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Early preterm delivery due to placenta previa is an independent risk factor for a subsequent spontaneous preterm birth

Authors:
  • Soroka University Medical Center

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Background To determine whether patients with placenta previa who delivered preterm have an increased risk for recurrent spontaneous preterm birth. Methods This retrospective population based cohort study included patients who delivered after a primary cesarean section (n = 9983). The rate of placenta previa, its recurrence, and the risk for recurrent preterm birth were determined. Results Patients who had a placenta previa at the primary CS pregnancy had an increased risk for its recurrence [crude OR of 2.65 (95% CI 1.3-5.5)]. The rate of preterm birth in patients with placenta previa in the primary CS pregnancy was 55.9%; and these patients had a higher rate of recurrent preterm delivery than the rest of the study population (p < .001). Among patients with placenta previa in the primary CS pregnancy, those who delivered preterm had a higher rate of recurrent spontaneous preterm birth regardless of the location of their placenta in the subsequent delivery [OR 3.09 (95% CI 2.1-4.6)]. In comparison to all patients with who had a primary cesarean section, patients who had placenta previa and delivered preterm had an independent increased risk for recurrent preterm birth [OR of 3.6 (95% CI 1.5-8.5)]. Conclusions Women with placenta previa, who deliver preterm, especially before 34 weeks of gestation, are at increased risk for recurrent spontaneous preterm birth regardless to the site of placental implantation in the subsequent pregnancy. Thus, strict follow up by high risk pregnancies specialist is recommended.
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R E S E A R C H A R T I C L E Open Access
Early preterm delivery due to placenta previa is
an independent risk factor for a subsequent
spontaneous preterm birth
Offer Erez
1*
, Lena Novack
2
, Vered Klaitman
1
, Idit Erez-Weiss
3
, Ruthy Beer-Weisel
1
, Doron Dukler
1
and Moshe Mazor
1
Abstract
Background: To determine whether patients with placenta previa who delivered preterm have an increased risk for
recurrent spontaneous preterm birth.
Methods: This retrospective population based cohort study included patients who delivered after a primary
cesarean section (n = 9983). The rate of placenta previa, its recurrence, and the risk for recurrent preterm birth were
determined.
Results: Patients who had a placenta previa at the primary CS pregnancy had an increased risk for its recurrence
[crude OR of 2.65 (95% CI 1.3-5.5)]. The rate of preterm birth in patients with placenta previa in the primary CS
pregnancy was 55.9%; and these patients had a higher rate of recurrent preterm delivery than the rest of the study
population (p < .001). Among patients with placenta previa in the primary CS pregnancy, those who delivered
preterm had a higher rate of recurrent spontaneous preterm birth regardless of the location of their placenta in the
subsequent delivery [OR 3.09 (95% CI 2.1-4.6)]. In comparison to all patients with who had a primary cesarean
section, patients who had placenta previa and delivered preterm had an independent increased risk for recurrent
preterm birth [OR of 3.6 (95% CI 1.5-8.5)].
Conclusions: Women with placenta previa, who deliver preterm, especially before 34 weeks of gestation, are at
increased risk for recurrent spontaneous preterm birth regardless to the site of placental implantation in the
subsequent pregnancy. Thus, strict follow up by high risk pregnancies specialist is recommended.
Keywords: Preterm birth, Placenta, Recurrent preterm delivery, Vaginal bleeding, Short cervix, Placenta previa
Background
Placenta previa is a risk factor for preterm birth, and
contributes to about 5% of all preterm deliveries. [1] The
prevalence of placenta previa is 0.3-0.5% of pregnancies
[2-10], and the risk for this complication increases
according to the number of prior cesarean deliveries
[11-14]. Placenta previa is associated with an increased
maternal morbidity including the need for blood and
blood products transfusion, urgent cesarean section, and
cesarean hysterectomy. Moreover, a higher rate of peri-
natal mortality and morbidity, especially respiratory
distress syndrome and anemia are associated with this
abnormal placentation [15,16].
Most of the patients with placenta previa are delivered
preterm [4,17], and these deliveries are regarded as indi-
cated preterm births due to excessive maternal
hemorrhage. Nevertheless, recent evidence suggests that
other mechanisms aside bleeding may lead to preterm
birth in women with placenta previa [18,19]. Patients
with placenta previa who delivered preterm had a higher
rate of intra-amniotic infection/inflammation than those
who delivered at term [18], suggesting that similarly to
spontaneous preterm birth, intra-amniotic infection or
inflammation may contribute to the process of preterm
parturition in patients with placenta previa. Moreover,
women with this complication who had a short cervical
length have an increased risk to deliver preterm [20-22].
* Correspondence: erezof@bgu.ac.il
1
Department of Obstetrics and Gynecology, Soroka University Medical
Center, School of Medicine, Faculty of Health Sciences, Ben Gurion University
of the Negev, P O Box 151, Beer Sheva 84101, Israel
Full list of author information is available at the end of the article
© 2012 Erez et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Erez et al. BMC Pregnancy and Childbirth 2012, 12:82
http://www.biomedcentral.com/1471-2393/12/82
Thus, the mechanisms leading to spontaneous preterm
parturition may play a similar role in patients with pla-
centa previa who deliver prematurely.
Placenta previa is a recurrent pregnancy complication;
reports suggest a recurrence rate of 2.3-3.2% [23,24].
The underlying mechanisms leading to this are not com-
pletely understood. Yet, it is not clear from the literature
whether patients with placenta previa who deliver pre-
term are at increased risk for recurrent preterm birth.
The objective of this study was to determine whether
women with placenta previa who delivered preterm are
at increased risk for recurrent preterm birth in the sub-
sequent pregnancy.
Methods
Study population, selection of patients
This is a retrospective population based cohort study in-
cluding all women who delivered subsequent to a pri-
mary cesarean section (CS) during the study period
(19882010) at the Soroka University Medical Center,
a regional tertiary medical center where all the births
take place, and met the inclusion criteria. This cohort
(n = 9983) was divided into two groups according to the
site of placentation at the primary CS: Patients with pla-
centa previa comprised the study group (n = 297), and
those with normal placental insertion served as the com-
parison group (n = 9686).
The patients were identified in a computerized data-
base including all data concerning demographic charac-
teristics, medical and obstetric history, pregnancy
outcomes as well as, maternal and neonatal morbidity
and mortality of all the deliveries at our medical center.
Women who lacked minimal prenatal care (less than
three visits in prenatal clinic), those with multiple gesta-
tions, and parturient carrying a fetus with known chromo-
somal or anatomical anomalies were excluded from the
study. The Institutional Review Board of Soroka University
Medical Center approved the study.
Outcome variables and clinical definitions
Parity groups were defined in the following order: prim-
ipara, multipara (25 deliveries) and grand multipara (6
or more deliveries). Gestational age was determined by
date of last menstrual period when reliable and sono-
graphic confirmation carried out by the first 20 weeks of
gestation and/or first trimester sonographic measure-
ment of crown- rump length. Hypertensive disorders of
pregnancy were defined according the American College
of Obstetrics and Gynecology (ACOG) criteria [25]. Pla-
centa previa was defined as a placenta that partially or
fully covers the internal cervical os, or when the lower
placental edge lies within 20 mm from it [3]. The loca-
tion of the placenta was diagnosed prenatally by ultra-
sound examination and verified during the cesarean
delivery. Preterm delivery was defined as delivery before
complete 37 weeks of gestation, early preterm birth was
defined as delivery <34 weeks of gestation, and late pre-
term birth was defined as delivery between 34 to 36.9
weeks of gestation. Small for gestational age (SGA) was
defined as birthweight below the 10
th
percentile [26].
Statistical analysis
The rate of placenta previa, its recurrence, and the risk
for preterm delivery at the subsequent delivery following
a placenta previa at the primary CS pregnancy, were
determined as primary outcomes.
Maternal demographic characteristics, peripartum com-
plications and perinatal outcome were compared between
women with and without placenta previa. Parametric and
non-parametric statistics were used for continues variables
according to their distribution. Chi-square and Fisher exact
test were used to compare categorical variables. Variables
found to be significantly associated with placenta previa
and preterm birth in the univariate analysis were included
in a multiple logistic regression. A two tailed P value of
0.05 was considered significant. Analysis was done by SPSS
package (Chicago, IL, USA) and SAS software version 9.2
(Cary, NC, USA).
Results
The rate of placenta previa in the primary CS pregnancy
was 3.0% (297/9983), and 1.08% (108/9983) in the subse-
quent pregnancy. The recurrence rate of placenta previa
among patients who had this complication at the pri-
mary CS pregnancy was higher than among those with-
out it [placenta previa- 2.69% (8/297) vs. normal
placentation- 1.03% (100/9686) crude odds ratio (OR) of
2.65 (95% CI 1.2-5.7)].
Women with placenta previa had a higher mean ma-
ternal age and grand multiparity rate than those with
normally implanted placentae in both pregnancies. The
rate of prior preterm birth did not differ between
patients with placenta previa and those with normal pla-
centation in neither of the pregnancies (Table 1).
Therateofpretermdeliveryamongpatientswithpla-
centa previa in the primary CS pregnancy was 55.9%
(166/297) and 51.9% (56/108) among those who had pla-
centa previa in the subsequent birth. In both pregnancies
studied, the rate of severe prematurity (<32 weeks of ges-
tation) was higher among women with placenta previa
than in those with normal placentation [primary CS -
normal placentation 4.1% (395/9686) vs. placenta previa
16.9% (50/297), OR 4.13 (95%CI 3.15-5.41), p < .001; sub-
sequent delivery- normal placentation 2% (195/9875) vs.
placenta previa 9.3% (10/108), OR 5.07 (95%CI 2.45-
10.18), p < 0.001] (Figure 1).
Women with placenta previa who delivered preterm
at the primary CS pregnancy had a higher rate of
Erez et al. BMC Pregnancy and Childbirth 2012, 12:82 Page 2 of 6
http://www.biomedcentral.com/1471-2393/12/82
recurrent preterm birth in the following delivery than
the rest of the study population [preterm placenta pre-
via: 18.7% (31/166) vs. study cohort: 9.9% (972/9817), p
< .001, OR = 2.09 (95%CI 1.41-3.11)]. Moreover, among
patients with a placenta previa in the primary CS preg-
nancy, those who delivered preterm had an OR = 3.09
(95% CI 2.1-4.6) for recurrent preterm birth in the sub-
sequent pregnancy in comparison to those who deliv-
ered at term (Figure 2). Women with placenta previa
who delivered before 34 weeks of gestation in the pri-
mary CS pregnancy had a higher risk to deliver preterm
in comparison to those with placenta previa who
Table 1 Demographics and clinical characteristics of the study groups in both pregnancies
Measure Index Pregnancy 2
nd
pregnancy
Normal placentation Placenta Previa P-value Normal placentation Placenta Previa P-value
N = 9686 N = 297 N = 9875 N = 108
Maternal Age (years) 27.18 ± 5.20 29.02 ± 5.04 <.001 30.03 ± 5.59 33.06 ± 4.92 <.001
Gravidity
1 42.2 (4086) 13.1 (39) <.001 0.0 (0) 0.0 (0) <.001
2-5 42.3 (4096) 60.6 (180) 77.0 (7603) 60.2 (65)
6+ 15.5 (1504) 26.3 (78) 22.9 (2263) 39.8 (43)
Parity
1 53.5 (4995) 20.4 (58) <.001 0.0 (0) 0.0 (0) <.001
2-5 38.0 (3552) 65.8 (187) 87.1 (8189) 79.2 (80)
6+ 8.5 (791) 13.7 (39) 12.4 (1169) 20.8 (21)
Prior preterm birth 17.0 (602/3541) 14.1 (26/185) .297 21.7 (2144/9875) 22.1 (24/108) .898
Infertility treatments 5.5 (531) 8.1 (24) .07 7.2 (709) 12.0 (13) .06
Mild preeclampsia 5.4 (520) 1.0 (3) <.001 3.5 (345) 2.8 (3) 1.0
Severe preeclampsia 5.3 (512) 1.7 (5) .003 1.7 (164) 0.9 (1) 1.0
Chronic Hypertension 2.5 (242) 1.3 (4) .25 3.0 (295) 2.8 (3) 1.0
GDM class A 6.4 (619) 7.7(23) .346 6.6 (651) 5.6 (6) .85
GDM class B-R 2.1 (201) 2.7 (8) .41 2.7 (265) 1.9 (2) 1.0
Hydramnios 6.5 (632) 5.4 (16) .55 5.5 (540) 4.6 (5) 1.0
Oligohydramnios 6.5 (627) 2.7 (8) .005 2.7 (265) 1.9 (2) 1.0
Preterm Delivery 16.6 (1611) 55.9 (166) <.001 9.6 (947) 51.9 (56) <.001
Cesarean section 100.0 (9686) 100 (297) 52.2 (5151) 96.3 (104) <.001
Data presented as percent (number) or mean ± standard deviation.
GDM- gestational diabetes.
Figure 1 Distribution of gestational age at delivery among the study groups in each pregnancy.
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delivered at term [early preterm delivery 25% (20/80)
vs. term delivery 5.3% (7/131), p < .001, RR 4.7, 95% CI
2.07-10.57). However, women with placenta previa who
had a late preterm birth, had an increased but not sta-
tistically significant rate of recurrent preterm birth in
comparison to those who delivered at term (late pre-
term birth 12.8% (11/86), p = .09).
In a multiple logistic regression model aimed to study
the recurrence of preterm delivery in patients with pla-
centa previa, regardless to site of placentation, preterm
birth in the second pregnancy was introduced as an out-
come. Previous preterm delivery due to preeclampsia,
intrauterine growth restriction (IUGR), placenta previa,
preterm prelabor rupture of membranes (PROM) and
spontaneous preterm parturition were included as cov-
ariates. Placenta previa at the primary CS pregnancy on
its own was not a risk factor for preterm birth at the
subsequent pregnancy. However, Patients with placenta
previa who delivered preterm in the primary CS preg-
nancy had an independent increased risk for spontan-
eous preterm birth in the subsequent delivery unrelated
to the presence of placenta previa in that pregnancy (OR
3.60, 95% CI 1.52-8.51) (Table 2).
Discussion
Principal findings of this study: Placenta previa is a re-
current pathology. Preterm birth in patients with pla-
centa previa is an independent risk factor for a recurrent
spontaneous preterm delivery in the subsequent preg-
nancy regardless to the site of placental implantation.
Placenta previa is a risk factor for preterm birth
[15,17]. Indeed, about 60% of the patients with placenta
previa in our study delivered preterm, mainly due to va-
ginal bleeding. It has been proposed that in cases of
placenta previa a certain degree of spontaneous placental
separation is an inevitable consequence of the formation
of the lower uterine segment and cervical dilatation,
leading to severe hemorrhage [27] and indicated preterm
birth. Moreover, there is evidence to support the delivery
of women with placenta previa between 36 to 37 weeks,
this practice is based upon the findings of Ananth et al.
[16], who demonstrated that women with placenta pre-
via have an increased perinatal mortality after 37 weeks
of gestation. Collectively, the combination of severe vagi-
nal bleeding that endangers the mother and the
increased unexplained stillbirth in these patients after 37
weeks contributes to the high proportion of preterm de-
liveries reported in patients with placenta previa. Never-
theless, it is not clear from the current literature
whether the increased risk for preterm birth is limited to
the pregnancy affected by placenta previa or does it
affect the subsequent ones as well.
In light of our findings and those of others [24], we
raise the question of whether preterm delivery due to
Figure 2 Recurrence of preterm delivery among patients with placenta previa who delivered preterm or at term in the primary CS
pregnancy.
Table 2 Risk factors at the index pregnancy for recurrent
preterm birth at the subsequent delivery
Factor Odds Ratio ( 95% confidence interval)
Spontaneous preterm birth 4.38 (3.71-5.17)
Preterm placenta previa 3.60 (1.52-8.51)
Preterm severe preeclampsia 2.82 (1.66-4.78)
Preterm IUGR 1.48 (1.003-2.18)
Severe preeclampsia 1.56 (1.01-2.53)
IUGR 1.52 (1.18-1.96)
Placenta previa 0.71 (.33-1.54)
Maternal age 1.03 (1.01-1.04)
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placenta previa is really an indicated preterm birth.
Could it be that the premature bleeding in patients with
placenta previa is the clinical presentation of a spontan-
eous preterm parturition? The answer to this question
may be deduced from epidemiological and clinical stud-
ies regarding the association of placenta previa and the
preterm parturition syndrome.
Shortening of the uterine cervix during gestation is a
risk factor for preterm birth in patients with normal pla-
centation [28,29], recent studies suggest that this is the
same in patients with placenta previa [20-22]. Indeed
among women with placenta previa, those who had a
cervical length <30 mm at the third trimester had a
higher rate of preterm delivery and a higher proportion
of them required delivery due to hemorrhage in com-
parison to those with longer cervical length [21]. In
addition, Ghi et al. [20] reported that patients with pla-
centa previa who had emergency cesarean section due to
bleeding at < 34 weeks of gestation had a significantly
shorter cervical length than those who had elective
cesarean delivery later during gestation. The authors
concluded that a short cervix in patients with placenta
previa may herald premature onset of labor and possible
detachment of the placenta from its low insertion [20].
Vaginal bleeding can be the only manifestation of
intra-amniotic infection and/or inflammation [30]. In-
deed, among patients with placenta previa and vaginal
bleeding the rate of intra amniotic infection was 5.7%
and intra-amniotic inflammation was detected in 17.9%
of these patients [19]. Moreover, among patients with
placenta previa, those who had intra-amniotic infection
or inflammation had a higher rate of delivery within 48
hours from admission and a lower mean gestational age
at delivery than those without it [19]. In a different
study, women with placenta previa who were admitted
with an episode of preterm labor with intact membranes
had a rate of 4.9% of intra-amniotic infection and 16.7%
of intra-amniotic inflammation [18]. In addition, women
with placenta previa who present with preterm labor
and have intra-amniotic inflammation had a higher risk
of intra-amniotic infection and a shorter admission to
delivery interval. Thus, similarly to women with normal
placentation, infection and or inflammation may be part
of the mechanisms that prematurely activate the com-
mon pathway of parturition in patients with placenta
previa, leading to preterm labor that is associated in
some of the cases with vaginal bleeding and eventually
progress to preterm birth.
Our finding that women with placenta previa who
delivered preterm are at increased risk for spontaneous
preterm birth in the subsequent delivery regardless to
the site of placental implantation is novel. Preterm deliv-
ery is a recurrent disease; both spontaneous and indi-
cated preterm births are associated with an increased
risk for recurrence in subsequent pregnancies [31,32].
Moreover, there is an inverse correlation between the
gestational age at delivery and the risk for recurrent pre-
term birth [31,32] and patients who experienced a spon-
taneous preterm parturition, have a higher recurrence
rate than the general population for any gestational age
in which the preterm delivery occurred.
Among multiparous patients, a prior preterm birth is
the most prominent risk factor for a recurrent preterm
delivery [33,34]. This is important since in our cohort
the rate of previous preterm birth did not differ signifi-
cantly between the study groups; suggesting that the in-
dependent risk for recurrent preterm birth in women
with placenta previa who delivered preterm is a novel
observation that does not the result from their obstetric
history. Similarly to spontaneous preterm birth, placenta
previa is a recurrent pathology. In our cohort, the recur-
rence rate of placenta previa was 2.7%. This is in accord
with previous reports that the recurrence rate of pla-
centa previa in different population varies from 2.3% to
3.2% [23,24,35]. The novel finding of this study that
women who had a preterm delivery as a result of pla-
centa previa have an independent increased risk (OR
3.6) for a spontaneous preterm birth in the subsequent
pregnancy, even in the absence of recurrent placenta
previa, is of importance. This odds ratio is higher than
that for repeated placenta previa (2.65), and is similar to
the risk of recurrent preterm birth in patients who had a
previous spontaneous preterm birth [36]; further sup-
porting the assumption that the mechanisms leading to
spontaneous preterm birth may be also involved in pre-
term parturition among patients with placenta previa.
The shortcoming of this study is its retrospective na-
ture, and the inherited weakness of studies based on a
large dataset. In addition due to the structure of the
database and the long time period the data was collected
information regarding cervical length in our patients is
missing. However, its population based scope and the
large number of cases allow us to identify valuable infor-
mation regarding the epidemiology of preterm birth
among patients with placenta previa.
Conclusions
We present herein evidence that preterm delivery in
patients with placenta previa, especially if it occurs be-
fore 34 weeks of gestation, is a recurrent event regard-
less to the site of placental implantation in the
subsequent pregnancy. Collectively, these findings sup-
port the notion that a preterm delivery in women pla-
centa previa has the epidemiologic characteristic of
spontaneous preterm birth. Thus, patients with placenta
previa who had an early preterm delivery may need to
be treated as patients with a previous spontaneous pre-
term birth in term of perinatal counseling and
Erez et al. BMC Pregnancy and Childbirth 2012, 12:82 Page 5 of 6
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preventive measures in their subsequent pregnancies.
The approach regarding women with placenta previa
who delivered at late preterm is not that clear since at
these gestational age some of the deliveries may be indi-
cated and dependent on physician decision.
Competing interests
On behalf of me and all of the co-authors I declare that we have no known
conflict of interest regarding this manuscript what so ever.
Authors' contributions
OE designed the study and performed the statistical analysis and drafted the
manuscript; LN performed the statistical analysis and contributed to the
manuscript; VK, IEW, and RBW participated in writing the manuscript; DD and
MM participated the design of the study and helped to draft the manuscript.
All authors read and approved the final manuscript.
Author details
1
Department of Obstetrics and Gynecology, Soroka University Medical
Center, School of Medicine, Faculty of Health Sciences, Ben Gurion University
of the Negev, P O Box 151, Beer Sheva 84101, Israel.
2
Departments of
Epidemiology, Faculty of Health Sciences, Ben Gurion University of the
Negev, Beer Sheva, Israel.
3
Departments of Family Medicine, Faculty of Health
Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Received: 27 April 2012 Accepted: 3 August 2012
Published: 10 August 2012
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doi:10.1186/1471-2393-12-82
Cite this article as: Erez et al.:Early preterm delivery due to placenta
previa is an independent risk factor for a subsequent spontaneous
preterm birth. BMC Pregnancy and Childbirth 2012 12:82.
Erez et al. BMC Pregnancy and Childbirth 2012, 12:82 Page 6 of 6
http://www.biomedcentral.com/1471-2393/12/82
... Moreover, some reproductive problems such as rupture of the uterus, vaginal bleeding which have occurred due to fall or stress; improper implantation like placenta previa, or artificial insemination/ in vitro fertilization have also contributed in PTL 11,18,45,48 . Studies have proven that positive familial history, genetic factors like gene mutation, single nucleotide polymorphisms (SNP), immunological polymorphisms linked with cyclin-dependent kinase (CDK) or interleukins have shown association with PTL. ...
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To estimate the relationship between cervical length and hemorrhage leading to preterm delivery in women with placenta previa. Between October 2007 and May 2009, transvaginal cervical-length measurements were obtained in all singleton pregnancies with placenta previa identified at or beyond 24 weeks of gestation. Only women who delivered liveborn or stillborn neonates at our hospital and had placenta previa confirmed at delivery were included. Cervical length of 30 mm or less was considered short. Clinicians were blinded to cervical-length measurements. Chi-square and logistic regression were used for analysis. Of 89 identified women with placenta previa at initial ultrasonography, 68 had placenta previa at delivery, and 29 (43%) of these had a short cervix. Gestational age at cervical-length measurement was 32+/-4 weeks in women with a short cervix and 33+/-2 weeks in those with a longer cervix (P=.4). Women with previa and a short cervix were more likely to require delivery for hemorrhage, 79% compared with 28%, and to deliver preterm, 69% compared with 21% (both P<.001). Tocodynamometer evidence of regular uterine contractions was more common with a short cervix than with a longer cervix, 69% compared with 21% (P<.001). Conversely, 64% with a cervical length greater than 30 mm had no bleeding episodes and progressed to term. In pregnancies with placenta previa, a third-trimester cervical length of 30 mm or less is associated with increased risk for hemorrhage, uterine activity, and preterm birth. II.