Preterm infants face health problems likely related to microbial exposures, including sepsis and necrotizing enterocolitis. However, the role of the gut microbiome in preterm infant health is poorly understood. Microbial colonization differs from that of healthy term babies because it occurs in the NICU and is often perturbed by antibiotics. We measured bacterial compositions and metabolomic profiles of 77 fecal samples from 32 preterm infants to investigate the differences between microbiomes in health and disease. Rather than finding microbial signatures of disease, we found that both the preterm infant microbiome and the metabolome were personalized and that the preterm infant gut microbiome is enriched in microbes that commonly dominate in the presence of antibiotics. These results contribute to the growing knowledge of the preterm infant microbiome and emphasize that a personalized view will be important to disentangle the health consequences of the preterm infant microbiome.

Platelet-activating factor (PAF) is implicated in pathogenesis of chronic hypoxia-induced pulmonary hypertension in some animal models and in neonates. Effects of chronic hypoxia on PAF receptor (PAF-R) system in fetal pulmonary vasculature are unknown. We investigated the effect of chronic high altitude hypoxia (HAH) in fetal lambs [pregnant ewes were kept at 3,801 m (12,470 ft) altitude from approximately 35 to 145 days gestation] on PAF-R-mediated effects in the pulmonary vasculature. Age-matched controls were kept at sea level. Intrapulmonary arteries were isolated, and smooth muscle cells (SMC-PA) were cultured from HAH and control fetuses. To determine presence of pulmonary vascular remodeling, lung tissue sections were subjected to morphometric analysis. Percentage medial wall thickness was significantly increased (P < 0.05) in arteries at all levels in the HAH lambs. PAF-R protein expression studied by immunocytochemistry and Western blot analysis on lung tissue SMC-PA demonstrated greater PAF-R expression in HAH lambs. PAF-R binding (femtomoles per 10(6) cells) in HAH SMC-PA was 90.3 +/- 4.08 and 66% greater than 54.3 +/- 4.9 in control SMC-PA. Pulmonary arteries from HAH fetuses synthesized >3-fold PAF than vessels from controls. Compared with controls SMC-PA of HAH lambs demonstrated 139% and 40% greater proliferation in 10% FBS alone and with 10 nM PAF, respectively. Our data demonstrate that exposure of ovine fetuses to HAH will result in significant upregulation of PAF synthesis, PAF-R expression, and PAF-R-mediated effects in pulmonary arteries. These findings suggest that increased PAF-R protein expression and increased PAF binding contribute to pulmonary vascular remodeling in these animals and may predispose them to persistent pulmonary hypertension after birth.

Safe handling and preparation of breastmilk within the hospital setting are often taken for granted, and the process may not be scrutinized until problems arise. Areas of concern focus on both risk of contamination of breastmilk feedings due to handling and fortification and risk of a breastmilk misadministration. In two phases, Children's Hospital of Orange County (Orange, CA) implemented centralized breastmilk handling and breastmilk bar code scanning. As a result of these process changes, reports of breastmilk administration errors decreased to zero. However, bar code scanning allowed for the tracking of near misses. During the first 6 months of breastmilk bar code scanning, 55 attempts to feed the wrong breastmilk to the wrong patient and 127 attempts to feed expired breastmilk were prevented. Our findings are consistent with current practice recommendations that support the use of centralized breastmilk handling and systems for proper identification of breastmilk.

The results of this initiative suggest that a multidisciplinary approach, including education, changes in workflow, and redefinition of roles, is effective in improving breastmilk rates at discharge in the VLBW patient population.

Human biology follows recurring daily rhythms that are governed by circadian cues in the environment. Here we show that human milk is a powerful form of "chrononutrition," formulated to communicate time-of-day information to infants. However, 85% of breastfed infants in the US consume some milk that does not come directly from the breast but is pumped and stored in advance of feeding. Expressed milk is not necessarily circadian-matched (e.g., an infant might drink breastmilk pumped in the evening on the following morning). Ingesting mistimed milk may disrupt infants' developing circadian rhythms, potentially contributing to sleep problems and decreased physiological attunement with their mothers and environments. Dysregulated circadian biology may compromise infant health and development. Despite wide-ranging public health implications, the timing of milk delivery has received little empirical study, and no major pediatric or public health organization has issued recommendations regarding the circadian-matching of milk. However, potential adverse developmental and health consequences could be ameliorated by simple, low-cost interventions to label and circadian-match stored milk. The current paper reviews evidence for human milk as chrononutrition and makes recommendations for future research, practice, and policy.

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12Background: The assembly of the intestinal microbiota of extremely low birthweight (ELBW) infants has 13 an important impact on both immediate and long term health. ELBW infants are frequently given 14 antibiotics which are likely to perturb the assembly of the microbiota. Health complications are not 15 uncommon for ELBW infants; they face health crises including sepsis and necrotizing enterocolitis (NEC). 16Microbes are thought to be involved in the pathogenesis of NEC, but the mechanisms are unclear. New 17 understanding of the importance of human milk oligosaccharides and the establishment of a 18Bifidobacteria-dominated gut microbiota early in infancy suggest that all preterm infants have abnormal 19 microbial colonization. The initial assembly of intestinal microbial communities may have significant 20 impact on immune development and lifelong health. 21Results: We measured the bacterial composition and metabolite profile of 32 ELBW infants by 16S rRNA 22 gene sequencing and untargeted gas chromatography mass spectrometry of fecal samples. Infants 23 either remained healthy, developed late-onset sepsis, or developed necrotizing enterocolitis. The 24 . CC-BY-NC 4.0 International license peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was not . http://dx.doi.org/10.1101/125922 doi: bioRxiv preprint first posted online Apr. 10, 2017; 2 bacterial compositions were similar to what has been observed in other studies of preterm infants. Fecal 25 samples are dominated by aero-tolerant bacterial species, specifically Enterococcus, Enterobacteriaceae, 26 and Staphylococcus. Only three ELBW infants were colonized by Bifidobacteria. Fecal samples from 27 infants who developed NEC were not distinguishable from other infant samples based on bacterial 28 compositions (Permanova R 2 < 0.001, p = 0.99) or metabolite profiles (Permanova R 2 = 0.05, p= 0.24). 29Instead the bacterial composition (R 2 = 0.63, p < 0.001) and metabolite profile (R 2 = 0.43, p < 0.001) were 30 highly personalized for each infant. There were not significant correlations between the bacterial 31 composition and metabolite profiles of fecal samples (Mantel test r= 0.18, p < 0.001). 32Conclusions: Although antibiotics likely contribute to the instability of the ELBW infant intestinal 33 microbiota, personalized signatures of bacteria and metabolites are still clearly present. Neither the 34 bacterial composition or metabolite profile was unique in cases of disease. While bacteria certainly 35 contribute to the profile of metabolites present in feces, in these ELBW infants, significant correlations 36 between bacterial relative abundances as determined by 16S rRNA gene sequencing and untargeted GC-37 MS metabolite profiles were not detectable. 38 39 Background 40The intestinal microbiota of infants initially assembles by exposure to the mother's microbiota as well as 41 exposure to microbes in the environment [1]. In the first few days, the intestines are colonized by 42...

Background: Safe handling of human milk (HM) and enteral formulas for patients of all ages is critical in healthcare. Barcode scanning is commonly used to reduce errors. The purpose of this study was to evaluate the impact of barcode scanning for HM and formulas on patient safety. Methods:Scanning is used at the time of feeding preparation for HM, facilityprepared formulas, and ready-to-feed enteral formulas for patients of all ages to confirm the feeding matches the provider order, record lot numbers, and ensure expired items are not used. HM feedings are scanned at the time of administration and discharge to ensure the correct milk is being provided to the correct patient. All formulas dispensed as samples to hospital inpatients and outpatients are scanned to record patient and product information in the event of a recall.Results: Seven-year data showed that scanning has prevented HM misadministration 1226 times. Data for 2 and a half years of fortifier and formula scanning show 480 errors have been prevented. The results show benefits for both patient safety and staff efficiency. Conclusion:The benefits of barcode scanning systems in healthcare are well documented. Beyond the scanning of HM, scanning of fortifiers and formulas can improve patient safety by preventing misadministration for patients of all ages. Systems that offer features such as calculating fortified HM and formula recipes, tracking product lot numbers, and verifying correct products to the provider order can further improve safety as well as efficiency.