Abstract
We sought to assess the ratio of sFlt-1 (soluble fms-like tyrosine kinase 1) to PlGF (placental growth factor) in maternal serum as a screening test for preeclampsia in unselected nulliparous women with a singleton pregnancy. We studied 4099 women recruited to the POP study (Pregnancy Outcome Prediction) (Cambridge, United Kingdom). The sFlt-1:PlGF ratio was measured using the Roche Cobas e411 platform at ≈20, ≈28, and ≈36 weeks of gestational age (wkGA). Screen positive was defined as an sFlt-1:PlGF ratio >38, but higher thresholds were also studied. At 28 wkGA, an sFlt-1:PlGF ratio >38 had a positive predictive value (PPV) of 32% for preeclampsia and preterm birth, and the PPV was similar comparing women with low and high prior risk of disease. At 36 wkGA, an sFlt-1:PlGF ratio >38 had a PPV for severe preeclampsia of 20% in high-risk women and 6.4% in low-risk women. At 36 wkGA, an sFlt-1:PlGF ratio >110 had a PPV of 30% for severe preeclampsia, and the PPV was similar comparing low- and high-risk women. Overall, at 36 wkGA, 195 (5.2%) women either had an sFlt-1:PlGF ratio of >110 or an sFlt-1:PlGF ratio >38 plus maternal risk factors: 43% of these women developed preeclampsia, about half with severe features. Among low-risk women at 36 wkGA, an sFlt-1:PlGF ratio ≤38 had a negative predictive value for severe preeclampsia of 99.2%. The sFlt-1:PlGF ratio provided clinically useful prediction of the risk of the most important manifestations of preeclampsia in a cohort of unselected nulliparous women.
Highlights
We sought to assess the ratio of sFlt-1 to PlGF in maternal serum as a screening test for preeclampsia in unselected nulliparous women with a singleton pregnancy
A substantial proportion of severe adverse perinatal outcomes occur as a consequence of preterm birth because of preeclampsia, and a substantial proportion of adverse maternal outcomes occurs in severe preeclampsia.[1]
Preeclampsia is associated with an altered maternal pattern of circulating placentally derived proteins regulating angiogenesis,[2,3] such as sFlt-1 and PlGF
Summary
We sought to assess the ratio of sFlt-1 (soluble fms-like tyrosine kinase 1) to PlGF (placental growth factor) in maternal serum as a screening test for preeclampsia in unselected nulliparous women with a singleton pregnancy. Preeclampsia is one of the most common adverse outcomes of pregnancy.[1] The condition consists of new onset hypertension and proteinuria in the second half of pregnancy but can be superimposed on preexisting hypertension or renal disease It is associated with increased risks of maternal and perinatal morbidity and mortality. A recent study of women with clinically suspected disease demonstrated that an sFlt-1:PlGF ratio cutoff of 38 provided clinically useful prediction of the risk of preeclampsia.[4] Higher sFlt-1:PlGF ratios, namely >85 at 28 weeks of gestational age (wkGA) and >110 at 36 wkGA, have been shown to be more strongly associated with the risk of preeclampsia.[5] evidence for the diagnostic effectiveness of the ratio in screening women without clinical suspicion of the disease is poor. Screen positive was defined on the basis of the previously described and validated cutoff of >38.4 We studied the most clinically important manifestations of preeclampsia, namely any severity of the disease leading to preterm birth or preeclampsia with severe features
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