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GPs urged to do more for pregnant women at risk of pre-eclampsia

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A leading obstetrician has raised concern about the under-use of aspirin prophylaxis in pregnancy for women at high risk of pre-eclampsia.

Professor Shaun Brennecke, director of the Department of Maternal-Fetal Medicine at the Royal Women’s Hospital in Melbourne told doctorportal: “It seems to me that many pregnant women who should commence on low dose aspirin in the first trimester of pregnancy fail to do so.”

Professor Brennecke said the issue was an important one given the potential to reduce serious complications of pregnancy, including perinatal death.

“We are seeing women arriving for their first hospital-based pregnancy care visit at gestations beyond the ideal time for staring low dose aspirin,” he said. “They will have often seen their GP to arrange a referral to the hospital in time to start low dose aspirin, but the opportunity is missed, and by the time they reach hospital it may be too late to usefully start the treatment.”

Professor Brennecke said women at high risk – for instance, those with a past history of pre-eclampsia – should commence 150mg aspirin daily at night no later than 16 weeks gestation.

A randomized controlled trial in the New England Journal of Medicine last year found 150mg aspirin daily, commenced at 11-14 weeks gestation, significantly reduced the risk of preterm pre-eclampsia compared with placebo in 1620 high risk women (OR: 0.38; 95% CI, 0.20 to 0.74; P=0.004).

Who is ‘high risk’?

In the NEJM study, ‘high risk’ was determined using an algorithm that combined maternal factors, mean arterial pressure, uterine-artery pulsatility index, and maternal serum pregnancy-associated plasma protein A and placental growth factor.

However, Professor Brennecke said GPs need not rely on complex multi-parametric testing, which is not widely available and affordable.

“Given low dose aspirin is safe and cheap, it would be reasonable for general practitioners to rely on maternal history features – previous preeclampsia, family history of preclampsia, high BMI, co-morbidities such as pre-existing hypertension, diabetes, renal disease and lupus – as indicating a justification for offering pregnant women low dose aspirin therapy for the prevention of preeclampsia,” Professor Brennecke said.

Clinical Associate Professor Gregory Jenkins of the University of Notre Dame and Westmead Hospital, said a past history of pre-eclampsia was one of the strongest risk factors for subsequent pre-eclampsia.

“All women with a past history of pre-eclampsia should be recommended low dose aspirin from 12 weeks in subsequent pregnancies unless there is a reason to advise otherwise,” he said.

He added: “Whilst algorithms for detailed testing are under development and some have found their way into clinical practice, their role and application is probably still to be evaluated.”

Associate Professor Jenkins coauthored a recent study evaluating the effectiveness of UK and US guidelines for predicting pre-eclampsia to guide aspirin prophylaxis.

The guidelines use routinely collected maternal factors to identify women at risk for pre-eclampsia. High risk factors include autoimmune disease, chronic hypertension, pre-pregnancy diabetes mellitus, chronic renal disease and previous hypertensive disease in pregnancy. Moderate risk factors include age 40 or older, elevated BMI and multiple pregnancy.

Associate Professor Jenkins and colleagues regarded patients as “screen positive” if they had at least one high risk factor or two moderate risk factors.

Their study found that while the guidelines offered a “simple and specific approach for recommending aspirin prophylaxis”, they lacked adequate sensitivity – especially in nulliparous women. A better risk prediction tool is needed.

Minimal risk with aspirin

Professor Brennecke said there was likely to be minimal risk of starting low dose aspirin in the first trimester for the majority of women, even though higher doses (eg. 600mg) are contraindicated in pregnancy.

“Low dose aspirin has been used around the world for several decades now in this context, which provides considerable reassurance,” he said. “There are occasional cases of sensitivity to aspirin, but doctors can check for this before recommending the treatment. There is a potential risk that low dose aspirin may exacerbate bleeding in pregnancy, but this does not seem to be significant in practice.”

A 2007 Cochrane review of 59 trials, involving 37,560 women, found low doses of aspirin reduced the risk of pre-eclampsia by about a sixth (17%), with a similar lowering in the risk of the baby dying (14%) and a small lowering in the risk of being born too early (8%).

The Society of Obstetric Medicine of Australia and New Zealand states in its 2014 guidelines that in a population with a 20% risk of preeclampsia, the number needed to treat to prevent one case of preeclampsia is 50.

The guidelines state: “In view of this potential benefit, and the relative absence of maternal or neonatal complications, low dose aspirin is indicated for women with at least moderate to high risk of preeclampsia (ie secondary prevention of preeclampsia in women at increased risk and in women with significantly increased risk in their first pregnancy.”)