Placenta 30 (2009) 613–618

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Placenta
journal homepage: www.elsevier.com/locate/placenta

The Frequency and Clinical Significance of Intra-Uterine Infection

and Inflammation in Patients with Placenta Previa and Preterm
Labor and Intact Membranes
C.-W. Park a, K.C. Moon b, J.S. Park a, J.K. Jun a, B.H. Yoon a, *
a
Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea
b
Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea
The intra-amniotic inflammatory response was stronger when inflammation was present in the chorionic plate (as well as choriodecidua),
than when it was restricted to the choriodecidua only, which was exposed to the cervical canal in placenta previa.

a r t i c l e i n f o a b s t r a c t

Article history: Objective: Histologic placental and/or intra-amniotic inflammation is frequently documented during
Accepted 14 April 2009
ascending intra-uterine infections in patients with preterm labor and intact membranes. Placenta previa
can be a clinical situation that shows the successive schema of histologic placental and intra-amniotic
Keywords: inflammation during the process of ascending intra-uterine infections. However, a paucity of information
Placenta previa
exists about the frequency and clinical significance of intra-uterine infections and inflammation in
Preterm labor
patients with placenta previa and preterm labor and intact membranes. The purpose of this study was to
Intra-amniotic inflammation
Histologic chorioamnionitis examine this issue.
Study design: Amniocentesis was performed on 42 patients with placenta previa and preterm labor and
intact membranes (gestational age < 37 weeks). Amniotic fluid (AF) was cultured for aerobic and
anaerobic bacteria and genital mycoplasmas, and AF white blood cell (WBC) count and matrix metal-
loproteinase-8 (MMP-8) concentrations were determined. The diagnosis of intra-amniotic inflammation
was made in patients with an elevated AF MMP-8 (23 ng/ml). Non-parametric statistics were used for
analysis.
Results: 1) Intra-amniotic inflammation was present in 16.7% (7/42), proven AF infection in 4.9% (2/41),
and histologic chorioamnionitis in 19.0% (8/42) of patients with placenta previa and preterm labor; 2)
Patients with intra-amniotic inflammation had significantly higher rates of a positive AF culture, histo-
logic chorioamnionitis, funisitis, and a shorter interval-to-delivery than those without intra-amniotic
inflammation (p < 0.05 for each); 3) Among patients with histologic chorioamnionitis, inflammation of
the choriodecidua, which was exposed to the cervical canal, existed in all cases (8/8), but inflammation of
the chorionic plate existed in 63% of patients (5/8); 4) Patients with inflammation of the chorionic plate
had significantly higher median AF MMP-8 concentrations and WBC counts, and higher rates of intra-
amniotic inflammation than those in whom inflammation was restricted to choriodecidua (p < 0.05 for
each).
Conclusions: Placental inflammation was present in 19.0% and intra-amniotic inflammation was present
in 16.7% of patients with placenta previa and preterm labor and intact membranes. The intra-amniotic
inflammatory response was stronger when inflammation was present in the chorionic plate and cho-
riodecidua, than when it was restricted to the choriodecidua only, which was exposed to the cervical
canal in placenta previa.
Ó 2009 Elsevier Ltd. All rights reserved.

1. Introduction

Placenta previa is a risk factor for bleeding in the second half of

pregnancy and preterm labor and/or delivery [1]. Substantial
* Corresponding author. Tel.: þ82 2 2072 2826; fax: þ82 2 765 3002. evidence indicates an association between intra-uterine infection
E-mail address: yoonbh@snu.ac.kr (B.H. Yoon). and/or inflammation and preterm labor and/or delivery [2–9].

0143-4004/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.placenta.2009.04.005
614 C.-W. Park et al. / Placenta 30 (2009) 613–618
Microorganisms ascending from the vagina can gain access to the
amniotic cavity via the choriodecidua/amnion through the cervical
canal, and eventually cause placental and intra-amniotic infection/
inflammation [5].
Placenta previa can be a clinical situation that demonstrates the
successive schema of placental and intra-amniotic inflammation
during the process of an ascending intra-uterine infection in
patients with preterm labor. Yet, a paucity of information exists
regarding the frequency and clinical significance of intra-amniotic
infection and/or inflammation and histologic chorioamnionitis in
patients with placenta previa and preterm labor. Moreover, cases
with placenta previa have been excluded from most studies
involving preterm births and intra-amniotic infection/inflamma-
tion due to the heterogeneous clinical characteristics compared to
those without placenta previa. To address this question, we con-
ducted a study designed to determine the frequency and clinical
significance of intra-amniotic infection/inflammation and placental
inflammation in patients with placenta previa and preterm labor
and intact membranes.
2. Materials and methods
2.1. Study design
The study population consisted of 42 consecutive patients who were admitted to
Seoul National University Hospital with the diagnosis of placenta previa and preterm
labor and intact membranes (<37 weeks of gestation) and singleton gestation, who
underwent amniocentesis between March 1993 and February 2008. At our institu-
tion, amniocentesis is routinely offered to all patients who are admitted with the
diagnosis of preterm labor for the assessment of microbiologic status of the amniotic
cavity and fetal lung maturity. Preterm labor was defined as the presence of regular
uterine contractions with a frequency of at least 2 every 10 min before 37 completed
weeks of gestation. Amniocentesis was performed after written informed consent
was obtained. After delivery, MMP-8 was measured in stored AF because previous
studies have indicated that this is a sensitive and specific index of intra-amniotic
inflammation and that it correlates well with the AF WBC count [10–13]. Proven AF
infection was defined as a positive AF culture. Intra-amniotic inflammation was
defined as an elevated AF MMP-8 concentration (>23 ng/ml), as previously reported
[14]. Placenta previa was defined as placenta previa totalis, placenta previa partialis,
or placenta previa marginalis. Low-lying placenta was not included in the definition
of placenta previa. The Institutional Review Board of Seoul National University
Hospital approved the collection and use of these samples and information for
research purposes. The Seoul National University has a Federal Wide Assurance with
the Office for Human Research Protections (OHRP) of the Department of Health and
Human Services of the United States.
2.2. Amniotic fluid
AF was cultured for aerobic and anaerobic bacteria and for genital mycoplasmas
(Ureaplasmas and Mycoplasma hominis) and analyzed for WBC count, according to
methods previously described [15,16]. The remaining fluid was centrifuged and
stored in polypropylene tubes at 70  C. MMP-8 concentrations in stored AF were
measured with a commercially available enzyme-linked immunosorbent assay
(Amersham Pharmacia Biotech, Inc., Little Chalfont, Bucks, UK). The sensitivity of the
test was <0.3 ng/ml. Both intra- and inter-assay coefficients of variation were <10%.
Details about this assay and its performance have been previously described [11].
2.3. Diagnosis of histologic chorioamnionitis, clinical chorioamnionitis,
and neonatal morbidity
Histologic chorioamnionitis was defined in the presence of acute inflammatory
changes on examination of a membrane roll and chorionic plate of the placenta;
inflammation of the choriodecidua or amnion was diagnosed in the presence of at
least 1 focus of >5 neutrophils in the choriodecidua or amnion; inflammation of the
chorionic plate was diagnosed in the presence of more than 1 focus of at least 10
neutrophilic collections or diffuse inflammation in subchorionic fibrin, or diffuse
and dense inflammation, neutrophilic infiltration into connective tissue of the
placental plate, or placental vasculitis; funisitis was diagnosed in the presence of
neutrophil infiltration into the umbilical vessel walls or Wharton’s jelly with the use
of criteria previously published [17]. The presence of acute inflammation was clas-
sified as grade 1 or 2 in each tissue (amnion, choriodecidua, chorionic plate and
umbilical cord) with the use of criteria previously published [17]. Clinical cho-
rioamnionitis was diagnosed when a temperature was elevated to 37.8  C and 2 of
the following criteria were present: uterine tenderness, malodorous vaginal
discharge, maternal leukocytosis (>15,000 cells/mm3), maternal tachycardia
(>100 beats/min), and fetal tachycardia (>160 beats/min). Neonatal morbidity was
diagnosed according to the definitions previously described in detail [18]. Congen-
ital neonatal sepsis was diagnosed in the presence of a positive blood culture result
within 72 h of delivery. The diagnosis of respiratory distress syndrome required the
presence of respiratory grunting and retracting, an increased oxygen requirement
(inspired oxygen fraction > 0.4), and diagnostic radiographic and laboratory findings
in the absence of evidence of other causes of respiratory disease. Early pneumonia
was diagnosed in the presence of definite clinical and radiologic findings, with or
without a positive culture result from tracheal aspirate or chest tube specimen
within 7 days of birth. Bronchopulmonary dysplasia was diagnosed according to the
following criteria proposed by Bancalari et al. [19]: (1) intermittent positive pressure
ventilation was required during the first week of life and for 3 days. (2) Clinical
signs of chronic respiratory disease developed, characterized by tachypnea, inter-
costal and subcostal retractions, and tales on auscultation, all persistent for >28
days. (3) Supplemental oxygen was required for >28 days to maintain
a PaO2 > 50 mm Hg. and (4) A chest radiograph showed persistent strands of
densities in both lungs alternating with areas of normal or increased lucency. In
some infants these areas became coalescent into larger structures resembling bullae.
Intraventricular hemorrhage was graded according to the system proposed by
McMenamin et al. [20]. Significant neonatal morbidity was defined as the presence
of any of the following conditions: respiratory distress syndrome, proven congenital
neonatal sepsis, early pneumonia, bronchopulmonary dysplasia, intraventricular
hemorrhage (grade  II), and necrotizing enterocolitis.
2.4. Statistical analysis
The Mann–Whitney U-test was used for comparison of continuous variables.
Comparisons of proportions were performed with Fisher’s exact test. The general-
ized Wilcoxon test for survival analysis was used to compare the amniocentesis-
to-delivery interval according to the presence or absence of intra-amniotic
inflammation. Statistical significance was defined as a p < 0.05.
3. Results
3.1. Intra-amniotic inflammation, proven AF infection, histologic
chorioamnionitis, and antepartum vaginal bleeding
Intra-amniotic inflammation was present in 16.7% (7/42), posi-
tive AF culture in 4.9% (2/41), histologic chorioamnionitis in 19.0%
(8/42), and antepartum vaginal bleeding in 90.5% (38/42) of patients
with placenta previa and preterm labor and intact membranes.
The only microorganism identified from the amniotic cavity was
Ureaplasma urealyticum.
3.2. Characteristics and outcomes of the study population
Table 1 compares the clinical characteristics, and pregnancy and
neonatal outcomes according to the presence or absence of intra-
amniotic inflammation. There were no significant differences in the
median gestational age at amniocentesis, parity, and maternal age
between patients with and without intra-amniotic inflammation
(p > 0.1 for each). However, patients with an intra-amniotic
inflammation had significantly higher rates of a positive AF culture,
histologic chorioamnionitis, and funisitis than those without an
intra-amniotic inflammation (p < 0.05 for each; Table 1).
3.3. Characteristics of cases with histologic chorioamnionitis
Table 2 describes the characteristics of 8 cases with histologic
chorioamnionitis among patients with placenta previa and preterm
labor and intact membranes. Inflammation of choriodecidua which
was exposed to the cervical canal was found in all cases (8/8), but
inflammation of the chorionic plate was found in 63% of patients (5/8)
with histologic chorioamnionitis. Intra-amniotic inflammation was
absent in all 3 patients in whom inflammation was restricted to the
choriodecidua (case No. 1–3). However, intra-amniotic inflammation
was present in all the other 5 patients in whom inflammation was
extended to the chorionic plate (case No. 4–8). Moreover, all 3
patients with amnionitis (case No. 6–8), which represents advanced
maternal inflammation [21], had severe intra-amniotic inflammation
 C.-W. Park et al. / Placenta 30 (2009) 613–618 615

Table 1
Clinical characteristics, and pregnancy and neonatal outcomes of the study population according to the presence or absence of intra-amniotic inflammation (IAI) among the
cases of placenta previa with preterm labor and intact membranes.

Absence of IAI (n ¼ 35), 83.3% (35/42) Presence of IAI (n ¼ 7), 16.7% (7/42) P-value
Mean maternal age, y (SD) 31.7  4.1 34.3  5.8 NS
Parity  1 57.1% (20/35) 85.7% (6/7) NS
Median gestational age at amniocentesis, wk (range) 33.4 (19.4–36.7) 32.9 (24.4–34.7) NS
Mean birth weight, g (SD) 2425  612 1965  639 NS
Median gestational age at delivery, wk (range) 35.0 (28.7–38.0) 32.9 (24.7–34.7) <.01
Type of placenta previa NS
Placenta previa totalis 89% (31/35) 71% (5/7)
Placenta previa partialis 3% (1/35) 14% (1/7)
Placenta previa marginalis 9% (3/35) 14% (1/7)
Previous cesarean section 23% (8/35) 14% (1/7) NS
Previous preterm births 9% (3/35) 0% (0/7) NS
The presence of accreta 6% (2/35) 0% (0/7) NS
Histologic chorioamnionitis 8.6% (3/35) 71.4% (5/7) <.005
Chorio-deciduitis 8.6% (3/35) 71.4% (5/7) <.005
Inflammation of chorionic plate 0% (0/35) 71.4% (5/7) <.001
Funisitis 0% (0/35) 57.1% (4/7) <.001
Amnionitis 0% (0/35) 42.9% (3/7) <.005
Clinical chorioamnionitis 5.7% (2/35) 28.6% (2/7) NS
Positive amniotic fluid culturea 0% (0/34) 28.6% (2/7) <.05
Episodes of antepartum bleeding 89% (31/35) 100% (7/7) NS
1-min Apgar score < 7 31.4% (11/35) 57.1% (4/7) NS
5-min Apgar score < 7 11.4% (4/35) 14.3% (1/7) NS
Significant neonatal morbidityb 17.6% (6/34) 33.4% (2/6) NS
a
Forty-two patients who underwent amniocentesis and had the results of AF MMP-8 concentration were included in this analysis. One patient did not have an AF culture
because of the limited amount of amniotic fluid remaining.
b
Two neonates were excluded from the analysis because they died shortly after delivery as a result of prematurity.

and significant neonatal morbidity. There was a strong correlation
between the total grade of histologic chorioamnionitis and AF MMP-8
concentration (r ¼ 0.976; p < .001; Spearman correlation test).
3.4. Amniocentesis-to-delivery interval
Fig. 1 compares the amniocentesis-to-delivery interval accord-
ing to the presence or absence of intra-amniotic inflammation
among the study population. Patients with intra-amniotic
inflammation had a significantly shorter median amniocentesis-to-
delivery interval than did those without intra-amniotic
inflammation (p < .05).
compares the AF MMP-8 concentrations and AF WBC counts
according to the presence or absence of inflammation in the cho-
riodecidua and chorionic plate. There were no significant differ-
ences in the median AF MMP-8 concentrations and the AF WBC
counts between patients without histologic chorioamnionitis and
those in whom inflammation was restricted to the choriodecidua
(p > 0.1). However, the intra-amniotic inflammatory response
(indicated as AF MMP-8 concentration and AF WBC count) was
stronger when inflammation was present in the chorionic plate (as
well as choriodecidua), than when it was restricted to the chorio-
decidua only, which was exposed to the cervical canal in placenta
previa (p < 0.05 for each; Fig. 3).

3.5. AF MMP-8 concentrations, AF WBC counts, and placental 4. Discussion

inflammation
Fig. 2 shows AF MMP-8 concentrations and AF WBC counts
according to the presence or absence of histologic chorioamnioni-
tis. Patients with histologic chorioamnionitis had significantly
higher median AF MMP-8 concentrations and WBC counts than
those without histologic chorioamnionitis (p < .05 for each). Fig. 3
4.1. Principal findings of this study
1) Intra-amniotic inflammation was present in 17%, positive AF
culture in 5%, and histologic chorioamnionitis in 19% of patients
with placenta previa and preterm labor and intact membranes; 2)
Patients with an intra-amniotic inflammation had significantly

Table 2
Characteristics of 8 cases with histologic chorioamnionitis among patients with placenta previa and preterm labor with intact membranes.

Case Gestational Significant AF study Amniocentesis- The presence and grade of placental inflammation Total grade of
No. age (week) neonatal to-delivery according to of anatomic section histologic
morbidity interval (h) chorioamnionitis
Amnio- Delivery Culture WBC MMP-8 Choriodecidua Chorionic Umbilical Amnion
centesis (cells/mm3) (ng/ml) plate cord
1 32.9 34.3 () () 0 0.3 247.8 (þ), grade 1 () () () 1
2 33.4 34.6 () () 0 5.3 248.8 (þ), grade 1 () () () 1
3 27.0 36.0 () () 7 17.2 1491.7 (þ), grade 1 () () () 1
4 32.0 32.1 () () 180 207.7 26.8 (þ), grade 1 (þ), grade 1 () () 2
5 33.4 33.6 NA () 360 251.6 1.3 (þ), grade 1 (þ), grade 1 (þ), grade 1 () 3
6 34.0 34.0 (þ) (þ) >1000 565.9 1.8 (þ), grade 1 (þ), grade 1 (þ), grade 1 (þ), grade 1 4
7 24.3 24.7 (þ) (þ) 426 743.9 37.0 (þ), grade 1 (þ), grade 1 (þ), grade 2 (þ), grade 1 5
8 30.1 30.3 (þ) () >1000 3116.7 1.1 (þ), grade 2 (þ), grade 2 (þ), grade 2 (þ), grade 2 8

NA, not available; AF, amniotic fluid; WBC, white blood cell.
All cases, except case No. 7, were delivered by cesarean section. The vaginal delivery was performed in case No. 2 due to very early preterm gestation in 1995, and the neonate
expired in the delivery room.
616 C.-W. Park et al. / Placenta 30 (2009) 613–618

intra-amniotic inflammation during the process of ascending intra-

1.0 Intra-amniotic inflammation (-)
P <.05
Intra-amniotic inflammation (+)
Proportion of undelivered patients
uterine infection. Indeed, all cases with histologic chorioamnionitis
had inflammation in the choriodecidua, which was exposed to the
cervical canal in placenta previa in the current study. Moreover, as

0.8 placental inflammation progressed upward from the choriodecidua

to the chorionic plate, and the amnion and/or umbilical cord, the
intra-amniotic inflammatory response gradually increased (Table 2
and Fig. 3).
0.6

4.3. Inflammation in the chorionic plate as the determinant factor

of intra-amniotic inflammation in cases with placenta previa and
0.4 preterm labor and intact membranes

In placenta previa, the chorionic plate occupies an intermediate

0.2
0.0
0 500 1000 1500
Amniocentesis-to-delivery interval (hours)
Fig. 1. Survival analysis of amniocentesis-to-delivery interval, according to the pres-
ence or absence of intra-amniotic inflammation among patients with placenta previa
and preterm labor (intra-amniotic inflammation (þ): median, 1.8 h [range, 0.5–3.1 h];
intra-amniotic inflammation (): median, 64.3 h [range, 0.01–430.8 h]; P < .05).
higher rates of a positive AF culture, histologic chorioamnionitis,
and funisitis, and a shorter interval-to-delivery than those without
an intra-amniotic inflammation (p < 0.05 for each); and 3) The
intra-amniotic inflammatory response was stronger when inflam-
mation was present in the chorionic plate than when it was
restricted to the choriodecidua, which was exposed to the cervical
canal in placenta previa.
4.2. Placenta previa: the clinical situation showing the successive
schema of ascending intra-uterine infection
The observation that histologic chorioamnionitis is more
common in the first-born twin than in the second twin in patients
with twin gestations because the membranes of the first twin are
generally apposed to the cervix is evidence of an ascending intra-
uterine infection in the context of preterm labor [5]. The findings in
the current study indicate that placenta previa may be another
clinical situation showing the successive schema of placental and
position between the amnion that lines the amniotic cavity and the
choriodecidua that is directly exposed to the cervical canal. While
a localized inflammation confined to the choriodecidua may be
insufficient to provoke intra-amniotic inflammation, the involve-
ment of the amnion in the inflammatory process of histologic
2000 2500 3000 3500 chorioamnionitis has been known to be associated with a more
advanced fetal and intra-amniotic inflammatory response than
chorionitis alone [21]. Therefore, the inflammation in the inter-
mediate zone such as the chorionic plate in placenta previa may be
the determinant factor of intra-amniotic inflammation. Indeed, our
data indicate that cases with inflammation restricted to the cho-
riodecidua did not have an intra-amniotic inflammation, but those
with inflammation extended to the chorionic plate provoked an
intense intra-amniotic inflammatory response, such as an AF MMP-
8 concentration >200 ng/ml.
4.4. Why is the frequency of inflammation lower in cases with
placenta previa than in those without placenta previa among
patients with preterm labor and intact membranes?
Our previous study demonstrated that proven AF infection was
present in 10%, intra-amniotic inflammation in 32%, and histologic
chorioamnionitis in 53% of patients with preterm labor [2].
However, proven AF infection was identified in only 5%, intra-
amniotic inflammation in 17%, and histologic chorioamnionitis in
19% of patients with placenta previa and preterm labor and intact
membranes in the current study. Several explanations for the low
frequency of infection/inflammation in patients with placenta
previa and preterm labor could be proposed: 1) A high rate of non-
infectious cause of preterm labor, such as vaginal bleeding in
patients with placenta previa, could lead to the low rate of intra-

a 3116.7
b
AF MMP8 concentration

3000
743.9
P <.005 565.9 P <.05
AF WBC (cells/mm3)

500
300 1200
(ng/ml)

250 1000
200 800
150 600
100 400
50 200
0 0

Histologic Histologic Histologic Histologic

chorioamnionitis (-) chorioamnionitis (+) chorioamnionitis (-) chorioamnionitis (+)

Fig. 2. AF MMP-8 concentrations (2a) and AF WBC counts (2b) according to the presence or absence of histologic chorioamnionitis. Patients with histologic chorioamnionitis had
significantly higher median AF MMP-8 concentrations and AF WBC counts than those without histologic chorioamnionitis (AF MMP-8: median, 229.7 ng/ml [range, 0.3–3116.7 ng/ml]
vs. median, 0.9 ng/ml [range, 0.3–79.1 ng/ml]; AF WBC: median, 270 cells/mm3 [range, 0–1000 cells/mm3] vs. median, 1 cell/mm3 [range, 0–650 cells/mm3]; each P-value is shown on
the graphs).
 C.-W. Park et al. / Placenta 30 (2009) 613–618 617

a P <.001
b P <.001
NS P <.05 NS P <.05
AF MMP8 concentration (ng/ml)
3000 3116.7
743.9
565.9
500

AF WBC (cells/mm3)
300 1200

250 1000

200 800

150 600
426
100 400

50 200

0 0

Choriodecidua (-) Choriodecidua (+) Choriodecidua (+) Choriodecidua (-) Choriodecidua (+) Choriodecidua (+)
Inflammatory site of Inflammatory site of
Chorionic plate (-) Chorionic plate (-) Chorionic plate (+) placental compartment Chorionic plate (-) Chorionic plate (-) Chorionic plate (+)
placental compartment

Fig. 3. AF MMP-8 concentrations (3a) and AF WBC counts (3b) according to the presence or absence of inflammation in choriodecidua and chorionic plate (AF MMP-8: chorio-
decidua () and chorionic plate (), median, 0.9 ng/ml [range, 0.3–79.1 ng/ml] vs. choriodecidua (þ) and chorionic plate (), median, 5.3 ng/ml [range, 0.3–17.2 ng/ml] vs. cho-
riodecidua (þ) and chorionic plate (þ), median, 565.9 ng/ml [range, 207.7–3116.7 ng/ml]; AF WBC: choriodecidua () and chorionic plate (), median, 1 cell/mm3 [range,
0–650 cells/mm3] vs. choriodecidua (þ) and chorionic plate (), median, 0 cell/mm3 [range, 0–7 cells/mm3] vs. choriodecidua (þ) and chorionic plate (þ), median, 426 cells/mm3
[range, 180–1000 cells/mm3]; each P-value is shown on the graphs).

amniotic infection and/or inflammation in the current study
population. Indeed, several investigators have reported that
decidual hemorrhage and/or vaginal bleeding are risk factors for
the development of preterm labor [22,23]. Vaginal bleeding was
present in most cases (90.5% [38/42]) of placenta previa with
preterm labor and intact membranes in the current study; 2) It is
likely that some patients with an early stage of preterm labor
before cervical change could have been included in the current
study population. This may be due to the difficulty to determine
the status of cervical dilatation by naked eye because most
patients (90.5%) had vaginal bleeding, in addition to the impossi-
bility of cervical examination for the risk of torrential bleeding.
Several investigators demonstrated that the greater the degree of
cervical dilatation, the greater the risk of AF infection [24–26]; 3)
The placenta is located close to the cervical canal in placenta
previa. Therefore, although there is not a definite localized
inflammatory reaction in the choriodecidua during the process of
ascending intra-uterine infection, excessive growth of organisms
in a cervical canal may provoke a cytokine response in the placenta
adjacent to the cervix. Ultimately, this cytokine response in the
placenta could result in preterm labor; 4) The gestational age at
amniocentesis in the current study population is higher than that
in patients with preterm labor and intact membranes of our
previous study [2]. It was reported that the higher the gestational
age, the lower the rate of intra-amniotic infection and/or inflam-
mation in patients with preterm labor [2].
4.5. Strengths and weaknesses of the study
This is the first study which examined the relationships among
preterm labor and intact membranes, placenta previa, and intra-
amniotic and placental inflammatory response. It included several
markers of infection and/or inflammation including AF culture, AF
MMP-8 concentration, and AF WBC count, as well as placental
pathology. Therefore, this study clearly examined the inflammatory
response in the amniotic cavity and placental compartments
among each study group (Fig. 3). The weak point of this study were:
1) it did not examine the fetal inflammatory response because it
was not possible to obtain umbilical cord blood in many cases
because of placental damage, which occurred during the process of
cesarean section; 2) Current study population includes patients
with preterm labor and intact membranes among cases with
placenta previa, and so we could not perform a cervical examina-
tion because even the gentlest examination of this sort can cause
torrential hemorrhage. Therefore, we could not incorporate cervical
characteristics (i.e., cervical dilatation greater than 1 cm, and
cervical effacement of 80 percent or greater) in the definition of
preterm labor in the current study. Moreover, vaginal bleeding was
present in most cases (90.5% [38/42]), and therefore it was difficult
even to define cervical dilatation by naked eye.
4.6. Conclusion
Intra-amniotic inflammation was present in 17% of patients with
placenta previa and preterm labor with intact membranes and was
associated with shorter interval-to-delivery, proven AF infection,
and histologic chorioamnionitis. The intra-amniotic inflammatory
response was stronger when inflammation was present in the
chorionic plate and choriodecidua, than when it was restricted to
the choriodecidua only, which was exposed to the cervical canal in
placenta previa.
Acknowledgements
This study was supported by General Research Grants (GRG),
and the Korea Science and Engineering Foundation of the Republic
of Korea (R01-2006-000-10607-0).
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