Urinary Levels of IL-1ß and GDNF in Preterm Neonates as Potential Biomarkers of Motor Development: A Prospective Study.

Objectives. To evaluate the association between inflammatory biomarkers, neurotrophic factors, birth conditions, and the presence of motor development abnormalities in preterm neonates. Methods. Plasma and urinary levels of cytokines (IL-1ß, IL-6, IL-10, TNF, and IL-12p70), chemokines (CXCL8/IL-8, CCL2/MCP-1, CCL5/RANTES, CXCL10/IP-10, and CXCL9/MIG), and neurotrophic factors (BDNF and GDNF) were evaluated in 40 preterm neonates born between 28 and 32 incomplete weeks of gestation, at four distinct time points: at birth (umbilical cord blood) (T0), at 48 (T1), at 72 hours (T2), and at 3 weeks after birth (T3). Biomarkers levels were compared between different time points and then associated with Test of Infant Motor Performance (TIMP) percentiles. Results. Maternal age, plasma, and urinary concentrations of inflammatory molecules and neurotrophic factors were significantly different between groups with normal versus lower than expected motor development. Higher levels of GDNF were found in the group with lower than expected motor development, while IL-1ß and CXCL8/IL-8 values were higher in the group with typical motor development. Conclusion. Measurements of cytokines and neurotrophic factors in spot urine may be useful in the follow-up of motor development in preterm neonates.

Rehabilitation Intervention Is Associated With Improved Neurodevelopment and Modulation of Inflammatory Molecules in Children With Cerebral Palsy.

AIM: To evaluate the effects of systematic rehabilitation on both the neuropsychomotor development, and on the peripheral response from immunological and neuroplastic mediators in children with cerebral palsy. METHODS: This is a prospective cohort study with 90 children with cerebral palsy at 18 months of age. Sixty children received rehabilitation for 6 months, and they were compared to 30 children that were placed in the waiting list. Peripheral biomarkers and neuropsychomotor parameters were compared between the Rehab vs the Nonrehab groups at baseline and at 6 months. RESULTS: Results showed higher Bayley III scores in the Rehab group, with significant differences in inflammatory and neurotrophic biomarkers between groups. Rehabilitation was associated to decreased levels of IL-12p70, IL-6, IL-1ß, CXCL8 IL-8, and CXCL9/MIG and increased levels of BDNF and GDNF. Nonrehab children had stable immune molecule levels but decreased BDNF levels over time. CONCLUSION: Rehabilitation improved neurodevelopment parameters and modulated levels of inflammatory (↓) and neurotrophic (↑) biomarkers.

Practitioner-led, peer-group sports intervention combined with a context-focused intervention for children with cerebral palsy: a protocol of a feasibility randomised clinical trial.

BACKGROUND: There is a need to investigate relevant, acceptable and feasible approaches that promote participation in leisure-time physical activity for children with cerebral palsy (CP). The aim of this study is to assess the feasibility of a randomised controlled trial comparing a peer-group intervention focused on improving physical literacy (Sports Stars) with the combination of Sports Stars and a context-focused intervention (Pathways and Resources for Engagement and Participation, PREP) for ambulant children with CP in Brazil. METHODS: In this feasibility trial, 18 ambulant children (aged 6-12 years) with CP will be randomised into two groups (nine per group): (1) Sports Stars and (2) Sports Stars plus PREP. The Sports Stars group will receive 8 weekly group sessions, focusing on developing the physical, social, cognitive and psychological skills required to participate in popular Brazilian sports. The combined Sports Stars and PREP group will receive Sports Stars in addition to eight individual PREP sessions focused on overcoming environmental barriers to participation. The primary outcome will include feasibility measures: willingness to participate in an RCT, eligibility and recruitment rates, maintenance of evaluator blinding, acceptability of screening procedures and random allocation, feasibility of evaluating outcomes, contamination between the groups, intervention adherence, treatment satisfaction, understanding of the intervention and implementation resources. Additional instruments will be applied to obtain data related to leisure-time physical activity participation goals, overall participation (home, school and community), physical literacy, level of physical activity and family empowerment. Outcomes will be assessed before, after and 12 weeks after intervention. ETHICS AND DISSEMINATION: This feasibility trial has been approved by ethical Federal University of Minas Gerais' Ethics Review Committee (CAAE: 33238520.5.0000.5149). All potential subjects will provide written informed consent. The results of this study will be published in peer-reviewed journals and be presented at academic conferences. TRIAL REGISTRATION NUMBERS: RBR-4m3b4b6, U1111-1256-4998.

Biomarkers of renal function in preterm neonates at 72h and 3weeks of life.

OBJECTIVE: Serum levels of creatinine in neonates are quite variable and suffer interference from the immature kidney and maternal creatinine concentration. The aim of this study was to measure novel biomarkers of glomerular and tubular function in healthy preterm neonates at 72h and 3 weeks of life. METHODS: Urine samples were collected in 40 preterm neonates with 28-34 incomplete weeks of gestational age. None of the participants had comorbidities, malformations and infections. The samples were collected at 72h of life and at 3 weeks after birth. Measurements of Calbindin, Collagen IV, FABP1, αGST, IP-10, KIM-1, Osteoactivin, Renin, TFF-3, TIMP-1, α-1-Microglobulin, Albumin, Clusterin, Cystatin C, EGF, Lipocalin-2/NGAL and Osteopontin were performed using panels 1 and 2 of multiplex kits of kidney injury. Data were analyzed using the software GraphPad Prism version 6.0. RESULTS: The preterm neonates included 55% of males with gestational age of 30±1 weeks. The most frequent maternal condition associated with preterm birth was preeclampsia (80%). Molecules related to glomerular function showed a significant increase in the concentrations obtained at 3 weeks of life compared to 72h of life. Markers related to tubular injury (KIM-1 and NGAL) also showed an increase. On the other hand, cystatin C did not change. CONCLUSION: The elevation of molecules related to glomerular function indicates an increase of glomerular filtration rate from 72h up until 3 weeks of life, which was not clearly detected with the measurement of cystatin C.

Inflammatory biomarkers in children with cerebral palsy: A systematic review.

BACKGROUND: An exacerbated systemic inflammatory response has been associated with the occurrence of central nervous system injuries that may determine, in long term, motor, sensorial and cognitive disabilities. Persistence of this exacerbated inflammatory response seems to be involved in the pathophysiology of cerebral palsy (CP). METHODS: A systematic search was conducted in Bireme, Embase, PubMed and Scopus including studies that were published until August 2019. The key words used were "cerebral palsy", "brain injury", "inflammation", "oxidative stress", "cytokines", "chemokines", "neuropsychomotor development", "neurodevelopment outcomes" and "child". The quality of the eligible studies was determined according to the criteria suggested by the Newcastle-Ottawa Scale (NOS). RESULTS: Fourteen eligible studies aimed to investigate the association between peripheral inflammatory molecules and neurodevelopment in infants. The studies differed regarding CP-related risk factors and its classification. Inflammatory proteins were measured in blood, plasma, serum, cerebrospinal fluid or urine. In ten studies, higher circulating levels of cytokines, including IL-1ß, IL-6, TNF and CXCL8/IL-8, were associated with abnormal neurological findings. CONCLUSION: The investigation of the potential association between inflammatory molecules and neurological development in children with CP requires further original studies in order to clarify the influence of prenatal and perinatal inflammation on neurological outcomes.

Biomarkers of renal function in preterm neonates at 72 h and 3 weeks of life

Abstract Objective: Serum levels of creatinine in neonates are quite variable and suffer interference from the immature kidney and maternal creatinine concentration. The aim of this study was to measure novel biomarkers of glomerular and tubular function in healthy preterm neonates at 72 h and 3 weeks of life. Methods: Urine samples were collected in 40 preterm neonates with 28-34 incomplete weeks of gestational age. None of the participants had comorbidities, malformations and infections. The samples were collected at 72 h of life and at 3 weeks after birth. Measurements of Calbindin, Collagen IV, FABP1, αGST, IP-10, KIM-1, Osteoactivin, Renin, TFF-3, TIMP-1, α-1-Microglobulin, Albumin, Clusterin, Cystatin C, EGF, Lipocalin-2/NGAL and Osteopontin were performed using panels 1 and 2 of multiplex kits of kidney injury. Data were analyzed using the software GraphPad Prism version 6.0. Results: The preterm neonates included 55% of males with gestational age of 30 ± 1 weeks. The most frequent maternal condition associated with preterm birth was preeclampsia (80%). Molecules related to glomerular function showed a significant increase in the concentrations obtained at 3 weeks of life compared to 72 h of life. Markers related to tubular injury (KIM-1 and NGAL) also showed an increase. On the other hand, cystatin C did not change. Conclusion: The elevation of molecules related to glomerular function indicates an increase of glomerular filtration rate from 72 h up until 3 weeks of life, which was not clearly detected with the measurement of cystatin C.