Gemma Stazzoni

Brain susceptibility to oxidative stress in the perinatal period

Abstract Oxidative stress (OS) occurs at birth in all newborns as a consequence of the hyperoxic challenge due to the transition from the hypoxic intrauterine environment to extrauterine life. Free radical (FRs) sources such as inflammation, hyperoxia, hypoxia, ischaemia-reperfusion, neutrophil and macrophage activation, glutamate and free iron release, all increases the OS during the perinatal period. Newborns, and particularly preterm infants, have reduced antioxidant defences and are not able to counteract the harmful effects of FRs. Energy metabolism is central to life because cells cannot exist without an adequate supply of ATP. Due to its growth, the mammalian brain can be considered as a steady-state system in which ATP production matches ATP utilisation. The developing brain is particularly sensitive to any disturbances in energy generation, and even a short-term interruption can lead to long-lasting and irreversible damage. Whenever energy failure develops, brain damage can occur. Accumulating evidence indicates that OS is implicated in the pathogenesis of many neurological diseases, such as intraventricular haemorrhage, hypoxic-ischaemic encephalopathy and epilepsy.

New pharmacologic and therapeutic approaches for hypoxic-ischemic encephalopathy in the newborn.

Hypoxic-ischemic encephalopathy is still an important cause of neonatal mortality and long-term disabilities. The understanding of the differential responses to hypoxia-ischemia as an initial insult leading to cellular degeneration in brain has opened the way to develop new pharmacologic and therapeutic approaches. Due to the complex pathophysiology, therapies can target early pathways such as oxidative stress, inflammation and apoptosis or delayed pathways such as the privation of growth factors and cell death. Pharmacological interventions should start at different points of time according to their mechanisms of action. The association of moderate hypothermia with neuroprotective drugs may decrease cell injury and optimize endogenous repair. More basic science research focusing on the mechanisms of injury are required. Moreover, clinical trials are needed to detect safely and effectiveness drugs and to establish the optimal time of action for each one.

Oxidative injury in neonatal erythrocytes

Erythrocytes are continuously exposed to free radicals (FR) injury due to their high cellular oxygen concentration and heme iron. The autoxidation of oxyhaemoglobin to methaemoglobin, generating superoxide anion radical, represents the main source of FR in erythrocytes. The erythrocyte membrane is particularly sensitive to oxidative damage due to its high polyunsaturated fatty acid content, and hence, it represents an important system to evaluate the effect of oxidative stress (OS). Information on how red cells OS is triggered and mechanisms of erythrocytes oxidative pressure from plasma may provide a partial answer to questions about the causes of the anaemia of prematurity and about red cell involvement in hypoxia. The recent insights about the mechanism of oxidative injury of red cells and the evidence of relationships between erythrocyte, OS and hypoxia suggest that increased haemolysis is induced by severe hypoxia and acidosis in the perinatal period.

Biomarkers of oxidative stress in fetal and neonatal diseases

Oxidative stress (OS) is strongly involved in the pathogenesis of many fetal and newborn diseases. A low efficient antioxidant systems in preterm babies are not able to counteract the harmful effects of free radicals (FRs), leading to “FRs-related disease” of newborns promoting cellular, tissue and organ damages. The dangerous effects of FRs are linked to their property of being very unstable molecules and their ability to react with lipids, proteins, polysaccharides, nucleic acids, causing functional alterations within the cell, until cell death. OS is difficult to be measured in vivo, because FRs have a very short half-life. Actually, measurements of lipid peroxidation reach high specificity and sensitivity with the discovery of stable compounds, isoprostanes. Recent studies evaluating the damaging effects of FRs in the perinatal period, have observed a direct relation between the degree of OS and the severity of oxidative damage in the course of pregnancy and in perinatal period, with an interesting predictive role of OS biomarkers for diseases resulting from oxidative injury. The validation of a biomarker profile for early identification of newborns at high risk of OS, will pave the way to new clinical preventative or therapeutic approaches to reduce the prevalence of neonatal disability.

How painful is a heelprick or a venipuncture in a newborn

Abstract Objective: Neonates undergo many painful procedures daily, in particular venipunctures and heelpricks. Our aim was to assess how painful these procedures actually are, and how effective are the common analgesic strategies to blunt this pain. Methods: We performed a MEDLINE/PubMed research from 1999 to 2013. We retrieved all papers in English language that evaluated pain during neonatal heelprick or venipuncture and that used as score the Premature Infant Pain Profile (PIPP), a widely used scale for evaluate acute pain in term and preterm babies. Results: Fifteen papers met the inclusion criteria, using different analgesic methods. Just in one case two studies used the same analgesic method. Most analgesic procedures show a relevant level of pain. We didn’t find univocal difference between heelprick and venipuncture. Topic creams, systemic analgesics, posture and oral glucose 10% have scarce analgesic effectiveness. The most effective procedures are the use of oral sweet solutions (sucrose or glucose) at concentrations greater than 20%, multisensory stimulations and non-nutritive sucking used along with 10% glucose. Conclusions: A large amount of analgesic methods was used, making comparisons difficult. Nevertheless, in the absence of analgesic treatment, heelpricks and venipunctures are moderately-severely painful, and among the proposed analgesic procedures, few seem to be effective.

Use of fetal analgesia during prenatal surgery

Objective: Recent progresses in fetal surgery have raised concern on fetal pain, its long-term consequences and the risks of sudden fetal movements induced by pain. In several studies, surgeons have directly administered opioids to the fetus, while others have considered sufficient the maternally administered analgesics. We performed a review of the literature to assess the state of the art. Methods: We performed a PubMed search to retrieve the papers that in the last 10 years reported studies of human fetal surgery and that described whether any fetal analgesia was administered. Results: We retrieved 34 papers. In three papers, the procedure did not hurt the fetus, being performed on fetal annexes, in two papers, it was performed in the first half of pregnancy, when pain perception is unlikely. In 10 of the 29 remaining papers, fetal surgery was performed using direct fetal analgesia, while in 19, analgesia was administered only to the mother. In most cases, fetal direct analgesia was obtained using i.m. opioids, and muscle relaxant. Rare drawbacks on either fetuses or mothers due to fetal analgesia were reported. Conclusion: Fetal direct analgesia is performed only in a minority of cases and no study gives details about fetal reactions to pain. More research is needed to assess or exclude its possible long-term drawbacks, as well as the actual consequences of pain during surgery.

C-reactive protein: a marker of neonatal stress?

Abstract Aim: To assess whether blood values of C-reactive protein (CRP) in healthy term newborns, are influenced by stress. Material and methods: Since different types of delivery (vaginal delivery [VD], emergency C-section [EMCS] and elective C-section [ELCS]) are notoriously characterized by different levels of stress for the baby, these three groups were used as models of different levels of stress. The mean CRP values of the three groups obtained in the first hours of life were compared. Results: We retrieved 1012 babies. Median values (3rd–97th ct) were: 0.05 (0.01–0.46), 0.17 (0.02–1.54), 0.30 (0.04–1.77), 0.43 (0.05–1.31), 0.40 (0.04–1.13) at 12, 24, 48, 72 and 96 h, respectively. Mean values in babies born after VD were statistically higher than those born after C-section, and higher CRP values were present in EMCS with respect to ELCS. Conclusion: This study described normal blood CRP values in a wide population of term babies. An influence of the type of delivery on blood CRP is evident, and this may be explained by the different amount of perinatal stress induced by anyone of the three types of delivery we considered.