The US Food and Drug Administration (FDA) has approved a blood test that can identify pregnant women who are at imminent risk of developing pre-eclampsia, the severe form of high blood pressure that is a leading cause of disability and death among childbearing women.
The new test may offer an early warning, identifying which of the many pregnant women who have suggestive symptoms will go develop the life-threatening disease within the next two weeks, and has been described as “revolutionary” by experts.
“It’s groundbreaking,” said Dr Doug Woelkers, a professor of maternal foetal medicine at the University of California, San Diego. “It’s the first step forward in pre-eclampsia diagnostics since 1900, when the condition was first defined.”
The New York Times reports that to what extent the test will improve outcomes and save lives is not clear, however, as there is no effective treatment for pre-eclampsia, which usually eases after birth.
“We don’t have a therapy that reverses or cures pre-eclampsia other than delivery of the baby, which is more like a last resort,” Woelkers said.
The new blood test, made by Thermo Fisher Scientific, has been available in Europe for several years. It is intended for pregnant women who are hospitalised for a blood pressure disorder in the 23rd to 35th weeks of gestation.
The test can tell, with up to 96% accuracy, who will not develop pre-eclampsia within the next two weeks and so can safely be discharged from the hospital. Two-thirds of the women who get a positive result, on the other hand, will progress to severe pre-eclampsia in that time, and their babies may need to be delivered early.
Distinguishing between the two groups of women is a challenge that has long vexed physicians.
“The warning signs of pre-eclampsia are not very specific,” said Dr Sarosh Rana, a professor of obstetrics and gynaecology at the University of Chicago who has studied the test. “A lot of women will have oedema and headaches, but we don’t really know who among those patients is at higher risk for the really adverse outcomes.”
Pre-eclampsia affects about one in 25 pregnancies, and has been on the rise in recent years in the US. The problem usually starts about halfway through a pregnancy, though it can also occur after childbirth. It can lead to eclampsia, which can lead to seizures and death.
Black women in the United States have pre-eclampsia rates much higher than those of white women, and are three times as likely to suffer kidney damage or death from pre-eclampsia. They are are also more likely to lose their babies.
The blood test measures the ratio of two proteins that are produced by the placenta. A study published in NEJM Evidence last year tracked 1 014 pregnant women admitted to hospital with a hypertensive disorder of pregnancy at 18 medical centres in the US from 2019 to 2021.
The researchers found that the two proteins were greatly unbalanced in the blood of women who developed severe pre-eclampsia. Those with the widest ratios had a 65% chance of progressing to severe pre-eclampsia and of delivering their baby within two weeks, either spontaneously or through induction.
“If your levels are among the highest, you deliver in a few days,” said Dr Ravi Thadhani, an author of the study.
Women who have symptoms suggesting pre-eclampsia but who test negative can be reassured and sent home, but they may need to have the test repeated every two weeks, Rana said.
Pre-eclampsia develops precipitously, and without the blood test, the warning signs can be vague.
“A woman can go from feeling fine and being completely healthy and having normal kidney and liver function, and within 24 to 48 hours those organs can fail and she develops brain swelling and seizures,” Thadhani said. “That is the scary part of the disease.”
Study details
Circulating Angiogenic Factor Levels in Hypertensive Disorders of Pregnancy
Ravi Thadhani, Elizabeth Lemoine, Sarosh Rana, Maged Costantine, Vinicius Calsavara, Kim Boggess, Blair Wylie, and Sarah Kilpatrick.
Published in the New England Journal of Medicine on 9 November 2022
Abstract
Background
Among women with hypertensive disorders of pregnancy, biomarkers may stratify risk for developing pre-eclampsia with severe features (sPE).
Methods
Across 18 US centres, we prospectively measured the ratio of serum soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) in pregnant women hospitalised between 23 and 35 weeks of gestation. The primary outcome was predicting sPE, and secondary outcomes included predicting adverse outcomes within 2 weeks. The prognostic performance of the sFlt-1:PlGF ratio was assessed by using a derivation/validation design.
Results
A total of 1 014 pregnant women were evaluated; 299 were included in the derivation cohort and 715 in the validation cohort. In the derivation cohort, the median sFlt-1:PlGF ratio was 200 (interquartile range, 53 to 458) among women who developed sPE compared with 6 (interquartile range, 3 to 26) in those who did not (P<0.001). The discriminatory ratio of ≥40 was then tested in the validation cohort and yielded a 65% positive (95% confidence interval [CI], 59 to 71) and a 96% negative (95% CI, 93 to 98) predictive value for the primary outcome. The ratio performed better than standard clinical measures (area under the receiver-operating characteristic curve, 0.92 versus <0.75 for standard-of-care tests). Compared with women with a ratio <40, women with a ratio ≥40 were at higher risk for adverse maternal outcomes (16.1% versus 2.8%; relative risk, 5.8; 95% CI, 2.8 to 12.2).
Conclusions
In women with a hypertensive disorder of pregnancy presenting between 23 and 35 weeks of gestation, measurement of serum sFlt-1:PlGF provided stratification of the risk of progressing to sPE within the coming fortnight.
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