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ObjectiveNecrotising enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm infants. The underlying mechanisms are poorly understood: mother’s own breast milk (MOM) is protective, possibly relating to human milk oligosaccharide (HMO) and infant gut microbiome interplay. We investigated the interaction between HMO profiles and infant gut microbiome development and its association with NEC.DesignWe performed HMO profiling of MOM in a large cohort of infants with NEC (n=33) with matched controls (n=37). In a subset of 48 infants (14 with NEC), we also performed longitudinal metagenomic sequencing of infant stool (n=644).ResultsConcentration of a single HMO, disialyllacto-N-tetraose (DSLNT), was significantly lower in MOM received by infants with NEC compared with controls. A MOM threshold level of 241 nmol/mL had a sensitivity and specificity of 0.9 for NEC. Metagenomic sequencing before NEC onset showed significantly lower relative abundance of Bifidobacterium longum and higher relative abundance of Enterobacter cloacae in infants with NEC. Longitudinal development of the microbiome was also impacted by low MOM DSLNT associated with reduced transition into preterm gut community types dominated by Bifidobacterium spp and typically observed in older infants. Random forest analysis combining HMO and metagenome data before disease accurately classified 87.5% of infants as healthy or having NEC.ConclusionThese results demonstrate the importance of HMOs and gut microbiome in preterm infant health and disease. The findings offer potential targets for biomarker development, disease risk stratification and novel avenues for supplements that may prevent life-threatening disease.

ObjectiveReview of age of onset of necrotising enterocolitis (NEC) and focal intestinal perforation (FIP) in very preterm (≤32 weeks) and/or very low birthweight (VLBW, ≤1500 g) infants.DesignPreregistered review undertaken according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses in July 2021 and updated October 2021.Data sourcesMEDLINE/ PubMed, Embase, CINAHL and Cochrane Central Register of Controlled Trials.EligibilityEligible studies reported age of onset of NEC and/or FIP in randomised controlled trials of >200 or observational studies of >500 infants.Data extraction and synthesisTitles/abstracts were screened; eligible articles underwent data extraction. Age of onset as day of life (DOL) and/or corrected gestational age (CGA) were extracted alongside study information, such as NEC definition, included population, intervention, location and dates studied. Weighted means were used to compare onset by birth gestation, study type, NEC definition, trial intervention, location and dates studied. Comparison was done by Mann-Whitney U test or one-way analysis of variance.ResultsOf the 747 screened studies 188 were eligible. Removal of duplicates, studies without onset data and ineligible populations left 10 RCTs and 14 observational studies contributing 51 NEC cohorts; 49 reported onset DOL and 14 CGA. 2984 cases of NEC had average DOL onset of 16.7 (15.5 in RCTs, 16.9 in observational studies), and CGA onset of 30.1 weeks. Gestation did not impact DOL onset. No other demographic feature impacted NEC onset. Few studies included data on FIP.ConclusionsAverage onset of NEC in exclusively very preterm/very low birthweight infants is in the third week of life and unlike in cohorts including more mature or heavier infants is not impacted by birth gestation.

BackgroundIgA and its secretory form sIgA impact protection from infection and necrotising enterocolitis but little is known about quantities in preterm mums own milk (MOM) or infant stool, onset of endogenous production in the preterm gut, and what affects these.MethodsWe measured by ELISA in MOM and stool from healthy preterm infants total IgA and sIgA longitudinally and additionally in MOM fresh, refrigerated, frozen, and after traversing feeding systems.ResultsIn 42 MOM (median gestation 26 weeks), we showed total IgA levels and sIgA were highest in colostrum, fell over 3 weeks, and were not impacted by gestation. Median IgA values matched previous term studies (700 mcg/ml). In MOM recipients stool IgA was detected in the first week, at around 30% of MOM quantities. Formula fed infants did not have detectable stool IgA until the third week. Levels of IgA and sIgA were approximately halved by handling processes.ConclusionsMOM in the 3 weeks after preterm delivery contains the highest concentrations of IgA and sIgA. Endogenous production after preterm birth occurs from the 3 week meaning preterm infants are dependent on MOM for IgA which should be optimised. Routine NICU practices halve the amount available to the infant.Impact(Secretory) Immunoglobulin A (IgA) is present in colostrum of maternal milk from infants as preterm as 23–24 weeks gestational age, falling over the first 3 weeks to steady levels similar to term.Gestation at birth does not impact (secretory) IgA levels in breast milk.IgA is present in very preterm infant stools from maternal milk fed infants from the first week of life, but not in formula milk fed preterm infants until week three, suggesting endogenous production from this point.Refrigeration, freezing, and feeding via plastic tubing approximately halved the amount of IgA available.

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Background To explore the associations between histologic chorioamnionitis with brain injury, maturation and size on magnetic resonance imaging (MRI) of preterm infants at term equivalent age. Methods Preterm infants (23–36 weeks’ gestational age) were recruited into two longitudinal cohort studies. Presence or absence of chorioamnionitis was obtained from placental histology and clinical data were recorded. MRI at term-equivalent age was assessed for brain injury (intraventricular haemorrhage, cysts, signal abnormalities), maturation (degree of myelination, gyral maturation) and size of cerebral structures (metrics and brain segmentation). Histologic chorioamnionitis was assessed as a predictor of MRI variables using linear and logistic regression, with adjustment for confounding perinatal variables. Results Two hundred and twelve infants were included in this study, 47 (22%) of whom had histologic chorioamnionitis. Histologic chorioamnionitis was associated with higher odds of intraventricular haemorrhage (odds ratio [OR] (95% confidence interval [CI]) = 7.4 (2.4, 23.1)), less mature gyral maturation (OR (95% CI) = 2.0 (1.0, 3.8)) and larger brain volume (mean difference in cubic centimeter (95% CI) of 14.1 (1.9, 26.2)); but all relationships disappeared following adjustment for perinatal variables. Conclusion Histologic chorioamnionitis was not independently associated with IVH, less mature gyral maturation or brain volume at term-equivalent age in preterm infants.

AimsSurgical necrotising enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are devastating pathologies of the preterm gut. They differ histologically but clinically can be challenging to differentiate. SIP generally presents earlier than NEC, but timing of presentation can overlap. Intestinal alkaline phosphatase (ALP) secretion has been linked to gastrointestinal ischemia, and an elevated ALP at presentation has been described as a means of differentiating SIP from NEC. We describe ALP levels around presentation in a cohort of preterm infants with histologically proven SIP and NEC.MethodsWe retrospectively identified preterm neonates (<32 weeks gestational age) with histologically confirmed SIP or surgical NEC cared for in our unit from 2012-2021 inclusive. We then compared serum ALP levels for the five-day period around their day of diagnosis (referred to as day 0). All statistics were run using SPSS with independent sample t-tests. Results were considered significant if p<0.05. Local Caldicott guardian approval was obtained for this work.ResultsOverall, a total of 86 neonates were identified; 38 with SIP and 48 with NEC. 44 were excluded due to either missing ALP data (36) or to a change in the ALP reference range (8). This left 42 neonates; 21 with SIP and 21 with NEC. The median age at diagnosis of SIP was 6 days compared to 16 days for NEC (p<0.001). Mean ALP level was higher on day -2 in the NEC group but every day thereafter was higher in the SIP group, with the greatest rise from day -2 to day -1 i.e. 24 hours prior to diagnosis. The highest proportion of ALP levels above the reference range was on the day of diagnosis (day 0) in both groups. Table 1 and figure 1 demonstrates mean ALP levels around diagnosis, day 0. None of these differences reached statistical significance.Abstract 785 Figure 1Abstract 785 Table 1ConclusionOur data demonstrate a trend towards an ALP rise especially in SIP prior to clinical diagnosis, suggesting that this may have a role as an early warning sign of evolving gut pathology in some babies. Our findings are limited by small sample size and missing data but further information may be obtained from similar evaluation of larger datasets.

BackgroundNecrotising enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are gastrointestinal pathologies affecting preterm neonates that are associated with significant morbidity and mortality. They can be challenging to differentiate clinically; although improved histological techniques designed to differentiate between the inflammatory, necrotic pathology of NEC and the isolated, often ileal perforation of SIP may explain the apparent recent increase in SIP diagnoses. It is important to be able to distinguish between NEC and SIP to allow the effective evaluation of new prevention and/or treatment strategies.ObjectivesTo explore differences in presentation, management and short-term outcomes of NEC and SIP in a cohort of infants born at <32 weeks corrected gestational age.MethodsA retrospective review of all neonates with surgical NEC or SIP managed in a single regional neonatal surgical centre over a nine-year period (2012 and 2020 inclusive). Data was extracted from the Badgernet database and medical records. Local Caldicott approval was obtained.Results50 infants with NEC and 31 with SIP were identified. Their background demographics are described in table 1. Infants with SIP present significantly earlier (median 6 versus 24 days) and at a younger corrected gestational age (median 26.4 versus 30.7 weeks) than those with NEC (table 1). A high percentage of both cohorts were commenced on maternal breast milk as first milk and those with SIP were more likely to have received a blood transfusion prior to diagnosis. Table 2 describes key short term outcome data for both groups. Mortality is higher in NEC, however rates of ROP requiring treatment, severe IVH and need for home oxygen were higher in SIP survivors (table 2).Abstract 1125 Table 1Demographics of NEC vs SIPn (%)* IQR NEC (50) SIP (31) P value Gestational age * 26.77 (25.14–28.21) 26.19 (24.42–27.28) 0.16 Birth weight * 912.7 (735–1065) 879.68 (660–1015) 0.45 Male 34/50 (67%) 17/31 (53%) 0.22 Multiple 15/50 (29%) 11/31 (32%) 0.77 Age at onset of symptoms (days) * 24 (15.75–38) 6.4 (4–7) < 0.0001 CGA at onset of symptoms * 30.72 (28.85–32.82) 26.42 (25.14–28.14) < 0.0001 Age at first feeds (days) * 3.46 (2–4.25) 3.89 (2–4) 0.31 First milk type (mEBM) 37/50 (74%) 24/31 (77%) 0.73 Blood transfusion 7/50 (14%) 22/31 (71%) < 0.0001 PDA (medical treatment) 20/50 (40%) 14/31 (45%) 0.65 Abstract 1125 Table 2Outcomes of NEC vs SIPn (%) NEC (50) SIP (31) P value Mortality 19/50 (38%) 6/31 (19%) 0.08 ROP treatment 7/31 (14%) 7/24 (29%) 0.16 ROP treatment/death 26/50 (52%) 13/31 (42%) 0.38 BPD (home oxygen) 14/31 (45%) 15/24 (63%) 0.11 BPD/death 33/50 (66%) 21/30* (73%) 0.49 * *One patient lost to follow up as transferred at 32w CGA ConclusionsNEC and SIP are catastrophic diagnoses with recognised adverse outcomes. Our data identifies a higher burden of morbidity in survivors of SIP, potentially reflecting the earlier insult at a time of greater susceptibility to multisystem injury in the most immature infants. It is important to differentiate between NEC and SIP, both to identify potentially causative associations, and to better predict complications and outcomes.

ObjectiveTo compare necrotising enterocolitis (NEC), late-onset sepsis (LOS), focal intestinal perforation (FIP) and mortality in infants from a single neonatal unit before and after probiotic introduction.DesignRetrospective review of infants <32 weeks admitted January 2009–December 2012 (no probiotic) and January 2013–December 2017 (routine probiotics). Infants included were admitted before day 3, and not transferred out before day 3. NEC, LOS and FIP were defined with standard definitions.Patients1061 infants were included, 509 preprobiotic and 552 postprobiotic. Median gestation, birth weight and antenatal steroid use did not differ, and proportions of extremely low birthweight infants were similar (37% and 41%).ResultsOverall unadjusted risk of NEC (9.2% (95% CI 7.1 to 12.1) vs 10.6% (95% CI 8.2 to 13.4), p=0.48), LOS (16.3% (95% CI 13.2 to 19.6) vs 14.1% (95% CI 11.5 to 17.4), p=0.37) and mortality (9.2% (95% CI 7.1 to 12.1) vs 9.7% (95% CI 7.6 to 12.6), p=0.76) did not differ, nor proportion of surgical NEC. In multiple logistic regression, accounting for gestation, birth weight, antenatal steroid, maternal milk, chorioamnionitis and sex, probiotic receipt was not significantly associated with NEC (adjusted OR (aOR) 1.08 (95% CI 0.71 to 1.68), p=0.73), LOS or mortality. In subgroup (645 infants) >28 weeks, aOR for NEC in the probiotic cohort was 0.42 (95% CI 0.2 to 0.99, p=0.047). FIP was more common in the probiotic cohort (OR 2.3 (95% CI 1.0 to 5.4), p=0.04), not significant in regression analysis (2.11 (95% CI 0.97 to 4.95), p=0.05).ConclusionsProbiotic use in this centre did not reduce overall mortality or rates of NEC, LOS or FIP but subgroup analysis identified NEC risk reduction in infants >28 weeks, and LOS reduction <28 weeks.

[Richard Abbott] said: \"At a time in Earth's history when animal and plant species are becoming extinct at an alarming rate, the discovery of the origin of a new plant species in Britain calls for a celebration as well as being of great scientific interest. The next few years will be critical as to whether it becomes a fully established component of the British flora or a temporary curiosity.\" The Latin name given to the new species is Senecio eboracensis, after Eboracum, the Roman name for York. The species has the same number of chromosomes as one of its parents and double that of its other parent. A necessary condition for demonstrating the origin of a new species is to show that it does not mate with its progenitors to produce viable offspring.