Magnetic Resonance Imaging in Pregnancy with Intrauterine Growth Restriction: A Pilot Study.

OBJECTIVE: Intrauterine growth restriction (IUGR) is a major cause of late stillbirth, though not all compromised babies remain small or are considered growth restricted as pregnancy progresses. Fetal Magnetic Resonance Imaging (f-MRI) represents a second-line tool to study pregnancies with IUGR fetuses. The aim of our study was to evaluate the usefulness of f-MRI on predicting fetal growth and the offspring's perinatal respiratory outcome. DESIGN: All f-MRI performed between 2014 and 2016 in Siena were analysed. Pregnancies with IUGR (Study group (SG)) were recruited together with a control population (Control group (CG)), coupled for gestational age (GA) at the time of f-MRI (mean GA 31 wks). Neonatal information was collected. The f-MRI protocol consisted of T2w images. Six regions of interest (ROI) were placed as follows: 2 on the lung, 2 on the liver, and 2 on the amniotic fluid. The signal intensities (SI) of each ROI were measured. The SI lung to liver ratio (SI lung/liver) and SI lung to amniotic fluid ratio (SI lung/amniotic fluid) were obtained for each fetus. Each ratio was compared between SG and CG. Therefore, SG was divided into two subgroups: adequate and small for gestational age (AGA and SGA) newborns. All measurements were related to offspring's perinatal respiratory outcome. RESULTS: SI lung/liver was linearly related with GA at the time of f-MRI and with EFW. SI lung/amniotic fluid was significantly higher in SG than in CG (p = 0,014). In contrast, among SG, lower values of SI lung/amniotic fluid were found in the SGA compared to AGA (p = 0,036). The days of oxygen supply were higher in the SGA subgroup than in the AGA subgroup (p = 0,028). CONCLUSIONS: SI lung/liver increases with fetal lung maturation and appears to be useful to estimate intrauterine fetal growth. SI lung/amniotic fluid seems to be a reliable predictive index to distinguish the IUGR fetuses that can recover their growth from those that were born SGA. f-MRI represents a promising frontier to predict IUGR fetus outcome, thus contributing to ameliorate the perinatal management.

The Free Radical Diseases of Prematurity: From Cellular Mechanisms to Bedside.

During the perinatal period, free radicals (FRs) are involved in several physiological roles such as the cellular responses to noxia, the defense against infectious agents, the regulation of cellular signaling function, and the induction of a mitogenic response. However, the overproduction of FRs and the insufficiency of an antioxidant mechanism result in oxidative stress (OS) which represents a deleterious process and an important mediator of damage to the placenta and the developing fetus. After birth, OS can be magnified by other predisposing conditions such as hypoxia, hyperoxia, ischemia, hypoxia ischemia-reperfusion, inflammation, and high levels of nonprotein-bound iron. Newborns are particularly susceptible to OS and oxidative damage due to the increased generation of FRs and the lack of adequate antioxidant protection. This impairment of the oxidative balance has been thought to be the common factor of the so-called "free radical related diseases of prematurity," including retinopathy of prematurity, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, kidney damage, and oxidative hemolysis. In this review, we provide an update focused on the factors influencing these diseases refining the knowledge about the role of OS in their pathogenesis and the current evidences of such relationship. Mechanisms governing FR formation and subsequent OS may represent targets for counteracting tissue damage.

Fetal programming and early identification of newborns at high risk of free radical-mediated diseases.

Nowadays metabolic syndrome represents a real outbreak affecting society. Paradoxically, pediatricians must feel involved in fighting this condition because of the latest evidences of developmental origins of adult diseases. Fetal programming occurs when the normal fetal development is disrupted by an abnormal insult applied to a critical point in intrauterine life. Placenta assumes a pivotal role in programming the fetal experience in utero due to the adaptive changes in structure and function. Pregnancy complications such as diabetes, intrauterine growth restriction, pre-eclampsia, and hypoxia are associated with placental dysfunction and programming. Many experimental studies have been conducted to explain the phenotypic consequences of fetal-placental perturbations that predispose to the genesis of metabolic syndrome, obesity, diabetes, hyperinsulinemia, hypertension, and cardiovascular disease in adulthood. In recent years, elucidating the mechanisms involved in such kind of process has become the challenge of scientific research. Oxidative stress may be the general underlying mechanism that links altered placental function to fetal programming. Maternal diabetes, prenatal hypoxic/ischaemic events, inflammatory/infective insults are specific triggers for an acute increase in free radicals generation. Early identification of fetuses and newborns at high risk of oxidative damage may be crucial to decrease infant and adult morbidity.

The role of oxidative stress on necrotizing enterocolitis in very low birth weight infants.

Necrotizing enterocolitis (NEC) is a devastating and common disease of very low birth weight (VLBW) infants with a mortality rate of 10% to 50% and a significant cause of morbidity in survivors. The incidence of NEC has increased from 5% to 7% in the last decades and this rate is likely to rise because of the increased survival of infants born at 24 weeks gestation, which are at high risk of developing NEC. NEC etiology is multifactorial: ischemia, infections, cytokines, enteral feeding and reactive oxygen species or free radicals (FRs) may contribute to the disruption of the immature gut barrier. In particular, ischemia, hypoxia-reperfusion, infection and inflammation are mechanisms capable of producing high levels of FRs, perturbing the normal redox balance and shifting cells to a state of oxidative stress (OS). Despite advances in neonatal medicine, the early diagnosis of NEC remains a major challenge. Early clinical signs are non specific and the laboratory findings are not fully reliable. Therefore, its delayed occurrence after birth, its rapid onset, the highly fulminant nature, and its severe morbidity, as well as the possibility of progression to death, strongly require the identification of new prospective biomarkers specific for high NEC risk. There is evidences that OS biomarkers in cord blood allow the early identification of infants at risk for NEC and thereby can be used to develop novel therapies for this devastating disease which predominantly occurs in premature infants.