Effects of Pre-Natal Vitamin D Supplementation with Partial Correction of Vitamin D Deficiency on Early Life Healthcare Utilisation: A Randomised Controlled Trial

December Effects of Pre-Natal Vitamin D Supplementation with Partial Correction of Vitamin D Deficiency on Early Life Healthcare Utilisation: A Randomised Controlled Trial Megan Griffiths 0 1 Stephen Goldring 0 1 Chris Griffiths 0 1 Seif O. Shaheen 0 1 Adrian Martineau 0 1 Louise Cross 0 1 Stephen Robinson 0 1 John O. Warner 0 1 Angela Devine 0 1 Robert J. Boyle 0 1 0 1 Department of Paediatrics, Imperial College London , London , United Kingdom , 2 Centre for Primary Care and Public Health, Blizard Institute, Queen Mary University of London , London , United Kingdom , 3 Department of Endocrinology, Imperial College London , London , United Kingdom 1 Editor: Cheryl S. Rosenfeld, University of Missouri , UNITED STATES Some observational studies have suggested that higher prenatal Vitamin D intake may be associated with improved health outcomes in childhood. However there have been mixed results in this area with some negative studies, especially for effects on atopic and respiratory outcomes. We examined the effect of prenatal Vitamin D on healthcare utilisation in the first three years of life. - OPEN ACCESS Data Availability Statement: All relevant data are included in the paper and its Supporting Information files. Funding: Funded by Asthma UK grant number 09/ 36. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Background Methods In an ethnically stratified randomised controlled trial conducted at St Mary’s Hospital Lon don, 180 women at 27 weeks gestation were allocated to no Vitamin D, 800 IU ergocalciferol daily until delivery, or a single oral bolus of 200,000 IU cholecalciferol. Participants were randomised in blocks of 15 using computer-generated numbers and investigators were blinded to group assignment. Supplementation increased maternal and cord blood 25 (OH) vitamin D concentrations, but levels remained lower than current recommendations. Primary health economic outcome was overall cost of unscheduled healthcare utilisation in the first three years of life as documented in the child’s electronic health record. Secondary outcomes included cost attributable to: primary and secondary healthcare visits, respiratory and atopic complaints, cost in years 1, 2 and 3 of life and cost and frequency of prescribed medication. All costs were calculated as pounds sterling. Differences between groups were analysed using unpaired t-test or Mann-Whitney U test, and analysis of variance for adjusted analyses. Results We assessed 99/180 (55%) complete electronic health records, control (n = 31), daily (n = 36) and bolus (n = 32). We found no difference in total healthcare utilisation costs between the control and daily (mean difference in costs in pounds sterling 1.02, 95%CI -1.60, 1.65; adjusted 1.07, 95%CI -1.62, 1.86) or control and bolus groups (mean difference -1.58, 95% CI -2.63, 1.06; adjusted –1.40, 95%CI -2.45, 1.24). There were no adverse effects of supplementation reported during the trial. Conclusions We found no evidence that prenatal vitamin D supplementation from 27 weeks gestation to delivery, at doses which failed to completely correct maternal vitamin D deficiency, influence overall healthcare utilisation in children in the first 3 years. Trial Registration Controlled-Trials.com ISRCTN68645785 Introduction Hypovitaminosis D is an increasing problem in many regions, where sedentary, indoor lifestyles are thought to be a major contributing factor [ 1 ]. There is mixed observational evidence with regards to the effect of pre-natal 25(OH) vitamin D status on child health outcomes. Several studies have linked low vitamin D status to a number of resource intensive childhood health problems including allergy and infection [ 2–7 ], in addition to the well-established effects on bone metabolism. However, these links remain controversial with other studies reporting no association [ 8–11 ]. Allergy alone accounts for 6% of primary care consultations and 70,000 hospital admissions a year in the UK [ 12 ] and the average pre-school UK child contracts 6–8 upper respiratory tract infections (URTIs) annually. Vitamin D supplementation during critical periods of immune development may represent a safe [ 13 ] and relatively inexpensive public health intervention to reduce this burden. Thus far there has been a lack of randomised controlled trial evidence to definitively confirm or refute the relationship between prenatal vitamin D and childhood health outcomes found in observational studies. Data published in 2013 from this trial, looking primarily at respiratory outcomes, found no difference between treatment and control arms with regards to a primary outcome of wheeze [ 14 ]. In the United Kingdom, all children registered with a primary care practice have an electronic health record (e-HR). This is a contemporaneous re (...truncated)