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Infant Respiratory Tract Infections or Wheeze and Maternal Vitamin D in Pregnancy: A Systematic Review

Christensen, Nikolas MD; Søndergaard, Jens MD, PhD; Fisker, Niels MD, PhD; Christesen, Henrik Thybo MD, PhD

The Pediatric Infectious Disease Journal: April 2017 - Volume 36 - Issue 4 - p 384–391
doi: 10.1097/INF.0000000000001452
Original Studies

Backgrounds: Respiratory tract infections (RTIs) are a common cause of morbidity and mortality in young children and can be associated with wheeze. Vitamin D can have a protective role against RTI.

Materials and Methods: A systematic search of PubMed, Embase and the Cochrane library was performed. Titles and abstracts were evaluated, and selected articles were reviewed by 2 authors. We included randomized controlled trials (RCTs) investigating the effect of vitamin D supplementation during pregnancy on RTIs or wheeze in children of 5 years of age or younger. Observational studies on the association between serum 25-hydroxyvitamin D during pregnancy, or at birth, and RTIs and/or wheeze were included. The protocol was registered on PROSPERO (Registration number: CRD42015019183).

Results: Of 4 RCTs, 1 showed a protective effect of a high daily dose (2000 IU) of vitamin D during pregnancy on offspring RTI doctor visits (P = 0.004; the RCT also included 800 IU/d supplement to the infants until 6 months). Meta-analysis of 3 RCTs showed a reduced relative risk for offspring wheeze when mothers were supplemented with vitamin D during pregnancy [relative risk: 0.81 (95% confidence interval: 0.68–0.97), P = 0.025]. In 3 of 4 strong-quality, and 5 of 10 moderate-quality observational studies, an inverse association between pregnancy and cord 25-hydroxyvitamin D and subsequent wheeze and/or RTI was seen.

Conclusion: Growing evidence supports a preventive role of vitamin D during pregnancy on offspring wheeze and/or RTI. Recommendations in future intervention studies may need to exceed current recommendations of vitamin D supplementation during pregnancy to show benefit against childhood wheeze or infections.

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From the *Hans Christian Andersen Children’s Hospital, Odense University Hospital, Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, and Research Unit of General Practice, Department of Public Health, University of Southern Denmark, Odense, Denmark.

Accepted for publication September 11, 2016.

This study was supported by Neomune from the Strategic Research Council, Region of Southern Denmark, University of Southern Denmark, Hans Christian Andersen Children’s Hospital, A.P. Møller Foundation and Arla Foods Ingredients.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (

Address for correspondence: Henrik Thybo Christesen, MD, PhD, Hans Christian Andersen Children’s Hospital, Odense University Hospital, Odense, Denmark. E-mail:

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