Impact of Common Treatments Given in the Perinatal Period on the Developing Brain

Abstract

Background: Over the last decades, considerable progress has been made in the perinatal management of high-risk preterm neonates, changing the landscape of pathological conditions associated with neurological impairments. Major focal destructive lesions are now less common, and the predominant neuropathological lesion is diffuse white-matter damage in the most immature infants. Similarly, over the last few years, we have observed a trend towards a decrease in neurological impairment in the absence of treatments specifically aimed at neuroprotection. Objectives: We examined whether recent changes in treatment strategies in perinatal care during the perinatal period could have had an indirect beneficial impact on the occurrence of brain lesions and their consequences. Methods: Thus, we reviewed the effects of the most common treatments administered during the perinatal period to the mother or to very preterm infants on brain damage and neurocognitive follow-up. Results: Antenatal steroids and exogenous surfactant are the two main treatments capable of leading to neuroprotection in very preterm infants. Randomized controlled trials are currently investigating the effects of inhaled nitric oxide and erythropoietin, while antenatal magnesium sulphate and caffeine are also likely to provide some neuroprotection, but this needs to be further investigated. Finally, other common treatments against pain, haemodynamic failure and patent ductus arteriosus have conflicting or no effects on the developing brain. Conclusion: While specific neuroprotective drugs are still awaited, recent advances in perinatal care have been associated with an unexpected but significant decrease in the incidence of both severe brain lesions and neurological impairment.

Neurodevelopmental Outcome at 2 Years of Age according to Patent Ductus Arteriosus Management in Very Preterm Infants

“…Recent cohort studies have found an association between the administration of anesthesia in infancy and early childhood NDI, although this association was weakened after adjustment for key covariates, such as perinatal characteristics, indication for anesthesia, and socioeconomic factors [19]. Exposure to neonatal analgesics/sedative drugs can impact the developing brain and neurodevelopmental outcome by the time the child reaches school age [20]. However, clinical data supporting an association between surgery/anesthesia and neurologic impact in preterm infants must be interpreted with caution, even when anesthetic agents have the potential to induce widespread neuroapoptosis through modulation of apoptotic pathways and neurotrophins in animal studies [21].…”

Cerebral and lung effects of a new generation synthetic surfactant with SP‐B and SP‐C analogs in preterm lambs

“…CHF5633, a new synthetic SF, has been described as a potential alternative to natural SF for the treatment of neonatal RDS . Due to the intrinsic relation between ventilation management and cerebral pathology in immature newborns, it is essential to evaluate the influence that a new pulmonary treatment may have on the developing brain. Our findings demonstrate for the first time that administration of new synthetic SF containing SP‐B and SP‐C analogs results in smaller cerebral hemodynamic and oxygen metabolism changes than Curosurf instillation, with neither SF formulation appearing to produce damage to the developing brain in our premature model.…”

“…In many premature neonates with RDS, early respiratory care is necessary. However, it has been suggested that some aspects of respiratory care itself are critical factors that may influence the immature brain and the progression toward brain injury . The risks of SF administration include bradycardia and hypoxemia during instillation.…”

“…However, it has been suggested that some aspects of respiratory care itself are critical factors that may influence the immature brain and the progression toward brain injury. 7,8 The risks of SF administration include bradycardia and hypoxemia during instillation. Such "peridosing" adverse effects may produce cerebral blood flow fluctuations, which have been cited as a potential risk factor for brain injury and long-term disability in preterm neonates with RDS.…”

Cerebral Palsy and Polymorphism of the Chemokine <b><i>CCL18</i></b> in Very Preterm Children

“…The prevalence rate is approximately 2 per 1,000 live births in Europe. In the era of advanced perinatal therapies, the rates of severe brain injuries and CP have declined in preterm born children [1] . However, CP is still over 30-fold more frequent among very preterm-born compared to term-born children [2] .…”