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  • 8/19/2019 Penyebab Kanker Paru- Paru Primer

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    See discussions, stats, and author profiles for this publication at: http://www.researchgate.net/publication/10695639

    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

    Impact Factor: 1.21 · DOI: 10.1080/jmf.13.3.175.190 · Source: PubMed

    CITATIONS

    96

    2 AUTHORS, INCLUDING:

    Cande Ananth

    Columbia University

    469 PUBLICATIONS  8,002 CITATIONS 

    SEE PROFILE

    Available from: Cande Ananth

    Retrieved on: 01 September 2015

    http://www.researchgate.net/profile/Cande_Ananth?enrichId=rgreq-ab3d55bf-77f1-4721-b18e-28400aaa2900&enrichSource=Y292ZXJQYWdlOzEwNjk1NjM5O0FTOjE2MTk1MzM4NTI5NTg3MkAxNDE1NjI0MTA0NjYx&el=1_x_7http://www.researchgate.net/profile/Cande_Ananth?enrichId=rgreq-ab3d55bf-77f1-4721-b18e-28400aaa2900&enrichSource=Y292ZXJQYWdlOzEwNjk1NjM5O0FTOjE2MTk1MzM4NTI5NTg3MkAxNDE1NjI0MTA0NjYx&el=1_x_7http://www.researchgate.net/profile/Cande_Ananth?enrichId=rgreq-ab3d55bf-77f1-4721-b18e-28400aaa2900&enrichSource=Y292ZXJQYWdlOzEwNjk1NjM5O0FTOjE2MTk1MzM4NTI5NTg3MkAxNDE1NjI0MTA0NjYx&el=1_x_7http://www.researchgate.net/?enrichId=rgreq-ab3d55bf-77f1-4721-b18e-28400aaa2900&enrichSource=Y292ZXJQYWdlOzEwNjk1NjM5O0FTOjE2MTk1MzM4NTI5NTg3MkAxNDE1NjI0MTA0NjYx&el=1_x_1http://www.researchgate.net/profile/Cande_Ananth?enrichId=rgreq-ab3d55bf-77f1-4721-b18e-28400aaa2900&enrichSource=Y292ZXJQYWdlOzEwNjk1NjM5O0FTOjE2MTk1MzM4NTI5NTg3MkAxNDE1NjI0MTA0NjYx&el=1_x_7http://www.researchgate.net/institution/Columbia_University?enrichId=rgreq-ab3d55bf-77f1-4721-b18e-28400aaa2900&enrichSource=Y292ZXJQYWdlOzEwNjk1NjM5O0FTOjE2MTk1MzM4NTI5NTg3MkAxNDE1NjI0MTA0NjYx&el=1_x_6http://www.researchgate.net/profile/Cande_Ananth?enrichId=rgreq-ab3d55bf-77f1-4721-b18e-28400aaa2900&enrichSource=Y292ZXJQYWdlOzEwNjk1NjM5O0FTOjE2MTk1MzM4NTI5NTg3MkAxNDE1NjI0MTA0NjYx&el=1_x_5http://www.researchgate.net/profile/Cande_Ananth?enrichId=rgreq-ab3d55bf-77f1-4721-b18e-28400aaa2900&enrichSource=Y292ZXJQYWdlOzEwNjk1NjM5O0FTOjE2MTk1MzM4NTI5NTg3MkAxNDE1NjI0MTA0NjYx&el=1_x_4http://www.researchgate.net/?enrichId=rgreq-ab3d55bf-77f1-4721-b18e-28400aaa2900&enrichSource=Y292ZXJQYWdlOzEwNjk1NjM5O0FTOjE2MTk1MzM4NTI5NTg3MkAxNDE1NjI0MTA0NjYx&el=1_x_1http://www.researchgate.net/publication/10695639_Etiology_and_risk_factors_for_placenta_previa_An_overview_and_meta-analysis_of_observational_studies?enrichId=rgreq-ab3d55bf-77f1-4721-b18e-28400aaa2900&enrichSource=Y292ZXJQYWdlOzEwNjk1NjM5O0FTOjE2MTk1MzM4NTI5NTg3MkAxNDE1NjI0MTA0NjYx&el=1_x_3http://www.researchgate.net/publication/10695639_Etiology_and_risk_factors_for_placenta_previa_An_overview_and_meta-analysis_of_observational_studies?enrichId=rgreq-ab3d55bf-77f1-4721-b18e-28400aaa2900&enrichSource=Y292ZXJQYWdlOzEwNjk1NjM5O0FTOjE2MTk1MzM4NTI5NTg3MkAxNDE1NjI0MTA0NjYx&el=1_x_2

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    Etiology and risk factors for placenta previa: anoverview and meta-analysis of observational studies

     A. S. Faiz1 and C. V. Ananth2

    1

    Division of Hematology, Department of Medicine, Robert Wood J ohnson Medical School, University of Medicine and Dentist ry of New J ersey, New Brunswick, New J ersey, USA2Section of Epidemiology and Biostat istics, Department of Obst etrics, Gynecology and Reproductive Sciences,Robert Wood J ohnson Medical School, Univers ity of Medicine and Dentist ry of New J ersey, New Brunswick,New Jersey, 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-trimesterbleeding. We performed a systematic literature review and identified 58 studies on placenta previapublished between 1966 and 2000.

    Study design:   Each study was reviewed independently by the two authors and was scored (on thebasis of established criteria) on method of diagnosis of placenta previa and on quality of studydesign. We extracted data on the prevalence rate of placenta previa, as well as associations withvarious risk factors from each study. A meta-analysis was then performed to determine the extentto 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 1000births, 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 case–controlstudies (3.5 per 1000 births), foreign-based studies (3.7 per 1000 births) and population-basedstudies (3.7 per 1000 births), respectively. Advancing maternal age, multiparity, previous Cesareandelivery and abortion, smoking and cocaine use during pregnancy, and male fetuses all conferredincreased risk for placenta previa. Strong heterogeneity in the associations between risk factorsand 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 forpotentially confounding e ffects 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-trimesterbleeding 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

    death2–5. 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 compli-

    cations 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

    The Journal of Maternal–Fetal and Neonatal Medicine 2003;13:175–190

    Correspondence: Dr A. S. Faiz, Divis ion of Hematology, Room 378, One Robert Wood J ohnson Place, PO Box 19, New Brunswick,NJ 08903, USA

    ã 2003 The Parthenon Publishin Grou 175 Received 24–06–02 Revised 28–10–02 Acce ted 29–11–02

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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 asso-ciation 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

    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 hyper-

    tension, pre-eclampsia, eclampsia, cigarette smoking anddrug 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

    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 placentaprevia. 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.

    Scoring of studies

    Both authors independently reviewed all the studies chosen

    for the meta-analysis. A numeric score on a five-level

    ordinal scale (1–5, with 5 being the best quality) on quality

    of study was assigned for each study. The study quality wasbased 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 (1–4, with 4 being the most accu-

    rate) 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 studies4–61 for the meta-analysis

    after excluding 42 studies2,3,62–101

    that did not meet ourinclusion/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 chance-

    corrected kappa statistic with 95% confidence interval

    (CI) for agreement in the scores between the two authors

    on study design and diagnosis of placenta previa, respec-

    tively, were 0.66 (95% CI 0.53, 0.79) and 0.85 (95% CI

    Etiology and risk factors for placenta previa Faiz and Ananth

     J ou rn al of Maternal–Fetal and Neonatal Medicine

    176

    Cohort

    studies

    Case–control

    studies Scoring criteria according to quality of study

    5

    4

    3

    2

    1

    5

    4

    3

    2

    1

    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)

    Table 1   Numeric scoring of quality of studies according to study design

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    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, weabstracted the year of publication, study design (cohort and

    case–control 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 meta-

    analysis or those that did not provide data for the compari-

    son 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.

    Statistical methods for meta-analysis

    The prevalence rate of placenta previa (per 1000 preg-

    nancies) 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 associated95% 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 thenumber of studies being pooled minus one. Random effect

    ORs were computed after pooling the studies. Random-

    effect analysis accounts for heterogeneity among studiesbeing 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. foreign-

    based studies) and source of data (hospital vs. population-

    based studies). The dose–response effect of maternal

    age and parity on the risk of placenta previa was also

    evaluated from each study based on the covariance-

    adjusted 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 hospital-

    based 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 dataon 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 case–control studies (3.5 per

    1000 pregnancies), 25 foreign-based studies (3.7 per 1000

    pregnancies) and five population-based studies (3.7 per

    Etiology and risk factors for placenta previa Faiz and Ananth

     J ou rn al of Maternal–Fetal and Neonatal Medicine

    Study

    score Criteria for scoring

    4

    3

    2

    1

    placenta previa confirmed at Cesarean delivery

    placenta previa confirmed by third-trimester ultrasound

    examinationplacenta 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

    Table 2   Numeric scoring of studys quality based on the method

    of diagnosis of placenta previa

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    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 studies6–14 that reported an asso-

    ciation between advancing maternal age and placenta

    previa (Figure 2). Results showed that odds ratios were

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

    USA-based studies7–10,12–14, six studies with probable

    diagnosis of placenta previa7–10,12,13, and three poorly

    designed studies6,9,14. Odds ratios ranged between 1.2 and

    2.5 for six case–control studies6–8,10,12,13 and six well-

    designed studies7,8,10–13. 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

     J ou rn al of Maternal–Fetal and Neonatal Medicine

    178

     Number of 

    pregnancies

    Placenta

    previa (per

    1000 births)

    Criteria

    for inclusion

    Criteria

    for exclusion

    Scores assigned

    Author Study years Study design Diagnosis

    Population-based case–control studies

    Kramer10

    Williams8

    Zhang16

    Taylor7

    McMahon13

    1984–871987–88

    1988–90

    1984–87

    1990

    309 320

    4.4

    singleton live birthssingleton births

    live births

    singleton live births

    singleton live births

    multiple births

    nulliparous

    55

    4

    4

    4

    12

    2

    2

    2

    Hospital-based case–control studies

    Grimes35

     Newton34

    Parson45

    Wolf 4

    Williams22

    Handler12

    Chelmow23Macones24

    Sauer30

    1975–79

    1981

    1982–85

    1980–90

    1977–80

    1988–90

    1992–941992–96

    1981–84

    28 665

    10 473

    54 969

    12 718

    55 314

    ——

    10 822

    3.4

    7.7

    3.9

    5.5

    5.9

    ——

    4.0

    > 500 g fetus

    singletons

    singletons

    births  20 weeksbirths  20 weeks

    multiple gestations

    ——

    3

    2

    2

    2

    5

    5

    33

    2

    3

    3

    1

    1

    2

    2

    41

    4

    Population-based cohort studies

    Hemminki49

    Iyasu41

    Demissie36

    1976–83

    1979–87

    1989–92

    447 963

    9.9

    4.8

    6.0

    live births

    live and stillbirths

    singleton live births

    1

    2

    4

    2

    1

    2

    Hospital-based cohort studies

     Niswander9

    Hibbard57

    Crenshaw43

    Brenner33

    Cotton54

    Barrett50

    Chervenak52

    Silver53

    D’Angelo55

    Clark14

    McShane46

     Jelsema40

    Frederiksen44

    1959–65

    1948–53

    1962–66

    1950–691962–69

    1975–78

    1972–74

    1979–80

    1978–82

    1974–80

    1979–81

    1977–83

    1975–82

    1976–97

    17 265

    102 670

    208 83731 070

    38 398

    16 029

    21 217

    97 799

    42 058

    6 576

    93 384

    6.0

    4.6

    3.76.0

    4.5

    4.3

    4.5

    3.0

    3.5

    16.8

    5.5

    singletons > 500 g

    live and stillbirths > 500 g

    —singletons

    > 500 g fetus

    > 28 weeks

    > 20 weeks

    ——

    2

    2

    12

    1

    2

    1

    1

    1

    2

    1

    1

    1

    1

    2

    22

    3

    4

    2

    4

    4

    4

    4

    4

    4

    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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    The relationship between parity and placenta previa was

    provided in 13 studies6–18

    (Figure 3). Among four cohortstudies9,11,14,15 and among ten studies with a probable

    diagnosis of placenta previa7–10,12,13,15–18 the odds ratios

    ranged between 1.1 and 2.9. Odds ratios for nine case– 

    control studies6–8,10,12,13,16–18 ranged from 0.9 to 2.3, and for

    three studies with definitediagnosis 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 studies7–10,12–14,16 and seven well-designed

    studies7,8,10–13,16, odds ratios ranged between 1.1 and 2.3.

    Prior Cesarean delivery as a risk factor for placenta

    previa was evaluated in 21 studies6,7,10,12,14,16,18–32

    (Table 6). The association was stronger among eight cohort

    studies14,19,25–29,32 (pooled OR 6.2) and for 12 foreign-based

    studies6,18–21,25–29,31,32 (pooled OR 4.8) compared with 13

    case–control studies6,7,10,12,16,18,20–24,30,31 (pooled OR 2.0)

    and nine studies7,10,12,14,16,22–24,30 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 previa6,12,14,20,23,25,28–31 (pooled

    OR 3.0) and in 17 poorly designed studies6,12,14,18–21,23–32

    (pooled OR 3.5).

    Etiology and risk factors for placenta previa Faiz and Ananth

     J ou rn al of Maternal–Fetal and Neonatal Medicine

     Number of 

    pregnancies

    Placenta

    previa (per

    1000 births)

    Criteria

    for inclusion

    Criteria

    for exclusion

    Scores assigned

    Author Study years Study design Diagnosis

    Population-based case–control studies

    Monica

    61

    1973–90 1 825 998 2.8 live and stillbirths> 28 weeks

    — 3 1

    Hospital-based case–control studies

     Neri5

    Rose20

    Gorodeski17

    Parazzini6

    Takayama30

    Abu Heija18

    1968–77

    1978–82

    1972–83

    1979–91

    1974–94

    1994–97

    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

    Ananth

    371986–93

    1980–93

    87 184

    121 082

    3.3

    3.4

    singletons

    singletons

    multiple gestations

    multiple gestations

    4

    4

    3

    3

    Hospital-based cohort studies

    Gabert60

    Dutta58

    Hill59

    Gorodeski21

    Singh27

     Nicolaides38

    MacGillivary15

     Nielsen28

     Jackobovitz42

    Leiberman48

    Chattopadhay25

    Makhseed19

    Rosen56

    Hershkowitz26

    Khashoggi47

    Love51

    Zaideh29

    Wang39

    Hendricks32

    1956–66

    1965–73

    1971–77

    1968–78

    1973–78

    1973–81

    1976–83

    1978–87

    1972–86

    1972–86

    1988–921981–92

    1991–93

    1985–92

    1988–91

    1991–93

    1995–96

    1989–98

    1993–97

    22 437

    19 888

    26 155

    12 040

    24 549

    114 470

    24 644

    26 858

    106 866

    41 206158 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

    5.45.0

    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

    21

    1

    3

    1

    1

    1

    4

    3

    2

    2

    2

    2

    1

    4

    1

    4

    1

    2

    41

    3

    2

    4

    3

    3

    2

    2

    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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    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 case–control

    studies6,13,16,18,21,30,31 that reported the association between

    previous abortions and risk of placenta previa. Previousabortion was more significantly associated with placenta

    previa in four foreign-based studies6,18,21,31 (pooledOR 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 werecase–control studies and only one study20 was foreign

    based. There was an increased risk of placenta previa with

    spontaneous abortion in three studies with definite diagno-

    sis 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 case–control studies7,10,12,22–24,34,35. With

    Etiology and risk factors for placenta previa Faiz and Ananth

     J ou rn al of Maternal–Fetal and Neonatal Medicine

    180

     Number of studies Rate of previa (derived) Number of studies Rate of previa (reported)

    Overall

    Cohort studies

    Case–control studies

    USA studies

    Foreign-based studiesPopulation-based studies

    Hospital-based studies

    44

    31

    13

    19

    255

    39

    4.0

    4.6

    3.5

    4.5

    3.73.7

    4.4

    58

    37

    21

    30

    2811

    47

    2.8 to 19.7

    3.0 to 19.7

    2.8 to 7.7

    3.0 to 16.8

    2.8 to 19.73.1 to 9.9

    2.8 to 19.7

    Table 5   Prevalence rate of placenta previa (per 1000 pregnancies) by type of study design and geographical location

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

    previafrom 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

     Figure 3   Association between parity and placenta previa from

    the 13 studies: odds ratios with 95% confidence intervals

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    Etiology and risk factors for placenta previa Faiz and Ananth

     J ou rn al of Maternal–Fetal and Neonatal Medicine

    Test of homogeneity of pooled odds ratios Random-effects

    pooled odds ratio

    (95% CI) Number of studies   c2

    Qh   Degrees of freedom  p Value

    Overall

    Cohort studies

    Case–control studiesUSA-based studies

    Foreign-based studies

    Definite previa

    Probable previa

    Well-designed studies

    Poorly designed studies

    21

    8

    139

    12

    10

    11

    4

    17

    60.3

    0.2

    11.77.1

    12.7

    27.5

    25.0

    2.2

    35.0

    20

    7

    128

    11

    9

    10

    3

    16

    < 0.001

    0.999

    0.4700.525

    0.313

    0.001

    0.009

    0.531

    0.006

    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 6   Association between prior Cesarean delivery and placenta previa

    Test of homogeneity of pooled odds ratios Random-effects

    pooled odds ratio

    (95% CI) Number of studies   c2

    Qh   Degrees of freedom  p Value

    Overall

    Cohort studies

    Case–control studies

    USA-based studies

    Foreign-based studies

    Definite previa

    Probable previa

    Well-designed studies

    Poorly designed studies

    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

    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)

    Qh, test statistic for homogeneity

    Table 7   Association between previous abortions (spontaneous or induced) and placenta previa

    Test of homogeneity of pooled odds ratios Random-effects

    pooled odds ratio

    (95% CI) Number of studies   c2

    Qh   Degrees of freedom  p Value

    OverallCohort studies

    Case–control studies

    USA-based studies

    Foreign-based studies

    Definite previa

    Probable previa

    Well-designed studies

    Poorly designed studies

    7—

    7

    6

    1

    3

    4

    4

    3

    6.6—

    6.6

    6.5

    1.2

    5.0

    5.0

    1.2

    6—

    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)

    Qh, test statistic for homogeneity

    Table 8   Association between prior spontaneous abortion and placenta previa

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    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 eightUSA-based case–control studies7,10,12,13,22–24,34. 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 studies7,10–13,22

    (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

    case–control studies in the USA12,23,24 (Table 11) also

    demonstrated a higher risk of placenta previa with cocaine

    use during pregnancy (pooled OR 2.9). There were two

    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

    case–control 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 threeforeign-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 diag-

    nosis 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 Faiz and Ananth

     J ou rn al of Maternal–Fetal and Neonatal Medicine

    182

    Test of homogeneity of pooled odds ratios Random-effects

    pooled odds ratio

    (95% CI) Number of studies   c2Qh   Degrees of freedom  p Value

    Overall

    Cohort studies

    Case–control studiesUSA-based studies

    Foreign-based studies

    Definite previa

    Probable previa

    Well-designed studies

    Poorly designed studies

    8

    88

    3

    5

    4

    4

    12.1

    12.112.1

    5.1

    5.5

    5.5

    5.1

    7

    77

    2

    4

    3

    3

    0.097

    0.0970.097

    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)

    Qh, test statistic for homogeneity

    Table 9   Association between prior induced abortion and placenta previa

    Test of homogeneity of pooled odds ratios Random-effectspooled odds ratio

    (95% CI) Number of studies   c2Qh   Degrees of freedom  p Value

    Overall

    Cohort studies

    Case–control studies

    USA-based studies

    Foreign-based studies

    Definite previa

    Probable previa

    Well-designed studies

    Poorly designed studies

    9

    1

    8

    8

    1

    3

    6

    6

    3

    26.0

    18.8

    18.8

    6.0

    5.6

    14.2

    8.1

    8

    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)

    Qh, test statistic for homogeneity

    Table 10   Association between maternal smoking and placenta previa

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    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).

    Etiology and risk factors for placenta previa Faiz and Ananth

     J ou rn al of Maternal–Fetal and Neonatal Medicine

    Test of homogeneity of pooled odds ratios Random-effects

    pooled odds ratio

    (95% CI) Number of studies   c2

    Qh   Degrees of freedom  p Value

    Overall

    Cohort studies

    Case–control studiesUSA-based studies

    Foreign-based studies

    Definite previa

    Probable previa

    Well-designed studies

    Poorly designed studies

    3

    33

    1

    2

    1

    2

    2.0

    2.02.0

    2.0

    0.0

    2

    22

    1

    1

    0.368

    0.3680.368

    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)

    Qh, test statistic for homogeneity

    Table 11   Association between maternal cocaine use and placenta previa

    Test of homogeneity of pooled odds ratios Random-effects

    pooled odds ratio(95% CI) Number of studies   c

    2Qh   Degrees of freedom  p Value

    Overall

    Cohort studies

    Case–control studies

    USA-based studies

    Foreign-based studies

    Definite previa

    Probable previa

    Well-designed studies

    Poorly designed studies

    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)

    Qh, test statistic for homogeneity

    Table 12   Association between sex of the fetus and placenta previa

    Test of homogeneity of pooled odds ratios Random-effects

    pooled odds ratio

    (95% CI) Number of studies   c2

    Qh   Degrees of freedom  p Value

    Overall

    Cohort studies

    Case–control studies

    USA-based studies

    Foreign-based studies

    Definite previa

    Probable previa

    Well-designed studies

    Poorly designed studies

    3

    2

    1

    2

    1

    2

    1

    1

    2

    2.4

    0.4

    2.3

    2.0

    2.2

    2

    1

    1

    1

    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)

    Qh, test statistic for homogeneity

    Table 13   Association between chronic hypertension and placenta previa

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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 studies37–39 (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

    case–control 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).

    DISCUSSION

    Placenta previa is an obstetric condition that leads to

    serious maternal and fetal complications. This condition

    has been reported to occur in 3–20 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 epi-demiological 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 

    Etiology and risk factors for placenta previa Faiz and Ananth

     J ou rn al of Maternal–Fetal and Neonatal Medicine

    184

    Test of homogeneity of pooled odds ratios Random-effects

    pooled odds ratio

    (95% CI) Number of studies   c2Qh   Degrees of freedom  p Value

    Overall

    Cohort studies

    Case–control studies

    USA-based studies

    Foreign-based studies

    Definite previa

    Probable previaWell-designed studies

    Poorly designed studies

    3

    3

    3

    2

    13

    4.8

    4.8

    4.8

    4.7

    —4.8

    2

    2

    2

    1

    —2

    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)

    Qh, test statistic for homogeneity

    Table 14   Association between pregnancy-induced hypertension and placenta previa

    Test of homogeneity of pooled odds ratios Random-effects

    pooled odds ratio

    (95% CI) Number of studies   c2Qh   Degrees of freedom  p Value

    Overall

    Cohort studies

    Case–control studies

    USA-based studies

    Foreign-based studies

    Definite previa

    Probable previa

    Well-designed studies

    Poorly designed studies

    3

    2

    1

    3

    2

    1

    3

    4.0

    4.0

    4.0

    2.0

    4.0

    2

    1

    2

    1

    2

    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)

    Qh, test statistic for homogeneity

    Table 15   Association between pre-eclampsia and placenta previa. Reprinted from reference 103, Ó  2003, with permission of Elsevier Science

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    placentae from older women that have revealed utero-

    placental 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 priorplacental 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 andgravidity 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 (1989–98)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 andprevious abortion. Our meta-analysis corroborates these

    general findings reported in several previous studies as well

    as a meta-analysis104. Damage and scarring to the endo-

    metrial and myometrial lining during Cesarean delivery

    and spontaneous and induced abortion are known to pre-

    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

    . Ithas 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 themenstrual 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 insemi-

    nation, 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 isnot 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

    Etiology and risk factors for placenta previa Faiz and Ananth

     J ou rn al of Maternal–Fetal and Neonatal Medicine

    Gravidity (number of pregnancies)

    Maternal age (years) 1 2 3 4    5

    < 20

    20–24

    25–29

    30–34

    35–39

     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)

    2.99 (2.79, 3.22)

    4.31 (4.04, 4.61)

    6.02 (5.65, 6.43)

    8.38 (7.82, 8.98)

    11.96 (10.80, 13.24)

    2.87 (2.28, 3.60)

    3.66 (3.37, 3.98)

    4.99 (4.65, 5.36)

    6.52 (6.08, 6.98)

    9.24 (8.59, 9.94)

    12.16 (10.90, 13.57)

    3.00 (2.05, 4.37)

    4.66 (4.26, 5.08)

    6.22 (5.80, 6.67)

    7.82 (7.31, 8.35)

    10.01 (9.35, 10.72)

    12.62 (11.59, 13.74)

    Table reprinted from reference 103, Ó 2003, with permission of Elsevier ScienceRelative 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

    Table 16   Jointeffectsof maternal age and gravidityon the risk of placenta previa:adjustedrelativerisks with 95% confidence intervals

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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 pregnancy-

    induced hypertension and pre-eclampsia. A better blood

    supply and oxygenation of the placenta in the lower uterine

    segment prevents the release of vasoactive substancesinto 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 like-lihood 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 hyper-

    tension. 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

    strength of association of all the risk factors with placenta

    previa and directionality of association with population-

    attributable 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 wouldpotentially be preventable. As cigarette smoking is pre-

    ventable, 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

    Etiology and risk factors for placenta previa Faiz and Ananth

     J ou rn al of Maternal–Fetal and Neonatal Medicine

    186

    AssociationsPopulation-attributable risk

    (%)Risk factors for placenta previa Strength Directionality

    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

    +++

    +++

    +

    +

    +

    ++

    +

    +

    +++

    +

    +

    ++

    +

    -

    ¯

    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

    Table 17   Strength and direction of association between various risk factors and conditions associated with placenta previa

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    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 mater-nal 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 placentalposition 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 wasa Primary Care/Health Services research fellow in the

    Department of Family Medicine, UMDNJ, and was

    supported through an NRSA Fellowship award (T32PE-

    10011) from the Health Resources and Services Adminis-

    tration. 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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