Assessment of Inflammation and Intestinal Permeability Following Therapeutic Use of Human Milk IgA in Newborns Undergoing Corrective Surgery for Gastroschisis

• Grant number: 25/04926-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2025
• End date: May 31, 2026
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Magda Maria Sales Carneiro-Sampaio
• Grantee: Manuela Greco Marques
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 22/13837-5 - Therapeutic use of human milk for high-risk neonates and immunosuppressed patients, AP.TEM

Abstract

Gastroschisis is a congenital malformation of the abdominal wall characterized by the exteriorization of intestinal loops through a paraumbilical orifice without a protective membrane. The global incidence of gastroschisis has increased in recent decades, ranging between 1 to 5 cases per 10,000 live births. Infection is the main or associated cause of neonatal death due to the immaturity of the immune system typical of this age group and the clinical-surgical manipulations required for treatment. The transfer of IgG antibodies through the placenta and secretory IgA (SIgA) present in colostrum and breast milk constitutes an essential defense mechanism for the newborn. IgA antibodies prevent the adherence and penetration of antigens through the mucosal epithelium in newborns without triggering inflammatory reactions, thereby protecting and stimulating the development and maturation of their immune system. A wide variety of pathogens come into contact with the human body, and the neonate relies primarily on the innate immune system as the first line of defense against microorganisms since this response matures faster than the adaptive immune response. During acute inflammation, neutrophils secrete myeloperoxidase (MPO) and elastase (ELA), which are lysosomal proteins released during the degranulation process, often increased in intestinal inflammation. Increased intestinal permeability generally accompanies the inflammatory process in the gut and can be identified by elevated zonulin levels, a protein that modulates the permeability of tight junctions in intestinal epithelial cells. Thus, the objective of this study is to evaluate the presence of MPO, ELA, and zonulin in the feces of newborns undergoing corrective gastroschisis surgery after therapeutic administration of human milk IgA. This project is a continuation of the pilot study entitled "Therapeutic use of human milk IgA in newborns submitted to gastroschisis corrective surgery" conducted with 40 neonates with gastroschisis who were treated via an orogastric catheter (OGC) with the liquid phase of human milk (n=20) or distilled water (n=20) every 8 hours throughout their entire hospitalization period. At the end of this study, we observed that the length of hospital stay and the number of infections were significantly lower in the neonates who received the liquid phase of human milk in combination with breast milk. In this project, we will analyze intestinal inflammation and permeability using stool samples that were collected weekly and immediately frozen at -80°C for later use. MPO, ELA, and zonulin levels will be measured using ELISA kits following the manufacturer's instructions. The statistical analysis will include calculations of mean, median, standard deviation, and confidence intervals. Continuous variables will be expressed as mean ± standard deviation or median (minimum and maximum), and compared using the t-test or Mann-Whitney test, depending on data normality. Linear associations will be assessed using Pearson or Spearman correlation tests. A significance level of p<0.05 will be adopted. The results obtained in this project will allow for a comparison between the treatment already carried out in the pilot study (every 8 hours) and the treatment to be performed with the administration of the liquid phase of human milk every 3 hours, as proposed in the ongoing thematic project (FAPESP Process 2022/13837-5, "Therapeutic use of human milk for high-risk neonates and immunosuppressed patients", subproject 1 - "Therapeutic use of human milk Immunoglobulin A in newborns undergoing corrective surgeries for malformations of the digestive tract and abdominal wall"). (AU)