Can Maternal Angiogenic Factor Levels Predict Progression of HDP to Severe Preeclampsia?
BACKGROUND AND PURPOSE:
Thadhani et al. (NEJM Evidence, 2022) identified and validated a ratio of soluble fms-like tyrosine kinase 1 (sFlt-1) to placental growth factor (PlGF) to stratify risk for developing preeclampsia with severe features (sPE)
Multicenter, blinded, prospective study
18 US tertiary and community hospitals
Pregnant women with hypertensive disorder of pregnancy
Hospitalized between 23w0d and 34w6d
sFlt-1: PlGF ratio
Researchers first used a derivation cohort to identify a ratio value that could discriminate between women likely to develop severe preeclampsia (sPE) vs those who did not
The above value threshold was then tested in a validation cohort
Development of sPE within 2 weeks of enrollment
Predicting adverse outcomes within 2 weeks
1014 pregnant women
Derivation cohort: 299 | Validation cohort: 715
Median sFlt-1:PlGF ratio in the derivation cohort
sPE: 200 (IQR, 53 to 458)
No sPE: 6 (IQR, 3 to 26)
Predictive values of a discriminatory ratio of ≥40 was then tested in the validation cohort for development of sPE
Positive predictive value: 65% (95% CI, 59 to 71)
Negative predictive value: 96% (95% CI, 93 to 98)
This ratio performed better than standard clinical measures
Ratio test: AUC 0.92
Standard-of-care tests: AUC <0.75
Compared with women with a ratio
Ratio <40: 16.1%
Ratio ≥40: 2.8%
Relative risk (RR) 5.8 (95% CI, 2.8 to 12.2)
The ratio of serum sFlt:PlGF predicted progression to severe preeclampsia among women with a hypertensive disorder of pregnancy presenting between 23 and 35 weeks
The authors state
In the current study, the AUC of sFlt-1:PlGF exceeded other standard measures used to predict sPE. In the subgroup of women with chronic hypertension, test performance characteristics were comparable to those seen in the entire cohort, suggesting that the ratio could be used to predict disease progression
Controlled trials are needed to determine if knowledge of the sFlt-1:PlGF ratio could lead to better obstetrical outcomes
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