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Dall'Asta A, Melito C, Valentini B, Capurso M, Baffa MT, Patey O, Thilaganathan B, Ghi T. Foetal Cardiac Function in Early Labour and Intrapartum Outcomes: A Prospective Observational Study. BJOG 2025. [PMID: 40400105 DOI: 10.1111/1471-0528.18224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2025] [Revised: 04/24/2025] [Accepted: 05/06/2025] [Indexed: 05/23/2025]
Abstract
OBJECTIVE To assess foetal myocardial deformation in normo-oxygenated foetuses in early labour and its relationship with intrapartum outcomes. DESIGN Single centre prospective study. SETTING Referral tertiary maternity unit. POPULATION Uncomplicated singleton term pregnancies in early labour. METHODS Two-dimensional (2D) ultrasound clips of the 4-chamber view of the foetal heart were collected in labour and sent to TomTec software for the offline speckle tracking echocardiography analysis. The left (LV) and right ventricular (RV) myocardial (MyoGLS) and endocardial longitudinal (EndoGLS) strain were evaluated. MAIN OUTCOME MEASURES Operative delivery including caesarean or assisted vaginal birth due to suspected intrapartum foetal compromise (IFC) as defined by standard CTG criteria. RESULTS In total, 208 cases were included. Operative delivery due to suspected IFC was recorded in 20 (9.6%) cases and was associated with higher LV ejection fraction (EF) (47.4 + 8.2 vs. 40.9 + 12.9%, p = 0.03) and increased RV MyoGLS (-15.9 + 4.0 vs. -12.5 + 4.3%, p < 0.01) and RV EndoGLS (-17.7 + 4.4 vs. -14.3 + 4.7%, p < 0.01) compared to cases not having operative delivery due to suspected IFC. Maternal age (OR 1.138, 95% CI [1.010-1.281], p = 0.03), baseline foetal heart rate at acquisition (OR 1.068, 95% CI [1.007-1.134], p = 0.03) and RV MyoGLS (OR 0.575, 95% CI [0.366-0.903], p = 0.02) were independently associated with the primary outcome. CONCLUSIONS Increased right ventricular myocardial deformation is associated with operative delivery due to suspected IFC, suggesting an early cardiac response to labour-related hypoxia.
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Affiliation(s)
- Andrea Dall'Asta
- Department of Medicine and Surgery, Obstetrics and Gynecology Unit, University of Parma, Parma, Italy
| | - Chiara Melito
- Department of Medicine and Surgery, Obstetrics and Gynecology Unit, University of Parma, Parma, Italy
| | - Beatrice Valentini
- Department of Medicine and Surgery, Obstetrics and Gynecology Unit, University of Parma, Parma, Italy
| | - Mariagrazia Capurso
- Department of Medicine and Surgery, Obstetrics and Gynecology Unit, University of Parma, Parma, Italy
| | - Maria Teresa Baffa
- Department of Medicine and Surgery, Obstetrics and Gynecology Unit, University of Parma, Parma, Italy
| | - Olga Patey
- Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, University of London, London, UK
- Royal Brompton and Harefield Hospitals, Guy's & St Thomas' NHS Foundation Trust, London, UK
| | - Basky Thilaganathan
- Fetal Medicine Unit, St George's University Hospitals NHS Foundation Trust, University of London, London, UK
- Molecular and Clinical Sciences Research Institute, Vascular Biology Research Center, St George's University of London, London, UK
| | - Tullio Ghi
- Department of Medicine and Surgery, Obstetrics and Gynecology Unit, University of Parma, Parma, Italy
- Department of Women and Child Health, Catholic University of Sacred Heart, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
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Packet B, Van Severen R, Richter J. Vertebroplacental ratio for prediction of perinatal outcome and operative delivery for suspected fetal compromise: prospective observational cohort study. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2025; 65:334-343. [PMID: 39998987 DOI: 10.1002/uog.29189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 01/06/2025] [Accepted: 01/14/2025] [Indexed: 02/27/2025]
Abstract
OBJECTIVE To investigate differences in fetal vertebroplacental ratio (VPR) depending on the occurrence of operative delivery for suspected fetal compromise (ODFC) and composite perinatal outcome (CPO) at delivery. METHODS This was a prospective observational cohort study conducted in the Department of Obstetrics and Gynecology at the University Hospitals of Leuven, Leuven, Belgium, between December 2022 and April 2024. Women with a term (37-42 gestational weeks) singleton pregnancy with an appropriate-for-gestational-age (AGA) fetus were recruited, before cervical dilatation reached 5 cm, for sonographic fetal weight estimation (EFW) and Doppler sonography of the umbilical artery (UA), umbilical vein (UV), middle cerebral artery (MCA) and vertebral artery (VA). The primary outcomes were differences in VPR multiples of the median (MoM) depending on the occurrence of ODFC and CPO at delivery (based on UA cord blood pH and base excess, 1-min and 5-min Apgar score, and neonatal intensive care unit admission). We explored the technical feasibility of fetal Doppler sonography in this setting and differences in Doppler findings from individual fetal vessels (UA, UV blood flow (UVF), MCA, VA) and related parameters (UVF/EFW and cerebroplacental ratio (CPR)). We also investigated whether adding individual sonographic variables to baseline clinical prediction models could improve discriminatory power (using the area under the receiver-operating-characteristics curve (AUC)) and predictive accuracy (using the Brier score) for both outcomes. RESULTS A total of 161 women were recruited. The mean ± SD maternal age was 32.2 ± 3.8 years and approximately half (53.4%) of the women were nulliparous. Most (88.2%) women had labor induced. The mean ± SD gestational age at delivery was 39.3 ± 1.0 weeks and the mean ± SD ultrasound-to-delivery interval was 10.4 ± 2.75 h. An adverse CPO occurred in 13.3% of cases and ODFC occurred in 17.4%. No difference in mean VPR MoM was observed between cases with normal vs adverse CPO (1.04 ± 0.26 vs 1.17 ± 0.25; P = 0.09), or between cases which underwent ODFC vs those which did not (1.06 ± 0.29 vs 1.06 ± 0.26; P = 0.97). Likewise, no differences in other Doppler variables (UA pulsatility index (PI) MoM, MCA-PI MoM, VA-PI MoM, CPR MoM) were observed for both outcomes, except for significantly higher UVF rates in the adverse CPO group (both absolute (P = 0.02) and corrected for EFW (P = 0.048)). For both outcomes, adding VPR MoM or any other sonographic variable to baseline prediction models, which consisted solely of clinical variables, did not improve predictive accuracy or discriminatory power. The baseline model AUC and Brier score values were 0.68 (95% CI, 0.57-0.79) and 0.14 for adverse CPO, and 0.72 (95% CI, 0.61-0.83) and 0.13 for ODFC, respectively. CONCLUSIONS Although technically feasible to measure in most women with an AGA fetus admitted for spontaneous or induced labor at term, no difference in VPR MoM was observed depending on the occurrence of ODFC or CPO at delivery. Moreover, adding VPR MoM or any other sonographic variable to a baseline clinical prediction model did not improve predictive accuracy or discriminatory power for either outcome. Hence, peripartum ultrasound for the assessment of fetal weight and placental function has limited added value for predicting adverse labor outcomes in a low-risk obstetric population. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.
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Affiliation(s)
- B Packet
- Department of Development and Regeneration, Unit Woman and Child, Catholic University of Leuven (KU Leuven), Leuven, Belgium
- Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium
| | - R Van Severen
- Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium
| | - J Richter
- Department of Development and Regeneration, Unit Woman and Child, Catholic University of Leuven (KU Leuven), Leuven, Belgium
- Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven, Belgium
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Reid SM, Hinwood GL, Guzys AT, Hunt RW, Reddihough DS. Major structural congenital anomalies and causal pathways in people with cerebral palsy. Dev Med Child Neurol 2025; 67:374-381. [PMID: 39233603 PMCID: PMC11794670 DOI: 10.1111/dmcn.16073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 07/18/2024] [Accepted: 07/29/2024] [Indexed: 09/06/2024]
Abstract
AIM To determine the proportion of persons with cerebral palsy (CP) with major congenital anomalies, factors associated with the presence of anomalies, body systems involved, potential contribution to CP aetiology, and causal pathway subgroups implicated. METHOD This population-based, observational study involved a cohort of 2238 persons born in one Australian state between 1999 and 2017. Major congenital anomalies were classified as affecting cerebral, cardiac, or other body systems, with further categorization as single or multisystem. We determined the potential for anomalies to contribute to the development of CP across causal pathway subgroups that were broadly categorized as developmental or involving destructive brain insults. RESULTS Of persons with CP, 23% had major congenital anomalies and 17% of the cohort had anomalies that potentially contributed to the development of CP. Consistent with higher odds of parental consanguinity, maternal grand multiparity, and dysmorphic features in the group with anomalies, 82% of pathogenic anomalies, present in 14% of the cohort, were cerebral and involved developmental causal pathways. Only 3% (predominantly severe cardiac anomalies) were related to destructive brain insults. INTERPRETATION The study provides context for the impact on rates of CP of preventive measures or other changes in incidence or management of congenital anomalies.
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Affiliation(s)
- Susan M. Reid
- Neurodisability and RehabilitationMurdoch Children's Research InstituteParkvilleVictoriaAustralia
- Department of PaediatricsUniversity of MelbourneParkvilleVictoriaAustralia
- Neurodevelopment and DisabilityThe Royal Children's HospitalParkvilleVictoriaAustralia
| | - Gina L. Hinwood
- Neurodisability and RehabilitationMurdoch Children's Research InstituteParkvilleVictoriaAustralia
- Neurodevelopment and DisabilityThe Royal Children's HospitalParkvilleVictoriaAustralia
- Victorian Paediatric Rehabilitation ServiceMonash Children's HospitalClaytonVictoriaAustralia
- Department of Perinatal MedicineThe Mercy Hospital for WomenHeidelbergVictoriaAustralia
| | - Angela T. Guzys
- Neurodisability and RehabilitationMurdoch Children's Research InstituteParkvilleVictoriaAustralia
- Neurodevelopment and DisabilityThe Royal Children's HospitalParkvilleVictoriaAustralia
| | - Rod W. Hunt
- Department of PaediatricsSchool of Clinical Sciences, Monash UniversityClaytonVictoriaAustralia
- Monash NewbornMonash Children's HospitalClaytonVictoriaAustralia
- Cerebral Palsy AllianceUniversity of SydneySydneyNew South WalesAustralia
| | - Dinah S. Reddihough
- Neurodisability and RehabilitationMurdoch Children's Research InstituteParkvilleVictoriaAustralia
- Department of PaediatricsUniversity of MelbourneParkvilleVictoriaAustralia
- Neurodevelopment and DisabilityThe Royal Children's HospitalParkvilleVictoriaAustralia
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Sancerni T, Montel V, Dereumetz J, Cochon L, Coq JO, Bastide B, Canu MH. Enduring effects of acute prenatal ischemia in rat soleus muscle, and protective role of erythropoietin. J Muscle Res Cell Motil 2025; 46:23-34. [PMID: 39549147 DOI: 10.1007/s10974-024-09684-6] [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: 09/30/2024] [Accepted: 11/07/2024] [Indexed: 11/18/2024]
Abstract
Motor disorders are considered to originate mainly from brain lesions. Placental dysfunction or maternal exposure to a persistently hypoxic environment is a major cause of further motor disorders such as cerebral palsy. Our main goal was to determine the long-term effects of mild intrauterine acute ischemic stress on rat soleus myofibres and whether erythropoietin treatment could prevent these changes. Rat embryos were subjected to ischemic stress at embryonic day E17. They then received an intraperitoneal erythropoietin injection at postnatal days 1-5. Soleus muscles were collected at postnatal day 28. Prenatal ischemic stress durably affected muscle structure, as indicated by the greater fiber cross-sectional area (+ 18%) and the greater number of mature vessels (i.e. vessels with mature endothelial cells) per myofibres (+ 43%), and muscle biochemistry, as shown by changes in signaling pathways involved in protein synthesis/degradation balance (-81% for 4EBP1; -58% for AKT) and Hif1α expression levels (+ 95%). Erythropoietin injection in ischemic pups had a weak protective effect: it increased muscle mass (+ 25% with respect to ischemic pups) and partially prevented the increase in muscle degradation pathways and mature vascularization, whereas it exacerbated the decrease in synthesis pathways. Hence, erythropoietin treatment after acute ischemic stress contributes to muscle adaptation to ischemic conditions.
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Affiliation(s)
- Tiphaine Sancerni
- Univ. Lille, Univ Artois, Univ Littoral Côte d'Opale, URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, ULR7369, Lille, F-59000, France
| | - Valérie Montel
- Univ. Lille, Univ Artois, Univ Littoral Côte d'Opale, URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, ULR7369, Lille, F-59000, France
| | - Julie Dereumetz
- Univ. Lille, Univ Artois, Univ Littoral Côte d'Opale, URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, ULR7369, Lille, F-59000, France
| | - Laetitia Cochon
- Univ. Lille, Univ Artois, Univ Littoral Côte d'Opale, URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, ULR7369, Lille, F-59000, France
| | - Jacques-Olivier Coq
- Institut des Sciences du Mouvement (ISM), Team 'Plasticité des Systèmes Nerveux et Musculaires', UMR 7287 CNRS, Aix-Marseille Université Faculté des Sports, Marseille Cedex 09, F-13288, France
| | - Bruno Bastide
- Univ. Lille, Univ Artois, Univ Littoral Côte d'Opale, URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, ULR7369, Lille, F-59000, France
| | - Marie-Hélène Canu
- Univ. Lille, Univ Artois, Univ Littoral Côte d'Opale, URePSSS - Unité de Recherche Pluridisciplinaire Sport Santé Société, ULR7369, Lille, F-59000, France.
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Santos da Silva Calado CM, Manhães-de-Castro R, Souza VDS, Cavalcanti Bezerra Gouveia HJ, da Conceição Pereira S, da Silva MM, Albuquerque GLD, Lima BMP, Lira AVSMD, Toscano AE. Early-life malnutrition role in memory, emotional behavior and motor impairments in early brain lesions with potential for neurodevelopmental disorders: a systematic review with meta-analysis. Nutr Neurosci 2025; 28:171-193. [PMID: 38963807 DOI: 10.1080/1028415x.2024.2361572] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/06/2024]
Abstract
OBJECTIVES The present study aims to evaluate the impact of early exposure to brain injury and malnutrition on episodic memory and behavior. METHODS For this, a systematic review was carried out in the Medline/Pubmed, Web of Science, Scopus, and LILACS databases with no year or language restrictions. RESULTS Initially, 1759 studies were detected. After screening, 53 studies remained to be read in full. The meta-analysis demonstrated that exposure to double insults worsens episodic recognition memory but does not affect spatial memory. Early exposure to low-protein diets has been demonstrated to aggravate locomotor and masticatory sequelae. Furthermore, it reduces the weight of the soleus muscle and the muscle fibers of the masseter and digastric muscles. Early exposure to high-fat diets promotes an increase in oxidative stress and inflammation in the brain, increasing anxiety- and depression-like behavior and reducing locomotion. DISCUSSION Epigenetic modifications were noted in the hippocampus, hypothalamus, and prefrontal cortex depending on the type of dietetic exposure in early life. These findings demonstrate the impact of the double insult on regions involved in cognitive and behavioral processes. Additional studies are essential to understand the real impact of the double insults in the critical period.
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Affiliation(s)
- Caio Matheus Santos da Silva Calado
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
| | - Raul Manhães-de-Castro
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
- Graduate Program in Nutrition, Center for Health Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
| | - Vanessa da Silva Souza
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
| | - Henrique José Cavalcanti Bezerra Gouveia
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
- Graduate Program in Nutrition, Center for Health Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
| | - Sabrina da Conceição Pereira
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
| | - Márcia Maria da Silva
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
- Graduate Program in Nutrition, Center for Health Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
| | - Glayciele Leandro de Albuquerque
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
| | - Bruno Monteiro Paiva Lima
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
| | | | - Ana Elisa Toscano
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
- Graduate Program in Nutrition, Center for Health Sciences, Federal University of Pernambuco, Recife-Pernambuco, Brazil
- Nursing Unit, Vitória Academic Center, Federal University of Pernambuco, Vitória de Santo Antão-Pernambuco, Brazil
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Kim F, Maitre N. Grand Rounds: How Do We Detect Cerebral Palsy Earlier in Neonates? J Pediatr 2025; 276:114299. [PMID: 39277080 DOI: 10.1016/j.jpeds.2024.114299] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 08/27/2024] [Accepted: 09/09/2024] [Indexed: 09/17/2024]
Affiliation(s)
- Faith Kim
- Department of Pediatrics, Columbia University Irving Medical Center/New York-Presbyterian Children's Hospital of New York, New York, NY.
| | - Nathalie Maitre
- Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA
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Collins B, Lemanski EA, Wright-Jin E. The Importance of Including Maternal Immune Activation in Animal Models of Hypoxic-Ischemic Encephalopathy. Biomedicines 2024; 12:2559. [PMID: 39595123 PMCID: PMC11591850 DOI: 10.3390/biomedicines12112559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 10/24/2024] [Accepted: 10/29/2024] [Indexed: 11/28/2024] Open
Abstract
Hypoxic-ischemic encephalopathy (HIE) is a perinatal brain injury that is the leading cause of cerebral palsy, developmental delay, and poor cognitive outcomes in children born at term, occurring in about 1.5 out of 1000 births. The only proven therapy for HIE is therapeutic hypothermia. However, despite this treatment, many children ultimately suffer disability, brain injury, and even death. Barriers to implementation including late diagnosis and lack of resources also lead to poorer outcomes. This demonstrates a critical need for additional treatments for HIE, and to facilitate this, we need translational models that accurately reflect risk factors and interactions present in HIE. Maternal or amniotic infection is a significant risk factor and possible cause of HIE in humans. Maternal immune activation (MIA) is a well-established model of maternal infection and inflammation that has significant developmental consequences largely characterized within the context of neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. MIA can also lead to long-lasting changes within the neuroimmune system, which lead to compounding negative outcomes following a second insult. This supports the importance of understanding the interaction of maternal inflammation and hypoxic-ischemic outcomes. Animal models have been invaluable to understanding the pathophysiology of this injury and to the development of therapeutic hypothermia. However, each model system has its own limitations. Large animal models such as pigs may more accurately represent the brain and organ development and complexity in humans, while rodent models are more cost-effective and offer more possible molecular techniques. Recent studies have utilized MIA or direct inflammation prior to HIE insult. Investigators should thoughtfully consider the risk factors they wish to include in their HIE animal models. In the incorporation of MIA, investigators should consider the type, timing, and dose of the inflammatory stimulus, as well as the timing, severity, and type of hypoxic insult. Using a variety of animal models that incorporate the maternal-placental-fetal system of inflammation will most likely lead to a more robust understanding of the mechanisms of this injury that can guide future clinical decisions and therapies.
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Affiliation(s)
- Bailey Collins
- Division of Biomedical Research, Nemours Children’s Health, Wilmington, DE 19803, USA; (B.C.); (E.A.L.)
- Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, USA
| | - Elise A. Lemanski
- Division of Biomedical Research, Nemours Children’s Health, Wilmington, DE 19803, USA; (B.C.); (E.A.L.)
- Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, USA
| | - Elizabeth Wright-Jin
- Psychological and Brain Sciences, University of Delaware, Newark, DE 19716, USA
- Division of Neurology, Nemours Children’s Health, Wilmington, DE 19803, USA
- Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA
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Sarman A, Tuncay S, Budak Y, Demirpolat E, Bulut İ. Anxiety, depression, and support needs of the mothers of children with cerebral palsy and determining their opinions: Mixed methods study. J Pediatr Nurs 2024; 78:e133-e140. [PMID: 38997912 DOI: 10.1016/j.pedn.2024.06.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 06/29/2024] [Accepted: 06/29/2024] [Indexed: 07/14/2024]
Abstract
PURPOSE This study aimed to determine the level of anxiety, depression, support needs and opinions of mothers of children with cerebral palsy. DESIGN AND METHODS The study used a descriptive qualitative design. The population of the study consisted of children with cerebral palsy who were educated in special education centers in a province of Eastern Turkey. All participants who volunteered for the study were accepted and the study was completed with 126 mothers. RESULTS Caregiver mothers with male cerebral palsy patients had higher carer support needs and anxiety total mean scores. The mean scores of depression and anxiety of the mothers who were older were statistically higher. This study found that mothers of children with diseases other than cerebral palsy had statistically higher mean depression scores. The mothers of child with cerebral palsy who had a high gross motor classification score had higher mean carer support needs, depression, and anxiety total scores. CONCLUSIONS According to the study, depression and trait anxiety were linked to greater maternal support needs. Qualitative interviews revealed that mothers experienced issues such as stigmatization and withdrawal from social activities as a result of their children's illness. PRACTICE IMPLICATIONS This study shows the relationship of need for support of mothers of children with cerebral palsy and mental problems such as depression and trait anxiety. Pediatric nurses should provide emotional support to mothers and guide them towards support groups and training programs.
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Affiliation(s)
- Abdullah Sarman
- Bingöl University, Faculty of Health Science, Department of Pediatric Nursing, Bingöl, Turkey.
| | - Suat Tuncay
- Bingöl University, Faculty of Health Science, Department of Pediatric Nursing, Bingöl, Turkey
| | - Yusuf Budak
- Bingöl University, Faculty of Health Science, Department of Pediatric Nursing, Bingöl, Turkey
| | - Eyyüp Demirpolat
- Bingöl University, Vocational School of Health Services, Physiotherapy Program, Bingöl, Turkey
| | - İrem Bulut
- Fırat University, Faculty of Medicine, Department of Public Health, Elazig, Turkey
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Kibrom Y, Tekeste E, Tesfamariam S, Ogbe Z, Mohammed M. Clinical profile and associated comorbidities of cerebral palsy in children visiting Orotta National Referral Hospital, Eritrea: a cross-sectional study. BMC Pediatr 2024; 24:458. [PMID: 39026171 PMCID: PMC11256470 DOI: 10.1186/s12887-024-04938-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 07/09/2024] [Indexed: 07/20/2024] Open
Abstract
BACKGROUND Cerebral Palsy (CP) is one of the most common physical disabilities in children. This study aimed to explore the clinical spectrum of CP at Orotta National Referral and Teaching Hospital, including CP subtypes, gross motor function, patterns of associated comorbidities, and possible risk factors in children aged 2 to 12 years. METHODS A hospital-based cross-sectional study was conducted from January to April 2022 in 153 children with suspected motor symptoms. The Surveillance of CP in Europe (SCPE) decision tree was used as an inclusion criteria guideline and the evaluation of the participants was done using a standardized questionnaire and clinical examination. Descriptive statistics, chi-square test, and logistic regression were employed to statistically analyze the data. RESULTS Eighty-four children who fulfilled the clinical criteria were included in the study. The median age was 5-years [IQR: 3.8] with an equal distribution of males and females. Quadriplegic CP was the most common subtype (51.2%) followed by unilateral (hemiplegic) CP (22.6%), and dyskinetic CP (14.3%). Most children had severe gross motor impairment GMFCS level IV-V and females were almost three times more likely to have GMFCS level IV/V than males (AOR: 2.70; CI: 1.08-6.72; p-value = 0.033.) More than half (52.4%) of the neonates either did not cry within five minutes and/or needed breathing resuscitation, 55.3% had to be admitted to the NICU with a median of 5 days' hospital stay. Between the first week of birth and the first year of life, 28.6% had trouble feeding, 26.2% had an infection, 10.7% had difficulty breathing, 20.2% had seizures and 6% had jaundice. Feeding problems (64.3%), speech problems of some sort (91.7%), and epilepsy (46.4%) were the most commonly associated comorbidities with CP. CONCLUSIONS The clinical profile of the CP patients was found to be dominated by the spastic subtype and moderate to severe disability. Since perinatal risk factors were found to be dominant, strengthening maternal and child healthcare systems is recommended to minimize incidents of preventable risk factors and the burden of the disability.
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Affiliation(s)
- Yohannes Kibrom
- Orotta National Referral and Teaching Hospital, Asmara, Eritrea.
| | | | - Sirak Tesfamariam
- Product Evaluation and Registration Unit, National Medicines and Food Administration, Asmara, Eritrea
| | - Zemichael Ogbe
- Orotta National Referral and Teaching Hospital, Asmara, Eritrea
- Orotta School of Medicine and Health Sciences, Asmara, Eritrea
| | - Mahmud Mohammed
- Orotta National Referral and Teaching Hospital, Asmara, Eritrea
- Orotta School of Medicine and Health Sciences, Asmara, Eritrea
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Reid SM, Hinwood GL, Guzys AT, Hunt RW, Reddihough DS. Neonatal well-being and timing of brain injury in persons with cerebral palsy born at term or late preterm. Dev Med Child Neurol 2024; 66:892-901. [PMID: 38111136 DOI: 10.1111/dmcn.15829] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 11/13/2023] [Accepted: 11/17/2023] [Indexed: 12/20/2023]
Abstract
AIM To describe the distribution of neuroimaging patterns in a term/late preterm population-based cohort with cerebral palsy (CP), ascertain associations between neuroimaging patterns and neonatal well-being, estimate the proportion with antenatal or perinatal timing of neuropathology, and apply this information to the understanding of common mechanisms of brain injury and causal pathways. METHOD The cohort for this observational study comprised 1348 persons born between 1999 and 2017 in Victoria, Australia. Using algorithms designed for the study, neonatal well-being and timing of brain injury were tabulated for the whole cohort and across neuroimaging patterns and birth epochs. RESULTS Clinical and demographic profiles, neonatal well-being, and timing of brain injury differed across neuroimaging patterns. An estimated 57% of the cohort had a complicated neonatal period. Timing of brain injury was antenatal in 57% and perinatal in 41%. A decrease in the relative proportions of perinatal timing of brain injury was observed over a period when the rates of CP in live births at term decreased. INTERPRETATION This study begins to bridge the knowledge gap about causation in CP, moving towards better description of the main mechanisms of brain injury and their contribution within CP cohorts, and facilitating the ability to monitor changes over time and the success of preventive measures. WHAT THIS PAPER ADDS In a population-based, term/late preterm cohort with cerebral palsy, 57% had a complicated neonatal period. In the same cohort, 57% had presumed antenatal timing of brain injury. The relative proportion with perinatal injury decreased over time.
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Affiliation(s)
- Susan M Reid
- Neurodisability and Rehabilitation, Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia
- Neurodevelopment and Disability, The Royal Children's Hospital, Parkville, Victoria, Australia
| | - Gina L Hinwood
- Neurodisability and Rehabilitation, Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Victorian Paediatric Rehabilitation Service, Monash Children's Hospital, Clayton, Victoria, Australia
- Department of Perinatal Medicine, The Mercy Hospital for Women, Heidelberg, Victoria, Australia
| | - Angela T Guzys
- Neurodisability and Rehabilitation, Murdoch Children's Research Institute, Parkville, Victoria, Australia
| | - Rod W Hunt
- Department of Paediatrics, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
- Monash Newborn, Monash Health, Clayton, Victoria, Australia
- Cerebral Palsy Alliance, University of Sydney, New South Wales, Australia
| | - Dinah S Reddihough
- Neurodisability and Rehabilitation, Murdoch Children's Research Institute, Parkville, Victoria, Australia
- Department of Paediatrics, University of Melbourne, Parkville, Victoria, Australia
- Neurodevelopment and Disability, The Royal Children's Hospital, Parkville, Victoria, Australia
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11
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Saranti A, Dragoumi P, Papavasiliou A, Zafeiriou D. Current approach to cerebral palsy. Eur J Paediatr Neurol 2024; 51:49-57. [PMID: 38824721 DOI: 10.1016/j.ejpn.2024.05.015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2024] [Revised: 05/26/2024] [Accepted: 05/28/2024] [Indexed: 06/04/2024]
Abstract
This teaching review aims to provide an overview of the current approach to children with cerebral palsy (CP), retrieving the best available evidence and summarizing existing knowledge in the field of CP in children. We also highlight areas where more research is needed and novel strategies for diagnosing and treating cerebral palsy. CP includes a group of permanent disorders of movement and posture that cause activity limitation. Multiple risk factors, occurring preconceptionally, prenatally, perinatally, or postneonatally, are involved in the pathogenesis of CP, with the prenatal ones accounting for 80-90 % of cases. Due to its heterogeneity, CP has various classifications, but usually is classified based on clinical findings and motor impairment. Standardized function classification systems have been developed to address inconsistencies in previous classifications. The combination of clinical assessment and validated predictive tools is recommended for an early diagnosis, which is important for early intervention and prevention of secondary impairments. The therapeutic regimen in CP involves prevention and management of the motor and associated problems. It includes the enhancement of motor performance, the enrichment of cognition and communication skills, the prevention of secondary impairments, and the support of parents and caregivers. The care of CP children demands a multidisciplinary approach focused on improving motor skills, reducing comorbidities, enhancing the quality of life, and prolonging survival.
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Affiliation(s)
- Anna Saranti
- 1th Department of Pediatrics, Aristotle University of Thessaloniki, G. Hippokration Hospital, Thessaloniki, Greece
| | - Pinelopi Dragoumi
- 1th Department of Pediatrics, Aristotle University of Thessaloniki, G. Hippokration Hospital, Thessaloniki, Greece
| | | | - Dimitrios Zafeiriou
- 1th Department of Pediatrics, Aristotle University of Thessaloniki, G. Hippokration Hospital, Thessaloniki, Greece.
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12
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Calado CMSDS, Manhães-de-Castro R, da Conceição Pereira S, da Silva Souza V, Barbosa LNF, Dos Santos Junior OH, Lagranha CJ, Juárez PAR, Torner L, Guzmán-Quevedo O, Toscano AE. Resveratrol Reduces Neuroinflammation and Hippocampal Microglia Activation and Protects Against Impairment of Memory and Anxiety-Like Behavior in Experimental Cerebral Palsy. Mol Neurobiol 2024; 61:3619-3640. [PMID: 38001357 DOI: 10.1007/s12035-023-03772-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2023] [Accepted: 10/20/2023] [Indexed: 11/26/2023]
Abstract
Cerebral palsy (CP) is a neurodevelopmental disorder characterized by motor and postural impairments. However, early brain injury can promote deleterious effects on the hippocampus, impairing memory. This study aims to investigate the effects of resveratrol treatment on memory, anxiety-like behavior, and neuroinflammation markers in rats with CP. Male Wistar rats were subjected to perinatal anoxia (P0-P1) and sensory-motor restriction (P2-P28). They were treated with resveratrol (10 mg/kg, 0.1 ml/100 g) or saline from P3-P21, being divided into four experimental groups: CS (n = 15), CR (n = 15), CPS (n = 15), and CPR (n = 15). They were evaluated in the tests of novel object recognition (NORT), T-Maze, Light-Dark Box (LDB), and Elevated Plus Maze (EPM). Compared to the CS group, the CPS group has demonstrated a reduced discrimination index on the NORT (p < 0.0001) and alternation on the T-Maze (p < 0.01). In addition, the CPS group showed an increase in permanence time on the dark side in LDB (p < 0.0001) and on the close arms of the EPM (p < 0.001). The CPR group demonstrated an increase in the object discrimination index (p < 0.001), on the alternation (p < 0.001), on the permanence time on the light side (p < 0.0001), and on the open arms (p < 0.001). The CPR group showed a reduction in gene expression of IL-6 (p = 0.0175) and TNF-α (p = 0.0007) and an increase in Creb-1 levels (p = 0.0020). The CPS group showed an increase in the activated microglia and a reduction in cell proliferation in the hippocampus, while CPR animals showed a reduction of activated microglia and an increase in cell proliferation. These results demonstrate promising effects of resveratrol in cerebral palsy behavior impairment through reduced neuroinflammation in the hippocampus.
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Affiliation(s)
- Caio Matheus Santos da Silva Calado
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil
| | - Raul Manhães-de-Castro
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil
- Graduate Program in Nutrition, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil
| | - Sabrina da Conceição Pereira
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil
| | - Vanessa da Silva Souza
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil
| | - Leticia Nicoly Ferreira Barbosa
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil
| | - Osmar Henrique Dos Santos Junior
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil
| | - Claudia Jacques Lagranha
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil
- Graduate Program in Biochemistry and Physiology, Federal University of Pernambuco, Recife, Pernambuco, Brazil
| | - Pedro Alberto Romero Juárez
- Laboratory of Experimental Neuronutrition and Food Engineering, Tecnológico Nacional de México (TECNM), Instituto Tecnológico Superior de Tacámbaro, 61651, Tacámbaro, Michoacán, Mexico
- Centro de Investigación Biomédica de Michoacán, Instituto Mexicano del Seguro Social, 58330, Morelia, Michoacán, Mexico
| | - Luz Torner
- Centro de Investigación Biomédica de Michoacán, Instituto Mexicano del Seguro Social, 58330, Morelia, Michoacán, Mexico
| | - Omar Guzmán-Quevedo
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil
- Laboratory of Experimental Neuronutrition and Food Engineering, Tecnológico Nacional de México (TECNM), Instituto Tecnológico Superior de Tacámbaro, 61651, Tacámbaro, Michoacán, Mexico
- Centro de Investigación Biomédica de Michoacán, Instituto Mexicano del Seguro Social, 58330, Morelia, Michoacán, Mexico
| | - Ana Elisa Toscano
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil.
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil.
- Graduate Program in Nutrition, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil.
- Nursing Unit, Vitória Academic Center, Federal University of Pernambuco, Rua Do Alto Do Reservatório S/N, Bela Vista, Vitória de Santo Antão, Pernambuco, 55608-680, Brazil.
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White TA, Miller SL, Sutherland AE, Allison BJ, Camm EJ. Perinatal compromise affects development, form, and function of the hippocampus part one; clinical studies. Pediatr Res 2024; 95:1698-1708. [PMID: 38519794 PMCID: PMC11245394 DOI: 10.1038/s41390-024-03105-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2023] [Revised: 01/30/2024] [Accepted: 02/05/2024] [Indexed: 03/25/2024]
Abstract
The hippocampus is a neuron-rich specialised brain structure that plays a central role in the regulation of emotions, learning and memory, cognition, spatial navigation, and motivational processes. In human fetal development, hippocampal neurogenesis is principally complete by mid-gestation, with subsequent maturation comprising dendritogenesis and synaptogenesis in the third trimester of pregnancy and infancy. Dendritogenesis and synaptogenesis underpin connectivity. Hippocampal development is exquisitely sensitive to perturbations during pregnancy and at birth. Clinical investigations demonstrate that preterm birth, fetal growth restriction (FGR), and acute hypoxic-ischaemic encephalopathy (HIE) are common perinatal complications that alter hippocampal development. In turn, deficits in hippocampal development and structure mediate a range of neurodevelopmental disorders, including cognitive and learning problems, autism, and Attention-Deficit/Hyperactivity Disorder (ADHD). In this review, we summarise the developmental profile of the hippocampus during fetal and neonatal life and examine the hippocampal deficits observed following common human pregnancy complications. IMPACT: The review provides a comprehensive summary of the developmental profile of the hippocampus in normal fetal and neonatal life. We address a significant knowledge gap in paediatric research by providing a comprehensive summary of the relationship between pregnancy complications and subsequent hippocampal damage, shedding new light on this critical aspect of early neurodevelopment.
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Affiliation(s)
- Tegan A White
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia.
- Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia.
| | - Suzanne L Miller
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
- Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia
| | - Amy E Sutherland
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
- Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia
| | - Beth J Allison
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia
- Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia
| | - Emily J Camm
- The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia.
- Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC, Australia.
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Marefi A, Husein N, Dunbar M, Dewey D, Letourneau N, Oskoui M, Kirton A, Shevell M. Risk Factors for Term-Born Spastic Diplegic Cerebral Palsy: A Case-Control Study. Pediatr Neurol 2024; 155:26-32. [PMID: 38581726 DOI: 10.1016/j.pediatrneurol.2024.03.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 01/06/2024] [Accepted: 03/12/2024] [Indexed: 04/08/2024]
Abstract
BACKGROUND To identify if a predetermined set of potential risk factors are associated with spastic diplegic cerebral palsy (SDCP) in term-born children. METHODS This is a case-control study with cases (n = 134) extracted from the Canadian Cerebral Palsy Registry (CCPR) and controls (n = 1950) from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Our primary variable was the SDCP phenotype in term-born children. Possible risk factors were selected a priori and include extreme maternal age (<19 or >35 years), pregnancy complications, maternal disease, substance use, perinatal infection, mode of delivery, perinatal adversity (i.e., neonatal encephalopathy presumably on the basis of intrapartum hypoxia-ischemia), sex, and birth weight. Multivariable analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Multivariable analysis revealed associations between term-born SDCP and pregnancy complications (OR = 4.73; 95% CI = 1.91 to 10.56), maternal disease (OR = 2.52; 95% CI = 1.57 to 3.93), substance use (OR = 3.11; 95% CI = 2.10 to 4.55), perinatal infection (OR = 2.72; 95% CI 1.32 to 5.10), Caesarean section (OR = 2.35; 95% CI = 1.62 to 3.40), and perinatal adversity (OR = 2.91; 95% CI = 1.94 to 4.50). Multiple regression analysis revealed associations between SDCP and pregnancy complications (OR = 3.28; 95% CI 1.20 to 8.15), maternal disease (OR = 2.52; 95% CI 1.50 to 4.12), substance use (OR = 3.59; 95% CI 2.37 to 5.40), perinatal infection (OR = 3.78, 95% CI 1.71 to 7.72), Caesarean section (OR = 2.72; 95% CI 1.82 to 4.03), and perinatal adversity (OR = 4.16; 95% CI 2.67 to 6.70). INTERPRETATION Antenatal (pregnancy complications, maternal disease, substance use) and perinatal (infections, Caesarean section, and perinatal adversity) risk factors are associated with an increased risk of SDCP in term-born children, suggesting variable interactions between risk factors to provide a clinicopathologic framework that is different from SDCP observed in preterm-born children.
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Affiliation(s)
- Amaar Marefi
- Department of Neurology & Neurosurgery, McGill University, Montréal, Québec, Canada; Department of Pediatrics, Montreal Children's Hospital-McGill University Health Center, Montreal, Quebec, Canada
| | - Nafisa Husein
- Department of Neurology & Neurosurgery, McGill University, Montréal, Québec, Canada; Department of Pediatrics, Montreal Children's Hospital-McGill University Health Center, Montreal, Quebec, Canada
| | - Mary Dunbar
- Departments of Pediatrics and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
| | - Deborah Dewey
- Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Departments of Pediatrics and Community Health Sciences, University of Calgary, Calgary, Alberta
| | - Nicole Letourneau
- Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Departments of Pediatrics and Community Health Sciences, University of Calgary, Calgary, Alberta; Faculty of Nursing and Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada
| | - Maryam Oskoui
- Department of Neurology & Neurosurgery, McGill University, Montréal, Québec, Canada; Department of Pediatrics, Montreal Children's Hospital-McGill University Health Center, Montreal, Quebec, Canada; Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Center, Montréal, Québec, Canada
| | - Adam Kirton
- Departments of Pediatrics and Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada
| | - Michael Shevell
- Department of Neurology & Neurosurgery, McGill University, Montréal, Québec, Canada; Department of Pediatrics, Montreal Children's Hospital-McGill University Health Center, Montreal, Quebec, Canada.
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15
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Letzkus L, Fairchild K, Lyons G, Pyata H, Ratcliffe S, Lake D. Heart Rate and Pulse Oximetry Dynamics in the First Week after Birth in Neonatal Intensive Care Unit Patients and the Risk of Cerebral Palsy. Am J Perinatol 2024; 41:e528-e535. [PMID: 36174590 PMCID: PMC10050229 DOI: 10.1055/s-0042-1756335] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
OBJECTIVE Infants in the neonatal intensive care unit (NICU) are at high risk of adverse neuromotor outcomes. Atypical patterns of heart rate (HR) and pulse oximetry (SpO2) may serve as biomarkers for risk assessment for cerebral palsy (CP). The purpose of this study was to determine whether atypical HR and SpO2 patterns in NICU patients add to clinical variables predicting later diagnosis of CP. STUDY DESIGN This was a retrospective study including patients admitted to a level IV NICU from 2009 to 2017 with archived cardiorespiratory data in the first 7 days from birth to follow-up at >2 years of age. The mean, standard deviation (SD), skewness, kurtosis and cross-correlation of HR and SpO2 were calculated. Three predictive models were developed using least absolute shrinkage and selection operator regression (clinical, cardiorespiratory and combined model), and their performance for predicting CP was evaluated. RESULTS Seventy infants with CP and 1,733 controls met inclusion criteria for a 3.8% population prevalence. Area under the receiver operating characteristic curve for CP prediction was 0.7524 for the clinical model, 0.7419 for the vital sign model, and 0.7725 for the combined model. Variables included in the combined model were lower maternal age, outborn delivery, lower 5-minute Apgar's score, lower SD of HR, and more negative skewness of HR. CONCLUSION In this study including NICU patients of all gestational ages, HR but not SpO2 patterns added to clinical variables to predict the eventual diagnosis of CP. Identification of risk of CP within the first few days of life could result in improved therapy resource allocation and risk stratification in clinical trials of new therapeutics. KEY POINTS · SD and skewness of HR have some added predictive value of later diagnosis of CP.. · SpO2 measures do not add to CP prediction.. · Combining clinical variables with early HR measures may improve the prediction of later CP..
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Affiliation(s)
- Lisa Letzkus
- University of Virginia School of Medicine; Department of Pediatrics; Neurodevelopmental and Behavioral Pediatrics, UVA Children’s, Charlottesville, Virginia, USA
| | - Karen Fairchild
- University of Virginia School of Medicine; Department of Pediatrics; Neonatology, UVA Children’s, Charlottesville, Virginia, USA
| | - Genevieve Lyons
- University of Virginia School of Medicine; Department of Public Health Sciences; Charlottesville, Virginia, USA
| | - Harshini Pyata
- University of North Carolina at Chapel Hill; Department of Pediatrics
| | - Sarah Ratcliffe
- University of Virginia School of Medicine; Department of Public Health Sciences; Charlottesville, Virginia, USA
| | - Doug Lake
- University of North Carolina at Chapel Hill; Department of Pediatrics
- University of Virginia School of Medicine; Department of Cardiovascular Medicine; Charlottesville, Virginia, USA
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Niedzwecki C, Barbuto A, Mitchell K, Wirt S, Seymour M, Thomas S, Schwabe A. Comparison of outcomes following surgical intervention and inpatient rehabilitation stays in children with cerebral palsy. PM R 2024; 16:449-461. [PMID: 37801614 DOI: 10.1002/pmrj.13075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 07/28/2023] [Accepted: 09/01/2023] [Indexed: 10/08/2023]
Abstract
INTRODUCTION Literature is limited on functional outcomes in children with cerebral palsy (CP) following surgical procedures and a subsequent inpatient rehabilitation unit (IRU) stay. OBJECTIVE To compare functional outcomes and length of stay (LOS) in children with CP following a surgical procedure and IRU stay based on the surgical procedure performed, pattern of involvement, etiology, and Gross Motor Function Classification System (GMFCS) level. DESIGN Retrospective cohort study. SETTING Tertiary care pediatrics. PARTICIPANTS Pediatric patients with CP who underwent one of three surgical procedures followed by an IRU stay. INTERVENTIONS Selective dorsal rhizotomy (SDR), single-event multilevel orthopedic surgery (SEMLS), or intrathecal baclofen (ITB) pump implantation and subsequent IRU stay. MAIN OUTCOME MEASURES IRU LOS, Functional Independence Measure for Children (WeeFIM) total score, sub-scores, and efficiency. RESULTS Children undergoing SDR had a longer LOS (p ≤ .015). Children with spastic diplegia, GMFCS level II, and prematurity-based CP had higher WeeFIM efficiency scores (p ≤ .046, ≤.021, and .034 respectively). Greater changes in WeeFIM™ scores were associated with spastic diplegia, SDR, GMFCS level II, longer LOS, and higher admission scores (p ≤ .045). CONCLUSIONS Although statistically and functionally significant improvements in children with CP following surgical interventions and an IRU stay were seen, those with higher WeeFIM change scores tended to have spastic diplegia, to have undergone SDR, GMFCS level II, longer LOS, and higher admission scores.
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Affiliation(s)
- Christian Niedzwecki
- Department of Physical Medicine & Rehabilitation, Baylor College of Medicine, Houston, Texas, USA
| | - Amy Barbuto
- Department of Physical and Occupational Therapy, Texas Children's Hospital-The Woodlands, The Woodlands, Texas, USA
| | - Katy Mitchell
- Department of Physical Therapy, Texas Woman's University-Houston, Houston, Texas, USA
| | - Steven Wirt
- Department of Physical and Occupational Therapy, Texas Children's Hospital-Main Campus, Houston, Texas, USA
| | - Michelle Seymour
- Department of Physical Medicine & Rehabilitation, Baylor College of Medicine, Houston, Texas, USA
| | - Sruthi Thomas
- Departments of Physical Medicine & Rehabilitation and Neurosurgery, Baylor College of Medicine, Houston, Texas, USA
| | - Aloysia Schwabe
- Department of Physical Medicine & Rehabilitation, Baylor College of Medicine, Houston, Texas, USA
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17
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Evans MI, Britt DW, Devoe LD. Etiology and Ontogeny of Cerebral Palsy: Implications for Practice and Research. Reprod Sci 2024; 31:1179-1189. [PMID: 38133768 DOI: 10.1007/s43032-023-01422-6] [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: 08/15/2023] [Accepted: 12/04/2023] [Indexed: 12/23/2023]
Abstract
Cerebral palsy (CP) has been recognized as a group of neurologic disorders with varying etiologies and ontogenies. While a percentage of CP cases arises during labor, the expanded use of electronic fetal monitoring (EFM) to include prevention of CP has resulted in decades of vastly increased interventions that have not significantly reduced the incidence of CP for infants born at term in the USA. Litigation alleging that poor obstetrical practice caused CP in most of these affected children has led to contentious arguments regarding the actual etiologies of this condition and often resulted in substantial monetary awards for plaintiffs. Recent advances in genetic testing using whole exome sequencing have revealed that at least one-third of CP cases in term infants are genetic in origin and therefore not labor-related. Here, we will present and discuss previous attempts to sort out contributing etiologies and ontogenies of CP, and how these newer diagnostic techniques are rapidly improving our ability to better detect and understand such cases. In light of these developments, we present our vision for an overarching spectrum for proper categorization of CP cases into that the following groups: (1) those begun at conception from genetic causes (nonpreventable); (2) those stemming from adverse antenatal/pre-labor events (possibly preventable with heightened antepartum assessment); (3) Those arising from intrapartum events (potentially preventable by earlier interventions); (4) Those occurring shortly after birth (possibly preventable with closer neonatal monitoring); (5) Those that appear later in the postnatal period from non-labor-related causes such as untreated infections or postnatal intracranial hemorrhages.
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Affiliation(s)
- Mark I Evans
- Fetal Medicine Foundation of America, New York, NY, USA.
- Comprehensive Genetics, PLLC, New York, NY, USA.
- Departments of Obstetrics, Gynecology, and Reproductive Sciences, Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
| | - David W Britt
- Fetal Medicine Foundation of America, New York, NY, USA
| | - Lawrence D Devoe
- Department of Obstetrics & Gynecology, The Medical College of Georgia at Augusta University, Augusta, GA, USA
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18
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Hu G, Zhao Y, Fu X, Hu D, Liang X. Maternal body mass index and cerebral palsy in children: A systematic review and dose-response meta-analysis. Paediatr Perinat Epidemiol 2024; 38:345-356. [PMID: 38146616 DOI: 10.1111/ppe.13033] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 10/20/2023] [Accepted: 12/07/2023] [Indexed: 12/27/2023]
Abstract
BACKGROUND Accumulating studies indicate that maternal obesity is associated with the risk of cerebral palsy (CP); however, their conclusions have been inconsistent. OBJECTIVES To quantitatively estimate the association between maternal body mass index (BMI) and CP in offspring. DATA SOURCES PubMed, Embase and Web of Science. STUDY SELECTION AND DATA EXTRACTION Articles published up to 18 September 2022 were searched that reported the correlation between maternal BMI and CP in children. Two reviewers independently extracted data and critically assessed articles. SYNTHESIS Pooled relative risks (RR) and 95% confidence intervals (CI) were estimated by the random-effects model. Subgroup analysis and meta-regression were performed to explore sources of heterogeneity. RESULTS In total, 11 articles (8,407,668 participants) were identified for inclusion in our meta-analysis. For maternal underweight, no significant association was found with CP risk (RR 1.11, 95% CI 0.90, 1.38). The risk of CP was increased by 25% (RR 1.25, 95% CI 1.06, 1.47), 38% (RR 1.38, 95% CI 1.18, 1.61) and 127% (RR 2.27, 95% CI 1.82, 2.83) for maternal overweight, obesity and obesity grade 3, respectively. In addition, we observed a positive linear dose-response relationship, with the pooled risk of cerebral palsy in offspring increasing by 3% with each unit increase in maternal BMI. CONCLUSION This meta-analysis indicates that the risk of CP in offspring grew with maternal overweight or obesity grades increasing, and was positively correlated with maternal BMI.
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Affiliation(s)
- Guomin Hu
- The Second Department of pediatrics, The First People's Hospital of Nanyang City, Nanyang, Henan, People's Republic of China
| | - Yang Zhao
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, People's Republic of China
| | - Xueru Fu
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, People's Republic of China
| | - Dongsheng Hu
- Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, People's Republic of China
- Department of Biostatistics and Epidemiology, School of Public Health, Shenzhen University Medical School, Shenzhen University, Shenzhen, Guangdong, People's Republic of China
| | - Xin Liang
- Administration Department of Nursing Affairs, The First People's Hospital of Nanyang City, Nanyang, Henan, People's Republic of China
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Marques KL, Rodrigues V, Balduci CTN, Montes GC, Barradas PC, Cunha-Rodrigues MC. Emerging therapeutic strategies in hypoxic-ischemic encephalopathy: a focus on cognitive outcomes. Front Pharmacol 2024; 15:1347529. [PMID: 38469401 PMCID: PMC10925695 DOI: 10.3389/fphar.2024.1347529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Accepted: 01/30/2024] [Indexed: 03/13/2024] Open
Abstract
Perinatal hypoxia-ischemia represents a significant risk to CNS development, leading to high mortality rates, diverse damages, and persistent neurological deficits. Despite advances in neonatal medicine in recent decades, the incidence of HIE remains substantial. Motor deficits can manifest early, while cognitive impairments may be diagnosed later, emphasizing the need for extended follow-up. This review aims to explore potential candidates for therapeutic interventions for hypoxic-ischemic encephalopathy (HIE), with a focus on cognitive deficits. We searched randomized clinical trials (RCT) that tested drug treatments for HIE and evaluated cognitive outcomes. The results included studies on erythropoietin, melatonin, magnesium sulfate, topiramate, and a combination of vitamin C and ibuprofen. Although there are several indications of the efficacy of these drugs among animal models, considering neuroprotective properties, the RCTs failed to provide complete effectiveness in the context of cognitive impairments derived from HIE. More robust RCTs are still needed to advance our knowledge and to establish standardized treatments for HIE.
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Affiliation(s)
- Kethely L. Marques
- Laboratory of Neurobiology, Pharmacology and Psychobiology Department, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Victor Rodrigues
- Faculty of Medical Sciences, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Cassiana T. N. Balduci
- Laboratory of Neurobiology, Pharmacology and Psychobiology Department, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
- Rare Diseases Sales Force, Daiichi Sankyo Brazil, São Paulo, Brazil
| | - Guilherme C. Montes
- Laboratory of Neurobiology, Pharmacology and Psychobiology Department, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Penha C. Barradas
- Laboratory of Neurobiology, Pharmacology and Psychobiology Department, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Marta C. Cunha-Rodrigues
- Laboratory of Neurobiology, Pharmacology and Psychobiology Department, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Rio de Janeiro, Brazil
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20
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Wu BA, Chand KK, Bell A, Miller SL, Colditz PB, Malhotra A, Wixey JA. Effects of fetal growth restriction on the perinatal neurovascular unit and possible treatment targets. Pediatr Res 2024; 95:59-69. [PMID: 37674023 PMCID: PMC10798895 DOI: 10.1038/s41390-023-02805-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 08/04/2023] [Accepted: 08/16/2023] [Indexed: 09/08/2023]
Abstract
The neurovascular unit (NVU) within the brain is a multicellular unit that synergistically acts to maintain blood-brain barrier function and meet cerebral metabolic demand. Recent studies have indicated disruption to the NVU is associated with neuropathology in the perinatal brain. Infants with fetal growth restriction (FGR) are known to be at increased risk of neurodevelopmental conditions including motor, learning, and behavioural deficits. There are currently no neuroprotective treatments for these conditions. In this review, we analyse large animal studies examining the effects of FGR on the perinatal NVU. These studies show altered vascularity in the FGR brain as well as blood-brain barrier dysfunction due to underlying cellular changes, mediated by neuroinflammation. Neuroinflammation is a key mechanism associated with pathological effects in the FGR brain. Hence, targeting inflammation may be key to preserving the multicellular NVU and providing neuroprotection in FGR. A number of maternal and postnatal therapies with anti-inflammatory components have been investigated in FGR animal models examining targets for amelioration of NVU disruption. Each therapy showed promise by uniquely ameliorating the adverse effects of FGR on multiple aspects of the NVU. The successful implementation of a clinically viable neuroprotective treatment has the potential to improve outcomes for neonates affected by FGR. IMPACT: Disruption to the neurovascular unit is associated with neuropathology in fetal growth restriction. Inflammation is a key mechanism associated with neurovascular unit disruption in the growth-restricted brain. Anti-inflammatory treatments ameliorate adverse effects on the neurovascular unit and may provide neuroprotection.
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Affiliation(s)
- Bing Anthony Wu
- Department of Paediatrics, Monash University, Melbourne, VIC, Australia
| | - Kirat K Chand
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Alexander Bell
- Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC, Australia
- The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, Australia
| | - Suzanne L Miller
- Department of Obstetrics and Gynaecology, Monash University, Melbourne, VIC, Australia
- The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, Australia
| | - Paul B Colditz
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
- Perinatal Research Centre, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
| | - Atul Malhotra
- Department of Paediatrics, Monash University, Melbourne, VIC, Australia
- The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, VIC, Australia
- Monash Newborn, Monash Children's Hospital, Melbourne, VIC, Australia
| | - Julie A Wixey
- UQ Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
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Abstract
Cerebral palsy (CP) is the most common physical disability across the lifespan, but historically, CP has not been diagnosed before the age of 2 years. Barriers to early diagnosis ranged from lack of available biomarkers, absence of curative treatments, perceived stigma associated with a lifelong diagnosis, and a desire to rule out other diagnoses first. Most importantly, the fundamental question that remained was whether children would benefit from earlier detection and intervention given the paucity of research. However, evidence-based guidelines published in 2017 demonstrated that the General Movements Assessment, the Hammersmith Infant Neurological Examination, and neuroimaging can be combined with other elements such as a clinical history and standardized motor assessments to provide the highest predictive value for diagnosing CP as early as age 3 months in high-risk newborns. Implementation of these guidelines has been successful in decreasing the age at CP diagnosis, particularly in high-risk infant follow-up clinics with expertise in performing these assessments. Early detection of CP allows for clinical and research opportunities investigating earlier interventions during a critical period of neuroplasticity, with the goal of improving developmental trajectories for children and their families. New guidelines and research are now being developed with a focus on early, targeted interventions that continue to be studied, along with global detection initiatives.
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Affiliation(s)
- Faith Kim
- Department of Pediatrics, Columbia University Irving Medical Center/NewYork-Presbyterian Children's Hospital of New York, New York, NY
| | - Nathalie Maitre
- Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, GA
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22
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Menezes KKP, Avelino PR, Nascimento LR. Addition of backward walking training to forward walking training improves walking speed in children with cerebral palsy: a systematic review with meta-analysis. Int J Rehabil Res 2023; 46:300-307. [PMID: 37581293 DOI: 10.1097/mrr.0000000000000598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/16/2023]
Abstract
The objective was to examine the effects of backward walking training for improving walking speed and balance in children with cerebral palsy. A systematic review of randomized trials was conducted. Trials had to include children with cerebral palsy, with a Gross Motor Function Classification System, between I and III, that delivered backward walking training as a solo intervention or in combination with forward walking training. The outcomes of interest were walking speed and balance. The methodological quality of included trials was assessed by the PEDro scale, and the quality of evidence was assessed according to Grading of Recommendations Assessment, Development and Evaluation. Eight papers, involving 156 participants, were included. Using random-effects meta-analysis, we estimated that backward walking training improved walking speed by 0.10 m/s [95% confidence interval (CI) 0.05-0.16] and by 2 points on the Pediatric Balance Scale (0-56) (95% CI 1.5-2.2) more than forward walking training. We also estimated that the addition of backward walking training increased walking speed by 0.20 m/s (95% CI 0.07-0.34) and reduced the angular excursion of the center of gravity by 0.5 degrees (95% CI -0.7 to -0.3). The quality of the evidence was classified as low to moderate. In conclusion, overall, backward walking training appears to be as effective or slightly superior to forward walking training for improving walking speed in children with CP. The addition of backward walking training statistically significantly and clinically important enhanced benefits on walking speed.
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Affiliation(s)
- Kênia K P Menezes
- NeuroGroup, Department of Physiotherapy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais
| | - Patrick R Avelino
- NeuroGroup, Department of Physiotherapy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais
| | - Lucas R Nascimento
- NeuroGroup, Department of Physiotherapy, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais
- Center of Health Sciences, Department of Physiotherapy, Universidade Federal do Espírito Santo, Vitória, Espírito Santo, Brazil
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23
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Vilhelmsson A, Rylander L, Jöud A, Lindh CH, Mattsson K, Liew Z, Guo P, Ritz B, Källén K, Thacher JD. Exposure to per- and polyfluoroalkyl substances in early pregnancy and risk of cerebral palsy in children. THE SCIENCE OF THE TOTAL ENVIRONMENT 2023; 899:165622. [PMID: 37474063 DOI: 10.1016/j.scitotenv.2023.165622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/30/2023] [Accepted: 07/16/2023] [Indexed: 07/22/2023]
Abstract
BACKGROUND Most cerebral palsy (CP) cases have an unexplained etiology, but a role for environmental exposures has been suggested. One purported environmental risk factor is exposure to endocrine-disrupting pollutants specifically per- and polyfluoroalkyl substances (PFAS). OBJECTIVES We investigated the association between prenatal PFAS exposures and CP in Swedish children. METHODS In this case-control study, 322 CP cases, 343 population controls, and 258 preterm controls were identified from a birth registry in combination with a CP follow-up program from 1995 to 2014 and linked to a biobank which contains serum samples from week 10-14 of pregnancy. Maternal serum concentrations of four PFAS compounds: perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctane sulfonate (PFOS) were analyzed using liquid chromatography-tandem-mass-spectrometry. We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for CP and each PFAS in quartiles and as continuous variables controlling for various sociodemographic and lifestyle factors. RESULTS In crude and adjusted analyses, we did not find consistent evidence of associations between serum PFHxS, PFOA, PFNA, PFOS and concentrations in early pregnancy and CP, except in preterm infants. The ORs comparing the highest PFAS quartiles to the lowest were 1.05 (95 % CI: 0.63-1.76), 0.96 (95 % CI: 0.55-1.68), 0.71 (95 % CI: 0.41-1.25), and 1.17 (95 % CI: 0.61-2.26), for PFHxS, PFOA, PFNA, and PFOS, respectively. Some positive associations were observed for preterm infants, but the results were imprecise. Similar patterns were observed in analyses treating PFAS as continuous variables. CONCLUSIONS In this study, we found little evidence that early pregnancy prenatal exposure to PFHxS, PFOA, PFNA, or PFOS increases the risk of CP. However, some positive associations were observed for preterm cases and warrant further investigation.
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Affiliation(s)
- Andreas Vilhelmsson
- Division of Occupational and Environmental Medicine, Lund University, Sweden
| | - Lars Rylander
- Division of Occupational and Environmental Medicine, Lund University, Sweden
| | - Anna Jöud
- Division of Occupational and Environmental Medicine, Lund University, Sweden; Department of Clinical Sciences Lund, Orthopaedics, Lund University, Faculty of Medicine, Sweden; Health Technology Assessment Skåne, Skåne University Hospital, Sweden
| | - Christian H Lindh
- Division of Occupational and Environmental Medicine, Lund University, Sweden
| | - Kristina Mattsson
- Division of Occupational and Environmental Medicine, Lund University, Sweden
| | - Zeyan Liew
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, USA; Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, USA
| | - Pengfei Guo
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, USA; Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, USA
| | - Beate Ritz
- Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, USA; Department of Neurology, School of Medicine, UCLA, Los Angeles, USA
| | - Karin Källén
- Division of Occupational and Environmental Medicine, Lund University, Sweden; Tornblad Institute, Lund University, Sweden
| | - Jesse D Thacher
- Division of Occupational and Environmental Medicine, Lund University, Sweden.
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24
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Zhuo H, Ritz B, Warren JL, Liew Z. Season of Conception and Risk of Cerebral Palsy. JAMA Netw Open 2023; 6:e2335164. [PMID: 37738049 PMCID: PMC10517373 DOI: 10.1001/jamanetworkopen.2023.35164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 08/16/2023] [Indexed: 09/23/2023] Open
Abstract
Importance Cerebral palsy (CP) is the most prevalent neuromotor disability in childhood, but for most cases the etiology remains unexplained. Seasonal variation in the conception of CP may provide clues for their potential etiological risk factors that vary across seasons. Objective To evaluate whether the month or season of conception is associated with CP occurrence. Design, Setting, and Participants This statewide cohort study examined more than 4 million live births that were registered in the California birth records during 2007 to 2015 and were linked to CP diagnostic records (up to year 2021). Statistical analyses were conducted between March 2022 and January 2023. Exposures The month and season of conception were estimated based on the child's date of birth and the length of gestation recorded in the California birth records. Main Outcomes and Measures CP status was ascertained from the diagnostic records obtained from the Department of Developmental Services in California. Poisson regression was used to estimate the relative risk (RR) and 95% CI for CP according to the month or the season of conception, adjusting for maternal- and neighborhood-level factors. Stratified analyses were conducted by child's sex and neighborhood social vulnerability measures, and the mediating role of preterm birth was evaluated. Results Records of 4 468 109 children (51.2% male; maternal age: 28.3% aged 19 to 25 years, 27.5% aged 26 to 30 years; maternal race and ethnicity: 5.6% African American or Black, 13.5% Asian, 49.8% Hispanic or Latinx of any race, and 28.3% non-Hispanic White) and 4697 with CP (55.1% male; maternal age: 28.3% aged 19 to 25 years, 26.0% aged 26 to 30 years; maternal race and ethnicity: 8.3% African American or Black, 8.6% Asian, 54.3% Hispanic or Latinx of any race, and 25.8% non-Hispanic White) were analyzed. Children conceived in winter (January to March) or spring (April to June) were associated with a 9% to 10% increased risk of CP (winter: RR, 1.09 [95% CI, 1.01-1.19]; spring: RR, 1.10 [95% CI, 1.02-1.20]) compared with summer (July to September) conceptions. Analyses for specific months showed similar results with children conceived in January, February, and May being at higher risk of CP. The associations were slightly stronger for mothers who lived in neighborhoods with a high social vulnerability index, but no child sex differences were observed. Only a small portion of the estimated association was mediated through preterm birth. Conclusions and Relevance In this cohort study in California, children conceived in winter and spring had a small increase in CP risk. These findings suggest that seasonally varying environmental factors should be considered in the etiological research of CP.
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Affiliation(s)
- Haoran Zhuo
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut
- Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, Connecticut
| | - Beate Ritz
- Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles
- Department of Neurology, School of Medicine, University of California, Los Angeles
| | - Joshua L. Warren
- Department of Biostatistics, Yale School of Public Health, New Haven, Connecticut
| | - Zeyan Liew
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut
- Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, Connecticut
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25
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Weyde KVF, Winterton A, Surén P, Andersen GL, Vik T, Biele G, Knutsen HK, Thomsen C, Meltzer HM, Skogheim TS, Engel SM, Aase H, Villanger GD. Association between gestational levels of toxic metals and essential elements and cerebral palsy in children. Front Neurol 2023; 14:1124943. [PMID: 37662050 PMCID: PMC10470125 DOI: 10.3389/fneur.2023.1124943] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 07/11/2023] [Indexed: 09/05/2023] Open
Abstract
Introduction Cerebral palsy (CP) is the most common motor disability in childhood, but its causes are only partly known. Early-life exposure to toxic metals and inadequate or excess amounts of essential elements can adversely affect brain and nervous system development. However, little is still known about these as perinatal risk factors for CP. This study aims to investigate the associations between second trimester maternal blood levels of toxic metals, essential elements, and mixtures thereof, with CP diagnoses in children. Methods In a large, population-based prospective birth cohort (The Norwegian Mother, Father, and Child Cohort Study), children with CP diagnoses were identified through The Norwegian Patient Registry and Cerebral Palsy Registry of Norway. One hundred forty-four children with CP and 1,082 controls were included. The relationship between maternal blood concentrations of five toxic metals and six essential elements and CP diagnoses were investigated using mixture approaches: elastic net with stability selection to identify important metals/elements in the mixture in relation to CP; then logistic regressions of the selected metals/elements to estimate odds ratio (OR) of CP and two-way interactions among metals/elements and with child sex and maternal education. Finally, the joint effects of the mixtures on CP diagnoses were estimated using quantile-based g-computation analyses. Results The essential elements manganese and copper, as well as the toxic metal Hg, were the most important in relation to CP. Elevated maternal levels of copper (OR = 1.40) and manganese (OR = 1.20) were associated with increased risk of CP, while Hg levels were, counterintuitively, inversely related to CP. Metal/element interactions that were associated with CP were observed, and that sex and maternal education influenced the relationships between metals/elements and CP. In the joint mixture approach no significant association between the mixture of metals/elements and CP (OR = 1.00, 95% CI = [0.67, 1.50]) was identified. Conclusion Using mixture approaches, elevated levels of copper and manganese measured in maternal blood during the second trimester could be related to increased risk of CP in children. The inverse associations between maternal Hg and CP could reflect Hg as a marker of maternal fish intake and thus nutrients beneficial for foetal brain development.
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Affiliation(s)
- Kjell Vegard F. Weyde
- Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Adriano Winterton
- Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Pål Surén
- Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Guro L. Andersen
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Torstein Vik
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Guido Biele
- Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Helle K. Knutsen
- Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Cathrine Thomsen
- Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Helle M. Meltzer
- Division of Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Thea S. Skogheim
- Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Stephanie M. Engel
- Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
| | - Heidi Aase
- Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway
| | - Gro D. Villanger
- Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway
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Gonzalez NA, Sanivarapu RR, Osman U, Latha Kumar A, Sadagopan A, Mahmoud A, Begg M, Tarhuni M, N Fotso M, Khan S. Physical Therapy Interventions in Children With Cerebral Palsy: A Systematic Review. Cureus 2023; 15:e43846. [PMID: 37736433 PMCID: PMC10510427 DOI: 10.7759/cureus.43846] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Accepted: 08/21/2023] [Indexed: 09/23/2023] Open
Abstract
Cerebral palsy is a group of disorders affecting individuals already from birth. It enormously impacts an individual's physical and emotional life and can bring many challenges to the individual, caregivers, and families. Therefore, it is crucial to investigate interventions that could improve various symptoms in children with cerebral palsy. Our systematic review intends to assess the effect of different exercise and physical therapy interventions in children with cerebral palsy. We used three databases for our article search: PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), and PubMed Central (PMC). The combined number of papers found in all databases was 65,412. We then applied our inclusion and exclusion criteria, filters, key terms, and Medical Subheadings (MeSH). After applying our quality assessment tools, we included nine papers in our systematic review. The studies included in our review used various interventions to assess for improvement in symptoms in individuals with cerebral palsy. Interventions included stretching and resistance exercises, horse riding, biking, core stability exercises, slackline training, a home exercise program using an online tool, sit-to-stand exercise program, and functional training. Many studies have shown that interventions improved symptoms like balance, coordination, gait, and cardiovascular endurance in cerebral palsy. This review suggests that some of the included interventions have great potential to improve the symptoms of cerebral palsy and, therefore, can be a great addition to existing training and rehabilitation programs. Given that studies included a relatively small number of participants and were conducted over a short time, more research with a more significant number of participants over a longer time is necessary.
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Affiliation(s)
- Natalie A Gonzalez
- Pediatrics, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Raghavendra R Sanivarapu
- Pulmonary and Critical Care Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Pulmonary and Critical Care Medicine, Nassau University Medical Center, East Meadow, USA
| | - Usama Osman
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
- Geriatrics, Michigan State University College of Human Medicine, East Lansing, USA
| | - Abishek Latha Kumar
- Internal medicine, pediatrics, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Aishwarya Sadagopan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Anas Mahmoud
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Maha Begg
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Mawada Tarhuni
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Monique N Fotso
- Obstetrics and Gynecology, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
| | - Safeera Khan
- Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA
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Abstract
PURPOSE To identify the earliest predictors of risk for diagnosis of cerebral palsy (CP). METHODS A comprehensive literature search was conducted using various databases. The publications were reviewed to identify risk factors for CP from conception to early infancy. Studies were critically appraised with Joanna Briggs Institute guidelines for quality appraisal and evaluated for risk of bias using the Agency for Health Care Research and Quality guidelines. RESULTS The initial search yielded 129 studies and 20 studies were included. Forty-seven risk factors for CP were extracted of which several were duplicate terms. The significant risk factors found to be indicative of CP were low birth weight (<1500 g), birth at less than 28 weeks of gestational age, periventricular leukomalacia, grade 3 or 4 intraventricular hemorrhage, preeclampsia, prematurity, an Apgar score of less than 4 at the first minute, birth asphyxia, preterm premature rupture of membrane, and absent fidgety movements. CONCLUSION Twenty-three factors were consistently reported as predictors of CP.
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Affiliation(s)
- Tanochni Mohanty
- Department of Pediatric Physiotherapy (Ms Mohanty), JSS College of Physiotherapy, Mysuru, Karnataka, India; Department of Musculoskeletal Physiotherapy (Dr Joseph), Lokmanya Tilak College of Physiotherapy, Navi Mumbai, Maharashtra, India; Department of Pediatrics (Drs Gunasekaran and Saini), All India Institute of Medical Sciences, Jodhpur, Rajasthan, India; Department of Pediatrics (Dr Doreswamy), JSS Medical College and Hospital, Mysuru, Karnataka, India
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Mwinbam MM, Suglo JN, Agyeman YN, Kukeba MW. Family caregivers' experience of care with a child with cerebral palsy: the lived experiences and challenges of caregivers in a resource-limited setting in northern Ghana. BMJ Paediatr Open 2023; 7:e001807. [PMID: 37407248 PMCID: PMC10335558 DOI: 10.1136/bmjpo-2022-001807] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Accepted: 06/22/2023] [Indexed: 07/07/2023] Open
Abstract
INTRODUCTION Caring for a child with cerebral palsy may be more emotionally and physically exhausting than caring for a typical growing child. The family caregivers' perspective of this phenomenon needs exploring to facilitate the development of services. Our study explored the challenges family caregivers face with children with cerebral palsy in a resource-limited context in northern Ghana. METHODS We conducted a qualitative study underpinned by phenomenological principles where it is believed that the reality of a phenomenon is tied to caregivers' perspectives of their own experiences. In this study, we unearthed caregivers' experiences/challenges from their own perspectives. The method of data analysis used was to allow the issues to emerge from the data (inductive process) using the content analysis approach. We recruited 13 caregivers of children with cerebral palsy from the physiotherapy unit at Tamale Teaching Hospital, and conducted individual in-depth interviews supported by an open-ended topic guide. Interviews were audio recorded, transcribed, and translated and coded inductively before conducting a content analysis of the data when grouped into themes. RESULTS We have identified barriers to managing a child with cerebral palsy, including sociocultural barriers (values, attitudes and belief systems within society), economic challenges and immediate physical care burdens. Specific barriers included discrimination and isolation, lack of family and societal support, with poor access to health information and formal education. Others were lack of information on the cause and course of cerebral palsy, caregivers' loss of jobs, increased healthcare expenditure and struggles in lifting and moving children, which resonate with evidence-based multidimensional model of caregiving process and caregiver burden. CONCLUSION Caregivers have the arduous task of caring for a child with cerebral palsy. Social support interventions and policy initiatives that seek to ameliorate caregivers' finances and make formal education accessible to this marginalised child population may be beneficial in this context.
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Affiliation(s)
- Mavis Mallory Mwinbam
- Department of Nursing, Nadowli District Hospital, Upper West Region, Nadowli, Ghana
- Faculty of Paediatric Nursing, Ghana College of Nurses and Midwives (GCNM), Accra, Ghana
| | - Joseph Ngmenesegre Suglo
- Department of Nursing and Midwifery, Presbyterian University College, Abetifi, Ghana
- Florence Nightingale Faculty of Nursing, Midwifery & Palliative Care, King's College London, London, UK
| | - Yaa Nyarko Agyeman
- Department of Population and Reproductive Health, School of Public Health, University for Development Studies, Tamale, Ghana
| | - Margaret Wekem Kukeba
- Department of Nursing, C K Tedam University of Technology and Applied Sciences, Navrongo, Ghana
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da Silva Souza V, Manhães-de-Castro R, Pereira SDC, Calado CMSDS, Souza de Silveira B, Araújo ERDS, Silva SCDA, Junior OHDS, Lagranha CJ, da Silva LKTM, Toscano AE. Neonatal treatment with resveratrol decreases postural and strength impairments and improves mitochondrial function in the somatosensory cortex rats submitted to cerebral palsy. Neurochem Int 2023:105568. [PMID: 37385449 DOI: 10.1016/j.neuint.2023.105568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 06/08/2023] [Accepted: 06/26/2023] [Indexed: 07/01/2023]
Abstract
Cerebral palsy is a neurodevelopmental disease characterized by postural, motor, and cognitive disorders, being one of the main causes of physical and intellectual disability in childhood. To minimize functional impairments, the use of resveratrol as a therapeutic strategy is highlighted due to its neuroprotective and antioxidant effects in different regions of the brain. Thus, this study aimed to investigate the effects of neonatal treatment with resveratrol on postural development, motor function, oxidative balance, and mitochondrial biogenesis in the brain of rats submitted to a cerebral palsy model. Neonatal treatment with resveratrol attenuated deficits in somatic growth, postural development, and muscle strength in rats submitted to cerebral palsy. Related to oxidative balance, resveratrol in cerebral palsy decreased the levels of MDA and carbonyls. Related to mitochondrial biogenesis, was observed in animals with cerebral palsy treated with resveratrol, an increase in mRNA levels of TFAM, in association with the increase of citrate synthase activity. The data demonstrated a promising effect of neonatal resveratrol treatment, improving postural and muscle deficits induced by cerebral palsy. These findings were associated with improvements in oxidative balance and mitochondrial biogenesis in the brain of rats submitted to cerebral palsy.
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Affiliation(s)
- Vanessa da Silva Souza
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil; Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil
| | - Raul Manhães-de-Castro
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil; Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil; Graduate Program in Nutrition, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil
| | - Sabrina da Conceição Pereira
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil; Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil
| | - Caio Matheus Santos da Silva Calado
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil; Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil
| | - Beatriz Souza de Silveira
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil; Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil
| | - Eulália Rebeca da Silva Araújo
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil; Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil
| | - Severina Cassia de Andrade Silva
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil
| | - Osmar Henrique Dos Santos Junior
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil
| | - Claudia Jacques Lagranha
- Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil; Graduate Program in Biochemistry and Physiology, Center for Biosciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil
| | - Luan Kelwyny Thaywã Marques da Silva
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil; Graduate Program in Nutrition, Physical Activity and Phenotypic Plasticity, Vitória Academic Center, Federal University of Pernambuco, Vitória de Santo Antão, Pernambuco, 55608-680, Brazil
| | - Ana Elisa Toscano
- Studies in Nutrition and Phenotypic Plasticity Unit, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil; Graduate Program in Neuropsychiatry and Behavioral Sciences, Center for Medical Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-901, Brazil; Graduate Program in Nutrition, Center for Health Sciences, Federal University of Pernambuco, Recife, Pernambuco, 50670-420, Brazil; Nursing Unit, Vitória Academic Center, Federal University of Pernambuco, Vitória de Santo Antão, Pernambuco, 55608-680, Brazil.
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Barron-Garza F, Coronado-Garza M, Gutierrez-Ramirez S, Ramos-Rincon JM, Guzman-de la Garza F, Lozano-Morantes A, Flores-Rodriguez A, Nieto-Sanjuanero A, Alvarez-Villalobos N, Flores-Villarreal M, Covarrubias-Contreras L. Incidence of Cerebral Palsy, Risk Factors, and Neuroimaging in Northeast Mexico. Pediatr Neurol 2023; 143:50-58. [PMID: 37001462 DOI: 10.1016/j.pediatrneurol.2023.02.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Revised: 11/17/2022] [Accepted: 02/10/2023] [Indexed: 05/22/2023]
Abstract
BACKGROUND Cerebral palsy (CP) comprises a group of lifelong motor and postural development disorders that can cause static motor encephalopathy. The etiology of CP is attributed to nonprogressive lesions of the central nervous system during fetal or infant brain development. A diagnosis of CP is based on a combination of clinical and neurological signs, typically identified between 12 and 24 months. A medical history, several available standardized tools, including the Neoneuro assessment, and the Hammersmith infant neurological examination (HINE) can be used to predict risk. Magnetic resonance imaging (MRI) can contribute to the diagnosis of CP. The incidence of CP is 2 to 3 per 1000 live births, and in Western industrialized nations, it is 2.0-2.5 per 1000 live births; to our knowledge, no epidemiological studies have reported the incidence of CP in Mexico. AIM To assess the incidence of CP in children aged up to 18 months in northeast Mexico and analyze the risk factors and neuroimaging findings. METHODS This was a multicenter, randomized, prospective, cohort, analytical study of newborn children in three community hospitals and an early intervention and CP center in Nuevo Leon, Mexico, from 2017 to 2021. This study included 3861 newborns randomly selected from a population of 75,951 mothers in the immediate puerperium. According to the Neoneuro tool, high-risk children (n = 432) had abnormal neurological results at birth; they were followed and assessed with the Spanish version of the HINE test by a pediatric neurologist and underwent neuroimaging studies. Neonates with normal results were randomly selected to be in the low-risk group (n= 864). These neonates were followed and assessed with the HINE by a neonatologist. RESULTS The incidence of CP was 4.4 of 1000 up to 18 months old, which was higher than that reported in developed countries. Perinatal risk factors were predominantly recognized in the etiology of CP, such as brain hemorrhage, and prematurity, in addition to congenital anomalies. The most frequent neuroimaging findings were ventricular dilation/cortical atrophy and intraventricular/subependymal hemorrhage and periventricular leukomalacia on MRI. CONCLUSIONS This study is the first on the incidence/prevalence of CP in Mexico, and there are no formal studies in this field in other Latin American countries either. The incidence of CP in northeast Mexico is higher than that reported in developed countries. The follow-up of high-risk young children must be reinforced in the Mexican population, as children with disabilities have high and sequential health-care needs and may usually be lost to follow-up. Neuroimaging of PVL was the more frequent finding by MRI in this population.
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Affiliation(s)
| | - Mario Coronado-Garza
- Facultad de Medicina, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México
| | | | | | | | - Alexia Lozano-Morantes
- Hospital Materno-Infantil, Secretaría de Salud, Guadalupe, Nuevo León, México; Hospital Metropolitano "Dr. Bernardo Sepúlveda", San Nicolás de los Garza, Nuevo León, México
| | | | | | - Neri Alvarez-Villalobos
- Facultad de Medicina, Universidad Autónoma de Nuevo León, San Nicolás de los Garza, Nuevo León, México
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Gallo DM, Romero R, Bosco M, Gotsch F, Jaiman S, Jung E, Suksai M, Ramón Y Cajal CL, Yoon BH, Chaiworapongsa T. Meconium-stained amniotic fluid. Am J Obstet Gynecol 2023; 228:S1158-S1178. [PMID: 37012128 PMCID: PMC10291742 DOI: 10.1016/j.ajog.2022.11.1283] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 11/09/2022] [Accepted: 11/09/2022] [Indexed: 04/04/2023]
Abstract
Green-stained amniotic fluid, often referred to as meconium-stained amniotic fluid, is present in 5% to 20% of patients in labor and is considered an obstetric hazard. The condition has been attributed to the passage of fetal colonic content (meconium), intraamniotic bleeding with the presence of heme catabolic products, or both. The frequency of green-stained amniotic fluid increases as a function of gestational age, reaching approximately 27% in post-term gestation. Green-stained amniotic fluid during labor has been associated with fetal acidemia (umbilical artery pH <7.00), neonatal respiratory distress, and seizures as well as cerebral palsy. Hypoxia is widely considered a mechanism responsible for fetal defecation and meconium-stained amniotic fluid; however, most fetuses with meconium-stained amniotic fluid do not have fetal acidemia. Intraamniotic infection/inflammation has emerged as an important factor in meconium-stained amniotic fluid in term and preterm gestations, as patients with these conditions have a higher rate of clinical chorioamnionitis and neonatal sepsis. The precise mechanisms linking intraamniotic inflammation to green-stained amniotic fluid have not been determined, but the effects of oxidative stress in heme catabolism have been implicated. Two randomized clinical trials suggest that antibiotic administration decreases the rate of clinical chorioamnionitis in patients with meconium-stained amniotic fluid. A serious complication of meconium-stained amniotic fluid is meconium aspiration syndrome. This condition develops in 5% of cases presenting with meconium-stained amniotic fluid and is a severe complication typical of term newborns. Meconium aspiration syndrome is attributed to the mechanical and chemical effects of aspirated meconium coupled with local and systemic fetal inflammation. Routine naso/oropharyngeal suctioning and tracheal intubation in cases of meconium-stained amniotic fluid have not been shown to be beneficial and are no longer recommended in obstetrical practice. A systematic review of randomized controlled trials suggested that amnioinfusion may decrease the rate of meconium aspiration syndrome. Histologic examination of the fetal membranes for meconium has been invoked in medical legal litigation to time the occurrence of fetal injury. However, inferences have been largely based on the results of in vitro experiments, and extrapolation of such findings to the clinical setting warrants caution. Fetal defecation throughout gestation appears to be a physiologic phenomenon based on ultrasound as well as in observations in animals.
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Affiliation(s)
- Dahiana M Gallo
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI; Department of Gynecology and Obstetrics, Universidad Del Valle, Cali, Colombia
| | - Roberto Romero
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI.
| | - Mariachiara Bosco
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
| | - Francesca Gotsch
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
| | - Sunil Jaiman
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Pathology, Wayne State University School of Medicine, Detroit, MI
| | - Eunjung Jung
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
| | - Manaphat Suksai
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
| | - Carlos López Ramón Y Cajal
- Unit of Prenatal Diagnosis, Service of Obstetrics and Gynecology, Álvaro Cunqueiro Hospital, Vigo, Spain
| | - Bo Hyun Yoon
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Tinnakorn Chaiworapongsa
- Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI
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Zhou L, Meng Q, von Ehrenstein OS, Xiao J, Gao Y, Wu YW, Ritz B, Liew Z. Parental Age and Childhood Risk for Cerebral Palsy in California. J Pediatr 2023; 255:147-153.e6. [PMID: 36372095 PMCID: PMC10121738 DOI: 10.1016/j.jpeds.2022.10.039] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 10/12/2022] [Accepted: 10/16/2022] [Indexed: 11/13/2022]
Abstract
OBJECTIVE To investigate the associations between maternal or paternal age at the time of delivery and offspring's risk for cerebral palsy (CP) in California. STUDY DESIGN We conducted a population-based, case-control study that included 8736 singleton CP cases and 90 250 singleton controls, matched by sex and birth year, selected from California birth certificate records from 1994 to 2010. We estimated OR and 95% CIs for CP diagnosis according to maternal and paternal age recorded on the birth certificates. Causal mediation analysis was performed to estimate direct and indirect effects of parental ages on CP with preterm delivery as a potential mediator. RESULTS Children born to younger mothers (≤19 years) or older mothers (35-39 years; ≥40 years) had a greater risk of CP compared with children of mothers aged 25-29 years (ORs ranging from 1.13 to 1.59). Compared with paternal age 25-29 years, older paternal age (40-44 years; ≥45 years) also was associated with an increased risk for CP independent of maternal age. When analyzing jointly using both parents of ages 20-34 years as the reference, the greatest risk was estimated for older parents (≥35 years). Preterm birth was estimated to mediate 19%-34% of the total effects between maternal or paternal age and offspring CP risk. CONCLUSIONS Young maternal age and an older age in either or both parents were associated with a greater risk of CP in their children. Although preterm birth was a mediator, additional factors related to parental age need further exploration to explain risk of CP.
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Affiliation(s)
- Lifang Zhou
- Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, China; Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, CT
| | - Qi Meng
- Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, CA
| | - Ondine S von Ehrenstein
- Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, CA; Department of Community Health Sciences, Fielding School of Public Health, UCLA, Los Angeles, CA
| | - Jingyuan Xiao
- Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, CT; Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT
| | - Yu Gao
- Department of Environmental Health, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yvonne W Wu
- Departments of Neurology and Pediatrics, UCSF, San Francisco, CA
| | - Beate Ritz
- Department of Epidemiology, Fielding School of Public Health, UCLA, Los Angeles, CA; Department of Neurology, School of Medicine, UCLA, Los Angeles, CA
| | - Zeyan Liew
- Yale Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, CT; Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT.
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Cabezas-López M. How Is Cerebral Palsy Different from Other Childhood Neurological Disorders? JOURNAL OF PEDIATRIC NEUROPSYCHOLOGY 2023. [DOI: 10.1007/s40817-023-00140-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2023]
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Usman S, Hanidu A, Kovalenko M, Hassan WA, Lees C. The sonopartogram. Am J Obstet Gynecol 2023; 228:S997-S1016. [PMID: 37164504 DOI: 10.1016/j.ajog.2022.06.027] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 06/15/2022] [Accepted: 06/16/2022] [Indexed: 03/17/2023]
Abstract
The assessment of labor progress from digital vaginal examination has remained largely unchanged for at least a century, despite the current major advances in maternal and perinatal care. Although inconsistently reproducible, the findings from digital vaginal examination are customarily plotted manually on a partogram, which is composed of a graphical representation of labor, together with maternal and fetal observations. The partogram has been developed to aid recognition of failure to labor progress and guide management-specific obstetrical intervention. In the last decade, the use of ultrasound in the delivery room has increased with the advent of more powerful, portable ultrasound machines that have become more readily available for use. Although ultrasound in intrapartum practice is predominantly used for acute management, an ultrasound-based partogram, a sonopartogram, might represent an objective tool for the graphical representation of labor. Demonstrating greater accuracy for fetal head position and more objectivity in the assessment of fetal head station, it could be considered complementary to traditional clinical assessment. The development of the sonopartogram concept would require further undertaking of serial measurements. Advocates of ultrasound will concede that its use has yet to demonstrate a difference in obstetrical and neonatal morbidity in the context of the management of labor and delivery. Taking a step beyond the descriptive graphical representation of labor progress is the question of whether a specific combination of clinical and demographic parameters might be used to inform knowledge of labor outcomes. Intrapartum cesarean deliveries and deliveries assisted by forceps and vacuum are all associated with a heightened risk of maternal and perinatal adverse outcomes. Although these outcomes cannot be precisely predicted, many known risk factors exist. Malposition and high station of the fetal head, short maternal stature, and other factors, such as caput succedaneum, are all implicated in operative delivery; however, the contribution of individual parameters based on clinical and ultrasound assessments has not been quantified. Individualized risk prediction models, including maternal characteristics and ultrasound findings, are increasingly used in women's health-for example, in preeclampsia or trisomy screening. Similarly, intrapartum cesarean delivery models have been developed with good prognostic ability in specifically selected populations. For intrapartum ultrasound to be of prognostic value, robust, externally validated prediction models for labor outcome would inform delivery management and allow shared decision-making with parents.
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Ahmed A, Rosella LC, Oskoui M, Watson T, Yang S. In utero Exposure to Maternal Diabetes and the Risk of Cerebral Palsy: A Population-based Cohort Study. Epidemiology 2023; 34:247-258. [PMID: 36722807 DOI: 10.1097/ede.0000000000001574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
BACKGROUND Evidence on the effects of in utero exposure to maternal diabetes on cerebral palsy (CP) in offspring is limited. We aimed to examine the effects of pregestational (PGDM) and gestational diabetes (GDM) separately on CP risk and the mediating role of increased fetal size. METHODS In a population-based study, we included all live births in Ontario, Canada, between 2002 and 2017 followed up through 2018 (n = 2,110,177). Using administrative health data, we estimated crude and adjusted associations between PGDM or GDM and CP using Cox proportional hazards models to account for unequal follow-up in children. For the mediation analysis, we used marginal structural models to estimate the controlled direct effect of PGDM (and GDM) on the risk of CP not mediated by large-for-gestational age (LGA). RESULTS During the study period, 5,317 children were diagnosed with CP (187 exposed to PGDM and 171 exposed to GDM). Children of mothers with PGDM showed an increased risk (hazard ratio [HR]: 1.84 [95% confidence interval (CI): 1.59, 2.14]) after adjusting for maternal sociodemographic and clinical factors. We found no associations between GDM and CP (adjusted HR: 0.91 [0.77, 1.06]). Our mediation analysis estimated that LGA explained 14% of the PDGM-CP association. CONCLUSIONS In this population-based birth cohort study, maternal pregestational diabetes was associated with increased risk of CP, and the increased risk was not substantially mediated by the increased fetal size.
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Affiliation(s)
- Asma Ahmed
- From the Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada
- Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, ON, Canada
| | - Laura C Rosella
- Dalla Lana School of Public Health, Division of Epidemiology, University of Toronto, Toronto, ON, Canada
- ICES, Toronto, ON, Canada
- Institute for Better Health, Trillium Health Partners, Mississauga, ON, Canada
- Temerty Faculty of Medicine, Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada
| | - Maryam Oskoui
- McGill University Health Center Research Institute (RI-MUHC), Child Health and Human Development Program, Centre for Outcomes Research and Evaluation, Montreal, QC, Canada
- Department of Pediatrics, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada
- Department of Neurology & Neurosurgery, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada
| | - Tristan Watson
- Dalla Lana School of Public Health, Division of Epidemiology, University of Toronto, Toronto, ON, Canada
- ICES, Toronto, ON, Canada
| | - Seungmi Yang
- From the Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada
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Ebbing C, Rasmussen S, Kessler J, Moster D. Association of placental and umbilical cord characteristics with cerebral palsy: national cohort study. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2023; 61:224-230. [PMID: 36722428 PMCID: PMC10108292 DOI: 10.1002/uog.26047] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 07/21/2022] [Accepted: 07/27/2022] [Indexed: 05/27/2023]
Abstract
OBJECTIVES Cerebral palsy (CP) is a group of movement disorders usually diagnosed in childhood. A substantial proportion are thought to be caused by antenatal events. Abnormalities of the umbilical cord and placenta are associated with an increased risk of adverse neonatal outcomes, but it is unclear whether these conditions also carry an increased risk of CP. We aimed to determine whether abnormalities of the umbilical cord or placenta are associated with CP and assess if these associations differ by sex of the child or gestational age at birth. METHODS We performed a national cohort study by linking data from The Medical Birth Registry of Norway with other national registries. All liveborn singletons born between 1999 and 2017 (n = 1 087 486) were included and followed up until the end of 2019. Diagnoses of CP were provided by the Norwegian National Insurance Scheme and the Norwegian Patient Register. We used generalized estimating equations and multilevel log binomial regression to calculate relative risks (RR), adjusted for year of birth, and stratified analyses were carried out based on sex and gestational age at birth. Exposures were abnormal umbilical cord (velamentous or marginal insertion, single umbilical artery (SUA), knots and entanglement), and placental abnormalities (retained placenta, placental abruption and previa). RESULTS A total of 2443 cases with CP (59.8% males) were identified. Velamentous cord insertion (adjusted RR (aRR), 2.11 (95% CI, 1.65-2.60)), cord knots (aRR, 1.53 (95% CI, 1.15-2.04)) and placental abnormalities (placenta previa (aRR, 3.03 (95% CI, 2.00-4.61)), placental abruption (aRR, 10.63 (95% CI, 8.57-13.18)) and retained placenta (aRR, 1.71 (95% CI, 1.32-2.22))) carried an increased risk of CP. Velamentous cord insertion was associated with CP regardless of gestational age or sex. A retained placenta was associated with a 2-fold increased risk for CP in males, while the associations of SUA and cord knot with CP were significant only among females. CONCLUSIONS The detection of placental and umbilical cord abnormalities may help identify children at increased risk of CP. The associations between placental or umbilical cord abnormalities and the risk of CP do not vary substantially with gestational age at birth or sex of the child. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
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Affiliation(s)
- C. Ebbing
- Department of Obstetrics and GynecologyHaukeland University HospitalBergenNorway
- Department of Clinical ScienceUniversity of BergenBergenNorway
| | - S. Rasmussen
- Department of Clinical ScienceUniversity of BergenBergenNorway
| | - J. Kessler
- Department of Obstetrics and GynecologyHaukeland University HospitalBergenNorway
- Department of Clinical ScienceUniversity of BergenBergenNorway
| | - D. Moster
- Department of Global Public Health and Primary CareUniversity of BergenBergenNorway
- Department of PediatricsHaukeland University HospitalBergenNorway
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Misan N, Michalak S, Kapska K, Osztynowicz K, Ropacka-Lesiak M, Kawka-Paciorkowska K. Does the Blood-Brain Barrier Integrity Change in Regard to the Onset of Fetal Growth Restriction? Int J Mol Sci 2023; 24:ijms24031965. [PMID: 36768287 PMCID: PMC9916066 DOI: 10.3390/ijms24031965] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 12/18/2022] [Accepted: 01/06/2023] [Indexed: 01/21/2023] Open
Abstract
The aim of the study was to determine whether early-onset and late-onset fetal growth restriction (FGR) differentially affects the blood-brain barrier integrity. Furthermore, the purpose of the study was to investigate the relationship between the blood-brain barrier breakdown and neurological disorders in FGR newborns. To evaluate the serum tight junction (TJ) proteins and the placental TJ proteins expression, an ELISA method was used. A significant difference in serum OCLN concentrations was noticed in pregnancies complicated by the early-onset FGR, in relation to the intraventricular hemorrhage (IVH) occurrence in newborns. No significant differences in concentrations of the NR1 subunit of the N-methyl-d-aspartate receptor (NR1), nucleoside diphosphate kinase A (NME1), S100 calcium-binding protein B (S100B), occludin (OCLN), claudin-5 (CLN5), zonula occludens-1 (zo-1), the CLN5/zo-1 ratio, and the placental expression of OCLN, CLN5, claudin-4 (CLN4), zo-1 were noticed between groups. The early-onset FGR was associated with a higher release of NME1 into the maternal circulation in relation to the brain-sparing effect and premature delivery. Additionally, in late-onset FGR, the higher release of the S100B into the maternal serum in regard to fetal distress was observed. Furthermore, there was a higher release of zo-1 into the maternal circulation in relation to newborns' moderate acidosis in late-onset FGR. Blood-brain barrier disintegration is not dependent on pregnancy advancement at the time of FGR diagnosis. NME1 may serve as a biomarker useful in the prediction of fetal circulatory centralization and extremely low birth weight in pregnancies complicated by the early-onset FGR. Moreover, the serum zo-1 concentration may have prognostic value for moderate neonatal acidosis in late-onset FGR pregnancies.
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Affiliation(s)
- Natalia Misan
- Department of Perinatology and Gynecology, Poznan University of Medical Sciences, 60-535 Poznan, Poland
- Correspondence:
| | - Sławomir Michalak
- Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, 60-355 Poznan, Poland
- Department of Neurosurgery and Neurotraumatology, Poznan University of Medical Sciences, 60-355 Poznan, Poland
| | - Katarzyna Kapska
- Department of Perinatology and Gynecology, Poznan University of Medical Sciences, 60-535 Poznan, Poland
| | - Krystyna Osztynowicz
- Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, 60-355 Poznan, Poland
| | - Mariola Ropacka-Lesiak
- Department of Perinatology and Gynecology, Poznan University of Medical Sciences, 60-535 Poznan, Poland
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Karaseridis K, Dermata A. Cerebral palsy: Oral manifestations and dental management. BALKAN JOURNAL OF DENTAL MEDICINE 2023. [DOI: 10.5937/bjdm2301001k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/12/2023] Open
Abstract
Cerebral palsy is a set of non-progressive neuromuscular disorders caused by defects in the developing fetal brain. Its prevalence is about 2:1000. Although CP does not directly result in any particular oral abnormalities, some conditions are more prevalent or severe in CP patients than in the general population. The purpose of a paediatric dentist is to promote overall oral health wellness and to motivate parents and other primary caregivers to practice good oral hygiene at home. The aim of this article is to provide a general overview of dental health issues that affect people with CP and to analyze key preventative and practical management techniques for this common comorbidity.
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Ahmed A, Rosella LC, Oskoui M, Watson T, Yang S. In Utero Exposure to Maternal Injury and the Associated Risk of Cerebral Palsy. JAMA Pediatr 2023; 177:53-61. [PMID: 36441546 PMCID: PMC9706397 DOI: 10.1001/jamapediatrics.2022.4535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 08/24/2022] [Indexed: 11/29/2022]
Abstract
Importance Although maternal unintentional injury during pregnancy has shown negative impacts on the mother and fetus, the evidence on its long-term associations with children's neurodevelopment is limited. Objective To examine the association between maternal unintentional injury and cerebral palsy (CP) in offspring. Design, Setting, and Participants This was a population-based, longitudinal, cohort study of all in-hospital live births born between April 1, 2002, and March 31, 2017, in a publicly funded health care system setting of Ontario, Canada. Infants born more than 20 weeks' gestation were included and followed up until March 31, 2018. Excluded from the analysis were stillbirths, infants with missing or invalid records, and births with missing or invalid birth characteristics. Data were analyzed from March 1 to June 30, 2021. Exposures Maternal unintentional injury during pregnancy ascertained based on inpatient or emergency department diagnoses. Main Outcomes and Measures CP diagnosis between birth and the end of follow-up in 2018 with the CP case definition of a single inpatient or 2 or more outpatient diagnoses at least 2 weeks apart between birth and age 16 years. Results Of 2 110 177 children included in this study (mean [SD] gestational age, 38.8 [1.9] weeks; 1 082 520 male [51.3%]), 81 281 (3.9%) were exposed in utero to maternal unintentional injury. During a median (IQR) follow-up time of 8 (4-12) years, 5317 children (0.3%) were diagnosed with CP (292 CP cases [5.5%] were exposed to maternal unintentional injury). The mean incidence rates of CP were 4.36 and 2.93 per 10 000 child-years in the exposed and the unexposed group, respectively. Children exposed to maternal unintentional injury had a modest increase in the risk of CP, compared with those unexposed (hazard ratio [HR], 1.33; 95% CI, 1.18-1.50) after adjusting for maternal sociodemographic and clinical characteristics. Severe injuries that resulted in hospitalization and delivery within 1 week from the injury conferred higher risks of CP (adjusted HR, 2.18; 95% CI, 1.29-3.68 and adjusted HR, 3.40; 95% CI, 1.93-6.00, respectively). Results were robust in multiple bias analyses. Conclusions and Relevance In this Canadian population-based birth cohort study, in utero exposure to maternal unintentional injury was associated with an increased risk of CP, with a higher risk with more severe injuries. These findings fill an important gap in knowledge on the potential role of maternal injury on children's neurodevelopment outcomes. Public health professionals and stakeholders should be aware of these potential long-term consequences on offspring when designing programs and providing recommendations about safety during pregnancy. Early monitoring and developmental assessment of children exposed to maternal injury might be warranted.
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Affiliation(s)
- Asma Ahmed
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
- Child Health Evaluative Sciences, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
| | - Laura C. Rosella
- Dalla Lana School of Public Health, Division of Epidemiology, University of Toronto, Toronto, Ontario, Canada
- ICES, Toronto, Ontario, Canada
- Institute for Better Health, Trillium Health Partners, Mississauga, Ontario, Canada
- Temerty Faculty of Medicine, Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, Ontario, Canada
| | - Maryam Oskoui
- McGill University Health Center Research Institute, Child Health and Human Development Program, Centre for Outcomes Research and Evaluation, Montreal, Quebec, Canada
- Department of Pediatrics, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec, Canada
- Department of Neurology & Neurosurgery, Faculty of Medicine and Health Sciences, McGill University, Montreal, Quebec, Canada
| | - Tristan Watson
- Dalla Lana School of Public Health, Division of Epidemiology, University of Toronto, Toronto, Ontario, Canada
- ICES, Toronto, Ontario, Canada
| | - Seungmi Yang
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
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40
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Liew Z, Zhuo H. Cerebral Palsy and Maternal Injury During Pregnancy. JAMA Pediatr 2023; 177:10-11. [PMID: 36441524 DOI: 10.1001/jamapediatrics.2022.4541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Zeyan Liew
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut.,Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, Connecticut
| | - Haoran Zhuo
- Department of Environmental Health Sciences, Yale School of Public Health, New Haven, Connecticut.,Yale Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, Connecticut
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41
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Magnetic resonance imaging findings and the clinical characteristics of children with cerebral palsy at a public sector hospital in Gauteng Province, South Africa. SOUTH AFRICAN JOURNAL OF CHILD HEALTH 2022. [DOI: 10.7196/sajch.2022.v16i4.1900] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Background. Cerebral palsy (CP) is a common cause of physical impairment in children. Brain magnetic resonance imaging (MRI) can define different neuropathological patterns of brain injury in CP. There are limited data available on MRI findings of children with CP in Africa.
Objective. To describe the clinical characteristics, risk factors and MRI findings of children with CP attending a developmental clinic at a tertiary hospital in South Africa; and to assess possible associations between the clinical characteristics and pathogenic neuro-imaging patterns.
Methods. This was a retrospective cross-sectional study. The cohort of 112 children was identified from the clinic’s REDcap database. Clinical information was obtained from existing medical records of the patients. Findings from brain MRI reports were classified according to the MRI classification system (MRICS) for CP. The MRI reports were rated independently by two study investigators. A descriptive analysis was conducted.
Results. A total of 112 patient files and MRI brain reports were reviewed. Spastic CP was the most common type of CP (n=75%). The most common perinatal risk factors included prematurity (31%) and low birthweight (28%). Nineteen (17%) children acquired CP after the neonatal period. CP sub-type showed a significant association with functional motor impairment classified as per the gross motor function classification system (GMFCS), p<0.001. Predominant grey matter injury (PGMI) was the most common pathogenic MRI pattern identified (30%). The radiological findings (per MRICS) had a significant association with both the CP sub-type (p<0.005) and functional impairment according to the GMFCS (p<0.001).
Conclusion. Standardised classification of neuro-imaging findings can assist in defining the pathogenesis and clinical manifestations of CP.
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Kamal S, Kamaralzaman S, Sharma S, Jaafar NH, Chern PM, Hassan NI, Toran H, Ismail NAS, Yusri G, Hamzaid NH. A Review of Food Texture Modification among Individuals with Cerebral Palsy: The Challenges among Cerebral Palsy Families. Nutrients 2022; 14:nu14245241. [PMID: 36558401 PMCID: PMC9782059 DOI: 10.3390/nu14245241] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 12/03/2022] [Accepted: 12/04/2022] [Indexed: 12/13/2022] Open
Abstract
Individuals with cerebral palsy (CP) frequently present with multiple feeding problems, which may require food texture modification to ensure safe feeding. This review aims to explore the challenges individuals with CP and their caregiver's face and recommend modified food textures to ensure safety and improve the quality of life and nutritional status. A systematic search was carried out through four databases (i.e., EBSCO (Medline), PubMed, Science Direct, and Web of Science) between January 2011 and May 2022. Out of 86 articles retrieved, seven were selected based on keywords and seven other studies through manual search-five cross-sectional studies, two qualitative studies, one correlational study, one mixed method study, one case-control study, two sections of books, and two educational materials. The findings suggest that preparation and intake of food with modified texture play a necessary role in the safety of swallowing in addition to physical, social, and environmental aspects. Safety was found to be the crucial part of the food texture modification provision besides considering the stress of the caregivers and the nutritional status of individuals with CP. Currently, there are no standard guidelines available pertaining to food texture modification. This led to uncertainties in the dietary provision among caregivers, which may lead to undernourishment. Hence, standard guidelines relating to food texture modification that focuses on food preparation and menus with calorie and nutrient information are timely to be developed.
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Affiliation(s)
- Sakinah Kamal
- Center for Rehabilitation and Special Needs Studies (iCaRehab), Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia
- Dietetics Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia
| | - Sazlina Kamaralzaman
- Center for Rehabilitation and Special Needs Studies (iCaRehab), Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia
| | - Shobha Sharma
- Center for Healthy Aging and Wellness (H-Care), Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia
| | - Nurul Hazirah Jaafar
- Department of Nutrition Sciences, Kulliyyah of Allied Health Sciences, International Islamic University Malaysia (IIUM), Jalan Sultan Ahmad Shah, Bandar Indera Mahkota, Kuantan 25200, Malaysia
| | - Phei Ming Chern
- Department of Rehabilitation Medicine (Paediatric Rehabilitation), Hospital Rehabilitasi Cheras, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
| | - Nurul Izzaty Hassan
- Department of Chemical Sciences, Faculty of Science & Technology, Universiti Kebangsaan Malaysia (UKM), Bandar Baru Bangi 43600, Malaysia
| | - Hasnah Toran
- Faculty of Education, Universiti Kebangsaan Malaysia (UKM), Bandar Baru Bangi 43600, Malaysia
| | - Noor Akmal Shareela Ismail
- Department of Biochemistry, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, Malaysia
| | - Ghazali Yusri
- Akademi Pengajian Bahasa, Universiti Teknologi Mara (UiTM), Shah Alam 40450, Malaysia
- Malaysian Advocates for Cerebral Palsy (MyCP), No 4., USJ3/4X, USJ3, Subang Jaya 47600, Malaysia
| | - Nur Hana Hamzaid
- Center for Rehabilitation and Special Needs Studies (iCaRehab), Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia
- Dietetics Program, Faculty of Health Sciences, Universiti Kebangsaan Malaysia (UKM), Jalan Raja Muda Abdul Aziz, Kuala Lumpur 50300, Malaysia
- Correspondence:
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Wilson YA, Smithers‐Sheedy H, Ostojic K, Waight E, Kruer MC, Fahey MC, Baynam G, Gécz J, Badawi N, McIntyre S. Common data elements to standardize genomics studies in cerebral palsy. Dev Med Child Neurol 2022; 64:1470-1476. [PMID: 35441707 PMCID: PMC9790418 DOI: 10.1111/dmcn.15245] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 03/23/2022] [Accepted: 03/23/2022] [Indexed: 01/31/2023]
Abstract
AIM To define clinical common data elements (CDEs) and a mandatory minimum data set (MDS) for genomic studies of cerebral palsy (CP). METHOD Candidate data elements were collated following a review of the literature and existing CDEs. An online, three-round Delphi survey was used to rate each data element as either 'core', 'recommended', 'exploratory', or 'not required'. Members of the International Cerebral Palsy Genomics Consortium (ICPGC) rated the core CDEs as either mandatory or not, to form the MDS. For both the CDEs and the MDS, a data element was considered to have reached consensus if more than 75% of respondents agreed. RESULTS Forty-six individuals from around the world formed the Delphi panel: consumers (n=2), scientists/researchers (n=17), medical (n=19), and allied health professionals (n=8). The CDEs include 107 data elements across six categories: demographics, diagnostics, family history, antenatal and neonatal details, clinical traits, and CP-specific assessments. Of these, 10 are mandatory, 42 core, 41 recommended, and 14 are exploratory. INTERPRETATION The ICPGC CDEs provide a foundation for the standardization of phenotype data captured in CP genomic studies and will benefit international collaborations and pooling of data, particularly in rare conditions. WHAT THIS PAPER ADDS A set of 107 common data elements (CDEs) for genomics studies in cerebral palsy is provided. The CDEs include standard definitions and data values domains. The CDEs will facilitate international data sharing, collaboration, and improved clinical interpretation of findings.
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Affiliation(s)
- Yana A. Wilson
- Sydney Medical School, Faculty of Medicine and HealthThe University of SydneySydneyNSWAustralia,Cerebral Palsy Alliance Research Institute, Specialty of Child & Adolescent Health, Faculty of Medicine and HealthThe University of SydneySydneyNSWAustralia
| | - Hayley Smithers‐Sheedy
- Sydney Medical School, Faculty of Medicine and HealthThe University of SydneySydneyNSWAustralia,Cerebral Palsy Alliance Research Institute, Specialty of Child & Adolescent Health, Faculty of Medicine and HealthThe University of SydneySydneyNSWAustralia
| | - Katarina Ostojic
- Sydney Medical School, Faculty of Medicine and HealthThe University of SydneySydneyNSWAustralia,Cerebral Palsy Alliance Research Institute, Specialty of Child & Adolescent Health, Faculty of Medicine and HealthThe University of SydneySydneyNSWAustralia
| | - Emma Waight
- Sydney Medical School, Faculty of Medicine and HealthThe University of SydneySydneyNSWAustralia,Cerebral Palsy Alliance Research Institute, Specialty of Child & Adolescent Health, Faculty of Medicine and HealthThe University of SydneySydneyNSWAustralia
| | - Michael C. Kruer
- Pediatric Movement Disorders ProgramBarrow Neurological InstitutePhoenixArizonaUSA,Departments of Child Health, Neurology, Cellular & Molecular Medicine and Program in GeneticsUniversity of Arizona College of MedicinePhoenixArizonaUSA
| | | | | | - Gareth Baynam
- Western Australian Register of Developmental Anomalies King Edward Memorial HospitalPerthWAAustralia,Faculty of Health and Medical Sciences, Division of PaediatricsUniversity of Western AustraliaPerthWAAustralia,Institute for Immunology and Infectious DiseasesMurdoch UniversityPerthWAAustralia,Telethon Kids InstituteUniversity of Western AustraliaWAAustralia,Spatial Sciences, Department of Science and EngineeringCurtin UniversityWAAustralia
| | - Jozef Gécz
- Robinson Research InstituteThe University of AdelaideAdelaideSAAustralia,Adelaide Medical SchoolThe University of AdelaideSAAustralia,South Australian Health and Medical Research InstituteAdelaideSAAustralia
| | - Nadia Badawi
- Sydney Medical School, Faculty of Medicine and HealthThe University of SydneySydneyNSWAustralia,Cerebral Palsy Alliance Research Institute, Specialty of Child & Adolescent Health, Faculty of Medicine and HealthThe University of SydneySydneyNSWAustralia,Grace Centre for Newborn Intensive Care, The Children's Hospital at WestmeadWestmeadNSWAustralia
| | - Sarah McIntyre
- Sydney Medical School, Faculty of Medicine and HealthThe University of SydneySydneyNSWAustralia,Cerebral Palsy Alliance Research Institute, Specialty of Child & Adolescent Health, Faculty of Medicine and HealthThe University of SydneySydneyNSWAustralia,Telethon Kids InstituteUniversity of Western AustraliaWAAustralia
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Fafolahan AO, Sodipo OP, Davis AO, Adeoye KK, Musa BO, David O, Muminat AA. Profile of pediatric out-patients managed by physiotherapists at Federal Medical Center, Abeokuta: a retrospective review. BULLETIN OF FACULTY OF PHYSICAL THERAPY 2022. [DOI: 10.1186/s43161-022-00109-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Abstract
Background
Pediatric physiotherapists help children to achieve their optimal physical development. The present study was aimed to evaluate the out-patient pediatric conditions managed by physiotherapists in Federal Medical Centre, Abeokuta, Nigeria (FMCA).
Methods
The present study included all children attended to at Pediatric Unit (outpatient) of FMCA in the period between the beginnings of May 20121 to the end of May 2022. The clinic runs every Tuesdays and Thursdays. All children below and equals to 15 years of age were included. Complete clinical, socio-demographic characteristics of patients and parents were manually scrapped from the electronic medical records (EMR) of the hospital. Descriptive statistics was used to present the results.
Results
During this period a total of 160 patients presented with different disorders were seen. There were 100 males (62.5%) and 60 females (37.5%). Cerebral palsy which can be classified as a neurological disorder was the most common condition managed (63.7%). Obstetric brachial palsy injury (OBPI), injection palsy, post-immobilization stiffness, congenital talipes equinivarus, and among others were managed during this period. Cerebral palsy was common among males, obstetric brachial palsy injury, and injection palsy. Cerebral palsy patients had late presentation for physiotherapy (1–5 years). Only 2 patients out of 11 with OBPI came for early physiotherapy. There is higher risk for cerebral palsy and OBPI among primiparous mothers.
Conclusions
It was concluded that neurological disorders are the most common pediatric cases managed by physiotherapists in Federal Medical Centre, Abeokuta, with cerebral palsy having higher prevalence.
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Espinoza ML, Brundler MA, Hasan SU, Mohammad K, Momin S, Al Shaikh B, Yusuf K. Placental pathology as a marker of brain injury in infants with hypoxic ischemic encephalopathy. Early Hum Dev 2022; 174:105683. [PMID: 36215816 DOI: 10.1016/j.earlhumdev.2022.105683] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Revised: 09/27/2022] [Accepted: 09/28/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Hypoxic Ischemic Encephalopathy (HIE) can lead to devastating consequences for the affected infant. Although therapeutic cooling benefits infants with moderate and severe HIE, differentiating mild from moderate-severe HIE may be challenging. The placenta reflects the fetal intrauterine environment and may reveal underlying processes that affect brain injury. AIM To describe placental histopathology using the Amsterdam Placental Workshop Group Criteria in different grades of HIE. STUDY DESIGN Retrospective cohort. SUBJECTS Infants admitted to a tertiary care neonatal intensive care unit with a diagnosis of HIE between 2011 and 2016. OUTCOME MEASURE Maternal and neonatal clinical variables and placental histopathology using the Amsterdam Placental Workshop Group Criteria were compared between mild and moderate-severe HIE. Mann-Whitney or t-test or ꭓ2 were performed for bivariate associations as appropriate. To explain the relationship between placental pathology and severity of HIE odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using logistic regression models. RESULTS Of the 73 infants in the study, 23 had mild and 50 moderate-sever HIE. There was no difference in maternal and neonatal characteristics except for sentinel events which were higher in the moderate- severe group. On placental histopathology, acute inflammation, including fetal inflammatory reaction (FIR) were significantly higher in the moderate-severe group. After adjusting for confounders, FIR remained significantly associated with moderate-severe HIE, ORs 6.29, 95 % CI 1.5-25. CONCLUSION Our study demonstrates FIR in the placenta is associated with severity of HIE.
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Affiliation(s)
- Maria Liza Espinoza
- Department of Pediatrics, University of Calgary, Section of Neonatology, Calgary, AB, Canada
| | - Marie-Anne Brundler
- Department of Pathology & Laboratory Medicine and Pediatrics, University of Calgary, Calgary, AB, Canada
| | - Shabih U Hasan
- Department of Pediatrics, University of Calgary, Section of Neonatology, Calgary, AB, Canada
| | - Khorshid Mohammad
- Department of Pediatrics, University of Calgary, Section of Neonatology, Calgary, AB, Canada
| | - Sarfaraz Momin
- Department of Pediatrics, University of Calgary, Section of Neonatology, Calgary, AB, Canada
| | - Belal Al Shaikh
- Department of Pediatrics, University of Calgary, Section of Neonatology, Calgary, AB, Canada
| | - Kamran Yusuf
- Department of Pediatrics, University of Calgary, Section of Neonatology, Calgary, AB, Canada.
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Jahan I, Al Imam MH, Muhit M, Chhetri AB, Badawi N, Khandaker G. Epidemiology of cerebral palsy among children in the remote Gorkha district of Nepal: findings from the Nepal cerebral palsy register. Disabil Rehabil 2022:1-10. [PMID: 36102553 DOI: 10.1080/09638288.2022.2118871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
PURPOSE To describe the epidemiology of cerebral palsy (CP) among children in Gorkha, Nepal. METHODS We established the first population-based register of children with CP aged <18 y in Gorkha, Nepal (i.e., Nepal CP Register). Children with suspected CP underwent detailed neurodevelopmental assessment by a multidisciplinary assessment team. Socio-demographic, etiology, motor severity, rehabilitation, and educational status were documented. RESULTS Between January and October 2018, 182 children with confirmed CP were registered (mean (standard deviation (SD)) age: 10 years 1 months (4 years 10 months), 37.4% females). The majority (88.3%) had CP acquired pre- or perinatally. Mean (SD) age of CP diagnosis was four years five months. Mothers who did not receive any formal schooling had 4.5, 3.1, and 6.3 times higher odds of having inadequate antenatal care, homebirth, and unskilled birth attendants, respectively, when adjusted for other factors. Most children had spastic CP (77.5%) and Gross Motor Function Classification System level III-V (54.9%). Overall, 45.8% had never received rehabilitation services, 58.0% of school-aged children were not attending schools. The median age of receiving rehabilitation services was three years zero months. CONCLUSIONS The delayed diagnosis and clinical severity indicate the overall poor health status of children with CP in Nepal which could be improved by ensuring early diagnosis and intervention. Implications for rehabilitationThe first population-based cerebral palsy register in Nepal suggests diagnosis of CP is considerably delayed among children.The high burden of severe motor impairment and poor communication skill with limited access to timely rehabilitation among children with CP in Nepal is concerning.Capacity development of community-based health workers and mothers of children with CP could help implementing community-based programs for prevention and early diagnosis of CP, and to promote early intervention for children with CP in remote Gorkha, Nepal.
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Affiliation(s)
- Israt Jahan
- CSF Global, Dhaka, Bangladesh
- Asian Institute of Disability and Development (AIDD), University of South Asia, Dhaka, Bangladesh
- School of Health, Medical and Applied Sciences, Central Queensland University, Rockhampton, Australia
| | - Mahmudul Hassan Al Imam
- CSF Global, Dhaka, Bangladesh
- Asian Institute of Disability and Development (AIDD), University of South Asia, Dhaka, Bangladesh
- School of Health, Medical and Applied Sciences, Central Queensland University, Rockhampton, Australia
- Central Queensland Public Health Unit, Central Queensland Hospital and Health Service, Rockhampton, Australia
| | - Mohammad Muhit
- CSF Global, Dhaka, Bangladesh
- Asian Institute of Disability and Development (AIDD), University of South Asia, Dhaka, Bangladesh
| | | | - Nadia Badawi
- Cerebral Palsy Alliance Research Institute, Specialty of Child & Adolescent Health, Sydney Medical School, Faculty of Medicine & Health, The University of Sydney, Sydney, Australia
- Grace Centre for Newborn Intensive Care, Sydney Children’s Hospital Network, The University of Sydney, Westmead, Australia
| | - Gulam Khandaker
- School of Health, Medical and Applied Sciences, Central Queensland University, Rockhampton, Australia
- Central Queensland Public Health Unit, Central Queensland Hospital and Health Service, Rockhampton, Australia
- Discipline of Child and Adolescent Health, Sydney Medical School, The University of Sydney, Sydney, Australia
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Pereira-Figueiredo D, Nascimento AA, Cunha-Rodrigues MC, Brito R, Calaza KC. Caffeine and Its Neuroprotective Role in Ischemic Events: A Mechanism Dependent on Adenosine Receptors. Cell Mol Neurobiol 2022; 42:1693-1725. [PMID: 33730305 PMCID: PMC11421760 DOI: 10.1007/s10571-021-01077-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2020] [Accepted: 03/05/2021] [Indexed: 02/07/2023]
Abstract
Ischemia is characterized by a transient, insufficient, or permanent interruption of blood flow to a tissue, which leads to an inadequate glucose and oxygen supply. The nervous tissue is highly active, and it closely depends on glucose and oxygen to satisfy its metabolic demand. Therefore, ischemic conditions promote cell death and lead to a secondary wave of cell damage that progressively spreads to the neighborhood areas, called penumbra. Brain ischemia is one of the main causes of deaths and summed with retinal ischemia comprises one of the principal reasons of disability. Although several studies have been performed to investigate the mechanisms of damage to find protective/preventive interventions, an effective treatment does not exist yet. Adenosine is a well-described neuromodulator in the central nervous system (CNS), and acts through four subtypes of G-protein-coupled receptors. Adenosine receptors, especially A1 and A2A receptors, are the main targets of caffeine in daily consumption doses. Accordingly, caffeine has been greatly studied in the context of CNS pathologies. In fact, adenosine system, as well as caffeine, is involved in neuroprotection effects in different pathological situations. Therefore, the present review focuses on the role of adenosine/caffeine in CNS, brain and retina, ischemic events.
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Affiliation(s)
- D Pereira-Figueiredo
- Neurobiology of the Retina Laboratory, Biomedical Sciences Program, Biomedical Institute, Fluminense Federal University, Niterói, RJ, Brazil
| | - A A Nascimento
- Neurobiology of the Retina Laboratory, Program of Neurosciences, Institute of Biology, Fluminense Federal University, Niterói, RJ, Brazil
| | - M C Cunha-Rodrigues
- Neurobiology of the Retina Laboratory, Program of Neurosciences, Institute of Biology, Fluminense Federal University, Niterói, RJ, Brazil
| | - R Brito
- Laboratory of Neuronal Physiology and Pathology, Cellular and Molecular Biology Department, Institute of Biology, Fluminense Federal University, Niterói, RJ, Brazil
| | - K C Calaza
- Neurobiology of the Retina Laboratory, Biomedical Sciences Program, Biomedical Institute, Fluminense Federal University, Niterói, RJ, Brazil.
- Neurobiology of the Retina Laboratory, Program of Neurosciences, Institute of Biology, Fluminense Federal University, Niterói, RJ, Brazil.
- Neurobiology Department, Biology Institute of Fluminense Federal University, Niteroi, RJ, Brazil.
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48
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Kavcic A. Is it time to rename hereditary cases of cerebral palsy? Brain 2022; 145:e82-e83. [PMID: 35776103 DOI: 10.1093/brain/awac230] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Accepted: 06/22/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
- Anamarija Kavcic
- Health Care Authority Aschaffenburg, Aschaffenburg 63739, Germany
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49
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Larsen ML, Rackauskaite G, Greisen G, Laursen B, Uldall P, Krebs L, Hoei-Hansen CE. Declining prevalence of cerebral palsy in children born at term in Denmark. Dev Med Child Neurol 2022; 64:715-722. [PMID: 34927722 DOI: 10.1111/dmcn.15136] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 11/21/2021] [Accepted: 11/22/2021] [Indexed: 11/26/2022]
Abstract
AIM To investigate reasons for the declining prevalence of cerebral palsy (CP) in children born at term in Denmark by evaluating obstetric and neonatal factors associated with CP, and their changes over time. METHOD In this cohort study, we included 987 495 children (504 600 [51.1%] males and 482 895 [48.9%] females) born after 37 completed gestational weeks during birth years 1997 to 2013. Risk ratios of CP for each factor were calculated with log-binominal regression analyses. Significant factors were evaluated concerning their development in prevalence over time. RESULTS In the antenatal period, there were significant associations with an increased risk of CP and high maternal body mass index (BMI), smoking during pregnancy, nulliparity, male sex, gestational age, and low birthweight. In the study period, fewer females smoked during pregnancy and fewer children were born post-term, dropping from 22.6% to 11.4% and 9.4% to 2.5% respectively. Conversely, the proportion of females with high BMI increased. Most significant risk factors were found in the neonatal period, with an increase in children with diagnosed birth defects and children admitted to neonatal care. INTERPRETATION Reasons for the declining prevalence of CP appear to be multifactorial and likely include the decline in maternal smoking and children born post-term along with centralization and advances in neonatal treatment.
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Affiliation(s)
- Mads L Larsen
- Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.,Department of Obstetrics and Gynaecology, Copenhagen University Hospital - Amager-Hvidovre, Hvidovre, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Gija Rackauskaite
- Department of Paediatrics and Adolescent Medicine, University Hospital Aarhus, Aarhus, Denmark
| | - Gorm Greisen
- Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.,Department of Neonatology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Bjarne Laursen
- National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark
| | - Peter Uldall
- Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Lone Krebs
- Department of Obstetrics and Gynaecology, Copenhagen University Hospital - Amager-Hvidovre, Hvidovre, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Christina E Hoei-Hansen
- Department of Paediatrics and Adolescent Medicine, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark.,Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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Androgens Upregulate Pathogen-Induced Placental Innate Immune Response. Int J Mol Sci 2022; 23:ijms23094978. [PMID: 35563368 PMCID: PMC9104209 DOI: 10.3390/ijms23094978] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 04/25/2022] [Accepted: 04/27/2022] [Indexed: 02/01/2023] Open
Abstract
Group B Streptococcus (GBS) is a leading cause of placental infection, termed chorioamnionitis. Chorioamnionitis is associated with an increased risk of neurobehavioral impairments, such as autism spectrum disorders, which are more prominent in males than in female offspring. In a pre-clinical model of chorioamnionitis, a greater inflammatory response was observed in placenta associated with male rather than female fetuses, correlating with the severity of subsequent neurobehavioral impairments. The reason for this sex difference is not understood. Our hypothesis is that androgens upregulate the placental innate immune response in male fetuses. Lewis dams were injected daily from gestational day (G) 18 to 21 with corn oil (vehicle) or an androgen receptor antagonist (flutamide). On G 19, dams were injected with saline (control) or GBS. Maternal, fetal sera and placentas were collected for protein assays and in situ analyses. Our results showed that while flutamide alone had no effect, a decrease in placental concentration of pro-inflammatory cytokines and infiltration of polymorphonuclear cells was observed in flutamide/infected compared to vehicle/infected groups. These results show that androgens upregulate the placental innate immune response and thus may contribute to the skewed sex ratio towards males observed in several developmental impairments resulting from perinatal infection/inflammation.
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