ABSTRACT
Objective
To study the effects of chorioamnionitis on uterine activity and to investigate associations between external and intrauterine monitoring methods and neonatal outcomes.
Design
Secondary analysis of a randomised controlled trial cohort.
Setting
Two labour wards, in a university tertiary hospital and a central hospital.
Population
Parturients with singleton pregnancies, gestational age ≥ 37 weeks and fetus in cephalic position. Clinical chorioamnionitis developed in 8.6% of cases (n = 130/1504).
Methods
Analyses of uterine activity (contractions/10 min or intrauterine pressure in Montevideo units) during the 4 h before birth adjusted for maternal characteristics and intrapartum factors.
Main Outcome Measures
Uterine activity with or without chorioamnionitis and the intervention of external versus intrauterine monitoring in relation to fetal distress (admission to neonatal intensive care with umbilical artery pH ≤ 7.10 or 5‐min Apgar score < 7), stratified by chorioamnionitis status.
Results
Uterine contraction frequency/10 min decreased in labours with chorioamnionitis during the final hour preceding birth (4.2 [SD 1.1] vs. 3.9 [SD 1.2], adjusted regression coefficient −0.383, 95% CI −0.654 to −0.112, p = 0.006) compared to non‐infected labors. In chorioamnionitis cases, mean frequency/10 min during last 4 h was higher with external versus intrauterine monitoring (4.2 [SD 0.8] vs. 3.8 [SD 0.9], MD 0.39, 95% CI 0.02–0.76, p = 0.038), and the intrauterine monitoring group had a lower incidence of fetal distress (6.7% vs. 23.1%, OR 0.24, 95% CI 0.07–0.79, p = 0.013).
Conclusions
Chorioamnionitis impairs uterine activity. Intrauterine monitoring may provide more accurate contraction analysis than external tocodynamometry and help reduce fetal compromise during labours complicated by chorioamnionitis.
Keywords: clinical chorioamnionitis, intrauterine pressure, neonatal outcome, uterine contraction
1. Introduction
Chorioamnionitis, also known as intra‐amniotic infection, is frequently observed among term parturients during labour. The condition poses a significant dilemma for obstetric care providers as it has been associated with acute neonatal morbidity and may increase the need for additional operative interventions. The inflammation may potentiate the adverse effects of tissue hypoxia, but infection alone is not an indication for immediate delivery [1, 2, 3].
The incidence of clinical chorioamnionitis in term deliveries is approximately 2%–5% [1, 4], but it has been reported to be up to 13% depending on the diagnostic criteria used [2]. The most significant risk factors associated with intra‐amniotic infection are prolonged labour and ruptured membranes [1, 2, 3]. The use of intrauterine pressure (IUP) catheters has also been associated with an increased risk of chorioamnionitis [5, 6, 7]. However, the evidence is debatable in these retrospective studies, as the risk of infection may be associated with prolonged deliveries requiring the use of IUP catheters. Interestingly, in two large randomised controlled trials (RCT), these catheters were reported not to increase the incidence of infections compared to external monitoring [8, 9], nor in the follow‐up of the first trial [10].
Clinical chorioamnionitis is associated with an increased risk of protraction and arrest disorders, ultimately leading to a higher number of operative deliveries [2, 3, 11]. Dysfunctional myometrial contractility caused by inflammation has been implicated in this association [12, 13].
Clinical chorioamnionitis has been associated with a 3.5‐fold increase in the risk of adverse neonatal outcomes among labours ≥ 34 weeks, such as pneumonia, sepsis, intracranial haemorrhage and neonatal death. Consequently, neonatal intensive care unit (NICU) admissions are more common among infants born to women with chorioamnionitis [14]. However, it remains uncertain to what extent inflammation is responsible for neonatal outcomes, or how intrapartum factors contribute. It is generally recognised that, in the presence of acidosis, labour contractions contribute to NICU admissions. Retrospective studies indicate that tachysystole increases the risk of neonatal encephalopathy in the context of chorioamnionitis [15, 16], and that the risk is elevated by hypoxia‐ischaemia associated with the inflammation [17].
We have previously reported that increasing IUP notably worsens fetal umbilical artery (UmA) pH in labours complicated by chorioamnionitis [18]. The objective of this study was to explore how intra‐amniotic inflammation affects contractility during labour. Additionally, it aimed to investigate whether contraction monitoring methods are associated with neonatal outcomes when signs of chorioamnionitis are present or absent.
2. Methods
This study is an exploratory examination of a prospective cohort derived from our RCT, which compared the effects of intrauterine (IT) and external tocodynamometries (ET) on labour outcomes. The present analysis focuses specifically on labours with and without clinical chorioamnionitis within the RCT population. The protocol and methods of the study have been published previously. The RCT was conducted between 2012 and 2017 and involved the recruitment of a total of 1504 parturients, initially with 736 in the intrauterine and 768 in the external group. The labour staff were permitted to change the monitoring method for obstetric reasons [9].
Information regarding parturients and newborns was gathered from medical records and original RCT materials. Nulliparous women, parous parturients with oxytocin augmentation during the first stage of labour and those with previous CS were enrolled. Only singleton pregnancies with gestational age ≥ 37 weeks, cephalic fetal position and cervical dilatation of ≤ 7 cm were eligible for recruitment. Women were excluded if they met any of the following criteria: estimated fetal birthweight > 4500 g, signs of fetal distress or intrauterine infection upon recruitment or positive results in serological tests for human immunodeficiency virus or hepatitis B or C virus [9].
In the RCT protocol, midwives administered oxytocin in incremental doses (with an addition of 2.0–2.5 mIU/min every 20–30 min) until 3–5 contractions /10 min or 150–300 MVU was reached, or until adequate labour progression was achieved. The baseline tone of the uterine muscle had to remain under 20 mmHg with observable relaxation between contractions. A sensor‐tipped catheter (Koala Intrauterine Pressure Catheters, Clinical Innovations) was inserted by a physician during the initial vaginal examination following randomisation. Cardiotocography data was recorded using Philips Avalon FM30 or FM50 Gemini equipment (Koninklijke Philips N.V., Amsterdam, the Netherlands).
Uterine contractile activity (UA) was analysed retrospectively by three researchers who were blinded to the parturients' basic characteristics, neonatal outcomes and labour outcomes. UA was measured by the frequency of contractions/10 min and IUP in Montevideo units (MVU) when available. These parameters were accounted at 30‐min intervals at four time points (15 min before and after exact times) 4, 3, 2 and 1 h before birth or the decision to perform a CS. The doses of oxytocin (mIU/min) were recorded simultaneously.
Clinical chorioamnionitis was defined according to the 2016 expert panel criteria [19]: Maternal pyrexia during labour was identified as temperature ≥ 38.0°C, along with either fetal tachycardia > 160/min persisting over 10 min or maternal leucocytosis > 15.0 × 109/L. This definition has changed since our original RCT, which accounts for a slight difference in the reported incidence of chorioamnionitis (31 cases fewer than in the RCT). Antibiotics were administered when these signs were observed during labour or if sampling for Streptococcus agalactiae was positive.
All participants were informed on recruitment to the study and written consent was obtained at enrolment. Parturients were not involved in planning the study and there was no questionnaire for them. A core outcome set (COS) for maternal and perinatal health research related to infectious diseases is currently under consideration by the COMET (Core Outcome Measures in Effectiveness Trials) initiative, but is not currently available [20].
2.1. Outcome Measures
The primary objective was to compare UA between cases of clinical chorioamnionitis and non‐infected cases, measured as the frequency of contractions/10 min and IUP in MVUs. The secondary objective was to evaluate the relationship between contraction monitoring methods (ET or IT based on the actual monitoring method used), in the presence or absence of clinical chorioamnionitis and indicators of fetal distress, such as admission to NICU with UmA pH ≤ 7.10 or 5‐min Apgar score < 7.
2.2. Statistical Analysis
Analyses were performed using IBM SPSS Statistics for Windows, Version 29.0. Armonk, NY: IBM Corp. Group differences were evaluated using the chi‐square test, Student's t‐test and Mann–Whitney U‐test as appropriate. Continuous variables were reported as means with standard deviations or medians with quartiles, and categorical variables as frequencies and percentages. The results were expressed as mean difference (MD), odds ratios (ORs) and 95% confidence intervals (95% CIs). For the primary objective, univariate linear regression was performed with uterine activity as the dependent variable, analysed in relation to chorioamnionitis and, separately, in relation to oxytocin dose (stratified by the presence or absence of chorioamnionitis). Multivariable linear and logistic regression analyses were adjusted for factors influencing uterine contractile activity and chorioamnionitis, including nulliparity, oxytocin dose, first stage labour duration, maternal age and body mass index. Additionally, linear regression was conducted with UmA pH as the dependent variable, analysed in relation to the two UA parameters, stratified by the presence or absence of chorioamnionitis. The results of the linear regression analyses were expressed as regression coefficients (β) and with adjusted β (aβ) for multivariable analyses. A probability value (p) of < 0.05 was considered statistically significant. All p‐values were two‐sided.
Ethical approval for the study was granted by the Ethics Committee of Pirkanmaa Hospital District (R12229) on 8 October 2012.
3. Results
A total of 1504 parturients participated in the study. As signs of intrauterine infection were an exclusion criterion at the time of enrolment, all infections were identified during delivery. Incidence of clinical chorioamnionitis was 8.6% (n = 130). Table 1 presents baseline characteristics and intrapartum factors, stratified by the presence or absence of clinical chorioamnionitis, as well as by the actual contraction monitoring method used (ET or IT).
TABLE 1.
Baseline characteristics and intrapartum factors stratified by the presence of clinical chorioamnionitis and further stratified by contraction monitoring method (external and intrauterine tocodynamometry).
| All parturients n = 1504 | External tocodynamometry n = 553 | Intrauterine tocodynamometry n = 951 | ||||
|---|---|---|---|---|---|---|
| Clinical chorioamnionitis | No signs of infection | Clinical chorioamnionitis | No signs of infection | Clinical chorioamnionitis | No signs of infection | |
| Number of birth records | 130 | 1374 | 26 | 527 | 104 | 847 |
| Maternal characteristics | ||||||
| Nulliparity (% of all births) | 100 (76.9) | 789 (57.4) | 22 (84.6) | 308 (58.4) | 78 (75.0) | 481 (56.8) |
| Maternal age (years), mean (SD) | 29.2 (5.0) | 29.4 (5.3) | 29.7 (5.3) | 29.2 (5.3) | 29.1 (4.9) | 29.5 (5.2) |
| Maternal height (cm), mean (SD) | 164.6 (5.9) | 166.1 (5.9) | 164.6 (6.5) | 166.5 (5.8) | 164.5 (5.8) | 165.9 (6.0) |
| Prepregnancy BMI (kg/m2), mean (SD) | 27.3 (6.5) | 26.0 (5.7) | 26.0 (6.8) | 25.4 (5.6) | 27.6 (6.4) | 26.4 (5.8) |
| Smoking a | 21 (17.6) | 236 (18.6) | 4 (19.0) | 82 (17.9) | 17 (17.3) | 154 (19.0) |
| Intrapartum factors | ||||||
| Gestational age (days), mean (SD) | 283.0 (8.6) | 280.5 (8.9) | 282.3 (9.5) | 279.9 (8.9) | 283.2 (8.4) | 281.0 (8.8) |
| Induction of labour | 81 (62.3) | 757 (55.1) | 16 (61.5) | 272 (51.6) | 65 (62.5) | 485 (57.3) |
| Epidural analgesia | 126 (96.9) | 1157 (84.2) | 25 (96.2) | 419 (79.5) | 101 (97.1) | 738 (87.1) |
| Streptococcus agalactiae colonisation b | 28 (23.5) | 258 (20.9) | 3 (12.5) | 89 (18.7) | 25 (26.3) | 169 (22.3) |
| Duration of labour 1st stage (hours), median (Q1–Q3) | 21.8 (15.3–27.4) | 14.2 (7.7–22.4) | 19.0 (10.8–28.6) | 13.8 (7.0–21.8) | 22.6 (16.0–27.4) | 15.0 (8.8–23.5) |
| Duration of labour 2nd stage (minutes), median (Q1–Q3) | 36 (20–41) | 20 (11–37) | 42 (27–51) | 20 (10–37) | 34 (18–49) | 20 (12–37) |
| Oxytocin mean dose/4 h (mIU/min), median (Q1–Q3) | 1.4 (0.5–2.0) | 0.9 (0.3–1.7) | 1.1 (0.5–2.0) | 0.6 (0.1–1.1) | 1.1 (0.6–2.0) | 1.0 (0.3–1.8) |
Abbreviations: BMI, body mass index; CS, caesarean section; Q, quartile; SD, standard deviation.
116 missing values.
151 missing values.
In the intention‐to‐treat analysis following randomisation, 65 parturients in the ET group and 65 in the IT group (130 in total) developed clinical chorioamnionitis. Clinicians had the option to change the method of tocodynamometry for obstetric reasons, and 60% (39 out of 65) opted to switch from ET to IT in cases of clinical chorioamnionitis. The reasons for switching to IT included non‐reliable tocogram (n = 12), dystocia (n = 8), non‐reassuring fetal heart rate (n = 7), obesity (n = 2), prior CS (n = 1) and others (n = 9). Duration of labour was significantly longer in parturients who underwent a switch in monitoring method compared to those in whom monitoring remained unchanged: 17.5 [Q1–Q3 11.6–27.1] vs. 14.2 [Q1–Q3 7.5–22.3] hours in the first stage (p < 0.001) and 23 [Q1–Q3 14–43] vs. 21 [Q1‐Q3 11–38] min in the second stage (p = 0.013).
In the final hour preceding birth, UA was observed to decrease in labours affected by chorioamnionitis compared to those without infection (Table 2). Chorioamnionitis was associated with a statistically significant reduction in contraction frequency in the multivariable analysis (aβ = −0.383, 95% CI −0.654 to −0.112, p = 0.006), but no significant differences were observed in IUP or oxytocin doses (Table 3). The maximum fever recorded during labour occurred at a median of 147 (Q1–Q3 81–286) min before birth.
TABLE 2.
Uterine activity and oxytocin use associated with clinical chorioamnionitis.
| Clinical chorioamnionitis n = 130 | No signs of infection n = 1374 | p | |||
|---|---|---|---|---|---|
| n/mean/median | SD/Q1–Q3 | n/mean/median | SD/Q1–Q3 | ||
| Contraction frequency/10 min | |||||
| Number of birth records analysed | 130 | 693 | |||
| Mean/4 h | 3.8 | 0.9 | 3.9 | 0.9 | 0.687 |
| 4 h prior to birth | 3.7 | 1.1 | 3.5 | 1.3 | 0.190 |
| 3 h prior to birth | 3.8 | 1.0 | 3.7 | 1.2 | 0.480 |
| 2 h prior to birth | 4.0 | 1.0 | 3.9 | 1.1 | 0.970 |
| 1 h prior to birth | 3.9 | 1.2 | 4.2 | 1.1 | 0.010 |
| IUP as Montevideo units | |||||
| Number of birth records analysed | 80 | 612 | |||
| Mean/4 h | 151 | 107–199 | 155 | 110–193 | 0.641 |
| 4 h prior to birth | 130 | 103–180 | 140 | 90–180 | 0.881 |
| 3 h prior to birth | 150 | 107–190 | 140 | 90–190 | 0.582 |
| 2 h prior to birth | 163 | 100–220 | 157 | 115–200 | 0.993 |
| 1 h prior to birth | 170 | 110–212 | 180 | 130–230 | 0.040 |
| Oxytocin dose, mIU/min | |||||
| Number of birth records analysed | 121 | 676 | |||
| Mean dose /4 h | 1.4 | 0.5–2.0 | 0.9 | 0.3–1.7 | 0.008 |
| 4 h prior to birth | 5.0 | 0.0–10.0 | 2.5 | 0.0–10.0 | 0.529 |
| 3 h prior to birth | 6.0 | 2.0–12.5 | 10.0 | 0.0–10.0 | 0.061 |
| 2 h prior to birth | 7.5 | 2.5–12.5 | 5.0 | 2.5–10.0 | 0.040 |
| 1 h prior to birth | 7.5 | 2.5–15.0 | 7.5 | 2.5–12.5 | 0.063 |
Note: Differences between groups by Mann–Whitney U‐test.
Abbreviations: IUP, intrauterine pressure; Q, quartile; SD, standard deviation.
TABLE 3.
Linear regression analyses of uterine activity and oxytocin doses as dependent variables in relation to clinical chorioamnionitis.
| Univariate | Multivariable | ||||||
|---|---|---|---|---|---|---|---|
| B | β | 95% CI | p | aβ | 95% CI | p | |
| Contraction frequency/10 min | |||||||
| 1 h prior to birth | 4.17 | −0.317 | −0.533 to −0.101 | 0.004 | −0.383 a | −0.654 to −0.112 | 0.006 |
| Intrauterine pressure as MVUs | |||||||
| 1 h prior to birth | 187 | −1.621 b | −3.743 to −0.500 | 0.134 | −0.232 a , b | −1.923 to −1.460 | 0.788 |
| Oxytocin dose mIU/min | |||||||
| Mean/4 h | 1.135 | 0.250 | 0.053 to 0.447 | 0.013 | 0.100 c | −0.127 to −0.326 | 0.388 |
| 2 h prior to birth | 7.116 | 1.400 | 0.129 to 2.670 | 0.031 | 0.384 c | −1.052 to −1.820 | 0.600 |
| 1 h prior to birth | 8.020 | 1.353 | 0.016 to 2.690 | 0.047 | 0.499 c | −3.306 to −4.752 | 0.515 |
Abbreviations: β, regression coefficient; aβ, adjusted regression coefficient; B, intercept; CI, confidence interval; MVU, Montevideo units.
Adjusted for nulliparity, mean oxytocin dose/4 h, duration of first stage of labour and maternal factors (age and prepregnancy body mass index).
For every increasing 10 Montevideo units.
Adjusted for nulliparity, duration of first stage of labour and maternal factors (age and prepregnancy body mass index).
Parturients without infection showed an adequate UA response to oxytocin: The mean oxytocin dose/4 h in relation to mean contractions /10 min β = 0.030, 95% CI 0.018–0.041, p < 0.001; mean IUP for every 10 MVUs β = 0.114, 95% CI 0.038–0.191, p = 0.003. In multivariable analysis (adjusted for nulliparity, first stage labour duration, maternal age and prepregnancy body mass index) the corresponding associations were aβ = 0.033 for mean contraction frequency, 95% CI 0.020–0.046, p < 0.001 and aβ = 0.121 for mean MVUs, 95% CI 0.034–0.207, p = 0.006. However, among women with chorioamnionitis, oxytocin did not exhibit a linear association: β = 0.012, 95% CI −0.011 to 0.036, p = 0.296 for every contraction/10 min and β = 0.027, 95% CI −0.168 to 0.2236, p = 0.782 for every 10 MVUs.
In the sub‐group of clinical chorioamnionitis cases, contraction monitoring methods (ET or IT) were compared (Table 4). Mean contraction frequency/10 min was lower in the IT group compared to the ET group, no such variation was observed in non‐infected labours (Table 5). Among chorioamnionitis cases, multivariable linear regression analysis showed that IT monitoring was associated with a lower contraction frequency/10 min (aβ = −0.430, 95% CI −0.840 to −0.021, p = 0.040). Differences in labour outcomes were also observed, with a lower incidence of fetal distress and diagnosed neonatal asphyxia in the IT group. Among labours without signs of infection (Table 5), although neonatal infections and the need for assisted ventilation appeared more frequent in the IT group, multivariable analysis did not reveal statistically significant differences.
TABLE 4.
Associations of intrapartum factors and labour outcomes in the sub‐group of clinical chorioamnionitis stratified by contraction monitoring method.
| External tocodynamometry n = 26 | Intrauterine tocodynamometry n = 104 | OR (MD) | 95% CI | p | ap | |||
|---|---|---|---|---|---|---|---|---|
| n/mean/median | %/SD/Q1–Q3 | n/mean/median | %/SD/Q1–Q2 | |||||
| Intrapartum factors | ||||||||
| Duration of labour 1st stage, hours | 19.0 | 10.8–28.6 | 22.6 | 16.0–27.4 | (−0.81) | −8.89 to 7.36 | 0.802 | |
| Duration of labour 2nd stage, minutes | 42 | 27–51 | 34 | 18–49 | (7.03) | −9.97 to 18.01 | 0.569 | |
| Labour contractions | ||||||||
| Contraction frequency/10 min, mean/4 h | 4.2 | 0.8 | 3.8 | 0.9 | (0.39) | 0.02 to 0.76 | 0.038 | 0.040 |
| Contraction frequency/10 min, 1 h prior to birth | 4.1 | 0.7 | 3.8 | 1.3 | (0.36) | −0.00 to 0.72 | 0.052 | |
| Use of oxytocin during labour | ||||||||
| Mean dose mIU/min | 1.1 | 0.5–2.0 | 1.1 | 0.6–2.0 | (−0.15) | −0.68 to 0.38 | 0.569 | |
| Labour outcomes | ||||||||
| Mode of delivery | ||||||||
| VD | 9 | 34.6 | 39 | 37.5 | 0.09 | 0.36 to 2.17 | 0.785 | |
| VAD | 8 | 30.8 | 20 | 19.2 | 0.54 | 0.20 to 1.41 | 0.201 | |
| VAD due to fetal distress | 5 | 19.2 | 8 | 7.7 | 0.35 | 0.10 to 1.18 | 0.079 | |
| CS | 9 | 34.6 | 45 | 43.3 | 1.44 | 0.59 to 3.53 | 0.423 | |
| CS due to fetal distress | 3 | 11.5 | 9 | 8.7 | 0.73 | 0.18 to 2.90 | 0.649 | |
| Birthweight, g | 3730 | 450 | 3780 | 390 | (−48.7) | −224.7 to 127.3 | 0.585 | |
| Umbilical artery pH | 7.21 | 0.10 | 7.23 | 0.09 | (0.018) | −0.087 to −0.123 | 0.730 | |
| UmA pH ≤ 7.10 | 5 | 19.2 | 8 | 7.7 | 0.35 | 0.10 to 1.18 | 0.079 | |
| 5‐min Apgar < 7 | 3 | 11.5 | 5 | 4.8 | 0.39 | 0.09 to 1.74 | 0.201 | |
| 5‐min Apgar < 7 or UmA pH ≤ 7.10 | 7 | 26.9 | 11 | 10.6 | 0.32 | 0.11 to 0.93 | 0.031 | |
| NICU admission | 6 | 23.1 | 21 | 20.2 | 0.84 | 0.30 to 2.36 | 0.746 | |
| NICU + Apgar < 7 | 3 | 11.5 | 5 | 4.8 | 0.39 | 0.09 to 1.74 | 0.201 | |
| NICU + UmA pH ≤ 7.10 | 4 | 15.4 | 4 | 3.8 | 0.22 | 0.05 to 0.95 | 0.029 | 0.071 |
| NICU + Apgar < 7 or UmA pH ≤ 7.10 (Fetal distress) | 6 | 23.1 | 7 | 6.7 | 0.24 | 0.07 to 0.79 | 0.013 | 0.004 |
| NICU length of stay > 2 days | 5 | 19.2 | 19 | 18.3 | 0.94 | 0.31 to 2.81 | 0.910 | |
| Paediatric diagnosis for NICU | ||||||||
| Neonatal asphyxia a | 4 | 19.0 | 3 | 3.9 | 0.18 | 0.04 to 0.85 | 0.018 | 0.030 |
| Infection | 4 | 15.4 | 13 | 12.5 | 0.81 | 0.12 to 5.50 | 0.831 | |
| Need for assisted ventilation | 3 | 11.5 | 12 | 11.5 | 0.89 | 0.12 to 6.48 | 0.756 | |
Note: ap‐values adjusted for nulliparity, first‐stage labour duration, mean oxytocin dose/4 h, maternal age and prepregnancy body mass index.
Abbreviations: CI, confidence interval; CS, caesarean section; MD, mean difference; NICU, neonatal intensive care unit; Q, quartile; SD, standard deviation; UmA, umbilical artery; VAD, vacuum assisted delivery; VD, vaginal delivery.
33 missing values.
TABLE 5.
Associations of intrapartum factors and labour outcomes in the sub‐group of non‐infected labours stratified by contraction monitoring method.
| External tocodynamometry n = 527 | Intrauterine tocodynamometry n = 847 | OR (MD) | 95% CI | p | ap | |||
|---|---|---|---|---|---|---|---|---|
| n/mean/median | %/SD/Q1–Q3 | n/mean/median | %/SD/Q1–Q2 | |||||
| Intrapartum factors | ||||||||
| Duration of labour 1st stage, hours | 13.8 | 7.0–21.8 | 15.0 | 8.8–23.5 | (−1.64) | −2.88 to −0.39 | 0.010 | 0.288 a |
| Duration of labour 2nd stage, minutes | 20 | 10–37 | 20 | 12–37 | (−0.50) | −3.91—2.91 | 0.774 | |
| Labour contractions | ||||||||
| Contraction frequency/10 min, mean/4 h | 3.9 | 0.9 | 3.9 | 0.9 | (−0.02) | −0.25—0.21 | 0.871 | |
| Contraction frequency/10 min, 1 h prior to birth | 4.0 | 1.1 | 4.2 | 1.1 | (−0.17) | −0.46 – 0.13 | 0.262 | |
| Use of oxytocin during labour | ||||||||
| Mean dose mIU/min | 0.6 | 0.1–1.1 | 1.0 | 0.3–1.8 | (−0.45) | −0.71 to −0.19 | < 0.001 | < 0.001 b |
| Labour outcomes | ||||||||
| Mode of delivery | ||||||||
| VD | 455 | 86.3 | 602 | 71.1 | 2.57 | 1.93–3.44 | < 0.001 | 0.975 |
| VAD | 48 | 9.1 | 120 | 14.2 | 1.65 | 1.16–2.35 | 0.005 | 0.247 |
| VAD due to fetal distress | 27 | 5.1 | 59 | 7.0 | 1.39 | 0.87–2.22 | 0.170 | |
| CS | 24 | 4.6 | 125 | 14.8 | 3.63 | 2.31–5.70 | < 0.001 | < 0.001 |
| CS due to fetal distress | 12 | 2.3 | 35 | 4.1 | 1.85 | 0.95–3.60 | 0.066 | |
| Birthweight, g | 3590 | 440 | 3660 | 480 | (−0.65) | −115.5 to −14.5 | 0.006 | 0.152 |
| Umbilical artery pH c | 7.23 | 0.08 | 7.23 | 0.08 | (−0.001) | −0.011 to 0.008 | 0.797 | |
| UmA pH ≤ 7.10 | 31 | 6.0 | 42 | 5.0 | 0.83 | 0.52–1.35 | 0.456 | |
| 5‐min Apgar < 7 | 6 | 1.1 | 11 | 1.3 | 1.14 | 0.42–3.11 | 0.794 | |
| 5‐min Apgar < 7 or UmA pH ≤ 7.10 | 7 | 1.3 | 15 | 1.8 | 1.34 | 0.54–3.31 | 0.525 | |
| NICU admission | 46 | 8.7 | 93 | 11.0 | 1.29 | 0.89–1.87 | 0.178 | |
| NICU + Apgar < 7 | 3 | 0.6 | 9 | 1.1 | 1.88 | 0.51–6.96 | 0.339 | |
| NICU + UmA pH ≤ 7.10 | 5 | 0.9 | 8 | 0.9 | 0.99 | 0.32–3.06 | 0.994 | |
| NICU + Apgar < 7 or UmA pH ≤ 7.10 (fetal distress) | 7 | 1.3 | 15 | 1.8 | 1.34 | 0.54–3.31 | 0.525 | |
| NICU length of stay > 2 days | 0 | 0.0 | 16 | 1.9 | 0.61 | 0.59–0.64 | 0.001 | 0.997 |
| Paediatric diagnosis for NICU | ||||||||
| Neonatal asphyxia d | 1 | 0.2 | 11 | 1.4 | 6.62 | 0.85–51.42 | 0.074 | |
| Infection | 0 | 0.0 | 31 | 3.7 | 0.61 | 0.58–0.63 | < 0.001 | 0.997 |
| Need for assisted ventilation | 0 | 0.0 | 13 | 1.5 | 0.64 | 0.56–0.73 | 0.008 | 0.999 |
Note: ap‐values adjusted for nulliparity, first‐stage labour duration, mean oxytocin dose/4 h, maternal age and prepregnancy body mass index.
Abbreviations: CI, confidence interval; CS, caesarean section; MD, mean difference; NICU, neonatal intensive care unit; Q, quartile; SD, standard deviation; UmA, umbilical artery; VAD, vacuum assisted delivery; VD, vaginal delivery.
Adjusted for nulliparity, mean oxytocin dose/4 h, maternal age and prepregnancy body mass index.
Adjusted for nulliparity, first‐stage labour duration, maternal age and prepregnancy body mass index.
23 missing values.
156 missing values.
Mean contraction frequency/4 h showed a linear association between UA and decreasing UmA pH among non‐infected parturients (β = −0.010, 95% CI −0.017 to −0.003, p = 0.007), but not among labours with clinical chorioamnionitis (β = −0.009, 95% CI −0.029 to 0.010, p = 0.361). Stratified analyses within the IT group revealed a linear association between the mean IUP/4 h and a decrease in UmA pH among non‐infected parturients (β = −0.020 counted per 100 MVUs, 95% CI −0.032 to −0.008, p < 0.001). This association was further intensified among labours complicated by chorioamnionitis (β = −0.044 counted per 100 MVUs, 95% CI −0.080 to −0.009, p = 0.015).
4. Discussion
4.1. Main Findings
UA was impaired during labours with clinical chorioamnionitis. Administration of oxytocin did not differ from parturients without intra‐amniotic infection, but the response appeared to be reduced among those with chorioamnionitis. Neonatal outcomes were better in the IT than in the ET monitoring group among chorioamnionitis cases. Therefore, during labours complicated by chorioamnionitis, IT was found to be more valuable as a monitoring method in protecting foetuses against excessive UA and acidosis.
4.2. Strengths and Limitations
The prospective nature of the study is a strength, as the parturients exhibited no signs of infection upon recruitment. It is acknowledged that using a clinical definition of chorioamnionitis may produce heterogeneous results [2]. Therefore, a weakness of the study is that placental histology was not assessed. As induced labours were emphasised by the study protocol, the population involved was selected. As the limit for recruitment was ≤ 7 cm dilatation of the cervix, and parous women not needing oxytocin augmentation were not included, the most rapidly progressing labours were not recruited. Overall, the study protocol highlighted the risk for dystocia, which may explain the higher incidence of chorioamnionitis than previously reported [1, 4]. However, the selection of our cohort did not affect the main outcome we focused on, namely contractility analysis. As the contraction interpretation was made by clinicians, blinding to the outcome of labour confirmed a nonbiased interpretation. Notably, in the ET monitoring group, there were missing data due to non‐interpretable external tocograms, resulting in fewer cases with values at each measurement point than the total number of participants. One limitation is that the duration of labour was not recorded for intrapartum CSs.
4.3. Interpretation
Clinical chorioamnionitis during term labour has controversial effects on UA. There seems to be a biphasic role for inflammation, as this may contribute to normal labour initiation, while excessive inflammation may inhibit labour progress [21]. There is evidence that infection is a risk factor for decreasing uterine response to oxytocin leading to prolonged delivery [12]. In turn, prolonged second stage is associated with higher odds of chorioamnionitis and the risk for neonatal complications [22]. In clinical practice, both prolonged labour and chorioamnionitis may necessitate interventions to prevent maternal and neonatal complications, leading to increased numbers of CS [23].
The present study found no difference in the oxytocin dosage between non‐infected labours and those with chorioamnionitis. It remains unclear whether the infection slows down labour progress or indicates reduced responsiveness to oxytocin. The absence of a linear association between oxytocin dosage and UA in labours affected by chorioamnionitis suggests reduced responsiveness to oxytocin in the presence of infection.
There is limited research on UA in chorioamnionitis. In a study by Duff et al. [13] UA was measured in term pregnancies that entered labour spontaneously and later developed chorioamnionitis (n = 65). Of these, 75% exhibited decreased UA despite oxytocin augmentation, and 34% required CS due to failure to progress. Our recent study also demonstrated that reduced contractility and chorioamnionitis are risk factors for intrapartum CS during a trial of labour after CS [24]. Zackler et al. [12] conducted a retrospective cohort study (n = 100) investigating the temporal association between diagnosis of clinical chorioamnionitis and IUP. They found that UA was maintained for 2 h after the onset of maternal fever but declined significantly thereafter, even though there were no changes in oxytocin dosage. This aligns with the findings of the present study.
Mode of delivery was not found to affect fetal distress. This supports existing evidence suggesting that CS should be performed based on standard obstetrical indications and that clinical chorioamnionitis alone is not an indication for CS. This is particularly important for the parturient as CS significantly increases the risk of adverse maternal outcomes in chorioamnionitis [3].
Most neonates, even those with notable acidosis, are born vigorous. Therefore, the fetal distress defined in this study highlights the role of contractions in NICU admissions. Impey et al. [17] found that acidosis, along with maternal fever, is a sign of labour at high risk for adverse neonatal consequences. They also cited experimental data: “products of infection or proinflammatory cytokines may reduce the threshold at which hypoxia leads to cellular damage”. This was confirmed in a recent study on 18 experimental sheep [25] which examined haemodynamic, gasometric and fetal heart rate variability changes during fetal inflammatory response syndrome. The study revealed that fetal adaptation to hypoxia is impaired during inflammation, and in cases of chorioamnionitis, acidosis during labour is likely to advance more rapidly.
In cases of protracted active labour, the use of IT is recommended [26], although the evidence supporting this strong recommendation is considered to be of low quality. In the present study, prolonged labour was strongly associated with switching from ET to IT in cases of clinical chorioamnionitis. The use of IT was not associated with an increased risk of infection in our primary RCT [9]. As mentioned, the risk of infection may be more closely related to prolonged labour requiring the use of IT rather than to the monitoring method itself. It should also be noted that the incidence of neonatal infections was similar in both ET and IT monitoring groups.
According to our current and previous research [18], it appears that IT monitoring offers benefits in terms of fetal tolerance, especially during high‐risk labours such as those complicated by chorioamnionitis. Two RCTs have previously reported smaller numbers of operative deliveries due to fetal distress in the IT monitoring groups, although the difference did not reach statistical difference in either study [8, 9].
Our study highlights the risk of excessive UA in labours with chorioamnionitis as it may compromise fetal well‐being. While the risk to the neonate during infection depends on various factors, it is important not to overlook UA when treating this condition. It seems that IT more readily directs actions to protect the fetus against fetal distress when treating women with intra‐amniotic infection.
5. Conclusions
Chorioamnionitis may lead to lower UA and a reduced response to oxytocin compared to deliveries without infection. IT was found to provide better control of contractions and a reduced risk of fetal distress in labours complicated by chorioamnionitis. Therefore, the use of internal monitors should not be avoided while managing chorioamnionitis.
Author Contributions
M.J.: contributed to planning the present study, collection of data, performed statistical analyses and is the principal author of the manuscript. T.H.: contributed to the whole process: providing the initial idea for the study structure of the original RCT, planning the study, recruited the parturients, collection of data, analysis of data. O.P. and J.U.: contributed to the planning, conduct and reporting phases of the study.
Disclosure
All authors have completed the ICMJE uniform disclosure form at form at www.icmje.org/coi_disclosure.pdf. There are no relationships or activities that could appear to have influenced the work.
Ethics Statement
Ethical approval was granted by the Ethics Committee of the Pirkanmaa Hospital District (R12229), in October 8, 2012.
Conflicts of Interest
The authors declare no conflicts of interest.
Acknowledgements
We thank Heini Huhtala, MSc, for her help with statistical analyses.
Funding: This work was supported by the Tampere University Hospital Support Foundation, Tampere University Hospital. The funding sources were not involved in the collection, analysis or interpretation of data or in the writing of the manuscript.
Data Availability Statement
The data from this study are available on reasonable request from the corresponding author.
References
- 1.“Committee Opinion No. 712: Intrapartum Management of Intraamniotic Infection,” Obstetrics and Gynecology 130, no. 2 (2017): e95–e101. [DOI] [PubMed] [Google Scholar]
- 2. Tita A. T. N. and Andrews W. W., “Diagnosis and Management of Clinical Chorioamnionitis,” Clinics in Perinatology 37, no. 2 (2010): 339–354. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Conde‐Agudelo A., Romero R., Jung E. J., and Garcia Sánchez Á. J., “Management of Clinical Chorioamnionitis: An Evidence‐Based Approach,” American Journal of Obstetrics and Gynecology 223, no. 6 (2020): 848–869. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Woodd S. L., Montoya A., Barreix M., et al., “Incidence of Maternal Peripartum Infection: A Systematic Review and Meta‐Analysis,” PLoS Medicine 16, no. 12 (2019): e1002984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Gee S. E., Ma'ayeh M., Ward C., Buhimschi C., Klebanoff M., and Rood K., “Intrauterine Pressure Catheter Use Is Associated With an Increased Risk of Postcesarean Surgical Site Infections,” American Journal of Perinatology 37, no. 6 (2020): 557–561. [DOI] [PubMed] [Google Scholar]
- 6. Soper D. E., Glen Mayhall C., and Dalton H. P., “Risk Factors for Intraamniotic Infection: A Prospective Epidemiologic Study,” American Journal of Obstetrics and Gynecology 161, no. 3 (1989): 562–568. [DOI] [PubMed] [Google Scholar]
- 7. Harper L. M., Shanks A. L., Tuuli M. G., Roehl K. A., and Cahill A. G., “The Risks and Benefits of Internal Monitors in Laboring Patients,” American Journal of Obstetrics and Gynecology 209, no. 1 (2013): 38.e1–38.e6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. Bakker J. J. H., Verhoeven C. J. M., Janssen P. F., et al., “Outcomes After Internal Versus External Tocodynamometry for Monitoring Labor,” New England Journal of Medicine 362, no. 4 (2010): 306–313. [DOI] [PubMed] [Google Scholar]
- 9. Hautakangas T., Uotila J., Huhtala H., and Palomäki O., “Intrauterine Versus External Tocodynamometry in Monitoring Labour: A Randomised Controlled Clinical Trial,” BJOG: An International Journal of Obstetrics & Gynaecology 127, no. 13 (2020): 1677–1686. [DOI] [PubMed] [Google Scholar]
- 10. Halem K. V., Bakker J. J. H., Verhoeven C. J., et al., “Does Use of an Intrauterine Catheter During Labor Increase Risk of Infection?,” Journal of Maternal‐Fetal and Neonatal Medicine 25, no. 4 (2012): 415–418. [DOI] [PubMed] [Google Scholar]
- 11. Rouse D. J., Landon M., Leveno K. J., et al., “The Maternal‐Fetal Medicine Units Cesarean Registry: Chorioamnionitis at Term and Its Duration—Relationship to Outcomes,” American Journal of Obstetrics and Gynecology 191, no. 1 (2004): 211–216. [DOI] [PubMed] [Google Scholar]
- 12. Zackler A., Flood P., Dajao R., Maramara L., and Goetzl L., “Suspected Chorioamnionitis and Myometrial Contractility: Mechanisms for Increased Risk of Cesarean Delivery and Postpartum Hemorrhage,” Reproductive Sciences 26, no. 2 (2019): 178–183. [DOI] [PubMed] [Google Scholar]
- 13. Duff P., Sanders R., and Gibbs R. S., “The Course of Labor in Term Patients With Chorioamnionitis,” American Journal of Obstetrics and Gynecology 147, no. 4 (1983): 391–395. [DOI] [PubMed] [Google Scholar]
- 14. Venkatesh K. K., Jackson W., Hughes B. L., Laughon M. M., Thorp J. M., and Stamilio D. M., “Association of Chorioamnionitis and Its Duration With Neonatal Morbidity and Mortality,” Journal of Perinatology 39, no. 5 (2019): 673–682. [DOI] [PubMed] [Google Scholar]
- 15. Hayes B. C., McGarvey C., Mulvany S., et al., “A Case‐Control Study of Hypoxic‐Ischemic Encephalopathy in Newborn Infants at >36 Weeks Gestation,” American Journal of Obstetrics and Gynecology 209, no. 1 (2013): 29.e1–29.e19. [DOI] [PubMed] [Google Scholar]
- 16. Reynolds A. J., Murray M. L., Geary M. P., Ater S. B., and Hayes B. C., “Uterine Activity in Labour and the Risk of Neonatal Encephalopathy: A Case Control Study,” European Journal of Obstetrics, Gynecology, and Reproductive Biology 274 (2022): 73–79. [DOI] [PubMed] [Google Scholar]
- 17. Impey L. W. M., Greenwood C. E. L., Black R. S., Yeh P. S. Y., Sheil O., and Doyle P., “The Relationship Between Intrapartum Maternal Fever and Neonatal Acidosis as Risk Factors for Neonatal Encephalopathy,” American Journal of Obstetrics and Gynecology 198, no. 1 (2008): 49.e1–49.e6. [DOI] [PubMed] [Google Scholar]
- 18. Juhantalo M., Hautakangas T., Palomäki O., and Uotila J., “Uterine Contractile Activity and Neonatal Outcome – A Blind Analysis of a Randomized Controlled Trial Cohort,” Acta Obstetricia et Gynecologica Scandinavica 103, no. 7 (2024): 1396–1407. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19. Higgins R. D., Saade G., Polin R. A., et al., “Evaluation and Management of Women and Newborns With a Maternal Diagnosis of Chorioamnionitis: Summary of a Workshop,” Obstetrics and Gynecology 127, no. 3 (2016): 426–436. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. COMET Initiative , “Development of a Core Outcome Set for Maternal and Perinatal Health Research and Surveillance in Light of Emerging and Ongoing Epidemic Threats,” 2024 November 22, https://www.cometinitiative.org/Studies/Details/3085. [DOI] [PMC free article] [PubMed]
- 21. Cierny J. T., Unal E. R., Flood P., et al., “Maternal Inflammatory Markers and Term Labor Performance,” American Journal of Obstetrics and Gynecology 210, no. 5 (2014): 447.e1–447.e6. [DOI] [PubMed] [Google Scholar]
- 22. Pergialiotis V., Bellos I., Antsaklis A., Papapanagiotou A., Loutradis D., and Daskalakis G., “Maternal and Neonatal Outcomes Following a Prolonged Second Stage of Labor: A Meta‐Analysis of Observational Studies,” European Journal of Obstetrics, Gynecology, and Reproductive Biology 252 (2020): 62–69. [DOI] [PubMed] [Google Scholar]
- 23. Mark S., Croughan‐Minihane M., and Kilpatrick S., “Chorioamnionitis and Uterine Function,” Obstetrics & Gynecology 95, no. 6 (2000): 909–912. [PubMed] [Google Scholar]
- 24. Hautakangas T., Uotila J., Huhtala H., and Palomäki O., “How Does Uterine Contractile Activity Affect the Success of Trial of Labour After Caesarean Section, and the Risk of Uterine Rupture? An Exploratory, Blinded Analysis of a Cohort From a Randomised Controlled Trial,” BJOG: An International Journal of Obstetrics & Gynaecology 129, no. 6 (2022): 976–984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25. Chevalier G., Garabedian C., De Stephano V., et al., “How Does Fetal Inflammatory Response Syndrome Change Fetal Response to Hypoxia? An Experimental Study in a Fetal Sheep Model,” Acta Obstetricia et Gynecologica Scandinavica 103 (2024): 2281–2288. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.“First and Second Stage Labor Management: ACOG Clinical Practice Guideline No. 8,” Obstetrics & Gynecology 143, no. 1 (2024): 144–162. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data from this study are available on reasonable request from the corresponding author.