Induction of Labour with Prostaglandins: Does Their Pro-Inflammatory Effect Mimic Chorioamnionitis After PROM?

Abstract

Purpose

Induction of labour (IOL) is commonly performed by administration of prostaglandin E (PGE). As pro-inflammatory agents, a known side-effect of PGE is maternal fever. This is problematic as it potentially mimics chorioamnionitis and may lead to unnecessary interventions such as administration of antibiotics or cesarean section. The aim of the study was therefore to investigate the effect of PGE on pregnancy outcomes.

Methods

Retrospective single-centre cohort study with inclusion of women ≥ 37 weeks of gestation who underwent IOL with PGE and subsequently developed PROM (Group 1) or women who presented with spontaneous PROM without contractions (Group 2). At the time of PROM, CRP and white blood count (WBC) were assessed. We compared rates of maternal fever, Triple I, mode of delivery, and administration of antibiotics between Group 1 and Group 2.

Results

A total of n = 850 women were included (Group 1: 200, Group 2: 650). CRP levels were higher in patients with more prolonged PGE administration (< 12 hours: 0.3 mg/dL vs. > 48 hours: 1.4 mg/dL, p = 0.002; r = 0.309; p < 0.001). WBCs were also higher after PGE administration (11.1 × 10⁹/L vs. 9.5 × 10⁹/L, p < 0.001). The logistic regression model revealed an association between IOL with PGE and antibiotics during labour. However, the rates of maternal fever and suspected Triple I did not differ significantly between the two groups, nor did the mode of delivery.

Conclusion

IOL with PGE increases maternal serum levels of CRP (time-dependently), as well as WBC. This might lead to overtreatment with antibiotics during labour. However, the diagnosis of maternal fever or rates of suspected Triple I were not affected in our cohort.

Zusammenfassung

Zielsetzung

Die Geburtseinleitung am Termin erfolgt häufig mittels Prostaglandin E (PGE). Ob aufgrund deren proinflammatorischer Wirkung mütterliche oder kindliche Nebenwirkungen wie erhöhte Infektparameter oder Fieber auftreten, wurde bisher nicht systematisch untersucht. Fieber unter Geburt ist aber auch das Leitsymptom einer Chorioamnionitis, weshalb die Geburtseinleitung mit PGE unnötige geburtshilfliche Interventionen wie die Gabe von Antibiotika nach sich ziehen könnte. Ziel dieser Studie war es daher, die Auswirkung einer Geburtseinleitung mit PGE auf maternale Infektparameter sowie den weiteren Geburtsverlauf zu untersuchen.

Methoden

Es handelt sich um eine retrospektive, monozentrische Kohortenstudie. Eingeschlossen wurden Frauen ≥ 37. SSW, die mit PGE eingeleitet wurden und unter Einleitung einen vorzeitigen Blasensprung entwickelten (Gruppe 1), und Frauen, die sich mit einem spontanen vorzeitigen Blasensprung vorstellten (Gruppe 2). Alle Frauen erhielten zum Zeitpunkt des Blasensprungs eine Blutentnahme mit Bestimmung der Infektparameter (CRP und Leukozyten). Es wurde die Häufigkeit von maternalem Fieber, Triple I, Entbindungsmodus und Antibiotikatherapie in beiden Gruppen verglichen.

Ergebnisse

Insgesamt wurden 850 Frauen eingeschlossen (Gruppe 1: n = 200, Gruppe 2: n = 650). Frauen mit vorangegangener PGE-Gabe hatten signifikant höhere CRP-Werte als Frauen mit vorzeitigem Blasensprung ohne PGE-Gabe, wobei die CRP-Werte umso höher waren, je länger PGE verabreicht wurde (< 12 h: 0,3 mg/dl vs. > 48 h: 1,4 mg/dl, p = 0,002; r = 0,309; p < 0,001). Auch die Leukozyten waren nach der PGE-Gabe erhöht (11,1 × 10⁹/l vs. 9,5 × 10⁹/l, p < 0,001). Die logistische Regressionsanalyse ergab, dass Gruppe 1 häufiger eine Therapie mit Antibiotika erhielt, obwohl sich die Raten von maternalem Fieber oder die Verdachtsdiagnose eines Triple I nicht unterschieden. Die Einleitung hatte keinen Einfluss auf den Geburtsmodus.

Diskussion

Die Einleitung mit PGE führt zu einer Erhöhung der maternalen Infektparameter (Leukozyten und CRP), was eine Übertherapie mit Antibiotika wahrscheinlicher macht. In der untersuchten Kohorte war kein Unterschied bezüglich des Geburtsmodus oder der Rate an maternalem Fieber zu beobachten.

Keywords

induction of labour - delivery - bacterial infection - due date

Schlüsselwörter

Geburtseinleitung - Wehen - bakterielle Infektion - Geburtstermin

Introduction

Induction of labour (IOL) is one of the most common obstetric interventions in term pregnancies. Reasons for IOL include safety concerns for the child and/or the mother [1]. If the cervix is unfavourable, the standard agent for pharmacological cervical ripening is prostaglandin E (PGE), which can be administered as dinoprostone (PGE2) or low-dose misoprostol (PGE1 analog) [1] [2] [3]. Yet, prostaglandins, as pro-inflammatory agents, may cause side effects such as maternal fever [3]. It is unclear if IOL with prostaglandins might mimic chorioamnionitis during labour.

During labour, an intraamniotic infection can only be suspected but not diagnosed definitively, as confirmation of a bacterial infection of the amniotic fluid, placenta, fetus, fetal membranes, or decidua requires time [4]. Therefore, the term “Triple I” is now commonly used when chorioamnionitis is suspected (intrauterine inflammation, infection or both) [5] [6]. It is defined as the occurrence of maternal fever in combination with either fetal tachycardia, maternal white blood cells (WBC) count > 15 × 10⁹/L or purulent fluid from the cervical os. Chorioamnionitis can be diagnosed by amniocentesis (gram strain, low glucose or positive culture) or by placental pathology [7]. When applying the criteria of Triple I, bacteria can be identified as the cause of fever in only 50% of cases after delivery, and an infection of the fetus is even less frequent (approximately 5%) [8]. Other reasons for maternal fever or suspected Triple I include sterile inflammation in the absence of bacteria or epidural anesthesia [9] [10].

Around 8–10% of women ≥ 37 weeks of gestation present with premature/prelabour rupture of membranes (PROM) [11] [12]. To reduce the risk of chorioamnionitis leading to severe fetal or maternal infections, current evidence and guidelines recommend IOL within 24 hours [1] [11] [12] [13].

The study aimed to investigate whether IOL induced by prostaglandins might cause maternal fever, thereby leading to unnecessary interventions, such as the administration of antibiotics or operative delivery. To this end, we compared women with spontaneous PROM and PROM after IOL using PGE. In addition, we assessed the occurrence of Triple I, pregnancy outcomes, treatment with antibiotics, and the effect on maternal serum levels of CRP and WBC.

Material and Methods

This study is a retrospective, single-centre cohort study conducted between 01/2009 and 01/2018 at a tertiary referral hospital. All singleton pregnancies with PROM between 37+0–42+0 weeks of gestation, who attempted vaginal delivery and had blood collection within six hours after PROM, were screened for inclusion. Exclusion criteria were the interruption of IOL due to various situations (e.g., patient request), other methods of IOL than PGE, or severe maternal or fetal morbidity, as well as intrauterine fetal demise ([Fig. 1]). The included patients were divided into two groups based on to the time between PGE administration and PROM ([Fig. 2]). Group 1 included patients who were admitted for IOL for other indications and in whom PROM occurred after PGE administration. Group 2 was admitted with spontaneous PROM without prior PGE administration. Group 1 was subsequently divided into subgroups depending on the time interval between first PGE administration and PROM: < 12 h, 12–24 h, 24–48 h and ≥ 48 h.

Fig. 1 Inclusion and exclusion criteria of the study cohort. IOL = induction of labour; PGE = prostaglandin E; (P)PROM = preterm premature rupture of membranes.

Fig. 2 Treatment of Group 1 and Group 2. CRP = c-reactive protein; PROM = premature rupture of membranes; WBC = white blood cells.

According to our standard operating procedure (SOP), bloods were collected within six hours after PROM to determine WBC and CRP if the woman presented within this time window (“CRP at PROM” or “WBC at PROM”). Women with spontaneous PROM were asked to come to the hospital promptly after PROM, but no later than 12 hours. CRP and WBC were assessed every eight hours until birth. All women in Group 1 underwent blood collection at the time of IOL, with determination of WBC (“WBC at baseline”). In some cases, CRP levels were also measured (“CRP at baseline”).

IOL after PROM was indicated within 12–24 hours according to national guidelines [1]. During the study period (2009–2019) the following induction methods were used [14]:

• PROPESS 10 mg (vaginal insert, agent: dinoprostone)

• MINPROSTIN E2 1–2 mg (vaginal gel, agent: dinoprostone)

• MISODEL 200 µgr (vaginal insert, agent: misoprostol)

The diagnosis of Triple I (“infection, inflammation, or both”) was made based on the following definition: Maternal fever defined as repeated temperature increase ≥ 37.9 °C without any other explainable cause plus one of the following criteria: fetal tachycardia above 160/min for at least 10 min, WBC > 15 10⁹/L without administration of corticosteroids and/or purulent fluoride from the cervix [15]. A confirmed Triple I/chorioamnionitis was diagnosed if bacterial culture of the placenta or the uterine cavity was positive or if there were signs of infection upon pathologic examination of the placenta.

All newborn with suspected infection received an ear swab and a blood culture, and the diagnosis of confirmed infection was based on national guidelines [16].

Due to our local SOP, women received antibiotic treatment with intravenous ampicillin 1 every four hours (loading dose 2 g) if PROM lasted longer than 18 hours or if they showed signs of infection (e.g., maternal fever, WBC > 15 × 10⁹/L or CRP > 1 mg/dL). In the presence of contraindications for ampicillin, clindamycin 600 mg i.v. every eight hours was administered. Women with positive B-streptococcus status received antibiotics prophylaxis after onset of labour or PROM.

Statistical analysis

IBM SPSS Statistics for Windows, version 28 (IBM Corp., Armonk, N.Y., USA) was used for our statistical analysis. Quantitative data are described by mean and standard deviations or median and interquartile range. Categorical data are presented as absolute and relative frequencies. Differences in the distributions of quantitative variables were tested using the Mann–Whitney U test, whereas categorical data were compared using Pearson’s Chi-square test or Fisher’s exact test. The Pearson correlation coefficient was used to describe correlations. Odds ratios were calculated using a multivariate logistic regression model. The regression model was used to determine whether CRP, WBC and duration of PGE treatment were correlated with suspected Triple I or antibiotic treatment and whether Group 1 was more likely to be affected. The duration between PROM and delivery and the duration of active labour are known to be associated with both Triple I and the use of antibiotics, and were therefore also included in the regression model.

All statistical tests were conducted two-sided and a p value < 0.05 was considered statistically significant.

Ethical approval

The study was approved by our local Institutional Ethic Board (number 2025–364-S-SB). The study was not registered in a public trial registry.

Results

Baseline characteristics

A total of n = 850 patients met the inclusion criteria and were included in the final analysis ([Fig. 1]). Of them, 200 women were induced with PGE with intact membranes (Group 1) and 650 women were admitted because of spontaneous PROM (Group 2; [Fig. 2]). Only 44 women of Group 2 developed spontaneous contractions, whereas 606 women required induction with prostaglandins (93%).

Women in the induction group (Group 1) were more likely to be affected by hypertensive pregnancy disorders, placental insufficiency or diabetes ([Table 1]). We did not observe a significant difference in BMI, parity, B-streptococcus status or smoking between the groups. The time from PROM to delivery was significantly shorter in Group 1 (12 vs. 22 hours, p < 0.001), but the time of active labour did not differ significantly (7 vs. 6 hours, p = 0.332). We did not observe relevant differences in mode of delivery, however, women with suspected Triple I were more likely to deliver by cesarean section (65% vs. 16%, p < 0.001).

Table 1 Baseline characteristics. Data are given as mean ± SD, n (%) or median (interquartile range). Bold characters: Significant difference between groups p < 0.05.

	Induction of labour with prostaglandins (Group 1) N = 200	Spontaneous PROM (Group 2) N = 650	p
BMI = body mass index; CRP = c-reactive protein; NICU = neonatal intensive care unit; PROM = premature rupture of membranes; WBC = white blood cells „at baseline“: admission to the hospital, „at PROM“: within six hours after the occurrence of PROM (Group 1) or within 12 hours after the occurrence of PROM (Group 2)
Maternal Age	33.8 (± 6.6)	31.0 (± 4.5)	< 0.001
BMI	23.1 (± 4.2)	23.5 (± 4.6)	0.271
Nulliparous	79.0% (158)	74.3% (483)	0.104
Smoking	2.0% (4)	2.9% (19)	0.622
Hypertensive disease of pregnancy	10.5% (21)	2.0% (13)	< 0.001
Any form of placental insufficiency	9.0% (18)	2.6% (17)	< 0.001
Any form of diabetes	15.0% (30)	9.1% (59)	0.024
Time from PROM to delivery	12.0 (8–19)	22.0 (18–29)	< 0.001
Active labour in hours	7.0 (4.0–11.0)	6.0 (3.0–10.0)	0.332
Group B Streptococcus status
Positive	16.0% (32)	13.1% (85)
Negative	66.5% (133)	68.9% (448)
Unknown	17.5% (35)	18.0% (117)
Weeks of gestation	39.34 (± 1.4)	38.8 (± 1.2)	< 0.001
CRP at baseline	0.5 (0.2–0.9)	0.4 (0.2–0.6)	0.359
CRP at PROM	0.6 (0.2–1.3)	0.4 (0.2–0.6)	< 0.001
WBC at baseline	9.3 (8.1–10.7)	9.5 (8.2–11.0)	0.209
WBC at PROM	11.1 (9.4–13.6)	9.5 (8.2–11.0)	< 0.001
Induction with prostaglandins	100% (200)	93.2% (606)	< 0.001
Antibiotics during labour	39.0% (78)	27.5% (179)	0.003
Maternal fever	4.5% (9)	4.2% (25)	0.681
Suspected Triple I	4.0% (8)	3.8% (23)	0.829
Mode of delivery
Spontaneous	70.0% (140)	70.1% (459)
Cesarean section	17.5% (35)	18.3% (119)
Vacuum-assisted delivery	12.5% (25)	11.1% (72)
Birth weight	3447 ± 465	3319 ± 380	< 0.001
NICU for any reason	15.0% (30)	7.8% (51)	0.004
Suspected infection of the newborn	5.5% (11)	3.7% (22)	0.207
Confirmed infection	54.5% (6/11) 3.0% (6/200)	36.3% (8/22) 1.2% (8/650)	0.459
Any form of proven infection after delivery (mother or child)	5.5% (11)	5.7% (37)	1.000
Confirmed Triple I by bacterial cultivation of the amniotic fluid or by histologic findings	50.0% (4/8) 2.0% (4/200)	56.5% (13/23) 2.0 (13/650)	0.550 1.000

Maternal serum parameters

In Group 1, WBC was determined in all cases and CRP was determined in 65 of 200 women prior to IOL. Compared to Group 2, that presented with spontaneous PROM, maternal WBC and CRP levels did not differ. However, levels of WBC and CRP were significantly elevated at the time of PROM after IOL with PGE (0.6 mg/dL vs. 0.4 mg/dL, p < 0.001). In Group 1, we observed a positive correlation between the length of treatment with PGE and the level of CRP (r = 0.309, p < 0.001). Women with PGE treatment for less than 12 hours had a median CRP of 0.3 mg/dL, whereas women with PGE treatment for more than 48 hours showed a median CRP of 1.4 mg/dL (p = 0.002, results are shown in [Fig. 3] and [Table 1]). WBC was significantly elevated after IOL with PGE, but then remained stable with longer administration of PGE (11.1 × 10⁹/L vs. 9.5 × 10⁹/L, p < 0.001).

Fig. 3 a Level of WBC at the time of PROM after induction with PGE (Group 1). The cases were divided in groups depending on the duration of PGE administration. b Level of CRP at the time of PROM after IOL with PGE (Group 1). The cases were divided in groups depending on the duration of PGE administration. CRP = c-reactive protein; PGE = prostaglandin E; PROM = premature rupture of membranes; WBC = white blood cells.

Antibiotics during labour

Significantly more women of Group 1 received antibiotics during labour compared to women of Group 2 (39 vs. 28%; p = 0.002).

The logistic regression model revealed an increased likelihood for antibiotic treatment, the higher the CRP levels were (OR 4.22, 95% CI: 2.77–6.43, p < 0.001), and the longer the time from PROM to delivery lasted (OR 1.25, 95% CI: 1.20–1.31; p < 0.001; results are shown in [Table 2]). However, WBC and duration of PGE administration were not independent risk factors for antibiotic treatment.

Table 2 Logistic regression model: probability of antibiotic therapy during labour. Bold characters: Significant difference between groups, p < 0.05.

	OR	95% CI	p
The logistic regression model revealed an increased probability of receiving antibiotic therapy, depending on CRP, duration of labour, and induction with PGE (Group 1). The duration of active labour or PGE treatment did not affect antibiotic treatment during labour. CRP = C-reactive protein; PGE = prostaglandin E; PROM = premature rupture of membranes; WBC = white blood cells
CRP at PROM	4.22	2.77–6.43	< 0.001
WBC at PROM	1.00	0.93–1.08	0.976
Time from PROM to delivery	1.25	1.20–1.31	< 0.001
Duration of active labour	1.03	0.98–1.08	0.215
Group 1	2.41	1.30–4.46	0.005
Duration of PGE treatment	1.00	0.98–1.02	0.801

Rate of Triple I

Comparing the rates of suspected Triple I, we did not find a difference in both groups (4.0 vs. 3.8%, p = 0.829). The logistic regression model identified the levels of CRP at PROM and the duration of active labour as risk factors for suspected Triple I (OR 1.48, 95% CI 1.20–1.83; p < 0.001 and OR 1.08, 95% CI 1.03–1.13; p = 0.001, respectively; [Table 3]). Although newborns in Group 1 were more likely to be admitted to NICU (15.0% vs. 7.8%, p = 0.004), there was no significant difference in the rates of suspected or confirmed infection ([Table 1]).

Table 3 Logistic regression model: diagnosis of suspected Triple I during labour. Bold characters: Significant difference between groups, p < 0.05.

	OR	95% CI	p
The logistic regression model revealed an increased probability of diagnosis of Triple I depending on CRP levels at the time of PROM and the duration of active labour. WBC, the time from PROM until delivery, IOL with PGE (Group 1) and the duration of PGE treatment did not affect the diagnosis of Triple I. CRP = C-reactive protein; PGE = prostaglandin E; PROM = premature rupture of membranes; WBC = white blood cells
CRP at PROM	1.48	1.20–1.83	< 0.001
WBC at PROM	1.03	0.90–1.17	0.700
Time from PROM to delivery	0.98	0.94–1.03	0.404
Duration of active labour	1.08	1.03–1.13	0.001
Group 1	0.83	0.28–2.45	0.825
Duration of PGE treatment	0.99	0.95–1.02	0.495

Discussion

In this study we demonstrated that induction with PGE has an impact on the pro-inflammatory parameters CRP and WBC in maternal blood serum, without being a risk factor for suspected or confirmed Triple I itself. The levels of CRP increased with the duration of PGE administration, whereas the levels of WBC were generally elevated, but not in a time-dependent manner. Women undergoing induction with PGE before PROM were more likely to receive antibiotic treatment during labour compared to women with spontaneous PROM. Induction with PGE had no impact on mode of delivery.

CRP is an acute-phase pro-inflammatory protein primarily produced by hepatocytes and induced, particularly by interleukin-6 [17]. Interleukin-6 is a promoter of PGE₂ production in amniotic and decidual cells, indicating an interaction of these pro-inflammatory proteins [18]. To our knowledge, the pathway of CRP release by PGE during labour has not been investigated yet. Our results suggest a time-dependent increase of CRP by PGE without increasing maternal fever or suspected Triple I.

Evidence for the usefulness of CRP in diagnosing chorioamnionitis is inconclusive. A significant number of publications indicates that CRP levels are elevated in women with proven chorioamnionitis or neonatal infection; however CRP levels are not specific and are not helpful for safely ruling in or out neonatal infection [19] [20] [21]. Therefore, determining CRP during labour is not recommended [22] [23]. Pregnancy itself induces several physiological changes in blood volume and viscosity, and therefore leads to elevated CRP levels in pregnant women in the absence of an infection. Wirestam et al. reported a median CRP level of 0.4 mg/dL in healthy pregnant women during the third trimester (compared to 0.2 mg/dL in the first trimester) [24]. It should be considered that elevation of CRP may occur for other reasons than infection, e.g., in women with preeclampsia [25]. During the study period, all women with CRP levels greater than 1 mg/dL received antibiotic therapy. Although the frequency of confirmed infections did not differ between the two groups, women who were induced with PGE were more likely to receive antibiotics (Group 1). This can be explained by the elevation of CRP by PGE and supports the recommendation that CRP should not be considered in routine monitoring for Triple I.

A WBC > 15 × 10⁹/L is one criterion for suspected Triple I, and the threshold represents the 80^th centile during labour [7] [26]. Although well established, the sensitivity for Triple I is modest, at 76%, with a poor specificity (30%) [10] [26]. Our finding that PGE administration affects WBC levels is one example of how many parameters beyond chorioamnionitis can influence WBC, and it provides an explanation for the low specificity of WBC. Also, reference values of WBC are affected by pregnancy, leading to an elevation of WBC in the absence of infection [27]. Additionally, the activation and increase of leukocytes during labour are physiological. For example, the process of cervical softening is associated by an influx of leukocytes that promotes collagenase release, an effect which is driven by misoprostol [28] [29] [30] [31].

Administration of antibiotics during labour is a standard procedure; however, there is emerging evidence about adverse effects on and neonates. Bank et al. conducted a retrospective analysis to describe the impact of treating isolated maternal fever during labour with antibiotics. Postpartum endometritis was significantly reduced after antibiotic treatment; however, the rates of admission to NICU or an Apgar < 7 was higher [32]. So far, it has not been proven that antibiotics themselves contribute to adverse neonatal outcomes. Yet, in cell culture, antibiotics can induce immune cells to release pro-inflammatory cytokines and it could be hypothesized that the resulting state of inflammation worsens neonatal outcome [33]. Despite these considerations, infant gut microbiota dysbiosis can be caused by antibiotics during labour and persist for at least 12 months [34]. Therefore, treatment with antibiotics during labour should only be initiated if a benefit is expected. The German Guidelines recommend administering antibiotic 18 hours after PROM to prevent adverse maternal outcomes [22]. Although Group 1 had a shorter time between PROM and delivery, they received antibiotics more frequently. Of note, in the study period, administration of antibiotics during labour was also based on CRP levels, which may be the cause of this finding, and makes overtreatment driven by PGE likely.

Mode of delivery did not differ relevantly between the two groups; however, women with suspected Triple I were more likely to have a cesarean section. This is in line with the literature, as the contractility of the uterus is negatively affected by intrapartum fever: inflammatory cytokines lead to a downregulation of the oxytocin receptor, causing arrested labour [35]. Other potential reasons include physician anxiety or changes of fetal heart rate patterns [36]. Although suspected Triple I might lead to operative delivery for non-reassuring fetal status or arrested labour, obstetricians should consider that a cesarean section in case of suspected Triple I does not improve neonatal outcome and even increases maternal morbidity, atony in particular [37]. However, chorioamnionitis remains one of the primary risk factors for poor neonatal outcomes, and further research is warranted to identify patients at risk of being affected by bacterial infection [38].

The incidence of maternal fever did not differ between the two groups (4.5% vs. 4.2%) and was in an expected range (0.6%–7%) [36]. However, the majority of women in Group 2 was also induced by PGE, even though they received a significantly lower cumulative dose. Therefore, we cannot draw any conclusions about the connection between maternal fever and PGE administration. Lu et al. investigated 444 women with maternal fever during labour, and they found a proven infection in 41% of cases. Women who received misoprostol were more likely to develop fever in the absence of an infection, a finding that obstetricians should consider if maternal fever occurs during labour [39].

Our study is limited by its retrospective design. Also, not all women who experienced fever during labour received bacterial sampling for culture, so we can only speculate about the rate of confirmed Triple I. Another limitation is that all PGE agents were vaginally administered because oral misoprostol was not officially approved during the study period. It is also possible that not PGE, but IOL itself alters the maternal serum levels of CRP and WBC. Ramsey et al. reported fewer incidences of maternal fever if oxytocin rather than PGE was used for IOL, however, they administered high dosages of misoprostol as they investigated IOL in the second trimester [40]. IOL with oxytocin was not routinely performed in our hospital during the study period, so we cannot compare different types of IOL in this study.

In conclusion, our results suggest that IOL with PGE does elevate levels of maternal WBC, as well as CRP levels in a time-dependent manner. This potentially results in overtreatment with antibiotics during labour. Our findings should be taken into account when performing IOL with PGE.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Publication History

Received: 16 August 2025

Accepted after revision: 02 December 2025

Article published online:
10 February 2026