Association between epidural-related maternal fever and short-and long-term prognosis of parturients: A prospective observational study

EDITED BY

Canio Martinelli,

University of Messina, Italy

REVIEWED BY

Nazan Yurtcu,

Sivas Cumhuriyet University Faculty of

Medicine, Turkey

Chao Zhang,

Southern Medical University, China

Guangyi Zhao,

ShengJing Hospital of China Medical University,

China

CORRESPONDENCE

Junxiang Jia

[email protected]

Baisong Zhao

[email protected]

†

These authors have contributed equally to this

work

SPECIALTY SECTION

This article was submitted to Obstetrics and

Gynecological Surgery, a section of the journal

Frontiers in Surgery

RECEIVED 08 October 2022

ACCEPTED 12 December 2022

PUBLISHED 10 January 2023

CITATION

Li B, Liao Y, Wang Q, He S, Yang L, Jia J and

Zhao B (2023) Association between epidural-

related maternal fever and short-and long-term

prognosis of parturients: A prospective

observational study.

Front. Surg. 9:1064272.

doi: 10.3389/fsurg.2022.1064272

This is an open-access article distributed under

the terms of the Creative Commons Attribution

License (CC BY). The use, distribution or

reproduction in other forums is permitted,

provided the original author(s) and the

original publication in this journal is cited, in

accordance with accepted academic practice.

No use, distribution or reproduction is

permitted which does not comply with these

terms.

Association between epidural-

related maternal fever and short-

and long-term prognosis of

parturients: A prospective

observational study

Bing Li

1†

, Yicong Liao

1†

, Qingning Wang

, Shiyuan He

Lulu Yang

, Junxiang Jia

and Baisong Zhao

Department of Anesthesiology, Women and Children’s Hospital, School of Medicine, Xiamen

University, Xiamen, China,

Department of Anesthesiology, Guangzhou Women and Children’s

Medical Center, Guangzhou Medical University, Guangzhou, China

We aimed to explore the association between epidural-related maternal fever

(ERMF) and prognosis of parturients. 159 parturients who underwent vaginal

delivery under labor epidural analgesia (LEA) received noninvasive continuous

core body temperature monitoring. 122 of them completed the 42-day

postpartum follow-up. Parturients with body temperature ≥38°C during labor

were categorized as the Fever group, while the others were categorized as

the No-Fever group. Compared to No-Fever group, Fever group had a

greater proportion of primiparas, greater gestational age of parturients, and

longer third stage of labor. The cesarean section and forceps delivery rates,

and the amount of intrapartum hemorrhage in Fever group were signiﬁcantly

higher. There were no signiﬁcant between-group differences with respect to

puerperal infection, and amniotic ﬂuid turbidity degree, neither signiﬁcant

between-group difference at 42-days postpartum. We found that ERMF was

associated with some short-term outcomes. However, it showed no relation

with long-term prognosis of the parturients at 42-days postpartum.

KEYWORDS

epidural-related, maternal, fever, labor epidural analgesia, long-term

Introduction

Intrapartum maternal fever, deﬁned as oral temperature ≥38°C during childbirth (1),

is known to be associated with increased incidence of postpartum adverse outcomes (2),

such as prolonged labor, increased rate of instrumental delivery, early postpartum

hemorrhage, and increased probability of placental retention (3). Labor epidural

analgesia (LEA) is one of the most common non-infective cause of intrapartum

maternal fever (4), and approximately 20% of pregnant women who receive LEA

would have epidural-related maternal fever (ERMF) (5). LEA duration is corelated

with ERMF; LEA greater than 6 h was shown to increase the risk of fever during

Abbreviations

BMI, body mass index; ERMF, epidural-related maternal fever; IV, intravenous; LEA, labor epidural

analgesia; LSD, least signiﬁcant difference.

TYPE Original Research

PUBLISHED 10 January 2023

DOI 10.3389/fsurg.2022.1064272

Frontiers in Surgery 01 frontiersin.org

labor (6). Whether ERMF needs intervention or not depends on

the harm it causes to the mother and newborn. Therefore, a

comprehensive understanding of the harmful effects of ERMF

is of much clinical signiﬁcance.

ERMF may further affect the prognosis of the parturient in

the postpartum period by changing the delivery experience of

the parturient and the outcomes of the newborn. However,

whether ERMF affects the short-term and long-term

prognosis of parturients is seldom reported. In this study, we

investigated the short-term and long-term (42 days

postpartum) outcomes of parturients who received LEA at a

single center. The objective was to explore whether ERMF is

associated with the short-term or long-term prognosis of

parturients.

Materials and methods

Research population

This study was approved by the Ethics Committee of the

Guangzhou Women and Children’s Medical Center (Protocol

number: 201939000) and registered at the Chinese Clinical

Trial Registry (http://www.chictr.org.cn/edit.aspx; ID:

ChiCTR1900025653; Principal investigator: Baisong Zhao;

Date of registration: Sep 5, 2019). This study adhered to the

STROBE reporting guidelines. This study recruited pregnant

women who planned to give birth during daytime hours from

30 September 2019 to 31 December 2019 and came to our

hospital for treatment. All participants provided written

informed consent before the start of the trial.

The inclusion criteria were as follows: (1) parturients

without fever before labor; (2) parturients with full-term

singleton pregnancy (gestational age >37 weeks); (3) vaginal

in-hospital delivery; (4) vertex presentation; (5) no risk of

mother-to-child transmission of an infectious disease; (6) no

suspected fetal coagulopathy; (7) parturients without prenatal

vaginitis; and (8) willingness to use LEA and ability to

provide informed consent. The exclusion criteria were: (1)

both upper extremities required for venous access; (2) absence

of both upper limbs; (3) history of severe heart disease like

myocardial infarction, heart failure; (4) history of severe

infectious diseases such as maternal hepatitis, or HIV

infection; (5) history of serious skin allergies, especially allergy

to silicone or plastic; (6) preeclampsia; (7) parturients who

took paracetamol within 6 h before receiving epidural

analgesia; (8) suspected fetal coagulopathy; and (9)

chorioamnionitis conﬁrmed by pathological examination.

Upon entering the delivery room, the researchers provided

all eligible women with information about the study and

obtained their informed consent for participation in the study.

All parturients were monitored continuously. Patients with

body temperature ≥38°C during labor were categorized as the

Fever group while those with body temperature <38°C were

categorized as No-Fever group. The data collection process

was blinded, and researchers who collected body temperature

data had no knowledge of the duration and dose of LEA. In

addition, personnel involved in acquisition of postpartum data

were blinded to maternal body temperature.

Measurement method of body

temperature and fever treatment

A wireless thermometer, iThermomonitor (Rui Ren

Medical, China), connected to the central control platform

was used to carry out axillary temperature measurement

during the whole delivery process (10 values per second). The

iThermonitor was ﬁxed to the shaved armpit using an

adhesive tape with low risk of allergic reaction. Women were

instructed to maintain the arm in the adducted position for

up to 5 min until the temperature value shown on the display

was stable; thereafter, the women were allowed free movement

of their arms (7). Generally, intravenous infusion of

unwarmed ﬂuid into the contralateral arm does not have any

effect on the use of iThermonitor for measuring the axillary

temperature.

The pregnant women reported the onset of delivery. Labor

room nurses were responsible for monitoring the patients and

executing the obstetrician’s orders, who did not participate in

the study. Fever was deﬁned as axillary temperature

(measured by iThermonitor) ≥38°C. In parturients with fever,

the following treatment measures were undertaken: When

axillary temperatures rose to 38°C–38.5°C, intravenous

rehydration was accelerated to replace water loss. When the

axillary temperature exceeded 38.5°C, Tylenol suspension was

administered orally (Johnson & Johnson Pharmaceutical Ltd.,

China).

Implementation of epidural analgesia

Epidural analgesia was initiated once uterine contractions

were regular and cervical dilatation was ≥1 cm, and was

continued to 2 h after the end of labor. Women receiving

LEA were administered intravenous Ringer’s lactate infusion

(2–4 ml/kg/h). The rescue drugs atropine and ephedrine were

always kept prepared. An epidural catheter was placed at the

L3–L4/L2–3 and epidural analgesia was controlled by the

parturients themselves. After the epidural catheter was ﬁxed, a

test dose of 4 ml of 1% lidocaine was administered via the

catheter. Five minutes later, in the absence of any side effects,

a 10 ml bolus dose of ropivacaine 0.0625% (lot number:

H20140763; Astra Zeneca, Sweden) plus 0.3 µg/ml sufentanil

(batch number: H20054256; Yichang Renfu Pharmaceutical,

China) was administered. Subsequently, the epidural catheter

Li et al. 10.3389/fsurg.2022.1064272

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was connected to the pulse pump and set as follows: loading

dose, 10 ml; injection rate, 6 ml/h; PCA dose, 8 ml; maximum

dose, 40 ml/h; and lockout interval, 10 min. At any time

during labor, women with excessive pains or a visual analogue

scale pain score >3 were administered an additional 5 ml of

ropivacaine 0.1%.

Data collection

Data for the following demographic and basic clinical

characteristics were collected from all enrolled women:

gestational age, height, weight, body mass index (BMI), and

time of delivery. Delivery-related data included the duration

of labor, neonatal Apgar scores, delivery outcomes, amount of

postpartum hemorrhage, occurrence of puerperal infection,

amniotic ﬂuid turbidity, lochia, and menstruation at 42 days

after delivery. We excluded data of patients with

pathologically conﬁ rmed chorioamnionitis.

Maternal blood pressure and heart rate was continuously

monitored during labor and the rate and volume of ﬂuid

administered was administered.

Statistical analysis

The required sample size was calculated based on the ratio

of abnormal delivery in parturients who did not develop fever

during labor and those who developed fever in our previous

trials. According to the ratio of 1:3 and with α = 0.05 and

power of 0.9, the minimum sample size required for the No-

Fever group was 111 and that for the Fever group was 37.

Use SPSS software (ver. 21.0; SPSS Inc., USA) was used to

conduct statistical analysis. Owing to the non-normal

distribution of gestational age, height, weight, BMI, amount of

hemorrhage during labor and 2 h after delivery, these data are

expressed as median and interquartile range [M (Q)] and the

between-group differences assessed using the rank sum test.

Categorical variables are expressed as frequency and

percentage [n(%)] and between-group differences assessed

using the Chi-squared test. P values < 0.05 were considered

indicative of statistical signiﬁcance. The duration of labor and

Apgar score are expressed as mean ± standard deviation and

between-group differences assessed using repeated measures

analysis of variance. When the differences were statistically

signiﬁcant, the least signiﬁcant difference (LSD) method was

further used to make pair-wise comparisons.

Results

This study used a convenience sampling method and

grouped parturients who received LEA into No-Fever group

and Fever group according to axillary temperature. Finally, a

total of 159 parturients who received LEA were recruited; of

these 117 were in the No-Fever group (maximal temperature

in the labor period <38°C) and 42 were in the Fever group

(maximal temperature in the labor period ≥38°C). A total of

122 women completed the 42-day postpartum follow-up; of

these, 90 were in the No-Fever group and 32 were in the fever

group (Figure 1). For the maternal demographic and clinical

characteristics, there were no signiﬁcant between-group

differences with respect to height weight and BMI. The

women in Fever group were more likely to be primiparous, in

addition, the gestational age of parturients in the Fever group

was greater (Table 1).

There was no signiﬁcant between-group difference with

respect to the duration of the ﬁrst (P = 0.084) and second (P

= 0.0584) stages of labor. However, the duration of the third

stage of labor in the No-Fever group was signiﬁcantly shorter

than that in the Fever group (P = 0.01) (Figure 2A). For the

short-term prognostic, the cesarean section rate in Fever

group was signiﬁcantly greater than that in the No-Fever

group (23.8% vs. 6.8%, P = 0.018). There were no signiﬁcant

between-group differences with respect to the rates of lateral

episiotomy, manual removal of placenta, and puerperal

infection (Figure 2B). The amount of intrapartum

hemorrhage in the Fever group was also signiﬁcantly greater

than that in the No-Fever group (P = 0.002); however, there

were no signiﬁcant between-group differences with respect to

the amount of hemorrhage in 2 h postpartum ( Figure 2C).

Moreover, there were no signiﬁcant between-group differences

with respect to the degree of turbidity of the amniotic ﬂuid

(Figure 2D). These results suggest that ERMF affects the

short-term prognosis of the puerpera.

From 1 to 10 min, there was no signiﬁcant difference in the

Apgar scores between the two groups (Figure 3). For the long-

term prognostic signiﬁcance, there were no signiﬁcant between-

group differences with respect to lochia, menstruation, peculiar

smell, and anti-infective treatment at 42-day postpartum follow-

up (Figure 4). These results suggest that ERMF has no effect on

the neonatal status and the long-term prognosis of puerpera.

Discussion

This study observed the incidence of related short-term and

long-term (42-day postpartum) adverse events in parturients

who received LEA. The baseline characteristics were

comparable in the two groups. The proportion of primipara

and the gestational age (despite the difference of 2 days) in

the Fever group were higher than those in the No-Fever

group, while the third stage of labor in the Fever group was

longer than that in the No-Fever group. The Fever group had

a signiﬁcantly higher cesarean section rate and rate of forceps

delivery, while the rates of lateral resection and manual

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removal of placenta were comparable in the two groups. The

amount of intrapartum bleeding was greater in the Fever

group, while the amount of 2 h postpartum bleeding was

comparable in the two groups. In addition, there was no

signiﬁcant difference in Apgar scores between the two groups.

At 42-day postpartum follow-up, there was no signiﬁcant

between-group difference with respect to the proportion of

women with clean lochia discharge, menstrual re-ﬂuidity,

secretions with unusual smell, and postpartum treatment with

antibiotics.

In this study, we deﬁned fever as core body temperature ≥38°

C. Intrapartum fever is associated with increased incidence of

postpartum adverse outcomes. In the study by Dior et al. (2),

intrapartum fever signiﬁcantly increased the probability of

emergency cesarean section and device-assisted delivery,

especially for parturients whose body temperature was >39°C.

However, no causal association was observed on stratiﬁed

analysis disaggregated by the degree of maternal fever. In the

study by Ashwal et al. (3), fever during labor was an

independent risk factor for maternal-related complications, and

was aassociated with prolonged second stage of labor, increased

instrumental delivery rate, cesarean section rate, and placental

retention rate. The authors did not divide the women into

groups according to whether they received LEA. In our study,

we excluded parturients with infectious factors, and the rates of

cesarean section and forceps delivery in the Fever group were

higher than those in the No-Fever group; in addition, the Fever

group had a greater amount of intrapartum hemorrhage.

However, we also found no difference in the rate of puerperal

infection and turbid amniotic ﬂuid between the Fever and No-

Fever groups. This indicated that the signiﬁcant between-group

differences with respect to the proportion of cesarean section

TABLE 1 Maternal demographic and clinical characteristics.

Indicators No-Fever

(n = 117)

Fever (n

= 42)

/z/

Maternal type [n (%)]

Primipara 73 (62.4) 34 (81.0) 4.837 0.028

Multipara 44 (37.6) 8 (19.0)

Gestational age [M

(Q), weeks]

39.9 (1.6) 40.1 (1.6) −2.171 0.030

Height [M (Q), cm] 160.0 (6.0) 160.0 (8.0) −1.610 0.107

Weight [M (Q), kg] 66.0 (9.3) 68.0 (11.0) −0.952 0.341

BMI [kg/m

, M (Q)] 25.9 (3.6) 27.1 (2.9) −1.842 0.065

BMI, body mass index. P < 0.05 indicates signiﬁcant between-group difference.

FIGURE 1

Experimental ﬂow graph.

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and forceps deliveries, and the amount of intrapartum

hemorrhage during delivery were not directly related to

puerperal infection and might be related to ERMF.

Given the observational nature of study, we can only analyze

the correlation of ERMF with increased rates of cesarean section

and forceps deliveries and increased intrapartum bleeding.

However, it is not clear whether ERMF directly affects the

delivery outcomes, delays the delivery of placenta, increases the

amount of intrapartum hemorrhage, or affects the delivery

outcome. Of note, that there were also differences between the

No-Fever and Fever groups with respect to the parity and

gestational age of parturients. The proportion of primiparous

women in the fever group was higher, and the gestational age was

also greater (despite the difference of 2 days). Compared with

primipara, the birth canal of the multiparas tends to be more

relaxed, and the fetus also gains weight with increase in the

FIGURE 2

Comparison of short-term prognostic indicators between the two groups. (A) Stage of labor (h). (B) The short-term prognostic indicators (%). (C)

Hemorrhage volume (mL). (D) Abnomal amniotic ﬂuid (%).

Li et al. 10.3389/fsurg.2022.1064272

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gestational age. Studies have conﬁrmed that primipara status (8)

and larger neonatal birth weight (9) are risk factors for increased

rates of cesarean section and forceps delivery. Excessive uterine

dilation and uterine laxity caused by overweight fetuses (10),

prolonged third stage of labor, and delayed placental delivery (11)

are also risk factors for increased intrapartum bleeding.

At the same time, the impact of intrapartum fever on neonates

has evoked increasing interest. The negative effects related to

newborns mainly include some neurosuppressive symptoms,

such as a decrease in the Apgar scores, the need for assisted

ventilation and oxygen therapy, and even a rised chance of

cardiopulmonary resuscitation (5, 12). Ashwal et al. (3), further

divided the febrile mothers into blood and/or placental culture

positive and negative groups. They found that the incidence of

adverse neonatal outcomes in the positive group was much

higher than that in the negative group, indicating that the

negative impact of fever on newborns is more related to

infectious factors. In this study, there was no difference in the

puerperal infection rate between the Fever group and the No-

Fever group; moreover, we observed no signiﬁcant between-

group difference with respect to amniotic ﬂuid turbidity and the

newborn Apgar score. This implies a lack of correlation between

ERMF and neonatal hypoxia. Other studies conducted by our

group (13) have also yielded similar results.

Uterine involution is usually completed within 42 days

postpartum. Prolonged lochia or peculiar smell is a sign of poor

postpartum uterine involution. In this study , parturients w ere

followed up 42 days after deliv ery. We found no signiﬁcant

between-group difference with respect to these indicators. This

suggests tha t ERMF may not a ffect uterine inv olution 42 day s

postpartum.

We still have some limitations in this study. This was a

single-center, observational study with a relatively small sample

size. A multicentre study with larger sample size and longer

duration of follow-up is needed to provide more robust evidence.

In this study, ERMF was associated with prolongation of the

third stage of labor, increased rates of cesarean section and

forceps delivery, and increased intrapartum hemorrhage.

However, ERMF was not found to affect the long-term

prognosis at 42 days postpartum. This means that, different

from infection-associated fever, ERMF has some association

with short-term prognosis of parturients, but no impact on

long-term postpartum recovery.

Data availability statement

The original contributions presented in the study are

included in the article/Supplementary Material, further

inquiries can be directed to the corresponding authors.

Ethics statement

The studies involving human participants were reviewed

and approved by This study was approved by the Ethics

Committee of the Guangzhou Women and Children’s Medical

Center (Protocol number: 201939000) and registered at the

Chinese Clinical Trial Registry (http://www.chictr.org.cn/edit.

aspx; ID: ChiCTR1900025653; Principal investigator: Baisong

Zhao; Date of registration: Sep 5, 2019). The patients/

participants provided their written informed consent to

participate in this study.

Author contributions

BZ designed and performed most of the investigation, data

analysis. BL wrote the manuscript. YL, QW and other authors

FIGURE 3

Apgar scores between the two groups.

FIGURE 4

Comparison of outcomes at 42-days postpartum between the two

groups.

Li et al. 10.3389/fsurg.2022.1064272

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assisted data collection. JJ provided research resources. All authors

contributed to the article and approved the submitted version.

Conﬂict of interest

The authors declare that the research was conducted in the

absence of any commercial or ﬁnancial relationships that could

be construed as a potential conﬂict of interest.

Publisher’s note

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authors and do not necessarily represent those of their

afﬁliated organizations, or those of the publisher, the editors

and the reviewers. Any product that may be evaluated in this

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