title: Vitamin D during pregnancy: why observational studies suggest deficiency and interventional studies show no improvement in clinical outcomes? A narrative review.
abstract: A considerable number of studies have examined vitamin D status during pregnancy. Although data from observational studies denote vitamin D hypovitaminosis (deficiency or insufficiency) during pregnancy is associated with a plethora of adverse maternal and neonatal outcomes, data from interventional (supplementation) trials fail to reveal a significant impact on maternal and offspring health. The aim of this narrative review was to critically appraise the methodology of the most representative published randomized controlled trials in an attempt to explain the difference between observational and supplementation results. We found that this difference could be attributed to a variety of factors, namely: (i) study design (lack of a specific outcome in conjunction with timing of supplementation, enrolment of participants with heterogeneous vitamin D status); (ii) pitfalls in the interpretation of vitamin D equilibrium (lack of determination of plasma half-life); (iii) supplementation regimen (administration of a wide range of regimens, in terms of dose, bolus and form); (iv) geographical characteristics (vitamin D needs could vary significantly within a country, particularly in areas with a wide range of latitude gradient); (v) adaptations of vitamin D metabolism during pregnancy (vitamin D and calcium equilibrium are changed during pregnancy compared with the non-pregnant state) and (vi) supplementation of populations with low baseline 25(OH)D values would likely manifest beneficial effects. All these parameters should be taken into consideration in the design of future vitamin D supplementation trials.
authors.affiliation: Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece. karraspiros@yahoo.gr.
authors.forename: S N
authors.initials: SN
authors.lastname: Karras
authors.affiliation: Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Anagnostis
authors.affiliation: School of Life Sciences, Kingston University, Kingston upon Thames, London, UK.
authors.forename: D
authors.initials: D
authors.lastname: Naughton
authors.affiliation: Robarts Research Institute, The University of Western Ontario, London, ON, Canada.|Department of Geriatric Medicine, UPRES EA 4638, University Hospital Angers, Angers, France.
authors.forename: C
authors.initials: C
authors.lastname: Annweiler
authors.affiliation: School of Life Sciences, Kingston University, Kingston upon Thames, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Petroczi
authors.affiliation: Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: D G
authors.initials: DG
authors.lastname: Goulis
mesh_terms: D005260:Female; D006801:Humans; D064887:Observational Studies as Topic; D017063:Outcome Assessment, Health Care; D011247:Pregnancy; D011248:Pregnancy Complications / Q000188:drug therapy*; D016032:Randomized Controlled Trials as Topic; D014807:Vitamin D / Q000097:blood / Q000627:therapeutic use*; D014808:Vitamin D Deficiency / Q000188:drug therapy*
chemical_list: D014807:Vitamin D
keywords: Hypovitaminosis D; Pregnancy; Randomized controlled trial; Vitamin D