Background: Immunomodulatory proteins in human milk (HM) can shape infant immune development. However, strategies to modulate their levels are currently unknown. This study investigated whether maternal prebiotic supplementation alters the levels of immunomodulatory proteins in HM. Methods: The study was nested within the SYMBA double-blind randomised controlled trial (ACTRN12615001075572), which is investigating the effects of maternal prebiotic (scGOS/lcFOS) supplementation from <21 weeks gestation during pregnancy until 6-months postnatal during lactation on child allergic disease risk. Mother-child dyads receiving prebiotics (n=46) or placebo (n=54) were included in this study. We measured the levels of 24 immunomodulatory proteins in HM collected at 2, 4 and 6 months. Results: Cluster analysis showed that the overall immunomodulatory protein composition of milk samples from both groups was similar. Prebiotic-supplemented women had decreased levels of TGF-β1 at 2 months, IgG1 at 4 months and sCD14 at 6 months (p=0.03, 0.03 and 0.04, respectively). IL-5 levels were increased in the prebiotic group compared to the control group at 4 and 6 months (p=0.02 and 0.04, respectively). After adjustment for multiple comparisons, the statistical differences between the prebiotic and placebo groups were no longer present (p>0.05). Conclusion: This study is the first to comprehensively trial scGOS/lcFOS intake during pregnancy and indicate potentially altered levels of immunomodulatory proteins in HM. Future research will elucidate the significance of change in milk content in immunomodulatory compounds in the prevention of allergy risk (and beyond), filling a major gap in dietary advice to pregnant and/or lactating women.

Background: Oral immunotherapy (OIT) has shown promise for peanut-allergic preschool children. Studies report it is safe and effective, with over 70% achieving sustained unresponsiveness. Knowledge about preschool OIT for other allergens and multiple food allergies is still limited. Objective: To assess the safety of a pragmatic OIT protocol in preschool children with single and multiple food allergies. Methods: This single-center prospective intervention study included children aged 9-24 months with proven food allergy (sensitization and a positive oral food challenge (OFC)). After a short dose escalation phase, children received one year of low-dose (300 mg protein/day) OIT, followed by an exit OFC four weeks after stopping therapy. Children with multiple food allergies received OIT for up to four allergens. Allergic dosing reactions (ADR) were recorded and classified using Sampson’s severity score (grades I-V). Results: Between May 2019 and Oct 2022, 124 children (median age 17, IQR 11-20 months) started OIT for 189 allergies. Peanut (n=52), cashew (n=46) and egg (n=38) allergies were the most common. ADR occurred in 89 children and 117 OIT trajectories, most frequently during dose escalation (65%). Reactions (95.3%) were mild (grade I-II) and mostly resolved spontaneously (55.6%) or with antihistamines (29.9%). Ten reactions were severe (grade III-IV). Reaction severity did not differ between single and multiple OIT or among the different allergens. Ten trajectories were discontinued due to side effects. Conclusions: OIT for various allergens and multiple food allergies appears safe for preschoolers. Side effects are common but typically mild. However, they may lead to therapy discontinuation.