Original Research ajog.

org

OBSTETRICS
Incidence of fever in labor and risk of neonatal sepsis
Craig V. Towers, MD; Angela Yates, MD; Nikki Zite, MD; Casey Smith, MS; Lindsey Chernicky, MS;
Bobby Howard, MD

BACKGROUND: The current recommendation regarding the man-
agement of a term newborn delivered of a mother with an intrapartum
fever or a diagnosis of clinical chorioamnionitis is that the neonate should
have baseline laboratory work drawn along with blood cultures and be
universally treated with antibiotics until culture results return. These
guidelines report that the rate of intrapartum fever is about 3%; however, a
few large studies suggest that the rate is higher at about 7%.
OBJECTIVE: We sought to prospectively evaluate the rate of fever
during labor in a large number of deliveries and determine the rate of early-
onset neonatal sepsis in newborns delivered from mothers with an
intrapartum fever compared with newborns delivered from mothers
without intrapartum fever.
STUDY DESIGN: This was a prospective cohort study of all temper-
atures obtained in women in labor from Jan. 1, 2011, through June 30,
2014. Every patient with a fever of
38 C at
36 weeks’ gestation was
evaluated for gestational age, parity, spontaneous or induced labor, group
B streptococcus status, regional anesthesia, mode of delivery, treatment
with intrapartum antibiotics, and whether a clinical diagnosis of cho-
rioamnionitis was made by the managing physician. Neonates were
assessed for blood culture results, neonatal intensive care unit admission,
length of stay, and any major newborn complications. Statistical analysis
involved c2, Fisher exact, and Student t test.
RESULTS: A total of 412 patients (6.8%; 95% confidence interval,
6.2e7.5%) developed a fever in 6057 deliveries at
36 weeks’ gestation.
No cases of maternal sepsis occurred. Of the 417 newborns (5 sets of
twins), only 1 (0.24%; 95% confidence interval, 0.01e1.3%) developed
early-onset neonatal sepsis with a positive blood culture for Escherichia
coli. There were 4 cases (0.07%; 95% confidence interval, 0.02e0.18%)
of early-onset neonatal sepsis in the 5697 newborns (52 sets of twins)
delivered from mothers who were not febrile and this difference was not
significant (P ¼ .3). The positive blood cultures in these 4 neonates were 3
group B streptococcus and 1 Enterococcus. The overall rate of early-onset
neonatal sepsis in this population of newborns delivered at
36 weeks’
gestation was 0.82/1000 deliveries.
CONCLUSION: The incidence of an intrapartum fever of
38 C in
pregnancies at
36 weeks’ gestation is common at 6.8% and this is
consistent with the findings of a few other large retrospective studies.
The rate of an intrapartum fever occurs in approximately 1 in 15
women in labor. The risk of neonatal sepsis in newborns delivered of
mothers with intrapartum fever or a diagnosis of clinical cho-
rioamnionitis is low at 0.24%, a rate that is <1 in 400. The recom-
mendation for universal laboratory work, cultures, and antibiotic
treatment pending culture results for this newborn population needs
further examination.
Key words: clinical chorioamnionitis, group B streptococcus, inflammation,
intraamniotic infection, intrapartum antibiotics, microbial infections in preg-
nancy, neonatal intensive care unit admission, newborn blood cultures, sepsis

Introduction Congress of Obstetricians and Gynecol- step-down unit to provide treatment,

Currently there is no published obstet-
rical guideline specifically devoted to the
topic of chorioamnionitis. Although
microbial causes for chorioamnionitis
are multiple, the Centers for Disease
Control and Prevention (CDC) guide-
lines on prevention of perinatal group B
streptococcal (GBS) disease discuss
clinical chorioamnionitis stating that
“well-appearing newborns whose
mothers had suspected chorioamnioni-
tis should undergo a limited evaluation
and receive antibiotic therapy pending
culture results.”1 This recommendation
was adopted by both the American
Cite this article as: Towers CV, Yates A, Zite N, et al.
Incidence of fever in labor and risk of neonatal sepsis. Am
J Obstet Gynecol 2017;216:596.e1-5.
0002-9378/$36.00
ª 2017 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajog.2017.02.022
ogists and the American Academy of
Pediatrics.2,3 The CDC guidelines
further state that “in an effort to avert
neonatal infections, maternal fever alone
in labor may be used as a sign of cho-
rioamnionitis and hence indication for
antibiotic treatment.” There are several
ways in which this recommendation may
be implemented in clinical practice.
Some institutions may choose to ignore
or are unaware of the guideline and this
practice choice could increase liability in
cases of a poor outcome. Those in-
stitutions that choose to follow the
guideline need to identify these neonates
and initiate treatment with intravenous
antibiotics; however, newborn treatment
location could be problematic. Some
facilities might be able to treat a neonate
with intravenous antibiotics in a regular
newborn nursery (if one exists), whereas
others will need to move the newborn
to a neonatal intensive care unit or
potentially separating the mother from
the newborn.
The CDC guidelines also report that
the rate of intrapartum fever of
38 C is
only 3.3% and physician diagnoses of
chorioamnionitis is 3.1%, some of which
comes from unpublished data.1 How-
ever, a few large studies suggest that the rate
of clinical chorioamnionitis or fever in
labor is >3% and may actually be closer
to 7%.4-7 In our institution, all newborns
room on the postpartum floor with their
mothers and there is no specific healthy
newborn nursery; therefore, intravenous
antibiotics have to be administered in the
neonatal intensive care unit.
The primary study purpose was to
evaluate the rate of fever during labor
in a large number of deliveries at
36
weeks’ gestation and assess the risk for
early-onset neonatal sepsis in new-
borns delivered from mothers with an
intrapartum fever (
38 C) compared

596.e1 American Journal of Obstetrics & Gynecology JUNE 2017

ajog.org
with those delivered from mothers
without fever. The secondary study
objective was to evaluate differences in
laboring patients with intrapartum
fever who were given a clinical diag-
nosis of chorioamnionitis by their
managing physician compared with
those not given a diagnosis of
chorioamnionitis.
Materials and Methods
A prospective cohort study was per-
formed obtaining all temperatures in
women in labor from Jan. 1, 2011,
through June 30, 2014. Every case with a
fever (defined as
38 C) at
36 weeks’
gestation detected during labor and up
to the time of delivery was examined for
numerous factors including gestational
age, parity, spontaneous or induced
labor, GBS status, regional anesthesia,
mode of delivery, and maternal treat-
ment with antibiotics. Each case was also
analyzed for whether or not a clinical
diagnosis of chorioamnionitis was
assigned by the primary attending
physician. A diagnosis of chorioamnio-
nitis made by the primary managing
physician’s clinical impression was not
based on any specified mandatory
criteria, except all patients had a tem-
perature of
38 C. Cases had to enter
labor afebrile and then develop a tem-
perature of
38 C prior to delivery with
no other infectious cause identified.
Temperatures were primarily taken
orally (if the patient had not recently
consumed cold liquid or ice) every 1-2
hours during labor (or more frequent if
elevated). If a cold substance had
recently been consumed, then tempera-
tures were obtained by using a temporal
artery thermometer with a single sweep
across a dry forehead, the temple area,
ending behind the ear. Elevations by this
method were verified by an oral or axil-
lary value. Any intrapartum and/or
postpartum complications were recor-
ded. Exclusions were all scheduled
nonlaboring cesarean deliveries, all de-
liveries <36 weeks’ gestation, patients
who entered labor with a fever, and de-
liveries with major fetal anomalies. We
chose
36 weeks’ gestation because all
newborns delivered in our institution
<36 weeks’ gestation are evaluated by
OBSTETRICS
the neonatal department and the
majority of level-1 institutions in our
region transfer the mother if the gesta-
tional age is <36 weeks’ gestation.
Neonates were assessed for Apgar
scores, birthweight, blood culture,
length of stay, and any postdelivery
complications. Blood cultures were per-
formed in enriched media broth;
included aerobic, anaerobic, and genital
mycoplasma organisms; and were
assessed for a minimum of 5 days before
a negative result was reported. All neo-
nates delivered at
36 weeks’ gestation
admitted to the neonatal intensive care
unit for suspected early-onset neonatal
sepsis were also prospectively collected
during the study period. A diagnosis of
early-onset neonatal sepsis was defined
as blood and/or cerebrospinal fluid
culture-positive microbial infection
occurring in a newborn at <7 days of
life.
The study received institutional re-
view board approval from University of
Tennessee Medical Center, Knoxville.
Statistical analysis involved c2, Fisher
exact, and Student t test and P < .05 was
considered significant. All tests were
considered against a 2-sided alternative
hypothesis. Poisson binomial 95% con-
fidence intervals (CI) were also calcu-
lated on proportions.
Results
A total of 412 patients (6.8%; 95% CI,
6.2e7.5%) developed a temperature of

38 C in 6057 deliveries at
36 weeks’
gestation. There were 5 sets of twins for a
total of 417 neonates, and of these, only 1
newborn (0.24%; 95% CI, 0.01e1.3%)
developed early-onset neonatal sepsis
with a positive blood culture for Escher-
ichia coli. Of the 5645 deliveries
36
weeks’ gestation that were afebrile with
no clinical diagnosis of chorioamnioni-
tis, there were 52 sets of twins for a total
of 5697 newborns. There were 4 cases of
early-onset neonatal sepsis (0.07%; 95%
CI, 0.02e0.18%) with positive blood
cultures in this group but this difference
was not significant (P ¼ .3). These 4
positive blood cultures in the neonates
delivered of afebrile patients were 3 GBS
and 1 Enterococcus (Table 1). The overall
rate of early-onset neonatal sepsis at
JUNE 2017 American Journal of Obstetrics & Gynecology
Original Research

36 weeks’ gestation was 0.82/1000
deliveries. No case of maternal sepsis
occurred.
Of the 412 cases with a fever as
defined, 233 (57%) were not given a
clinical diagnosis of chorioamnionitis
by their respective managing physician,
possibly due to concern that the
newborn might go to the neonatal
intensive care unit at our institution.
The breakdown of maternal fever was
similar between the years with 115
cases (6.7%; 95% CI, 5.6e8.0%) in
1716 deliveries in 2011; 126 cases
(6.9%; 95% CI, 5.8e8.2%) in 1825
deliveries in 2012; 116 cases (6.9%;
95% CI, 5.7e8.2%) in 1689 deliveries
in 2013; and 55 cases (6.7%; 95% CI,
5.1e8.6%) in 827 deliveries through
June 2014.
Table 2 compares the demographics
and other variables between the cases
given a clinical diagnosis of cho-
rioamnionitis by their managing
physician compared with those not
given the diagnosis in the 412 patients
who had a fever
38 C. There were
slightly more nulliparous patients in
the chorioamnionitis group (P ¼ .043).
Interestingly, more patients with pri-
vate insurance were not given a clinical
diagnosis of chorioamnionitis (P ¼
.015). Regarding labor management,
the cases given a diagnosis of cho-
rioamnionitis were more likely to un-
dergo cesarean delivery and receive
intrapartum antibiotics (P < .0001). As
expected, there was also a higher
number of neonates admitted to the
neonatal intensive care unit and a
longer length of stay in those newborns
delivered of mothers given a diagnosis
of chorioamnionitis (P < .0001).
All of the 181 newborns (2 sets of
twins) delivered from pregnancies given
a diagnosis of chorioamnionitis were
admitted to the neonatal intensive care
unit per hospital protocol. The 1 case of
early-onset neonatal sepsis with
Escherichia coli was in this group of
newborns. These neonates had labora-
tory work performed along with blood
cultures and were treated universally
with antibiotics. Of the 236 neonates
delivered of mothers not given a diag-
nosis of chorioamnionitis, 37 (16%)
596.e2
Original Research
TABLE 1
Five cases of early-onset neonatal sepsis in 6114 neonates delivered at ‡36 weeks’ gestation
(rate of 0.82/1000 live births)
Gestational age, wk Bacterium
36.4 GBS
38.1 Escherichia coli 39.1
40.0 GBS
40.3 Enterococcus
41.1 GBS
GBS, group B streptococcus.
a
First dose of penicillin was being administered as she delivered.
Towers et al. Intrapartum fever and neonatal sepsis. Am J Obstet Gynecol 2017.
were admitted to the neonatal intensive
care unit.
Comment
Principal findings
These study results demonstrate that the
incidence of an intrapartum fever at
36
weeks’ gestation is common at 6.8%
occurring at a rate of about 1 in 15
women in labor; whereas the incidence
of early-onset neonatal sepsis is low in
this newborn population at 0.24%
occurring at a rate of <1 in 400 new-
borns delivered of a mother who had a
fever in labor.
Meaning of our observations as it
relates to other studies
The incidence of a maternal temperature

38 C in labor in this study was 6.8%
and was double the rate listed in the
CDC guidelines of 3.3%.1 However, our
rate correlates with a few other large
studies. Braun et al4 recently reported
retrospective electronic medical record
data from 13 Kaiser facilities and found
an intrapartum fever rate of 9% and a
chorioamnionitis rate of 7% in 31,112
deliveries at
35 weeks’ gestation. Their
study included all patients with a fever
(defined as
38 C) that occurred within
24 hours before to 4 hours after delivery
and a diagnosis of chorioamnionitis
required that intravenous antibiotic
treatment was administered to the
pregnant pateint.4 Wendel et al5 reported
a chorioamnionitis rate of 6.9% in
27,118 patients in their retrospective
database from 1994 through 1995.
596.e3 American Journal of Obstetrics & Gynecology JUNE 2017
OBSTETRICS
Maximum temperature,  C GBS status Nulliparous Duration of labor, h
36.3 Positive No
Negative No
37.4 Negative Yes
37.6 Negative Yes
37.2 Negative Yes
Chorioamnionitis in their study was
defined as a fever of
38 C without
another clinical cause and preterm was
defined as <36 weeks’ gestation. The rate
was 7.6% in 1994 before GBS prophy-
laxis and 6.3% in 1995 after GBS pro-
phylaxis.5 Towers et al,6 in a prospective
study from 4 hospitals in California, re-
ported a 7.0% rate of a maternal intra-
partum fever of
38 C in 5410 deliveries
at
24 weeks’ gestation. Lastly, Alex-
ander et al7 reported retrospective data
from 101,170 deliveries of infants who
weighed >2500 g and found a rate of
chorioamnionitis of 5%. Chorioamnio-
nitis in their study was defined as a fever
of
38 C not explained by another
source of infection along with fetal
tachycardia, uterine tenderness, or foul
odor at delivery.7
Overall, the incidence of neonatal
sepsis is rare in this population of women
who had a fever in labor. Our rate of 0.82
per 1000 live births at
36 weeks’ gesta-
tion is similar to Braun et al,4 who re-
ported a rate of neonatal sepsis of 0.61 per
1000 live births at
35 weeks’ gestation
and Wortham et al,8 who reported a rate
of 0.98 per 1000 live births for all gesta-
tional ages down to a birthweight of
400 g. This low neonatal sepsis rate is not
completely unexpected because the bac-
terial cause for the majority of cho-
rioamnionitis cases are obligate anaerobic
organisms or genital mycoplasmas and
these microorganisms rarely if ever cause
early-onset neonatal sepsis.9-11
Furthermore, a recent study by
Romero et al11 showed that in laboring
ajog.org
5, But only 1 in hospitala
7
16, GBS culture obtained at 35 wk gestation
13
11, GBS culture obtained at 36 wk gestation
patients with a diagnosis of cho-
rioamnionitis (defined as a fever with
2
other clinical findings of a tender uterus,
foul-smelling amniotic fluid, fetal
tachycardia, maternal tachycardia, and/
or maternal leukocytosis of >15,000
cells/mm3), only 61% had microorgan-
isms by culture or polymerase chain re-
action analysis in amniotic fluid
obtained by amniocentesis. This means
that the cause for an intrapartum fever or
a diagnosis of chorioamnionitis in up to
40% of women in labor is not a micro-
bial infection. True chorioamnionitis is a
maternal response, whereas funisitis or
chorionic vasculitis is a fetal response.12
Chorioamnionitis or the maternal
response has been reproduced in an an-
imal model with administered lipopoly-
saccharide to promote inflammation.13
Therefore, a microbial infection is not a
requirement for producing a maternal
response of fever.14,15
Clinical and research implications
Of interest, our study data showed a
significantly lower rate of a cho-
rioamnionitis diagnosis given in the
private insurance population. A poten-
tial concern of this finding is that a
clinical diagnosis of chorioamnionitis
might not be made in some laboring
patients for fear that the newborn
might be separated from the mother
for evaluation and treatment. There-
fore, a management approach that
allows for a diagnosis of chorioamnio-
nitis to be made without fear of neonatal
repercussions would be important.
ajog.org
TABLE 2
Patients (n [ 412) ‡36 weeks’ gestation with maternal fever of ‡38 C given
clinical diagnosis of chorioamnionitis by managing physician compared
with those not given diagnosis of chorioamnionitis
Diagnosis of No diagnosis of
Category chorioamnionitis chorioamnionitis
No. 179 233
Caucasian 152 (85%) 201 (86%)
Maternal age, y 25.8  5.1 26.1  4.8
Private insurance patient 45 (25%) 86 (37%)
Gestational age, wk 39.02  0.9 39.17  1.0
Nulliparity 148 (83%) 172 (74%)
GBS positive 35 (20%) 52 (22%)
Labor management
Induction of labor 90 (50%) 121 (52%)
Epidural 165 (92%) 213 (91%)
Cesarean delivery 92 (51%) 67 (29%)
Treated with intrapartum antibiotics 162 (91%) 60 (26%)
Newborn information
NICU admissiona 181 (100%) 37 (16%)
Length of stay, d 4.2  1.1 3.1  0.7
Values are n (%) or mean  SD unless otherwise specified.
GBS, group B streptococcus; NICU, neonatal intensive care unit.
a
No. of neonates in 179 chorioamnionitis cases was 181 (2 sets of twins). No. of neonates in 233 cases with no diagnosis of
clinical chorioamnionitis was 236 (3 sets of twins).
Towers et al. Intrapartum fever and neonatal sepsis. Am J Obstet Gynecol 2017.
Patients given a clinical diagnosis of Romero et al17 demonstrated that the
chorioamnionitis in our study did have a accuracy of the clinical signs of uterine
higher rate of intrapartum antibiotic tenderness, malodorous amniotic fluid,
administration compared with those not maternal tachycardia of >100 beats per
given the diagnosis. Saccone and Ber- minute, fetal tachycardia >160 beats per
ghella,16 through meta-analysis, re- minute, and/or maternal leukocytosis of
ported that maternal antibiotic >15,000 cells/mm3 in identifying an
treatment for term or near-term pre- intraamniotic microbial infection was
mature rupture of membranes does only about 50%. Unfortunately, there
decrease the rate of endometritis in those currently is no prospective intrapartum
patients with a latency >12 hours, but diagnostic test that can either confirm or
antibiotics did not change the rate of rule out true infection, except possibly
neonatal sepsis. amniocentesis. However, performing
If a pregnant patient enters labor at amniocenteses on laboring patients who

36 weeks’ gestation afebrile and during develop a fever is not likely to become
the intrapartum process spikes a tem- common practice universally, especially
perature to
38 C sometime thereafter, when many of these patients may not
can any clinician be 100% certain “pro- have adequate pockets of fluid for testing
spectively” that this specific patient does following membrane rupture. There-
not have an intraamniotic infection, but fore, the diagnosis of chorioamnionitis is
rather has a fever related to some other primarily left to the clinical judgment of
source? It is clear that not all fevers in the attending health care providers based
women in labor are caused by microbial on maternal temperature along with
organisms.11,14,15 Further research by other possible clinical findings.4,7,11,18
JUNE 2017 American Journal of Obstetrics & Gynecology
OBSTETRICS Original Research
Numerous questions remain re-
garding the etiology of an elevated
maternal temperature during labor
including parity, epidural, temperature
curves, maximum temperatures, white
blood cell count, maternal tachycardia,
P value fetal tachycardia, fundal tenderness, and
foul-smelling discharge. These topics are
.81
being fully analyzed in a follow-up study
from the database correlated with
.55 placental pathology findings. Because
.015 many fevers are not related to microbial
.12 infection,11,14,15 many of the microbes
that cause chorioamnionitis do not
.043
cause neonatal sepsis,9-11 and the accu-
.58 racy of clinical signs seen in connection
with an intrapartum fever is only 50%,17
.82 to simplify the process for all health care
providers attending a woman in labor,
.92
we would recommend that all patients
<.0001 who spike an intrapartum fever
38 C,
<.0001 regardless of what the clinical impression
might be, be categorized as “a fever in
labor.” This information can then be
<.0001 forwarded to pediatrics for them to
<.0001 examine the newborn and determine
observation or workup with treatment
rather than universally testing and
treating these neonates. Our proposal
would correlate with the current CDC
guidelines that state “fever alone in labor
may be used as a sign of chorioamnio-
nitis” by erring on the side of safety.1
Furthermore, this recommendation
would also concur with the pediatric
commentary of Benitz et al19 that “well-
appearing late-preterm and term infants
should be managed closely with close
clinical observation, because of the low
sensitivity of risk factors in ascertain-
ment of early-onset sepsis in this group.”
Although a cost-effective analysis was
not performed, the need to treat from
our data is 1/417 neonates, which is
similar to Braun et al4 of 1/492 newborns
(6/2950 cases) and Wortham et al,8 who
estimated that a minimum of 60 up to a
maximum of 1400 newborns would
need to be evaluated and treated for
every infected asymptomatic neonate,
depending on the rate of chorioamnio-
nitis. Additionally, if universal newborn
evaluation and treatment requires
neonatal intensive care unit admission,
this would only add to the overall costs
for this rare event in newborns.
596.e4
Original Research OBSTETRICS
Strengths and limitations
The strength of this study is the pro-
spective nature and large number of
patients evaluated over 3.5 years. All 412
patients with a documented fever and
their 417 newborns were fully evaluated
for any readmissions that might have
occurred within 7 days of delivery related
to infection. The study is limited by the
fact that not all of the newborns deliv-
ered from afebrile labors were as
intensely followed postdischarge and a
readmission to another institution could
have occurred. However, this would only
increase the incidence of neonatal sepsis
in the nonfever control population.
Secondly, the lack of difference in early-
onset neonatal sepsis in the febrile
group compared with the afebrile group
could represent a type II error due to a
lack of numbers. If the proportions in
this study remained the same, we would
need 5 times more patients in each arm
to reach significance.
Conclusion
In conclusion, the incidence of intra-
partum fever is in the range of 7% and to
uniformly perform laboratory studies
with culture along with universal anti-
biotic treatment in well-appearing new-
borns delivered of these patients does
not seem clinically sound, especially
when the risk of early-onset neonatal
sepsis in this population is low. n NeoReviews 2015;16:e221-30.
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Author and article information
From the Department of Obstetrics and Gynecology,
University of Tennessee Medical Center, Knoxville, TN.
Received Dec. 13, 2016; revised Feb. 7, 2017;
accepted Feb. 9, 2017.
The authors report no conflict of interest.
Presented as the Best Obstetrical Award Poster no. 16
at the annual meeting of the Central Association of
Obstetricians and Gynecologists, Charleston, SC, Oct.
21-24, 2015.
Corresponding author: Craig V. Towers, MD.
ctowers@utmck.edu