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To assess the effect of heliox, a helium-oxygen mixture, on respiratory distress symptoms in young infants. Prospective, randomized, double-blind study. Pediatric ICU (PICU) of a university hospital. Twenty infants, all < 3 months old, admitted to the PICU with moderate-to-severe acute respiratory syncytial virus bronchiolitis. All infants were randomly and blindly assigned to inhale either heliox or an air-oxygen mixture (airox) for 1 h under an oxyhood. After 1 h, the respiratory distress score was significantly lower in the heliox group compared with the airox group (3.05 vs 5.5, p < 0.01), with a significant reduction in accessory muscles use (p < 0.05) and expiratory wheezing (p < 0.01). In contrast, inspiratory breath sounds and cyanosis did not significantly differ between groups. The ex-premature infants of the heliox group had a higher respiratory distress score at baseline compared with the term infants of this group (5.8 vs 5.2, p < 0.05) and a comparable decrease in the score at 60 min. In young infants, even those born prematurely, heliox breathing induced a rapid reduction in accessory muscles use and expiratory wheezing. Further studies are needed to confirm the decreased respiratory muscle work of breathing during heliox inhalation in this population.

ABSTRACT Background MicroRNAs (miRNAs) are small noncoding RNAs involved in posttranscriptional regulation. miRNAs can be secreted and found in many body fluids, and although they are particularly abundant in breastmilk, their functions remain elusive. Human milk (HM) miRNAs start to raise considerable interest, but a comprehensive understanding of the repertoire and expression profiles along lactation has not been well characterized. Objectives This study aimed to characterize the longitudinal profile of HM miRNA between the second week and third month postpartum. Methods We used a new sensitive technology to measure HM miRNAs in a cohort of 44 French mothers [mean ± SD age: 31 ± 3.5; BMI (in kg/m2) 21.8 ± 2.3] who delivered at term and provided HM samples at 3 time points (17 ± 3 d, 60 ± 3 d, and 90 ± 3 d) during follow-up visits. Results We detected 685 miRNAs, of which 35 showed a high and stable expression along the lactation period analyzed. We also described for the first time a set of 11 miRNAs with a dynamic expression profile. To gain insight into the potential functional relevance of this set of miRNAs, we selected miR-3126 and miR-3184 to treat undifferentiated Caco-2 human intestinal cells and then assessed differentially expressed genes and modulation of related biological pathways. Conclusions Overall, our study provides new insights into HM miRNA composition and, to our knowledge, the first description of its longitudinal dynamics in mothers who delivered at term. Our in vitro results obtained in undifferentiated Caco-2 human intestinal cells transfected with HM miRNAs also provide further support to the hypothesized mother-to-neonate signaling role of HM miRNAs. This trial was registered at clinicaltrials.gov as NCT01894893.

Background: Post-natal gut maturation in infants interrelates maturation of the morphology, digestive, and immunological functions and gut microbiota development. Here, we explored both microbiota development and markers of gut barrier and maturation in healthy term infants during their early life to assess the interconnection of gut functions during different infant formulae regimes. Methods: A total of 203 infants were enrolled in this randomized double-blind controlled trial including a breastfed reference group. Infants were fed starter formulae for the first four weeks of life, supplemented with different combination of nutrients (lactoferrin, probiotics (Bifidobacterium animal subsp. Lactis) and prebiotics (Bovine Milk-derived Oligosaccharides—BMOS)) and subsequently fed the control formula up to eight weeks of life. Stool microbiota profiles and biomarkers of early gut maturation, calprotectin (primary outcome), elastase, α-1 antitrypsin (AAT) and neopterin were measured in feces at one, two, four, and eight weeks. Results: Infants fed formula containing BMOS had lower mean calprotectin levels over the first two to four weeks compared to the other formula groups. Elastase and AAT levels were closer to levels observed in breastfed infants. No differences were observed for neopterin. Global differences between the bacterial communities of all groups were assessed by constrained multivariate analysis with hypothesis testing. The canonical correspondence analysis (CCA) at genus level showed overlap between microbiota profiles at one and four weeks of age in the BMOS supplemented formula group with the breastfed reference, dominated by bifidobacteria. Microbiota profiles of all groups at four weeks were significantly associated with the calprotectin levels at 4 (CCA, p = 0.018) and eight weeks of age (CCA, p = 0.026). Conclusion: A meaningful correlation was observed between changes in microbiota composition and gut maturation marker calprotectin. The supplementation with BMOS seems to favor gut maturation closer to that of breastfed infants.

Background: Prebiotics and probiotics exert beneficial effects by modulating gut microbiota and immune system. This study evaluates efficacy and safety of an infant formula containing bovine milk-derived oligosaccharides and Bifidobacterium animalis ssp lactis ( B. lactis ) (CNCM I-3446) on incidence of diarrhea and febrile infections during the first year of life (primary outcome). Methods: Full-term infants receiving Test or Control (without bovine milk-derived oligosaccharide and B. lactis) formulae were enrolled in a multicenter, randomized, controlled, and double-blind trial with a reference breastfeeding group. . Results: 413 infants were assigned between Test ( n = 206) and Control ( n = 207) formula. There was no significant difference for diarrhea and febrile infections incidence between groups at 6 (odds ratio (95% confidence interval) = 0.56 (0.26–1.15), P = 0.096) and 12 mo (odds ratio = 0.66 (0.38–1.14), P = 0.119). Test formula was well tolerated, anthropometrics parameters were not significantly different between groups and aligned with WHO growth standards up to 12 mo. Data from test group showed that gut microbiota pattern, fecal IgA and stool pH were brought to be closer to those of breastfed infants. Conclusion: An infant formula enriched with bovine milk-derived oligosaccharide and B. lactis supports normal infant growth, is well tolerated and improves intestinal health markers. No differences in diarrhea and febrile infection incidence were found in the population studied.

The effect of protein intake on growth velocity in infancy may be mediated by insulin-like growth factor-1 (IGF-1). This study aimed to determine the effects of formulae containing 1·8 (F1·8) or 2·7 g (F2·7) protein/418·4 kJ (100 kcal) on IGF-1 concentrations and growth. Healthy term infants were randomly assigned to receive F1·8 (n 74) or F2·7 (n 80) exclusively for the first 4 months of life. A group of breast-fed infants (n 84) was followed-up simultaneously (reference). Growth and body composition were measured at 0·5, 4, 6, 12, 36, 48 and 60 months of life. The IGF-1 concentrations at 4 months (primary outcome) were similar in the F1·8 (67·1 (sd 20·8) ng/l; n 70) and F2·7 (71·2 (sd 27·5) ng/l; n 73) groups (P=0·52). Both formula groups had higher IGF-1 concentrations than the breast-fed group at 4 and 9 months of age (P≤0·0001). During the first 60 months of life, anthropometric parameters in the F1·8 group were lower compared with the F2·7 group, and the differences were significant for head circumference from 2 to 60 months, body weight at 4 and 6 months and length at 9, 12 and 36 months of age. There were no significant differences in body composition between these two groups at any age. We conclude that, in formula-fed infants, although increased protein intake did not affect the IGF-1 concentration during the first 12 months of life, it did affect length and head circumference growth, suggesting that factors other than IGF-1 could play roles in determining growth velocity.

Preterm infants require fortification of human milk (HM) with essential fatty acids (FA) to ensure adequate post-natal development. As part of a larger randomized controlled study, we investigated FA metabolism in a subset of 47 clinically stable preterm infants (birth weight ≤1500 g or gestational age ≤32 weeks). Infants were randomized to receive HM supplemented with either a new HM fortifier (nHMF; n = 26) containing 12.5 g medium-chain FA (MCFA), 958 mg linoleic acid (LA), 417 mg α-linolenic acid (ALA), and 157 mg docosahexaenoic acid (DHA) per 100 g of powder (in compliance with the latest guidelines) or a fat-free HMF (cHMF; n = 21). Plasma phospholipid (PL) and triacylglycerol (TAG), and red blood cell phosphatidylcholine (RBC-PC) and phosphatidylethanolamine (RBC-PE) FA profiles were assessed before and after 21 days of feeding. In the nHMF group, significantly increased levels of n-9 monounsaturated fatty acids were observed, formed most likely by elongation and desaturation of dietary saturated fatty acids present in HM. ALA fortification increased ALA assimilation into plasma TAG. Similarly, DHA fortification enriched the DHA content in RBC-PE, which, in this compartment, was not associated with lower arachidonic acid levels as observed in plasma TAG and phospholipids. RBC-PE, a reliable indicator of FA metabolism and accretion, was the most sensitive compartment in this study.

ObjectiveTo assess the association between histological chorioamnionitis without maternal clinical symptoms and neurodevelopmental disabilities at age 5 years in children born very preterm.Design French national prospective population-based cohort study, EPIPAGE-2 (Etude épidémiologique sur les petits âges gestationnels).SettingAll births from 22 to 34 weeks of gestational age in France in 2011 were eligible.PopulationInfants born alive between 24+0 and 31+6 weeks following preterm labour (PTL) or preterm premature rupture of membranes (PPROMs).ExposureHistological chorioamnionitis without maternal clinical symptoms, also called isolated histological chorioamnionitis, was defined as the presence of neutrophils in the chorionic plate, excluding clinical chorioamnionitis.Main outcome measuresNeurodevelopmental disabilities, a composite outcome including cerebral palsy, developmental coordination disorders, sensory impairment, developmental cognitive deficiencies or behavioural difficulties. These assessments were comprehensive, standardised and conducted by trained neuropsychologists and paediatricians at age 5 years.ResultsAmong 1296 children alive at 5 years of age, 486 (36.3%) were born in a context of isolated histological chorioamnionitis. Overall, 47% vs 33.6% of children exposed and not exposed to isolated histological chorioamnionitis had mild neurodevelopmental disabilities, and 13.8% vs 13.3% had moderate-to-severe neurodevelopmental disabilities. After multiple imputation and multivariable analysis, isolated histological chorioamnionitis was found not to be associated with the occurrence of mild or moderate-to-severe neurodevelopmental disabilities (adjusted OR: 1.0, 95% CI: 0.7 to 1.4 and 0.9, 0.6 to 1.2).ConclusionWe did not find any association between isolated histological chorioamnionitis and neurodevelopmental disabilities at age 5 years in children born very preterm after PTL or PPROM.

ObjectiveTo compare mortality and rates of significant neurosensory impairment (sNSI) at 18–36 months’ corrected age in infants born extremely preterm across three international cohorts.DesignRetrospective analysis of prospectively collected neonatal and follow-up data.SettingThree population-based observational cohort studies: the Australian and New Zealand Neonatal Network (ANZNN), the Canadian Neonatal and Follow-up Networks (CNN/CNFUN) and the French cohort Etude (Epidémiologique sur les Petits Ages Gestationnels: EPIPAGE-2).PatientsExtremely preterm neonates of <28 weeks’ gestation in year 2011.Main outcome measuresPrimary outcome was composite of mortality or sNSI defined by cerebral palsy with no independent walking, disabling hearing loss and bilateral blindness.ResultsOverall, 3055 infants (ANZNN n=960, CNN/CNFUN n=1019, EPIPAGE-2 n=1076) were included in the study. Primary composite outcome rates were 21.3%, 20.6% and 28.4%; mortality rates were 18.7%, 17.4% and 26.3%; and rates of sNSI among survivors were 4.3%, 5.3% and 3.3% for ANZNN, CNN/CNFUN and EPIPAGE-2, respectively. Adjusted for gestational age and multiple births, EPIPAGE-2 had higher odds of composite outcome compared with ANZNN (OR 1.71, 95% CI 1.38 to 2.13) and CNN/CNFUN (OR 1.72, 95% CI 1.39 to 2.12). EPIPAGE-2 did have a trend of lower odds of sNDI but far short of compensating for the significant increase in mortality odds. These differences may be related to variations in perinatal approach and practices (and not to differences in infants’ baseline characteristics).ConclusionsComposite outcome of mortality or sNSI for extremely preterm infants differed across high-income countries with similar baseline characteristics and access to healthcare.

This corrects the article DOI: 10.1038/pr.2016.270