Low sFlt-1-PlGF ratio linked to short-term absence of preeclampsia: The PROGNOSIS study

1. Preeclampsia is a partially understood condition in which circulating maternal serum levels of soluble fms-like tyrosine kinase 1 (sFlt-1) are increased and placental growth factor (PlGF) levels are decreased.

2. sFlt-PlGF ratios of 38 or lower had a negative predictive value of 99.3% for the outcome of no diagnosis of preeclampsia, eclampsia, or the HELLP syndrome within 1 week of blood draw.

Evidence Rating Level: 2 (Good)        

Study Rundown: Preeclampsia is a major contributor to pregnancy-associated morbidity and mortality, and research is underway to delineate potential diagnostic biomarkers to aid in its management. One such biomarker is the ratio of sFlt-1 to PlGF; in preeclampsia, circulating maternal serum levels of sFlt-1 are increased and PlGF levels are decreased. PROGNOSIS (Prediction of Short-Term Outcome in Pregnant Women with Suspected Preeclampsia Study) was designed to derive and validate a cut-off point for the prediction of the short-term absence or presence of preeclampsia in pregnant women suspected of having this condition.

Building a prediction model from a cohort of 500 women and validating this in a cohort of 550, the authors determined the sFlt-PlGF ratio of 38 as clinically meaningful. A ratio equal to or less than 38 had a negative predictive value of no preeclampsia in the subsequent week of 99.3%; a ratio higher than this cut-off had a positive predictive value (PPV) of preeclampsia, eclampsia, or HELLP syndrome within 4 weeks of 36.7%. Thus, the sFlt-1:PlGF ratio has potential utility in helping clinicians risk-stratify pregnant women who are suspected to be at risk of preeclampsia, and may help prevent unnecessary hospitalizations for this important condition. However, these data, sponsored by the corporate entity producing this technology, are observational in nature; randomized control studies will be necessary to affirm the true utility of this ratio.

Click to read the study, published today in NEJM

Relevant Reading: Risk of pre-eclampsia in first and subsequent pregnancies

In-Depth [prospective cohort]: This prediction study enrolled 1273 pregnant women, aged 18 years of age or older, with suspected preeclampsia. A total of 500 were included in the development cohort, from which the prediction model was derived, and 550 in the validation cohort. The gestational age at first visit ranged from 24 weeks to 36 weeks and 6 days. The development cohort was used to derive the sFlt-1:PlGF ratio cut-off of 38. In the validation cohort, a ratio of 38 or lower had a negative predictive value (NPV) of 99.3% (95% [CI], 97.9%-99.9%) for the outcome of no diagnosis of preeclampsia, eclampsia, or the HELLP syndrome within 1 week. A ratio of greater than 38 had a PPV of 36.7% (95% [CI], 28.4%-45.7%) for the outcome of a diagnosis of preeclampsia, eclampsia, or HELLP syndrome within 4 weeks of the blood draw. There were only two adverse outcomes involving mothers enrolled in the study, both occurring in participants with elevated sFlt-PlGF ratios. Additionally, in the posthoc analysis, a sFlt-PlGF ratio of 38 or lower was associated with the absence of fetal adverse outcomes within 1 week, with a NPV in the validation cohort of 99.3% (95% [CI], 97.9%-99.9%).

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