Research highlights – 27 May 2011

Research questions“Research highlights” is a weekly round-up of research papers appearing in the print BMJ. We start off with this week’s research questions, before providing more detail on some individual research papers and accompanying articles.

Nutritional supplements and pre-eclampsia
As a general medical journal the BMJ has published what might seem a surprisingly high number of rather specialised papers on the risks, natural history, and possible causes of pre-eclampsia. But given the condition’s high burden of disease, we’re pleased to keep receiving such submissions. Now Felipe Vadillo-Ortega and colleagues’ three arm randomised controlled trial asks whether nutritional supplements with potential to improve placental haemodynamics might prevent pre-eclampsia in women at high risk. They randomised pregnant women in Mexico to receive food bars containing either the amino acid L-arginine plus antioxidant vitamins, those vitamins alone, or placebo. The incidence of pre-eclampsia was significantly lower (P<0.001) in women randomised to L-arginine plus antioxidant vitamins compared with placebo (absolute risk reduction 0.17, 95% confidence interval 0.12 to 0.21).

Editorialists Liam Smeeth and David Williams point out that pre-eclampsia accounts for more than a quarter of maternal deaths in Latin America and agree on the need for a low cost intervention. They discuss the pros and cons of this new trial, and conclude that its findings are important. But it’s crucial, they say, that no more trials should be done until we have a rigorous systematic review of the numerous inconsistent strands of evidence relating to L-arginine and its possible effects on pre-eclampsia.

Performance of HPV test used in screening for cervical cancer
The NHS screening programme has just started to use testing for human papillomavirus (HPV) DNA to triage women with borderline or low grade cervical abnormalities and reduce the need for unnecessary interventions and anxiety. As of April 2011, this approach is being rolled out in England. But what is the best way to test for HPV DNA? To date, use of these tests has proved to be more sensitive than cervical cytology but not very specific, yielding a lot of false positives.

So Matejka Rebolj and colleagues did a systematic review, examining four randomised controlled trials of primary cervical screening using the widely used hybrid capture 2 test for HPV, to determine the test cutoffs that will optimise sensitivity, specificity, and positive predictive value. Again, this is a rather specialised paper, but the BMJ published much of the earlier work on HPV triage in cervical screening and we thought this paper was an important new brick in that wall. Its detailed findings will mostly interest those who design cervical screening programmes and run testing. But the overall message, that cervical screening is getting more reliable and effective and less invasive and unpleasant for women, should interest many BMJ readers.

Dietary calcium and risk of fracture
Might increasing dietary intake of calcium help to protect older bones against osteoporosis and fractures? Previous evidence has led to uncertain conclusions, as reflected by the wide variety of daily calcium recommendations for individuals older than 50 (700 mg in the UK, 800 mg in Scandinavia, 1200 mg in the United States, and 1300 mg in Australia and New Zealand).

Eva Warensjö and colleagues attempted to clarify the association in a prospective longitudinal study of women in the Swedish Mammography Cohort. They divided the results by quintiles of dietary calcium intake, with the middle quintile as the reference; women with the lowest levels of intake had an increased risk of fracture and osteoporosis, but the risk varied little between the other quintiles. The rate of hip fracture was even increased in those who consumed the most calcium.

Does this help to clarify what intake of calcium should be recommended? Although the investigators controlled for some important confounders—such as nulliparity, smoking, socioeconomic status, physical activity, nutrients other than calcium, educational level, and comorbidity—residual confounding is still possible, as in all observational studies, so some uncertainty still remains. However, the findings are useful in suggesting that increasing calcium intake may only be beneficial up to a point.