Tag Archives: Vitamins

Computer Interpretation of Foetal Heart Rates Does Not Help Distinguishing Babies That Need a Caesarean from Those That Do Not

In an earlier life I was involved in obtaining treatment costs for a pilot trial of computerised foetal heart monitoring versus standard foetal heart monitoring (CTG). The full trial, funded by NIHR, has now been published in the Lancet,[1] featuring Sara Kenyon from our CLAHRC WM theme 1. With over 46,000 participants the trial found no difference in a composite measure of foetal outcome or intervention rates. Perinatal mortality was only 3 per 10,000 women across both arms and the incidence of hypoxic encephalopathy was less than 1 per 1,000. Of course, the possibility of an educational effect from the computer decision support (‘contamination’) may have reduced the observed effect, but this could only be tested by a cluster trial. However, such a design would create its own set of problems, such as loss of precision and bias through interaction between method used and baseline risk across interventions and control sites. Also, the control group was not care as usual, but the visual display IT system shorn of its decision support (artificial intelligence) module.[2] Some support for the idea that control condition affected care in a positive direction, making any marginal effect of decision support hard to detect, comes from the low event rate across both study arms. Meanwhile, the lower than expected baseline event rates mean that any improvement in outcome will be hard to detect in future studies. So here is another topic that, like vitamin D given routinely to elderly people,[3] now sits below the “horizon of science” – the combination of low event rates and low plausible effect sizes mean that we can move on from this subject – at least in a high-income context. If you want to use the computerised method, and its costs are immaterial, then there is no reason not to; economics aside there appear to be no trade-offs here, since both benefits and harms were null.

— Richard Lilford, CLAHRC WM Director

References:

  1. The INFANT Collaborative Group. Computerised interpretation of fetal heart rate during labour (INFANT): a randomised controlled trial. Lancet. 2017.
  2. Keith R. The INFANT study – a flawed design foreseen. Lancet. 2017.
  3. Lilford RJ. Effects of Vitamin D Supplements. NIHR CLAHRC West Midlands News Blog. 24 March 2017.

Effects of Vitamin D Supplements

Bolland and colleagues have written a lovely summary of the evidence on the effects of vitamin D supplements, with or without calcium, on health.[1] Their careful and comprehensive systematic overview based on a large sample, and providing narrow confidence limits, finds that there is no evidence that vitamin D, with or without calcium, reduces the risk of fractures in elderly people with no known bone disease. It is, as expected, efficacious in people with established osteomalacia. Systematic reviews of lower quality or based on per protocol analyses, tend to find the more optimistic results, but the data, taken in the round, yield a null result. The reviewers find that additional research is unlikely to further clarify the issue, as an effect of more than a 10% reduction in fracture has been ‘excluded’ by the existing studies. From a Bayesian perspective, further data are unlikely to have much effect on credible limits. The studies do not find any evidence that calcium plus vitamin D have either harmful or beneficial effects on the other (non-skeletal) outcomes, such as cancer or heart disease. Perhaps this is an example of the horizon of science; science cannot prove a null result, merely exclude a positive or negative effect beyond certain limits. We will never know everything, but let’s just forget about the use of vitamin D and calcium as prophylaxis in healthy people as any benefit must be nugatory – less than 10% relative risk reduction, which equates to a very small absolute reduction.

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Bolland MJ, Leung W, Tai V, et al. Calcium intake and risk of fracture: systematic review. BMJ. 2015; 350: h4580.

 

Golden Rice Controversy

Genetically modified rice – called ‘golden rice’ – can increase yields and, since it produces beta-carotene, can prevent the sequelae of vitamin A deficiency that is common in those with a predominantly rice-based diet. For an interesting article on the controversy over use of this GM crop in Bangladesh, and its potential costs-benefit, please read Uttam Deb’s article from the Copenhagen Consensus Center.[1]

— Richard Lilford, CLAHRC WM Director

Reference:

  1. Deb U. Returns to Golden Rice Research in Bangladesh: An Ex-ante Analysis. Bangladesh Priorities, Copenhagen Consensus Center, 2016.

 

Vitamin A Supplementation at Birth in Populations with High Mortality and Putative Low Levels of Vitamin A

Three trials have recently reported on this topic from Ghana,[1] Tanzania,[2] and India [3] with a total of 100,038 participants. The African trials are statistically null with point estimates showing increased risk in the intervention group, while the Indian trial was borderline positive (at the 0.05 significance level). Taken in the round, results are null. Vitamin A supplementation also yields null results in separate studies of babies 1–5 months of age, but it is effective in older babies. The CLAHRC WM Director surmises that vitamin A only becomes effective once the child has reached an age where it has lost the passive immunity it acquired from its mother while it was in the womb.

— Richard Lilford, CLAHRC WM Director

References:

  1. Edmond KM, Newton S, Shannon C, et al. Efficacy of early neonatal vitamin A supplementation on mortality during infancy in Ghana (Neovita): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 385: 1315-23.
  2. Masanja H, Smith ER, Muhihi A, et al. Effect of neonatal vitamin A supplementation on mortality in infants in Tanzania (Neovita): a randomised, double-blind, placebo-controlled trial. Lancet. 2015; 385: 1324-32.
  3. Mazumder S, Taneja S, Bhatia K, et al. Efficacy of early neonatal supplementation with vitamin A to reduce mortality in infancy in Haryana, India (Neovita): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 385: 1333-42.