Do Lower Levels of Fetal Hemoglobin in Preterm Infants Relate to Oxidative Stress?

Fetal hemoglobin (HbF) has a higher affinity to oxygen than adult hemoglobin, allowing for a slower oxygen transfer to peripheral tissue, creating a microenvironment conducive to adequate fetal development in utero. However, most preterm infants receive packed red blood cell transfusions from adult donors leading to a drastic nonphysiological descent of circulating HbF. We hypothesized that this drop could enhance oxygen delivery to peripheral tissues generating a hyperoxic pro-oxidant environment. To investigate this, we assessed differences in oxidative stress biomarkers determined in urine samples in a cohort of 56 preterm infants born <32 weeks' gestation. Median oxidative stress biomarkers were compared between patients with circulating HbF above or below median HbF levels using Wilcoxon rank sum test. Oxidative stress biomarkers were significantly higher in the group of patients with lower levels of HbF. This study provides the initial evidence indicating elevated levels of oxidative stress biomarkers in preterm neonates with lower HbF levels. Based on the results, we hypothesize that HbF may contribute to preventing free radical-associated conditions during the newborn period. Antioxid. Redox Signal. 40, 453-459.

Corrigendum to "Myocardial Infarction in Neonates: A Diagnostic and Therapeutic Challenge".

[This corrects the article DOI: 10.1155/2019/7203407.].

Fact-based nutrition for infants and lactating mothers-The NUTRISHIELD study.

Background: Human milk (HM) is the ideal source of nutrients for infants. Its composition is highly variable according to the infant's needs. When not enough own mother's milk (OMM) is available, the administration of pasteurized donor human milk (DHM) is considered a suitable alternative for preterm infants. This study protocol describes the NUTRISHIELD clinical study. The main objective of this study is to compare the % weight gain/month in preterm and term infants exclusively receiving either OMM or DHM. Other secondary aims comprise the evaluation of the influence of diet, lifestyle habits, psychological stress, and pasteurization on the milk composition, and how it modulates infant's growth, health, and development. Methods and design: NUTRISHIELD is a prospective mother-infant birth cohort in the Spanish-Mediterranean area including three groups: preterm infants <32 weeks of gestation (i) exclusively receiving (i.e., >80% of total intake) OMM, and (ii) exclusively receiving DHM, and (iii) term infants exclusively receiving OMM, as well as their mothers. Biological samples and nutritional, clinical, and anthropometric characteristics are collected at six time points covering the period from birth and until six months of infant's age. The genotype, metabolome, and microbiota as well as the HM composition are characterized. Portable sensor prototypes for the analysis of HM and urine are benchmarked. Additionally, maternal psychosocial status is measured at the beginning of the study and at month six. Mother-infant postpartum bonding and parental stress are also examined. At six months, infant neurodevelopment scales are applied. Mother's concerns and attitudes to breastfeeding are registered through a specific questionnaire. Discussion: NUTRISHIELD provides an in-depth longitudinal study of the mother-infant-microbiota triad combining multiple biological matrices, newly developed analytical methods, and ad-hoc designed sensor prototypes with a wide range of clinical outcome measures. Data obtained from this study will be used to train a machine-learning algorithm for providing dietary advice to lactating mothers and will be implemented in a user-friendly platform based on a combination of user-provided information and biomarker analysis. A better understanding of the factors affecting milk's composition, together with the health implications for infants plays an important role in developing improved strategies of nutraceutical management in infant care. Clinical trial registration: https://register.clinicaltrials.gov, identifier: NCT05646940.

Assessment of SARS-CoV-2 neutralizing antibody titers in breastmilk from convalescent and vaccinated mothers.

Breastmilk contains antibodies that could protect breastfed infants from infections. In this work, we examined if antibodies in breastmilk could neutralize SARS-CoV-2 in 84 breastmilk samples from women that were either vaccinated (Comirnaty, mRNA-1273, or ChAdOx1), infected with SARS-CoV-2, or both infected and vaccinated. The neutralization capacity of these sera was tested using pseudotyped vesicular stomatitis virus carrying either the Wuhan-Hu-1, Delta, or BA.1 Omicron spike proteins. We found that natural infection resulted in higher neutralizing titers and that neutralization correlated positively with levels of immunoglobulin A in breastmilk. In addition, significant differences in the capacity to produce neutralizing antibodies were observed between both mRNA-based vaccines and the adenovirus-vectored ChAdOx1 COVID-19 vaccine. Overall, our results indicate that breastmilk from naturally infected women or those vaccinated with mRNA-based vaccines contains SARS-CoV-2 neutralizing antibodies that could potentially provide protection to breastfed infants from infection.

Joint Microbiota Activity and Dietary Assessment through Urinary Biomarkers by LC-MS/MS.

Accurate dietary assessment in nutritional research is a huge challenge, but essential. Due to the subjective nature of self-reporting methods, the development of analytical methods for food intake and microbiota biomarkers determination is needed. This work presents an ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) method for the quantification and semi quantification of 20 and 201 food intake biomarkers (BFIs), respectively, as well as 7 microbiota biomarkers applied to 208 urine samples from lactating mothers (M) (N = 59). Dietary intake was assessed through a 24 h dietary recall (R24h). BFI analysis identified three distinct clusters among samples: samples from clusters 1 and 3 presented higher concentrations of most biomarkers than those from cluster 2, with dairy products and milk biomarkers being more concentrated in cluster 1, and seeds, garlic and onion in cluster 3. Significant correlations were observed between three BFIs (fruits, meat, and fish) and R24h data (r > 0.2, p-values < 0.01, Spearman correlation). Microbiota activity biomarkers were simultaneously evaluated and the subgroup patterns detected were compared to clusters from dietary assessment. These results evidence the feasibility, usefulness, and complementary nature of the determination of BFIs, R24h, and microbiota activity biomarkers in observational nutrition cohort studies.

Effects of Sepsis on Immune Response, Microbiome and Oxidative Metabolism in Preterm Infants.

This is a narrative review about the mechanisms involved in bacterial sepsis in preterm infants, which is an illness with a high incidence, morbidity, and mortality. The role of the innate immune response and its relationship with oxidative stress in the pathogenesis are described as well as their potential implementation as early biomarkers. Moreover, we address the impact that all the mechanisms triggered by sepsis have on the dysbiosis and the changes on neonatal microbiota.

Early molecular markers of ventilator-associated pneumonia in bronchoalveolar lavage in preterm infants.

INTRODUCTION: Ventilator-associated pneumonia (VAP) constitutes a serious nosocomial infection. Our aim was to evaluate the reliability of cytokines and oxidative stress/inflammation biomarkers in bronchoalveolar lavage fluid (BALF) and tracheal aspirates (TA) as early biomarkers of VAP in preterm infants. METHODS: Two cohorts were enrolled, one to select candidates and the other for validation. In both, we included preterms with suspected VAP, according to BALF culture, they were classified into confirmed VAP and no VAP. Concentration of 16 cytokines and 8 oxidative stress/inflammation biomarkers in BALF and TA was determined in all patients. RESULTS: In the first batch, IL-17A and TNF-α in BALF, and in the second one IL-10, IL-6, and TNF-α in BALF were significantly higher in VAP patients. BALF TNF-α AUC in both cohorts was 0.86 (sensitivity 0.83, specificity 0.88). No cytokine was shown to be predictive of VAP in TA. A statistically significant increase in the VAP group was found for glutathione sulfonamide (GSA) in BALF and TA. CONCLUSIONS: TNF-α in BALF and GSA in BALF and TA were associated with VAP in preterm newborns; thus, they could be used as early biomarkers of VAP. Further studies with an increased number of patients are needed to confirm these results. IMPACT: We found that TNF-α BALF and GSA in both BALF and TA are capable of discriminating preterm infants with VAP from those with pulmonary pathology without infection. This is the first study in preterm infants aiming to evaluate the reliability of cytokines and oxidative stress/inflammation biomarkers in BALF and TA as early diagnostic markers of VAP. We have validated these results in two independent cohorts of patients. Previously studies have focused on full-term neonates and toddlers and determined biomarkers mostly in TA, but none was exclusively conducted in preterm infants.

Isolation and Lipidomic Screening of Human Milk Extracellular Vesicles.

Extracellular vesicles (EVs) are secreted by cells and can be found in biological fluids (e.g., blood, saliva, urine, cerebrospinal fluid, and milk). EV isolation needs to be optimized carefully depending on the type of biofluid and tissue. Human milk (HM) is known to be a rich source of EVs, and they are thought to be partially responsible for the benefits associated with breastfeeding. Here, a workflow for the isolation and lipidomic analysis of HM-EVs is described. The procedure encompasses initial steps such as sample collection and storage, a detailed description for HM-EV isolation by multistage ultracentrifugation, metabolite extraction, and analysis by liquid chromatography coupled to mass spectrometry, as well as data analysis and curation.

Galectins-1, -3 and -9 Are Present in Breast Milk and Have a Role in Early Life Development.

Galectins (Gal) are a family of conserved soluble proteins with high affinity for ß-galactoside structures. They have been recognized as important proteins for successful pregnancy. However, little is known about their presence in breast milk and their role in early infancy. Gal-1, -3 and -9 concentrations were evaluated by Multiplex immunoassays in mother-infant pairs from the MAMI cohort in maternal plasma (MP) (n = 15) and umbilical cord plasma (UCP) (n = 15) at birth and in breast milk samples (n = 23) at days 7 and 15 postpartum. Data regarding mother and infant characteristics were collected. Gal-9 was present in a lower concentration range than Gal-1 and Gal-3 in plasma, specifically in UCP. A major finding in the current study is that Gal-1, -3 and -9 were detected for the first time in all the transitional breast milk samples and no differences were found when comparing the two breastfeeding time points. Finally, Gal levels were associated with some maternal and infant characteristics, such as gestational age, pregnancy weight gain, maternal diet, the gender, infant growth and infant infections. In conclusion, Gal levels seem to be involved in certain developmental aspects of early life.

Direct Derivatization in Dried Blood Spots for Oxidized and Reduced Glutathione Quantification in Newborns.

The glutathione (GSH)-to-glutathione disulfide (GSSG) ratio is an essential node contributing to intracellular redox status. GSH/GSSG determination in whole blood can be accomplished by liquid chromatography-mass spectrometry (LC-MS) after the derivatization of GSH with N-ethylmaleimide (NEM). While this is feasible in a laboratory environment, its application in the clinical scenario is cumbersome and therefore ranges reported in similar populations differ noticeably. In this work, an LC-MS procedure for the determination of GSH and GSSG in dried blood spot (DBS) samples based on direct in situ GSH derivatization with NEM of only 10 µL of blood was developed. This novel method was applied to 73 cord blood samples and 88 residual blood volumes from routine newborn screening performed at discharge from healthy term infants. Two clinical scenarios simulating conditions of sampling and storage relevant for routine clinical analysis and clinical trials were assessed. Levels of GSH-NEM and GSSG measured in DBS samples were comparable to those obtained by liquid blood samples. GSH-NEM and GSSG median values for cord blood samples were significantly lower than those for samples at discharge. However, the GSH-NEM-to-GSSG ratios were not statistically different between both groups. With DBS testing, the immediate manipulation of samples by clinical staff is reduced. We therefore expect that this method will pave the way in providing an accurate and more robust determination of the GSH/GSSG values and trends reported in clinical trials.

Maternal and Neonatal Prognostic Factors for Cardiorespiratory Events in Healthy Term Neonates During Early Skin-to-Skin Contact.

Background: During early skin-to-skin contact (ESSC), alterations in peripheral oxygen saturation (SpO2) and heart rate (HR) have been frequently observed. Objectives: This study aimed to determine the incidence of cardiorespiratory events (CREs) during ESSC in healthy term newborns (HTNs) and estimate the association of maternal and neonatal prognostic factors with the risk of CREs. Methods: A pooled analysis of the cohort from a clinical trial involving healthy mother-child dyads during ESSC was performed. Pulse oximetry was employed to continuously monitor SpO2 and HR within 2 h after birth. The individual and combined prognostic relevance of the demographic and clinical characteristics of dyads for the occurrence of a CRE (SpO2 <91% or HR <111 or >180 bpm) was analyzed through logistic regression models. Results: Of the 254 children assessed, 169 [66.5%; 95% confidence interval (95% CI), 60.5-72.5%] had at least one CRE. The characteristics that increased the risk of CRE were maternal age ≥35 years (odds ratio, 2.21; 95% CI, 1.19-4.09), primiparity (1.96; 1.03-3.72), gestational body mass index (BMI) >25 kg/m2 (1.92; 1.05-3.53), and birth time between 09:00 p.m. and 08:59 a.m. (2.47; 1.02-5.97). Conclusion: CREs were more frequent in HTNs born during nighttime and in HTNs born to first-time mothers, mothers ≥35 years, and mothers with a gestational BMI >25 kg/m2. These predictor variables can be determined during childbirth. Identification of neonates at higher risk of developing CREs would allow for closer surveillance during ESSC.

Neurodevelopmental Outcome and Epigenetic Changes at 2 Years Associated with the Oxygen Load Received upon Postnatal Stabilization: A Pilot Study.

INTRODUCTION: The oxygen load provided to preterm infants during postnatal stabilization caused significant modifications of DNA methylation in the preterm epigenome. We aimed to assess if there was an association between DNA methylation changes and neurodevelopmental outcomes. METHODS: Preterm infants were followed until 2 years after birth. Dried blood spots were processed, and DNA methylation was measured using the MassARRAY technology of Sequenom. We selected specific genes that corresponded to differentially methylated CpG sites that correlated with the oxygen load at 2 h after birth. Neurodevelopmental outcome was blindly assessed using Bayley-III scale. RESULTS: Of 32 eligible patients, we completed the methylation analysis in 19 patients and the neurodevelopmental evaluation in 22. Comparison of differential methylation analysis between time 0 (cord blood) and 2 h after birth showed 74 significant CpGs, out of which 14 correlated with the oxygen load received at birth. Out of these 14 genes, only TRAPPC9 showed statistically significant differences at 2 years of age between the infants who received >500 mL versus <500 mL O2/kg. Premature who received >500 mL O2/kg showed significantly lower motor composite scores. DISCUSSION/CONCLUSIONS: Premature who received higher oxygen load scored lower motor composite scores and showed a hypermethylation pattern of TRAPPC9 at 2 years of age. TRAPPC9 mutations are associated with neurodevelopmental delay and intellectual disability, so changes in the CpG methylation of this gene and its subsequent expression alteration can produce a similar phenotype. Further studies with a greater sample size are needed to confirm these findings.

GC-MS analysis of short chain fatty acids and branched chain amino acids in urine and faeces samples from newborns and lactating mothers.

BACKGROUND: Short chain fatty acids (SCFAs) and branched chain amino acids (BCAAs) are frequently determined in faeces, and widely used as biomarkers of gut-microbiota activity. However, collection of faeces samples from neonates is not straightforward, and to date levels of these metabolites in newborn's faeces and urine samples have not been described. METHODS: A targeted gas chromatography - mass spectrometry (GC-MS) method for the determination of SCFAs and BCAAs in both faeces and urine samples has been validated. The analysis of 210 urine and 137 faeces samples collected from preterm (PI), term infants (TI) and their mothers was used to report faecal and urinary SCFA and BCAA levels in adult and neonatal populations. RESULTS: A significant correlation among five SCFAs and BCAAs in faeces and urine samples was observed. Reference ranges of SCFAs and BCAAs in mothers, PI and TI were reported showing infant's lower concentrations in faeces and higher concentrations in urine. CONCLUSION: This method presents a non-invasive approach for the simultaneous assessment of SCFAs and BCAAs in faecal and urine samples and the results will serve as a knowledge base for future experiments that will focus on the study of the impact of nutrition on the microbiome of lactating mothers and their infants.

Anti-SARS-CoV-2 IgA and IgG in human milk after vaccination is dependent on vaccine type and previous SARS-CoV-2 exposure: a longitudinal study.

BACKGROUND: Breast milk is a vehicle to transfer protective antibodies from the lactating mother to the neonate. After SARS-CoV-2 infection, virus-specific IgA and IgG have been identified in breast milk, however, there are limited data on the impact of different COVID-19 vaccine types in lactating women. This study is aimed to evaluate the time course of induction of SARS-CoV-2-specific IgA and IgG in breast milk after vaccination. METHODS: In this prospective observational study in Spain, 86 lactating women from priority groups receiving the vaccination against SARS-CoV-2 were included. Breast milk samples were collected longitudinally at seven or eight-time points (depending on vaccine type). A group with confirmed SARS-CoV-2 infection (n=19) and a group of women from pre-pandemic time (n=20) were included for comparison. RESULTS: Eighty-six vaccinated lactating women [mean age, 34.6 ± 3.7 years] of whom 96% were Caucasian and 92% were healthcare workers. A total number of 582 milk samples were included, and vaccine distribution was BioNTech/Pfizer (BNT162b2, n=34), Moderna (mRNA-1273, n=20), and AstraZeneca (ChAdOx1 nCoV-19, n=32). For each vaccine, 7 and 8 longitudinal time points were collected from baseline up to 30 days after the second dose for mRNA vaccines and adenovirus-vectored vaccines, respectively. A strong reactivity was observed for IgG and IgA after vaccination mainly after the 2nd dose. The presence and persistence of specific SARS-CoV-2 antibodies in breast milk were dependent on the vaccine type, with higher IgG and IgA levels in mRNA-based vaccines when compared to AstraZeneca, and on previous virus exposure. High intra- and inter-variability were observed, being relevant for IgA antibodies. In milk from vaccinated women, anti-SARS-CoV-2 IgG was significantly higher while IgA levels were lower than in milk from COVID-19-infected women. Women with previous COVID-19 increased their IgG antibodies levels after the first dose to a similar level observed in vaccinated women after the second dose. CONCLUSIONS: COVID-19 vaccination induced anti-SARS-CoV-2 IgA and IgG in breast milk with higher levels after the 2nd dose. Levels of anti-SARS-CoV-2 IgA and IgG are dependent on the vaccine type. Further studies are warranted to demonstrate the protective antibody effect against COVID-19 in infants from vaccinated and infected mothers. TRIAL REGISTRATION: NCT04751734 (date of registration is on February 12, 2021).

The effect of Holder pasteurization on the lipid and metabolite composition of human milk.

Human milk (HM) is the gold standard for newborn nutrition. When own mother's milk is not sufficiently available, pasteurized donor human milk becomes a valuable alternative. In this study we analyzed the impact of Holder pasteurization (HoP) on the metabolic and lipidomic composition of HM. Metabolomic and lipidomic profiles of twelve paired HM samples were analysed before and after HoP by liquid chromatography-mass spectrometry (MS) and gas chromatography-MS. Lipidomic analysis enabled the annotation of 786 features in HM out of which 289 were significantly altered upon pasteurization. Fatty acid analysis showed a significant decrease of 22 out of 29 detectable fatty acids. The observed changes were associated to five metabolic pathways. Lipid ontology enrichment analysis provided insight into the effect of pasteurization on physical and chemical properties, cellular components, and functions. Future research should focus on nutritional and/or developmental consequences of these changes.

SARS-CoV-2 RNA and antibody detection in breast milk from a prospective multicentre study in Spain.

OBJECTIVES: To develop and validate a specific protocol for SARS-CoV-2 detection in breast milk matrix and to determine the impact of maternal SARS-CoV-2 infection on the presence, concentration and persistence of specific SARS-CoV-2 antibodies. DESIGN AND PATIENTS: This is a prospective, multicentre longitudinal study (April-December 2020) in 60 mothers with SARS-CoV-2 infection and/or who have recovered from COVID-19. A control group of 13 women before the pandemic were also included. SETTING: Seven health centres from different provinces in Spain. MAIN OUTCOME MEASURES: Presence of SARS-CoV-2 RNA in breast milk, targeting the N1 region of the nucleocapsid gene and the envelope (E) gene; presence and levels of SARS-CoV-2-specific immunoglobulins (Igs)-IgA, IgG and IgM-in breast milk samples from patients with COVID-19. RESULTS: All breast milk samples showed negative results for presence of SARS-CoV-2 RNA. We observed high intraindividual and interindividual variability in the antibody response to the receptor-binding domain of the SARS-CoV-2 spike protein for each of the three isotypes IgA, IgM and IgG. Main Protease (MPro) domain antibodies were also detected in milk. 82.9% (58 of 70) of milk samples were positive for at least one of the three antibody isotypes, with 52.9% of these positive for all three Igs. Positivity rate for IgA was relatively stable over time (65.2%-87.5%), whereas it raised continuously for IgG (from 47.8% for the first 10 days to 87.5% from day 41 up to day 206 post-PCR confirmation). CONCLUSIONS: Our study confirms the safety of breast feeding and highlights the relevance of virus-specific SARS-CoV-2 antibody transfer. This study provides crucial data to support official breastfeeding recommendations based on scientific evidence. Trial registration number NCT04768244.

Transcriptome profiles discriminate between Gram-positive and Gram-negative sepsis in preterm neonates.

BACKGROUND: Genome-wide expression profiles have been previously employed as clinical research diagnostic tools for newborn sepsis. We aimed to determine if transcriptomic profiles could discriminate between Gram-positive and Gram-negative bacterial sepsis in preterm infants. METHODS: Prospective, observational, double-cohort study was conducted in very low birth weight infants with clinical signs and culture-positive sepsis. Blood samples were collected when clinical signs became apparent. Total RNA was processed for transcriptomic analysis. Results were validated by both reverse-transcription polymerase chain reaction and a mathematical model. RESULTS: We included 25 septic preterm infants, 17 with Gram-positive and 8 with Gram-negative bacteria. The principal component analysis identified these two clusters of patients. We performed a predictive model based on 21 genes that showed an area under the receiver-operating characteristic curve of 1. Eight genes were overexpressed in Gram-positive septic infants: CD37, CSK, MAN2B2, MGAT1, MOB3A, MYO9B, SH2D3C, and TEP1. The most significantly overexpressed pathways were related to metabolic and immunomodulating responses that translated into an equilibrium between pro- and anti-inflammatory responses. CONCLUSIONS: The transcriptomic profile allowed identification of whether the causative agent was Gram-positive or Gram-negative bacteria. The overexpression of genes such as CD37 and CSK, which control cytokine production and cell survival, could explain the better clinical outcome in sepsis caused by Gram-positive bacteria. IMPACT: Transcriptomic profiles not only enable an early diagnosis of sepsis in very low birth weight infants but also discriminate between Gram-positive and Gram-negative bacteria as causative agents. The overexpression of some genes related to cytokine production and cell survival could explain the better clinical outcome in sepsis caused by Gram-positive bacteria, and could lead us to a future, targeted therapy.

Mother's Bed Incline and Desaturation Episodes in Healthy Term Newborns during Early Skin-to-Skin Contact: A Multicenter Randomized Controlled Trial.

INTRODUCTION: Early skin-to-skin contact (ESSC) is associated with rare, sudden, unexpected postnatal collapse episodes. Placing the newborn in ESSC closer to an upright position may reduce the risk of airway obstruction and improve respiratory mechanics. This study assessed whether a greater inclination of the mother's bed during ESSC would reduce the proportion of healthy term newborns (HTNs) who experienced episodes of pulse oximeter saturation (SpO2) <91%. METHODS: We conducted a multicenter randomized controlled trial comparing the effect of the mother's bed incline, 45° versus 15°, on desaturation in HTNs during ESSC. Before delivery on 1,271 dyads, randomization was conducted, and stringent criteria to select healthy mothers and term newborns were monitored until after birth. Preductal SpO2 was continuously monitored between 10 min and 2 h after birth. The primary outcome was the occurrence of at least one episode of SpO2 <91%. RESULTS: 254 (20%) mother-infant dyads were eligible for analysis (45°, n = 126; 15°, n = 128). Overall, 57% (95% confidence interval [CI]: 51%-63%) of newborns showed episodes of SpO2 <91%. The proportion of infants with SpO2 <91% episodes was 52% in 45° and 62% in 15° (relative risk: 0.80; 95% CI: 0.6-1.07). CONCLUSIONS: We did not show that a high mother bed inclination during ESSC led to significantly fewer HTNs who experienced episodes of SpO2 <91%. Desaturation episodes from 10 min to 2 h after birth occurred in more than half of HTNs.

miRNomic Signature in Very Low Birth-Weight Neonates Discriminates Late-Onset Gram-Positive Sepsis from Controls.

BACKGROUND AND OBJECTIVES: Neonatal sepsis is a serious condition with a high rate of mortality and morbidity. Currently, the gold standard for sepsis diagnosis is a positive blood culture, which takes 48-72 h to yield results. We hypothesized that identifying differentially expressed miRNA pattern in neonates with late-onset Gram-positive sepsis would help with an earlier diagnosis and therapy. METHODS: This is a prospective observational study in newborn infants with late-onset Gram positive bacterial sepsis and non-septic controls. Complementary to blood culture, an aliquot of 0.5 mL of blood was used to determine small non-coding RNA expression profiling using the GeneChip miRNA 4.0 Array. RESULTS: A total of 11 very low birth-weight neonates with late-onset Gram-positive sepsis and 16 controls were analyzed. Further, 217 differentially expressed miRNAs were obtained between both groups. Subsequently, a combined analysis was performed with these miRNAs and 4297 differentially expressed genes. We identified 33 miRNAs that regulate our mRNAs, and the most relevant biological processes are associated with the immune system and the inflammatory response. CONCLUSIONS: The miRNA profiling in very low birth-weight neonates distinguishes late-onset Gram-positive sepsis versus control neonates.

Early-onset sepsis: a cohort study comparing serial clinical observation with laboratory testing.

OBJECTIVE: Early onset sepsis (EOS) remains a serious and potentially fatal illness. We aimed to demonstrate that serial clinical observation (SCO) is a feasible strategy associated with fewer laboratory evaluations and unnecessary antibiotic use. STUDY DESIGN: We compared the admissions and antibiotic therapy in neonates ≥35 weeks' gestation at risk for EOS in a prospective cohort after the implementation of a new protocol based on SCO (n = 381) with a historical cohort which received laboratory testing (n = 417). RESULTS: There was a significant reduction in admissions for suspected sepsis (7.2% vs 2.9%, p = 0.006) and the use of antibiotics (6.1% vs 0.7%, p = 0.000) in the cohort based on SCO. There was no delay in diagnosis. CONCLUSIONS: SCO in neonates ≥35 weeks' gestation at risk for EOS, including chorioamnionitis-exposed infants, is a feasible measure that reduces laboratory evaluations and the overuse of antibiotics respecting the bonding mother-infant.