Efeito do Conceito Neuroevolutivo Bobath nos marcadores inflamatórios, fator neurotrófico derivado do cérebro, componentes da sinalização purinérgica e função neurológica de bebês nascidos prematuros

Abstract

Prematurity is a major public health concern and is associated with an increased risk of neurological, motor, and functional impairments throughout child development. Preterm infants are more vulnerable to neuroinflammation and central nervous system (CNS) immaturity, which negatively affects brain maturation. In this context, early follow-up combined with appropriate therapeutic intervention is essential. The Bobath Neurodevelopmental Concept is widely used in pediatric physical therapy to promote motor and functional development; however, its effects on biological markers and their relationship with neurological function in preterm infants remain poorly understood. The aim of this study was to analyze the effects of the Bobath Neurodevelopmental Concept on inflammatory markers, brain-derived neurotrophic factor (BDNF), components of purinergic signaling, and neurological function in preterm infants. This dissertation was structured into two methodological manuscripts. Manuscript 1 consists of a literature review addressing the relationship between inflammation, purinergic signaling, and neurodevelopment in prematurity, highlighting extracellular ATP release, P2X7 receptor activation, deficiency of essential fatty acids, increased pro-inflammatory cytokine levels, and reduced adenosinergic signaling mediated by the A2A receptor, all of which are associated with impaired myelination and neural connectivity. Manuscript 2 consists of a prospective, single-arm pilot study with a quasi-experimental pre–post design conducted in 18 preterm infants up to 18 months of age. Neurological function was assessed using the Hammersmith Infant Neurological Examination (HINE), and blood samples were collected before and after the intervention to analyze pro- and anti-inflammatory cytokines, BDNF, and purinergic system enzymes. The intervention based on the Bobath Neurodevelopmental Concept was carried out over a 12-week period, with two 45-minute sessions per week. Data collection took place from May 2025 to March 2026. Data normality was assessed using the Shapiro–Wilk test. Pre- and post-intervention comparisons were performed using the paired Student’s t-test, while associations between clinical and laboratory variables were investigated using Pearson’s correlation. Statistical significance was set at p<0.05. All analyses were performed using GraphPad Prism software. The majority of participants were female, with a mean gestational age of 31 weeks and a mean age of 5 months at the initial assessment. The results demonstrated a statistically significant increase in the global HINE score following the intervention (p<0.0001), accompanied by significant improvements across all assessed sections and complete resolution of the neuromotor asymmetries observed during the pre- intervention period (p<0.0001). Regarding the biomarkers, a significant reduction in ADA activity (p=0.0004) and extracellular ATP (eATP) levels (p=0.0002) was observed. Additionally, a significant negative correlation was identified between HINE scores and eATP levels (r=-0.623; p=0.049), demonstrating that better neurological outcomes were associated with lower extracellular ATP concentrations and establishing a relationship between functional recovery and modulation of purinergic signaling. Early physiotherapeutic intervention based on the Neurodevelopmental Treatment (NDT) Bobath Concept significantly improved neurological function in preterm infants, concomitantly with reductions in ADA activity and eATP levels. The association between clinical improvement and modulation of these biomarkers, particularly the negative correlation between HINE scores and eATP levels, provides evidence that purinergic signaling is involved in the neurobiological adaptations resulting from early intervention. These findings broaden the understanding of the biological mechanisms associated with neurodevelopmental physiotherapy and, for the first time, integrate functional outcomes and molecular biomarkers in preterm infants, highlighting ADA and eATP as potential biomarkers for monitoring therapeutic response and opening new perspectives for translational research in the field of neurodevelopment. Early physiotherapeutic intervention based on the Neurodevelopmental Bobath Concept promoted significant improvements in neurological function in preterm infants, concomitant with reductions in ADA activity and eATP levels. The association between clinical improvement and the modulation of these biomarkers, particularly the negative correlation between HINE scores and eATP levels, represents an innovative finding and provides evidence that purinergic signaling is involved in the neurobiological mechanisms underlying functional recovery induced by early intervention. To the best of our knowledge, this is the first study to integrate clinical outcomes and molecular biomarkers in preterm infants, strengthening the hypothesis that ADA and, especially, eATP are promising biomarkers for monitoring therapeutic response. These findings expand the current understanding of the biological mechanisms underlying early neuroplasticity and open new perspectives for translational research aimed at developing biomarker-guided therapeutic strategies in the field of neurodevelopment.