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.