We should not write off vitamin D supplementation — especially in pregnancy
Testing all pregnant women for insufficient vitamin D levels is expensive, but two systematic reviews suggest that providing them all with vitamin D supplements could reduce risk of pre-eclampsia, gestational diabetes and low birth weight.
Vitamin D supplements are available in every community pharmacy and pregnant women are recommended to consider taking them. However, the supplements are often described as ‘useless’ or a ‘waste of money’ and their benefits are still subject to debate.
There is a case for their use; surveys suggest that many people in the UK have low circulating levels of vitamin D and are at risk of vitamin D deficiency. The National Diet and Nutrition Survey found that, between 2008 and 2012, 21.7% of women in the UK had low vitamin D levels (measured as serum/plasma 25-hydroxyvitamin D concentration less than 25 nanomol/L),. And, while there are no nationally representative data for women who are pregnant or breastfeeding, UK-based cohort studies suggest that 25–29% of people in this group have low vitamin D levels in the summer, rising to 49–76% in the winter,,.
Testing all mothers for vitamin D deficiency may be expensive, compared with giving them all vitamin D supplements
A low level of vitamin D in pregnant women has been associated with higher blood pressures (pre-eclampsia), higher rates of gestational diabetes and lower birth weight babies. However, testing for vitamin D deficiency is expensive and carrying out these tests across all mothers may not be cost-effective compared with offering universal supplementation.
The World Health Organization does not currently recommend provision of vitamin D supplements for pregnancy as part of routine care. The Royal College of Gynaecologists (RCOG) recommends that all pregnant women should take 400 international units (IU) — equating to 10 micrograms — of vitamin D daily, while UK health guidelines recommend that pregnant women consider taking this amount.
In the UK, these supplements are available for free only to pregnant women from low-income backgrounds, through the Healthy Start programme. But the debate continues over whether all pregnant women should take them, and if so, how much vitamin D should be supplemented.
Reviewing the evidence
In 2019, Cochrane published two systematic reviews that sought to settle this. In July 2019, one review reported on 30 trials involving a total of 7,033 women, in which pregnant women received supplements of vitamin D versus placebo or no intervention.
Supplementation with vitamin D alone appeared to reduce the risk of pre-eclampsia, compared with placebo or no intervention (risk ratio [RR] 0.48, 95% confidence interval [CI] 0.30–0.79) in four trials involving 499 women. The authors observed a reduction in gestational diabetes (RR 0.51, 95% CI 0.27–0.97) in four trials involving 446 women, and they found a reduction in the risk of women having a baby with low birth weight (less than 2,500g; RR 0.55, 95% CI 0.35–0.87) in five trials involving 697 women. The Cochrane authors ranked these findings as moderate-certainty evidence using criteria from the GRADE (grading of recommendations, assessment, development and evaluations) framework. Low-certainty evidence was found in relation to severe postpartum haemorrhage in a single trial involving 1,134 women (RR 0.68, 95% CI 0.51–0.91).
Supplementing with 200 IU of vitamin D daily during pregnancy can confer benefits relating to high blood pressure, gestational diabetes and low birth weight
In a follow-up review, published in October 2019, the authors examined trials of different regimens of vitamin D supplementation. They looked at the effects of using more or less than 600 IU, and more or less than 4000 IU supplementation daily. Across the 15 trials reviewed (4,763 women were included), supplementation with 4,000 IU or more made no difference to the risks of pre-eclampsia, gestational diabetes or low birth weight when compared with doses lower than this. Among these lower doses of supplementation, it was observed that those given more than 600 IU daily had a reduced risk of gestational diabetes (RR 0.54, 95% CI 0.34–0.86; five trials involving 1,846 participants). This was graded as moderate-certainty evidence.
These analyses suggest that taking 200 IU of vitamin D daily during pregnancy may confer benefits in relation to high blood pressure, gestational diabetes, low birth weight and possibly severe post-partum haemorrhage, although more data are required to support this effect. Supplementation with more than 200 IU has little effect on these outcomes, with the exception of gestational diabetes, in which a dose of 600 IU may confer benefits.
Understanding the mother–placenta–foetus relationship
Large cohort studies conducted in Ireland and Denmark found women with lower serum vitamin D levels displayed higher rates of eclampsia,. These Cochrane reviews support the idea that vitamin D supplementation can promote a healthy and effective link between the infant, placenta and uterus. From the earliest stages of the trophoblast (the outer layer of the fertilised egg) implanting into the lining of the uterus, vitamin D is thought to optimise the development of blood vessels, and could ensure more efficient transfer of nutrients to the foetus and lower rates of pregnancy-induced hypertension or eclampsia,.
It has been proposed that sufficient placental tissue levels of vitamin D are more important to pregnancy outcomes than serum levels; the placenta can carry out the second hydroxylation of vitamin D to make 1,25-dihydroxyvitamin D (the active form of vitamin D), just as the kidney does. It is also thought that placental vitamin D metabolism has a role in modulating the mother’s circulating vitamin D metabolites during pregnancy, so it is worth taking note of low serum or plasma levels, which may have clinical relevance.
Other benefits of vitamin D
There may also be other benefits of vitamin D to explore in the weeks after birth, such as the relationship between postpartum anxiety/depression and low prenatal maternal vitamin D levels. A systematic review suggests this association, but it was limited by variability in association measures, time, and scales of depression and anxiety assessments across the studies. No trial has yet evaluated supplementation of vitamin D as a possible preventative treatment for these conditions.
Adding to the body of evidence
According to Cochrane, there are currently six ongoing trials that, once published, will add to the existing body of evidence,. More data will be required to ascertain when to supplement with vitamin D, with how much, and for how long, to prevent all potential complications of vitamin D insufficiency or deficiency.
Consumers are enthusiastic about taking over-the-counter supplements, but they may not be adequately informed about them
In the meantime, research by the Food Standards Agency suggests that, in the UK, there is public enthusiasm for taking supplements purchased over the counter, but consumers may not be adequately informed about them. We believe that UK professionals should follow the RCOG’s lead and recommend 400 IU vitamin D daily for pregnant women, as well as improved communication with vulnerable mothers, perhaps by involving midwives or community pharmacists, which will also be a powerful measure.
Colin Michie, associate dean of academic affairs, American University of the Caribbean School of Medicine, St Maarten, Lesser Antilles; fellow, Royal College of Paediatrics and Child Health; fellow, Royal Society for Public Health
Sucharat Tayarachakul, medical student, American University of the Caribbean School of Medicine, St Maarten, Lesser Antilles
Correspondence to: firstname.lastname@example.org
Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2019.20207349
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