Preventing Atopic Dermatitis and ALLergy in children

PreventADALL has two main objectives; to investigate if atopic dermatitis (AD) and or food allergy can be prevented by skin-and/or food interventions in the first year of life, and identify factors early in life that implicated in development of non-communicable diseases, including asthma and other allergic diseases, including obesity, diabetes and cardiovascular disease. This project was supported to establish the study with the two main objectives and conduct data collection up to two years of age. In this multi-national prospective mother-child randomized clinical trial (RCT) 2395 children were randomized at birth to one of four groups; skin intervention, food intervention, both or no intervention. Data collection started December 2014 with completed recruitment within 22 months of 2697 women (2701 pregnancies) in Oslo, Østfold and Stockholm (Sweden). Further, we included 2395 of their newborn infants who are currently followed-up to 3-years of age. Collected data include investigations at enrolment of mother and fetus, clinical investigations and biological samples at birth-3-6-12-24-36 months, as well as electronic questionnaires at 18-34 weeks pregnancies and 3-6-9-12-18-24-30-36 months of age. Additional fetal ultrasound measures were done at 18 weeks (in around 2600 women) and 30 weeks gestational age in 450, while clinical investigations included anthropometric measures at all visits, lung function measures (3-12-36 months), blood pressure measures (3-6-12-36 months), microbiological sampling from skin/nose/feces (all visits), allergy diagnostics (all visits), samples of blood, urine and breast milk). Completion of the 36-month visit was delayed until September 2020 due to Covid-19, with results in terms of food allergies (at 3 years) expected primo 2021. Results so far: -Atopic dermatitis (AD) at 12 months was the first main outcome for the RCT. We found no reduction in AD by either skin- or food-intervention. Although unexpected, similar was found in a parallel study in Great Britain using daily emollient cream in high-risk infants. -around 15 000 clinical investigations, more than 70 000 questionnaires/diaries and interviews have been completed, parents performed around 100 000 oil-baths of their infant, and our biobank has stored around 140 000 bio-samples for analyses. Microbiome is an area of focus, with 20 000 fecal samples and 25 000 skin microbiome samples up to 3 years. Most research questions among the 24 PhD candidates and many Master candidates and other researchers are related to identifying early life factors involved in NCD development. In hitherto 14 published papers and 1 completed PhD thesis (+ 1 submitted), we have shown: -more than half of 3-month-old infants had dry skin, often with a reduced skin barrier that was found to increase the risk of AD at 6 months -While daughters often inherit risk of AD from their mothers, sons appear to do so from their fathers -the use of nicotine products during pregnancy and breastfeeding, as well as assessed the effects on placenta function and effects on infant size at birth - high level of stress, more common in mid- compared to late pregnancy, was associated with symptoms of asthma and other allergic diseases. Ongoing studies assess if high stress in pregnancy is associated with off-spring health. -nutritional content in pregnancy was similar to the population at large, but deficient in micronutrients as well as exceeding the recommended doses of coffee and alcohol. -fetal ultrasound measures in around 2600 women at enrolment and at 30-uker in 450 women are assessed for potential risk of fetal growth and effects on NCD development. - amniotic fluid from uncomplicated pregnancies with intact membranes was sterile, but in case of ruptured membranes bacterial colonization was established. - Gut flora in the newborn resembled maternal gut-flora on to a limited extent, while butyrate, a metabolic substrate levels increased from 6-12 months of age, particularly in the presence of certain bacteria. Analyses are ongoing to determine their role for allergic disease development. A new methodology was developed at NMBU for optimizing gut flora characterization. We are currently extending into a large international collaboration for micriobiota research. Our local, regional and international collaboration is continuously expanding, including participation in a prospective meta-analysis of primary prevention of AD, as well as research into early life risk of NCD development.

PreventADALL er verdens største med hud- og matintervensjon i spedbarnsalder for å forebygge atopisk eksem og matallergi. Våre funn bidro i stor grad til en internasjonal konklusjon om å ikke anbefale slike tiltak til spedbarn for å forebygge eksemutvikling. Det er stor interesse knyttet til resultatene for matallergi ved 3-år, trolig tilgjengelige første del av 2020. Studien har samlet inn detaljert informasjon fra undersøkelser, biologisk materiale og spørreskjemadata fra fosterlivet til 3-års alder. Dette danner et unikt fundament for oppfølgingsundersøkelser for å identifisere faktorer som kan inngå i forebygging eller tidlig behandling for å redusere byrden av ikke-smittsomme folkesykdommer. I tillegg til vitenskapelige resultater, har PreventADALL bidratt vesentlig til forskerutdanning, med 24 pågående PhD stipendiater og Masterstudenter som benytter tilgjengelig materiale for sine oppgaver. Studien har, og vil øke forskersamarbeid lokalt, regionalt og internasjonalt.

Allergic diseases, the most common chronic disorders worldwide in children and adults, affect 25-45% of the population, also in Norway have huge individual, societal and health economic impact. WHO predicts that the diseases will affect 50 % of the world population by 2030 unless effective primary prevention strategies are identified and implemented. To date, no primary prevention strategies are available. Although the causes are unknown, environmental changes including reduced diversity of gut and environmental microbiota and increased exposure to xenobiotics are likely to be involved in immune deviation by interacting with genes (epigenetics). Allergic and other non-communicable diseases (NCDs) appear to start, at least partly in utero, with factors affecting immune- and organ development possibly before and during pregnancy. The present internationally collaborative, innovative randomized controlled interventional birth cohort study will test if it is possible to reduce allergic diseases by simple, low-cost primary prevention strategies. Also, the project concerns identification of early origins of development of health and disease (DOHAD) focusing on NCDs (including allergic, cardiovascular, obesity, and diabetes), with data from 18 weeks of pregnancy. PreventADALL is a randomised factorially designed interventional birth cohort study including 3000 babies, recruited first by their mothers at 18 weeks gestation thereafter by new-born babies of at least 35 weeks gestation. Babies are randomised to one of four groups by the two interventions; improving skin barrier by skin care from 0.5-9 months of age, and early introduction of major allergenic foods. The study focuses on frequent biological sampling and close clinical assessments of allergic disease outcomes in the first years of life, and annually thereafter planning for long term follow-up. The study is unique and innovative. If successful interventions, the study will have a major impact world-wide.