Study design
A retrospective cohort study was carried out in women with clinical suspicion of pre-eclampsia. A total of 381 pregnant women were enrolled at Hospital Universitario Central de Asturias (HUCA) between January 2015 and November 2018. The inclusion criteria were: high blood pressure, proteinuria, worsening of pre-existing hypertension or proteinuria, abnormal uterine artery Doppler scan, headache not responding to analgesics, visual symptoms and/or severe edema. An abnormal uterine artery Doppler scan was defined as a pulsatility index above the 95th percentile for the Spanish population.
Of all pregnant women enrolled, 17 twin pregnancies and one pregnancy with incomplete data were excluded.
We adopted a repeated measures design instead of using baseline measurements only as the former allows risk to be continually reassessed at each gestational week if clinical suspicion of pre-eclampsia persisted. 152 samples were excluded to ensure a minimum interval between subsequent determinations of seven days. The final number was 363 women and 522 samples (Figure 1).
We considered samples with an sFlt-1/PlGF ratio of 38 or below as at low risk of pre-eclampsia leading to delivery within one week (309 samples from 253 pregnancies) and developed the predictive models with samples with an sFlt-1/PlGF ratio above 38 (213 samples from 123 pregnancies). Twelve pregnancies initially had an sFlt-1/PlGF ratio of 38 or below but subsequently rose above 38 and only one pregnancy did the opposite.
As the severity of pre-eclampsia can vary greatly, the evaluated endpoint was diagnosis of early-onset pre-eclampsia leading to delivery within one week from the measurement. The majority of deliveries with pre-eclampsia were induced deliveries. The clinical staff members making the decision to expedite delivery were blinded to the marker results. Women who had manifested pre-eclampsia were not excluded, as this would reduce the external validity of the study.
The laboratory staff members were blinded to subjects’ clinical information. The study was approved by the Independent Ethics Committee of Asturias. Written informed consent was obtained from each woman.