New Test Identifies Preeclampsia Requiring Delivery.


Preeclampsia complicates up to 8% of pregnancies and has been difficult to accurately diagnose with traditional markers.

Now, British researchers report that a new test (Triage, Alere, San Diego, CA) that measures the level of placental growth factor (PlGF) in the blood can help doctors determine with a high degree of accuracy if a woman will develop preeclampsia during her pregnancy[1].

In a prospective multicenter study of 625 pregnant women presenting before 35 weeks’ gestation with suspected preeclampsia, low plasma PlGF (lower than the fifth centile for gestation) had very high sensitivity and very low negative predictive value for pinpointing those women who actually had the disorder and would need delivery within 14 days.

The study is published online November 4, 2013 in Circulation.

“For many years we’ve tried to work out which women have preeclampsia and need delivery, and we relied on high blood pressure and protein in the urine to tell us that,” lead author Dr Lucy Chappell (King’s College, London, UK) told heartwire .

And for the first time, we have a highly accurate blood test that we think will change antenatal care practice because it tells you with 96% certainty that a woman has preeclampsia, which is going to require delivery within 14 days. And that’s important for the woman, it’s important for the doctor, and it’s important for the health service,” Chappell said.

Placental growth factor increases during pregnancy and can rise as high as 3000 pg/mL. A sign of a healthy, growing placenta, PlGF peaks at around 30 weeks’ gestation and then starts to decline. Any value above 100 pg/mL is considered normal.

A great deal of time and effort is spent trying to pick out the women who are at highest risk for preeclampsia. The real importance of the test is to flag the women who need greater surveillance, Chappell said.

“All obstetricians and family physicians see a considerable proportion of the women under their care come through with suspected preeclampsia, with readings of high blood pressure or a bit of protein in their urine or headache, and it’s very difficult out of those women to tell who is going to need more monitoring and who could continue on with usual levels of monitoring. A lot of time and effort is spent trying to pick the women at highest risk, and that is exactly what this blood test does,” she said.

“It’s got such high accuracy for determining the women who are going to get preeclampsia and require urgent delivery. It doesn’t tell you to deliver the baby, it tells you whom you should be shining your spotlight on and whom you can leave alone.”

In addition to determining the accuracy of low plasma PlGF (defined as being below the fifth centile for gestational age) in predicting the need to deliver within 14 days in women before 35 weeks’ gestation, the researchers also looked at its accuracy at 35 to 36 weeks’ and at 37 or more weeks’ gestation.

They also looked at the accuracy of the test when using a lower threshold (<12 pg/mL) of PlGF.

Of the 625 women who took part in the study, 346 (55%) developed confirmed preeclampsia.

Overall, 287 women were enrolled at 20 to 24 weeks’ gestation, 137 women at 35 to 36 weeks’ gestation, and 201 between 37 and 40 weeks’ gestation.

The researchers found that the test was most accurate in the earlier stages of pregnancy. Between 20 and 34 weeks, the sensitivity of the assay in predicting the need for delivery within 14 days was 0.96 (95% CI 0.89–0.99) and its negative predictive value was 0.98 (95% CI 0.93–0.995).

Between 35 and 36 weeks’ gestation, the sensitivity of low PlGF in predicting the need for delivery within 14 days was 0.70 (95% CI 0.58–0.81) and its negative predictive value was 0.69 (95% CI 0.57–0.80).

At 37 weeks or more, the test’s sensitivity was 0.57 (95% CI 0.46–0.68) and its negative predictive value was 0.70 (95% CI 0.62–0.78).

The researchers also found that a PlGF less than 100 pg/mL was just as good as a PlGF <5% at predicting preeclampsia requiring delivery within 14 days, with the same sensitivity and negative predictive value between 20 and 34 weeks’ gestation and a sensitivity of 0.95 (95% CI 0.83–0.99) and negative predictive value of 0.94 (95% CI 0.80–0.99) at 35 to 36 weeks’ gestation.

“This is of great importance to clinicians,” Chappell said. “The doctor can do this test in the office; anything less than 100 pg/mL would mean increased, careful surveillance. In our study, levels under 100 pg/mL indicated an average time to delivery of 23 days.”

Very low levels of PlGF (<12 pg/mL) indicated an average time to delivery of only nine days.

The PlGF test was significantly better than all other commonly used tests, such as systolic and diastolic blood pressure, uric acid, alanine transaminase, and proteinuria, in determining preeclampsia requiring delivery within 14 days, when used alone or in combination (p<0.001 for all comparisons).

“This information is quite useful for an obstetrician, because if the women’s levels were very low, then you would want to step up your surveillance. In the UK, we would certainly be admitting those women and monitoring them carefully. So this blood test can really discriminate between those who don’t have a problem and those who need stepped-up surveillance,” she said.

Levels 100 pg/mL and above are reassuring and would mean that the time to delivery is 62 days or nine weeks, Chappell added.

The ability to home in on at-risk women more accurately will result in improved outcomes for mother and baby, at least that is the hope for this test, she said.

“It might help to reduce the number of women who are delivered too soon, because if we target our care correctly, we can reduce unnecessary harm as well,” she said.

Magnesium sulfate therapy of preeclampsia: an old tool with new mechanism of action and prospect in management and prophylaxis.


A disturbed balance between angiogenic and antiangiogenic growth factors is a highly accepted mechanism in the pathogenesis of pregnancy-induced hypertension and proteinuria, which is clinically known as preeclampsia (PE). We investigated the effect of magnesium sulfate (MgSO4) therapy on vascular endothelial growth factor (VEGF), placental growth factor (PlGF), nitric oxide (NO) metabolites, soluble fm-like tyrosine kinase-1 (sFlt-1) and endoglin levels in PE rats and the effect of this treatment on the feto-maternal outcome. The PE group showed hypertension, proteinuria and decreased number and weight of live pups relative to the control group. This result was associated with increased sFlt-1, VEGF receptor-2 (VEGFR-2), VEGFR-3 and endoglin levels but decreased NO metabolites. MgSO4 therapy ameliorated systolic hypertension and proteinuria and decreased sFlt-1, VEGFR-2, VEGFR-3 and endoglin levels but increased NO metabolites in the treated group. Physiological and biochemical changes and improved pup weight and viability were observed in the treated group. The vasodilator action of MgSO4 and increased NO production are expected to increase placental blood flow and help fetal nutrition and development. Relief of placental ischemia decreases the production of antiangiogenic growth factors and restores the bioavailability of angiogenic factors (PlGF and VEGF). These changes resulted in better fetal outcome and an improved clinical picture of PE. These findings are promising and encourage further study of the mechanism of action of MgSO4 to support its widespread use in the prevention and management of the etiopathological changes underlying the vast majority of the manifestations and complications of PE.

Source: Hypertension Research/nature.