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Etiology and risk factors for placenta previa:

An overview and meta-analysis of
observational studies
ARTICLE in JOURNAL OF MATERNAL-FETAL AND NEONATAL MEDICINE APRIL 2003
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The Journal of MaternalFetal and Neonatal Medicine 2003;13:175 190

Etiology and risk factors for placenta previa: an

overview and meta-analysis of observational studies
A. S. Faiz 1 and C. V. Ananth 2
1

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Division of Hematology, Department of Medicin e, Robert Wood J ohnson Medical School, University of Medicin e
and Dentistry of New J ersey, New Brunswick, New J ersey, USA
2
Section of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology and Reproductive Sciences,
Robert Wood J ohnson Medical School, University of Medicin e and Dentistry of New J ersey, New Brunswick,
New J ersey, USA

Objective: Several clinical and epidemiologic studies have reported disparate data on the preva-

lence rate as well as risk factors associated with placenta previa a major cause of third-trimester
bleeding. We performed a systematic literature review and identified 58 studies on placenta previa
published between 1966 and 2000.
Study design: Each study was reviewed independently by the two authors and was scored (on the
basis of established criteria) on method of diagnosis of placenta previa and on quality of study
design. We extracted data on the prevalence rate of placenta previa, as well as associations with
various risk factors from each study. A meta-analysis was then performed to determine the extent
to which different risk factors predispose women to placenta previa.
Results: Our results showed that the overall prevalence rate of placenta previa was 4.0 per 1000
births, with the rate being higher among cohort studies (4.6 per 1000 births), USA-based studies
(4.5 per 1000 births) and hospital-based studies (4.4 per 1000 births) than among casecontrol
studies (3.5 per 1000 births), foreign-based studies (3.7 per 1000 births) and population-based
studies (3.7 per 1000 births), respectively. Advancing maternal age, multiparity, previous Cesarean
delivery and abortion, smoking and cocaine use during pregnancy, and male fetuses all conferred
increased risk for placenta previa. Strong heterogeneity in the associations between risk factors
and placenta previa were noted by study design, accuracy in the diagnosis of placenta previa and
population-based versus hospital-based studies.
Conclusion: Future etiological studies on placenta previa must, at the very least, adjust for
potentially confounding effects of maternal age, parity, prior Cesarean delivery and abortions.
Key words: PLACENTA PREVIA ; ETIOLOGY ; EPIDEMIOLOGY ; META-ANALYSIS ; OVERVIEW

INTRODUCTION

Placenta previa is an obstetric complication in which the

maturing placenta partially or completely obstructs the
internal cervical os. It is a major cause of third-trimester
bleeding and has been associated with serious maternal
complications and adverse perinatal outcomes1. Maternal
complications associated with placenta previa include
hemorrhage requiring blood transfusion, disseminated
intravascular coagulation and partial or total hysterectomy.
Pregnancies complicated by placenta previa also result in
greater frequencies of prematurity and fetal and neonatal
death25. Despite early diagnosis and careful surveillance of
women with placenta previa and great advances in neo-

natal care, it is still challenging to avoid maternal complications and to improve perinatal outcomes among women
with this condition.
The etiology of placenta previa remains largely obscure,
but several clinical and epidemiological studies have
observed increased occurrence of placenta previa among
women with advanced maternal age, multiparity, male
fetuses, multiple pregnancy, prior Cesarean delivery and
prior spontaneous or induced abortion. Furthermore,
behavioral factors that have been implicated with
increased occurrence of placenta previa include maternal
smoking and drug use during pregnancy. Finally, women

Corr espondence: Dr A. S. Faiz, Division of Hem atology, Room 378, One Robert Wood J ohnson Place, PO Box 19, New Brunswick,
NJ 08903, USA
2003 The Par thenon Publish ing Group

175

Received 240602 Revised 281002 Accepted 291102

Etiology and risk factors for placenta previa

Faiz and Ananth

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with a history of placenta previa in a prior pregnancy are at

higher risk of developing this condition in a subsequent
pregnancy.
The prevalence rate of placenta previa and the extent to
which various risk factors predispose women to develop
placenta previa vary greatly in the previous studies. We
therefore performed a systematic review of the literature
to estimate the prevalence of placenta previa and its association with various risk factors. A meta-analysis was
then performed to identify sources of heterogeneity across
studies, as well as to evaluate the strength and magnitude
of the association of placenta previa with these risk factors.

MATERIALS AND METHODS

Scoring of studies

Literature review

Observational studies published in the English language

between January 1966 and March 2000 were potentially
eligible for inclusion in this overview. Identification of
such studies was based on a comprehensive MEDLINE
search, as well as by identifying studies cited in the
references of published papers. The MEDLINE search was
based on the following medical subject headings (MeSH):
placenta pr(a)evia, placental disorders, antepartum
h(a)emorrhage, and antepartum and uteroplacental
bleeding. The other key words used in conjunction with
previa were maternal age, gravidity, parity, C(a)esarean
delivery/section, uterine surgery, uterine instrumentation,
abortion, spontaneous abortion, induced abortion, elective
abortion, chronic hypertension, pregnancy-induced hypertension, pre-eclampsia, eclampsia, cigarette smoking and
drug use. Both the primary author and the librarian in our
institution conducted the searches independently using
these key words.
Published case reports on placenta previa and studies on
placental abruption were excluded. No attempts were made
to locate any unpublished studies or those published in
abstract form. We excluded studies in which placenta

Table 1
Cohort
studies

previa was diagnosed in early pregnancy (first or second

trimesters), as these studies were predominantly focused
on evaluating the accuracy of an early diagnosis of placenta
previa by sonographic methods. If more than one study
had the same data source covering overlapping time
periods, then only one study was chosen for inclusion in the
meta-analysis. The choice of study in such instances was
based on the availability of data on risk factors for placenta
previa. If two or more studies using the same patient
population provided information on placenta previa
cross-classified by the same risk factors, then the study
that was published first was arbitrarily chosen for inclusion
in the meta-analysis.

Both authors independently reviewed all the studies chosen

for the meta-analysis. A numeric score on a five-level
ordinal scale (15, with 5 being the best quality) on quality
of study was assigned for each study. The study quality was
based primarily on study design and adjustment for
four important confounding factors: maternal age, parity,
previous Cesarean delivery and previous spontaneous or
induced abortion. Similarly, each study was scored on a
four-level ordinal scale (14, with 4 being the most accurate) for the method of diagnosis of placenta previa used
in each study. The criteria used for scoring the study
quality and method of diagnosis of placenta previa were
determined a priori, and are shown in Tables 1 and 2,
respectively.
We were left with 58 studies461 for the meta-analysis
after excluding 42 studies2,3,62101 that did not meet our
inclusion/exclusion criteria. Both authors gave identical
scores to 36 studies on study quality and to 48 studies for
method of diagnosis of placenta previa. The chancecorrected kappa statistic with 95% confidence interval
(CI) for agreement in the scores between the two authors
on study design and diagnosis of placenta previa, respectively, were 0.66 (95% CI 0.53, 0.79) and 0.85 (95% CI

Numeric scoring of quality of studies according to study design

Casecontrol
studies

4
3
2
1

4
3
2
1

Scoring criteria according to quality of study

studies in which no obvious biases could be identified or potential confounders were adequately
controlled for
studies in which adjustment was made for potential biases but residual confounding appeared likely
studies in which adjustment for potential confounders was done poorly
studies in which no adjustment was made for potential confounders
studies without appropriate control subjects

Studies that controlled for maternal age, parity, previous Cesarean delivery, previous spontaneous or induced abortion were considered
as those without obvious biases (score of 5)
176
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Etiology and risk factors for placenta previa

Table 2 Numeric scoring of studys quality based on the method

of diagnosis of placenta previa
Study
score
4
3
2

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Criteria for scoring

placenta previa confirmed at Cesarean delivery
placenta previa confirmed by third-trimester ultrasound
examination
placenta previa as reported by attendant at delivery or by
digital examination at the time of delivery
criteria for the diagnosis of placenta previa not well
defined

0.76, 0.94). The scoring was different for quality of study

in 22 studies and for diagnosis of placenta previa in ten
studies, and in such cases the two authors discussed
the reasons and reassigned the scores after resolving the
discrepancy.
Based on the scores for the quality of study, 12 studies
(20%) with the score of 4 and 5 were classified as
well-designed studies and 46 studies with scores of less than
3 were classified as poorly designed. Similarly, based on the
method of diagnosis of placenta previa, 25 studies (43%)
with the score of 3 and 4 were classified as studies with
definite placenta previa and the remaining 33 studies
with scores of 1 and 2 were classified as studies with
probable placenta previa.
Data extraction

For each of those 58 studies that met our criteria, we

abstracted the year of publication, study design (cohort and
casecontrol study), geographical location where data
were collected (USA-based and foreign-based), source of
data (hospital-based, population-based, vital records) and
time and duration of data collection.
All studies were critically reviewed and information was
abstracted on total number of pregnancies and the number
of pregnancies complicated by placenta previa. Data on all
risk factors related to placenta previa examined in each
study were abstracted. Risk factors that were examined in
this study included maternal age, parity, prior Cesarean
delivery, prior spontaneous or induced abortion, smoking,
alcohol and cocaine use during pregnancy, hypertensive
disorders (chronic and pregnancy-induced hypertension
and pre-eclampsia/eclampsia), sex of the fetus, multiple
pregnancy and placental abruption. Studies that did
not provide sufficient information to carry out the metaanalysis or those that did not provide data for the comparison group were excluded from the meta-analysis. However,
these studies were still included in the review as well as
for the calculation of rates (of placenta previa) when data
were available.

Faiz and Ananth

Statistical methods for meta-analysis

The prevalence rate of placenta previa (per 1000 pregnancies) was either abstracted from the study directly or
derived by dividing the number of cases of placenta previa
by the total number of pregnancies. Data on placenta
previa cross-classified by the presence or absence of risk
factors were abstracted from every study, and were
organized in 2 2 tables. Odds ratios (OR) with associated
95% CI were computed as the measure of effect.
A meta-analysis was then performed by pooling the data
for each risk factor across all studies. We did not pool the
data for multiple pregnancies, recurrent placenta previa
and placental abruption as risk factors for placenta previa,
owing to lack of data. Prior to pooling data across studies,
we tested the homogeneity of studies being pooled. The test
statistic for homogeneity, Qh, was then compared with
the c2 distribution, with degrees of freedom equal to the
number of studies being pooled minus one. Random effect
ORs were computed after pooling the studies. Randomeffect analysis accounts for heterogeneity among studies
being pooled and assumes that these studies are a sample
from a larger population of similar but unidentified studies.
We also performed subgroup analysis for each risk factor
by grouping studies based on study design (cohort vs. case
control studies), geographic location (USA vs. foreignbased studies) and source of data (hospital vs. populationbased studies). The doseresponse effect of maternal
age and parity on the risk of placenta previa was also
evaluated from each study based on the covarianceadjusted method102.

RESULTS

Fifty-eight studies met our criteria for inclusion in the

meta-analysis, and were scored and classified according
to geographic location, source of data and study design
(Tables 3 and 4). There were 30 United States-based, and
28 were foreign-based studies; 37 cohort and 21 case
control studies; and 11 population-based and 47 hospitalbased studies.
The prevalence rate of placenta previa ranged between
2.8 and 19.7 per 1000 pregnancies in 58 studies (Table 5).
Of the 58 studies, there were 44 studies that reported data
on prevalence rates of placenta previa. There were a total
of 4.5 million pregnancies, of which 18 000 were identified
with placenta previa (4.0 per 1000 pregnancies). Amongst
the 44 studies that provided prevalence data, the frequency
of placenta previa was higher among 31 cohort studies (4.6
per 1000 pregnancies), 19 USA-based studies (4.5 per 1000
pregnancies) and 39 hospital-based studies (4.4 per 1000
pregnancies) than among 13 casecontrol studies (3.5 per
1000 pregnancies), 25 foreign-based studies (3.7 per 1000
pregnancies) and five population-based studies (3.7 per
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Etiology and risk factors for placenta previa

Faiz and Ananth

Table 3 Description of studies conducted within the USA and scores assigned to each study based on study design and diagnosis of
placenta previa

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Author

Study years

Placenta
Number of previa (per
pregnancies 1000 births)

Scores assigned
Criteria
for inclusion

Criteria
for exclusion

multiple births

Study design

Diagnosis

nulliparous

5
5
4
4
4

1
2
2
2
2

Population-based casecontrol studies

Kramer10
198487

Williams8
198788
Zhang 16
198890
309 320
Taylor7
198487

13
McMahon
1990

4.4

singleton live births

singleton births
live births
singleton live births
singleton live births

Hospital-based casecontrol studies

Grimes35
197579
28 665
Newton34
1981

Parson45
198285
10 473
Wolf4
198090
54 969
Williams22
197780
12 718
Handler12
198890
55 314
Chelmow23
199294

Macones24
199296

30
Sauer
198184
10 822

3.4

7.7
3.9
5.5
5.9

4.0

> 500 g fetus

singletons

singletons

births 20 weeks
births 20 weeks

multiple gestations

3
2
2
2
5
5
3
3
2

3
3
1
1
2
2
4
1
4

Population-based cohort studies

Hemminki49
197683

Iyasu41
197987

36
Demissie
198992
447 963

9.9
4.8
6.0

live births
live and stillbirths
singleton live births

1
2
4

2
1
2

17 265
102 670

6.0
4.6

singletons > 500 g

live and stillbirths > 500 g

2
2

1
2

208 837
31 070
38 398

3.7
6.0
4.5

singletons

1
2
1
2

2
2
3
4

16 029
21 217

97 799
42 058
6 576
93 384

4.3
4.5

3.0
3.5
16.8
5.5

> 500 g fetus

> 28 weeks

> 20 weeks

1
1
1
2
1
1
1

2
4
4
4
4
4
4

Hospital-based cohort studies

Niswander9
195965
Hibbard57
194853
196266
Crenshaw43
195069
Brenner33
196269
Cotton54
197578
Barrett50
197274
197980
Chervenak52
197882
Silver53
197480
DAngelo55
197981
Clark14
197783
McShane46
197582
Jelsema40

Frederiksen44
197697

1000 pregnancies), respectively. Furthermore, the

prevalence of placenta previa showed no temporal trends
(Figure 1).
The odds ratios based on the covariance-adjusted
method showed that both advanced maternal age and high
parity were associated with an increased risk of placenta
previa. There were nine studies614 that reported an association between advancing maternal age and placenta
previa (Figure 2). Results showed that odds ratios were
178
J ournal of MaternalFetal and Neonatal Medicin e

between 1.2 and 2.7 for three cohort studies9,11,14, seven

USA-based studies710,1214, six studies with probable
diagnosis of placenta previa710,12,13, and three poorly
designed studies6,9,14. Odds ratios ranged between 1.2 and
2.5 for six casecontrol studies68,10,12,13 and six welldesigned studies7,8,1013. For two foreign based
studies6,11 and for three studies with definite diagnosis
of placenta previa6,11,14 pooled odds ratios ranged between
1.5 and 2.5.

Etiology and risk factors for placenta previa

Faiz and Ananth

Table 4 Description of studies conducted outside the USA and scores assigned to each study based on study design and diagnosis
of placenta previa

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Author

Placenta
Number of previa (per
Study years pregnancies 1000 births)

Scores assigned
Criteria
for inclusion

Criteria
for exclusion

Study design

Diagnosis

Population-based casecontrol studies

61
Monica
197390
1 825 998

2.8

live and stillbirths

> 28 weeks

Hospital-based casecontrol studies

Neri5
196877
Rose20
197882
Gorodeski17
197283
Parazzini6
197991
Takayama30
197494
18
Abu Heija
199497

29 486
20 377

49 765
15 255
27 483

5.4
3.9
5.0
2.8
5.8
3.1

multiple gestations

2
3
2
3
2
3

3
4
2
4
4
1

Population-based cohort studies

Ananth11
198693
37
Ananth
198093

87 184
121 082

3.3
3.4

singletons
singletons

multiple gestations
multiple gestations

4
4

3
3

Hospital-based cohort studies

Gabert60
195666
Dutta58
196573
Hill59
197177
Gorodeski21
196878
Singh27
197378
Nicolaides38
197381
MacGillivary15
197683
Nielsen28
197887
Jackobovitz42
197286
Leiberman48
197286
Chattopadhay25 198892
Makhseed19
198192
Rosen56
199193
Hershkowitz26
198592
Khashoggi47
198891
Love51
199193
Zaideh29
199596
Wang39
198998
Hendricks32
199397

22 437
19 888
26 155

12 040
24 549
114 470
24 644
26 858
106 866
41 206
158 006

58 633
13 032
15 930
18 651
25 844
16 169

4.0
10.6
9.1
5.0
19.7
8.2
3.4
3.3
5.4
4.6
5.4
5.0

4.8
7.4
3.6
3.5
4.9
1.0

singletons

singletons, primigravida
singletons

twins

nulliparous

congenital anomaly

1
1
1
1
1
4
2
1
2
1
2
1
1
3
1
1
1
4
3

2
2
2
2
1
4
1
4
1
2
4
1
3
2
4
3
3
2
2

The relationship between parity and placenta previa was

provided in 13 studies618 (Figure 3). Among four cohort
studies9,11,14,15 and among ten studies with a probable
diagnosis of placenta previa710,12,13,1518 the odds ratios
ranged between 1.1 and 2.9. Odds ratios for nine case
control studies68,10,12,13,1618 ranged from 0.9 to 2.3, and for
three studies with definite diagnosis of placenta previa6,11,14
they were between 0.9 and 2.0. Odds ratios were between
0.9 and 2.9 for five foreign-based studies6,11,15,17,18 and
six poorly designed studies6,9,14,15,17,18. Among the eight
USA-based studies710,1214,16 and seven well-designed
studies7,8,1013,16, odds ratios ranged between 1.1 and 2.3.

Prior Cesarean delivery as a risk factor for placenta

previa was evaluated in 21 studies6,7,10,12,14,16,1832
(Table 6). The association was stronger among eight cohort
studies14,19,2529,32 (pooled OR 6.2) and for 12 foreign-based
studies6,1821,2529,31,32 (pooled OR 4.8) compared with 13
casecontrol studies6,7,10,12,16,18,2024,30,31 (pooled OR 2.0)
and nine studies7,10,12,14,16,2224,30 conducted in the USA
(pooled OR 2.0). With Cesarean delivery, the risk of
placenta previa was higher in ten studies with definite
diagnosis of placenta previa6,12,14,20,23,25,2831 (pooled
OR 3.0) and in 17 poorly designed studies6,12,14,1821,2332
(pooled OR 3.5).
179
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Etiology and risk factors for placenta previa

Table 5

Prevalence rate of placenta previa (per 1000 pregnancies) by type of study design and geographical location

Overall
Cohort studies
Casecontrol studies
USA studies
Foreign-based studies
Population-based studies
Hospital-based studies

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Faiz and Ananth

Number of studies

Rate of previa (derived)

Number of studies

Rate of previa (reported)

44
31
13
19
25
5
39

4.0
4.6
3.5
4.5
3.7
3.7
4.4

58
37
21
30
28
11
47

2.8 to 19.7
3.0 to 19.7
2.8 to 7.7
3.0 to 16.8
2.8 to 19.7
3.1 to 9.9
2.8 to 19.7

Figure 1 Prevalence rate (per 1000 singleton births) of placenta

previa from each study based on year of data collection. The size of
the bubble denotes the study size

Figure 2 Association between maternal age and placenta previa

from the nine studies: odds ratios with 95% confidence intervals

Previous abortion conferred a 90% increase in the risk

of placenta previa in eight studies6,13,16,18,21,30,31,33 (Table
7). There were one cohort33 and seven casecontrol
studies6,13,16,18,21,30,31 that reported the association between
180
J ournal of MaternalFetal and Neonatal Medicin e

Figure 3 Association between parity and placenta previa from

the 13 studies: odds ratios with 95% confidence intervals

previous abortions and risk of placenta previa. Previous

abortion was more significantly associated with placenta
previa in four foreign-based studies6,18,21,31 (pooled OR 2.7)
than in the four USA-based studies13,16,30,33 (pooled OR
1.8). The risk of placenta previa was similar in three
studies with definite diagnosis6,30,31 and in five studies with
probable diagnosis of placenta previa13,16,18,21,33 (pooled
OR 1.9). However, the risk was higher among six poorly
designed studies6,18,21,30,31,33 (pooled OR 2.4) than in two
well-designed studies13,16(pooled OR 1.8).
There was a higher risk of placenta previa with previous
spontaneous abortion (pooled OR 2.0) in seven
studies7,10,12,20,22,23,34 (Table 8). All the studies were
casecontrol studies and only one study20 was foreign
based. There was an increased risk of placenta previa with
spontaneous abortion in three studies with definite diagnosis of placenta previa20,23,34 and three poorly designed
studies20,23,34 (pooled OR 2.3) than in four studies with
probable diagnosis of placenta previa7,10,12,22 and in four
well-designed studies7,10,12,22 (pooled OR 2.0).
In the presence of previous induced abortion there was a
50% increase in placenta previa (Table 9). All eight studies
were USA-based casecontrol studies7,10,12,2224,34,35. With

Etiology and risk factors for placenta previa

Table 6

Faiz and Ananth

Association between prior Cesarean delivery and placenta previa

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Test of homogeneity of pooled odds ratios

2

Number of studies

c Qh

Degrees of freedom

21
8
13
9
12
10
11
4
17

60.3
0.2
11.7
7.1
12.7
27.5
25.0
2.2
35.0

20
7
12
8
11
9
10
3
16

Overall
Cohort studies
Casecontrol studies
USA-based studies
Foreign-based studies
Definite previa
Probable previa
Well-designed studies
Poorly designed studies

p Value
< 0.001
0.999
0.470
0.525
0.313
0.001
0.009
0.531
0.006

Random-effects
pooled odds ratio
(95% CI)
2.7 (2.3, 3.2)
6.2 (3.6, 10.5)
2.0 (1.8, 2.3)
2.0 (1.7, 2.3)
4.8 (3.8, 6.2)
3.0 (2.3, 3.2)
2.3 (2.0, 2.7)
1.9 (1.7, 2.2)
3.5 (2.7, 4.6)

Qh, test statistic for homogeneity

Table 7

Association between previous abortions (spontaneous or induced) and placenta previa

Test of homogeneity of pooled odds ratios
Number of studies

c Qh

Degrees of freedom

p Value

Random-effects
pooled odds ratio
(95% CI)

8
1
7
4
4
3
5
2
6

13.4

12.8
3.0
4.5
0.0
13.4
1.7
5.7

6
3
3
2
4
1
5

0.063

0.046
0.391
0.212
1.000
0.009
0.192
0.336

1.9 (1.7, 2.2)

2.1 (1.6, 2.9)
1.9 (1.6, 2.1)
1.8 (1.6, 2.0)
2.7 (2.0, 3.7)
1.9 (0.8, 5.0)
1.9 (1.7, 2.2)
1.8 (1.6, 2.0)
2.4 (2.0, 3.0)

Overall
Cohort studies
Casecontrol studies
USA-based studies
Foreign-based studies
Definite previa
Probable previa
Well-designed studies
Poorly designed studies

Qh, test statistic for homogeneity

Table 8

Association between prior spontaneous abortion and placenta previa

Test of homogeneity of pooled odds ratios
Number of studies

c Qh

Degrees of freedom

p Value

Random-effects
pooled odds ratio
(95% CI)

7
6
1
3
4
4
3

6.6

6.6
6.5

1.2
5.0
5.0
1.2

6
5

2
3
3
2

0.359

0.359
0.261

0.548
0.172
0.172
0.753

2.0 (1.7, 2.3)

2.0 (1.7, 2.3)

2.0 (1.7, 2.3)
2.1 (1.1, 4.4)
2.3 (1.4, 3.5)
2.0 (1.7, 2.3)
2.0 (1.7, 2.3)
2.3 (1.3, 3.5)

Overall
Cohort studies
Casecontrol studies
USA-based studies
Foreign-based studies
Definite previa
Probable previa
Well-designed studies
Poorly designed studies

Qh, test statistic for homogeneity

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Etiology and risk factors for placenta previa

Table 9

Faiz and Ananth

Association between prior induced abortion and placenta previa

Test of homogeneity of pooled odds ratios
Number of studies

c Qh

Degrees of freedom

p Value

Random-effects
pooled odds ratio
(95% CI)

8
8

3
5
4
4

12.1

12.1
12.1

5.1
5.5
5.5
5.1

7
7

2
4
3
3

0.097

0.097
0.097

0.078
0.239
0.139
0.164

1.5 (1.3, 1.9)

1.5 (1.3, 1.9)

1.5 (1.3, 1.9)

1.3 (0.6, 2.7)

1.6 (1.4, 2.0)
1.6 (1.3, 2.0)
1.2 (0.7, 2.3)

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Overall
Cohort studies
Casecontrol studies
USA-based studies
Foreign-based studies
Definite previa
Probable previa
Well-designed studies
Poorly designed studies

Qh, test statistic for homogeneity

Table 10

Association between maternal smoking and placenta previa

Test of homogeneity of pooled odds ratios
Number of studies

c Qh

Degrees of freedom

p Value

Random-effects
pooled odds ratio
(95% CI)

9
1
8
8
1
3
6
6
3

26.0

18.8
18.8

6.0
5.6
14.2
8.1

7
7

2
5
5
2

0.001

0.009
0.009

0.049
0.347
0.014
0.017

1.6 (1.4, 1.8)

1.2 (0.9, 1.5)
1.7 (1.5, 1.9)
1.7 (1.5, 1.9)
1.2 (0.9, 1.5)
1.1 (0.8, 1.5)
1.8 (1.6, 2.0)
1.6 (1.5, 1.8)
1.4 (0.7, 2.9)

Overall
Cohort studies
Casecontrol studies
USA-based studies
Foreign-based studies
Definite previa
Probable previa
Well-designed studies
Poorly designed studies

Qh, test statistic for homogeneity

previous induced abortion, the risk of placenta previa was

higher in five studies with probable diagnosis of placenta
previa7,10,12,22,24 and in four well-designed studies7,10,12,22
(pooled OR 1.6) than in studies with a definite diagnosis of
placenta previa23,34,35 (pooled OR 1.3) and in four poorly
designed studies23,24,34,35 (pooled OR 1.2).
Smoking during pregnancy was associated with a 60%
increase in the risk of placenta previa (Table 10). There
was one foreign-based cohort study11 and there were eight
USA-based casecontrol studies7,10,12,13,2224,34. The risk of
placenta previa was higher among smokers in six studies
with probable diagnosis of placenta previa7,10,12,13,22,24
(pooled OR 1.8) and in six well-designed studies7,1013,22
(pooled OR 1.6) than in three studies11,23,34 with definite
diagnosis of placenta previa (pooled OR 1.1) and in three
poorly designed studies23,24,34 (pooled OR 1.4). Three
casecontrol studies in the USA 12,23,24 (Table 11) also
demonstrated a higher risk of placenta previa with cocaine
use during pregnancy (pooled OR 2.9). There were two
182
J ournal of MaternalFetal and Neonatal Medicin e

studies with probable diagnosis of placenta previa23,24

(pooled OR 3.0) and two poorly designed studies23,24
(pooled OR 5.2).
There were seven studies4,6,11,15,22,33,36 describing the
association of male fetuses with risk of placenta previa
(Table 12). There were four cohort11,15,33,36 and three
casecontrol studies4,6,22 with similar risk of placenta previa
(pooled OR 1.2 and 1.1, respectively). Male fetuses were
associated with higher risk of placenta previa in three
foreign-based studies6,11,15 (pooled OR 1.3) than in four
USA-based studies4,22,33,36 (pooled OR 1.1). With male
fetuses there was a higher risk of placenta previa in two
studies with definite diagnosis of placenta previa6,11
(pooled OR 1.5) than in five studies with probable diagnosis of placenta previa4,15,22,33,36 (pooled OR 1.2).
However, the risk was similar for three well-designed11,22,36
and four poorly designed studies4,6,15,33 (pooled OR 1.2).
There was a 50% increased risk of placenta previa due to
chronic hypertension in three studies33,34,37 (Table 13).

Etiology and risk factors for placenta previa

Table 11

Faiz and Ananth

Association between maternal cocaine use and placenta previa

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Test of homogeneity of pooled odds ratios

Number of studies

c Qh

Degrees of freedom

p Value

Random-effects
pooled odds ratio
(95% CI)

3
3

1
2
1
2

2.0

2.0
2.0

2.0

0.0

2
2

0.368

0.368
0.368

0.157

1.000

2.9 (1.9, 4.3)

2.9 (1.9, 4.3)

2.9 (1.9, 4.3)

4.3 (0.3, 72.0)

3.0 (1.8, 5.0)
2.5 (1.6, 3.9)
5.2 (0.7, 39.0)

Overall
Cohort studies
Casecontrol studies
USA-based studies
Foreign-based studies
Definite previa
Probable previa
Well-designed studies
Poorly designed studies

Qh, test statistic for homogeneity

Table 12

Association between sex of the fetus and placenta previa

Test of homogeneity of pooled odds ratios
Number of studies

c Qh

Degrees of freedom

p Value

Random-effects
pooled odds ratio
(95% CI)

7
4
3
4
3
2
5
3
4

7.7
6.1
1.2
1.0
2.1
0.4
2.4
6.0
1.3

6
3
2
3
2
1
4
2
3

0.261
0.107
0.549
0.801
0.349
0.527
0.662
0.049
0.729

1.2 (1.1, 1.3)

1.2 (1.1, 1.3)
1.1 (0.9, 1.4)
1.1 (1.0, 1.2)
1.3 (1.2, 1.5)
1.5 (1.2, 1.8)
1.2 (1.1, 1.3)
1.2 (1.1, 1.3)
1.2 (1.1, 1.5)

Overall
Cohort studies
Casecontrol studies
USA-based studies
Foreign-based studies
Definite previa
Probable previa
Well-designed studies
Poorly designed studies

Qh, test statistic for homogeneity

Table 13

Association between chronic hypertension and placenta previa

Test of homogeneity of pooled odds ratios
Number of studies

c Qh

Degrees of freedom

p Value

Random-effects
pooled odds ratio
(95% CI)

3
2
1
2
1
2
1
1
2

2.4
0.4

2.3

2.0

2.2

2
1

0.301
0.527

0.129

0.157

0.138

1.5 (0.8, 2.7)

1.2 (0.7, 2.4)
4.7 (1.0, 22.0)
1.6 (0.8, 3.3)
1.2 (0.4, 3.7)
2.0 (0.7, 6.4)
1.3 (0.6, 2.7)
1.2 (0.4, 3.7)
1.9 (0.7, 5.0)

Overall
Cohort studies
Casecontrol studies
USA-based studies
Foreign-based studies
Definite previa
Probable previa
Well-designed studies
Poorly designed studies

Qh, test statistic for homogeneity

Two studies were cohort studies33,37 (pooled OR 1.2) and

two were USA-based studies33,34 (pooled OR 1.6). There
was significant risk of placenta previa due to chronic hyper-

tension in two studies with definite placenta previa34,37

(pooled OR 2.0) and in two poorly designed studies33,34
(pooled OR 1.9).
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Pregnancy-induced hypertension showed a significant

protective effect on the risk of placenta previa (Table 14).
All three studies that examined pregnancy-induced
hypertension were USA-based cohort studies3739 (pooled
OR 0.4). All three were well-designed studies and
pregnancy-induced hypertension had a similar protective
effect in two studies37,38 with a definite diagnosis and
in one study39 with a probable diagnosis of placenta previa
(pooled OR 0.3).
Pre-eclampsia also showed a protective effect on the
risk of placenta previa (Table 15). All three studies were
USA-based studies33,34,40 (pooled OR 0.9). There was one
casecontrol study34 and two cohort studies33,40. All
studies were poorly designed and one study33 with a
probable diagnosis of placenta previa showed that the risk
of placenta previa increases with pre-eclampsia (pooled OR
1.3). However, studies with a definite diagnosis of placenta
previa34,40 confirmed the protective effect of pre-eclampsia
on the risk of placenta previa (pooled OR 0.7).
Table 14

DISCUSSION
Placenta previa is an obstetric condition that leads to
serious maternal and fetal complications. This condition
has been reported to occur in 320 per 1000 pregnancies.
The wide variation in the prevalence rate can be attributed
to inclusion of varying degrees of placenta previa, different
methods and timing of diagnosis, and diversity of the
patient population across studies. Many clinical and epidemiological studies have reported the rate of placenta
previa to be higher among older and multiparous women,
those with a previous Cesarean delivery, prior spontaneous
or induced abortion as well as among women who smoked
or used cocaine during pregnancy.
This meta-analysis confirms the higher risk of placenta
previa associated with advancing maternal age. Among
older women, there may be atherosclerotic changes in the
uterine blood vessels causing compromised uteroplacental
blood flow. This has been shown by microscopic studies of

Association between pregnancy-induced hypertension and placenta previa

Test of homogeneity of pooled odds ratios
Number of studies

c Qh

Degrees of freedom

p Value

Random-effects
pooled odds ratio
(95% CI)

3
2
1
3

4.8

4.8

4.8
4.7

4.8

2
1

0.091

0.091

0.091
0.030

0.091

0.4 (0.2, 0.5)

0.4 (0.2, 0.5)

0.4 (0.2, 0.5)

0.3 (0.2, 0.6)
0.3 (0.3, 1.0)
0.4 (0.2, 0.5)

Overall
Cohort studies
Casecontrol studies
USA-based studies
Foreign-based studies
Definite previa
Probable previa
Well-designed studies
Poorly designed studies

Qh, test statistic for homogeneity

Table 15 Association between pre-eclampsia and placenta previa. Reprinted from reference 103, 2003, with permission of
Elsevier Science
Test of homogeneity of pooled odds ratios
Number of studies

c Qh

Degrees of freedom

p Value

Random-effects
pooled odds ratio
(95% CI)

3
2
1
3

2
1

4.0
4.0

4.0

2.0

4.0

2
1

0.135
0.045

0.135

0.157

0.135

0.9 (0.5, 1.4)

0.8 (0.3, 2.1)
0.9 (0.5, 1.7)
0.9 (0.5, 1.4)

0.7 (0.4, 1.2)

1.3 (0.7, 2.7)

0.9 (0.5, 1.4)

Overall
Cohort studies
Casecontrol studies
USA-based studies
Foreign-based studies
Definite previa
Probable previa
Well-designed studies
Poorly designed studies
Qh, test statistic for homogeneity
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Etiology and risk factors for placenta previa

Faiz and Ananth

placentae from older women that have revealed uteroplacental underperfusion and large placental infarcts8. To
maintain optimal blood flow, an increased surface area may
be required for placental attachment, and this may result in
placental encroachment on the lower uterine segment8.
Our results also show a greater risk of placenta previa with
higher parity, confirming findings from earlier studies. This
may be due to endometrial scarring at the site of prior
placental attachments resulting in lower placental
implantation. The other possibility may be that blood
vessels at the sites of prior placental attachments undergo
changes that may lead to decreased uteroplacental blood
flow3. This, in turn, may result in a larger placenta
encroaching on the cervical os with repeated pregnancies.
In this meta-analysis we analyzed only maternal age and
parity as independent risk factors for placenta previa.
However, since women with higher parity are likely to
be older, it is possible that advanced maternal age and
increased parity are not independent risk factors for the
placenta previa risk. This combined effect of age and
gravidity on the risk of placenta previa was demonstrated in
a large (n = 37 956 020), population-based, cohort study
of singleton births from the USA (198998)103. This
study showed that the risk of placenta previa was not
independent of maternal age and parity, but rather that
both factors exerted a joint influence on placenta previa
risk. In other words, increasing maternal age and increasing
parity conferred the greatest risk of placenta previa
compared with that of primigravid women aged < 20 years
(Table 16).
There is an increased risk of placenta previa among
women with a history of previous Cesarean delivery and
previous abortion. Our meta-analysis corroborates these
general findings reported in several previous studies as well
as a meta-analysis104. Damage and scarring to the endometrial and myometrial lining during Cesarean delivery
and spontaneous and induced abortion are known to pre-

Table 16

dispose to the low implantation of the placenta in the

uterus.
There is a higher risk of placenta previa with cigarette
smoking and maternal cocaine use during pregnancy, as
previously reported. Placental enlargement has been noted
among women who smoke cigarettes and this has been
attributed to the vasoactive properties of nicotine and to
chronic hypoxia associated with carbon monoxide22,62,63. It
has also been observed that there are chronic hypoxic
changes in the uterine vasculature of smokers, resulting in a
larger placenta with increased likelihood of placental
encroachment on the cervical os22,74. Similarly, maternal
cocaine use is known to cause catecholamine-mediated
vasoconstriction and vasospasm in blood vessels innervated
by the sympathetic nervous system. This is likely to result
in underperfusion of the uteroplacental vessels and a larger
placenta encroaching on the cervical os12,22.
This meta-analysis confirms an increased male/female
ratio at birth among women with placenta previa. It has
been proposed that early and late insemination during the
menstrual cycle may cause an increase in the conception of
males as well as lower implantation of the placenta15. With
early insemination it may be possible that the embryo
reaches the lower uterine segment before the endometrial
lining is ready for implantation. Similarly, with late insemination, the ovum may be in the lower uterine segment
when it is fertilized, resulting in lower uterine implantation
in both cases.
There is an increased frequency of placenta previa
among women with pre-existing or chronic hypertension.
The exact mechanism that leads to lower implantation of
the placenta among women with chronic hypertension is
not clear. However, placenta previa has a protective effect
on the risk of pregnancy-induced hypertension and
pre-eclampsia. Although the precise mechanism is unclear,
it has been suggested that, owing to the wider diameter and
less restricted course of blood vessels, there is better

Joint effects of maternal age and gravidity on the risk of placenta previa: adjusted relative risks with 95% confidence intervals
Gravidity (number of pregnancies)

Maternal age (years)

< 20
2024
2529
3034
3539
40

1.00 (referent)
1.61 (1.50, 1.72)
2.82 (2.63, 3.00)
4.71 (4.41, 5.03)
7.30 (6.78, 7.86)
10.41 (9.25, 11.72)

1.72 (1.57, 1.89)

2.21 (2.07, 2.37)
3.59 (3.37, 3.83)
5.24 (4.92, 5.59)
7.87 (7.35, 8.44)
9.95 (8.93, 11.08)

2.13 (1.86, 2.44)

2.87 (2.28, 3.60)
3.00 (2.05, 4.37)
2.99 (2.79, 3.22)
3.66 (3.37, 3.98)
4.66 (4.26, 5.08)
4.31 (4.04, 4.61)
4.99 (4.65, 5.36)
6.22 (5.80, 6.67)
6.02 (5.65, 6.43)
6.52 (6.08, 6.98)
7.82 (7.31, 8.35)
8.38 (7.82, 8.98)
9.24 (8.59, 9.94)
10.01 (9.35, 10.72)
11.96 (10.80, 13.24) 12.16 (10.90, 13.57) 12.62 (11.59, 13.74)

Table reprinted from reference 103, 2003, with permission of Elsevier Science
Relative risks were adjusted for the confounding effects of maternal anemia, intrapartum fever, preterm premature rupture of
membranes, hydramnios, maternal diabetes, placental abruption, unexplained uterine bleeding and male sex
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oxygenation of the placenta implanted in the lower uterine

segment48. With higher implantation of the placenta in
the uterine cavity there may be restricted blood flow,
causing hypoxia and release of vasoactive substances into
the blood stream, resulting in a greater risk of pregnancyinduced hypertension and pre-eclampsia. A better blood
supply and oxygenation of the placenta in the lower uterine
segment prevents the release of vasoactive substances
into the blood stream and thus reduces the risk of
pregnancy-induced hypertension and pre-eclampsia in
cases of placenta previa47,48. An alternative hypothesis
suggests that venous drainage from the placenta implanted
in the fundal part of the uterus is through ovarian veins,
causing visceral congestion and vasoconstriction, resulting
in pre-eclampsia. However, when the placenta is implanted
in the lower uterine segment, drainage is through uterine
veins and there is no visceral congestion; therefore,
placenta previa has a protective effect on pre-eclampsia
and pregnancy-induced hypertension105.
There are a number of risk factors that increase the likelihood of developing placenta previa. These include
advanced maternal age, multiparity, smoking during
pregnancy, alcohol and drug use during pregnancy, prior
Cesarean delivery and abortion, multiple pregnancy,
prior placenta previa, maternal anemia and diabetes,
hydramnios, placental abruption and chronic hypertension. Although we calculated pooled odds ratios for all
the risk factors for which data were available, there were
not enough data for the analysis of certain risk factors. The
Table 17

strength of association of all the risk factors with placenta

previa and directionality of association with populationattributable risk are presented in Table 17.
The population-attributable risk for placenta previa
indicates that smoking has the greatest effect (26%)
followed by previous abortion (16%) and Cesarean delivery
(10%). This implies that, if all women were to quit smoking
during pregnancy, 26% of placenta previa cases would
potentially be preventable. As cigarette smoking is preventable, it would be beneficial to encourage pregnant
women to quit smoking, especially those women suspected
of being at increased risk for placenta previa. Similarly,
Cesarean deliveries and abortions should be performed
with more caution and only in cases where there is
evidence of fetal or maternal distress, in order to reduce
the risk of placenta previa in future pregnancies.
In this study, we attempted to identify all published
studies between 1966 and March 2000. However, in spite of
our best efforts we may have missed some that may have
reported data on placenta previa. To account for this bias,
the random-effects analysis formed the basis of pooling of
data across studies. Thus, we assume that studies included
in our meta-analysis are a (random) sample from a larger
population of similar studies. In this meta-analysis, each
study was individually reviewed and scored by the two
authors on the basis of established criteria for study quality
and for method of diagnosis of placenta previa.
The careful review of studies indicated that there is a
wide variation in the definition of placenta previa and

Strength and direction of association between various risk factors and conditions associated with placenta previa
Associations

Risk factors for placenta previa

Advanced maternal age ( 35 years)*
Multiparity (parity 3)*
Smoking during pregnancy
Alcohol use during pregnancy*
Drug use during pregnancy
Prior Cesarean delivery
Prior abortion
Multiple pregnancy*
Prior placenta previa
Maternal anemia*
Maternal diabetes*
Hydramnios*
Placental abruption*
Chronic hypertension
Pre-eclampsia/PIH

Strength

Directionality

Population-attributable risk
(%)

+++
+++
+
+
+
++
+
+
+
++
+
+
++
+
-

25.7

6.7
10.2
16.0

2.7

0.3
1.4

PIH, pregnancy-induced hypertension

*Data from reference 103

Data from references 21 and 61

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Etiology and risk factors for placenta previa

method used for the diagnosis of placenta previa across

studies. This ranged from studies that did not give any
definition of placenta previa or method used for the
diagnosis of placenta previa to studies that explicitly
defined placenta previa and included only those women
with the placenta completely covering the internal cervical
os and who were diagnosed at the time of Cesarean
delivery. Similarly, risk factors including advanced maternal age, higher parity, prior Cesarean delivery and the
potential confounders for placenta previa were controlled
in varying degrees across studies. This ranged from studies
that controlled for all potential confounders to studies that
had no control group. These discrepancies make it difficult
to compare the results of these individual studies.
In conclusion, meta-analysis is a useful technique not
only for quantitatively summarizing the results but also for
calculating the strength of association between placenta
previa and various risk factors. However, we recommend
that future studies should confirm a diagnosis of placenta
previa through sonographic visualization of the placental
position in the lower uterine segment, either partially or
completely covering the internal cervical os. In the absence
of such a diagnosis, placenta previa must be confirmed at
the time of Cesarean section. Potential confounders should
also be controlled adequately in order to minimize possible
biases in the study findings. This will help to clarify the
epidemiology of placenta previa and its impact on adverse
maternal and perinatal outcomes.

ACKNOWLEDGEMENTS

At the time of the study, Ambarina Faiz MD, MPH was

a Primary Care/Health Services research fellow in the
Department of Family Medicine, UMDNJ, and was
supported through an NRSA Fellowship award (T32PE10011) from the Health Resources and Services Administration. Cande Ananth, PhD, MPH is partly supported
through a grant (HD-38902) awarded to him from the
National Institutes of Health.
This study formed part of Dr Faizs post-doctoral
research under the direction of Dr Ananth.
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