3. Results
A study design flowchart is presented in Figure 1. Of the 460-singleton
pregnant woman recruited into this study, 423 (92%) completed the
follow-up until delivery. In 11 cases (2.6%), GCF-PLAP samples were
unsatisfactory for analysis and were excluded from the study; therefore,
412 cases (89.6%) were available for analysis.
The baseline characteristics of the study population are summarized in
Table 1. Of the 423 pregnant women recruited and followed throughout
pregnancy, 18 of them subsequently developed PE (4.3%), and five
(1.2%) required delivery before 37 weeks of gestation. Maternal age,
maternal weight and height, body mass index, and smoking status did not
differ significantly between patients with PE and controls. Systolic
blood pressure (p<0.001), diastolic blood pressure (p=0.007),
and median arterial blood pressure (p=0.006), measured during early
pregnancy, were significantly higher in women who developed PE when
compared to controls. No statistically significant differences in
periodontal parameters were identified between patients who developed PE
and controls, and no statistically significant association was
identified between periodontal clinical diagnosis and the subsequent
development of PE (p=0.617) (Table 2). The median maternal GCF-PLAP
concentration was 63.7 (interquartile range [IQR]: 88.9) pg/ml in
healthy patients, 46.6 (IQR: 47.2) pg/ml in patients with gingivitis,
and 42.4 (IQR: 46.7), 41.1 (IQR: 51.8), 34.7 (IQR: 46.88) pg/ml at
periodontitis stage I, stage II – III and stage IV, respectively,
without statistically significant differences among them (p=0.407).
GCF-PLAP concentrations at 11-14 weeks were compared between patients
who subsequently developed PE and controls. The median maternal GCF-PLAP
concentration was significantly higher in the PE group than that of the
controls (77.5 pg/ml (IQR: 41.5) vs. 41.3 pg/ml (IQR: 50.1), p=0.015)
(Figure 2A). In addition, PLAP concentrations were also measured in
paired plasma and GCF samples from 80 women from the same cohort. The
median plasma PLAP concentrations were 24.2 pg/ml (IQR: 2.5) and 24.6
pg/ml (IQR: 7.6) in the control and PE groups, respectively. In the
paired GCF samples, median PLAP concentrations were 66.1 pg/ml (IQR:
4.3) and 99 pg/ml (IQR: 17.8) in the control and PE groups, respectively
(p=0.011) (Figure 2B). There was no correlation between plasma and
GCF-PLAP concentrations. The observed amount of PLAP in GCF was 3- to
6-fold higher than in plasma samples.
Multiple logistic regression analysis identified an association between
first-trimester systolic blood pressure (OR: 1.07; 95% CI 1.00-1.015;
p=0.004) and GCF-PLAP concentrations (OR: 1.008, 95% CI 1.000-1.015;
p=0.034) (Table 3) in women who subsequently developed PE. The results
of the bootstrap analysis were similar to those observed in the logistic
regression model (Table 3). The GCF-PLAP concentration combined with
systolic blood pressure at 11-14 weeks of gestation was found to be a
good predictor of PE, with a specificity of 72%, a sensitivity of 83%,
a PPV of 12%, and an NPV of 99%. The positive likelihood ratio was
2.9, and the negative likelihood ratio was 0.3. The model correctly
classified 72% of the women who developed PE. The AUC for GCF-PLAP
concentrations alone at 11-14 weeks of gestation was 0.67; for systolic
blood pressure, 0.74, and for GCF-PLAP concentrations and systolic blood
pressure, 0.77 (95% CI: 0.70 – 0.85) (Figure 2C). In the sub-analysis,
dividing the PE pregnancies into preterm PE (≤ 37 weeks) and term PE
(> 37 weeks), the observed AUC was 0.85 (95% CI: 0.81 –
0.93) for preterm PE and 0.72 (95% CI: 0.58 - 0.82) for term PE (Figure
2D and 2D, respectively). All five cases (100%) of preterm PE observed
in the current study were correctly classified by the model.