Elsevier Editorial System(tm) for Best

Practice & Research Clinical Obstetrics & Gynecology

Manuscript Draft

Manuscript Number: YBEOG-D-20-963

Title: A comparison of recent guidelines in the diagnostic and management

of placenta accreta spectrum disorders

Article Type: Issue on PASD (GE_EC)

Corresponding Author: Professor Eric Jauniaux, MD, PhD, FRCOG

Corresponding Author's Institution: Royal Free and University College

London

First Author: Eric Jauniaux, MD, PhD, FRCOG

Order of Authors: Eric Jauniaux, MD, PhD, FRCOG; John Kingdom

Cover Letter

London 29th May 2020

The Editor
BP&R in Clin Ob Gyn

Dear Edwin,

Please find enclosed our manuscript entitled “A comparison of recent guidelines in the
diagnostic and management of placenta accreta spectrum disorders” and the
corresponding MCQs.

The final version has been approved by all authors who have equally contributed to the
development of this project and have no conflict of interest to declare.

The length of the manuscript including the main text, references and the 2 tables is around 7000
words as required.

Very best regards

Eric Jauniaux

Institute for Women’s Health,

University College London
86-96 Chenies Mews London WC1E 6HX
Tel: +44 (0)20 7679 6651 Fax: +44 (0)20 7383 7429
www.instituteforwomenshealth.ucl.ac.uk
*Highlights (for review)

Highlights:
*Manuscript
Click here to view linked References

1
2
A comparison of recent guidelines in
3
4 the diagnostic and management of
5
6
7
placenta accreta spectrum disorders
8
9
10 Eric Jauniaux1, John Kingdom2, Robert M. Silver3,
11
12
13
14
1
15 EGA Institute for Women’s Health, Faculty of Population Health Sciences,
16 University College London (UCL), London, UK.
17 2
Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of
18
19 Toronto, Toronto, ON, Canada.
3
20 Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of
21 Toronto, Toronto, ON, Canada
22
23
24
25 The authors report no conflict of interest.
26
27
28 The views expressed in this document reflect the opinion of the individuals and not
29
30 necessarily those of the institutions that they represent.
31
32
33 Word count Text & references: 6444
34
35
36
37 Corresponding author: Professor Eric Jauniaux,
38 EGA Institute for Women’s Health, University College London,
39 86-96 Chenies Mews, London WC1E 6HX, UK.
40
41 Telephone numbers: +44/207/3908113
42 Fax: +44/207/3908115
43 E-mail: [email protected]
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59 ABSTRACT (max 150 words)
60
61
62
63
64
1
65
 1 Accreta placentation and in particular its invasive forms are impacting maternal
2
3
4 health outcomes globally and the prevalence of placenta accreta spectrum (PAS)
5
6 continues to increase. The Royal College of Obstetricians and Gynaecologists
7
8
9
(RCOG) and the American College of Obstetricians and Gynecologists (ACOG) with
10
11 the Society for Maternal-Fetal Medicine (SMFM) have updated their national
12
13 guidelines whereas the Federation International of Gynecology and Obstetrics
14
15
16 (FIGO) and the Society of Obstetricians and Gynecologists of Canada (SOGC) have
17
18 developed new guidelines on the diagnosis and management PAS. A comparison of
19
20
21 these guidelines highlights common strong recommendations on the need to
22
23 carefully evaluate women at high-risk for PAS (e.g. prior uterine surgery presenting
24
25
26 with anterior low-lying placenta or placenta previa), using multi-modal ultrasound
27
28 imaging. For women diagnosed with PAS, multidisciplinary team-based care, with full
29
30
logistic support structures (immediate access to comprehensive blood products,
31
32
33 adult and neonatal intensive care) and established expertise in complex pelvic
34
35 surgery, is critical to maximize safe outcomes for mother and newborn.
36
37
38
39
40
41
42
43
44
45 Key Words: Placenta accreta; increta; percreta; prenatal diagnosis, risk factors,
46
47 conservative management, surgical management, guidelines.
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
2
65
 BACKGROUND
1
2
3
4 A. Historical perspective
5
6 The first fully documented cases of birth complicated by accreta placentation were
7
8
9
published almost one hundred years ago [1-4]. In 1937, Irving and Hertig published a
10
11 cohort of 18 cases with similar clinical and pathological observations, characterized
12
13 by abnormal mechanical adherence of the placenta to the underlying uterine wall,
14
15
16 associated with severe post-partum hemorrhage (PPH), and requiring a
17
18 hysterectomy in a majority of 15 cases [5]. Histologic observations noted partial or
19
20
21 complete absence of the decidual layer which is normally present between the
22
23 anchoring placental villi and the superficial myometrium. Although this series did not
24
25
26 include a single case of placental tissue invading beyond the uterine wall, these
27
28 seminal observations by Irving and Hertig remain in use today as key criteria for the
29
30
diagnosis of both adherent and invasive placentation. However, they are often
31
32
33 applied to describe the retained placenta as also being pathologically-adherent to the
34
35 uterine wall [6-10]. This trend has subsequently led to increasing, and highly
36
37
38 variable, reported rates in the overall prevalence of placenta accreta, ranging
39
40 between 0.01% and 1% of livebirths [11,12].
41
42
43 Lukes et al. [13], in 1966 were the first group to propose a detailed histologic
44
45 classification for placenta accreta based on the depth of the villous penetration of the
46
47
48
myometrium; starting with placenta adherenta or creta (PC) when the villi adhere
49
50 directly to the myometrium without a decidual interface. Further invasion was defined
51
52 as placenta increta (PI) when the villi invade into the myometrium. Finally, placenta
53
54
55 percreta (PP) occurs when the villi invade the full thickness of the uterine wall either
56
57 to the serosa or beyond to involve extra-uterine structures, such as the bladder.
58
59
60 They also observed that penetration of the myometrium by placental villi is rarely a
61
62
63
64
3
65
 uniform process, such that areas of normal villi attached to decidua, adherent villi
1
2 attached to myometrium, and invasive villi deeper within the myometrium, may all co-
3
4
5 exist within the same specimen. To address this constellation of variable findings, a
6
7 majority of experts use the term “placenta accreta spectrum” (PAS). This term
8
9
10 includes all grades of abnormal placentation and is used as the basis for the
11
12 development of a new clinical classification proposed by the Federation International
13
14
15 of Gynecology and Obstetrics (FIGO) [14].
16
17 Many clinicians and the World Health Organization (WHO) international
18
19
20
classification of diseases (www.who.int/classifications/icd) continue to use the 1937
21
22 Irving and Hertig definition for placenta accreta and therefore make no distinction
23
24 between different grades of PAS. Only 10% of studies on the prenatal diagnosis of
25
26
27 PAS and placenta previa accreta provide detailed histopathology data on the
28
29 different grades of PAS, and the corresponding distribution varies widely (Table 1).
30
31
32 In addition, many authors and the WHO are adding to the confusion by using a 19th
33
34 century “morbidly adherent placenta” terminology which refers only to abnormally
35
36
37
adherent PAS. This has led to many authors to over-diagnose the incidence of PAS
38
39 by including cases which present as complete or partial placental retention, or with
40
41 excessive bleeding from the placental bed at Cesarean delivery [6,8,10].
42
43
44 Furthermore, in women delivered by repeat Cesarean, there may be a tendency to
45
46 over-diagnose PAS in circumstances where the low-lying anterior placenta is visible
47
48
49 through the old thin scar region due to lower-segment dehiscence. This scar may
50
51 expand during pregnancy to create a large uterine “window” through which a portion
52
53
54 of the placenta is visible - without any villous tissue truly invading the serosa and/or
55
56 the surrounding myometrium [15].
57
58
59
60
61
62
63
64
4
65
 A new standardised classification and reporting guidelines for the pathology
1
2 diagnosis of PAS has also been recently proposed by an expert panel [16]. This new
3
4
5 classification, together with the 2016 standardized ultrasound and MRI descriptions
6
7 and proforma reporting for suspected antenatally with placenta accreta, [17-19] have
8
9
10 been established with the intent of improving the overall quality of epidemiologic data
11
12 on PAS incidence. This system also may improve management outcome data, by
13
14
15 allowing stratification using the standardized different grades of PAS.
16
17
18
19
20
B. Epidemiology
21
22 Until the 1950s, the predisposing factors for PAS in subsequent pregnancies were
23
24 manual removal of the placenta, endometritis and/or “vigorous” uterine curettage
25
26
27 during a prior delivery [5]. Today, over 95% of women diagnosed prenatally with PAS
28
29 present with a low-lying/placenta previa and a surgical history of at least one prior
30
31
32 uterine surgery, most commonly Cesarean delivery (CD) [20-22]. The rapid increase
33
34 in CD rates around the world, together with a greater prevalence of prior gynecologic
35
36
37
surgery (myomectomy, uterine adhesiolysis, septal resection), means that up to 6%
38
39 of the pregnant population have the combination of a low-lying anterior placenta and
40
41 prior uterine surgery, at their 12-week nuchal translucency ultrasound examination
42
43
44 (Panaitova et al., USOG 2018). Advanced reproductive age at conception and use
45
46 of in-vitro fertilization methods have also contributed to the increased incidence of
47
48
49 placenta previa. For example, there is strong epidemiologic evidence that the
50
51 incidence of placenta previa accreta increases with the number of prior CDs (22-24).
52
53
54 The ratio of adherent/invasive accreta placentas has changed from 7/3 in the 1970s
55
56 to 5/5 in the last two decades [22], a change that is directly linked to the increase in
57
58
the number of grand multiparas with multiple CD scars undertaking further
59
60
61
62
63
64
5
65
 pregnancies [25,26]. Pregnancy following multiple CDs is also a major risk factor for
1
2 large cesarean scar defects (CSD), and for the development of cesarean scar
3
4
5 pregnancies (CSP) in the cervico-isthmic niche created by focal myometrial loss at
6
7 the site of prior CDs [27]. The diagnosis of CSP in the first trimester is increasingly
8
9
10 common, such that the natural history of evolution to PAS has now been clearly
11
12 established, especially for type-2 CSP. Since CSPs may lead to early uterine rupture
13
14
15 and emergency hysterectomy [28], or more increasingly, be managed immediately
16
17 by medical, or laparoscopic surgery methods (PMID 28601471), their diagnosis and
18
19
20
management will further alter the epidemiology of PAS at birth.
21
22 PAS is not exclusively a consequence of CD and has been reported in
23
24 primiparous women with a history of operative hysteroscopy, suction curettage,
25
26
27 surgical termination, endometrial ablation, uterine pathology such as bicornuate
28
29 uterus, adhesiolysis for Asherman’s syndrome, adenomyosis, endometrial resection,
30
31
32 polyvinyl bead embolization of fibroids, and myotonic dystrophy [22,25,29]. In fact,
33
34 any procedure causing surgical or substantial and chronic damage to the integrity of
35
36
37
the uterine wall, especially if the endometrium fails to re-epithelize in an area of scar
38
39 formation, has been associated with PAS [25,26]. Accreta placentation can occur
40
41 after myomectomy but the risk is low [30] unless the uterine cavity is entered,
42
43
44 because the endoscopic removal of intramural or sub-serous fibroids does not
45
46 involve the uterine cavity [31]. Though the removal of fibroids in the upper part of the
47
48
49 uterus is less likely to lead to uterine dehiscence [32], focal PAS may still occur.
50
51 Undoubtedly PAS has increased as a consequence of modern obstetric and
52
53
54 reproductive medical practices, and has been accentuated by decisions to delay
55
56 childbearing, the need for subsequent reproductive assistance and the prevalence of
57
58
prior gynecologic surgery [25].
59
60
61
62
63
64
6
65
 1
2 C. The “World No 1” surgical procedure effect
3
4
5 Safe Caesarean delivery (CD) is an essential component of a secure, functioning
6
7 and comprehensive maternity system, and is now the most commonly performed
8
9
10 major operation around the world, with more than 1 million procedures performed
11
12 each year in the USA alone [33]. In 1985, a group of experts advising the WHO
13
14
15 highlighted an unjustified and remarkable increase in CD rates worldwide in the prior
16
17 decade [34]. They stated there was no justification for any country or region to have
18
19
20
a caesarean section rate higher than 10–15%. This recommendation has had little
21
22 impact on the rates of CD in most countries of the world, which have continued to
23
24 rise over the following four decades [35]. In 2011, Solheim et al., published a
25
26
27 decision-analytic model using data on national birthing order trends after CD rates in
28
29 the U.S. between 1995 and 2005. They estimated that if the number of primary and
30
31
32 secondary CDs continue to rise, by 2020 the CD rate will be 56.2%, and that as a
33
34 consequence there will be an additional 6236 placenta praevias, 4504 PAS, and 130
35
36
37
maternal deaths annually [36]. The CD rates have not risen to this level in the U.S.
38
39 but have risen above 40% over the past decade in many middle-income countries
40
41 around the world with mixed public-private health care systems, such as Brazil,
42
43
44 Turkey, Italy, Egypt, Argentina, Iran, South Korea and Mexico. Solheim et al.,
45
46 calculated that the rise in CD-associated complications will lag behind the rise in
47
48
49 CDs by around 6 years [36]. These data highlight the need for local health providers
50
51 to become prepared for a significant rise in the numbers of pregnancies complicated
52
53
54 by placenta previa accreta. In particular, in middle-income countries with high-birth
55
56 rates such as Turkey and Egypt, where more than half of all births are via CD, the
57
58
59
60
61
62
63
64
7
65
 prevalence and negative impacts of PAS have now outweighed the benefits of
1
2 improved access to quality obstetric care at the population-based level.
3
4
5 The 2017 report from the UK and Ireland Confidential Enquiries into Maternal
6
7 Deaths indicated that although there was no significant change in the maternal death
8
9
10 rate in the UK between 2010–12 and 2013–15, an increase in the number of deaths
11
12 associated with PAS was observed [37]. Not surprisingly, as PAS has become a
13
14
15 new risk factor for major obstetric complications, there has been an exponential
16
17 increase in the number of articles published in the medical literature over the last
18
19
20
decade. In an editorial for the special issue of the International Journal in
21
22 Gynecology and Obstetrics we reported that a PubMed
23
24 (www.ncbi.nlm.nih.gov/pubmed) search of the term “placenta accreta” up to 1st of
25
26
27 December 2017 generated 2296 hits [20]. Through the 1st of May 2020, there have
28
29 been another 569 new articles published. Each year since 2010, more publications
30
31
32 on placenta accreta have occurred than during the entire period between 1947-1962.
33
34 These new data have stimulated the development of new national and international
35
36
37
guidelines and the updating of previous guidelines. These guidelines have extracted,
38
39 analyzed and summarized recent quality evidence-based data on diagnosis and
40
41 management of PAS. They are therefore essential to inform local and international
42
43
44 policies and health provision for the development of maternity centres with specialist
45
46 surgeons, equipment, drugs, blood bank and intensive care infrastructure to safely
47
48
49 manage the new epidemy of women presenting with PAS.
50
51
52
53
54 CLINICAL GUIDELINES FOR DIAGNOSIS AND MAGEMENT OF PAS
55
56
57 A. New and updated guidelines
58
59
60
61
62
63
64
8
65
 There are currently two recently updated and two new guidelines on the diagnosis
1
2 and management of PAS available in the recent international medical literature:
3
4
5 - The 2018 Royal College of Obstetricians and Gynaecologists (RCOG) Green-
6
7 top Guideline No. 27a which includes both placenta praevia and placenta
8
9
10 accreta and has replaced the 2011 edition of the guidelines Placenta Praevia,
11
12 Placenta Praevia Accreta and Vasa Praevia: Diagnosis and Management.
13
14
15 This is the 4th edition of this guidelines and the first to be published in the
16
17 British Journal of Obstetrics and Gynaecology [38]. The first edition, published
18
19
20
in 2001, was entitled Placenta Praevia: Diagnosis and thus did not include
21
22 placenta accreta.
23
24 - The 2018 American College of Obstetricians and Gynecologists (ACOG)
25
26
27 obstetric care consensus was developed jointly with the Society for Maternal-
28
29 Fetal Medicine (SMFM) and endorsed by the Society of Gynecologic
30
31
32 Oncology (SGO) and replaced the Committee Opinion No. 529, of July 2012
33
34 and SMFM Clinical Guideline of November 2010. These guidelines were
35
36
37
published simultaneously in Obstetrics and Gynecology [39], the official
38
39 journal of ACOG and the American Journal of Obstetrics and Gynecology
40
41 (40).
42
43
44 - The 2018 FIGO consensus guidelines on placenta accreta spectrum disorders
45
46 were developed by the Safe Motherhood and Newborn Health Committee
47
48
49 [41]. The guidelines are presented in four separated expert reviews:
50
51 Epidemiology [22], prenatal diagnosis and screening [42], non-conservative
52
53
54 surgical management [43] and conservative management [44] and were
55
56 published simultaneously on the FIGO website and a special issue of the
57
58
59
60
61
62
63
64
9
65
 International Journal of Gynaecology and Obstetrics, the official journal of the
1
2 FIGO.
3
4
5 - The 2019 Society of Obstetricians and Gynecologists of Canada (SOGC) No.
6
7 383-screening, diagnosis, and management of placenta accreta spectrum
8
9
10 disorders [45] which was published simultaneously in English and French in
11
12 the Journal of Obstetrics and Gynaecology of Canada, the official journal of
13
14
15 the SOGC.
16
17
18
19
20
B. Development process
21
22 - The RCOG guidelines are developed by stakeholders representing heath care
23
24 in the UK from the best research evidence. They are recommendations for
25
26
27 good practice that are not meant to dictate care, but rather to support
28
29 healthcare professionals in their work; some recommendations may not be
30
31
32 transferable to non-UK settings. The guideline authors included a lead
33
34 developer and a team of local and international multidisciplinary group of
35
36
37
experts who assessed the evidence gathered in a systematic matter. The
38
39 authors evaluated the methodology of each study and graded the evidence
40
41 from level 1 to level 4 depending on its individual value for the guidelines. The
42
43
44 guideline authors drew up recommendations for each point, which are graded
45
46 A, B, C and “good practice” according to the strength of the evidence that
47
48
49 supports them (Table 2). The draft guideline document then went through a
50
51 process of consultation and peer-review and the final version was approved
52
53
54 by the Guidelines Committee and the RCOG Clinical Quality Board. In
55
56 addition to the guidelines, the RCOG produced an information leaflet for the
57
58
public.
59
60
61
62
63
64
10
65
 1 - The ACOG and SMFM guidelines are developed in a fashion quite similar to
2
3
4 the RCOG document. They are also considered recommendations or
5
6 guidelines, with the recognition that not all clinicians and settings have
7
8
9
equivalent resources. The guideline authors included a lead developer and a
10
11 national team of maternal-fetal-medicine based experts with representation
12
13 from both societies. The authors were provided a compilation of available
14
15
16 studies and data that were gathered in a systematic matter. The authors
17
18 evaluated the methodology of each study and used them to make
19
20
21 recommendations. Recommendations were given as strong (1), weak (2), or
22
23 best practices (in the absence of evidence). In addition, the quality of
24
25
26 evidence was graded as A (high), B (moderate) and C (low) (Table 3). The
27
28 draft guideline document then went through a process of consultation and
29
30
peer-review and the final version was approved by the ACOG Obstetric
31
32
33 Guidelines Committee and the SMFM publications committee.
34
35
36
37
38 - The FIGO guidelines: were developed as expert evidence-based opinions
39
40 with the aim of helping clinicians, policymakers, and patients to make well-
41
42
43 considered decisions about health care for a particular condition. The
44
45 guidelines were intended to be transferable to an international setting and
46
47
48
were therefore based on consensus from a group of international specialists
49
50 who were individually proposed for their expertise by their national
51
52 professional societies of obstetricians and gynaecologists. The guidelines
53
54
55 provided clear, well-reasoned information such that decision makers can use
56
57 them effectively both nationally and globally. The quality of evidence was
58
59
60 graded as high, medium or low according to the methodology of the studies
61
62
63
64
11
65
 reviewed. The guideline authors drew up recommendations which were
1
2 graded as strong or weak and combined these into a table with the quality of
3
4
5 evidence. The final version was approved by the FIGO Safe Motherhood and
6
7 Newborn Health Committee.
8
9
10
11
12 - The SOGC guidelines: were developed by the multidisciplinary team
13
14
15 members based at the largest site providing care for women with PAS in
16
17 Canada with prior approval by the national society SOGC. The final guideline
18
19
20
was approved by both the maternal-fetal medicine and the diagnostic imaging
21
22 guideline committees using the established evidence-based grading systems
23
24 used for all SOGC national clinical practice guidelines. Broad consensus was
25
26
27 achieved across Canada as reflected by the final author listing. Members from
28
29 this guideline also contributed to the FIGO guidelines.
30
31
32
33
34
35
36
37
COMPARISON OF THE RCOG, ACOG/SMFM, FIGO AND SOCG GUIDELINES
38
39
40 The classification of evidence levels and recommendations provided by the different
41
42
43 guidelines is directly linked to the quality of the data available in studies published at
44
45 the time of the development of the corresponding guidelines. The recommendations
46
47
48
therefore changed to some extent with time, as is illustrated by the RCOG and
49
50 ACOG/SMFM guidelines, which are now in their 3rd editions. In the case of PAS,
51
52 most of the cohort studies published before 2015 are retrospective and thus lack the
53
54
55 more accurate modern clinical descriptions and detailed histopathologic
56
57 examinations required to confirm the diagnosis of the different grades of PAS, and
58
59
60 therefore their specific management recommendations. Recent systematic reviews
61
62
63
64
12
65
 and meta-analyses on the overall prevalence of PAS and the incidence of placenta
1
2 previa accreta show large amounts of heterogeneity between population studies for
3
4
5 the prevalence, incidence and distribution of the different grades PAS, as well as
6
7 rates of peripartum hysterectomy, haemorrhage requiring transfusions and maternal
8
9
10 mortality. These wide variations between studies are due to inconsistency with
11
12 regards to the criteria used to diagnose and confirm the nature of PAS at birth
13
14
15 [12,21]. Surprisingly there is also high heterogeneity in qualitative and diagnostic
16
17 data on the ultrasound criteria used in cohort studies, reporting on placenta previa
18
19
20
accreta, for the much simpler ultrasound diagnosis of placenta previa and the
21
22 gestational at confirmation of the diagnosis [21].
23
24
25
26
27 A. On prenatal diagnosis
28
29 A 2017-2018 international survey of practices used in the diagnosis and
30
31
32 management of PAS disorders found that 92% of respondents indicated that their
33
34 department routinely performs prenatal screening of women identified as being at
35
36
37
high risk of PAS disorder [46]. Of those, a similar % reported that such screening
38
39 was prompted by a prior history of uterine surgery and/or cesarean delivery plus a
40
41 low-lying placenta or placenta previa at mid-pregnancy using grey-scale
42
43
44 transabdominal ultrasonography. The most common additional method of diagnosis
45
46 among women with a high suspicion for PAS disorders was transvaginal sonography
47
48
49 (TVS) and over 61% use both ultrasonography and magnetic resonance imaging
50
51 (MRI).
52
53
54 All the guidelines agree that:
55
56  Antenatal diagnosis of PAS is crucial in planning its management and has
57
58
been shown to reduce maternal morbidity and mortality.
59
60
61
62
63
64
13
65
  Ultrasonography is a relatively inexpensive and widely available imaging
1
2 modality and therefore should be the first line for the diagnosis of PAS.
3
4
5  Previous CD and the presence of an anterior low-lying/placenta praevia
6
7 should alert the antenatal care team of the higher risk of PAS.
8
9
10  MRI is not essential for making a prenatal diagnosis of suspected PAS and is
11
12 therefore not the preferred primary imaging modality for the initial evaluation
13
14
15 of women at risk of PAS.
16
17 The RCOG guidelines identify ultrasound imaging as highly accurate (> 95%) when
18
19
20
performed by a skilled operator with experience in diagnosing PAS (Grade C) and
21
22 the ACOG/SMFM highlights that although ultrasound evaluation is important, the
23
24 absence of ultrasound findings does not preclude a diagnosis of PAS and that
25
26
27 clinical risk factors remain equally important as predictors of PAS by ultrasound
28
29 findings (Grade 1A). In addition, the SOGC states that the effectiveness of
30
31
32 ultrasound in the context of PAS depends upon awareness of clinical risk factors,
33
34 imaging quality, operator experience, gestational age, imaging modalities, and
35
36
37
adequate bladder filling. The FIGO strongly recommends that the ultrasound signs of
38
39 PAS should be described using standardised protocols. On the basis of at least one
40
41 systematic review and meta-analysis, the RCOG guidelines recommend referral of
42
43
44 women with any ultrasound features suggestive of PAS to a specialist unit with
45
46 imaging expertise (Grade B). The ACOG/SMFM suggest performance of ultrasound
47
48
49 examinations at approximately 18-20, 28-30, and 32-34 weeks of gestation
50
51 in asymptomatic patients. The RCOG indicates that TVS has an important role in
52
53
54 the early diagnosis, follow-up, differential diagnosis between adherent and invasive
55
56 accreta placentation and overall management of PAS [Evidence level 4].
57
58
For the RCOG, FIGO and SOGC, MRI may be useful in evaluating the pelvic
59
60
61
62
63
64
14
65
 extension of a placenta percreta or areas difficult to evaluate on ultrasound, though
1
2 its effectiveness is currently limited by the relative contraindication to the use of a
3
4
5 gadolinium contrast enhancing agent. For ACOG it is unclear whether MRI improves
6
7 diagnosis of PAS beyond that achieved with ultrasonography alone. On the basis of
8
9
10 two systematic reviews and meta-analyses, the RCOG concluded that the diagnostic
11
12 value of ultrasound imaging and MRI in detecting PAS is similar (Grade C).
13
14
15 Furthermore, the focus and experience of the supervising/reporting radiologist
16
17 remains an important and less well-studied factor in the diagnostic accuracy of MRI,
18
19
20
since access to expert radiologists with a special interest in pregnancy is highly
21
22 variable between centers.
23
24
25
26
27 B. On preparing for delivery
28
29 A recent anonymous survey of the 154 obstetrical services in NHS England found
30
31
32 that of the 114 that responded, 70% manage their PAS cases "in-house", despite
33
34 one third of these units reporting that they manage on average only one case per
35
36
37
year [47]. The 23 units that describe themselves as “specialist centres” managed a
38
39 median of four cases per year. There is mounting evidence from before and after the
40
41 publications of the new guidelines that women with PAS diagnosed prenatally and
42
43
44 managed by a multidisciplinary team (MDT) in a centre of excellence (CoE) are less
45
46 likely to require emergency surgery, large-volume blood transfusion and reoperation
47
48
49 within 7 days of delivery for bleeding complications compared with women managed
50
51 by standard obstetric care without a specific protocol [48]. Although, there is no
52
53
54 evidence for an ideal minimal number of cases of PAS managed per month or year,
55
56 maternal outcomes are improved over time with increasing experience within a well-
57
58
established MDT performing 2–3 cases per month [49,50].
59
60
61
62
63
64
15
65
 There are also wide variations between healthcare providers within the U.S.
1
2 [51,52] and between different countries [46,53] in the preparation for the surgical
3
4
5 procedure such as the use of cystoscopy and placement of ureteral stents, the
6
7 involvement of different surgical specialities in the operating team, the choice of
8
9
10 anaesthesia technique and the use of additional techniques such as interventional
11
12 radiology (IR) pre-operative placement of an arterial balloon either in the lower aorta,
13
14
15 common iliac or anterior divisions of the internal iliac arteries.
16
17
18
19
20
All the guidelines recommend that:
21
22  Patients diagnosed with PAS should be cared for by a MDT with expertise in
23
24 complex pelvic surgery in a specialist centre with logistic support for
25
26
27 immediate access to blood products, adult and neonatal intensive care.
28
29  Preoperative coordination with protocol-based interdisciplinary care including
30
31
32 anesthesiology, hematology/blood bank, maternal-fetal medicine,
33
34 neonatology, and expert pelvic surgeons to optimize intraoperative and post-
35
36
37
operative outcomes.
38
39  Preoperative counselling should include review of planned and possible
40
41 alternate surgical strategies and complications and that a contingency plan for
42
43
44 emergency delivery should be developed, including the use of an institutional
45
46 protocol for the management of maternal haemorrhage.
47
48
49
50
51 All the guidelines agree that:
52
53
54  Use of antenatal corticosteroids for lung maturation by 32-34 weeks is
55
56 appropriate in women with antenatally diagnosed PAS and with current
57
58
59
60
61
62
63
64
16
65
 national and international gestational age-based recommendations for
1
2 anticipated delivery before term.
3
4
5  No amniocentesis is necessary because data regarding pulmonary maturity
6
7 do not change clinical recommendations for emergency delivery before 36
8
9
10 weeks.
11
12  There are currently insufficient data to recommend the routine use of
13
14
15 cystoscopic assessment of the bladder and placement of ureteric stents but
16
17 collaboration with a urologic surgeon is advisable in cases with suspected
18
19
20
bladder wall involvement.
21
22  Optimizing hemoglobin values during pregnancy is important and when iron
23
24 deficiency is noted oral replacement or intravenous infusions should be
25
26
27 implemented and when available intraoperative cell salvage may be utilized or
28
29 be on “stand-by”.
30
31
32  Timing of delivery decisions need to balance maternal risks and benefits with
33
34 those of the fetus or neonate.
35
36
37
38 The guidelines give different opinions for the optimal timing for delivery. For the
39
40 ACOG/SMFM between 34+0 and 35+6 weeks of gestation is the recommended
41
42
43 gestational age for scheduled cesarean delivery or hysterectomy absent extenuating
44
45 circumstances in a stable patient (1A) whereas for the RCOG, in the absence of risk
46
47
48
factors for preterm delivery and/or bleeding from a placenta previa, indicate that
49
50 planned delivery at 35+0-36+6 weeks of gestation provides the best balance between
51
52 fetal maturity and the risk of unscheduled delivery [GPP]. The SOGC recommends
53
54
55 that for otherwise healthy women with no history of vaginal bleeding, the optimal
56
57 timing of elective CD is around 34−36 weeks of gestation (II-3B). FIGO guidelines
58
59
60 are based on consensus from expert from high-, medium- and low-resources
61
62
63
64
17
65
 countries. Low resource countries, in particular in Africa have often limited or no
1
2 access to blood products and ICU and thus the FIGO does not formally recommend
3
4
5 a preferred time for delivery as for low resources countries moving the delivery date
6
7 as close as possible to 37 weeks has a direct impact in reducing poor neonatal
8
9
10 outcome.
11
12 A survey of 26 Israeli hospital maternities reported that general anesthesia was
13
14
15 used almost exclusively among women with high suspicion for PAS disorders [53].
16
17 The international survey of FIGO experts found that spinal–epidural anesthesia was
18
19
20
used by 44% of the respondents [46]. The RCOG recommends that the choice of
21
22 anaesthesia technique should be should be made by the anaesthetist conducting the
23
24 procedure in consultation with the patient in advance [GPP] whereas for the SOGC,
25
26
27 regional epidural anaesthesia is considered safer than general anaesthesia in most
28
29 instances, is associated with reduced blood loss, is preferred by patients and their
30
31
32 partners and affords a 24-hour window of effective post-operative pain relief (II-2A).
33
34 The RCOG also recommend that the patient should be informed that the surgical
35
36
37
procedure can be performed safely with regional anaesthesia but should be advised
38
39 that it may be necessary to convert to general anaesthesia if required and asked to
40
41 consent [D]. The ACOG/SMFM does not comment on this issue and the FIGO
42
43
44 guidelines highlight that there is insufficient evidence to support the use of one
45
46 technique over the other.
47
48
49
50
51 C. On management
52
53
54 Overall four management approaches have been described alone or in combination
55
56 with additional procedures mainly iliac or uterine artery devascularisation techniques,
57
58
either surgical or using interventional radiology (IR).
59
60
61
62
63
64
18
65
 The radical techniques are:
1
2 - Primary hysterectomy (PH) following immediately the delivery of the infant,
3
4
5 without attempting placental separation.
6
7 - Delayed or secondary hysterectomy between 3 days and 12 weeks after
8
9
10 delivery of the infant, leaving the placenta in situ, with repair of the
11
12 hysterotomy incision.
13
14
15 The conservative techniques are:
16
17 - Leaving partially or totally the placenta in situ after delivery of the infant,
18
19
20
avoiding the placenta, with repair of the hysterotomy incision (expectant
21
22 management).
23
24 - Partial myometrial resection (partial excision of the accreta area) following the
25
26
27 delivery of the infant, and without disturbing the placenta, followed by repair of
28
29 the uterus.
30
31
32 Planned preterm caesarean hysterectomy with the placenta left in situ has been
33
34 the recommended management strategy for PAS by both RCOG and ACOG/SMFM
35
36
37
in the previous version of their guidelines. Not surprisingly, surveys of healthcare
38
39 providers in the U.S. published in 2012 [51] and 2013 [52] found that most ACOG
40
41 fellows SMFM members proceeded with hysterectomy and only 14.9%–32.0%
42
43
44 reported attempting conservative management. The 2018 international survey
45
46 reported that around 60% of the respondents favored a radical surgical management
47
48
49 approach with cesarean hysterectomy i.e. primary cesarean hysterectomy with the
50
51 placenta left in situ, whereas 10 (28%) would perform a partial myometrial resection
52
53
54 or radical dissection whenever possible [46]. Primary attempt at placental removal
55
56 and compression sutures were attempted by a quarter of experts and around half of
57
58
the respondents used intra-arterial balloons or arterial embolization [46].
59
60
61
62
63
64
19
65
 1
2 All the guidelines recommend that:
3
4
5  The delivery hysterotomy should be performed high without incising through
6
7 the placenta.
8
9
10  No attempt should be made to remove the placenta (extirpative approach or
11
12 forcible manual removal of the placenta) if it shows no signs of separation as
13
14
15 this may cause substantial hemorrhage.
16
17  If at the time of an elective repeat caesarean section, PAS is suspected based
18
19
20
on uterine appearance and there are no extenuating circumstances
21
22 mandating immediate delivery, the caesarean section should be delayed until
23
24 until optimal surgical expertise arrives and adequate blood products are
25
26
27 available.
28
29  Conservative management or expectant management should be considered
30
31
32 only for carefully selected cases of PAS after detailed counseling about the
33
34 risks, uncertain benefits, and efficacy and local arrangements need to be
35
36
37
made to ensure regular review, ultrasound examination and access to
38
39 emergency care should the patient experience complications.
40
41  Uterus-preserving surgical techniques should only be attempted by surgeons
42
43
44 working in teams with appropriate expertise to manage such cases.
45
46  MTX adjuvant therapy should not be used for expectant management as it is
47
48
49 of unproven benefit and has significant adverse effects, including maternal
50
51 mortality.
52
53
54
55
56 All the guidelines agree that:
57
58
59
60
61
62
63
64
20
65
  There is insufficient evidence to recommend giving or withholding uterotonic
1
2 drugs after delivery of the fetus
3
4
5  There is insufficient evidence to recommend routine IR techniques such as
6
7 embolisation or placement of an arterial segment balloon designed to arrest
8
9
10 arterial blood flow that may supply the gravid uterus.
11
12
13
14
15 The RCOG guidelines indicate that when the extent of the placenta accreta is
16
17 limited in depth and surface area, and the entire placental implantation area is
18
19
20
accessible and visualised (i.e. completely anterior, fundal or posterior without deep
21
22 pelvic invasion), uterus-preserving surgery may be appropriate, including partial
23
24 myometrial resection. [GPP]. The ACOG/SMFM guidelines highlight that because of
25
26
27 a lack of comparative data, choice of skin incision is left to operator judgment,
28
29 although many employ vertical incisions for better access and visualization whereas
30
31
32 both the FIGO and SOGC guidelines recommend midline skin incision sufficiently
33
34 high to allow a hysterotomy above the superior placental margin in high-suspicion
35
36
37
PAS with major anterior previa. The ACOG/SMFM and FIGO guidelines indicate that
38
39 in most cases when hysterectomy is necessary, a total hysterectomy is required
40
41 because lower uterine segment or cervical bleeding due to cervical involvement
42
43
44 frequently precludes a supra-cervical (partial) hysterectomy, Total hysterectomy also
45
46 reduces the potential risk of malignancy developing in the cervical stump, the need
47
48
49 for regular cervical cytology and other associated problems such as bleeding or
50
51 discharge.
52
53
54
55
56 UNRESOLVED ISSUES
57
58
59
60
61
62
63
64
21
65
 All authors and experts involved in developing the different guidelines noted that
1
2 most current information on both prenatal diagnosis and management is derived
3
4
5 from retrospective cohort studies without controls, case series and expert opinion.
6
7 A search of PubMed using the MeSH headings for “placenta accreta, placenta
8
9
10 increta, placenta percreta, abnormally invasive placenta and morbidly adherent
11
12 placenta” published between May 2019 and May 2020 found 189 articles including
13
14
15 122 retrospective and two prospective cohort studies, 30 cases reports, 22 expert
16
17 opinions, 7 case series, five systematic review and meta-analyses and only one RCT
18
19
20
[54]. Furthermore, the absence of detailed histopathological evidence and lack of
21
22 standardized clinical or photographic evidence of PAS at birth in around 90% of
23
24 cohort studies [11,12] considerably limits the value of the corresponding data and
25
26
27 make it is impossible to reproduce such results in other centers or populations, or
28
29 carry out meaningful meta-analysis. This highlights the difficulties of finding high
30
31
32 quality evidence to support strong recommendations.
33
34 There are some generally agreed upon strategies, but comparison of the
35
36
37
different guidelines shows (Table 5), that even those recommendations graded as
38
39 strong, in particular regarding management, are not supported by well-performed
40
41 RCTs. Interestingly, both the FIGO and SOGC strongly recommend the use of
42
43
44 tranexamic acid during surgery for PAS but there are no cohort series available in
45
46 the literature and only one small RCTs in cases of (non-accreta) placenta previa
47
48
49 combining bilateral uterine artery ligation with tranexamic acid [55].
50
51 The pivotal role of ultrasound imaging in the screening women at risk and in
52
53
54 accurately diagnosing PAS prenatally is highlighted in all guidelines. However, the
55
56 ACOG/SMFM guidelines indicate that the standardized description of
57
58
ultrasonography features of PAS [17] and pro forma for standardized reporting of
59
60
61
62
63
64
22
65
 ultrasound [18] proposed by an international group of imaging experts are not yet in
1
2 widespread use in the U.S. and there is no evidence that they are routinely used in
3
4
5 many other countries. The diagnosis of PAS is not part of general ultrasound training
6
7 courses in the U.K [56] and it has only been added to the fetal medicine foundation
8
9
10 website earlier this year (www//coursesf.etalmedicine.com). However, such
11
12 ultrasound training and screening programs have existed for more than two decades
13
14
15 for the detection of fetal anomalies such as congenital heart defect. Surprisingly, as
16
17 this was one of the first objective of the use of ultrasound in obstetrics, the criteria
18
19
20
used by authors of cohort series and gestational age at confirmation diagnosis of
21
22 placenta previa remains highly variable [12]. Considering the increasing incidence of
23
24 placenta previa accreta around the world and the high maternal morbidity and
25
26
27 mortality at delivery of undiagnosed cases, similar international screening protocols
28
29 with standard anatomical views for both low-lying/placenta previa and PAS should be
30
31
32 implemented.
33
34
35
36
37
38
39
40
41
42 Conflicts of interest
43
44
45
The authors have no conflicts of interest.
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
23
65
 SUMMARY (max 250 words)
1
2 The changes in the epidemiology of placenta previa and placenta accreta spectrum
3
4
5 (PAS) have been closely linked to the rapid rise in caesarean delivery (CD) rates
6
7 over the last three decades. From a rare pathologic condition, PAS has become a
8
9
10 new risk factor for major obstetric complications. The changes in the prevalence of
11
12 PAS lag behind the rise in CDs by around 6 years and health providers must prepare
13
14
15 for a significant rise in the numbers of pregnancies complicated by placenta previa
16
17 accreta. New national and international guidelines or the update of existing ones for
18
19
20
the diagnosis and management of PAS have highlighted the importance of the early
21
22 identification of women with the condition. This is especially true for those
23
24 presenting with an anterior low-lying/placenta praevia and one or more prior CD
25
26
27 since they are at the highest risk of PAS. The crucial role of ultrasound imaging for
28
29 the antenatal screening and diagnosis, the need for women diagnosed with PAS to
30
31
32 be cared for by a multidisciplinary team and the importance of avoiding the placenta
33
34 during the hysterotomy and/or attempt to remove it when PAS is suspected at
35
36
37
delivery are key to reducing morbidity. Most current information on both prenatal
38
39 diagnosis and management is derived from uncontrolled retrospective cohort studies
40
41 and case series; in around 90% of cases there is no detailed histopathological
42
43
44 evidence to confirm the severity of the PAS encountered. All guidelines agree on the
45
46 need for new prospective controlled cohort studies and randomized controlled trials
47
48
49 to compare the efficacy of the different therapeutic approaches and the use
50
51 additional management techniques.
52
53
54
55
56
57
58
59
60
61
62
63
64
24
65
 PRACTICE POINTS
1
2
3
 Women presenting with low-lying/placenta previa and a history of one or more
4
5 CDs should be carefully assessed for PAS.
6
7  The diagnosis of PAS should be confirmed by trained operators in ultrasound
8
9
10 imaging and regular follow-up should be arranged until delivery.
11
12  MRI is not essential for the diagnosis of PAS and its used is limited by cost
13
14
15 and the availability of radiology experts in the evaluation of PAS
16
17  Delivery should be planned and managed by an MDT with regular established
18
19
20 expertise in complex uterine surgery and access to blood products and adult
21
22 and neonatal ICUs.
23
24
25  The optimal time of delivery is guided by maternal symptoms associated with
26
27 placenta previa and must balance the risks and advantages for mother and
28
29
30 baby which may be different in low- median- and high-income countries.
31
32
33
34
RESEARCH AGENDA
35
36
37 Health provision for the development of MDT with specialist surgeons, equipment,
38
39 drugs, blood bank and intensive care infrastructure to safely manage women
40
41
42 presenting with PAS requires an accurate evaluation of its prevalence and outcome
43
44 which entails the use of standardized antenatal and post-natal diagnostic protocols.
45
46
47 Within this context, there is a need for prospective multi-centre studies with
48
49 participatory methodologies involving local service providers and management
50
51
52
adapted to the grade of PAS and local facilities. There is also a need to evaluate the
53
54 health and economic consequences of high caesarean section rates on maternal
55
56 health within particular population context.
57
58
59
60
61
62
63
64
25
65
 REFERENCES
1
2 1. Polak JO, Phelan GW. Placenta accreta; incidence, pathology, and
3
4 management, Surg Gynec Obst 1924;38:1815.
5
6 2. Andrews CJ. Report of a case of retained placenta, clinically placenta accreta.
7
8 JAMA. 1924;82:1780.
9
10 3. Forster DS. A case of placenta accreta. Can Med Assoc J. 1927;17:204-7.
11
12 4. Nathanson JL. The anatomy, genesis and clinical considerations of placenta
13 accreta. Am J Obstet Gynecol. 1928;16:44-50.
14
15 5. Irving C, Hertig AT. A study of placenta accreta. Surg Gynecol Obstet
16
17 1937;64:178-200.
18
19 6. Gielchinsky Y, Rojansky N, Fasouliotis SJ, Ezra Y. Placenta accreta--
20
21 summary of 10 years: a survey of 310 cases. Placenta. 2002;23:210-4.
22
23
7. Sheiner E, Levy A, Katz M, Mazor M. Identifying risk factors for peripartum
24 cesarean hysterectomy. A population-based study. J Reprod Med.
25
26 2003;48:622-6.
27
28 8. Bencaiova G, Burkhardt T, Beinder E. Abnormal placental invasion
29
30 experience at 1 center. J Reprod Med. 2007;52:709-14.
31
32 9. Woodring TC, Klauser CK, Bofill JA, Martin RW, Morrison JC. Prediction
33
34
of placenta accreta by ultrasonography and color Doppler imaging. J Matern
35 Fetal Neonatal Med. 2011;24:118-21.
36
37 10. Klar M, Laub M, Schulte-Moenting J, Proempeler H, Kunze M. Clinical risk
38
39 factors for complete and partial placental retention: a case-control study. J
40
41 Perinat Med. 2014;41:529–34.
42
43 11. Jauniaux E, Bunce C, Grønbeck L, Langhoff-Roos J. Prevalence and main
44
outcomes of placenta accreta spectrum: a systematic review and
45
46 metaanalysis. Am J Obstet Gynecol. 2019;9:e031193.
47
48 12. Jauniaux E, Grønbeck L, Bunce C, Langhoff-Roos J, Collins SL.
49
50 Epidemiology of placenta previa accreta: a systematic review and meta-
51
52 analysis. BMJ Open. 2019;9:e031193.
53
54 13. * Luke RK, Sharpe JW, Greene RR. Placenta accreta: The adherent or
55 invasive placenta. Am J Obstet Gynecol 1966;95:660–8.
56
57 14. Jauniaux E, Ayres-de-Campos D, Langhoff-Roos J, Fox KA, Collins S; FIGO
58
59 Placenta Accreta Diagnosis and Management Expert Consensus Panel. FIGO
60
61
62
63
64
26
65
 classification for the clinical diagnosis of placenta accreta spectrum disorders.
1
2 Int J Gynaecol Obstet. 2019;146:20-24.
3
4 15. Jauniaux E, Hussein AM, Fox KA, Collins SL. New evidence-based diagnostic
5
6
and management strategies for placenta accreta spectrum disorders. Best
7 Pract Res Clin Obstet Gynaecol. 2019;61:75-88.
8
9 16. Hecht JL, Baergen R, Ernst LM, Katzman PJ, Jacques SM, Jauniaux E et al.
10
11 Classification and reporting guidelines for the pathology diagnosis of placenta
12
13 accreta spectrum (PAS) disorders: recommendation from an expert panel.
14
15 Modern Pathol 2020; in press.
16 17. * Collins SL, Ashcroft A, Braun T, Calda P, Langhoff-Ross J, Morel O et al.,
17
18 Proposed for standardized ultrasound descriptions of abnormally invasive
19
20 placenta (AIP). Ultrasound Obstet Gynecol. 2016;47:271-275.
21
22 18. Alfirevic Z, Tang A-W, Collins SL, Robson SC, Palacios-Jaraquemadas, on
23
24 behalf of the Ad-hoc International AIP Expert group. Pro forma for ultrasound
25
26 reporting in suspected abnormally invasive placenta (AIP); an international
27 consensus. Ultrasound Obstet Gynecol. 2016;47:276-278.
28
29 19. Morel O, Collins SL, Uzan-Augui J, Masselli G, Duan J, Chabot-Lecoanet AC,
30
31 et al; International Society for Abnormally Invasive Placenta (IS-AIP). A
32
33 proposal for standardized magnetic resonance imaging (MRI) descriptors of
34
35 abnormally invasive placenta (AIP) - From the International Society for
36
37
AIP.Diagn Interv Imaging 2019;100:319-325.
38 20. Jauniaux E, Silver RM, Matsubara S. The new world of placenta accreta
39
40 spectrum disorders. Int J Gynaecol Obstet. 2018;140:259-260.
41
42 21. Silver RM, Landon MB, Rouse DJ, Leveno KJ, Spong CY, Thom EA, et al.
43
44 National Institute of Child Health and Human Development Maternal-Fetal
45
46 Medicine Units Network. Maternal morbidity associated with multiple repeat
47
48
cesarean deliveries. Obstet Gynecol. 2006;107:1226–32.
49 22. *Jauniaux E, Chantraine F, Silver RM, Langhoff-Roos J; FIGO Placenta
50
51 Accreta Diagnosis and Management Expert Consensus Panel. FIGO
52
53 consensus guidelines on placenta accreta spectrum disorders: Epidemiology.
54
55 Int J Gynaecol Obstet. 2018;140:265-273.
56
57 23. Gurol-Urganci I, Cromwell DA, Edozien LC, et al. Risk of placenta previa in
58
59
second birth after first birth cesarean section: a population-based study and
60 meta-analysis. BMC Pregnancy Childbirth. 2011;11:95.
61
62
63
64
27
65
 24. Fitzpatrick KE, Sellers S, Spark P, Kurinczuk JJ, Brocklehurst P, Knight M.
1
2 Incidence and risk factors for placenta accreta/increta/percreta in the UK: a
3
4 national case-control study. PLoS One. 2012;7:e52893.
5
6
25. Jauniaux E, Jurkovic D. Placenta accreta: pathogenesis of a 20th century
7 iatrogenic uterine disease. Placenta. 2012;33:244-51.
8
9 26. Jauniaux E, Bhide A, Burton GJ. Pathophysiology of accreta. In: Silver R, ed.
10
11 Placenta accreta syndrome. Portland: CRC Press, 2017:13–28.
12
13 27. Zosmer N, Fuller J, Shaikh H, Johns J, Ross JA. Natural history of early first-
14
15 trimester pregnancies implanted in Cesarean scars. Ultrasound Obstet
16 Gynecol. 2015;46:367-75.
17
18 28. Calì G, Timor-Tritsch IE, Palacios-Jaraquemada J, Monteaugudo A, Buca D,
19
20 Forlani F, et al. Outcome of Cesarean scar pregnancy managed expectantly:
21
22 systematic review and meta-analysis. Ultrasound Obstet Gynecol.
23
24 2018;51:169-175.
25
26 29. Baldwin HJ, Patterson JA, Nippita TA, Torvaldsen S, Ibiebele I, Simpson JM,
27 Ford JB. Antecedents of abnormally invasive placenta in primiparous women:
28
29 risk associated with gynecologic procedures. Obstet Gynecol. 2018;131:227-
30
31 33.
32
33 30. Gyamfi-Bannerman C, Gilbert S, Landon MB, Spong CY, Rouse DJ, Varner
34
35 MW et al; Eunice Kennedy Shriver National Institute of Child Health and
36
37
Human Development (NICHD) Maternal-Fetal Medicine Units (MFMU)
38 Network. Risk of uterine rupture and placenta accreta with prior uterine
39
40 surgery outside of the lower segment. Obstet Gynecol. 2012;120:1332-7.
41
42 31. Jauniaux E, Moffett A, Burton GJ. Placental Implantation Disorders. Obstet
43
44 Gynecol Clin North Am. 2020;47:117-132.
45
46 32. Jauniaux E, Hussein AM, Zosmer N, Elbarmelgy RM, Elbarmelgy RA, Shaikh
47
48
H, Burton GJ. A new methodologic approach for clinico-pathologic
49 correlations in invasive placenta previa accreta. Am J Obstet Gynecol. 2020;
50
51 222:379.e1-379.e11369.
52
53 33. Jauniaux E, Grobmann W. Caesarean section: The world No 1 operation. A
54
55 textbook of caesarean section. Edts: Jauniaux E, Grobman W. Oxford
56
57 University Press. Oxford. 1-8, 2016.
58
59
34. Appropriate technology for birth. Lancet 1985;2:436–7.
60
61
62
63
64
28
65
 35. Boerma T, Ronsmans C, Melesse DY, Barros AJD, Barros FC, Juan L, et al.
1
2 Global epidemiology of use of and disparities in caesarean sections. Lancet.
3
4 2018;392:1341-1348.
5
6
36. Solheim KN, Esakoff TF, Little SE, Cheng YW, Sparks TN, Caughey AB. The
7 effect of cesarean delivery rates on the future incidence of placenta previa,
8
9 placenta accreta, and maternal mortality. J Matern Fetal Neonatal Med.
10
11 2011;24:1341-6.
12
13 37. Knight M, Nair M, Tuffnell D, Shakespeare J, Kenyon S, Kurinczuk JJ (Eds.)
14
15 on behalf of MBRRACE-UK. Saving Lives, Improving Mothers’ Care –
16 Lessons learned to inform maternity care from the UK and Ireland Confidential
17
18 Enquiries into Maternal Deaths and Morbidity 2013–15. Oxford: National
19
20 Perinatal Epidemiology Unit, University of Oxford; 2017 [www.npeu.ox.ac.
21
22 uk/mbrrace-uk].
23
24 38. * Jauniaux E, Alfirevic Z, Bhide AG, Belfort MA, Burton GJ, Collins SL et al;
25
26 Royal College of Obstetricians and Gynaecologists. Placenta Praevia and
27 Placenta Accreta: Diagnosis and Management: Green-top Guideline No. 27a.
28
29 BJOG. 2019;126:e1-e48.
30
31 39. * Obstetric Care Consensus No. 7 Summary: Placenta Accreta Spectrum.
32
33 Obstet Gynecol. 2018;132:1519-21.
34
35 40. Society of Gynecologic Oncology; American College of Obstetricians and
36
37
Gynecologists and the Society for Maternal–Fetal Medicine, Cahill AG, Beigi
38 R, Heine RP, Silver RM, Wax JR. Placenta Accreta Spectrum. Am J Obstet
39
40 Gynecol. 2018;219:B2-B16.
41
42 41. Jauniaux E, Ayres-de-Campos D; FIGO Placenta Accreta Diagnosis and
43
44 Management Expert Consensus Panel. FIGO consensus guidelines on
45
46 placenta accreta spectrum disorders: Introduction. Int J Gynaecol Obstet.
47
48
2018;140:261-264.
49 42. Jauniaux E, Bhide A, Kennedy A, Woodward P, Hubinont C, Collins S; FIGO
50
51 Placenta Accreta Diagnosis and Management Expert Consensus Panel. FIGO
52
53 consensus guidelines on placenta accreta spectrum disorders: Prenatal
54
55 diagnosis and screening. Int J Gynaecol Obstet. 2018;140:274-280.
56
57 43. Allen L, Jauniaux E, Hobson S, Papillon-Smith J, Belfort MA; FIGO Placenta
58
59
Accreta Diagnosis and Management Expert Consensus Panel. FIGO
60
61
62
63
64
29
65
 consensus guidelines on placenta accreta spectrum disorders: Non-
1
2 conservative surgical management. Int J Gynaecol Obstet. 2018;140:281-90.
3
4 44. Sentilhes L, Kayem G, Chandraharan E, Palacios-Jaraquemada J, Jauniaux
5
6
E; FIGO Placenta Accreta Diagnosis and Management Expert Consensus
7 Panel. FIGO consensus guidelines on placenta accreta spectrum disorders:
8
9 Conservative management. Int J Gynaecol Obstet. 2018;140:291-298.
10
11 45. Hobson SR, Kingdom JC, Murji A, Windrim RC, Carvalho JCA, Singh SS, et
12
13 al. No. 383-Screening, Diagnosis, and Management of Placenta Accreta
14
15 Spectrum Disorders. J Obstet Gynaecol Can. 2019;41:1035-49.
16 46. Cal M, Ayres-de-Campos D, Jauniaux E. International survey of practices
17
18 used in the diagnosis and management of placenta accreta spectrum
19
20 disorders. Int J Gynaecol Obstet. 2018;140:307-311.
21
22 47. Sargent W, Collins SL. Are women antenatally diagnosed with abnormally
23
24 invasive placenta receiving optimal management in England? An
25
26 observational study of planned place of delivery. Acta Obstet Gynecol Scand.
27 2019;98:337-41.
28
29 48. Bartels HC, Rogers AC, O'Brien D, McVey R, Walsh J, Brennan DJ.
30
31 Association of Implementing a multidisciplinary team approach in the
32
33 management of morbidly adherent placenta with maternal morbidity and
34
35 mortality. Obstet Gynecol. 2018;132:1167-76.
36
37
49. Shamshirsaz AA, Fox KA, Salmanian B, Diaz-Arrastia CR, Lee W, Baker BW,
38 et al. Maternal morbidity in patients with morbidly adherent placenta treated
39
40 with and without a standardized multidisciplinary approach. Am J Obstet
41
42 Gynecol. 2015;212:218.e1-9.
43
44 50. Shamshirsaz AA, Fox KA, Erfani H, Clark SL, Salmanian B, Baker BW et al.,
45
46 Multidisciplinary team learning in the management of the morbidly
47
48
adherent placenta: outcome improvements over time. Am J Obstet Gynecol.
49 2017;216:612.e1-612.e5.
50
51 51. Esakoff TF, Handler SJ, Granados JM, Caughey AB. PAMUS: placenta
52
53 accreta management across the United States. J Matern Fetal Neonatal Med.
54
55 2012;25:761-5.
56
57 52. Wright JD, Silver RM, Bonanno C, Gaddipati S, Lu YS, Simpson LL, et al.
58
59
Practice patterns and knowledge of obstetricians and gynecologists regarding
60 placenta accreta. J Matern Fetal Neonatal Med. 2013;26:1602–9.
61
62
63
64
30
65
 53. Ioscovich A, Shatalin D, Butwick AJ, Ginosar Y, Orbach-Zinger S, Weiniger
1
2 CF. Israeli survey of anesthesia practice related to placenta previa and
3
4 accreta. Acta Anaesthesiol Scand. 2016;60:457-64.
5
6
54. Hussein AM, Dakhly DMR, Raslan AN, Kamel A, Abdel Hafeez A, Moussa M,
7 et al. The role of prophylactic internal iliac artery ligation in abnormally
8
9 invasive placenta undergoing caesarean hysterectomy: a randomized control
10
11 trial. J Matern Fetal Neonatal Med. 2019;32:3386-92.
12
13 55. Abbas AM, Shady NW, Sallam HF. Bilateral uterine artery ligation plus
14
15 intravenous tranexamic acid during cesarean delivery for placenta previa: a
16 randomized double-blind controlled trial. J Gynecol Obstet Hum Reprod.
17
18 2019;48:115-9.
19
20 56. National Collaborating Centre for Womens and Children’s Health. Antenatal
21
22 care: routine care for the healthy pregnant woman. Clinical Guideline. London:
23
24 RCOG Press; 2010.
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
31
65
 Table 1: Summary of epidemiology data and distribution of PAS grades in population
1 studies [11] and studies of placenta previa accreta [12] diagnosed antenatally.
2
3 Population Placenta previa accreta
4
5
No of articles included in 29 20
6 study
7 Retrospective/Prospective 22/7 13/7
8 No of cases of PAS/births & 7,001/5,719,992 587/1,231,160 (0.05%)
9 pregnancies (Prevalence) (0.12%) 1/2,097
10 1/817
11 No of PAS cases with 770/832 283/309
12
detailed histopathology/total (92.5%) (91.6%)
13
14 No of cases in study (%)
15 Placenta creta/adherenta 473 (61.4%) 171 (60.4%)
16 Range 34.8-81.6% Range 30.4-92.3%
17 Placenta increta 126 (16.4%) 74 (26.2%)
18 Range 3.7-43.5% Range 0-45.7%
19 Placenta percreta 171 (22.2%) 38 (13.4%)
20
Range 6.6-51.9% Range 2.4-35.3%
21
22 PAS= Placenta Accreta Spectrum
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
32
65
 Table 2. RCOG
1 Classification of evidence levels
2 1++ High-quality meta-analyses, systematic reviews of randomised controlled trials or randomised
3
4
controlled trials with a very low risk of bias
5 1+ Well-conducted meta-analyses, systematic reviews of randomised controlled trials or
6 randomised controlled trials with a low risk of bias
7 1– Meta-analyses, systematic reviews of randomised controlled trials or randomised controlled
8 trials with a high risk of bias
9
2++ High-quality systematic reviews of case–control or cohort studies or high-quality
10
11 case–control or cohort studies with a very low risk of confounding, bias or chance and a
12 high probability that the relationship is causal
13 2+ Well-conducted case–control or cohort studies with a low risk of confounding, bias or chance
14 and a moderate probability that the relationship is causal
15 2– Case–control or cohort studies with a high risk of confounding, bias or chance and a
16
17 significant risk that the relationship is not causal
18 3 Non-analytical studies, e.g. case reports, case series
19 4 Expert opinion
20
21
22
Grades of Recommendation
23 A At least one meta-analysis, systematic reviews or RCT rated as 1++, and directly applicable
24 to the target population; or a systematic review of RCTs or a body of evidence consisting
25 principally of studies rated as 1+, directly applicable to the target population and
26 demonstrating overall consistency of results
27
28 B A body of evidence including studies rated as 2++ directly applicable to the target
29 population, and demonstrating overall consistency of results; or
30 Extrapolated evidence from studies rated as 1++ or 1+
31 A body of evidence including studies rated as 2+ directly applicable to the target
32 C
population, and demonstrating overall consistency of results; or
33
34
Extrapolated evidence from studies rated as 2++
35 D Evidence level 3 or 4; or
36 Extrapolated evidence from studies rated as 2+
37 Good Practice Points (GPP) Recommended best practice based on the clinical experience of the
38 guideline development group
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
33
65
 Table 3. ACOC/SMFM
1
2 Grading of recommendations assessment Quality of supporting evidence
3 1A. Strong recommendation, Consistent evidence from well performed
4 high-quality evidence RCTs or overwhelming evidence of some other
5
6
form. Further research is unlikely to change
7 confidence in the estimate of benefit and risk.
8 1B. Strong recommendation, Evidence from RCTs with important limitations
9 moderate-quality evidence (inconsistent results, methodologic flaws,
10 indirect or imprecise), or very strong evidence
11 of some other research design. Further research
12 (if performed) is likely to have an impact on
13 confidence in the estimate of benefit and risk
14
and may change the estimate.
15
16 1C. Strong recommendation, Evidence from observational studies,
17 low-quality evidence unsystematic clinical experience, or from RCTs
18 with serious flaws. Any estimate of effect is
19 uncertain.
20 2A. Weak recommendation, Consistent evidence from well performed RCTs
21 high-quality evidence or overwhelming evidence of some other form.
22 Further research is unlikely to change
23
24
confidence in the estimate of benefit and risk.
25 2B. Weak recommendation, Evidence from RCTs with important limitations
26 moderate-quality evidence (inconsistent results, methodologic flaws,
27 indirect or imprecise), or very strong evidence
28 of some other research design. Further research
29 (if performed) is likely to have an effect on
30 confidence in the estimate of
31 benefit and risk and may change the estimate.
32
33
2C. Weak recommendation, Evidence from observational studies,
34 low-quality evidence unsystematic clinical experience, or from RCTs
35 with serious flaws. Any estimate of effect is
36 uncertain.
37 Best practice Recommendation in which either (i) there is
38 enormous amount of indirect evidence that
39 clearly justifies strong recommendation (direct
40 evidence would be challenging, and inefficient
41
42
use of time and resources, to bring together and
43 carefully summarize), or (ii) recommendation to
44 contrary would be unethical.
45 RCT= randomized controlled trial.
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
34
65
 Table 4. SOGC Key to evidence statements and grading of recommendations
1
2 Quality of evidence assessment Classification of recommendations
3 I: Evidence obtained from at least one properly A. There is good evidence to recommend the
4 RCT. clinical preventive action.
5
6
II-1: Evidence from well-designed controlled B. There is fair evidence to recommend the
7 trials without randomization. clinical preventive action.
8 II-2: Evidence from well-designed cohort C. The existing evidence is conflicting and does
9 (prospective or retrospective) or case-control not allow to make a recommendation for or
10 studies, preferably from more than one centre against use of the clinical preventive action;
11 or research group. however, other factors may influence decision-
12 making.
13
II-3: Evidence obtained from comparisons D. There is fair evidence to recommend against
14
15 between times or places with or without the the clinical preventive action.
16 intervention. Dramatic results in uncontrolled E. There is good evidence to recommend against
17 experiments (such as the results of treatment the clinical preventive action.
18 with penicillin in the 1940s) could also be
19 included in this category
20 III: Opinions of respected authorities, based on L. There is insufficient evidence (in quantity or
21 clinical experience, descriptive studies, or quality) to make a recommendation;
22
reports of expert committees however, other factors may influence decision
23
24 making.
25 RCT= randomized controlled trial.
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
35
65
*Practice Points

PRACTICE POINTS

 Women presenting with low-lying/placenta previa and a history of one or more

CDs should be carefully assessed for PAS.

 The diagnosis of PAS should be confirmed by trained operators in ultrasound

imaging and regular follow-up should be arranged until delivery.

 MRI is not essential for the diagnosis of PAS and its used is limited by cost and

the availability of radiology experts in the evaluation of PAS

 Delivery should be planned and managed by an MDT with regular established

expertise in complex uterine surgery and access to blood products and adult and

neonatal ICUs.

 The optimal time of delivery is guided by maternal symptoms associated with

placenta previa and must balance the risks and advantages for mother and baby

which may be different in low- median- and high-income countries.

*Research Agenda

RESEARCH AGENDA

Health provision for the development of MDT with specialist surgeons, equipment,

drugs, blood bank and intensive care infrastructure to safely manage women presenting

with PAS requires an accurate evaluation of its prevalence and outcome which entails

the use of standardized antenatal and post-natal diagnostic protocols. Within this

context, there is a need for prospective multi-centre studies with participatory

methodologies involving local service providers and management adapted to the grade

of PAS and local facilities. There is also a need to evaluate the health and economic

consequences of high caesarean section rates on maternal health within particular

population context.
*MCQs

MCQs for the manuscript: A comparison of recent guidelines in the

diagnostic and management of placenta accreta spectrum disorders

1. The following is true about the epidemiology of PAS:

a. Less than 30% of women diagnosed prenatally with PAS present
with a low-lying/placenta previa and a surgical history of at least
one prior uterine surgery, most commonly cesarean delivery (CD).
b. The incidence of placenta previa accreta increases with the number
of prior CDs.
c. Prior gynecologic surgery (myomectomy, uterine adhesiolysis,
septal resection) and some uterine pathology such as bicornuate
uterus have not been associated with the development of PAS in
subsequent pregnancies.
d. Large cesarean scar defects (CSD) can lead to the development of
cesarean scar pregnancies (CSP) which can be a precursor for the
development of PAS

a= F; b= T; c= F; d= T

Explanation to the answers for Question 1:

a. CD rates have risen worldwide over the last decades sometime above 40% in
countries such as Brazil, Turkey, Italy, Egypt, Argentina, Iran, South Korea
and Mexico. As CD scar increase the risk of both previa and accreta
placentation Today, over 95% of women diagnosed prenatally with PAS
present with a low-lying/placenta previa and a surgical history of at least one
prior CD.
b. Multiple CDs create substantial and chronic damage to the integrity of the
uterine wall, especially if the endometrium fails to re-epithelize in an area of
scar formation facilitating the development of PAS.
c. Accreta placentation has been described after most minor gynaecologic
surgical procedure including myomectomy but the risk is low unless the
uterine cavity is entered or the myometrium is perforated.
d. The diagnosis of CSP in the first trimester is increasingly common, such that
the natural history of evolution to PAS has now been clearly established,
especially for type-2 CSP.
 2. On the prenatal diagnosis of PAS the RCOG, ACOG/SMFM, FIGO & SOGC
agree that:
a. Antenatal diagnosis of PAS is crucial in planning its management
and has been shown to reduce maternal morbidity and mortality.
b. Previous uterine curettages and the presence of an anterior low-
lying/placenta praevia should alert the antenatal care team of the
higher risk of PAS.
c. Ultrasonography is a relatively inexpensive and widely available
imaging modality and therefore should be the first line for the
diagnosis of PAS.
d. MRI is essential for making a prenatal diagnosis of suspected PAS
and should be performed in all cases of women at risk of PAS.

a =T; b= F; c= T; d= F

Explanation to the answers for Question 2:

a. There is mounting evidence that women with PAS diagnosed prenatally

and managed by a multidisciplinary team (MDT) in a centre of excellence
(CoE) are less likely to require emergency surgery, large-volume blood
transfusion and reoperation within 7 days of delivery for bleeding
complications compared with women managed by standard obstetric care
without a specific protocol.
b. Uterine curettage in particular if complicated with uterine perforation
usually damage the myometrium above the lower segment. These can be
associated with focal PAS of the anterior uterine wall or fundus but the
patients with the highest risk of PAS are those with prior multiple CDs
presenting with an anterior low-lying/placenta previa.
c. Ultrasound is operator dependent and until recently there was no training
available for the ultrasound diagnosis of PAS but in expert hands it has a
positive predictive value, negative predictive value and detection rate
above 95%. The diagnosis of PAS is not part of general ultrasound training
courses in the U.K and it has only been added to the fetal medicine
foundation website earlier this year (www//coursesf.etalmedicine.com).
d. MRI may be useful in evaluating the pelvic extension of a placenta
percreta or areas difficult to evaluate on ultrasound, but not essential and
its effectiveness is currently limited by the relative contraindication to the
use of a gadolinium contrast enhancing agent.
 3. On preparation for delivery and management of PAS the RCOG,
ACOG/SMFM, FIGO & SOGC recommend that:
a. Women diagnosed with PAS can be cared for by obstetricians with
experience in complex CDs in a local hospital close to the patient
home.
b. Antenatal corticosteroids should be given for lung maturation at 30
weeks for planned delivery at 36-37 weeks of gestation.
c. No attempt should be made to remove the placenta (extirpative
approach or forcible manual removal of the placenta) if it shows no
signs of separation as this may cause substantial hemorrhage.
d. Conservative management or expectant management with adjuvant
therapy such as methotrexate (MTX) should be considered in all
cases of PAS.

a =F; b= F; c= T; d= F

Explanation to the answers for Question 3:

a. Patients diagnosed with PAS should be cared for by a MDT with expertise
in complex pelvic surgery in a specialist centre with logistic support for
immediate access to blood products, adult and neonatal intensive care,
using a preoperative coordination with protocol-based interdisciplinary
care including anesthesiology, hematology/blood bank, maternal-fetal
medicine, neonatology, and expert pelvic surgeons to optimize
intraoperative and post-operative outcomes.
b. As the timing of delivery decisions needs to balance maternal risks and
benefits with those of the fetus or neonate and most patients presents with
a placenta previa accreta antenatal, corticosteroids should be used for
lung maturation following the international gestational age-based
recommendations for anticipated delivery before term. Here the guidelines
differ regarding the timing of delivery with the ACOG/SMFM
recommending 34+0-35+6 weeks of gestation for scheduled cesarean
delivery in a stable patient whereas for the RCOG, recommends delivery
at 35+0-36+6 weeks of gestation in the absence of risk factors for preterm
delivery
c. Attempt at removing the placenta at delivery in case of PAS is inevitably
associated with massive obstetric hemorrhage and a high maternal
morbidity and some maternal mortality. If at the time of an elective repeat
caesarean section, PAS is suspected based on uterine appearance and
there are no extenuating circumstances mandating immediate delivery, the
caesarean section should be delayed until until optimal surgical expertise
arrives and adequate blood products are available rather than attempting
at delivering the placenta.
d. Conservative management or expectant management should be
considered only for carefully selected cases of PAS after detailed
counseling about the risks, uncertain benefits, and efficacy and local
arrangements need to be made to ensure regular review, ultrasound
examination and access to emergency care should the patient experience
complications. MTX adjuvant therapy should not be used for expectant
management as it is of unproven benefit and has significant adverse
effects, including maternal mortality.