Methods
Within the Maternal Vitamin D Osteoporosis Study (MAVIDOS), a
multicentre, double‐blind, randomised, placebo‐controlled trial, women
were randomised to receive cholecalciferol 1000 IU/day or matched
placebo, from 14 weeks’ gestation until delivery. The trial methods and
primary findings have been published.11, 12 Pregnant
women were invited to participate at their early pregnancy ultrasound
screening appointment. Eligible women were recruited and randomised at
14 weeks’ gestation (or as soon as possible before 17 weeks’ gestation
if recruited later) to either cholecalciferol 1000 IU/day or matched
placebo [Merck KGaA, Darmstadt, Germany)/Sharp Clinical Services
(previously DHP‐Bilcare), Crickhowell, UK], taken until delivery.
Inclusion criteria were women aged over 18 years, having a singleton
pregnancy with a gestational age <17 weeks based on last
menstrual period and ultrasound measurements, and serum 25(OH)D between
25 and 100nmol/l and calcium <2.75mmol/l. Due to an ethics
committee stipulation, only women with a baseline 25(OH)D between
25-100nmol/l were eligible to participate. Women were excluded if they
had known metabolic bone disease, renal stones, hyperparathyroidism or
hypercalciuria; were taking medication known to interfere with fetal
growth or more than 400 IU/day vitamin D supplementation, or if their
fetus had a major anomaly. All participants received standard antenatal
care, and could continue self‐administration of dietary supplements
containing up to 400 IU/day vitamin D.
The MAVIDOS trial was conducted at three UK study sites 2008-2014:
Southampton, Oxford and Sheffield, with a total of 965
births.11 Follow up for this study was restricted to
704 Southampton children (352 intervention group and 352 placebo
(Supplementary Figure 1)), who were assessed for eczema at ages 12
(n=636), 24 (n=611) and 48 (n=450) months. Case definition was based on
the UK Working Party diagnostic criteria for the definition on atopic
eczema,13 assessed by trained research nurses who
undertook a standardised questionnaire and examination. Itchy skin
condition in the past 12 months was a mandatory criterion in addition to
three of: onset age <2 years, history of eczema (flexural or
of cheeks and extensors in under 18 months), history of dry skin the
last year, and visible flexural eczema (or visible eczema of the cheeks
and extensors if under 18 months). A personal history of atopy was
omitted as a criterion given the young age of the infants, who were not
old enough to have developed clearly defined asthma or hay fever.
The trial was approved by the Southampton and South West Hampshire
Research Ethics Committee. MAVIDOS was registered prospectively
(International Standard Randomised Controlled Trial Registry: ISRCTN
82927713; European Clinical Trials Database: EudraCT 2007‐001716‐23).
Written informed consent was obtained from all parents.