Placental protein imbalance may predict preeclampsia risk


Testing the ratio between 2 placental proteins may be an early predictor of women at risk of developing preeclampsia with severe features.

A specific imbalance of 2 placental proteins may indicate women at risk of developing preeclampsia with severe features (sPE), according to research published in NEJM Evidence.

“We discovered that a blood test measuring the ratio between two proteins involved in blood vessel development in the placenta could identify which of the women would develop preterm preeclampsia with severe features,” said study co-senior author Sarah Kilpatrick, MD, PhD, chair of the Department of Obstetrics and Gynecology at Cedars-Sinai Medical Center. “This test was significantly better than all the standard-of-care markers for preeclampsia with severe features. It predicted with over 90% accuracy whether the patient would develop preeclampsia with severe features or not, while the usual markers were accurate less than 75% of the time.”

Investigators evaluated a total of 1014 pregnant women across 18 US centers. They prospectively measured the ratio of serum soluble tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) in pregnant women hospitalized between 23 and 35 weeks gestation. The study’s primary outcome was predicting sPE, and secondary outcomes included predicting adverse outcomes within 2 weeks.

They ultimately included 299 women in the derivation cohort and 715 in the validation cohort. For the derivation group, the median sFlt-1 to 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.

In women with hypertensive disorders of pregnancy between 23 and 35 weeks gestation, investigators concluded that the measurement of serum sFlt-1 to PlGF provided stratification of the risk of progressing to sPE within the upcoming 2 weeks.


Circulating Angiogenic Factor Levels in Hypertensive Disorders of Pregnancy | NEJM Evidence. NEJM Evidence. Published November 9, 2022. Accessed November 28, 2022.

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