Explore the vast range of titles available.

Preterm birth is an increasing worldwide problem. Prematurity is the second most common cause of death in children under 5 years of age. It is associated with a higher risk of several pathologies in the perinatal period and adulthood. Maternal milk, a complex fluid with several bioactive factors, is the best option for the newborn. Its dynamic composition is influenced by diverse factors such as maternal age, lactation period, and health status. The aim of the present review is to summarize the current knowledge regarding some bioactive factors present in breastmilk, namely antioxidants, growth factors, adipokines, and cytokines, paying specific attention to prematurity. The revised literature reveals that the highest levels of these bioactive factors are found in the colostrum and they decrease along the lactation period; bioactive factors are found in higher levels in preterm as compared to full-term milk, they are lacking in formula milk, and decreased in donated milk. However, there are still some gaps and inconclusive data, and further research in this field is needed. Given the fact that many preterm mothers are unable to complete breastfeeding, new information could be important to develop infant supplements that best match preterm human milk.

Morbidities of impaired immunity and dysregulated inflammation are common in preterm infants. Postnatal Intestinal development plays a critical role in the maturation of the immune system and is, in part, driven by exposure to an enteral diet. The aim of this study was to evaluate the influence of the timing of the first enteral feeding on intestinal inflammation and risk of disease. 130 infants <33 weeks' gestation were studied. Maternal and infant data were abstracted from the medical record. Single and multiplex ELISA assays quantified cytokines from fecal and serum samples at two weeks postnatal age. A delay in enteral feedings after the third postnatal day is associated with a 4.5 (95% CI 1.8-11.5, p=0.002) fold increase in chronic lung disease, 2.9 (1.1-7.8, p=0.03) fold increase in retinopathy of prematurity, and 3.4 (1.2-9.8, p=0.02) fold increase in multiple comorbidities compared to infants fed on or before the third day. Additionally, a delay in the initiation of feedings is associated with increased fecal IL-8 levels and a decreased IL-10:IL-8 ratio. A delay in enteral feeding is associated with intestinal inflammation and increased risks of morbidities. To improve neonatal outcomes, early nutritional practices need to be reevaluated.

Infants born at extremely low gestational age are at high risk for bronchopulmonary dysplasia and continuing lung disease. There are no early clinical biomarkers for pulmonary outcome and limited therapeutic interventions. We performed global proteomics of premature infant tracheal aspirate (TA) and plasma to determine the composition and source of lung fluid proteins and to identify potential biomarkers of respiratory outcome. TA samples were collected from intubated infants in the TOLSURF cohort before and after nitric oxide treatment, and plasma was collected from NO CLD infants. Protein abundance was assayed by HPLC/tandem mass spectrometry and Protein Prospector software. mRNA abundance in mid-gestation fetal lung was assessed by RNA sequencing. Pulmonary morbidity was defined as a need for ventilatory support at term and during the first year. Abundant TA proteins included albumin, hemoglobin, and actin-related proteins. 96 of 137 detected plasma proteins were present in TA (r = 0.69, p<0.00001). Based on lung RNAseq data, ~88% of detected TA proteins in injured infant lung are derived at least in part from lung epithelium with overrepresentation in categories of cell membrane/secretion and stress/inflammation. Comparing 37 infants at study enrollment (7-14 days) who did or did not develop persistent pulmonary morbidity, candidate biomarkers of both lung (eg., annexin A5) and plasma (eg., vitamin D-binding protein) origin were identified. Notably, levels of free hemoglobin were 2.9-fold (p = 0.03) higher in infants with pulmonary morbidity. In time course studies, hemoglobin decreased markedly in most infants after enrollment coincident with initiation of inhaled nitric oxide treatment. We conclude that both lung epithelium and plasma contribute to the lung fluid proteome in premature infants with lung injury. Early postnatal elevation of free hemoglobin and heme, which are both pro-oxidants, may contribute to persistent lung disease by depleting nitric oxide and increasing oxidative/nitrative stress.

Adequate foetal growth is primarily determined by nutrient availability, which is dependent on placental nutrient transport and foetal metabolism. We have used (1)H nuclear magnetic resonance (NMR) spectroscopy to probe the metabolic adaptations associated with premature birth. The metabolic profile in (1)H NMR spectra of plasma taken immediately after birth from umbilical vein, umbilical artery and maternal blood were recorded for mothers delivering very-low-birth-weight (VLBW) or normo-ponderal full-term (FT) neonates. Clear distinctions between maternal and cord plasma of all samples were observed by principal component analysis (PCA). Levels of amino acids, glucose, and albumin-lysyl in cord plasma exceeded those in maternal plasma, whereas lipoproteins (notably low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) and lipid levels were lower in cord plasma from both VLBW and FT neonates. The metabolic signature of mothers delivering VLBW infants included decreased levels of acetate and increased levels of lipids, pyruvate, glutamine, valine and threonine. Decreased levels of lipoproteins glucose, pyruvate and albumin-lysyl and increased levels of glutamine were characteristic of cord blood (both arterial and venous) from VLBW infants, along with a decrease in levels of several amino acids in arterial cord blood. These results show that, because of its characteristics and simple non-invasive mode of collection, cord plasma is particularly suited for metabolomic analysis even in VLBW infants and provides new insights into the materno-foetal nutrient exchange in preterm infants.

Low-grade germinal matrix-intraventricular hemorrhage (GM-IVH) is the most common complication in extremely premature neonates. The occurrence of GM-IVH is highly associated with hemodynamic instability in the premature brain, yet the long-term impact of low-grade GM-IVH on cerebral blood flow and neuronal health have not been fully investigated. We used an innovative combination of frequency-domain near infrared spectroscopy and diffuse correlation spectroscopy (FDNIRS-DCS) to measure cerebral oxygen saturation (SO 2 ) and an index of cerebral blood flow (CBF i ) at the infant’s bedside and compute an index of cerebral oxygen metabolism (CMRO 2i ). We enrolled twenty extremely low gestational age (ELGA) neonates (seven with low-grade GM-IVH) and monitored them weekly until they reached full-term equivalent age. During their hospital stay, we observed consistently lower CBF i and CMRO 2i in ELGA neonates with low-grade GM-IVH compared to neonates without hemorrhages. Furthermore, lower CBF i and CMRO 2i in the former group persists even after the resolution of the hemorrhage. In contrast, SO 2 does not differ between groups. Thus, CBF i and CMRO 2i may have better sensitivity than SO 2 in detecting GM-IVH-related effects on infant brain development. FDNIRS-DCS methods may have clinical benefit for monitoring the evolution of GM-IVH, evaluating treatment response and potentially predicting neurodevelopmental outcome.

Apnea of prematurity (AOP) is a significant clinical problem manifested by an unstable respiratory rhythm reflecting the immaturity of respiratory control systems. This review will address the pathogenesis of and treatment strategies for AOP. Although the neuronal mechanisms leading to apnea are still not well understood, recent decades have provided better insight into the generation of the respiratory rhythm and its modulation in the neonate. Ventilatory responses to hypoxia and hypercarbia are impaired and inhibitory reflexes are exaggerated in the neonate. These unique vulnerabilities predispose the neonate to the development of apnea. Treatment strategies attempt to stabilize the respiratory rhythm. Caffeine remains the primary pharmacological treatment modality and is presumed to work through blockade of adenosine receptors A 1 and A 2 . Recent evidences suggest that A 2A receptors may have a greater role than previously thought. AOP typically resolves with maturation suggesting increased myelination of the brainstem.

Premature infants are exposed to increased generation of reactive oxygen species, and on the other hand, they have a deficient antioxidant defense system. Oxidative insult is a salient part of lung injury that begins as acute inflammatory injury in respiratory distress disease and then evolves into chronic and structural scarring leading to bronchopulmonary dysplasia. Oxidative stress is also involved in the pathogenesis of pulmonary hypertension in newborns through the modulation of the vascular tone and the response to pulmonary vasodilators, with consequent decrease in the density of the pulmonary vessels and thickening of the pulmonary arteriolar walls. Oxidative stress has been recognized as both a trigger and an endpoint for several events, including inflammation, hypoxia, hyperoxia, drugs, transfusions, and mechanical ventilation, with impairment of pulmonary function and prolonged lung damage. Redoxomics is the most fascinating new measure to address lung damage due to oxidative stress. The new challenge is to use omics data to discover a set of biomarkers useful in diagnosis, prognosis, and formulating optimal and individualized neonatal care. The aim of this review was to examine the most recent evidence on the relationship between oxidative stress and lung diseases in preterm newborns. What is currently known regarding oxidative stress-related lung injury pathogenesis and the available preventive and therapeutic strategies are also discussed.

Objective To test the hypothesis that a higher pulsoximetric arterial oxygen saturation (SpO2) target range is associated with reduced cerebral tissue oxygen desaturations from baseline during events of hypoxaemia or bradycardia. Design Randomised crossover trial. Setting Single tertiary care neonatal intensive care unit. Patients Sixteen preterm infants with severe intermittent hypoxaemia or bradycardia. Interventions SpO2 target was set to 80–92% and 85–96% for 4 h each in random sequence. On a subsequent day, the target sequence was reversed and the study was repeated. Main outcome measures We simultaneously recorded cerebral tissue oxygen saturation (cerebral StO2), SpO2 and heart rate. Cerebral StO2 was measured by near infrared spectroscopy. The primary outcome was the cumulative cerebral StO2 desaturation score representing the area below a cerebral StO2 baseline value before onset of each hypoxaemic or bradycardic event. Results During low SpO2 target range the median (IQR) cumulative cerebral StO2 desaturation score was higher (27384 (15825–37396) vs 18103 (6964–32946), p=0.011) and the mean (±SD) number of events was higher (29.1 (±15.3) vs 21.1 (±11.4), p=0.001). More time was spent with SpO2 below 80% (57.2 (±24.8) min vs 34.0 (±29.6) min, p=0.006). Total time of hyperoxaemia (defined as SpO2 ≥97% and ≥99%, respectively) and total time with cerebral StO2 <60% and <55% were similar. Conclusions A lower SpO2 target range was associated with a greater cumulative cerebral StO2 desaturation score, caused by more frequent SpO2 desaturations. However, time at very low cerebral StO2 was not affected. Episodes of hyperoxaemia were not reduced.

Key Points The intrauterine environment and growth during early life can influence the development of chronic noncommunicable diseases, such as type 2 diabetes mellitus and cardiovascular disease Children born premature or small for gestational age are at increased risk of these metabolic diseases, especially those who gain weight rapidly during infancy Timing of adrenarche, frequency of clinical manifestations (axilarche/pubarche) and onset of puberty seem to be altered, although studies have produced conflicting results This cluster of adrenal–gonadal–metabolic abnormalities has not been confirmed among boys Conditions affecting intrauterine growth and development predispose individuals to early onset of hypertension, chronic kidney disease and endothelial, vascular and metabolic abnormalities Preventive strategies should start early during postnatal life to avoid rapid weight gain Mericq and colleagues review human data supporting an increased risk of metabolic diseases among children born premature or small for gestational age. The adrenal and pubertal modifications that contribute to this risk and the metabolic changes that occur during adolescence and adulthood are discussed. Accumulating evidence suggests that both the intrauterine environment and growth during early life can influence the development of chronic noncommunicable diseases, such as type 2 diabetes mellitus and cardiovascular disease, in adulthood. Here, we review the available human data supporting increased metabolic risk among children born premature or small for gestational age; the adrenal and pubertal modifications that contribute to this risk; metabolic changes that occur during adolescence and early adulthood; and approaches to potentially modify or decrease risk of metabolic disease. The risks associated with delivery at term or preterm are compared for each period of life. Knowledge of these associations is fundamental for the paediatric community to develop preventive strategies early during postnatal life.

BackgroundAccelerated infant weight gain in individuals born full term is linked to cardiovascular risk in adulthood, but data in those born preterm are inconsistent.ObjectiveTo investigate the association between weight gain in infancy and childhood with later markers of the metabolic syndrome in adolescents who were born preterm.Study designLongitudinal cohort study.SettingChildren born preterm with regular assessments of infant growth had auxology, body composition (dual X-ray absorptiometry), blood pressure, insulin sensitivity and lipid profile determined in adolescence.ResultsWe reviewed 153 children (mean gestation 30.8 weeks, median birth weight 1365 g) of whom 102 consented to venepuncture at a median age of 11.5 years. Adolescent height and weight standard deviation scores (SDS) were similar to population averages (0.01±0.92 and 0.3±1.2, respectively) and did not differ between infants when grouped according to degree of catch-up in weight gain in the immediate postdischarge period to 12 weeks of age. There were no significant associations between infant weight gain (change in weight SDS adjusted for length) and later metabolic outcome. However, there were strong associations between more rapid childhood weight gain (after 1 year of age) and subsequent body composition (higher fat mass %, fat mass index and waist circumference) and metabolic markers (higher fasting insulin, blood pressure and lower insulin sensitivity).ConclusionsThe association of rapid weight gain on health is time critical in those born preterm; in early infancy, this does not impact on metabolic status in adolescence, in contrast to rapid weight gain in childhood, which should be discouraged. However, given the critical importance of brain growth in the neonatal period and infancy, further research is needed before strategies that discourage infant weight gain or catch-up can be recommended for infants born preterm.