Early N-Terminal Pro B-Type Natriuretic Peptide (NTproBNP) Plasma Values and Associations with Patent Ductus Arteriosus Closure and Treatment-An Echocardiography Study of Extremely Preterm Infants.

The aim was to investigate the association of gestational age (GA), echocardiographic markers and levels of plasma N-terminal pro-B-type natriuretic peptide (NTproBNP) with the closure rate of a haemodynamically significant patent ductus arteriosus (hsPDA). Ninety-eight Swedish extremely preterm infants, mean GA 25.7 weeks (standard deviation 1.3), born in 2012-2014, were assessed with echocardiography and for levels of NTproBNP. Thirty-three (34%) infants had spontaneous ductal closure within three weeks of age. Infants having spontaneous closure at seven days or less had significantly lower NTproBNP levels on day three, median 1810 ng/L (IQR 1760-6000 ng/L) compared with: infants closing spontaneously later, 10,900 ng/L (6120-19,200 ng/L); infants treated either with ibuprofen only, 14,600 ng/L (7740-28,100 ng/L); or surgery, 32,300 ng/L (29,100-35,000 ng/L). Infants receiving PDA surgery later had significantly higher NTproBNP values on day three than other infants. Day three NTproBNP cut-off values of 15,001-18,000 ng/L, predicted later PDA surgery, with an area under the curve in ROC analysis of 0.69 (0.54-0.83). In conclusion, the spontaneous PDA closure rate is relatively high in extremely preterm infants. Early NTproBNP levels can be used with GA in the management decisions of hsPDA.

A novel cysteine-linked antibacterial surface coating significantly inhibits bacterial colonization of nasal silicone prongs in a phase one pre-clinical trial.

Ventilator associated pneumonia and sepsis are frequent complications in neonatal care. Bacterial colonization of medical devices and interfaces used for respiratory support may contribute by functioning as a bacterial reservoir seeding bacteria into airways. We have developed an antibacterial surface coating based on a cysteine ligand covalently coupled via a spacer to a carboxylic backbone layer on an acrylic acid grafted silicone surface. This coating was applied on a commercially available nasal prong and the antibacterial effect was evaluated both in vitro and in vivo in a first-in-human phase 1 trial. The coated nasal prongs had strong antibacterial activity against both Gram-negative and Gram-positive bacteria in vitro. In a randomized pre-clinical trial study of 24 + 24 healthy adult volunteers who carried coated or non-coated nasal prongs for 18 h, a 10log difference in mean bacterial colonization of 5.82 (p < 0.0001) was observed. These results show that this coating technique can prevent colonization by the normal skin and mucosal flora, and thus represent a promising novel technology for reduction of medical device-associated hospital acquired infections.

Lactose in human breast milk an inducer of innate immunity with implications for a role in intestinal homeostasis.

Postpartum, infants have not yet established a fully functional adaptive immune system and are at risk of acquiring infections. Hence, newborns are dependent on the innate immune system with its antimicrobial peptides (AMPs) and proteins expressed at epithelial surfaces. Several factors in breast milk are known to confer immune protection, but which the decisive factors are and through which manner they work is unknown. Here, we isolated an AMP-inducing factor from human milk and identified it by electrospray mass spectrometry and NMR to be lactose. It induces the gene (CAMP) that encodes the only human cathelicidin LL-37 in colonic epithelial cells in a dose- and time-dependent manner. The induction was suppressed by two different p38 antagonists, indicating an effect via the p38-dependent pathway. Lactose also induced CAMP in the colonic epithelial cell line T84 and in THP-1 monocytes and macrophages. It further exhibited a synergistic effect with butyrate and phenylbutyrate on CAMP induction. Together, these results suggest an additional function of lactose in innate immunity by upregulating gastrointestinal AMPs that may lead to protection of the neonatal gut against pathogens and regulation of the microbiota of the infant.

Activation of the right fronto-temporal cortex during maternal facial recognition in young infants.

BACKGROUND/AIM: Within the first days of life infants can already recognize their mother. This ability is based on several sensory mechanisms and increases during the first year of life, having its most crucial phase between 6 and 9 months when cortical circuits develop. The underlying cortical structures that are involved in this process are still unknown. Herein we report how the prefrontal cortices of healthy 6- to 9-month-old infants react to the sight of their mother's faces compared to that of an unknown female face. METHODS: Concentrations of oxygenated haemoglobin [HbO2] and deoxygenated haemoglobin [HHb] were measured using near infrared spectroscopy (NIRS) in both fronto-temporal and occipital areas on the right side during the exposure to maternal and unfamiliar faces. RESULTS: The infants exhibited a distinct and significantly higher activation-related haemodynamic response in the right fronto-temporal cortex following exposure to the image of their mother's face, [HbO2] (0.75 micromol/L, p < 0.001), as compared to that of an unknown face (0.25 micromol/L, p < 0.001). CONCLUSION: Event-related haemodynamic changes, suggesting cortical activation, in response to the sight of human faces were detected in 6- to 9-month old children. The right fronto-temporal cortex appears to be involved in face recognition processes at this age.

Antimicrobial components of the neonatal gut affected upon colonization.

Antimicrobial peptides (AMP) produced throughout our body are important effectors in the defense barrier of innate immunity. Here, we have analyzed antimicrobial activity and polypeptide composition of meconium versus neonatal feces to address the development of antimicrobial defense of the neonatal gut. Extracts of meconium exhibited antimicrobial activity against Bacillus megaterium, Escherichia coli, and group B streptococci (GBS) but not against the yeast Candida albicans. Extracts of neonatal feces were found to possess low activity against E. coli, GBS, and C. albicans. However, the anti-B. megaterium activity was higher in the fecal extracts than in meconium. All activities were reduced or abolished when salt was added to the antimicrobial assay. The AMP cathelicidin LL-37, alpha-defensin HNP-1-2, alpha-defensin HD 5, and lysozyme were identified in both meconium and fecal extracts. In addition, HNP-3 and a fragment of azurocidin were found in meconium, whereas the holoprotein azurocidin was detected in feces. In meconium, histones H2A and H4 were isolated and identified by their antimicrobial activity. Notably, LL-37 and lysozyme were found at significantly higher levels in feces than in meconium. Our findings reveal that meconium and feces contain AMP, acting in the defense of the neonatal gut, and may be implicated in the control of the initial colonization.