Journal of Endocrinological Investigation

, Volume 38, Issue 12, pp 1265–1275 | Cite as

Vitamin D during pregnancy: why observational studies suggest deficiency and interventional studies show no improvement in clinical outcomes? A narrative review

  • S. N. Karras
  • P. Anagnostis
  • D. Naughton
  • C. Annweiler
  • A. Petroczi
  • D. G. Goulis


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.


Vitamin D Randomized controlled trial Hypovitaminosis D Pregnancy 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study formal consent is not required.


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Copyright information

© Italian Society of Endocrinology (SIE) 2015

Authors and Affiliations

  • S. N. Karras
    • 1
  • P. Anagnostis
    • 1
  • D. Naughton
    • 2
  • C. Annweiler
    • 3
    • 4
  • A. Petroczi
    • 2
  • D. G. Goulis
    • 1
  1. 1.Unit of Reproductive Endocrinology, First Department of Obstetrics and Gynecology, Medical SchoolAristotle University of ThessalonikiThessalonikiGreece
  2. 2.School of Life SciencesKingston UniversityKingston upon ThamesUK
  3. 3.Robarts Research InstituteThe University of Western OntarioLondonCanada
  4. 4.Department of Geriatric Medicine, UPRES EA 4638University Hospital AngersAngersFrance

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