Physiological oxidative stress plays a pivotal role in supporting proper growth and development. While moderate oxidative stress is essential for activating key metabolic pathways and maintaining normal cellular signaling, excessive production of reactive oxygen species (ROSs) can overwhelm the immature antioxidant systems of newborns, potentially leading to cellular damage and impaired physiological function. This vulnerability is particularly pronounced in the central nervous system, where limited detoxification capacity exacerbates the risk of oxidative damage, following hypoxic–ischemic events. Antioxidants agents—such as melatonin, erythropoietin, allopurinol, N-acetylcisteine, selenium, iminobiotin, taurine, and acetyl-L-carnitine—have demonstrated significant neuroprotective effects in preclinical experimental studies, reducing markers of oxidative injury and improving neurological outcomes. These neuroprotective agents have also been evaluated in clinical trials, demonstrating antioxidant effects. A major issue lies in the complexity of neurological damage, which is not associated with a single pathological pathway. Additionally, the inability of these agents to reach effective concentrations within the central nervous system, along with inconsistencies across clinical trials in terms of dosage and administration methods, hinders the ability to obtain robust results. Future efforts should therefore focus on the development of delivery systems capable of crossing the blood–brain barrier and on establishing standardized clinical trial protocols and study designs. This educational review aims to provide a comprehensive overview of emerging protective strategies, including antioxidant bioactive agents and nutritional interventions. It also explores the underlying mechanisms of oxidative stress and its impact on neonatal brain injury.

Gestational diabetes mellitus (GDM) affects intrauterine glucose regulation and influences heart rate variability (HRV) and cortisol levels in newborns, which are markers of autonomic and hypothalamic-pituitary-adrenal axis function. This study aimed to evaluate HRV and cortisol levels in newborns of healthy mothers and those with GDM within the first 24 h of life, and to compare these measures between sexes. A total of 59 newborns were monitored for heart rate (HR) and HRV from the 6 h of life. Salivary cortisol levels were measured 3-6 h (T1) and 20-24 h (T2) after birth. HRV parameters included the root mean square of successive differences (RMSSD), the high (HF) and low (LF) band power of HRV, and the LF/HF ratio. GDM newborns showed lower HR, higher RMSSD, and a lower LF/HF ratio compared to controls. GDM females had lower HR than control females and GDM males, while GDM males had higher RMSSD and HF than control males. Cortisol levels decreased from T1-T2 in both groups with no sex differences. Newborns from mothers with GDM exhibited lower HR and higher cardiac vagal modulation, with sex-specific differences. GDM females showed a decrease in HR without changes in HRV, whereas GDM males showed an increase in vagally mediated HRV without changes in HR. GDM does not seem to affect cortisol levels in newborns. These findings highlight sex-specific cardiac autonomic responses to birth stress in GDM-exposed newborns across the first day of life, which play an important role in shaping different behavioral, resilience, and well-being trajectories in early infancy.

Reactive oxygen and nitrogen species participate in physiological signaling and adaptation during fetal and neonatal development, whereas excessive, prolonged, or spatially dysregulated production may contribute to oxidative and nitrosative tissue injury. Redox dysregulation has been extensively investigated in neonatal conditions, including bronchopulmonary dysplasia (BPD), hypoxic‐ischemic encephalopathy, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), congenital heart disease (CHD), and hyperbilirubinemia. Its relationship with bone metabolism is well established in adult and pediatric disorders, including osteoporosis, inflammatory bone loss, and iron‐overload‐related bone disease. However, the potential contribution of perinatal redox imbalance to early skeletal development remains comparatively underexplored. This narrative review critically examines the biochemical mechanisms of reactive species generation, their interaction with inflammatory pathways, and the experimental and clinical evidence linking redox dysregulation to neonatal organ injury. Particular attention is given to the developing skeleton as a potentially underrecognized target. Experimental studies indicate that excessive reactive species can impair chondrogenesis, alter osteoblast and osteoclast activity, disrupt collagen and osteogenic signaling, and interfere with skeletal growth. Human evidence is predominantly observational. Preliminary longitudinal data show inverse associations between cord‐blood markers of oxidative DNA and protein modification and REMS‐derived skeletal Z‐scores during the first year of life. These findings suggest that early redox imbalance may impair bone quality and growth trajectories in newborns. Prospective studies integrating standardized redox biomarkers, bone‐metabolism indices, imaging, nutrition, medication exposure, growth, and fracture outcomes are needed to determine whether redox dysregulation independently contributes to impaired skeletal development.