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

2019

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

Abstract
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
significant.
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-

Labor is a complex process with one of the most
severe pains which could cause a series of neurophys-
iological changes such as increasing maternal stress
hormones, elevating blood pressure, inducing hyper-
ventilation and reducing fetal oxygen transport.1 In
recent years, labor analgesia began to be more and
more widely used in China. Meanwhile, attention has
been paid to the maternal and neonatal influence of
labor analgesia.
A few studies have observed that women receiving
epidural analgesia were at increased risk for intra-
partum fever.2–5 Women with maternal pyrexia are
mental delivery and maternal pyrexia may also be
associated with adverse neonatal outcomes including
low Apgar scores, respiratory distress, hypotonia and
neonatal seizures.3,6 However, another study
suggested that epidural fever may be a benign rise in
temperature not associated with neonatal neurological
consequences.7 The etiology of the relation between
maternal fever and epidural analgesia remains
unclear and whether epidural analgesia would cause
adverse obstetric outcomes were controversial. Anes-
thesia effects on the duration of the second stage of
labor, instrumental vaginal delivery, labor epidural-
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
effect of duration time of epidural analgesia on mater-
nal and neonatal outcomes were also absent. Current
and future work on these areas may enhance clini-
cian’s ability to personalize obstetric anesthesia thera-
pies and interventions.
Therefore, the objective of this study was to explore
the relation between epidural analgesia and intra-
partum fever and whether epidural analgesia would
cause adverse effect on maternal and neonatal out-
comes. As some studies suggested that epidural fever
took time to develop, this study also focused on the
effect of duration time of epidural analgesia to pro-
vide evidence for clinicians to timely make correlated
interventions.
Methods
This was a retrospective cohort study in a tertiary
obstetrics and gynecology hospital for all deliveries
over 2 months from November 2017 to December
2017. For the present analysis, we limited the popula-
tion to women with singleton and term pregnancies
(≥37 weeks gestation). Sample size was calculated by
the following formula for a cohort study:
" pffiffiffiffiffi pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi#2
Zα 2pq + Zβ p0 q0 + p1 q1
n= 2 . Based on the previous stud-
ð p1 − p0 Þ
ies, p1 (proportion in cases) = 10.5%, p0 (proportion in
control) = 2.3%.9Considering the loss rate and incom-
plete data, the estimated final sample size was
500 cases. Women were divided into epidural and
non-epidural groups by whether to receive analgesia
in labor according to their wills. Pregnancies compli-
cated with fetal growth restriction or oligoamnios
which may be associated with low placental function
were excluded from the study. In addition, women
with demonstrated infection, a fever before labor or a
basal body temperature higher than or equal to
37.5$ C were also excluded from this study. This study
was approved by the Research Ethics Committee in
the Obstetrics and Gynecology Institute, Fudan Uni-
versity Shanghai Medical College (Number: 2018–14,
Date: 2018.3.20).
Epidural analgesia was performed on women when
they had 2 cm of cervical dilatation or more. The epi-
dural space was at the L2–L3 interspace, and an epi-
dural catheter was advanced 3–5 cm into the epidural
space. An analgesic mixture of 4–10 mL 0.1%
ropivacaine with 2–5 μg sufentanil was administered
2 © 2019 Japan Society of Obstetrics and Gynecology
as a loading dose. The patient-analgesia (PCEA) was
connected 10 min later with 100 mL 0.1% ropivacaine
and 0.5 μg/mL sufentanil repeating during labor on
demand. PCEA was set as 5 mL/h for continuous
infusion, 5 mL for single press and 15 min for locking.
PCEA was stopped after the second stage of labor
and the catheter was removed 2 h after delivery.
Data extracted from the medical record included
maternal age, height, weight, complications, gesta-
tional weeks, labor type (spontaneous vs induced
labor), group B streptococcus status (positive vs nega-
tive), results of blood routine test before delivery, time
and way of membrane rupture and duration of labor
(from the beginning of labor to the delivery of new-
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-
eclampsia and gestational hypertension according to
the American College of Obstetrics and Gynecology
(ACOG) guideline.10 Diabetes included both
pregestational diabetes mellitus (PGDM) and gesta-
tional diabetes mellitus (GDM) and GDM was diag-
nosed by the 75 g oral glucose tolerance test (OGTT)
at 24–28 weeks of gestation. Thyroid disorders were
diagnosed by abnormal results of thyroid function
tests. Anemia was defined as the concentration of
hemoglobin lower than 110 g/L. Maternal outcomes
included mode and time of delivery, duration of the
second stage and total duration of labor, use of antibi-
otics (oral, intravenous or not), the amount of post-
partum hemorrhage and hospital stay after delivery.
Neonatal data included 1 min Apgar scores, fetal dis-
tress, assisted ventilation, admission to the neonatal
unit and length of stay, hyperbilirubinemia, the diag-
nosis of neonatal infection and use of antibiotics. Elec-
tronic fetal monitoring (EFM) was adopted during
stages and fetal distress was considered when cate-
gory III tracing or repeated category II tracing was
presented.11 Assisted ventilation included positive
pressure ventilation, mask resuscitation, intubation
and chest compressions. Admission to neonatal unit
was at the discretion of experienced neonatologists.
The intrapartum maternal fever was defined as a tem-
perature of greater than or equal to 37.5$ C any time
during labor and delivery.12,13 Baseline temperatures
of women were routinely recorded on admission to
the labor and delivery room. Temperatures were
assessed orally by nurses every 4 hours during labor
and once a temperature of 37.5$ C was reached, the
obstetric doctor is notified to further evaluation.
 Impact of epidural analgesia on labor

Indications for antibiotic use were as follows: Women
were given erythrocin orally when 12 h after the rup-
ture of membrane; If a patient was group B strepto-
coccus status positive, cephalosporin were used
intravenously as soon as the rupture of membrane or
regular contractions; Women were also given cephalo-
sporin intravenously after the diagnosis of maternal
fever.
Data were analyzed by SPSS Statistics version 22.0.
Normal distribution for continuous variables was
determined using the Shapiro–Wilk test. Quantitative
variables were expressed as mean ! standard devia-
tion (SD) and qualitative variables as percentages.
Categorical data were compared using the χ 2 test or
Fisher’s exact tests. Continuous data were compared
using the Student’s t-test. A multivariable logistic
regression model was estimated to evaluate the asso-
ciation between maternal fever and epidural analge-
sia. Receiver operating characteristic curve was
adopted to further explore the relation between the
duration time of epidural analgesia and intrapartum
fever and to find out whether there is a cut-off point.
P<0.05 was considered statistically significant.
Results
A total of 506 deliveries were involved in this study
with 371 women in epidural group and 135 women in
non-epidural group. Demographics were shown in
Table 1. There were no differences between the two
groups in terms of maternal height, weight, gesta-
tional age, complications, labor type, rate of
premature rupture of membranes (PROM) or rate of
group B streptococcus status positive status.
Statistics for maternal and neonatal outcomes were
shown in Table 2. The incidence of intrapartum fever
was 25.07% and 6.67% in epidural and non-epidural
group, respectively (P<0.001). The relative risk (RR) of
intrapartum fever was 3.76 (95% confidence interval
[CI[:1.95–7.24) compared with the non-epidural
group. Besides, mother in the epidural group were
more likely to receive antibiotics, and mainly in intra-
venous way (36.66% vs 17.04%, P<0.001) and time of
the second stage and total duration of labor were lon-
ger in the epidural group (58.55 ! 33.75 min vs
47.39 ! 28.36 min，P = 0.001; 790.32 ! 433.71 vs
461.33 ! 270.39 min，P<0.001*). However, there was
no difference in the way of delivery. The rate of spon-
taneous vaginal delivery was 88.41% and 91.11% in
epidural and non-epidural group, respectively
(P = 0.41) and no difference was showed in the
amount of post-partum hemorrhage in the two
groups (308.42 ! 75.31 vs 310.30 ! 103.51 mL,
P = 0.87) or mother’s hospital stay after delivery as
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,
neonatal infection, antibiotic administration or hyper-
bilirubinemia between two groups.
A multivariable logistic regression model was
adopted to exclude the impact of other risk factors
that may be associated with maternal fever. Candi-
date independent variables were as follows: epidural
analgesia (used or not), group B streptococcus status
(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
blood cell and neutrophile granulocyte (N) of women
before delivery. Results of the multivariable logistic
regression were presented in Table 3. It showed that
epidural analgesia was an independent risk factor for
maternal fever with adjusted odds ratio of 3.28 (95%
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
by receiver operating characteristic curve. It showed
that time of epidural analgesia was a good predictor
of maternal fever with area under the curve of 0.71
(Figure 1). The cut-off point was 355 min with the best
Youden index of 0.41. At this point, the sensitivity
was 0.77, the specificity was 0.65. According to the

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*
(min)
Baseline temperature 0.85 0.36–2.04 0.72
($ C)
WBC before delivery 0.97 0.86–1.09 0.60
(109/L)
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
the duration time of analgesia by 6 h and calculated
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),
which had no statistical significance, while the RR of
intrapartum fever with analgesia time longer than 6 h
increased to 5.23 (95% CI = 2.71–10.10, P<0.001),
showed in Table 4.
As women with epidural analgesia more than 6 h
were at higher risk of intrapartum fever, we contin-
ued to analyze that whether epidural analgesia more
than 6 h would cause more adverse maternal or neo-
natal outcomes. Results were similar with conclusions
above. It showed that mother with epidural time
more than 6 h experienced longer time of the second
stage and longer total duration of labor, and were
more likely to receive antibiotics (P<0.001). However,
there was no difference in mother’s way of delivery,
amount of post-partum hemorrhage and hospital stay
after delivery and no difference was shown in any
neonatal outcomes we studied as well (Table 5).
Discussion
In this study, we found that first, epidural analgesia
was an independent risk factor for maternal intra-
partum pyrexia even after adjusting for other intra-
partum factors and it was associated with more use of
antibiotics, longer time of second stage and longer
total duration of labor. However, it did not increase
other adverse maternal and neonatal outcomes we
studied. Second, time-effect analyses showed that epi-
dural analgesia less than 6 h did not increase the risk
of intrapartum fever; however, when epidural analge-
sia lasted over 6 h, it significantly increased the risk of
fever but did not cause more adverse outcomes.
Our study confirmed that epidural analgesia did
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
(mL)
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
(days)
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
relation between maternal fever and epidural analgesia
remains controversial.14,15 It was suggested that the
underlying mechanism may be due to non-infectious
inflammation.16–18 Several studies have demonstrated
elevated levels of interleukin-6 (IL-6) in inflammatory
etiologies of maternal fever.3,19 Riley et al. compared
rates of inflammatory markers and placental infection
in women with and without epidural analgesia during
labor，they found that the prevalence of infection was
the same in the two groups, but women with an epi-
dural were more likely to experience maternal fever
and women with higher IL-6 levels on admission were
at increased risk of developing fever.2 The non-
infectious inflammation hypothesis was also supported
by a double-blind, placebo-controlled trial with antibi-
otics given before epidural analgesia and showed no
difference in the rate of maternal fever or placental
inflammation between groups.20 Sultan et al. suggested
another possible explanation that epidural analgesia
incites an inflammatory response and possible causes
of inflammation include trauma from epidural catheter
insertion, labor, and local anesthetics.16 In our study,
mother with demonstrated infection or fever before
labor were excluded from the beginning. Besides,
results of previous studies may be affected by some
bias including induction and duration of labor or way
of ruptured membranes, our study showed that epidu-
ral analgesia was associated with maternal intrapartum
pyrexia even after adjusting these intrapartum factors.
Overall, it appears that the relation between epidural
analgesia and maternal fever involves noninfectious
inflammation and it is important to define the relation
in the next step.
In the aspects of maternal and neonatal outcomes,
conclusions drew from other studies were also contro-
versial.7,21,22 Intrapartum maternal fever has been
associated with signs of neurological depression in
neonates such as low Apgar scores, hypotonia, sup-
plemental oxygen requirements, assisted ventilation,
or cardiopulmonary resuscitation.23,24 Neonates of
mother who received epidurals were more often eval-
uated for sepsis and received antibiotics, although the
incidence of actual neonatal sepsis is very low.24 Our
study showed that epidural analgesia increased use of
antibiotics of mother, but had no effect on other out-
comes we studied. This was in accordance with some
studies. Törnell et al. found that epidural analgesia
was associated with a lower Apgar score but was not
associated with neonatal neurological consequences.7
In our study, women with epidural analgesia more
6 © 2019 Japan Society of Obstetrics and Gynecology
than 6 h had a much higher rate of maternal fever,
however, further analyses showed that epidural anal-
gesia over 6 h did not increase adverse maternal or
neonatal outcomes we studied, which confirmed that
although the risk of maternal fever increased, epidu-
ral analgesia was still safe to be applied during labor.
These findings are helpful for clinicians to make
correlated decisions. First, epidural analgesia was
associated with more use of antibiotics of mother
which may conversely present the question that
whether antibiotics were overused in women with
epidural fever and should be used more discreetly in
the future. Second, although epidural analgesia did
not increase other adverse outcomes we studied, the
risk of intrapartum fever raised significantly when
epidural analgesia lasted over 6 h. Greenwell et al.
found that adverse neonatal outcomes including
assisted ventilation, hypotonia, Apgar scores<7 and
early-onset seizures increased with maximum mater-
nal intrapartum temperature in the absence of demon-
strated infection，but epidural use without
temperature elevation was not associated with any of
the adverse outcomes they studied.3 So it is still neces-
sary to monitor women’s temperature during labor,
especially women with epidural analgesia more than
6 h. While adverse neonatal outcomes were associated
with higher maximum maternal temperature during
labor, it should be alerted when mother’s temperature
reached 38$ C. Since epidural fever takes time to
develop, strategies of shortening duration of epidural
analgesia should be considered such as delaying epi-
dural placement, and once an epidural is placed, oxy-
tocin could be used in proper time to accelerate the
labor process and thereby reduce the risk of maternal
fever. The efficacy of such interventions would need
to be studied to meet the balance of maternal satisfac-
tion and reducing maternal fever.
There were also some limitations about our study.
Data like maternal IL-6 level or placental pathology
were missing, leading difficultly to further analyze
the underlying reason of epidural-related fever. We
plan to add further surveillance in next studies.
Besides, the small sample size of this study was also a
limitation. What’s more, the decision for admission to
neonatal unit and management of neonatal complica-
tions were unstandardized and at the discretion of
neonatologists, which may cause bias.
Our study showed that epidural analgesia was
associated with maternal intrapartum pyrexia and
more use of antibiotics, longer time of second stage
and longer total duration of labor. Time-effect

analyses showed that epidural analgesia less than 6 h
did not increase the risk of intrapartum fever, but epi-
dural analgesia more than 6 h was an independent
risk factor for maternal intrapartum pyrexia even after
adjusting other intrapartum factors but it did not
increase more adverse outcomes.
There is still much to learn about the mechanisms
underlying epidural-related fever. Once these mecha-
nisms are understood, effective interventions can be
adopted to prevent and treat epidural-related fever.
What’s more, fever itself may cause far-reaching conse-
quences for some exposed fetuses, but adverse effects
of epidural related fever were still controversial. Fur-
ther study focus on the newborn consequences of non-
infectious fever in labor may be helpful to determine
whether epidural analgesia is harmful to newborn in
the subset of women with fever.
Acknowledgments
The study was supported by the National Natural Sci-
ence Foundation of China (grant no. 81571460).
Disclosure
None declared.
References
1. Hawkins JL. Epidural analgesia for labor and delivery. N
Engl J Med 2010; 362: 1503–1510.
2. Riley LE, Celi AC, Onderdonk AB et al. Association of
epidural-related fever and noninfectious inflammation in
term labor. Obstet Gynecol 2011; 117 : 588–595.
3. Greenwell EA, Wyshak G, Ringer SA et al. Intrapartum tem-
perature elevation, epidural use, and adverse outcome in
term infants. Pediatrics 2012; 129: e447–e454.
4. de Orange FA, Passini R Jr, Amorim MMR, Almeida T,
Barros A. Combined spinal and epidural anaesthesia and
maternal intrapartum temperature during vaginal delivery:
A randomized clinical trial. Br J Anaesth 2011; 107 : 762–768.
5. Douma MR, Stienstra R, Middeldorp JM, Arbous MS,
Dahan A. Differences in maternal temperature during labour
with remifentanil patient-controlled analgesia or epidural
analgesia: A randomised controlled trial. Int J Obstet Anesth
2015; 24 : 313–322.
6. Burgess APH, Katz JE, Moretti M, Lakhi N. Risk factors for
Intrapartum fever in term gestations and associated mater-
nal and neonatal Sequelae. Gynecol Obstet Invest 2017; 82:
508–516.
7. Törnell S, Ekéus C, Hultin M, Hakansson S, Thunberg J,
Hogberg U. Low Apgar score, neonatal encephalopathy and
© 2019 Japan Society of Obstetrics and Gynecology
Impact of epidural analgesia on labor
epidural analgesia during labour: A Swedish registry-based
study. Acta Anaesthesiol Scand 2015; 59: 486–495.
8. Lim G, Facco FL, Nathan N et al. A review of the impact of
obstetric anesthesia on maternal and neonatal outcomes.
Anesthesiology 2018; 1: 192-215.
9. Evron S, Ezri T, Protianov M et al. The effects of remifentanil
or acetaminophen with epidural ropivacaine on body tem-
perature during labor. J Anesth 2008; 22: 105–111.
10. American College of Obstetricians and Gynecologists; Task
Force on Hypertension in Pregnancy. Hypertension in preg-
nancy. Report of the American College of Obstetricians and
Gynecologists’ task force on hypertension in pregnancy.
Obstet Gynecol 2013; 122: 1122–1131.
11. Macones GA, Hankins GD, Spong CY et al. The 2008
National Institute of Child Health and Human Development
workshop report on electronic fetal monitoring: Update on
definitions, interpretation, and research guidelines. J Obstet
Gynecol Neonatal Nurs 2010; 37 : 510–515.
12. Jia R, Fan S, Yuan H et al. Intravertebral anesthesia in labor
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.
14. Mayer D, Chescheir N, Spielman F. Increased intrapartum
antibiotic administration associated with epidural analgesia
in labor. Am J Perinatol 1997; 14 : 83–86.
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.
Anesth Analg 2016; 122: 1546–1553.
17. Neal JL, Lamp JM, Lowe NK, Gillespie SL, Sinnott LT,
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.
18. Sharma SK, Rogers BB, Alexander JM, Mcintire DD,
Leveno KJ. A randomized trial of the effects of antibiotic
prophylaxis on epidural-related fever in labor. Anesth Analg
2014; 118: 604–610.
19. Wang L-Z, Hu X-X, Liu X, Qian P, Ge J-M, Tang B-L. Influ-
ence of epidural dexamethasone on maternal temperature
and serum cytokine concentration after labor epidural anal-
gesia. Int J Gynaecol Obstet 2011; 113: 40–43.
20. Goetzl L, Rivers J, Evans T et al. Prophylactic acetaminophen
does not prevent epidural fever in nulliparous women: A
double-blind placebo-controlled trial. J Perinatology 2004; 24 :
471–475.
21. Ginosar Y, Reynolds F, Halpern S, Weiner CP. Regional analgesia,
maternal fever, and its effect on the fetus and neonate. In: Anesthe-
sia and the Fetus. Chichester: Wiley-Blackwell, 2012; 277–284.
22. Dior UP, Liron K, Ronit CM et al. The association of mater-
nal intrapartum subfebrile temperature and adverse obstet-
ric and neonatal outcomes. Paediatr Perinat Epidemiology
2014; 28: 39–47.
23. Lieberman E, Lang J, Richardson DK. Intrapartum maternal
fever and neonatal outcome. Pediatrics 2001; 105: 8–13.
24. Impey LW, Greenwood CE, Black RS, Yeh PS, Sheil O,
Doyle P. The relationship between intrapartum maternal
fever and neonatal acidosis as risk factors for neonatal
encephalopathy. Am J Obstet Gynecol 2008; 198: 1–6.
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