The purpose of this review is to serve as an introduction to understanding sleep in the fetus, the preterm neonate and the term neonate. Sleep appears to have numerous important roles, particularly in the consolidation of new information. The sleep cycle changes over time, neonates spend the most time in active sleep and have a progressive shortening of active sleep and lengthening of quiet sleep. Additionally, the sleep cycle is disrupted by many things including disease state and environment, and the amplitude integrated EEG can be a useful tool in evaluating sleep, and sleep disturbances, in neonates. Finally, there are protective factors for infant sleep that are still being studied.

The term “encephalopathy of prematurity” encompasses not only the acute brain injury (such as intraventricular hemorrhage) but also complex disturbance on the infant’s subsequent brain development. In premature infants, the most frequent recognized source of brain injury is intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL). Furthermore 20-25% infants with birth weigh less than 1,500 g will have IVH and that proportion increases to 45% if the birth weight is less than 500-750 g. In addition, nearly 60% of very low birth weight newborns will have hypoxic-ischemic injury. Therefore permanent lifetime neurodevelopmental disabilities are frequent in premature infants. Innovative approach to prevent or decrease brain injury in preterm infants requires discovery of biomarkers able to discriminate infants at risk for injury, monitor the progression of the injury and assess efficacy of neuroprotective clinical trials. In this article, we will review biomarkers studied in premature infants with IVH, Post-hemorrhagic ventricular dilation (PHVD) and PVL including: S100b, Activin A, erythropoietin, chemokine CCL 18, GFAP and NFL will also be examined. Some of the most promising biomarkers for IVH are S100β and Activin. The concentrations of TGF-β1, MMP-9 and PAI-1 in cerebrospinal fluid could be used to discriminate patients that will require shunt after post-hemorrhagic ventricular dilation. Neonatal brain injury is frequent in premature infants admitted to the neonatal intensive care and we hope to contribute to the awareness and interest in clinical validation of established as well as novel neonatal brain injury biomarkers.

Surgery is frequently associated with excessive oxidative stress. Melatonin acts as an antioxidant and transient melatonin deficiency has been described in neonatal surgical patients. This randomized, blinded, prospective pilot study tested the hypothesis that oral melatonin supplementation in newborn infants undergoing surgery is effective in reducing perioperative oxidative stress. A total of twenty-three newborn infants requiring surgery were enrolled: 10 received a single dose of oral melatonin 0.5 mg/kg in the morning, before surgery (MEL group), and 13 newborns served as the control group (untreated group). Plasma concentrations of melatonin, Non-Protein-Bound Iron (NPBI), Advanced Oxidation Protein Products (AOPP), and F2-Isoprostanes (F2-IsoPs) were measured. Both in the pre- and postoperative period, melatonin concentrations were significantly higher in the MEL group than in the untreated group (preoperative: 1265.50 ± 717.03 vs. 23.23 ± 17.71 pg/mL, p < 0.0001; postoperative: 1465.20 ± 538.38 vs. 56.47 ± 37.18 pg/mL, p < 0.0001). Melatonin significantly increased from the pre- to postoperative period in the untreated group (23.23 ± 17.71 vs. 56.47 ± 37.18 pg/mL; pg/mL p = 0.006). In the MEL group, the mean blood concentrations of NPBI, F2-IsoPs, and AOPP significantly decreased from the pre- to the postoperative period (4.69 ± 3.85 vs. 1.65 ± 1.18 micromol/dL, p = 0.049; 128.40 ± 92.30 vs. 50.25 ± 47.47 pg/mL, p = 0.037 and 65.18 ± 15.50 vs. 43.98 ± 17.92 micromol/dL, p = 0.022, respectively). Melatonin concentration increases physiologically from the pre- to the postoperative period, suggesting a defensive physiologic response to counteract oxidative stress. The administration of exogenous melatonin in newborn infants undergoing surgery reduces lipid and protein peroxidation in the postoperative period, showing a potential role in protecting babies from the deleterious consequences of oxidative stress.