale de Port-Royal, groupe hospitalier Cochin-Broca, Hôtel-Dieu, AP-HP, 123, boulevard de Port-Royal, 75014 Paris, France.
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Garfinkle J, Shevell MI. Predictors of outcome in term infants with neonatal seizures subsequent to intrapartum asphyxia. J Child Neurol 2011; 26:453-9. [PMID: 21270469 DOI: 10.1177/0883073810382907] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
The objective of this study was to define potential clinical prognostic factors for term infants with neonatal seizures subsequent to intrapartum asphyxia. The authors completed a retrospective analysis of 62 term infants with clinical neonatal seizures subsequent to intrapartum asphyxia. Logistic regression analysis was applied to determine the independent prognostic indicators of an adverse outcome. A total of 23 (37%) infants had a normal outcome, 34 (55%) survived with 1 or more neurodevelopmental impairments (23 cerebral palsy, 28 global developmental delay, 15 epilepsy, with 18 combination of two, and 9 all three), and 5 (8%) died. Six variables were associated with an adverse outcome, but only the presence of meconium aspiration, a low (≤ 3) 1-minute Apgar score, seizure type other than focal clonic, and moderately severely abnormal electroencephalography (EEG) background findings were independently associated with an adverse outcome. Signs of acute distress are predictors of adverse outcome, alongside seizure semiology and moderate to severe EEG background abnormalities.
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Affiliation(s)
- Jarred Garfinkle
- Departments of Neurology/Neurosurgery & Pediatrics, McGill University, and Division of Pediatric Neurology, Montreal Children's Hospital-McGill University Health Center, Montreal, Quebec Canada
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Weis SN, Schunck RVA, Pettenuzzo LF, Krolow R, Matté C, Manfredini V, do Carmo R Peralba M, Vargas CR, Dalmaz C, Wyse ATS, Netto CA. Early biochemical effects after unilateral hypoxia-ischemia in the immature rat brain. Int J Dev Neurosci 2011; 29:115-20. [PMID: 21255637 DOI: 10.1016/j.ijdevneu.2010.12.005] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2010] [Revised: 11/25/2010] [Accepted: 12/26/2010] [Indexed: 11/30/2022] Open
Abstract
Perinatal hypoxia-ischemia (HI) gives rise to inadequate substrate supply to the brain tissue, resulting in damage to neural cells. Previous studies at different time points of development, and with different animal species, suggest that the HI insult causes oxidative damage and changes Na+, K+-ATPase activity, which is known to be very susceptible to free radical-related lipid peroxidation. The aim of the present study was to establish the onset of the oxidative damage response in neonatal Wistar rats subjected to brain HI, evaluating parameters of oxidative stress, namely nitric oxide production, lipoperoxidation by thiobarbituric acid reactive substances (TBA-RS) production and malondialdehyde (MDA) levels, reactive species production by DCFH oxidation, antioxidant enzymatic activities of catalase, glutathione peroxidase, superoxide dismutase as well as Na+, K+-ATPase activity in hippocampus and cerebral cortex. Rat pups were subjected to right common carotid ligation followed by exposure to a hypoxic atmosphere (8% oxygen and 92% nitrogen) for 90 min. Animals were sacrificed by decapitation 0, 1 and 2 h after HI and both hippocampus and cerebral cortex from the right hemisphere (ipsilateral to the carotid occlusion) were dissected out for further experimentation. Results show an early decrease of Na+, K+-ATPase activity (at 0 and 1 h), as well as a late increase in MDA levels (2 h) and superoxide dismutase activity (1 and 2 h after HI) in the hippocampus. There was a late increase in both MDA levels and DCFH oxidation (1 and 2 h) and an increase in superoxide dismutase activity (2 h after HI) in cortex; however Na+, K+-ATPase activity remained unchanged. We suggest that neonatal HI induces oxidative damage to both hippocampus and cortex, in addition to a decrease in Na+, K+-ATPase activity in hippocampus early after the insult. These events might contribute to the later morphological damage in the brain and indicate that it would be essential to pursue neuroprotective strategies, aimed to counteract oxidative stress, as early as possible after the HI insult.
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Affiliation(s)
- Simone N Weis
- Programa de Pós-Graduação em Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Brazil.
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