Вы находитесь на странице: 1из 7

doi:10.1111/jog.13988 J. Obstet. Gynaecol. Res.


A cohort study of the impact of epidural analgesia

on maternal and neonatal outcomes

Huifen Yin and Rong Hu

Department of Obstetrics, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China

Aim: To explore the impact of epidural analgesia on maternal and neonatal outcomes, especially the relation
between epidural analgesia and intrapartum fever.
Methods: A retrospective cohort study was conducted in a tertiary hospital for all deliveries from November
2017 to December 2017. A total of 506 women were divided into epidural and non-epidural group by
whether to receive analgesia or not. Univariate and multivariate analyses were performed with P < 0.05 as
Results: Epidural analgesia was associated with higher risk of maternal intrapartum fever (relative risk
[RR] = 3.28, 95% confidence interval, 1.55–6.95), more intravenous use of antibiotics (36.66% vs 17.04%,
P<0.001), longer time of second stage (58.55 ! 33.75 vs 47.39 ! 28.36 min,P = 0.001) and longer total dura-
tion of labor (790.32 ! 433.71 vs 461.33 ! 270.39 min,P<0.001), but had no influence on mode of delivery,
the amount of post-partum hemorrhage or hospital stay after delivery and all the neonatal outcomes we
studied. Further time effect analysis found that epidural analgesia less than 6 h did not increase the risk of
intrapartum fever (RR = 1.73, P = 0.15), however, when epidural analgesia lasted over 6 h, it significantly
increased the risk of fever (RR = 5.23, P<0.001) but did not increase more adverse outcomes.
Conclusion: Having epidural anesthesia 6 h or more increases the risk of developing fever, but the prognosis
of mothers and children is less affected.
Key words: epidural analgesia, intrapartum fever, labor, maternal outcomes, neonatal outcomes.

Introduction more likely to receive antibiotics and undergo instru-

mental delivery and maternal pyrexia may also be
Labor is a complex process with one of the most associated with adverse neonatal outcomes including
severe pains which could cause a series of neurophys- low Apgar scores, respiratory distress, hypotonia and
iological changes such as increasing maternal stress neonatal seizures.3,6 However, another study
hormones, elevating blood pressure, inducing hyper- suggested that epidural fever may be a benign rise in
ventilation and reducing fetal oxygen transport.1 In temperature not associated with neonatal neurological
recent years, labor analgesia began to be more and consequences.7 The etiology of the relation between
more widely used in China. Meanwhile, attention has maternal fever and epidural analgesia remains
been paid to the maternal and neonatal influence of unclear and whether epidural analgesia would cause
labor analgesia. adverse obstetric outcomes were controversial. Anes-
A few studies have observed that women receiving thesia effects on the duration of the second stage of
epidural analgesia were at increased risk for intra- labor, instrumental vaginal delivery, labor epidural-
partum fever.2–5 Women with maternal pyrexia are associated fever and neonatal acid–base status

Received: September 27 2018.

Accepted: April 11 2019.
Correspondence: Dr Rong Hu,Department of Obstetrics, Obstetrics and Gynecology Hospital of Fudan University, Fangxie Road,
Shanghai, China. Email: hurongwy@sina.com

© 2019 Japan Society of Obstetrics and Gynecology 1

H. Yin and R. Hu

continue to be explored.8 Besides, studies about the as a loading dose. The patient-analgesia (PCEA) was
effect of duration time of epidural analgesia on mater- connected 10 min later with 100 mL 0.1% ropivacaine
nal and neonatal outcomes were also absent. Current and 0.5 μg/mL sufentanil repeating during labor on
and future work on these areas may enhance clini- demand. PCEA was set as 5 mL/h for continuous
cian’s ability to personalize obstetric anesthesia thera- infusion, 5 mL for single press and 15 min for locking.
pies and interventions. PCEA was stopped after the second stage of labor
Therefore, the objective of this study was to explore and the catheter was removed 2 h after delivery.
the relation between epidural analgesia and intra- Data extracted from the medical record included
partum fever and whether epidural analgesia would maternal age, height, weight, complications, gesta-
cause adverse effect on maternal and neonatal out- tional weeks, labor type (spontaneous vs induced
comes. As some studies suggested that epidural fever labor), group B streptococcus status (positive vs nega-
took time to develop, this study also focused on the tive), results of blood routine test before delivery, time
effect of duration time of epidural analgesia to pro- and way of membrane rupture and duration of labor
vide evidence for clinicians to timely make correlated (from the beginning of labor to the delivery of new-
interventions. born). Maternal complications were defined as fol-
lows: Hypertensive disorders of pregnancy included
preeclampsia-eclampsia, chronic hypertension (of any
cause), chronic hypertension with superimposed pre-
Methods eclampsia and gestational hypertension according to
the American College of Obstetrics and Gynecology
This was a retrospective cohort study in a tertiary (ACOG) guideline.10 Diabetes included both
obstetrics and gynecology hospital for all deliveries pregestational diabetes mellitus (PGDM) and gesta-
over 2 months from November 2017 to December tional diabetes mellitus (GDM) and GDM was diag-
2017. For the present analysis, we limited the popula- nosed by the 75 g oral glucose tolerance test (OGTT)
tion to women with singleton and term pregnancies at 24–28 weeks of gestation. Thyroid disorders were
(≥37 weeks gestation). Sample size was calculated by diagnosed by abnormal results of thyroid function
the following formula for a cohort study: tests. Anemia was defined as the concentration of
" pffiffiffiffiffi pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi#2
Zα 2pq + Zβ p0 q0 + p1 q1 hemoglobin lower than 110 g/L. Maternal outcomes
n= 2 . Based on the previous stud-
ð p1 − p0 Þ included mode and time of delivery, duration of the
ies, p1 (proportion in cases) = 10.5%, p0 (proportion in second stage and total duration of labor, use of antibi-
control) = 2.3%.9Considering the loss rate and incom- otics (oral, intravenous or not), the amount of post-
plete data, the estimated final sample size was partum hemorrhage and hospital stay after delivery.
500 cases. Women were divided into epidural and Neonatal data included 1 min Apgar scores, fetal dis-
non-epidural groups by whether to receive analgesia tress, assisted ventilation, admission to the neonatal
in labor according to their wills. Pregnancies compli- unit and length of stay, hyperbilirubinemia, the diag-
cated with fetal growth restriction or oligoamnios nosis of neonatal infection and use of antibiotics. Elec-
which may be associated with low placental function tronic fetal monitoring (EFM) was adopted during
were excluded from the study. In addition, women stages and fetal distress was considered when cate-
with demonstrated infection, a fever before labor or a gory III tracing or repeated category II tracing was
basal body temperature higher than or equal to presented.11 Assisted ventilation included positive
37.5$ C were also excluded from this study. This study pressure ventilation, mask resuscitation, intubation
was approved by the Research Ethics Committee in and chest compressions. Admission to neonatal unit
the Obstetrics and Gynecology Institute, Fudan Uni- was at the discretion of experienced neonatologists.
versity Shanghai Medical College (Number: 2018–14, The intrapartum maternal fever was defined as a tem-
Date: 2018.3.20). perature of greater than or equal to 37.5$ C any time
Epidural analgesia was performed on women when during labor and delivery.12,13 Baseline temperatures
they had 2 cm of cervical dilatation or more. The epi- of women were routinely recorded on admission to
dural space was at the L2–L3 interspace, and an epi- the labor and delivery room. Temperatures were
dural catheter was advanced 3–5 cm into the epidural assessed orally by nurses every 4 hours during labor
space. An analgesic mixture of 4–10 mL 0.1% and once a temperature of 37.5$ C was reached, the
ropivacaine with 2–5 μg sufentanil was administered obstetric doctor is notified to further evaluation.

2 © 2019 Japan Society of Obstetrics and Gynecology

Impact of epidural analgesia on labor

Indications for antibiotic use were as follows: Women premature rupture of membranes (PROM) or rate of
were given erythrocin orally when 12 h after the rup- group B streptococcus status positive status.
ture of membrane; If a patient was group B strepto- Statistics for maternal and neonatal outcomes were
coccus status positive, cephalosporin were used shown in Table 2. The incidence of intrapartum fever
intravenously as soon as the rupture of membrane or was 25.07% and 6.67% in epidural and non-epidural
regular contractions; Women were also given cephalo- group, respectively (P<0.001). The relative risk (RR) of
sporin intravenously after the diagnosis of maternal intrapartum fever was 3.76 (95% confidence interval
fever. [CI[:1.95–7.24) compared with the non-epidural
Data were analyzed by SPSS Statistics version 22.0. group. Besides, mother in the epidural group were
Normal distribution for continuous variables was more likely to receive antibiotics, and mainly in intra-
determined using the Shapiro–Wilk test. Quantitative venous way (36.66% vs 17.04%, P<0.001) and time of
variables were expressed as mean ! standard devia- the second stage and total duration of labor were lon-
tion (SD) and qualitative variables as percentages. ger in the epidural group (58.55 ! 33.75 min vs
Categorical data were compared using the χ 2 test or 47.39 ! 28.36 min,P = 0.001; 790.32 ! 433.71 vs
Fisher’s exact tests. Continuous data were compared 461.33 ! 270.39 min,P<0.001*). However, there was
using the Student’s t-test. A multivariable logistic no difference in the way of delivery. The rate of spon-
regression model was estimated to evaluate the asso- taneous vaginal delivery was 88.41% and 91.11% in
ciation between maternal fever and epidural analge- epidural and non-epidural group, respectively
sia. Receiver operating characteristic curve was (P = 0.41) and no difference was showed in the
adopted to further explore the relation between the amount of post-partum hemorrhage in the two
duration time of epidural analgesia and intrapartum groups (308.42 ! 75.31 vs 310.30 ! 103.51 mL,
fever and to find out whether there is a cut-off point. P = 0.87) or mother’s hospital stay after delivery as
P<0.05 was considered statistically significant. well (3.15 ! 0.72 vs 3.10 ! 0.83 days, P = 0.85). In the
neonatal aspect, there were no difference in Apgar
score at 1 min, the rate of fetal distress, admission to
neonatal ward and length of stay, assisted ventilation,
Results neonatal infection, antibiotic administration or hyper-
bilirubinemia between two groups.
A total of 506 deliveries were involved in this study A multivariable logistic regression model was
with 371 women in epidural group and 135 women in adopted to exclude the impact of other risk factors
non-epidural group. Demographics were shown in that may be associated with maternal fever. Candi-
Table 1. There were no differences between the two date independent variables were as follows: epidural
groups in terms of maternal height, weight, gesta- analgesia (used or not), group B streptococcus status
tional age, complications, labor type, rate of (positive vs negative), membrane rupture (PROM or

Table 1 Demographics of women

Epidural (n = 371) Non-epidural (n = 135) P value
Maternal age (years) 28.66 ! 2.95 28.67 ! 3.11 0.96
Maternal height (cm) 162.66 ! 4.75 163.75 ! 4.60 0.22
Maternal weight (kg) 70.07 ! 9.50 69.83 ! 9.11 0.82
Gestational weeks, (weeks ! days) 39.36 ! 2.81 39.04 ! 3.10 0.13
Complications, n (%)
Hypertensive disorders of pregnancy 15 (4.04%) 5 (3.70%) 0.86
Diabetes 49 (13.21%) 18 (13.33%) 0.97
Thyroid disorders 41 (11.05%) 17 (12.59%) 0.63
Anemia 24 (6.47%) 6 (4.44%) 0.39
PROM, n (%) 103 (27.76%) 32 (23.70%) 0.36
GBS positive, n (%) 36 (9.70%) 8 (5.93%) 0.21
Labor type, n (%) 0.10
Induced 122 (32.88%) 34 (25.19%)
Spontaneous 249 (67.12%) 101 (74.81%)
*Significance values. GBS, group B streptococcus status; PROM: premature rupture of membranes.

© 2019 Japan Society of Obstetrics and Gynecology 3

H. Yin and R. Hu

Table 2 Maternal and neonatal outcomes in the two groups

Epidural (n = 371) Non-epidural (n = 135) P value
Mode of delivery, n (%) 0.41
Spontaneous vagina delivery 328 (88.41%) 123 (91.11%)
Caesarean section 21 (5.66%) 8 (5.93%)
Instrumental vagina delivery 22 (5.93%) 4 (2.96%)
Maternal Fever, n (%) 93 (25.07%) 9 (6.67%) <0.001*
Duration of the second stage (min) 58.55 ! 33.75 47.39 ! 28.36 0.001*
Total duration of labor (min) 790.32 ! 433.71 461.33 ! 270.39 <0.001*
Antibiotic administration, n (%) 197 (52.53%) 44 (32.59%) <0.001*
Oral 61 (16.27%) 21 (15.56%) 0.14
Intravenous 136 (36.66%) 23 (17.04%) <0.001*
Amount of post-partum hemorrhage, (mL) 308.42 ! 75.31 310.30 ! 103.51 0.87
Hospital stay after delivery, (days) 3.15 ! 0.72 3.10 ! 0.83 0.85
Apgar score <7 at 1 min, n (%) 3 (0.81%) 1 (0.74%) 1.00
Fetal distress, n (%) 57 (15.36%) 13 (9.63%) 0.10
Admission to neonatal ward, n (%) 98 (26.42%) 29 (21.48%) 0.26
Length of stay in neonatal ward (days) 3.52 ! 1.45 3.45 ! 1.57 0.55
Assisted ventilation n (%) 27 (7.28%) 5 (3.70%) 0.14
Neonatal Infection n (%) 34 (9.16%) 11 (8.15%) 0.72
Antibiotic administration, n (%) 48 (12.94%) 12 (8.89%) 0.21
Hyperbilirubinemia, n (%) 73 (19.68%) 23 (17.04%) 0.50
*Significance values.

not), duration of labor, baseline temperature, white by receiver operating characteristic curve. It showed
blood cell and neutrophile granulocyte (N) of women that time of epidural analgesia was a good predictor
before delivery. Results of the multivariable logistic of maternal fever with area under the curve of 0.71
regression were presented in Table 3. It showed that (Figure 1). The cut-off point was 355 min with the best
epidural analgesia was an independent risk factor for Youden index of 0.41. At this point, the sensitivity
maternal fever with adjusted odds ratio of 3.28 (95% was 0.77, the specificity was 0.65. According to the
CI = 1.55–6.95) even after excluding other risk factors
including PROM and the duration of labor.
We further explored the relation between the dura-
tion time of epidural analgesia and intrapartum fever

Table 3 Results of the logistic regression analysis of fac-

tors associated with intrapartum fever
Risk factors OR 95% CI P value
Epidural analgesia 3.14 1.48–6.67 <0.01*
(0 = not,1 = yes)
PROM (0 = not, 2.04 1.25–3.36 <0.01*
1 = yes)
GBS (0 = not, 0.63 0.26–1.52 0.30
1 = yes)
Total duration of labor 1.001 1.000–1.002 <0.001*
Baseline temperature 0.85 0.36–2.04 0.72
($ C)
WBC before delivery 0.97 0.86–1.09 0.60
N before delivery (%) 0.996 0.96–1.04 0.85
*Significance values. CI, confidence interval; GBS, group B
streptococcus status; N, neutrophile granulocyte; OR, odds Figure 1 Receiver operating characteristic curve of the
ratio, PROM, premature rupture of membranes; WBC, white duration time of epidural analgesia and intrapartum
blood cell. fever.

4 © 2019 Japan Society of Obstetrics and Gynecology

Impact of epidural analgesia on labor

Table 4 RR of groups of different epidural time

Intrapartum fever (n) No-fever (n) P value RR 95% CI
Non-epidural 9 (6.67%) 126 (93.33%)
Epidural <6 h 18 (11.54%) 138 (88.46%) 0.15 1.73 0.80–3.72
Epidural ≥6 h 75 (34.88%) 140 (65.12%) <0.001* 5.23 2.71–10.10
*Significance values. CI, confidence interval; RR, relative risk.

calculated cut-off point, we sub-grouped women by after delivery and no difference was shown in any
the duration time of analgesia by 6 h and calculated neonatal outcomes we studied as well (Table 5).
RR of each group. Statistics showed that RR of intra-
partum fever of women with analgesia time shorter
than 6 h was 1.73 (95% CI = 0.80–3.72, P = 0.15), Discussion
which had no statistical significance, while the RR of
intrapartum fever with analgesia time longer than 6 h In this study, we found that first, epidural analgesia
increased to 5.23 (95% CI = 2.71–10.10, P<0.001), was an independent risk factor for maternal intra-
showed in Table 4. partum pyrexia even after adjusting for other intra-
As women with epidural analgesia more than 6 h partum factors and it was associated with more use of
were at higher risk of intrapartum fever, we contin- antibiotics, longer time of second stage and longer
ued to analyze that whether epidural analgesia more total duration of labor. However, it did not increase
than 6 h would cause more adverse maternal or neo- other adverse maternal and neonatal outcomes we
natal outcomes. Results were similar with conclusions studied. Second, time-effect analyses showed that epi-
above. It showed that mother with epidural time dural analgesia less than 6 h did not increase the risk
more than 6 h experienced longer time of the second of intrapartum fever; however, when epidural analge-
stage and longer total duration of labor, and were sia lasted over 6 h, it significantly increased the risk of
more likely to receive antibiotics (P<0.001). However, fever but did not cause more adverse outcomes.
there was no difference in mother’s way of delivery, Our study confirmed that epidural analgesia did
amount of post-partum hemorrhage and hospital stay associate with maternal fever, and mainly in women

Table 5 Maternal and neonatal outcomes in three groups

Epidural≥6 h Epidural<6 h Non- P value
(n = 215) (n = 156) epidural (n = 135)
Mode of delivery, n (%) 0.42
Spontaneous vagina delivery 186 (86.51%) 142 (91.03%) 123 (91.11%)
Caesarean section 15 (6.98%) 6 (3.85%) 8 (5.93%)
Instrumental vagina delivery 14 (6.51%) 8 (5.13%) 4 (2.96%)
Duration of the second stage (min) 63.38 ! 36.50 52.12 ! 28.57 47.39 ! 28.36 <0.001*
Total duration of labor (min) 957.25 ! 442.15 560.25 ! 295.33 461.33 ! 270.40 <0.001*
Antibiotic administration, n (%) 125 (58.14%) 72 (46.15%) 44 (32.60%) <0.001*
Oral 31 (14.42%) 30 (19.23%) 21 (15.56%)
Intravenous 94 (43.72%) 42 (26.92%) 23 (17.04%)
Amount of post-partum hemorrhage 314.07 ! 71.87 300.64 ! 79.39 310.30 ! 103.51 0.31
Hospital stay after delivery (days) 3.17 ! 0.34 3.13 ! 0.69 3.10 ! 0.83 0.74
Apgar score <7 at 1 min, (n%) 2 (0.93%) 1 (0.64%) 1 (0.74%) 0.95
Fetal distress, n (%) 32 (14.88%) 25 (16.03%) 13 (9.63%) 0.24
Admission to neonatal ward, n (%) 58 (26.98%) 40 (25.64%) 29 (21.48%) 0.26
Length of stay in neonatal ward 3.64 ! 1.40 3.35 ! 1.53 3.45 ! 1.57 0.62
Assisted ventilation, n (%) 17 (7.91%) 10 (6.41%) 5 (3.70%) 0.29
Neonatal Infection, n (%) 23 (10.70%) 11 (7.05%) 11 (8.15%) 0.45
Antibiotic administration, n (%) 34 (15.81%) 15 (9.62%) 12 (8.89%) 0.21
Hyperbilirubinemia, n (%) 40 (18.60%) 33 (21.16%) 24 (17.78%) 0.47
*Significance values.

© 2019 Japan Society of Obstetrics and Gynecology 5

H. Yin and R. Hu

with epidural time more than 6 h. The etiology of the than 6 h had a much higher rate of maternal fever,
relation between maternal fever and epidural analgesia however, further analyses showed that epidural anal-
remains controversial.14,15 It was suggested that the gesia over 6 h did not increase adverse maternal or
underlying mechanism may be due to non-infectious neonatal outcomes we studied, which confirmed that
inflammation.16–18 Several studies have demonstrated although the risk of maternal fever increased, epidu-
elevated levels of interleukin-6 (IL-6) in inflammatory ral analgesia was still safe to be applied during labor.
etiologies of maternal fever.3,19 Riley et al. compared These findings are helpful for clinicians to make
rates of inflammatory markers and placental infection correlated decisions. First, epidural analgesia was
in women with and without epidural analgesia during associated with more use of antibiotics of mother
labor,they found that the prevalence of infection was which may conversely present the question that
the same in the two groups, but women with an epi- whether antibiotics were overused in women with
dural were more likely to experience maternal fever epidural fever and should be used more discreetly in
and women with higher IL-6 levels on admission were the future. Second, although epidural analgesia did
at increased risk of developing fever.2 The non- not increase other adverse outcomes we studied, the
infectious inflammation hypothesis was also supported risk of intrapartum fever raised significantly when
by a double-blind, placebo-controlled trial with antibi- epidural analgesia lasted over 6 h. Greenwell et al.
otics given before epidural analgesia and showed no found that adverse neonatal outcomes including
difference in the rate of maternal fever or placental assisted ventilation, hypotonia, Apgar scores<7 and
inflammation between groups.20 Sultan et al. suggested early-onset seizures increased with maximum mater-
another possible explanation that epidural analgesia nal intrapartum temperature in the absence of demon-
incites an inflammatory response and possible causes strated infection,but epidural use without
of inflammation include trauma from epidural catheter temperature elevation was not associated with any of
insertion, labor, and local anesthetics.16 In our study, the adverse outcomes they studied.3 So it is still neces-
mother with demonstrated infection or fever before sary to monitor women’s temperature during labor,
labor were excluded from the beginning. Besides, especially women with epidural analgesia more than
results of previous studies may be affected by some 6 h. While adverse neonatal outcomes were associated
bias including induction and duration of labor or way with higher maximum maternal temperature during
of ruptured membranes, our study showed that epidu- labor, it should be alerted when mother’s temperature
ral analgesia was associated with maternal intrapartum reached 38$ C. Since epidural fever takes time to
pyrexia even after adjusting these intrapartum factors. develop, strategies of shortening duration of epidural
Overall, it appears that the relation between epidural analgesia should be considered such as delaying epi-
analgesia and maternal fever involves noninfectious dural placement, and once an epidural is placed, oxy-
inflammation and it is important to define the relation tocin could be used in proper time to accelerate the
in the next step. labor process and thereby reduce the risk of maternal
In the aspects of maternal and neonatal outcomes, fever. The efficacy of such interventions would need
conclusions drew from other studies were also contro- to be studied to meet the balance of maternal satisfac-
versial.7,21,22 Intrapartum maternal fever has been tion and reducing maternal fever.
associated with signs of neurological depression in There were also some limitations about our study.
neonates such as low Apgar scores, hypotonia, sup- Data like maternal IL-6 level or placental pathology
plemental oxygen requirements, assisted ventilation, were missing, leading difficultly to further analyze
or cardiopulmonary resuscitation.23,24 Neonates of the underlying reason of epidural-related fever. We
mother who received epidurals were more often eval- plan to add further surveillance in next studies.
uated for sepsis and received antibiotics, although the Besides, the small sample size of this study was also a
incidence of actual neonatal sepsis is very low.24 Our limitation. What’s more, the decision for admission to
study showed that epidural analgesia increased use of neonatal unit and management of neonatal complica-
antibiotics of mother, but had no effect on other out- tions were unstandardized and at the discretion of
comes we studied. This was in accordance with some neonatologists, which may cause bias.
studies. Törnell et al. found that epidural analgesia Our study showed that epidural analgesia was
was associated with a lower Apgar score but was not associated with maternal intrapartum pyrexia and
associated with neonatal neurological consequences.7 more use of antibiotics, longer time of second stage
In our study, women with epidural analgesia more and longer total duration of labor. Time-effect

6 © 2019 Japan Society of Obstetrics and Gynecology

Impact of epidural analgesia on labor

analyses showed that epidural analgesia less than 6 h epidural analgesia during labour: A Swedish registry-based
did not increase the risk of intrapartum fever, but epi- study. Acta Anaesthesiol Scand 2015; 59: 486–495.
8. Lim G, Facco FL, Nathan N et al. A review of the impact of
dural analgesia more than 6 h was an independent
obstetric anesthesia on maternal and neonatal outcomes.
risk factor for maternal intrapartum pyrexia even after Anesthesiology 2018; 1: 192-215.
adjusting other intrapartum factors but it did not 9. Evron S, Ezri T, Protianov M et al. The effects of remifentanil
increase more adverse outcomes. or acetaminophen with epidural ropivacaine on body tem-
There is still much to learn about the mechanisms perature during labor. J Anesth 2008; 22: 105–111.
10. American College of Obstetricians and Gynecologists; Task
underlying epidural-related fever. Once these mecha-
Force on Hypertension in Pregnancy. Hypertension in preg-
nisms are understood, effective interventions can be nancy. Report of the American College of Obstetricians and
adopted to prevent and treat epidural-related fever. Gynecologists’ task force on hypertension in pregnancy.
What’s more, fever itself may cause far-reaching conse- Obstet Gynecol 2013; 122: 1122–1131.
quences for some exposed fetuses, but adverse effects 11. Macones GA, Hankins GD, Spong CY et al. The 2008
National Institute of Child Health and Human Development
of epidural related fever were still controversial. Fur-
workshop report on electronic fetal monitoring: Update on
ther study focus on the newborn consequences of non- definitions, interpretation, and research guidelines. J Obstet
infectious fever in labor may be helpful to determine Gynecol Neonatal Nurs 2010; 37 : 510–515.
whether epidural analgesia is harmful to newborn in 12. Jia R, Fan S, Yuan H et al. Intravertebral anesthesia in labor
the subset of women with fever. analgesia can induce maternal Intrapartum fever. J Practical
Obstet Gynecol 2015; 9: 31.
13. Guo D, Xu M. Effects of combined spinal epidural analgesia
on the outcomes of labor and intrapartum fever. Chniese J
Med 2016; 51: 75–78.
Acknowledgments 14. Mayer D, Chescheir N, Spielman F. Increased intrapartum
antibiotic administration associated with epidural analgesia
The study was supported by the National Natural Sci- in labor. Am J Perinatol 1997; 14 : 83–86.
ence Foundation of China (grant no. 81571460). 15. Sharpe EE, Arendt KW. Epidural labor analgesia and mater-
nal fever. Clin Obstet Gynecol 2017; 60: 365–374.
16. Sultan P, David AL, Fernando R, Ackland GL. Inflammation
and epidural-related maternal fever: Proposed mechanisms.
Disclosure Anesth Analg 2016; 122: 1546–1553.
17. Neal JL, Lamp JM, Lowe NK, Gillespie SL, Sinnott LT,
None declared. McCarthy DO. Differences in inflammatory markers
between nulliparous women admitted to hospitals in
preactive vs active labor. Am J Obstet Gynecol 2015; 212: 1–8.
References 18. Sharma SK, Rogers BB, Alexander JM, Mcintire DD,
Leveno KJ. A randomized trial of the effects of antibiotic
1. Hawkins JL. Epidural analgesia for labor and delivery. N prophylaxis on epidural-related fever in labor. Anesth Analg
Engl J Med 2010; 362: 1503–1510. 2014; 118: 604–610.
2. Riley LE, Celi AC, Onderdonk AB et al. Association of 19. Wang L-Z, Hu X-X, Liu X, Qian P, Ge J-M, Tang B-L. Influ-
epidural-related fever and noninfectious inflammation in ence of epidural dexamethasone on maternal temperature
term labor. Obstet Gynecol 2011; 117 : 588–595. and serum cytokine concentration after labor epidural anal-
3. Greenwell EA, Wyshak G, Ringer SA et al. Intrapartum tem- gesia. Int J Gynaecol Obstet 2011; 113: 40–43.
perature elevation, epidural use, and adverse outcome in 20. Goetzl L, Rivers J, Evans T et al. Prophylactic acetaminophen
term infants. Pediatrics 2012; 129: e447–e454. does not prevent epidural fever in nulliparous women: A
4. de Orange FA, Passini R Jr, Amorim MMR, Almeida T, double-blind placebo-controlled trial. J Perinatology 2004; 24 :
Barros A. Combined spinal and epidural anaesthesia and 471–475.
maternal intrapartum temperature during vaginal delivery: 21. Ginosar Y, Reynolds F, Halpern S, Weiner CP. Regional analgesia,
A randomized clinical trial. Br J Anaesth 2011; 107 : 762–768. maternal fever, and its effect on the fetus and neonate. In: Anesthe-
5. Douma MR, Stienstra R, Middeldorp JM, Arbous MS, sia and the Fetus. Chichester: Wiley-Blackwell, 2012; 277–284.
Dahan A. Differences in maternal temperature during labour 22. Dior UP, Liron K, Ronit CM et al. The association of mater-
with remifentanil patient-controlled analgesia or epidural nal intrapartum subfebrile temperature and adverse obstet-
analgesia: A randomised controlled trial. Int J Obstet Anesth ric and neonatal outcomes. Paediatr Perinat Epidemiology
2015; 24 : 313–322. 2014; 28: 39–47.
6. Burgess APH, Katz JE, Moretti M, Lakhi N. Risk factors for 23. Lieberman E, Lang J, Richardson DK. Intrapartum maternal
Intrapartum fever in term gestations and associated mater- fever and neonatal outcome. Pediatrics 2001; 105: 8–13.
nal and neonatal Sequelae. Gynecol Obstet Invest 2017; 82: 24. Impey LW, Greenwood CE, Black RS, Yeh PS, Sheil O,
508–516. Doyle P. The relationship between intrapartum maternal
7. Törnell S, Ekéus C, Hultin M, Hakansson S, Thunberg J, fever and neonatal acidosis as risk factors for neonatal
Hogberg U. Low Apgar score, neonatal encephalopathy and encephalopathy. Am J Obstet Gynecol 2008; 198: 1–6.

© 2019 Japan Society of Obstetrics and Gynecology 7