The entire group's mean age was 30.2 ± 7.39 (29.5) years, as detailed in Table 1, which comprehensively evaluates demographic data. The groups were examined in two parts: a comparison of non-pregnant normal patients and patients with appendicitis and a comparison of pregnant normal patients and pregnant patients with appendicitis.
a. Evaluation of Non-Pregnant Patients (HW and UHW)
The mean age of the healthy female group was calculated as 29.53 ± 6.97 (31.00) years, while the mean age of the appendicitis female group was 27.73 ± 7.05 (25.50) years, with no statistically significant difference observed (p = 0.245). The mean WBC count was 7.19 ± 1.56 (7.15) in the healthy female group, whereas it was 13.01 ± 4.83 (13.28) in the appendicitis female group, showing a statistically significant increase (p < 0.001). The mean neutrophil count was 5.72 ± 0.95 (5.52) in the healthy female group and 10.05 ± 4.66 (9.92) in the appendicitis group, with a statistically significant difference observed (p < 0.001). When examined in terms of lymphocyte count, the mean lymphocyte count was 2.21 ± 0.53 (2.33) in the healthy female group, and 2.05 ± 1.07 (1.75) in the patient female group, with no statistically significant difference observed (p = 0.067).
Variables | All Patients | Non-Pregnant Patients | Pregnant Patients | Normal | Appendicitis | Statistical Significance | Pregnant | Pregnant Appendicitis | Statistical Significance |
Age | 30.20 ± 7.39 (29.5) | 28.63 ± 7.00 (29.50) | 28.77 ± 6.49 (28.00) | 29.53 ± 6.97 (31.00) | 27,73 ± 7,05 (25,50) | 0,245 | 30,00 ± 5,53 (29,50) | 27,53 ± 7,21 (25,50) | 0,094 |
Gestational Weeks | 19.02 ± 8.75 (20) | | 19.02 ± 8.75 (20.00) | | 21,23 ± 10,05 (24,50) | 16,80 ± 6,68 (17,50) | 0,035 |
WBC | 10.59 ± 4.37 (9.52) | 10.10 ± 4.61 (8.52) | 11.08 ± 4.09 (9.74) | 7.19 ± 1.56 (7.15) | 13,01 ± 4,83 (13,28) | < 0,001 | 9,43 ± 1,89 (9,62) | 12,73 ± 4,97 (12,61) | 0,002 |
HGB | 12.03 ± 1.35 (12) | 12.31 ± 1.47 (12.50) | 11.75 ± 1.16 (11.85) | 12.41 ± 1.60 (12.60) | 12,21 ± 1,35 (12,40) | 0,596 | 12,01 ± 0,94 (12,00) | 11,49 ± 1,31 (11,80) | 0,085 |
NE | 8.23 ± 3.94 (6.96) | 7.88 ± 3.99 (6.66) | 8.58 ± 3.90 (7.19) | 5.72 ± 0.95 (5.52) | 10,05 ± 4,66 (9,92) | < 0,001 | 6,86 ± 1,60 (6,78) | 10,30 ± 4,71 (9,78) | 0,005 |
LY | 1.87 ± 0.77 (1.83) | 2.13 ± 0.84 (2.17) | 1.61 ± 0.60 (1.72) | 2.21 ± 0.53 (2.33) | 2,05 ± 1,07 (1,75) | 0,067 | 1,79 ± 0,42 (1,76) | 1,43 ± 0,70 (1,44) | 0,020 |
PLT | 250.41 ± 71.69 (244.5) | 270.48 ± 65.49 (268.00) | 230.33 ± 72.50 (217.00) | 286.07 ± 68.31 (280.00) | 254,90 ± 59,64 (255,50) | 0,069 | 232,93 ± 71,61 (233,00) | 227,73 ± 74,51 (207,00) | 0,589 |
MPV | 10.04 ± 1.28 (10.05) | 10.15 ± 1.25 (10.15) | 9.93 ± 1.31 (9.85) | 10.40 ± 1.43 (10.30) | 9,90 ± 0,98 (9,95) | 0,242 | 10,44 ± 0,99 (10,40) | 9,42 ± 1,40 (9,25) | 0,002 |
Alb | 3.82 ± 0.61 (3.85) | 4.23 ± 0.34 (4.20) | 3.42 ± 0.54 (3.50) | 4.23 ± 0.30 (4.20) | 4,22 ± 0,38 (4,20) | 0,949 | 3,15 ± 0,57 (3,05) | 3,68 ± 0,36 (3,70) | < 0,001 |
CRP | 6.84 (3.02–183) | 3.23 (3.02–152) | 10.1 (3.02–183) | 3.14 (3.02–6.38) | 24,9 (3,02-152) | < 0,001 | 8,31 (3,3–21,1) | 22,45 (3,02-183) | < 0,001 |
MO | 0.58 ± 0.24 (0.54) | 0.59 ± 0.27 (0.52) | 0.58 ± 0.21 (0.59) | 0.55 ± 0.25 (0.47) | 0,63 ± 0,28 (0,58) | 0,178 | 0,60 ± 0,16 (0,63) | 0,56 ± 0,25 (0,55) | 0,482 |
NLR | 3.73 (1.33–56.13) | 2.91 (1.33–28.06) | 4.44 (2.04–56.13) | 2.52 (1.69–8.48) | 4,59 (1,33 − 28,06) | 0,001 | 3,91 (2,09 − 7,07) | 7 (2,04–56,13) | 0,001 |
PLR | 132.36 (43.66-803.85) | 125.05 (52.21–575) | 148.12 (43.66-803.85) | 120.7 (67.5–575) | 130,66 (52,21–487,1) | 0,745 | 126,62 (67,3-232,63) | 168,78 (43,66–803,85) | 0,011 |
CAR | 2.24 (0.64–54.85) | 0.8 (0.64–33.78) | 3.3 (0.7-54.85) | 0.76 (0.64–1.56) | 5,3 (0,66 − 33,78) | < 0,001 | 2,38 (0,79 − 6,39) | 6,08 (0,7–54,85) | 0,001 |
PMR | 24.24 (8.54–59.34) | 25.53 (8.54–59.3) | 22.34 (9.83–59.34) | 25.83 (12.35–59.3) | 24,97 (8,54 − 51,15) | 0,274 | 22,3 (9,83 − 43,3) | 22,45 (12,19–59,34) | 0,574 |
MLR | 0.3 (0.13–2.75) | 0.24 (0.13–0.9) | 0.36 (0.15–2.75) | 0.22 (0.13–0.65) | 0,33 (0,13 − 0,9) | 0,040 | 0,36 (0,16 − 0,53) | 0,35 (0,15 − 2,75) | 0,425 |
Table 1: All patients and groups data and comparison of variables between groups | PGIndex | 5.22 (1.57–20.62) | 18.71 (1.74–438.3) | < 0.001 |
No statistically significant difference was observed in the mean hemoglobin levels between the healthy and appendicitis female groups (p = 0.596). Similarly, the two groups had no significant difference in platelet counts (p = 0.069). No significant difference was observed in the mean MPV and albumin levels between the two groups (p = 0.242 and p = 0.949, respectively). The median CRP was 3.14 (3.02–6.38) in the healthy female group, while it was 24.9 (3.02–152) in the appendicitis female group, indicating a statistically significant increase in CRP levels (p < 0.001). No statistically significant difference was observed in mean monocyte counts between the two groups (p = 0.178).
When the NLR values of both groups were examined, the median NLR was 2.52 (1.69–8.48) in the healthy female group and 4.59 (1.33–28.06) in the appendicitis female group, showing a statistically significant difference (p = 0.001). The median CAR in the healthy female group was 0.76 (0.64–1.56), whereas it was 5.3 (0.66–33.78) in the appendicitis female group, indicating a significantly higher level, with a statistically significant difference observed (p < 0.001). Regarding MLR, the median MLR was 0.22 (0.13–0.65) in the healthy female group and 0.33 (0.13–0.9) in the appendicitis female group, showing a statistically significant difference (p = 0.04).
When comparing the mean PLR and PMR of non-pregnant women groups, no statistically significant difference was observed (p = 0.745 and p = 0.274, respectively) (Table 1).
b. Diagnostic Evaluation of Discriminating Markers in the Non-Pregnant Group (HW vs UHW)
NLR, CAR, and MLR markers, showing significant differences between the non-pregnant normal (HW) and appendicitis (UHW) groups, were evaluated for their ability to distinguish between these groups using the area under the ROC curve and the Youden index. For NLR, a cut-off value of 3.33 (OR 18, 95% CI 4.378–74.012, p < 0.001) was found with 66.7% sensitivity and 90% specificity. For CAR, a cut-off value of 1.08 (OR 79.75, 95% CI 9.276-685.633, p < 0.001) was found with 73.3% sensitivity and 96.7% specificity. For MLR, a cut-off value of 0.33 (OR 4, 95% CI 1.272–12.578, p = 0.029) was found with 50% sensitivity and 80% specificity (Table 2) (Fig. 1).
Table 2
Cut-off points and diagnostic values of variables for the distinction between normal and appendicitis patients
Variables | Cut-Off | Diagnostic Values | ROC Curve | Odds Ratio |
Sensitivity | Specificity | PPV | NPV | Accuracy | Area (SE) | %95 CI | p | Odds Ratio | %95 CI | p |
NLR | 3.33 | 66.7% | 90.0% | 87.0% | 73.0% | 78.3% | 0.751 (0.070) | 0.613–0.889 | 0.001 | 18 | 4.378–74.012 | < 0.001 |
CAR | 1.08 | 73.3% | 96.7% | 95.7% | 78.4% | 85.0% | 0.834 (0.058) | 0.722–0.947 | < 0.001 | 79.75 | 9.276-685.633 | < 0.001 |
MLR | 0.33 | 50.0% | 80.0% | 71.4% | 61.5% | 65.0% | 0.654 (0.072) | 0.514–0.795 | 0.040 | 4 | 1.272–12.578 | 0.029 |
c. Evaluation of pregnant patients (HPW and UPW)
The mean age of healthy pregnant women (HPW) was calculated as 30.00 ± 5.53 (29.50) years, while the mean age of pregnant patients with appendicitis (UPW) was 27.53 ± 7.21 (25.50) years. Although the mean age of the appendicitis group appeared slightly younger, no statistically significant difference was observed (p = 0.094). The mean gestational week was 21.23 ± 10.05 (24.50) weeks for healthy pregnant women (HPW) and 16.80 ± 6.68 (17.50) weeks for pregnant patients with appendicitis (UPW), showing a significant difference (p = 0.035).
When examining the mean WBC count, it was significantly higher in pregnant patients with appendicitis (UPW) with a mean of 12.73 ± 4.97 (12.61), compared to 9.43 ± 1.89 (9.62) in healthy pregnant women (HPW) (p = 0.002). The mean neutrophil count was 10.30 ± 4.71 (9.78) in pregnant patients with appendicitis (UPW) and 6.86 ± 1.60 (6.78) in healthy pregnant women (HPW), showing a significant increase in neutrophil count in pregnant patients (p = 0.005). The mean lymphocyte count was 1.79 ± 0.42 (1.76) in healthy pregnant women (HPW) and 1.43 ± 0.70 (1.44) in pregnant patients with appendicitis (UPW), indicating a statistically significant decrease in lymphocyte count in the presence of inflammation (p = 0.02). No statistically significant difference was observed in the mean monocyte count between the two groups (p = 0.482).
No significant difference was observed in the mean hemoglobin and platelet values between non-appendicitis pregnant women and the appendicitis group (p = 0.085 and p = 0.589, respectively). The mean MPV was 10.44 ± 0.99 (10.40) in healthy pregnant women (HPW) and 9.42 ± 1.40 (9.25) in pregnant patients with appendicitis (UPW), showing a statistically significant decrease in the appendicitis group (p = 0.002).
When examining the mean albumin, it was 3.15 ± 0.57 (3.05) in healthy pregnant women (HPW) and 3.68 ± 0.36 (3.70) in pregnant patients with appendicitis (UPW), indicating a statistically significant difference (p < 0.001). The median CRP was 8.31 (3.3–21.1) in healthy pregnant women (HPW) and 22.45 (3.02–183) in pregnant patients with appendicitis (UPW), showing a significantly higher value in the appendicitis group (p < 0.001).
When comparing the mean NLR values, the median NLR was 3.91 (2.09–7.07) in non-appendicitis pregnant women and 7.00 (2.04–56.13) in pregnant patients with appendicitis, showing a significantly higher value in the appendicitis group (p = 0.001). Evaluation of PLR medians revealed 126.62 (67.3-232.63) in the normal pregnant group and 168.78 (43.66-803.85) in the pregnant appendicitis group, indicating a statistically significant difference (p = 0.011). The mean CAR was 2.38 (0.79–6.39) in the normal pregnant group and 6.08 (0.7-54.85) in the pregnant appendicitis group, significantly higher in the appendicitis group (p = 0.001).
No statistically significant difference was observed between the two groups regarding PMR and MLR mean comparisons (p = 0.574, p = 0.425, respectively) (Table 1).
d. Diagnostic Evaluation of Markers with Differences in the Pregnancy Group
To differentiate between non-appendicitis (HPW) and appendicitis (UPW) groups in pregnant individuals, the significant differences in NLR, PLR, and CAR markers were evaluated using the area under the ROC curve and the Youden index. It is noteworthy that MLR, which was found to be significant in the distinction of appendicitis in non-pregnant patients, loses its significance in pregnant patients, while the PLR value becomes significant. In pregnant women, the cut-off values were determined as follows: 53.3% sensitivity and 96.7% specificity for NLR at 6.51 (OR 33, 95% CI 3.984-275.727, p < 0.001), 50% sensitivity and 86.7% specificity for PLR at 170.04 (OR 6.5, 95% CI 1.820-23.213, p = 0.005), and 60% sensitivity and 90% specificity for CAR at 4.87 (OR 13.5, 95% CI 3.333–54.673, p < 0.001). It is noteworthy that NLR and CAR cut-off values in pregnant appendicitis patients (UPW) have higher threshold values compared to non-pregnant appendicitis patients (UW), which should be considered as an important point (Table – 3) (Figure – 2).
Table 3
Cut-off points and diagnostic values of variables for the distinction between pregnant non-appendicitis and pregnant appendicitis patientsPGIndex: NE*CRP/MPV
Variables | Cut-Off | Diagnostic Values | ROC Curve | Odds Ratio |
Sensitivity | Specificity | PPV | NPV | Accuracy | Area (SE) | %95 CI | p | Odds Ratio | %95 CI | p |
NLR | 6.51 | 53.3% | 96.7% | 94.1% | 67.4% | 75.0% | 0.751 (0.066) | 0.622–0.880 | 0.001 | 33 | 3.984-275.727 | < 0.001 |
PLR | 170.04 | 50.0% | 86.7% | 78.9% | 63.4% | 68.3% | 0.691 (0.070) | 0.553–0.829 | 0.011 | 6.5 | 1.820-23.213 | 0.005 |
CAR | 4.87 | 60.0% | 90.0% | 85.7% | 69.2% | 75.0% | 0.749 (0.067) | 0.617–0.881 | 0.001 | 13.5 | 3.333–54.673 | < 0.001 |
PGIndex | 10.62 | 73.3% | 96.7% | 95.7% | 78.4% | 85.0% | 0.842 (0.056) | 0.733–0.952 | < 0.001 | 79.75 | 9.276-685.633 | < 0.001 |
e. Diagnostic Power of PGIndex in Distinguishing Appendicitis in Pregnant Women
To better assess the differences between pregnant women without appendicitis (HPW) and pregnant women with appendicitis (UPW), a binomial logistic regression analysis was conducted, including neutrophil count, lymphocyte count, albumin level, mean platelet volume (MPV), and C-reactive protein (CRP), which showed significant differences in comparisons between the two groups. Neutrophil count, CRP level, and MPV did not lose their significance in multivariable regression analysis, but lymphocyte count, and albumin level individually lost their determinative value (p = 0.046, p = 0.016, p = 0.005, p = 0.514, and p = 0.151, respectively).
An attempt was made to establish a new evaluation criterion based on the relationship of the values maintaining significance in multivariable analysis with the groups. The Pregnant Index (PGIndex) was defined as PGIndex = NE*CRP/MPV based on the positive significance of blood values in pregnant appendicitis cases.
In pregnant women without appendicitis (HPW), the median PGIndex was found to be 5.22 (1.57–20.62), whereas, in pregnant women with appendicitis (UPW), this value was 18.71 (1.74–438.3), significantly higher than the other group (p < 0.001).
When the PGIndex value that best distinguished between the two groups was calculated using the ROC curve and the Youden index, the cut-off value was found to be 10.62 with 73.3% sensitivity, 96.7% specificity, 95.7% positive predictive value, 78.4% negative predictive value, and 85% test accuracy (OR 79.75; 9.276-685.633; p < 0.001). Compared to other markers, PGIndex had the highest accuracy value, and it was observed that the likelihood of belonging to the appendicitis group in patients with a PGIndex above 10.62 was 78.75 times higher than in a patient below this threshold (Table – 3) (Figure – 2).