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expert reaction to study looking at vitamin D in pregnancy and immune response tested in babies’ cord blood

A new study published in the Journal of Allergy and Clinical Immunology investigates whether taking vitamin D supplements in pregnancy can positively modify the immune system of  a newborn.

 

Prof. Martin Hewison, Professor of Molecular Endocrinology, University of Birmingham, and member of the Society for Endocrinology, said:

“The manuscript describes a study that is a spin-off from a major National Institutes of Health (NIH) randomised double blind placebo control trial to assess the effects of vitamin D supplementation in pregnancy – this was known as the VDAART trial.  That trial involved pregnant women whose children had a high risk of developing of asthma.  One of the distinguishing features of that trial was that the dose of supplementary vitamin D used was much higher than used in most other studies – 4,400 IU/day.  This was carried out to ensure that women receiving vitamin D achieved a clear difference in vitamin D ‘status’.  Importantly, no adverse effects were associated with this higher level of supplementation.  Also, the placebo in that trial was actually a lower dose of vitamin D supplementation (400 IU/day) – this was used because it is ethically wrong to not provide vitamin D supplements if a subject is found to have low vitamin D at the start of the trial.  It is notable that the placebo in the trial is the dose of vitamin D supplementation currently recommended by the UK Science Advisory Council on Nutrition (SACN) for supplementation in UK people!

“In the original report published for that trial, published in 20161 it was shown that supplementation with this higher dose of vitamin D significantly increased the vitamin D levels of the pregnant women. The placebo low dose had no effect. Also, in this 2016 paper this higher dose of vitamin D was associated with a 6.1% lower incidence of asthma and wheezing in children born to the pregnant women. This was not quite statistically significant.

“The current study investigates in more detail the effects of vitamin D supplementation in these pregnant women by defining immune cell function in cord blood (blood from the baby rather than mother) taken from a sub-set of the original trial participants.

“In summary this is a high quality sub-study of the largest and most comprehensive vitamin D supplementation in pregnancy trial.  The current report describes important effects of vitamin D supplementation in pregnant women on the immune ‘status’ of their children.  The authors are cautious in their conclusions, but their data demonstrate for the first time that vitamin D supplementation during pregnancy not only influences the pregnancy itself, but may have lasting impact on the immune ‘health’ of children, presumably through effects that occur during pregnancy. Thus, vitamin D supplementation during pregnancy may have importance beyond established adverse events in pregnancy such as preeclampsia and preterm birth – conversely vitamin D-deficiency during pregnancy may have a much wider range of detrimental effects that extend to the children.

“The current study does not assess the health of the children in question but instead demonstrates significant changes in specific immune cell populations that may impact on a wide range of health issues – in future studies it will be important to carry out longer term assessment of the children from these supplemented mothers to determine if the changes in immune cells influence the health of the children, particularly with infections and disorders such as asthma.

“The current study supports other recent studies of vitamin D supplementation in pregnancy that have shown effects on the children born to supplemented mothers2.

“This is a very comprehensive and interesting study.”

  1. JAMA. 2016 Jan 26;315(4):362-70. doi: 10.1001/jama.2015.18589. ‘Effect of Prenatal Supplementation With Vitamin D on Asthma or Recurrent Wheezing in Offspring by Age 3 Years: The VDAART Randomized Clinical Trial.’ Litonjua AA, Carey VJ, Laranjo N, Harshfield BJ, McElrath TF, O’Connor GT, Sandel M, Iverson RE Jr, Lee-Paritz A, Strunk RC, Bacharier LB, Macones GA, Zeiger RS, Schatz M, Hollis BW, Hornsby E, Hawrylowicz C, Wu AC, Weiss ST.
  1. Notably ‘Gestational vitamin D deficiency and autism-related traits: the Generation R Study.’ Vinkhuyzen AA, Eyles DW, Burne TH, Blanken LM, Kruithof CJ, Verhulst F, Jaddoe VW, Tiemeier H, McGrath JJ. Mol Psychiatry. 2016 Nov 29. doi: 10.1038/mp.2016.213. [Epub ahead of print].

 

Dr Sheena Cruickshank, Senior Lecturer in Immunology, University of Manchester, said:

“Vitamin D may have multiple healthy effects for the mother including helping maintain strong healthy bones which can be otherwise weakened by pregnancy.  This study is interesting but very preliminary.  It’s a small group size and differences between the cord blood samples in low and high dose vitamin D supplementation were modest and the results were very variable, making it very hard to draw a conclusion about differences in cytokine responses between groups.

“This study did not investigate prevalence of asthma in the children of the vitamin D treated mothers, thus it is too preliminary to claim whether it may impact on asthma development.

“Asthma, like many other immune mediated diseases is a complex, multifactorial disease and many things will factor in whether someone develops the disease or not – a combination of genetic predisposition with a strong influence from environmental drivers such as exposure to microbes and pollutants.”

 

* ‘Vitamin D supplementation during pregnancy: Effect on the neonatal immune system in a randomized controlled trial’ by Eve Hornsby et al. will be published in the Journal of Allergy and Clinical Immunology on Friday 26 May 2017.

 

Declared interests

Prof. Martin Hewison: “I was a member of the Data and Safety Monitoring Committee for the VDAART Trial for two years.  I have no conflict of interest with the VDAART trial or the sub-study reported in the current paper.”

Dr Sheena Cruickshank: “I have no conflicts of interest.”

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