A novel three-step approach for predicting the imminent onset of preeclampsia within 4 weeks after blood sampling at 19-31 weeks of gestation

Our aim was to develop a novel screening method to detect the imminent onset of preeclampsia (PE) within 4 weeks after blood sampling. We prospectively collected data regarding past history of PE/gestational hypertension (GH), blood pressure levels at 16-23 weeks and plasma levels of soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) twice at 19-31 weeks, which were measured using an automated electrochemiluminescence immunoassay. We found that a three-step approach by sequential selection using maternal factors, including a past history of PE/GH or blood pressure levels >= 120/80mmHg at 16-23 weeks (first step), followed by plasma levels of PlGF in the < 5th percentile (second step) and plasma levels of sFlt-1 in the >= 95th percentile (third step) yielded both high sensitivity and specificity. The imminent onset of PE occurred in 2 of 1199 (0.2%) women recruited at 19-25 weeks and in 6 of 798 (0.8%) women recruited at 26-31 weeks. The sensitivity, specificity, positive likelihood ratio (95% confidence interval), negative likelihood ratio (95% confidence interval), positive predictive value and negative predictive value of the three-step approach for predicting the imminent onset of PE at 19-25 weeks were 100%, 99.8%, 599 (150-2390), 0%, 50% and 100%, respectively; and those at 26-31 weeks were 83%, 99.1%, 94 (42-214), 0.17 (0.03-1.01), 42% and 99.9%, respectively. In conclusion, the three-step approach is a highly sensitive and specific screening method for detecting the imminent onset of PE within 4 weeks after blood sampling at 19-31 weeks of gestation.