Introduction
Atopic eczema is a chronic inflammatory condition that can substantially
impact affected individuals, their families and the healthcare system.
The estimated prevalence of atopic eczema is 9.5% in children under age
4 years1, with a rise observed globally over recent
decades.2 There is increasing evidence that atopic
eczema partly originates in utero , where genetic susceptibility
and environmental exposures can affect the developing immune system and
alter the skin barrier. Understanding the role of early life
environmental exposures, such as maternal micronutrient status, may
identify potential preventative strategies.
Inadequate gestational vitamin D status is highly prevalent in many
populations. Supplementation is recommended to prevent deficiency.3 Maternal serum levels of 25(OH)D correlate with
offspring levels at birth4 and maternal vitamin D
status has been extensively linked to offspring risk of atopic eczema
and other atopic diseases, but with inconsistent evidence. One
intervention study with high dose maternal antenatal vitamin D
supplementation (2400 or 4000 IU) daily compared with placebo
demonstrated a 25% reduction in the offspring’s risk of ‘asthma’ at age
0-3 years.5 Conversely, in an observational study,
children born to mothers with a late pregnancy serum 25(OH)D
>75nmol/L had a higher risk of infantile eczema at age 9
months and childhood asthma age 9 years compared to children whose
mothers had a concentration of <30 nmol/l.6A trial in women at high risk of having offspring with asthma reported
no significant difference in rates of offspring eczema at age 3 years
following maternal antenatal supplementation with high (4400 IU/d) vs
low (400 IU/d) dose vitamin D.7 Maternal vitamin D
supplementation during pregnancy (2000 IU/d from 27 weeks gestation)
increased vitamin D activity in breast milk,8 raising
the possibility that benefits of gestational supplementation may arise
from higher infant intakes after birth in supplemented mothers who
breastfeed their infant.9
In this study, our aim was to examine the hypothesis that maternal
supplementation with 1000 IU/day cholecalciferol during pregnancy would
decrease the risk of atopic eczema in the offspring in the setting of a
randomised controlled trial. We also sought to determine whether any
associations varied by breastfeeding status and whether genetic variants
previously associated with serum 25(OH)D
concentrations10 were related to offspring atopic
eczema.