Håvard Ove Skjerven1, Eva Maria Rehbinder2, Riyas Vettukattil3, Marissa LeBlanc4, Berit Granum5, Guttorm Haugen6, Gunilla Hedlin7, Linn Landrø8, Benjamin J Marsland9, Knut Rudi10, Kathrine Dønvold Sjøborg11, Cilla Söderhäll7, Anne Cathrine Staff6, Kai-Håkon Carlsen3, Anna Asarnoj7, Karen Eline Stensby Bains3, Oda C Lødrup Carlsen12, Kim M Advocaat Endre3, Peder Annæus Granlund13, Johanne Uthus Hermansen12, Hrefna Katrín Gudmundsdóttir3, Katarina Hilde6, Geir Håland3, Ina Kreyberg3, Inge Christoffer Olsen14, Caroline-Aleksi Olsson Mägi7, Live Solveig Nordhagen15, Carina Madelen Saunders3, Ingebjørg Skrindo16, Sandra G Tedner7, Magdalena R Værnesbranden17, Johanna Wiik18, Christine Monceyron Jonassen19, Björn Nordlund7, Karin C Lødrup Carlsen3. 1. Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: h.o.skjerven@medisin.uio.no. 2. Department of Dermatology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 3. Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 4. Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway. 5. Department of Environmental Health, Norwegian Institute of Public Health, Oslo, Norway. 6. Division of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 7. Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden; Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden. 8. Department of Dermatology, Oslo University Hospital, Oslo, Norway. 9. Department of Immunology and Pathology, Monash University, Melbourne, VIC, Australia; Department of Biology and Medicine, Centre Hospitalier Universitaire Vaudois-Universitu of Lausanne, Lausanne, Switzerland. 10. Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway. 11. Department of Gynecology and Obstetrics, Østfold Hospital Trust, Kalnes, Norway. 12. Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway. 13. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. 14. Research Support Services, Clinical Trials Unit, Oslo University Hospital, Oslo, Norway. 15. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; VID Specialized University, Oslo, Norway. 16. Department of Otorhinolaryngology, Akershus University Hospital, Lørenskog, Norway. 17. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Gynecology and Obstetrics, Østfold Hospital Trust, Kalnes, Norway. 18. Department of Gynecology and Obstetrics, Østfold Hospital Trust, Kalnes, Norway; Department of Obstetrics and Gynecology, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden. 19. Department of Chemistry, Biotechnology and Food Science, Norwegian University of Life Sciences, Ås, Norway; Center for Laboratory Medicine, Østfold Hospital Trust, Kalnes, Norway.
Abstract
BACKGROUND:Skin emollients applied during early infancy could prevent atopic dermatitis, and early complementary food introduction might reduce food allergy in high-risk infants. The study aimed to determine if either regular skin emollients applied from 2 weeks of age, or early complementary feeding introduced between 12 and 16 weeks of age, reduced development of atopic dermatitis by age 12 months in the general infant population. METHODS: This population-based 2×2 factorial, randomised clinical trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway; and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine ultrasound pregnancy screening at 18 weeks were cluster-randomised at birth from 2015 to 2017 to the following groups: (1) controls withno specific advice on skin care while advised to follow national guidelines on infant nutrition (no intervention group); (2) skin emollients (bath additives and facial cream; skin intervention group); (3) early complementary feeding of peanut, cow's milk, wheat, and egg (food intervention group); or (4) combined skin and food interventions (combined intervention group). Participants were randomly assigned (1:1:1:1) using computer- generated cluster randomisation based on 92 geographical living area blocks as well as eight 3-month time blocks. Carers were instructed to apply the interventions on at least 4 days per week. Atopic dermatitis by age 12 months was the primary outcome, based on clinical investigations at 3, 6 and 12 months by investigators masked to group allocation. Atopic dermatitis was assessed after completing the 12-month investigations and diagnosed if either of the UK Working Party and Hanifin and Rajka (12 months only) diagnostic criteria were fulfilled. The primary efficacy analyses was done by intention-to-treat analysis on all randomly assigned participants. Food allergy results will be reported once all investigations at age 3 years are completed in 2020. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). The study is registered at clinicaltrials.gov, NCT02449850. FINDINGS:2697 women were recruited between Dec 9, 2014, and Oct 31, 2016, from whom 2397 newborn infants were enrolled from April 14, 2015, to April 11, 2017. Atopic dermatitis was observed in 478 (8%) of 596 infants in the no intervention group, 64 (11%) of 575 in the skin intervention group, 58 (9%) of 642 in the food intervention group, and 31 (5%) of 583 in the combined intervention group. Neither skin emollients nor early complementary feeding reduced development of atopic dermatitis, with a risk difference of 3·1% (95% CI -0·3 to 6·5) for skin intervention and 1·0% (-2·1 to 4·1) for food intervention, in favour of control. No safety concerns with the interventions were identified. Reported skin symptoms and signs (including itching, oedema, exanthema, dry skin, and urticaria) were no more frequent in the skin, food, and combined intervention groups than in the no intervention group. INTERPRETATION: Neither early skin emollients nor early complementary feeding reduced development of atopic dermatitis by age 12 months. Our study does not support the use of these interventions to prevent atopic dermatitis by 12 months of age in infants. FUNDING: The study was funded by several public and private funding bodies: The Regional Health Board South East, The Norwegian Research Council, Health and Rehabilitation Norway, The Foundation for Healthcare and Allergy Research in Sweden-Vårdalstiftelsen, Swedish Asthma and Allergy Association's Research Foundation, Swedish Research Council-the Initiative for Clinical Therapy Research, The Swedish Heart-Lung Foundation, SFO-V at the Karolinska Institute, Freemason Child House Foundation in Stockholm, Swedish Research Council for Health, Working Life and Welfare-FORTE, Oslo University Hospital, the University of Oslo, and Østfold Hospital Trust.
RCT Entities:
BACKGROUND: Skin emollients applied during early infancy could prevent atopic dermatitis, and early complementary food introduction might reduce food allergy in high-risk infants. The study aimed to determine if either regular skin emollients applied from 2 weeks of age, or early complementary feeding introduced between 12 and 16 weeks of age, reduced development of atopic dermatitis by age 12 months in the general infant population. METHODS: This population-based 2×2 factorial, randomised clinical trial was done at Oslo University Hospital and Østfold Hospital Trust, Oslo, Norway; and Karolinska University Hospital, Stockholm, Sweden. Infants of women recruited antenatally at the routine ultrasound pregnancy screening at 18 weeks were cluster-randomised at birth from 2015 to 2017 to the following groups: (1) controls with no specific advice on skin care while advised to follow national guidelines on infant nutrition (no intervention group); (2) skin emollients (bath additives and facial cream; skin intervention group); (3) early complementary feeding of peanut, cow's milk, wheat, and egg (food intervention group); or (4) combined skin and food interventions (combined intervention group). Participants were randomly assigned (1:1:1:1) using computer- generated cluster randomisation based on 92 geographical living area blocks as well as eight 3-month time blocks. Carers were instructed to apply the interventions on at least 4 days per week. Atopic dermatitis by age 12 months was the primary outcome, based on clinical investigations at 3, 6 and 12 months by investigators masked to group allocation. Atopic dermatitis was assessed after completing the 12-month investigations and diagnosed if either of the UK Working Party and Hanifin and Rajka (12 months only) diagnostic criteria were fulfilled. The primary efficacy analyses was done by intention-to-treat analysis on all randomly assigned participants. Food allergy results will be reported once all investigations at age 3 years are completed in 2020. This was a study performed within ORAACLE (the Oslo Research Group of Asthma and Allergy in Childhood; the Lung and Environment). The study is registered at clinicaltrials.gov, NCT02449850. FINDINGS: 2697 women were recruited between Dec 9, 2014, and Oct 31, 2016, from whom 2397 newborn infants were enrolled from April 14, 2015, to April 11, 2017. Atopic dermatitis was observed in 478 (8%) of 596 infants in the no intervention group, 64 (11%) of 575 in the skin intervention group, 58 (9%) of 642 in the food intervention group, and 31 (5%) of 583 in the combined intervention group. Neither skin emollients nor early complementary feeding reduced development of atopic dermatitis, with a risk difference of 3·1% (95% CI -0·3 to 6·5) for skin intervention and 1·0% (-2·1 to 4·1) for food intervention, in favour of control. No safety concerns with the interventions were identified. Reported skin symptoms and signs (including itching, oedema, exanthema, dry skin, and urticaria) were no more frequent in the skin, food, and combined intervention groups than in the no intervention group. INTERPRETATION: Neither early skin emollients nor early complementary feeding reduced development of atopic dermatitis by age 12 months. Our study does not support the use of these interventions to prevent atopic dermatitis by 12 months of age in infants. FUNDING: The study was funded by several public and private funding bodies: The Regional Health Board South East, The Norwegian Research Council, Health and Rehabilitation Norway, The Foundation for Healthcare and Allergy Research in Sweden-Vårdalstiftelsen, Swedish Asthma and Allergy Association's Research Foundation, Swedish Research Council-the Initiative for Clinical Therapy Research, The Swedish Heart-Lung Foundation, SFO-V at the Karolinska Institute, Freemason Child House Foundation in Stockholm, Swedish Research Council for Health, Working Life and Welfare-FORTE, Oslo University Hospital, the University of Oslo, and Østfold Hospital Trust.
Authors: Maeve M Kelleher; Suzie Cro; Victoria Cornelius; Karin C Lodrup Carlsen; Håvard O Skjerven; Eva M Rehbinder; Adrian J Lowe; Eishika Dissanayake; Naoki Shimojo; Kaori Yonezawa; Yukihiro Ohya; Kiwako Yamamoto-Hanada; Kumiko Morita; Emma Axon; Christian Surber; Michael Cork; Alison Cooke; Lien Tran; Eleanor Van Vogt; Jochen Schmitt; Stephan Weidinger; Danielle McClanahan; Eric Simpson; Lelia Duley; Lisa M Askie; Joanne R Chalmers; Hywel C Williams; Robert J Boyle Journal: Cochrane Database Syst Rev Date: 2021-02-05
Authors: Cristina Gomez-Casado; Javier Sanchez-Solares; Elena Izquierdo; Araceli Díaz-Perales; Domingo Barber; María M Escribese Journal: Foods Date: 2021-04-28
Authors: Helen A Brough; Kari C Nadeau; Sayantani B Sindher; Shifaa S Alkotob; Susan Chan; Henry T Bahnson; Donald Y M Leung; Gideon Lack Journal: Allergy Date: 2020-05-18 Impact factor: 13.146
Authors: Christopher H Arehart; Michelle Daya; Monica Campbell; Meher Preethi Boorgula; Nicholas Rafaels; Sameer Chavan; Gloria David; Jon Hanifin; Mark K Slifka; Richard L Gallo; Tissa Hata; Lynda C Schneider; Amy S Paller; Peck Y Ong; Jonathan M Spergel; Emma Guttman-Yassky; Donald Y M Leung; Lisa A Beck; Christopher R Gignoux; Rasika A Mathias; Kathleen C Barnes Journal: J Allergy Clin Immunol Date: 2021-06-07 Impact factor: 10.793
Authors: Morten Nilsen; Carina Madelen Saunders; Inga Leena Angell; Magnus Ø Arntzen; Karin C Lødrup Carlsen; Kai-Håkon Carlsen; Guttorm Haugen; Live Heldal Hagen; Monica H Carlsen; Gunilla Hedlin; Christine Monceyron Jonassen; Björn Nordlund; Eva Maria Rehbinder; Håvard O Skjerven; Lars Snipen; Anne Cathrine Staff; Riyas Vettukattil; Knut Rudi Journal: Genes (Basel) Date: 2020-10-22 Impact factor: 4.096
Authors: Joanne R Chalmers; Rachel H Haines; Lucy E Bradshaw; Alan A Montgomery; Kim S Thomas; Sara J Brown; Matthew J Ridd; Sandra Lawton; Eric L Simpson; Michael J Cork; Tracey H Sach; Carsten Flohr; Eleanor J Mitchell; Richard Swinden; Stella Tarr; Susan Davies-Jones; Nicola Jay; Maeve M Kelleher; Michael R Perkin; Robert J Boyle; Hywel C Williams Journal: Lancet Date: 2020-02-19 Impact factor: 202.731