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.