Reassessing acquired neonatal intestinal diseases using unsupervised machine learning.

BACKGROUND: Acquired neonatal intestinal diseases have an array of overlapping presentations and are often labeled under the dichotomous classification of necrotizing enterocolitis (which is poorly defined) or spontaneous intestinal perforation, hindering more precise diagnosis and research. The objective of this study was to take a fresh look at neonatal intestinal disease classification using unsupervised machine learning. METHODS: Patients admitted to the University of Florida Shands Neonatal Intensive Care Unit January 2013-September 2019 diagnosed with an intestinal injury, or had imaging findings of portal venous gas, pneumatosis, abdominal free air, or had an abdominal drain placed or exploratory laparotomy during admission were included. Congenital gastroschisis, omphalocele, intestinal atresia, malrotation were excluded. Data was collected via retrospective chart review with subsequent hierarchal, unsupervised clustering analysis. RESULTS: Five clusters of intestinal injury were identified: Cluster 1 deemed the "Low Mortality" cluster, Cluster 2 deemed the "Mature with Inflammation" cluster, Cluster 3 deemed the "Immature with High Mortality" cluster, Cluster 4 deemed the "Late Injury at Full Feeds" cluster, and Cluster 5 deemed the "Late Injury with High Rate of Intestinal Necrosis" cluster. CONCLUSION: Unsupervised machine learning can be used to cluster acquired neonatal intestinal injuries. Future study with larger multicenter datasets is needed to further refine and classify types of intestinal diseases. IMPACT: Unsupervised machine learning can be used to cluster types of acquired neonatal intestinal injury. Five major clusters of acquired neonatal intestinal injury are described, each with unique features. The clusters herein described deserve future, multicenter study to determine more specific early biomarkers and tailored therapeutic interventions to improve outcomes of often devastating neonatal acquired intestinal injuries.

Clinical Characteristics of Necrotizing Enterocolitis Diagnosed by Independent Adjudication of Abdominal Radiographs, Laparotomy, or Autopsy in Preterm Infants in the "Connection Trial".

OBJECTIVE: Necrotizing enterocolitis (NEC) classically is diagnosed by radiographic demonstration of pneumatosis intestinalis/portal venous gas (PI/PVG). This study examines clinical characteristics of NEC confirmed by independent evaluation of abdominal radiographs, taken for clinical signs of NEC, or by pathologic findings at laparotomy or autopsy (confirmed NEC [cNEC]). STUDY DESIGN: The investigated cohort included 1,382 extremely low birth weight (BW) infants (BW range: 500-1,000 g) with median 27 weeks (range: 23-32) gestational age (GA) at birth. They were randomized into the placebo-controlled "Connection Trial" of the new biological drug candidate IBP-9414 with cNEC as one primary endpoint. RESULTS: Total 119 infants (8.6%) had cNEC diagnosed at median 14 days of age by confirming PI/PVG at X-ray adjudication (n = 111) and/or by surgery/autopsy (n = 21). Sixteen percent of cNEC cases died. Adverse events of NEC were reported in 8.5% of infants and 4.1% had NEC diagnosed by radiology and surgery/autopsy at the participating centers. Regression analyses showed that the risk of cNEC decreased by 11 to 30% for every 100-g increment in BW and single-week increment in GA and associated cNEC with odds ratios (ORs) > 2.0 for gastrointestinal (GI) perforation and obstruction, hypotension, hypokalemia, hypophosphatemia, and death. Comparing risks of cNEC in infants below and above 750-g BW showed higher ORs (2.7-4.3) for GI perforation, hypotension, hypokalemia, and renal complications in the smaller infants, whereas the bigger infants had higher ORs (1.9-3.2) for serious non-GI events, late-onset sepsis (LOS), and death. Predictors of cNEC (hazard ratio, HR > 1.5) included serious non-GI events (mainly infections), hyponatremia, and hyperglycemia, whereas the HR was 0.52 for intravenous antibiotics. After cNEC diagnosis, there were higher rates of GI perforation and obstruction, hypotension, hypokalemia, and LOS. CONCLUSION: Independent adjudication of abdominal radiographs increased radiological recognition of NEC and proved to be feasible in a multicenter study setting as well as able to diagnose clinically relevant NEC. KEY POINTS: · Independent adjudication of abdominal radiographs in ELBW infants increased NEC recognition.. · Risk of NEC decreased by 11 to 30% with every 100-g increment in BW and GA week.. · In infants with BW 750 to 1,000 g, the risk of death from NEC was almost twice that in infants with BW 500 to 749 g. · Infants with NEC received antibiotics during one-third and parenteral nutrition during half of the first 7 postnatal weeks..

COVID-19 booster enhances IgG mediated viral neutralization by human milk in vitro.

Background: Facilitated by the inability to vaccinate, and an immature immune system, COVID-19 remains a leading cause of death among children. Vaccinated lactating mothers produce specific SARS-CoV-2 antibodies in their milk, capable of neutralizing the virus in vitro. Our objective for this study is to assess the effect of COVID-19 booster dose on SARS-CoV-2 antibody concentration and viral neutralization in milk, plasma, and infant stool. Methods: Thirty-nine mothers and 25 infants were enrolled from December 2020 to May 2022. Milk, maternal plasma, and infants' stool were collected at various time-points up to 12 months following mRNA COVID-19 vaccination. A subgroup of 14 mothers received a booster dose. SARS-CoV-2 antibody levels and their neutralization capacities were assessed. Results: Booster vaccination led to significantly higher IgG levels within human milk and breastfed infants' stool. In vitro neutralization of VSV-gfp-SARS-CoV-2-S-gp, a laboratory safe SARS-CoV-2 like pseudovirus, improved following the booster, with a 90% increase in plasma neutralization and a 60% increase in milk neutralization. We found that post-booster neutralization by human milk was highly correlated to SARS-CoV-2 IgG level. In support of our correlation result, Protein G column depletion of IgG in milk yielded a significant reduction in viral neutralization (p = 0.04). Discussion: The substantial increase in neutralizing IgG levels in milk and breastfed infants' stool post-booster, coupled with the decrease in milk neutralization capabilities upon IgG depletion, underscores the efficacy of booster doses in augmenting the immune response against SARS-CoV-2 in human milk.

An expert panel on the adequacy of safety data and physiological roles of dietary bovine osteopontin in infancy.

Human milk, due to its unique composition, is the optimal standard for infant nutrition. Osteopontin (OPN) is abundant in human milk but not bovine milk. The addition of bovine milk osteopontin (bmOPN) to formula may replicate OPN's concentration and function in human milk. To address safety concerns, we convened an expert panel to assess the adequacy of safety data and physiological roles of dietary bmOPN in infancy. The exposure of breastfed infants to human milk OPN (hmOPN) has been well-characterized and decreases markedly over the first 6 months of lactation. Dietary bmOPN is resistant to gastric and intestinal digestion, absorbed and cleared from circulation within 8-24 h, and represents a small portion (<5%) of total plasma OPN. Label studies on hmOPN suggest that after 3 h, intact or digested OPN is absorbed into carcass (62%), small intestine (23%), stomach (5%), and small intestinal perfusate (4%), with <2% each found in the cecum, liver, brain, heart, and spleen. Although the results are heterogenous with respect to bmOPN's physiologic impact, no adverse impacts have been reported across growth, gastrointestinal, immune, or brain-related outcomes. Recombinant bovine and human forms demonstrate similar absorption in plasma as bmOPN, as well as effects on cognition and immunity. The panel recommended prioritization of trials measuring a comprehensive set of clinically relevant outcomes on immunity and cognition to confirm the safety of bmOPN over that of further research on its absorption, distribution, metabolism, and excretion. This review offers expert consensus on the adequacy of data available to assess the safety of bmOPN for use in infant formula, aiding evidence-based decisions on the formulation of infant formula.

Gastroenterología y nutrición

Contenido: Generalidades científicas y perspectivas del desarrollo. Desarrollo gastrointestinal: morfogénesis y mecanismos moleculares. Regulación dietética de la expresión de los genes. Páncreas exocrino. Inmunidad innata y biología epitelial. Microflora intestinal y microbioma. Función de la barrera intestinal: implicancias para el recién nacido y la vida posterior. Intestino como órgano neuroendocrino. Factores tróficos en el tubo digestivo neonatal. Colestasis en recién nacidos y lactantes. Regulación de la síntesis de proteínas y la proteólisis por la alimentación en el recién nacido. Técnicas no invasivas para controlar la nutrición en el recién nacido. Requerimientos nutricionales del recíén nacido con muy bajo peso. Macronutrientes y micronutrientes. Diversas funciones de los lípidos en la fisiología y en el desarrollo neonatal. Enterocolotis necrosante: patogenia, atención clínica y prevención. Síndrome del intestino corto. Consecuencias de la nutrición neonatal y fetal en el adulto: mecanismos