Effectiveness of an antenatal maternal supplementation with prebiotics for preventing atopic dermatitis in high-risk children (the PREGRALL study): protocol for a randomised controlled trial

Abstract

IntroductionAtopic dermatitis (AD) is a chronic inflammatory disease affecting 10%–15% of children in Europe. There is a need for new primary preventive therapeutic strategies in at-risk populations. Recent research has indicated that atopic diseases are associated with a disrupted gut microbial ‘balance’ in early life raising the possibility that interventions which yield optimal patterns of microflora could improve host’s health. Prebiotics, sugars with immunomodulatory properties that stimulate the diversity of the digestive microbiota, are ideal candidates for such research. So far, most clinical trials have focused on improving infant gut colonisation postnatally. However, prenatal life is a crucial period during which different tolerance mechanisms are put in place. We aim to determine whether antenatal prebiotics supplementation prevents AD in high-risk children.Methods and analysisThis is a randomised, multicentre, double-blind, trial to evaluate the effectiveness of antenatal prebiotic maternal supplementation (galacto-oligosaccharide/inulin) in pregnant women versus placebo on the occurrence of AD at 1 year of age in at-risk children (defined as having a maternal history of atopic disease). Participating women will be randomised to daily ingestion of a prebiotics or placebo (maltodextrin) from 20 weeks’ gestation until delivery. The primary outcome is the prevalence of AD at 1 year of age, using the version of the UK Working Party Diagnostic Criteria optimised for preventive studies. Key secondary endpoints are AD severity, quality of life and prebiotics tolerance. The target sample size is 376 women (188 patients per group) which will provide 80% power to detect a 33% reduction of the risk of AD in the verum group (α=0.05). The primary analysis will be based on the intention-to-treat principle.Ethics and disseminationResults will be presented in peer-reviewed journals and at international conferences. Ethics approval for the study was obtained from the institutional ethical review board of ‘Comité de Protection des Personnes Sud Ouest—Outre-Mer III’ of the University Hospital Centre of Bordeaux (2017/13).Trial registration numberNCT03183440; Pre-results.

The role of the changing human microbiome in the asthma pandemic

“…In one ongoing trial pregnant women and prospective mothers of at-risk offspring are being enrolled and given the prebiotic inulin to determine effects on the occurrence of atopic dermatitis as a primary end point and early predictive readout of allergy. 77 The results of this study are still pending.…”

Human Milk Oligosaccharides: Their Effects on the Host and Their Potential as Therapeutic Agents

“…SYMBA investigates the effects of maternal prebiotic supplementation from 18–20 weeks gestation during pregnancy until 6 months of lactation on the development of infant allergic disease ( 135 ). PREGRALL aims to evaluate the effectiveness of gestational prebiotic supplementation (from 20th week of gestation until delivery) on the occurrence of AD at 1 year of age in at-risk children ( 136 ). Because lactation is also a crucial period for the implementation of major systems, HMO supplementation of breastfed babies from non-secretor mother could be considered as preventive strategy for non-communicable diseases.…”

Human Milk From Atopic Mothers Has Lower Levels of Short Chain Fatty Acids

“…Further, murine studies have demonstrated that prebiotic fiber supplementation during pregnancy or lactation reduces risk of atopy in offspring (11,12). Similar trials are currently underway in humans [SYMBA (13) and PREGRALL (14)]. Recently, Lee-Sarwar et al reported higher fecal acetate levels (relative to total SCFA) in pregnant women of children less likely to develop atopic disease (15).…”