TY - JOUR
T1 - Daily emollient during infancy for prevention of eczema
T2 - the BEEP randomised controlled trial
AU - BEEP study team
AU - Chalmers, Joanne R.
AU - Haines, Rachel H.
AU - Bradshaw, Lucy E.
AU - Montgomery, Alan A.
AU - Thomas, Kim S.
AU - Brown, Sara J.
AU - Ridd, Matthew J.
AU - Lawton, Sandra
AU - Simpson, Eric L.
AU - Cork, Michael J.
AU - Sach, Tracey H.
AU - Flohr, Carsten
AU - Mitchell, Eleanor J.
AU - Swinden, Richard
AU - Tarr, Stella
AU - Davies-Jones, Susan
AU - Jay, Nicola
AU - Kelleher, Maeve M.
AU - Perkin, Michael R.
AU - Boyle, Robert J.
AU - Williams, Hywel C.
N1 - Funding Information:
Funding for the trial was obtained from the National Institute for Health Research (NIHR) Health Technology Assessment funding stream (reference 12/67/12). Additional funding for the food allergy and sensitisation tests was obtained from Goldman Sachs Gives and the Sheffield Children's Hospital Research Fund (reference CA15008). Research nurse support was provided by the NIHR Clinical Research Networks. The trial was developed with and supported by the UK Dermatology Clinical Trials Network (UK DCTN). SJB holds a Wellcome Trust Senior Research Fellowship in Clinical Science (reference 106865/Z/15/Z). CF holds an NIHR Career Development Fellowship (CDF-2014–07–037) and is supported by the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. MK holds an NIHR Transitional Research Fellowship (TRF-2017–10–003). MJR holds a Post-Doctoral Research Fellowship from NIHR (PDF-2014–07–013). The views expressed here are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The UK DCTN is grateful to the British Association of Dermatologists and the University of Nottingham for financial support of the Network. We would like to thank the parents and infants who took time to participate in this trial, and the patients who contributed to trial design by providing helpful feedback at different stages of trial development. We would like to thank Sheila C Wright (Skin Research Group, Division of Molecular and Clinical Medicine, University of Dundee, UK) for cataloguing and processing the saliva samples for DNA analysis, Daniel Simpkins from the Nottingham CTU for providing the trial database, and Douglas Grindlay (Centre of Evidence Based Dermatology, University of Nottingham, UK) for assistance with literature searches. Chris Partlett (Nottingham CTU) independently validated the analysis for the primary outcome, main food allergy outcome, and skin infection safety outcome. Reuben Ogollah (Nottingham CTU) helped with the complier average causal effect analysis.
Funding Information:
Funding for the trial was obtained from the National Institute for Health Research (NIHR) Health Technology Assessment funding stream (reference 12/67/12). Additional funding for the food allergy and sensitisation tests was obtained from Goldman Sachs Gives and the Sheffield Children's Hospital Research Fund (reference CA15008). Research nurse support was provided by the NIHR Clinical Research Networks. The trial was developed with and supported by the UK Dermatology Clinical Trials Network (UK DCTN). SJB holds a Wellcome Trust Senior Research Fellowship in Clinical Science (reference 106865/Z/15/Z). CF holds an NIHR Career Development Fellowship (CDF-2014?07?037) and is supported by the NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. MK holds an NIHR Transitional Research Fellowship (TRF-2017?10?003). MJR holds a Post-Doctoral Research Fellowship from NIHR (PDF-2014?07?013). The views expressed here are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The UK DCTN is grateful to the British Association of Dermatologists and the University of Nottingham for financial support of the Network. We would like to thank the parents and infants who took time to participate in this trial, and the patients who contributed to trial design by providing helpful feedback at different stages of trial development. We would like to thank Sheila C Wright (Skin Research Group, Division of Molecular and Clinical Medicine, University of Dundee, UK) for cataloguing and processing the saliva samples for DNA analysis, Daniel Simpkins from the Nottingham CTU for providing the trial database, and Douglas Grindlay (Centre of Evidence Based Dermatology, University of Nottingham, UK) for assistance with literature searches. Chris Partlett (Nottingham CTU) independently validated the analysis for the primary outcome, main food allergy outcome, and skin infection safety outcome. Reuben Ogollah (Nottingham CTU) helped with the complier average causal effect analysis.
Funding Information:
Informed consent was obtained from mothers during pregnancy, or from the mother, father, or guardian after delivery. The trial was overseen by an independent Trial Steering Committee ( appendix p3 ) and approved by the West Midlands Ethics Committee, UK (14/WM/0162). The study was sponsored by the University of Nottingham, coordinated by the Nottingham Clinical Trials Unit (CTU), and funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment Programme. Supplementary funding was obtained for inclusion of food allergy outcomes and skin prick tests subsequent to study initiation, which was provided by Goldman Sachs Gives and Sheffield Children's Hospital Charity. The full protocol and changes made after the trial started are available online on the trial website and in the appendix (p 10) . A protocol summary was published previously. 18
Funding Information:
RJB received personal fees from the Dairy Goat Cooperative, Cochrane, DBV Technologies, Prota Therapeutics, ALK Abelo, and from expert witness work, outside of the submitted work. RJB's employing institution Imperial College London has a formal research and innovation partnership with Nestlé, who manufacture and market nutritional products for managing food allergy and sponsor infant nutrition research related to eczema and food allergy. CF received a grant from the EU IMI grant scheme (Horizon 2020), outside of the submitted work. ELS received personal fees from AbbVie, Anacor Pharma, Celgene, Dermira Pharmaceuticals, Eli Lilly and Company, Galderma, and Genentech; and grants from GlaxoSmithKline, LEO Pharma, Menlo Therapeutics, Pfizer, Regeneron Pharmaceuticals, Sanofi Genzyme, Valeant Pharmaceutical, Novartis, Dermavant, and Pierre Fabre Dermo Cosmetique outside of the submitted work. ELS also received grants from Anacor Pharma, Eli Lilly and Company, LEO Pharma, Regeneron Pharmaceuticals, MedImmune, Novartis, Roivant Sciences, Vanda Pharmaceuticals, Tioga Pharmaceuticals, Kyowa Hakko Kirin, and Target Pharmaceutical Solutions. MJC received grants and personal fees from Sanofi-Genzyme/Regeneron, Pfizer, Leo Pharma, L'Oreal/LaRoche Possay, Johnson & Johnson, Perrigo/ACO Nordic, and grants from Galapagos, outside of the submitted work. HCW is director of the NIHR Health Technology Assessment Programme and THS is a member of the NIHR Health Technology Assessment Programme commissioning committee. Neither had any part in the decision making for funding this study. All other authors declare no competing interests.
Publisher Copyright:
© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
PY - 2020/3/21
Y1 - 2020/3/21
N2 - Background: Skin barrier dysfunction precedes eczema development. We tested whether daily use of emollient in the first year could prevent eczema in high-risk children. Methods: We did a multicentre, pragmatic, parallel-group, randomised controlled trial in 12 hospitals and four primary care sites across the UK. Families were approached via antenatal or postnatal services for recruitment of term infants (at least 37 weeks' gestation) at high risk of developing eczema (ie, at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma, diagnosed by a doctor). Term newborns with a family history of atopic disease were randomly assigned (1:1) to application of emollient daily (either Diprobase cream or DoubleBase gel) for the first year plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). The randomisation schedule was created using computer-generated code (stratified by recruiting centre and number of first-degree relatives with atopic disease) and participants were assigned to groups using an internet-based randomisation system. The primary outcome was eczema at age 2 years (defined by UK working party criteria) with analysis as randomised regardless of adherence to allocation for participants with outcome data collected, and adjusting for stratification variables. This trial is registered with ISRCTN, ISRCTN21528841. Data collection for long-term follow-up is ongoing, but the trial is closed to recruitment. Findings: 1394 newborns were randomly assigned to study groups between Nov 19, 2014, and Nov 18, 2016; 693 were assigned to the emollient group and 701 to the control group. Adherence in the emollient group was 88% (466 of 532) at 3 months, 82% (427 of 519) at 6 months, and 74% (375 of 506) at 12 months in those with complete questionnaire data. At age 2 years, eczema was present in 139 (23%) of 598 infants with outcome data collected in the emollient group and 150 (25%) of 612 infants in the control group (adjusted relative risk 0·95 [95% CI 0·78 to 1·16], p=0·61; adjusted risk difference –1·2% [–5·9 to 3·6]). Other eczema definitions supported the results of the primary analysis. Mean number of skin infections per child in year 1 was 0·23 (SD 0·68) in the emollient group versus 0·15 (0·46) in the control group; adjusted incidence rate ratio 1·55 (95% CI 1·15 to 2·09). Interpretation: We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children and some evidence to suggest an increased risk of skin infections. Our study shows that families with eczema, asthma, or allergic rhinitis should not use daily emollients to try and prevent eczema in their newborn. Funding: National Institute for Health Research Health Technology Assessment.
AB - Background: Skin barrier dysfunction precedes eczema development. We tested whether daily use of emollient in the first year could prevent eczema in high-risk children. Methods: We did a multicentre, pragmatic, parallel-group, randomised controlled trial in 12 hospitals and four primary care sites across the UK. Families were approached via antenatal or postnatal services for recruitment of term infants (at least 37 weeks' gestation) at high risk of developing eczema (ie, at least one first-degree relative with parent-reported eczema, allergic rhinitis, or asthma, diagnosed by a doctor). Term newborns with a family history of atopic disease were randomly assigned (1:1) to application of emollient daily (either Diprobase cream or DoubleBase gel) for the first year plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). The randomisation schedule was created using computer-generated code (stratified by recruiting centre and number of first-degree relatives with atopic disease) and participants were assigned to groups using an internet-based randomisation system. The primary outcome was eczema at age 2 years (defined by UK working party criteria) with analysis as randomised regardless of adherence to allocation for participants with outcome data collected, and adjusting for stratification variables. This trial is registered with ISRCTN, ISRCTN21528841. Data collection for long-term follow-up is ongoing, but the trial is closed to recruitment. Findings: 1394 newborns were randomly assigned to study groups between Nov 19, 2014, and Nov 18, 2016; 693 were assigned to the emollient group and 701 to the control group. Adherence in the emollient group was 88% (466 of 532) at 3 months, 82% (427 of 519) at 6 months, and 74% (375 of 506) at 12 months in those with complete questionnaire data. At age 2 years, eczema was present in 139 (23%) of 598 infants with outcome data collected in the emollient group and 150 (25%) of 612 infants in the control group (adjusted relative risk 0·95 [95% CI 0·78 to 1·16], p=0·61; adjusted risk difference –1·2% [–5·9 to 3·6]). Other eczema definitions supported the results of the primary analysis. Mean number of skin infections per child in year 1 was 0·23 (SD 0·68) in the emollient group versus 0·15 (0·46) in the control group; adjusted incidence rate ratio 1·55 (95% CI 1·15 to 2·09). Interpretation: We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children and some evidence to suggest an increased risk of skin infections. Our study shows that families with eczema, asthma, or allergic rhinitis should not use daily emollients to try and prevent eczema in their newborn. Funding: National Institute for Health Research Health Technology Assessment.
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U2 - 10.1016/S0140-6736(19)32984-8
DO - 10.1016/S0140-6736(19)32984-8
M3 - Article
C2 - 32087126
AN - SCOPUS:85081671544
VL - 395
SP - 962
EP - 972
JO - The Lancet
JF - The Lancet
SN - 0140-6736
IS - 10228
ER -