Identifying immune signatures of sepsis to increase diagnostic accuracy in very preterm babies.

Bacterial infections are a major cause of mortality in preterm babies, yet our understanding of early-life disease-associated immune dysregulation remains limited. Here, we combine multi-parameter flow cytometry, single-cell RNA sequencing and plasma analysis to longitudinally profile blood from very preterm babies (<32 weeks gestation) across episodes of invasive bacterial infection (sepsis). We identify a dynamically changing blood immune signature of sepsis, including lymphopenia, reduced dendritic cell frequencies and myeloid cell HLA-DR expression, which characterizes sepsis even when the common clinical marker of inflammation, C-reactive protein, is not elevated.

How frequent is routine use of probiotics in UK neonatal units?

Objective: There is a lack of UK guidance regarding routine use of probiotics in preterm infants to prevent necrotising enterocolitis, late-onset sepsis and death. As practices can vary, we aimed to determine the current usage of probiotics within neonatal units in the UK.

Design And Setting: Using NeoTRIPS, a trainee-led neonatal research network, an online survey was disseminated to neonatal units of all service levels within England, Scotland, Northern Ireland and Wales in 2022.

Intravenous antibiotics in preterm infants have a negative effect upon microbiome development throughout preterm life.

Background: Intestinal dysbiosis is implicated in the origins of necrotising enterocolitis and late-onset sepsis in preterm babies. However, the effect of modulators of bacterial growth (e.g.

Paediatric research in the times of COVID-19.

The COVID-19 pandemic poses many direct and indirect consequences for children's health and associated research. Direct consequences include participation of children in COVID-19 research trials, pausing other research in children and the potential implications of a global economic downturn on future research funding. Collaborative and networked research together with streamlined research processes and use of remote technology have been central to efforts by clinicians and scientists around the world and have proved essential for reducing COVID-19 morbidity and mortality.

Bifidobacterium breve BBG-001 and intestinal barrier function in preterm babies: Exploratory Studies from the PiPS Trial.

Background: Uncertainty remains about the role of probiotics to prevent necrotising enterocolitis (NEC) some of which arises from the variety of probiotic interventions used in different trials, many with no prior evidence of potential efficacy. Mechanistic studies of intestinal barrier function embedded in a large probiotic trial could provide evidence about which properties of probiotics might be important for NEC prevention thus facilitating identification of strains with therapeutic potential.

Methods: Intestinal permeability, stool microbiota, SCFAs and mucosal inflammation were assessed from the second postnatal week in babies enrolled to a randomised controlled trial of B.

Perinatal inflammation influences but does not arrest rapid immune development in preterm babies.

Infection and infection-related complications are important causes of death and morbidity following preterm birth. Despite this risk, there is limited understanding of the development of the immune system in those born prematurely, and of how this development is influenced by perinatal factors. Here we prospectively and longitudinally follow a cohort of babies born before 32 weeks of gestation.

Evaluating preterm care across Europe using the eNewborn European Network database.

Background: The inefficiency of recording data repeatedly limits the number of studies conducted. Here we illustrate the wider use of data captured as part of the European eNewborn benchmarking programme.

Methods: We extracted data on 39,529 live-births from 22 weeks 0 days to 31 weeks 6 days gestational age (GA) or ≤1500 g birth weight.

Historical aspects of probiotic use to prevent necrotising enterocolitis in preterm babies.

Over the last few decades, numerous studies have evaluated probiotic use for the prevention of necrotising enterocolitis in preterm babies. Early 'proof of concept' studies evaluating whether probiotics are capable of colonising the preterm gut have translated into multiple observational studies, small and large randomised controlled trials. Some show evidence of benefit while others have produced disappointing results.

The United Kingdom National Neonatal Research Database: A validation study.

Background: The National Neonatal Research Database (NNRD) is a rich repository of pre-defined clinical data extracted at regular intervals from point-of-care, clinician-entered electronic patient records on all admissions to National Health Service neonatal units in England, Wales, and Scotland. We describe population coverage for England and assess data completeness and accuracy.

Methods: We determined population coverage of the NNRD in 2008-2014 through comparison with data on live births in England from the Office for National Statistics.

Incidence of neonatal necrotising enterocolitis in high-income countries: a systematic review.

Objective: To conduct a systematic review of neonatal necrotising enterocolitis (NEC) rates in high-income countries published in peer-reviewed journals.

Methods: We searched MEDLINE, Embase and PubMed databases for observational studies published in peer-reviewed journals. We selected studies reporting national, regional or multicentre rates of NEC in 34 Organisation for Economic Co-operation and Development countries.

The Microbiome of Infants Recruited to a Randomised Placebo-controlled Probiotic Trial (PiPS Trial).

The microbial dysbiosis associated with necrotizing enterocolitis (NEC) in preterm infants suggests that early exposure to probiotics may decrease and antibiotics may increase NEC risk. However, administration of Bifidobacterium breve strain BBG-001 to preterm infants did not affect NEC incidence in a multicenter randomised controlled phase 3 trial (PiPS trial). Using a subset of these subjects we compared the fecal microbiome of probiotic and placebo groups and assessed the impact of early antibiotic treatment.

Incidence and enteral feed antecedents of severe neonatal necrotising enterocolitis across neonatal networks in England, 2012-13: a whole-population surveillance study.

Background: Necrotising enterocolitis is a neonatal gastrointestinal inflammatory disease with high mortality and severe morbidity. This disorder is growing in global relevance as birth rates and survival of babies with low gestational age improve. Population data are scant and pathogenesis is incompletely understood, but enteral feed exposures are believed to affect risk.

Development of a Gestational Age-Specific Case Definition for Neonatal Necrotizing Enterocolitis.

Importance: Necrotizing enterocolitis (NEC) is a major cause of neonatal morbidity and mortality. Preventive and therapeutic research, surveillance, and quality improvement initiatives are hindered by variations in case definitions.

Objective: To develop a gestational age (GA)-specific case definition for NEC.

Impact of obstetric interventions on condition at birth in extremely preterm babies: evidence from a national cohort study.

Background: To investigate perinatal decision-making and the use of obstetric interventions, we examined the effects of antenatal steroids, tocolysis, and delivery mode on birth in a good condition (defined as presence of an infant heart rate >100 at five minutes of age) and delivery-room (DR) death in extremely preterm deliveries.

Methods: Prospective cohort of all singleton births in England in 2006 at 22-26 weeks of gestation where the fetus was alive at the start of labour monitoring or decision to perform caesarean section. Odds ratios adjusted for potential confounders (aOR) were calculated using logistic regression.

A randomised controlled trial of the probiotic Bifidobacterium breve BBG-001 in preterm babies to prevent sepsis, necrotising enterocolitis and death: the Probiotics in Preterm infantS (PiPS) trial.

Background: Necrotising enterocolitis (NEC) and late-onset sepsis remain important causes of death and morbidity in preterm babies. Probiotic administration might strengthen intestinal barrier function and provide protection; this is supported by published meta-analyses, but there is a lack of large well-designed trials.

Objective: To test the use of the probiotic Bifidobacterium breve strain BBG-001 to prevent NEC, late-onset sepsis and death in preterm babies while monitoring probiotic colonisation of participants.

Investigating increased admissions to neonatal intensive care in England between 1995 and 2006: data linkage study using Hospital Episode Statistics.

Background: A 44 % increase was observed in admissions to neonatal intensive care of babies born ≤26 weeks completed gestational age in England between 1995 and 2006. Hospital Episode Statistics (HES) may provide supplementary information to investigate this. The methods and results of a probabilistic data linkage exercise are reported.

ESBL-producing Enterobacteriaceae in 24 neonatal units and associated networks in the south of England: no clustering of ESBL-producing Escherichia coli in units or networks.

Objectives: The objectives of this study were to characterize ESBL-producing Enterobacteriaceae present in 24 neonatal units (NNUs) in eight networks participating in a multicentre probiotic study and to test the hypothesis that specific strains would cluster within individual units and networks.

Methods: We performed analysis of stool samples for the presence of ESBL-producing Enterobacteriaceae at 2 weeks post-natal age and 36 weeks post-menstrual age. ESBL-producing Enterobacteriaceae were characterized and typed using molecular methods.

Bifidobacterium breve BBG-001 in very preterm infants: a randomised controlled phase 3 trial.

Background: Probiotics may reduce necrotising enterocolitis and late-onset sepsis after preterm birth. However, there has been concern about the rigour and generalisability of some trials and there is no agreement about whether or not they should be used routinely. We aimed to test the effectiveness of the probiotic Bifidobacterium breve BBG-001 to reduce necrotising enterocolitis, late-onset sepsis, and death in preterm infants.

Interleukin-8 (CXCL8) production is a signatory T cell effector function of human newborn infants.

In spite of their precipitous encounter with the environment, newborn infants cannot readily mount T helper type 1 (TH1) cell antibacterial and antiviral responses. Instead, they show skewing toward TH2 responses, which, together with immunoregulatory functions, are thought to limit the potential for inflammatory damage, while simultaneously permitting intestinal colonization by commensals. However, these collective capabilities account for relatively few T cells.

Perinatal outcomes for extremely preterm babies in relation to place of birth in England: the EPICure 2 study.

Background: Expertise and resources may be important determinants of outcome for extremely preterm babies. We evaluated the effect of place of birth and perinatal transfer on survival and neonatal morbidity within a prospective cohort of births between 22 and 26 weeks of gestation in England during 2006.

Methods: We studied the whole population of 2460 births where the fetus was alive at the admission of the mother to hospital for delivery.

Impact of ethnicity and extreme prematurity on infant pulmonary function.

The impact of birth before 27 completed weeks of gestation on infant pulmonary function (PF) was explored in a multi-ethnic population in comparison to more mature preterm controls (PTC) and healthy fullterm infants. Plethysmographic lung volume (FRCpleth ) and forced expired volume (FEV0.5 ) were obtained at ∼12 months post-term age in 52 extremely preterm (EP) infants (median [range] gestational age [GA]: 26 [23-27] weeks; 40% White mothers; 79% with BPD), 41 PTC (GA:35 [30-36] weeks; 37% White mothers) and 95 fullterm infants (GA:40 [37-42] weeks; 86% White mothers).

Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies).

Objective: To determine survival and neonatal morbidity for babies born between 22 and 26 weeks' gestation in England during 2006, and to evaluate changes in outcome since 1995 for babies born between 22 and 25 weeks' gestation.

Design: Prospective national cohort studies.

Setting: Maternity and neonatal units in England.