RESULTS
During the study period 86 women were admitted for early-onset severe
PE. 68 of them had no maternal complications at admission and no fetal
indication for imminent delivery. Blood samples for angiogenic factors
measurement were not collected from 4 of these patients due to a breach
of the study protocol. In one additional case, blood sample was not
obtained at delivery. Thus, a total of 63 women were available for
analysis with both at-admission and at-delivery measurements. Out of
them, 23 patients (36.5%) had a complication. Table 1 shows the
baseline characteristics by the presence of complications and
supplementary table 1 details the maternal complications. The median
time interval between admission and delivery was 9 days (ranging from 2
to 24). It was shorter in complicated pregnancies [7 (2-22)] vs
[10 (2-24)] in those without complications.
Supplementary table 2 shows the levels of the angiogenic factors at
admission and at delivery, with the delta values (expressing average
daily change). Of note, all the evaluated angiogenic factors
significantly differed between admission and delivery. Table 2 and
supplementary figure 1 depict the angiogenic factors levels in
uncomplicated and complicated pregnancies. Only the sFlt-1 delta values
were significantly different between those without and with complication
(median values: 343.7 vs. 1079.5 pg/mL/day; p=0.04). Expressed as
relative changes from the admission values, this corresponds to 2.6%
vs. 8.2% daily increase. Supplementary figure 2 shows the individual
and averaged changes of sFlt-1 by the occurrence of complications.
On the multivariate analysis, the baseline model (PREP-L risk score and
sFlt-1 at admission) explained 6.6% of the uncertainty of complications
occurrence (R2 Naegelkerke). The addition of sFlt-1
delta values significantly improved this performance
(R2 Naegelkerke of 23.2%; p=0.004). Table 3 shows the
logistic regression model which includes all three predictors. While the
area under the curve of the baseline model was 0.6 (95%CI 0.46-0.75),
it increased to 0.75 (95% CI 0.62-0.87) when the sFlt-1 delta was
added. For a 20%, 30% and 40% of false-positive rates, detection
rates were better for the model including sFlt-1 delta: 57.1% vs.
33.3%; 66.7% vs. 38.1%; and 76.2% vs. 47.6%, respectively. Figure 1
shows both ROC curves.
Figure 2 shows the Kaplan-Meier graph of the time interval to delivery:
the median time was 3 days (95%CI 1.96-4.05) in those in the highest
quartile of delta sFlt-1 values vs. 10 (95%CI 8.1-11.9) in those in the
1st-3rd quartiles [Log Rank
(Mantel-Cox) p<0.001].
Table 3 shows the Cox regression modelling of the time interval from
admission to delivery. Of note, to meet the proportional hazards
assumption, log-transformed sFlt-1 delta values had to be categorized in
quartiles and entered in the model as binary (highest quartile vs. those
the 1st-3rd quartile): hazard ratio
of 3.15 (95%CI 1.67-5.86; p<0.001).