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Maternal antenatal vitamin D supplementation and offspring risk of atopic eczema in the first 4 years of life: evidence from a randomized controlled trial

Maternal antenatal vitamin D supplementation and offspring risk of atopic eczema in the first 4 years of life: evidence from a randomized controlled trial
Maternal antenatal vitamin D supplementation and offspring risk of atopic eczema in the first 4 years of life: evidence from a randomized controlled trial

Background: Evidence linking prenatal maternal vitamin D supplementation with the offspring’s risk of atopic eczema is inconsistent, with most data coming from observational studies. Objectives: To examine the influence of maternal cholecalciferol supplementation during pregnancy on the risk of atopic eczema in the offspring at ages 12, 24 and 48 months. Methods: Within the UK Maternal Vitamin D Osteoporosis Study (MAVIDOS) double-blind, randomized placebo-controlled trial, we examined the relationship of maternal vitamin D supplementation during pregnancy with offspring atopic eczema at ages 12, 24 and 48 months. In MAVIDOS, pregnant women were allocated to either cholecalciferol 1000 IU per day or matched placebo, taken from around 14 weeks’ gestation until delivery, with the primary outcome of neonatal whole-body bone mineral content. The prevalence of atopic eczema in the offspring was ascertained at ages 12 (n = 635), 24 (n = 610) and 48 (n = 449) months, based on the UK Working Party criteria for the definition of atopic dermatitis. The trial was registered with ISRCTN (82927713) and EudraCT (2007-001716-23). Results: The characteristics of mothers and offspring were similar between the intervention and placebo groups, apart from longer breastfeeding duration in the intervention group. Adjusting for breastfeeding duration, offspring of mothers who received cholecalciferol 1000 IU daily had a lower odds ratio (OR) of atopic eczema at age 12 months [OR 0·55, 95% confidence interval (CI) 0·32–0·97, P = 0·04]; this effect weakened and was not statistically significant at ages 24 months (OR 0·76, 95% CI 0·47–1·23) or 48 months (OR 0·75, 95% CI 0·37–1·52). The statistical interaction of intervention and breastfeeding duration in relation to eczema at age 12 months was not significant (P = 0·41), but stratification showed reduced infantile eczema risk in the intervention group for infants breastfed for ≥ 1 month (OR 0·48, 95% CI 0·24–0·94, P = 0·03) but not in those breastfed for < 1 month (OR 0·80, 95% CI 0·29–2·17, P = 0·66). Conclusions: Our data provide the first randomized controlled trial evidence of a protective effect of antenatal cholecalciferol supplementation on the risk of infantile atopic eczema, with the effect potentially being via increased breast milk cholecalciferol levels. The findings support a developmental influence on atopic eczema, and point to a potentially modifiable perinatal influence on atopic eczema. What is already known about this topic? There are currently no antenatal interventions proven to reduce the incidence of infantile atopic eczema in the general population. However, observational studies have led to speculation that antenatal vitamin D supplementation may be beneficial.

0007-0963
659-666
El-Heis, Sarah
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D'angelo, Stefania
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Curtis, Elizabeth
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Healy, Eugene
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Moon, Rebecca
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Crozier, Sarah
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Inskip, Hazel
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Cooper, Cyrus
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Harvey, Nicholas
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Godfrey, Keith
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MAVIDOS Trial Group
El-Heis, Sarah
6d7d2e03-3d63-4510-8b7e-fcbe4653db13
D'angelo, Stefania
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Curtis, Elizabeth
12aba0c3-1e9e-49ef-a7e9-3247e649cdd6
Healy, Eugene
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Moon, Rebecca
954fb3ed-9934-4649-886d-f65944985a6b
Crozier, Sarah
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Inskip, Hazel
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Cooper, Cyrus
e05f5612-b493-4273-9b71-9e0ce32bdad6
Harvey, Nicholas
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Godfrey, Keith
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El-Heis, Sarah, D'angelo, Stefania, Curtis, Elizabeth, Healy, Eugene, Moon, Rebecca, Crozier, Sarah, Inskip, Hazel, Cooper, Cyrus, Harvey, Nicholas and Godfrey, Keith , MAVIDOS Trial Group (2022) Maternal antenatal vitamin D supplementation and offspring risk of atopic eczema in the first 4 years of life: evidence from a randomized controlled trial. British Journal of Dermatology, 187 (5), 659-666. (doi:10.1111/bjd.21721).

Record type: Article

Abstract

Background: Evidence linking prenatal maternal vitamin D supplementation with the offspring’s risk of atopic eczema is inconsistent, with most data coming from observational studies. Objectives: To examine the influence of maternal cholecalciferol supplementation during pregnancy on the risk of atopic eczema in the offspring at ages 12, 24 and 48 months. Methods: Within the UK Maternal Vitamin D Osteoporosis Study (MAVIDOS) double-blind, randomized placebo-controlled trial, we examined the relationship of maternal vitamin D supplementation during pregnancy with offspring atopic eczema at ages 12, 24 and 48 months. In MAVIDOS, pregnant women were allocated to either cholecalciferol 1000 IU per day or matched placebo, taken from around 14 weeks’ gestation until delivery, with the primary outcome of neonatal whole-body bone mineral content. The prevalence of atopic eczema in the offspring was ascertained at ages 12 (n = 635), 24 (n = 610) and 48 (n = 449) months, based on the UK Working Party criteria for the definition of atopic dermatitis. The trial was registered with ISRCTN (82927713) and EudraCT (2007-001716-23). Results: The characteristics of mothers and offspring were similar between the intervention and placebo groups, apart from longer breastfeeding duration in the intervention group. Adjusting for breastfeeding duration, offspring of mothers who received cholecalciferol 1000 IU daily had a lower odds ratio (OR) of atopic eczema at age 12 months [OR 0·55, 95% confidence interval (CI) 0·32–0·97, P = 0·04]; this effect weakened and was not statistically significant at ages 24 months (OR 0·76, 95% CI 0·47–1·23) or 48 months (OR 0·75, 95% CI 0·37–1·52). The statistical interaction of intervention and breastfeeding duration in relation to eczema at age 12 months was not significant (P = 0·41), but stratification showed reduced infantile eczema risk in the intervention group for infants breastfed for ≥ 1 month (OR 0·48, 95% CI 0·24–0·94, P = 0·03) but not in those breastfed for < 1 month (OR 0·80, 95% CI 0·29–2·17, P = 0·66). Conclusions: Our data provide the first randomized controlled trial evidence of a protective effect of antenatal cholecalciferol supplementation on the risk of infantile atopic eczema, with the effect potentially being via increased breast milk cholecalciferol levels. The findings support a developmental influence on atopic eczema, and point to a potentially modifiable perinatal influence on atopic eczema. What is already known about this topic? There are currently no antenatal interventions proven to reduce the incidence of infantile atopic eczema in the general population. However, observational studies have led to speculation that antenatal vitamin D supplementation may be beneficial.

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e-pub ahead of print date: 28 June 2022
Published date: November 2022
Additional Information: Funding Information: This work was supported by grants from Arthritis Research UK (17702), Medical Research Council (4050502589), Bupa Foundation, National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, and NIHR Musculoskeletal Biomedical Research Unit, University of Oxford. Inez Schoenmakers and Ann Prentice (MAVIDOS Trial Group) were funded by the MRC (programme code U105960371). K.M.G. is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (Senior Investigator; NF-SI-0515-10042), NIHR Southampton 1000DaysPlus Global Nutrition Research Group (17/63/154), NIHR Southampton Biomedical Research Centre (IS-BRC-1215-20004), the European Union (Erasmus+ Programme ImpENSA 598488-EPP-1-2018-1-DE-EPPKA2-CBHE-JP) and the British Heart Foundation (RG/15/17/3174). The work leading to these results was supported by the European Union’s Seventh Framework Programme (FP7/2007-2013), projects EarlyNutrition and ODIN under grant agreements numbers 289346 and 613977, and by the BBSRC (HDHL-Biomarkers, BB/P028179/1), as part of the ALPHABET project, supported by an award made through the ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL), Horizon 2020 grant agreement number 696295. We are extremely grateful to Merck GmbH for the kind provision of the Vigantoletten supplement. Merck GmbH had no role in the trial execution, data collection, analysis or manuscript preparation. Funding Information: This work was supported by grants from Arthritis Research UK (17702), Medical Research Council (4050502589), Bupa Foundation, National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, and NIHR Musculoskeletal Biomedical Research Unit, University of Oxford. Inez Schoenmakers and Ann Prentice (MAVIDOS Trial Group) were funded by the MRC (programme code U105960371). K.M.G. is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (Senior Investigator; NF‐SI‐0515‐10042), NIHR Southampton 1000DaysPlus Global Nutrition Research Group (17/63/154), NIHR Southampton Biomedical Research Centre (IS‐BRC‐1215‐20004), the European Union (Erasmus+ Programme ImpENSA 598488‐EPP‐1‐2018‐1‐DE‐EPPKA2‐CBHE‐JP) and the British Heart Foundation (RG/15/17/3174). The work leading to these results was supported by the European Union’s Seventh Framework Programme (FP7/2007‐2013), projects EarlyNutrition and ODIN under grant agreements numbers 289346 and 613977, and by the BBSRC (HDHL‐Biomarkers, BB/P028179/1), as part of the ALPHABET project, supported by an award made through the ERA‐Net on Biomarkers for Nutrition and Health (ERA HDHL), Horizon 2020 grant agreement number 696295. We are extremely grateful to Merck GmbH for the kind provision of the Vigantoletten supplement. Merck GmbH had no role in the trial execution, data collection, analysis or manuscript preparation. Publisher Copyright: © 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.

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Local EPrints ID: 468270
URI: http://eprints.soton.ac.uk/id/eprint/468270
ISSN: 0007-0963
PURE UUID: 5c698b44-aa52-4079-bd90-1d10f16d89b6
ORCID for Sarah El-Heis: ORCID iD orcid.org/0000-0003-4277-7187
ORCID for Stefania D'angelo: ORCID iD orcid.org/0000-0002-7267-1837
ORCID for Elizabeth Curtis: ORCID iD orcid.org/0000-0002-5147-0550
ORCID for Sarah Crozier: ORCID iD orcid.org/0000-0002-9524-1127
ORCID for Hazel Inskip: ORCID iD orcid.org/0000-0001-8897-1749
ORCID for Cyrus Cooper: ORCID iD orcid.org/0000-0003-3510-0709
ORCID for Nicholas Harvey: ORCID iD orcid.org/0000-0002-8194-2512
ORCID for Keith Godfrey: ORCID iD orcid.org/0000-0002-4643-0618

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Date deposited: 09 Aug 2022 16:38
Last modified: 18 Mar 2024 03:38

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Contributors

Author: Sarah El-Heis ORCID iD
Author: Stefania D'angelo ORCID iD
Author: Eugene Healy
Author: Rebecca Moon
Author: Sarah Crozier ORCID iD
Author: Hazel Inskip ORCID iD
Author: Cyrus Cooper ORCID iD
Author: Nicholas Harvey ORCID iD
Author: Keith Godfrey ORCID iD
Corporate Author: MAVIDOS Trial Group

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