Search

Background: The pathophysiology of bilirubin neurotoxicity in course of hypoxic-ischemic encephalopathy (HIE) in term and preterm infants is still poorly understood. We hypothesized that oxidative stress may be a common mechanism that link hyperbilirubinemia and HIE. Objectives: The objective of the present study was to evaluate whether unconjugated bilirubin (UCB) may enhance the HI brain injury by increasing oxidative stress and to test pioglitazone and allopurinol as new antioxidant therapeutic drugs in vitro . Methods: The effects of UCB were tested on organotypic hippocampal slices subjected to 30 min oxygen-glucose deprivation (OGD), used as in vitro model of HIE. The experiments were performed on mature (14 days in culture) and immature (7 days in culture) slices, to mimic the brains of term and preterm infants, respectively. Mature and immature slices were exposed to UCB, human serum albumin (HSA), pioglitazone, and/or allopurinol for 24 h, immediately after 30 min OGD. Neuronal injury was assessed using propidium iodide (PI) fluorescence. ROS formation was quantified by using the 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA) method. Results: In mature slices, we found that the neurotoxicity, as well as oxidative stress, induced by OGD were enhanced by UCB. HSA significantly prevented UCB-increased neurotoxicity, but had a slight reduction on ROS production. Allopurinol, but not pioglitazone, significantly reduced UCB-increased neurotoxicity induced by OGD. In immature slices exposed to OGD, no increase of neuronal death was observed, whereas oxidative stress was detected after UCB exposure. HSA, pioglitazone and allopurinol have no protective effects on both OGD-induced neuronal death and on UCB-induced oxidative stress. For this reason, UCB, pioglitazone and allopurinol was also tested on ischemic preconditioning protocol. We found that UCB abolished the neuroprotection induced by preconditioning and increased oxidative stress. These effects were restored by allopurinol but not pioglitazone. Conclusions: UCB characterized a different path of neuronal damage and oxidative stress in mature and immature hippocampal slice model of HIE. Management of hyperbilirubinemia in a complex pathological condition, such as HIE and hyperbilirubinemia, should be very careful. Allopurinol could deserve attention as a novel pharmacological intervention for hyperbilirubinemia and HIE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dani, Pratesi, Mannaioni and Gerace.)

Background: Great variability in enteral feeding practices for very preterm (<32 weeks gestational age-GA) and very low birth weight infants (VLBW; ≤1,500 g) have been reported. We aimed to describe data on enteral feeding in Tuscany (Italy), where a network of 6 donor milk banks is in place. Methods: A 4-years (2012-2015) observational study was performed analyzing the database "TIN Toscane online" on very preterm and VLBW infants. The database covers all 25 hospitals with a neonatal unit. Results: Data concerning the beginning of enteral nutrition were available for 1,302 newborns with a mean (standard deviation) GA of 29.3 (2.9) weeks, while information at the time of full enteral nutrition was available for 1,235 and at discharge for 1,140. Most infants (74.1%) started enteral feeding during the first 24 h of life. Overall, 80.1% of newborns were fed exclusive human milk, donor milk having the larger prevalence of use (66.8%). Few infants (13.3%) started with exclusive mother's milk. Full enteral feeding was achieved using exclusive human milk in most cases (80%). Full enteral feeding was reached earlier in newborns who were fed human milk than in those fed formula, regardless of GA. Sixty-four percent of infants were still fed with any human milk at discharge. When data at the achievement of full enteral nutrition and at discharge were analyzed stratified by the type of milk used to start enteral feeding, newborns initially fed donor milk presented the highest prevalence (91.3%) of exclusive human milk at full enteral feeding, an important period to prevent necrotizing enterocolitis, while no differences were observed at discharge. Conclusions: Donor milk was widely used for newborns during the first hours of life, when mother's milk availability may be quite challenging. Starting enteral nutrition with donor milk was associated with early start of enteral feeding and early achievement of full enteral nutrition without affecting mother lactation. The overall prevalence of human milk at discharge (when donor milk is not available anymore) was high (64%), irrespective of the type of milk used to start nutrition.

At delivery, if the cord is not clamped, blood continues to pass from the placenta to the newborn during the first minutes of life, allowing the transfer of 25-35 ml/kg of placental blood to the newborn, depending on gestational age, the timing of cord clamping, the position of the infant at birth, the onset of respiration, and administration of uterotonics to the mother. However, deriving benefits from delayed cord clamping (DCC) are not merely related to placental-to-fetal blood transfusion; establishing spontaneous ventilation before cutting the cord improves venous return to the right heart and pulmonary blood flow, protecting the newborn from the transient low cardiac output, and systemic arterial pressure fluctuations. Recent meta-analyses showed that delayed cord clamping reduces mortality and red blood cell transfusions in preterm newborns and increases iron stores in term newborns. Various authors suggested umbilical cord milking (UCM) as a safe alternative when delayed cord clamping is not feasible. Many scientific societies recommend waiting 30-60 s before clamping the cord for both term and preterm newborns not requiring resuscitation. To improve the uptake of placental transfusion strategies, in 2016 an Italian Task Force for the Management of Umbilical Cord Clamping drafted national recommendations for the management of cord clamping in term and preterm deliveries. The task force performed a detailed review of the literature using the GRADE methodological approach. The document analyzed all clinical scenarios that operators could deal with in the delivery room, including cord blood gas analysis during delayed cord clamping and time to cord clamping in the case of umbilical cord blood banking. The panel intended to promote a more physiological and individualized approach to cord clamping, specifically for the most preterm newborn. A feasible option to implement delayed cord clamping in very preterm deliveries is to move the neonatologist to the mother's bedside to assess the newborn's clinical condition at birth. This option could safely guarantee the first steps of stabilization before clamping the cord and allow DCC in the first 30 s of life, without delaying resuscitation. Contra-indications to placental transfusion strategies are clinical situations that may endanger mother 's health and those that may delay immediate newborn's resuscitation when required.