Placental Growth Factor Testing to Assess Women With Suspected Preeclampsia: A Multicenter, Pragmatic, Stepped-Wedge Cluster-Randomized Controlled Trial

Hypertension affects 10% of pregnant women, and approximately 3% of singleton pregnancies are complicated by preeclampsia. Preeclampsia often presents ambiguously, and the risks for women with suspected preeclampsia are complex. Angiogenic factors, such as placental growth factor (PlGF), are associated with the pathophysiology of preeclampsia. Studies have shown that detection of low circulating maternal PlGF concentrations has a 96%sensitivity and 98%negative predictive value in diagnosing preeclampsia that required delivery within 14 days in women with suspected preeclampsia. However, the effectiveness of PlGF testing has not been examined in a real-world setting. Therefore, the researchers sought to determine whether circulating PlGF concentration, along with a clinical management algorithm, would lower the clinical time needed to diagnose women with suspected preeclampsia or whether this approach reduced adverse maternal or perinatal outcomes. The researchers performed a multicenter, pragmatic, stepped-wedge cluster-randomized controlled trial in 11 maternity units in the United Kingdom, each responsible for 3000 to 9000 deliveries per year. Inclusion criteria for the study were women 18 years and older presenting with suspected preeclampsia between 20 + 0 weeks and 36 + 6 weeks of gestation with a live, singleton fetus.Women identified at routine antenatal appointments or following acute clinical presentation with symptoms were included in the trial, whereas women with a documented diagnosis of preeclampsia at presentation were ineligible. Suspected preeclampsia was defined as new-onset or worsening of existing hypertension, dipstick proteinuria, epigastric or right upper-quadrant pain, headache with visual disturbances, fetal growth restriction, or abnormal maternal blood tests that were suggestive of disease (such as thrombocytopenia or hepatic or renal dysfunction). Primary outcome was time from presentation with suspected preeclampsia to documented preeclampsia for women in the trial who received that diagnosis. For the study period between June 13, 2016 and October 27, 2017, 1035women with suspected preeclampsia were enrolled in the trial; 1023 of these women met eligibility criteria. Of these, 576 women (56%) were assigned to the intervention group (testing revealed), and 447 women (44%) were assigned to receive their usual care with additional concealed testing. Three women in the first group were lost during follow-up, leaving 573 women in the revealed testing group; one woman in the concealed testing group withdrew consent, leaving 446 women in the concealed testing group. In the concealed testing group, the mean time to preeclampsia diagnosis was 4.1 days, whereas in the revealed testing group, it was 1.9 days. Severematernal adverse outcomes were reported in 24 (5%) of the 447 women in the concealed testing group and in 22 (4%) of the 573 women in the revealed testing group (adjusted odds ratio, 0.32; 95% confidence interval [CI], 0.11-0.96; P = 0.043), whereas there was no evidence of difference in perinatal adverse outcomes (15% vs 14%; adjusted odds ratio, 1.45; CI, 0.73-2.90) or gestational age at delivery (36.6 vs 36.8 weeks; mean difference, 0.52; 95% CI, 0.63-0.73). The researchers concluded that revealing PlGF test results substantially reduced the time to confirm a suspected preeclampsia diagnosis. In patients where PlGF testing was revealed, there was a lower incidence of maternal adverse outcomes, consistent with surveillance of these patients and as recommended in the management algorithm. The authors suggest that their data support PlGF testing in women with suspected preeclampsia as a diagnostic adjunct.