Postnatal growth and gut microbiota development influenced early childhood growth in preterm infants.

Background: Preterm infants are at high risk for growth failure and childhood weight problems due to the disruption of normal intrauterine growth and nutrition. Early nutritional support and microbiome acquisition can play an important role in childhood growth. Objective: Our study examined potential postnatal indicators, including gut bacterial compositions, macronutrients, and catch-up growth, of growth pattern from infancy into early childhood. Methods: This is a retrospective study of preterm infants born < 35 weeks who were followed up in the university complex care clinic from 2012-2018. Weight and length z-scores at birth, 1, 2, 4, 6, 12 and 15 months, and body mass index (BMI) and length z-scores from 2 to 5 years of age were collected. Catch-up growths were calculated by changes in z-scores and divided into early (birth-4 months) and late (4-18 months). Postnatal nutritional data and fecal samples were collected. Fecal microbiome data obtained from 16S RNA V4 sequencing was analyzed against clinical and growth data using a regression model. Results: 160 infants included in the final analysis had birth weight and gestational age of 1,149 ± 496 grams and 28 ± 3 weeks. Early weight gain positively correlated with length z-scores but not with BMI at 2 years of age. BMI at 2 years of age strongly correlated with BMI at 3, 4, and 5 years of age. Postnatal abundance of Gammaproteobacteria was negatively associated with early growth while Bacteroides and Lactobacillus were positively associated with childhood BMI. Conclusion: Our findings suggest that optimal postnatal nutrition promoted early catch-up growth in weight as well as improved linear growth without influence on childhood BMI. Postnatal gut microbial colonization, which is a modifiable factor, was associated with childhood growth in preterm infants.

Testing Epithelial Permeability in Fetal Tissue-Derived Enteroids.

Human fetal tissue-derived enteroids are emerging as a promising in vitro model to study intestinal injuries in preterm infants. Enteroids exhibit polarity, consisting of a lumen with an apical border, tight junctions, and a basolateral outer layer exposed to growth media. The consequences of intestinal injuries include mucosal inflammation and increased permeability. Testing intestinal permeability in vulnerable preterm human subjects is often not feasible. Thus, an in vitro fetal tissue-derived intestinal model is needed to study intestinal injuries in preterm infants. Enteroids can be used to test changes in epithelial permeability regulated by tight junction proteins. In enteroids, intestinal stem cells differentiate into all epithelial cell types and form a three-dimensional structure on a basement membrane matrix secreted by mouse sarcoma cells. In this article, we describe the methods used for establishing enteroids from fetal intestinal tissue, characterizing the enteroid tight junction proteins with immunofluorescent imaging, and testing epithelial permeability. As gram-negative dominant bacterial dysbiosis is a known risk factor for intestinal injury, we used lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria, to induce permeability in the enteroids. Fluorescein-labeled dextran was microinjected into the enteroid lumen, and serial dextran concentrations leaked into the culture media were measured to quantify the changes in paracellular permeability. The experiment showed that apical exposure to LPS induces epithelial permeability in a concentration-dependent manner. These findings support the hypothesis that gram-negative dominant dysbiosis contributes to the mechanism of intestinal injury in preterm infants.

Neonatal pain assessment: Do we have the right tools?

Background: The assessment and management of neonatal pain is crucial for the development and wellbeing of vulnerable infants. Specifically, neonatal pain is associated with adverse health outcomes but is often under-identified and therefore under-treated. Neonatal stress may be misinterpreted as pain and may therefore be treated inappropriately. The assessment of neonatal pain is complicated by the non-verbal status of patients, age-dependent variation in pain responses, limited education on identifying pain in premature infants, and the clinical utility of existing tools. Objective: We review research surrounding neonatal pain assessment scales currently in use to assess neonatal pain in the neonatal intensive care unit. Methods: We performed a systematic review of original research using PRISMA guidelines for literature published between 2016 and 2021 using the key words "neonatal pain assessment" in the databases Web of Science, PubMed, and CINAHL. Fifteen articles remained after review, duplicate, irrelevant, or low-quality articles were eliminated. Results: We found research evaluating 13 neonatal pain scales. Important measurement categories include behavioral parameters, physiological parameters, continuous pain, acute pain, chronic pain, and the ability to distinguish between pain and stress. Provider education, inter-rater reliability and ease of use are important factors that contribute to an assessment tool's success. Each scale studied had strengths and limitations that aided or hindered its use for measuring neonatal pain in the neonatal intensive care unit, but no scale excelled in all areas identified as important for reliably identifying and measuring pain in this vulnerable population. Conclusion: A more comprehensive neonatal pain assessment tool and more provider education on differences in pain signals in premature neonates may be needed to increase the clinical utility of pain scales that address the different aspects of neonatal pain.