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The authors reviewed the published evidence on the presence of oligosaccharides in human milk (HMO) and their benefits in in vitro and in vivo studies. The still limited data of trials evaluating the effect of mainly 2′-fucosyllactose (2′-FL) on the addition of some of HMOs to infant formula were also reviewed. PubMed was searched from January 1990 to April 2018. The amount of HMOs in mother’s milk is a dynamic process as it changes over time. Many factors, such as duration of lactation, environmental, and genetic factors, influence the amount of HMOs. HMOs may support immune function development and provide protection against infectious diseases directly through the interaction of the gut epithelial cells or indirectly through the modulation of the gut microbiota, including the stimulation of the bifidobacteria. The limited clinical data suggest that the addition of HMOs to infant formula seems to be safe and well tolerated, inducing a normal growth and suggesting a trend towards health benefits. HMOs are one of the major differences between cow’s milk and human milk, and available evidence indicates that these components do have a health promoting benefit. The addition of one or two of these components to infant formula is safe, and brings infant formula closer to human milk. More prospective, randomized trials in infants are need to evaluate the clinical benefit of supplementing infant formula with HMOs.

The importance of DHA to support fetal development and maternal health is well established. In this study, we applied the natural abundance approach to determine the contribution of 200 mg/d of DHA supplement to the plasma DHA pool in nineteen healthy pregnant women. Women received DHA, from week 20 until delivery, from an algal source (n 13, Algae group) or from fish oil (n 6, Fish group) with slightly different content of 13C. We measured plasma phospholipids DHA 13C:12C ratio (reported as δ13C) prior to supplementation (T0), after 10 (T1) and 90 days (T2) and prior to delivery (T3). The δ13C of DHA in algae and fish supplements were −15·8 (sd 0·2) mUr and −25·3 (sd 0·2) mUr (P < 0·001). DHA δ13C in the Algae group increased from −27·7 (sd 1·6) mUr (T0) to −21·9 (sd 2·2) mUr (T3) (P < 0·001), whereas there were not significant changes in the Fish group (–27·8 (sd 0·9) mUr at T0 and −27·3 (sd 1·1) mUr at T3, P = 0·09). In the Algae group, 200 mg/d of DHA contributed to the plasma phospholipid pool by a median value of 53 % (31–75 % minimum and maximum). This estimation was not possible in the Fish group. Our results demonstrate the feasibility of assessing the contribution of DHA from an algal source to the plasma DHA pool in pregnant women by the natural abundance approach. Plasma δ13C DHA did not change when consuming DHA of fish origin, with almost the same δ13C value of that of the pre-supplementation plasma δ13C DHA.

Small for gestational age (SGA) preterm neonates (birth weight < −2 SDS) are considered to have increased risk of bronchopulmonary dysplasia (BPD) compared to appropriate for GA (AGA) neonates. It is unclear if SGA infants have increased risk for respiratory distress syndrome (RDS) and mortality. We analyzed data from 515 neonates born <30 weeks GA, 98(19%) were SGA. SGA were compared to AGA by univariate analysis and logistic regression analysis (LRA). Significant variables at univariate analysis were IUGR (67 vs 7%, p  = 0.000), chorioamnionitis (1 vs 13%, p  = 0.017), pre-eclampsia (62 vs 18%, p  = 0.000), surfactant retreatment (47 vs 25%, p  = 0.000), BPD (32 vs 20%, p  = 0.015), death (30 vs 12%, p  = 0.000), SatO2/FiO2 on day 3 (376 vs 433, p  = 0.013), and SatO2/FiO2 ratio on day 28 (400 vs 448, p  = 0.000). LRA found the following associations: regarding mortality, a decreased Sat/FiO2 ratio on day 3 (OR 1.99, 95% CI 1.26–3.16, p  = 0.003); regarding BPD, surfactant retreatment (3.70, 2.11–6.49, p  = 0.000), being SGA (2.69, 1.36–5.36, p  = 0.005), decreasing GA (1.05, 1.03–1.08, p  = 0.000), decreasing SatO2/FiO2 ratio on day 3 (1.25, 1.11–1.40, p  = 0.000); and regarding severe RDS, pre-eclampsia (2.68, 1.58–4.55, p  = 0.000) and decreasing GA (1.06, 1.04–1.08, p  = 0.000). Conclusions : In our cohort of preterm infants, being SGA was significantly associated with BPD, but not with increased risk of mortality or RDS due to multiple pathophysiologic mechanisms. What is Known : • Small for gestational age preterm neonates are considered to have increased risk of bronchopulmonary dysplasia (BPD) compared to appropriate for GA neonates . • It is still unclear if SGA infants have increased risk for respiratory distress syndrome (RDS) and mortality . What is New : • In our cohort of 515 preterm infants (19% SGA), being SGA was significantly associated with BPD, but not with increased risk of mortality or RDS . • These results may be explained by the heterogeneity of mechanisms leading to SGA condition and by multiple mechanisms involving lung growth impairment and other factors .

The risk of bronchopulmonary dysplasia was significantly lower, and the risk of death slightly but not significantly higher, among extremely preterm infants who were randomly assigned to inhaled budesonide soon after birth than among those assigned to placebo. About one half of preterm infants (gestational age, <28 weeks) have bronchopulmonary dysplasia, 1 , 2 which is a major cause of early death. 1 , 3 Infants with bronchopulmonary dysplasia who survive have increased risks of neurodevelopmental impairment 4 and respiratory problems later in life. 5 , 6 Bronchopulmonary dysplasia results from ongoing lung injury and simultaneous repair 7 , 8 ; inflammation related to chorioamnionitis, postnatal infections, or iatrogenic causes (such as the use of ventilation or oxygen) contributes to lung fibrosis and arrested lung development. 7 , 9 Systemic glucocorticoids have been shown to reduce the incidence of bronchopulmonary dysplasia, but they may cause short-term and long-term adverse . . .

ObjectivesTo analyze the need for parenteral nutrition (PN) in infants with a birth weight (BW) between 1250 and 1499 g.MethodsRetrospective evaluation of clinical, nutritional, growth and neurodevelopmental data of infants with a BW between 1250 and 1499 g consecutively admitted to our institution between 2004 and 2020.ResultsOf the 503 infants admitted during the study period, 130 (26%) received PN: in 97 (19%) PN was medically indicated, while in 33 (7%) there was no clear indication. Patients who received medically indicated PN were younger, smaller, and sicker than the 373 infants who were managed with enteral nutrition, and their weight gain was lower (14.6 ± 4.1 vs 16.9 ± 4.2 g∙kg−1 ∙ d−1, p = 0.000). Body size at 36 weeks and 2-year anthropometry and neurodevelopment of the infants managed with enteral nutrition were not different from our reference values.ConclusionsAfter lowering the BW threshold for bridging PN from 1500 to 1250 g, we found that PN was started in only 20% of infants with a BW between 1250 and 1500 g. Withholding PN if not medically indicated did not result neither in growth faltering nor in reduced neurodevelopment.

BackgroundThis study aimed to investigate the effect of nutrition and growth during the first 4 weeks after birth on cerebral volumes and white matter maturation at term equivalent age (TEA) and on neurodevelopmental outcome at 2 years' corrected age (CA), in preterm infants.MethodsOne hundred thirty-one infants born at a gestational age (GA) <31 weeks with magnetic resonance imaging (MRI) at TEA were studied. Cortical gray matter (CGM) volumes, basal ganglia and thalami (BGT) volumes, cerebellar volumes, and total brain volume (TBV) were computed. Fractional anisotropy (FA) in the posterior limb of internal capsule (PLIC) was obtained. Cognitive and motor scores were assessed at 2 years' CA.ResultsCumulative fat and enteral intakes were positively related to larger cerebellar and BGT volumes. Weight gain was associated with larger cerebellar, BGT, and CGM volume. Cumulative fat and caloric intake, and enteral intakes were positively associated with FA in the PLIC. Cumulative protein intake was positively associated with higher cognitive and motor scores (all P<0.05).ConclusionOur study demonstrated a positive association between nutrition, weight gain, and brain volumes. Moreover, we found a positive relationship between nutrition, white matter maturation at TEA, and neurodevelopment in infancy. These findings emphasize the importance of growth and nutrition with a balanced protein, fat, and caloric content for brain development.

IntroductionTransposition of the great arteries (TGA) is a cyanotic congenital heart defect that requires surgical correction, with the use of cardiopulmonary-bypass (CPB), usually within 3 weeks of life. The use of CPB in open heart surgery results in brain hypoperfusion and in a powerful systemic inflammatory response and oxidative stress.ObjectiveWe aimed to develop a novel untargeted metabolomics approach to detect early postoperative changes in metabolic profile following neonatal cardiac surgery.MethodsWe studied 14 TGA newborns with intact ventricular septum undergoing arterial switch operation with the use of CPB. Urine samples were collected preoperatively and at the end of the surgery and were analyzed using an untargeted metabolomics approach based on UHPLC-high resolution mass spectrometry.ResultsSince post surgery metabolic spectra were heavily contaminated by metabolites derived from administered drugs, we constructed a list of drugs used during surgery and their related metabolites retrieved from urine samples. This library was applied to our samples and 1255 drugs and drug metabolites were excluded from the analysis. Afterward, we detected over 39,000 unique compounds and 371 putatively annotated metabolites were different between pre and post-surgery samples. Among these metabolites, 13 were correctly annotated or identified. Metabolites linked to kynurenine pathway of tryptophan degradation displayed the highest fold change.ConclusionsThis is the first report on metabolic response to cardiac surgery in TGA newborns. We developed an experimental design that allowed the identification of perturbed metabolic pathways and potential biomarkers of brain damage, limiting drugs interference in the analysis.

Bacterial pneumonia in newborns often leads to surfactant deficiency or dysfunction, as surfactant is inactivated or its production/turnover impaired. No data are available in vivo in humans on the mechanism of surfactant depletion in neonatal pneumonia. We studied the kinetics of surfactant's major component, disaturated-phosphatidylcholine (DSPC), in neonatal pneumonia, and we compared our findings with those obtained from control newborn lungs. We studied thirty-one term or near-term newborns (gestational age 39.7±1.7 weeks, birth weight 3185±529 g) requiring mechanical ventilation. Fifteen newborns had pneumonia, while 16 newborns were on mechanical ventilation but had no lung disease. Infants received an intratracheal dose of 13C labeled dipalmitoyl-phosphatidylcholine at the study start. We measured the amount and the isotopic enrichment of DSPC-palmitate from serial tracheal aspirates by gas chromatography and gas chromatography-mass spectrometry, respectively, and we calculated the DSPC half-life (HL) and pool size (PS) from the isotopic enrichment curves of surfactant DSPC-palmitate. The mean DSPC amount obtained from all tracheal aspirates did not differ between the two groups. DSPC HL was 12.7 (6.5-20.2) h and 25.6 (17.9-60.6) h in infants with pneumonia compared with control infants (p = 0.003). DSPC PS was 14.1 (6.6-30.9) mg/kg in infants with pneumonia and 34.1 (25.6-65.0) mg/kg in controls, p = 0.042. Myeloperoxidase (MPO) activity, as a marker of lung inflammation, was 1322 (531-2821) mU/ml of Epithelial Lining Fluid (ELF) and 371(174-1080) mU/ml ELF in infants with pneumonia and in controls, p = 0.047. In infants with pneumonia, DSPC PS and HL significantly and inversely correlated with mean Oxygenation Index (OI) during the study (DSPC PS vs. OI R = -0.710, p = 0.004 and HL vs. OI R = -0.525, p = 0.044, respectively). We demonstrated for the first time in vivo in humans that DSPC HL and PS were markedly impaired in neonatal pneumonia and that they inversely correlated with the degree of respiratory failure.

Background Chorioamnionitis is associated with preterm delivery and morbidities; its role in lung disease is controversial. The aim of this study is to assess the effect of chorioamnionitis on metabolite and lipid profiles of epithelial lining fluid in preterm newborns with respiratory distress syndrome (RDS). Methods The study involved 30 newborns with RDS, born from mothers with or without histological chorioamnionitis (HCA): HCA+, N  = 10; HCA−, N  = 20. Patients had a gestational age ≤30 weeks; the groups were matched for age and birth weights. Tracheal aspirates were collected within 24 h after birth and analyzed using liquid chromatography/mass spectrometry-based untargeted lipidomics. Results According to Mann–Whitney U tests, 570 metabolite features had statistically significantly higher or lower concentrations ( p  < 0.05) in tracheal aspirates of HCA+ compared to HCA−, and 241 metabolite features were putatively annotated and classified. The most relevant changes involved higher levels of glycerophospholipids (fold change 2.42–17.69) and sphingolipids, with lower concentration of all annotated sphingomyelins in HCA+ (fold change 0.01–0.50). Conclusions Untargeted lipidomics of tracheal aspirates suggested the production of lipid mediators in the context of an ongoing inflammatory status in HCA+ babies. However, the effect of chorioamnionitis on epithelial lining fluid composition deserves further investigations on a larger group of infants. Impact Our lipidomics investigation on tracheal aspirates of preterm newborns at birth suggested that exposure to maternal histological chorioamnionitis may cause changes in epithelial lining fluid composition. This is the first description of epithelial lining fluid lipidomic profiles in preterm infants with and without exposition to chorioamnionitis. These results could provide novel link between placental membrane inflammation and newborns’ respiratory outcome.

Background Noninvasive high frequency oscillatory ventilation through nasal prongs (nHFOV) has been proposed as a new respiratory support in neonatology. We studied the effect of ventilation parameters and nasal prongs on nHFOV efficacy and mechanics. Methods Customized sealed circuits connecting a SM3100A oscillator to a neonatal lung model were developed to evaluate the effect of applying HFOV via two different sized nasal prongs on delivered tidal volume and pressure. Measurements were made across a range of frequencies and pressures; amplitude was set to obtain visible lung oscillation. Results Volume delivered by peak-to-peak oscillation, ventilation, and pressure significantly differed among the interfaces, being higher for large cannulae and the control circuit ( p  < 0.0001). The interposition of a large or small nasal prong reduced volume to 56 and 26%, ventilation to 32 and 9%, and mean pressure to 83 and 79%, respectively, of the values measured for the direct connection of the oscillator to the test lung. Volume and ventilation were inversely related to frequency, which was particularly evident with larger diameter circuits due to higher delivered tidal volume ( R 2  > 0.9). Increasing ventilation was associated with larger tidal volume and nasal prong diameter (adjusted R 2  = 0.97). Conclusions nHFOV using common nasal prongs is technically possible. Efficiency of tidal volume delivery is significantly affected by prong diameter.