From May 2019 to April 2020, there were 1762 pregnant women planning a vaginal delivery in the Affiliated Hospital of Xuzhou Medical University. After exclusions and eliminations, 696 patients were included in the study. Of these, 487 patients collected from May 2019 to December 2019 were formed into a training cohort to assess the risk factors of intrapartum fever and develop a nomogram. According to whether intrapartum body temperature exceeds 38℃, they were divided into afebrile group (n = 415) and febrile group (n = 72). The remaining 209 cases abstracted from January 2020 to April 2020 were formed into a validation cohort to test the nomogram. The patient recruitment flowchart is shown in Fig. 1.
Table 1 presents the general demographic characteristics and perinatal factors of the training cohort and the validation cohort. No statistically significant difference was found between two groups.
Table 1
Comparison of demographic characteristics and perinatal factors between training cohort and validation cohort
Variable
|
Training cohort
(n = 487)
|
Validation cohort(n = 209)
|
P
|
Age [M (IQR)]
|
28(4)
|
29(5)
|
0.081
|
BMI [M (IQR)]
|
26.67(3.89)
|
26.40(4.72)
|
0.565
|
Gestational age [M (IQR)]
|
275(11)
|
274(10)
|
0.402
|
Accompany disease (%)
GDM
Abnormal thyroid function
Hypertension during pregnancy
|
62(12.7%)
8(1.6%)
20(4.2%)
|
24(11.5%)
3(1.4%)
10(4.8%)
|
0.647
0.841
0.729
|
Parity (%)
Primipara
Multipara
|
294(60.4%)
193(39.6%)
|
123(58.9%)
86(41.1%)
|
0.708
|
Body temperature on admission [M (IQR)]
|
36.5(0.2)
|
36.5(0.2)
|
0.232
|
WBC counts on admission [M (IQR)]
|
8.3(2.7)
|
8.7(3.0)
|
0.168
|
HB on admission [M (IQR)]
|
12.1(2)
|
12(2)
|
0.508
|
Premature rupture of membranes (%)
Yes
No
|
72(14.8%)
415(85.2%)
|
25(12%)
184(88%)
|
0.324
|
Time from rupture of membranes to delivery [M (IQR)]
|
188(434)
|
234(480)
|
0.836
|
Method of membrane rupture (%)
Spontaneous
Surgical
|
224(46.0%)
263(54%)
|
89(42.6%)
120(57.4%)
|
0.407
|
Oxytocin usage (%)
Yes
No
|
276(56.7%)
211(43.3%)
|
110(52.6%)
99(47.4%)
|
0.325
|
Fetal weight [M (IQR)]
|
3340(490)
|
3350(580)
|
0.749
|
Amniotic fluid pollution Ⅲ。 (%)
Yes
No
|
20(4.1%)
467(95.9%)
|
11(5.3%)
198(94.7%)
|
0.686
|
Duration of the first stage of labor [M (IQR)]
|
470(450)
|
420(438)
|
0.203
|
Duration of the second stage of labor [M (IQR)]
|
31(46)
|
28(48)
|
0.120
|
Number of vaginal examinations [M (IQR)]
|
2(1)
|
2(2)
|
0.803
|
Epidural labor analgesia (%)
Yes
No
|
139(28.5%)
348(71.5%)
|
59(28.2%)
150(71.8%)
|
0.933
|
Analgesia time [M (IQR)]
|
0(160)
|
0(133)
|
0.834
|
Abbreviations: |
BMI, body mass index; GDM, gestational diabetes; WBC, white blood cell; HB, Hemoglobin; IQR, interquartile range |
The data of 487 parturient in the training cohort were analyzed to examine the influencing factors of intrapartum fever. The univariate analysis results of the influencing factors related to intrapartum fever were shown in Table 2. The results showed: nulliparity, premature rupture of membranes, time from rupture of membranes to delivery, fetal weight, method of membrane rupture, oxytocin usage, amniotic fluid state, duration of the first stage of labor, duration of the second stage of labor, number of vaginal examinations, epidural labor analgesia and analgesia time were related to intrapartum fever (P < 0.2).
Table 2
Univariate analysis of factors related to intrapartum fever (Training cohort)
|
Febrile
(n = 72)
|
Afebrile
(n = 415)
|
P
|
Age [M (IQR)]
|
28(4)
|
28(4)
|
0.760
|
BMI [M (IQR)]
|
26.29(3.79)
|
26.77(3.85)
|
0.756
|
Gestational age [M (IQR)]
|
275.5(11)
|
275(11)
|
0.466
|
Accompany disease (%)
GDM
Abnormal thyroid function
Hypertension during pregnancy
|
10(13.9%)
3(4.2%)
1(1.4%)
|
52(12.5%)
14(3.5%)
7(1.7%)
|
0.749
0.667
0.854
|
Parity (%)
Primipara
Multipara
|
59(81.9%)
13(18.1%)
|
235(56.6%)
180(43.4%)
|
< 0.001
|
Premature rupture of membranes (%)
Yes
No
|
20(27.8%)
52(72.2%)
|
52(12.5%)
363(87.5%)
|
0.001
|
Body temperature on admission [M (IQR)]
|
36.5(0.2)
|
36.5(0.2)
|
0.414
|
WBC counts on admission [M (IQR)]
|
7.95(3.2)
|
8.4(2.5)
|
0.360
|
HB on admission [M (IQR)]
|
12.05 ± 1.24
|
12.07 ± 1.1
|
0.995
|
Time from rupture of membranes to delivery [M (IQR)]
|
318.5(671)
|
168(406)
|
0.009
|
Method of membrane rupture (%)
Spontaneous
Surgical
|
40(55.6%)
32(44.4%)
|
184(44.3%)
231(55.7%)
|
0.078
|
Oxytocin usage (%)
Yes
No
|
52(72.2%)
20(27.8%)
|
224(54%)
191(46%)
|
0.004
|
Fetal weight [M (IQR)]
|
3410(508)
|
3320(480)
|
0.175
|
Amniotic fluid pollution Ⅲ degree (%)
Yes
No
|
12(16.6%)
60(83.4%)
|
8(1.9%)
407(98.1%)
|
< 0.001
|
Duration of the first stage [M (IQR)]
|
695.9(192.3)
|
417.5(443.1)
|
< 0.001
|
Duration of the second stage [M (IQR)]
|
83.8(48.5)
|
28(38)
|
< 0.001
|
Number of vaginal examinations [M (IQR)]
|
3(2)
|
2(2)
|
< 0.001
|
Epidural labor analgesia (%)
Yes
No
|
50(69.4%)
22(30.6%)
|
89(21.4%)
326(78.6%)
|
< 0.001
|
Analgesia time [M (IQR)]
|
330(433)
|
0(100)
|
< 0.001
|
Abbreviations: BMI, body mass index; GDM, gestational diabetes; WBC, white blood cell; HB, Hemoglobin; IQR, interquartile range |
The above 12 factors with significant univariate analysis results were assigned, and then included in the multivariate logistic regression analysis, using forward stepwise regression. The results were shown in Table 3.
Table 3
Multivariate analysis of related factors of intrapartum fever
Risk factor
|
B
|
SE
|
Wald
|
P
|
OR
|
95%CI
|
Primipara
|
0.889
|
0.383
|
5.400
|
0.02
|
2.433
|
1.149–5.150
|
Premature rupture of membranes
|
0.861
|
0.377
|
5.213
|
0.022
|
2.366
|
1.130–4.954
|
Epidural labor analgesia
|
1.061
|
0.438
|
5.872
|
0.015
|
2.890
|
1.225–6.818
|
Amniotic fluid pollution Ⅲ degree
|
2.341
|
0.585
|
15.991
|
0.000
|
10.391
|
3.299–32.729
|
The second stage of the labor ≥ 120 min
|
1.473
|
0.573
|
6.612
|
0.010
|
4.363
|
1.419–13.410
|
Fetal weight
|
2.014
|
0.645
|
9.738
|
0.002
|
7.492
|
2.115–26.542
|
Analgesia time < 4 h
|
|
|
11.823
|
0.003
|
|
|
Analgesia time(4–6 h)
|
-0.815
|
0.555
|
2.513
|
0.142
|
0.443
|
0.149–1.315
|
Analgesia time > 6 h
|
0.798
|
0.519
|
2.364
|
0.124
|
2.220
|
0.803–6.135
|
Constant
|
-2.941
|
0.670
|
19.274
|
0.000
|
0.053
|
|
Abbreviations: OR, odds ratio; CI, confidence interval |
On multivariate logistic regression analysis, with results reported as OR [odds ratio] (95% CI), nulliparity (2.433[1.149–5.150]), epidural labor analgesia (2.890[1.225–6.818]), premature rupture of membranes (2.366[1.130–4.954]), second stage of labor ≥ 120 min (4.363[1.419–13.410]), amniotic fluid pollution Ⅲ degree (10.391[3.299–32.729]), fetal weight ≥ 4000 g (7.492[2.115–26.542]) were significantly related to intrapartum fever. According to clinical experience and previous studies, 12,13 the duration of epidural analgesia also played a significant role in intrapartum fever. Although in our study, this variable did not show any significance, we still incorporated it into nomogram development.
Figure 2 shows the nomogram formed to predict the risk of intrapartum fever based on these selected parameters. By drawing a vertical line to the first row, the observed value of each parameter is designated as a certain point. Then calculate the total score, which corresponds to the individual's risk of intrapartum fever.
Nomogram to estimate the risk of intrapartum fever. To use the nomogram, find the position of each variable on the corresponding axis, draw a line to the points axis for the number of points, add the points from all of the variables, and draw a line from the total points axis to determine the fever probabilities at the lower line of the nomogram
The nomogram demonstrated good accuracy in estimating the risk of intrapartum fever, with an AUC of 0.855 (95% CI 0.810–0.899). In addition, Hosmer-Lemeshow goodness-of-fit test (X2 = 4.585, P = 0.801) and calibration plots graphically indicated good agreement between the predicted value of the model and the actual observed value, all of these showed good agreement on the presence of intrapartum fever.
In the testing cohort, the nomogram displayed an AUC of 0.808 (95%CI 0.727–0.889), and the risk estimate also had a good calibration curve. The ROC curve and calibration diagram of the training cohort and the verification cohort were shown in Fig. 3.
The best cut-off value for the total score of the nomogram was determined to be 167. The sensitivity, specificity, positive predictive value, and negative predictive value used to distinguish the occurrence of intrapartum fever were 88.6%, 66.7%, 97.6%, and 27.8% in the training cohort, and 88.5%, 52.9%, 95.5% and 29.0% in the validation cohort, respectively. (Table 4).
Table 4
Accuracy of the prediction scores of the nomogram for estimating the risk of intrapartum fever
Variable
|
Value(95%CI)
|
Training Cohort Validation Cohort
|
Area under ROC curve,
Concordance index
|
0.855(0.810–0.899)
|
0.808(0.727–0.889)
|
Cutoff score
|
167
|
167
|
Sensitivity, %
|
88.6(85.3–91.3)
|
88.5(83.0-92.5)
|
Specificity, %
|
66.7(47.1–82.1)
|
52.9(28.5–76.1)
|
Positive predictive value, %
|
97.6(95.5–98.8)
|
95.5(91.0-97.9)
|
Negative predictive value, %
|
27.8(18.2–39.8)
|
29.0(14.9–48.2)
|
Positive likelihood ratio
|
2.659(1.601–4.415)
|
1.882(1.134–3.123)
|
Negative likelihood ratio
|
0.171(0.128–0.228)
|
0.216(0.132–0.355)
|
Abbreviations: ROC, receiver operating characteristic; CI, confidence interval |
In addition, we also paid attention to the perinatal outcomes of mothers and infants in the febrile group and the afebrile group. The results confirmed that maternal fever during delivery increased the rate of cesarean delivery, the rate of bleeding during delivery, and increased the chance of antibiotic use. Because only Apgar scores records in the obstetrical records, so we just analyzed the Apgar score < 7 at 1 minute and 5 minutes, and found that the febrile group had lower Apgar scores of newborns. (Table 5)
Table 5
Comparison of maternal and infant perinatal outcomes between febrile group and afebrile group
|
Febrile
(n = 104)
|
Afebrile
(n = 593)
|
P
|
Transferred to cesarean delivery
|
27(26%)
|
0(0%)
|
< 0.001
|
Bleeding during delivery
|
250(100)
|
300(200)
|
< 0.001
|
Antibiotic
Yes
No
|
65(90.3%)
7(9.7%)
|
106(25.5%)
309(74.5%)
|
< 0.001
|
Apgar score < 7 at 1 minute
|
9(8.7%)
|
8(1.3%)
|
< 0.001
|
Apgar score < 7 at 5 minutes
|
6(5.8%)
|
4(0.7%)
|
0.001
|