Ultrasound Obstet Gynecol 2022; 59: 465–473

Published online in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.24804

Evaluation of classic and novel ultrasound signs of placenta

accreta spectrum
D. W. SKUPSKI1,2,3 , C. M. DUZYJ4 , J. SCHOLL1,2,3 , A. PEREZ-DELBOY5 , K. RUHSTALLER6 ,
L. A. PLANTE7 , L. A. HART8 , K. T. S. PALOMARES9 , B. AJEMIAN5 , T. ROSEN4 , W. L. KINZLER10
and C. ANANTH11,12,13,14 , for the Perinatal Research Consortium
1
Department of Obstetrics & Gynecology, Division of Maternal Fetal Medicine, New York Presbyterian Queens, Flushing, NY, USA; 2 The
Institute for Placental Medicine, New York Presbyterian Queens, Flushing, NY, USA; 3 Weill Cornell Medicine, New York, NY, USA;
4
Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ,
USA; 5 Columbia University School of Medicine, Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, New
York, NY, USA; 6 Department of Obstetrics & Gynecology, Division of Maternal Fetal Medicine, Christiana Care Health System,
Wilmington, DE, USA; 7 Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Drexel University School of
Medicine, Philadelphia, PA, USA; 8 Department of Obstetrics and Gynecology, Lewis Katz School of Medicine at Temple University,
Philadelphia, PA, USA; 9 Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Saint Peter’s University Hospital,
New Brunswick, NJ, USA; 10 Departments of Obstetrics and Gynecology and Graduate Medical Education, NYU Langone Hospital – Long
Island and NYU Long Island School of Medicine, Mineola, NY, USA; 11 Division of Epidemiology and Biostatistics, Department of
Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA;
12 Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA; 13 Cardiovascular Institute of New

Jersey (CVI-NJ), Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA; 14 Environmental and Occupational Health
Sciences Institute (EOHSI), Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA

K E Y W O R D S: area under the curve; placenta; placenta accreta; placenta accreta spectrum; placenta increta; placenta percreta;
pregnancy; ROC curve; ultrasound

CONTRIBUTION underwent third-trimester transvaginal ultrasound and

What are the novel findings of this work?
Classic ultrasound signs of placenta accreta spectrum
(PAS) are helpful in raising suspicion and establishing a
diagnosis of PAS. Novel ultrasound signs show promise
and require prospective evaluation.
What are the clinical implications of this work?
The presence of more than one ultrasound sign of PAS
markedly increases the risk of PAS and should prompt
preparation for delivery in a referral center.
ABSTRACT
Objectives Improvement in the antenatal diagnosis of
placenta accreta spectrum (PAS) would allow preparation
for delivery in a referral center, leading to decreased
maternal morbidity and mortality. Our objectives were
to assess the performance of classic ultrasound signs and
to determine the value of novel ultrasound signs in the
detection of PAS.
Methods This was a retrospective cohort study of
women with second-trimester placenta previa who
all women with PAS in seven medical centers. A
retrospective image review for signs of PAS was
conducted by three maternal–fetal medicine physicians.
Classic signs of PAS were defined as placental lacunae,
bladder-wall interruption, myometrial thinning and
subplacental hypervascularity. Novel signs were defined as
small placental lacunae, irregular placenta–myometrium
interface (PMI), vascular PMI, non-tapered placental
edge and placental bulge towards the bladder. PAS
was diagnosed based on difficulty in removing the
placenta or pathological examination of the placenta.
Multivariate regression analysis was performed and
receiver-operating-characteristics (ROC) curves were
generated to assess the performance of combined novel
signs, combined classic signs and a model combining
classic and novel signs.
Results A total of 385 cases with placenta previa were
included, of which 55 had PAS (28 had placenta
accreta, 11 had placenta increta and 16 had placenta
percreta). The areas under the ROC curves for classic
markers, novel markers and a model combining classic
and novel markers for the detection of PAS were
0.81 (95% CI, 0.75–0.88), 0.84 (95% CI, 0.77–0.90)

Correspondence to: Dr D. W. Skupski, New York Presbyterian Queens, 56–45 Main Street, Room S-365, Flushing, NY 11355, USA (e-mail:
dwskupsk@med.cornell.edu)
Accepted: 13 October 2021

© 2021 International Society of Ultrasound in Obstetrics and Gynecology. ORIGINAL PAPER

466
and 0.88 (95% CI, 0.82–0.94), respectively. A model
combining classic and novel signs performed better than
did the classic or novel markers individually (P = 0.03).
An increasing number of signs was associated with a
greater likelihood of PAS. With the presence of 0, 1, 2
and ≥ 3 classic ultrasound signs, PAS was present in 5%,
24%, 57% and 94% of cases, respectively.
Conclusions We have confirmed the value of classic
ultrasound signs of PAS. The use of novel ultrasound
signs in combination with classic signs improved the
detection of PAS. These findings have clinical implications
for the detection of PAS and may help guide the obstetric
management of patients diagnosed with these placental
disorders. © 2021 International Society of Ultrasound in
Obstetrics and Gynecology.
INTRODUCTION
Ultrasound signs diagnostic of placenta accreta spectrum
(PAS) were established nearly 30 years ago1,2 . Systematic
evaluation of these signs has confirmed their predictive
value, but primarily in patients with prior uterine
surgery3–6 . The classic signs include loss of the
retroplacental clear zone, placental lacunae, bladder-wall
interruption, myometrial thinning and subplacental
hypervascularity.
Although signs predictive of the eventual development
of PAS have been identified in the first trimester7,8 , late
presentation to prenatal care of many women highlights
the importance of predictive signs in the second and third
trimesters. Studies investigating ultrasound signs of PAS
in the second and third trimesters, and specifically of pla-
centa accreta alone, are needed. We have identified several
promising novel ultrasound signs of PAS on transvaginal
ultrasound in several cases of PAS. These include
small lacunae in the body of the placenta, an irregular
placenta–myometrium interface (PMI) and a vascular
PMI. We have also identified two novel ultrasound signs
of PAS in the literature, whose diagnostic ability has
not been evaluated formally, these being non-tapered
placental edge and placental bulge toward the bladder9,10 .
Each of these novel signs either has been associated
with abnormal placentation or could be attributed to
a lack of normal decidua. In addition, improvements
in imaging resolution of transvaginal ultrasound since
the original description of the classic ultrasound signs
of PAS have enabled a more reliable visualization of
these signs11 .
The objective of this study was to evaluate the
diagnostic ability of classic and novel transvaginal
ultrasound signs and a model combining novel and classic
signs for all types of PAS and for placenta accreta alone.
We hypothesized that classic ultrasound signs would be
highly diagnostic of all types of PAS, that the use of novel
ultrasound signs in combination with classic signs would
improve further the diagnostic performance and that
novel signs would be useful in the diagnosis of placenta
accreta alone.
© 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Skupski et al.
METHODS
This was a retrospective cohort study performed
in the Perinatal Research Consortium (PRC) (www
.perinatalresearchconsortium.org), which is a collabora-
tion of 12 academic institutions and medical centers in
the Northeastern United States with a combined deliv-
ery volume of over 45 000 births per year. Seven PRC
centers participated in the study. Institutional review
board approval was obtained at each institution. At each
institution, ultrasound databases were queried to include
patients with a second-trimester diagnosis of placenta
previa on ultrasound who also underwent third-trimester
transvaginal ultrasound; all cases of PAS at each center
over the years of the study were also included. PAS cases
were identified through ultrasound database searches and
coding searches of the electronic medical records at each
site. The methods of searching and identifying these cases
differed across institutions owing to the use of differ-
ent electronic medical systems at each center. The study
period for all sites spanned from 2008 to 2019; each
site contributed data obtained across a different time
period owing to the technical aspects of accessing imaging
databases, with the shortest time period at an individ-
ual center being 2 years and the longest being 10 years
(Table S1). The reason for the differing number of years
across centers was that some centers had changed their
imaging system and data from the previous system were
not available. Taking into account that curettage may
be a risk factor for placenta accreta in the absence of
prior Cesarean delivery, we included nulliparous women
in order to analyze the diagnostic ability of ultrasound
signs for placenta accreta alone, as opposed to placenta
increta or percreta. The only exclusion criterion was the
lack of the primary outcome, i.e. the presence or absence
of PAS.
Anonymized second- and third-trimester ultrasound
images were uploaded using Health Insurance Porta-
bility and Accountability Act (HIPAA)-compliant tech-
nology to a cloud-based storage site (http://tricefy4
.com). Third-trimester transvaginal images were reviewed
independently by three board certified maternal–fetal
medicine specialists (D.W.S., C.M.D., J.S.) who were
blinded to the outcome. Prior to review of the ultra-
sound images, a single face-to-face meeting of the three
reviewers was held to define each positive finding, and
examine representative images as examples. In order to
minimize the heterogeneity of terms in the literature, we
used the terms and definitions for classic signs published
recently by an international consensus group12 , which are
summarized in Table 1. Representative examples of each
of the classic and novel signs are shown in Figures 1 and
2, respectively.
A positive ultrasound sign was defined as visualization
of the sign by at least two reviewers on third-trimester
transvaginal ultrasound. Maternal demographic charac-
teristics and clinical outcomes were extracted from chart
review. The presence or absence of PAS was the primary
outcome. PAS was diagnosed based on either difficulty in
removing the placenta described in the operative report
Ultrasound Obstet Gynecol 2022; 59: 465–473.
Ultrasound signs of placenta accreta spectrum 467

Table 1 Definitions of ultrasound signs of placenta accreta spectrum

Ultrasound sign Definition

Classic signs*
Placental lacunae One or more hypoechoic areas in body of placenta ≥ 1 cm in diameter
Myometrial thinning < 1 mm or undetectable
Bladder-wall interruption Loss or interruption of white line between myometrium and bladder
Subplacental hypervascularity Increased color Doppler signal seen in subplacental myometrium
Novel signs†
Small placental lacunae One or more hypoechoic areas in body of placenta < 1 cm in diameter
Irregular placenta–myometrium interface Trophoblastic interface with myometrium with > 3 mm variation from straight line
Vascular placenta–myometrium interface Primarily vascular trophoblastic interface with myometrium on color Doppler
Non-tapered placental edge Presence of a blunt or wide amount of trophoblast at the placental edge in sagittal plane
Placental bladder bulge Deviation of uterine serosa away from expected plane, associated with abnormal bulge of
placental tissue toward bladder

*Classic signs were determined using a combination of transabdominal and transvaginal ultrasound in the third trimester. †Novel signs were
determined using only transvaginal ultrasound in the third trimester.

B
P M
C

M
C
P
C
M

P
P

Figure 1 Grayscale (a) and color Doppler (b–d) ultrasound images showing classic signs of placenta accreta spectrum in patients with
confirmed diagnosis, including: (a) placental lacunae (arrows), (b) myometrial thinning, with arrow indicating myometrial thickness < 1 mm,
(c) bladder-wall disruption (thin arrow indicates the line of the bladder wall and thick arrows show bladder-wall interruption) and (d) sub-
placental hypervascularity. B, bladder; C, cervix; M, myometrium; P, placenta.

© 2021 International Society of Ultrasound in Obstetrics and Gynecology. Ultrasound Obstet Gynecol 2022; 59: 465–473.
468 Skupski et al.

C
B
M

P
M M
P
P M

M
P

C
M
P

AF

Figure 2 Grayscale (a,b) and color/power Doppler (c–e)

ultrasound images showing novel ultrasound signs of placenta
accreta spectrum in patients with a confirmed diagnosis, including:
(a) small placental lacuna (arrow), (b) irregular placenta–
myometrium interface, (c) vascular placenta–myometrium
B interface, which is not as prominent as the classic sign of
subplacental hypervascularity, (d) non-tapered placental edge, with
P the lower sagittal edge of the placenta nearly perpendicular to the
myometrial plane (arrow) and (e) placental bladder bulge, with the
placenta bulging towards the bladder and impinging on the bladder
lumen (indicated between the arrows). AF, amniotic fluid; B, blad-
der; C, cervix; M, myometrium; P, placenta.

the placenta is a necessary clinical criterion for the diagno-

sis of placenta accreta. Pathological confirmation of PAS
was performed by pathologists at each center, but there
was no standardized protocol for pathological diagnosis.

or placental pathology demonstrating PAS. Placenta acc-
reta, as opposed to placenta increta or percreta, does not
require hysterectomy in all cases. Given that there is lim-
ited interoperator consistency in pathological diagnosis of
the placenta or placental fragments, difficulty in removing
Statistical analysis
The diagnostic performance of classic and new ultra-
sound signs of PAS was evaluated by calculating
sensitivity, specificity, positive and negative predictive
values and accuracy. Accuracy was calculated using
the following formula: ((true positive + true negative)/
total number of subjects) × 100. Multivariate logistic
regression models were fitted to predict the probability

© 2021 International Society of Ultrasound in Obstetrics and Gynecology. Ultrasound Obstet Gynecol 2022; 59: 465–473.
Ultrasound signs of placenta accreta spectrum 469

of PAS diagnosis based on the ultrasound markers, and 24% of patients having PAS with one classic sign, 57%
receiver-operating-characteristics (ROC) curves were gen- of patients having PAS with two classic signs and 94%
erated to assess the diagnostic performance of (1) the of patients having PAS with three or more classic signs
combination of classic signs; (2) the combination of novel present. This analysis indicated an approximately 5-fold,
signs; and (3) the combination of novel and classic signs. 11-fold and 19-fold increase in diagnostic performance
Areas under the ROC curves (AUCs) with 95% CIs were associated with the presence of one, two and three or more
calculated for each of the three models. Additional ana- ultrasound signs, respectively, compared with when no
lysis was carried out to assess the diagnostic performance sign was present. The false-positive rate for the presence
of the presence of more than one ultrasound sign. The of at least one classic sign, novel sign and combined classic
weighted kappa (κ) statistic was computed to assess agree- and novel signs was 17%, 79% and 81%, respectively.
ment among the three reviewers for each of the ultrasound There were two nulliparous women with PAS in our
signs. cohort. One was a non-Hispanic black woman who
delivered one twin vaginally and one by Cesarean section
at 38 weeks’ gestation. The patient had no history of
RESULTS uterine curettage and needed peripartum hysterectomy
A total of 385 cases met the study entry criteria and were for placenta increta. The other patient was a Hispanic
evaluated, of which 28 (7.3%) had placenta accreta, woman with a history of one prior uterine curettage
11 (2.9%) had placenta increta and 16 (4.2%) had who underwent Cesarean section at 32 weeks. She
placenta percreta. Maternal demographic characteristics did not require hysterectomy, but her placenta was
of the study population are shown in Table 2, and the difficult to remove, and she was diagnosed with placenta
proportions of cases with individual classic and novel accreta.
signs according to type of PAS (accreta, increta, percreta) The analysis showed substantial to almost perfect
are shown in Table 3. The diagnostic performance of agreement among the three reviewers for the majority
individual ultrasound signs is summarized in Table 4. of ultrasound signs. The weighted κ values were
Many of the individual ultrasound signs had reasonable
accuracy, with 6/9 signs having an accuracy above 70% Table 2 Maternal demographic characteristics of patients included
for all PAS types and 6/9 signs having an accuracy above in the study
70% for placenta accreta alone.
Characteristic Value
Figure 3 shows ROC curves for the three models based
on classic signs, novel signs and combining both classic Maternal age (years) 34.3 ± 5.9
and novel signs, with AUCs of 0.81 (95% CI, 0.75–0.88), Gravidity
Primigravid 60/203 (29.6)
0.84 (95% CI, 0.77–0.90) and 0.88 (95% CI, 0.82–0.94),
Multigravid 143/203 (70.4)
respectively, for the prediction of all PAS types. The model Parity
combining classic and novel signs had the best predictive Nulliparous 112/203 (55.2)
performance for PAS (P = 0.03). Parous 91/203 (44.8)
Additional ROC-curve analysis was performed for Race
the prediction of placenta accreta, placenta increta and White 72/203 (35.5)
Black 20/203 (9.9)
placenta percreta individually using the same three mod-
Hispanic 14/203 (6.9)
els (Figure 4). The AUC values for classic, novel and Asian 61/203 (30.0)
combined models were 0.76 (95% CI, 0.66–0.86), 0.82 Other 36/203 (17.7)
(95% CI, 0.73–0.91) and 0.86 (95% CI, 0.78–0.93), BMI (kg/m2 )* 27.7 ± 4.9
respectively, for placenta accreta. The respective val- Smoker 3/185 (1.6)
ues were 0.81 (95% CI, 0.66–0.97), 0.73 (95% CI, Prior preterm birth 12/202 (5.9)
Previous Cesarean delivery
0.53–0.94) and 0.87 (95% CI, 0.72–1.00) for placenta
0 146/202 (72.3)
increta and 0.91 (95% CI, 0.81–1.00), 0.96 (95% CI, 1 35/202 (17.3)
0.93–0.99) and 0.98 (95% CI, 0.95–1.00) for placenta 2 16/202 (7.9)
percreta. The combined model performed significantly ≥3 5/202 (2.5)
better than did the classic or the novel one individually Planned Cesarean delivery 116/204 (56.9)
in predicting placenta accreta and placenta percreta. Pla- Prior curettage 39/187 (20.9)
Cesarean hysterectomy
centa accreta alone was diagnosed based on documented
Planned 30/205 (14.6)
difficulty in removing the placenta without histopatho- Performed 34/205 (16.6)
logical confirmation in six of the 28 cases. The remaining Admission to ICU 8/205 (3.9)
cases of placenta accreta, as well as all the cases of Mode of delivery
placenta increta and placenta percreta, had pathological Vaginal 44/205 (21.5)
confirmation. Figure 5 shows the diagnostic performance Cesarean 161/205 (78.5)
of the presence of classic, novel and combined classic Data are given as mean ± SD or n/N (%). Data were missing for
and novel ultrasound signs according to the number of most variables owing to retrospective nature of data acquisition
signs present. We found a ‘dose–response’ relationship, and lack of consistent documentation. *Data were available for
with 5% of patients having PAS without any classic sign, 272 women. BMI, body mass index; ICU, intensive care unit.

© 2021 International Society of Ultrasound in Obstetrics and Gynecology. Ultrasound Obstet Gynecol 2022; 59: 465–473.
470 Skupski et al.

Table 3 Proportions of placenta accreta spectrum (PAS) cases demonstrating each ultrasound sign in cases with adequate ultrasound images

Accreta Increta Percreta All PAS No PAS

Ultrasound sign (n = 28) (n = 11) (n = 16) (n = 55) (n = 330)

Classic signs*
Placental lacunae 14/22 (64) 6/10 (60) 13/13 (100) 33/45 (73) 53/238 (22)
Myometrial thinning 6/23 (26) 2/10 (20) 9/12 (75) 17/45 (38) 2/317 (1)
Bladder-wall interruption 9/23 (39) 2/9 (22) 10/12 (83) 21/44 (48) 3/287 (1)
Subplacental hypervascularity 5/15 (33) 5/8 (63) 9/9 (100) 19/32 (59) 8/174 (5)
Novel signs†
Small placental lacunae 11/17 (65) 5/8 (63) 12/13 (92) 28/38 (74) 20/251 (8)
Irregular placenta–myometrium interface 0/20 (0) 0/9 (0) 0/14 (0) 0/43 (0) 145/228 (64)
Vascular placenta–myometrium interface 0/20 (0) 0/9 (0) 0/14 (0) 0/43 (0) 73/160 (46)
Non-tapered placental edge 6/14 (43) 6/8 (75) 1/6 (17) 13/28 (46) 202/238 (85)
Placental bladder bulge 5/21 (24) 2/8 (25) 9/11 (82) 16/40 (40) 3/287 (1)

Data are given as n/N (%). Data were missing owing to inadequate images. *Classic signs were determined using a combination of
transabdominal and transvaginal ultrasound. †Novel signs were determined using only transvaginal ultrasound.

Table 4 Univariate diagnostic performance characteristics of ultrasound signs for the diagnosis of all placenta accreta spectrum types and
for placenta accreta alone

Placenta accreta spectrum (n = 55) Placenta accreta alone (n = 28)

Sens Spec PPV NPV Acc Sens Spec PPV NPV Acc
Ultrasound sign (%) (%) (%) (%) (%) (%) (%) (%) (%) (%)

Classic signs*
Placental lacunae 73 78 38 94 77 64 78 21 96 77
Myometrial thinning 38 99 89 92 92 26 99 75 95 94
Bladder-wall interruption 48 99 88 93 92 39 99 75 95 95
Subplacental hypervascularity 59 95 70 93 90 33 95 38 94 90
Novel signs†
Small placental lacunae 74 92 58 96 90 65 92 35 97 90
Irregular placenta–myometrium interface 0 36 0 66 31 0 36 0 81 33
Vascular placenta–myometrium interface 0 54 0 67 43 0 54 0 81 48
Non-tapered placental edge 46 15 6 71 18 43 15 3 82 17
Placental bladder bulge 40 99 84 92 92 24 99 63 95 94

*Classic signs were determined using a combination of transabdominal and transvaginal ultrasound. †Novel signs were determined using
only transvaginal ultrasound. Acc, accuracy; NPV, negative predictive value; PPV, positive predictive value; Sens, sensitivity; Spec, specificity.

1.00 (95% CI, 0.98–1.00) for placental lacunae, 0.61

1.00 (95% CI, 0.55–0.68) for myometrial thinning, 0.93
(95% CI, 0.90–0.96) for bladder-wall interruption, 0.91
(95% CI, 0.84–0.97) for subplacental hypervascularity,
0.75 0.71 (95% CI, 0.61–0.81) for small placental lacunae,
0.92 (95% CI, 0.85–0.99) for irregular PMI, 0.34
(95% CI, 0.27–0.41) for vascular PMI, 0.63 (95% CI,
Sensitivity

0.55–0.72) for non-tapered placental edge and 0.49

0.50
(95% CI, 0.41–0.58) for placental bladder bulge.

0.25 DISCUSSION

In this study, we confirmed the diagnostic capabil-

ity of classic signs of PAS, showed an incremental
0.00
diagnostic performance of classic signs in combination
0.00 0.25 0.50 0.75 1.00 with novel signs and demonstrated a high diagnostic
1 – Specificity performance associated with the presence of more
than one classic ultrasound sign, consistent with prior
Figure 3 Receiver-operating-characteristics curves for classic literature13 .
ultrasound signs ( ; area under the curve (AUC), 0.8146)), novel The model combining classic and novel signs showed a
ultrasound signs ( ; AUC, 0.8377) and a model combining high performance in determining the presence or absence
classic and novel signs ( ; AUC, 0.8767) in the prediction of all
of PAS, with an AUC of 0.88. The univariate negative
types of placenta accreta spectrum.
predictive value for each of the classic signs individually

© 2021 International Society of Ultrasound in Obstetrics and Gynecology. Ultrasound Obstet Gynecol 2022; 59: 465–473.
Ultrasound signs of placenta accreta spectrum 471

(a) (b) (c)

1.00 1.00 1.00

0.75 0.75 0.75

Sensitivity

Sensitivity

Sensitivity
0.50 0.50 0.50

0.25 0.25 0.25

0.00 0.00 0.00

0.00 0.25 0.50 0.75 1.00 0.00 0.25 0.50 0.75 1.00 0.00 0.25 0.50 0.75 1.00
1 – Specificity 1 – Specificity 1 – Specificity

Figure 4 Receiver-operating-characteristics (ROC) curves for classic signs ( ), novel signs ( ) and a model combining classic and novel
signs ( ) in the prediction of placenta accreta (a), placenta increta (b) and placenta percreta (c). The areas under the curve for classic,
novel and combined models, respectively, were 0.7640, 0.8174 and 0.8560 for placenta accreta, 0.8142, 0.7318 and 0.8657 for placenta
increta and 0.9077, 0.9639 and 0.9780 for placenta percreta.

100 16/17
(94%)

90

80
Incidence of one or more sign(s) (%)

70
14/23
8/14 (61%)
60 (57%)
34/69
50 (49%)

40

30 16/67
(24%)
20/108
(19%)
20
6/74 15/180 8/94
10 3/65 (8%) 15/287 10/157 (8%) (9%)
(5%) (5%) (6%)

0
0 1 2 ≥3
Number of signs present

Figure 5 Incidence of one or more ultrasound signs in patients with any type of placenta accreta spectrum (PAS) abnormality. The
numerator above each bar is the number of patients with any type of PAS. The denominator above each bar is the number of patients with
the designated number of ultrasound signs (0, 1, 2 or ≥ 3). The rate appearing above each bar is the rate of any type of PAS being present
when images showed the designated number of ultrasound signs. , Combined classic and novel signs; , novel signs; , classic signs.

and each of the novel signs individually ranged from including 23 studies and 3707 pregnancies, reported
92% to 96% and from 66% to 97%, respectively, in an average sensitivity of 90.7% (95% CI, 87.2–93.6%)
the diagnosis of any type of PAS and placenta accreta and specificity of 96.9% (95% CI, 96.3–97.5%)15 . Our
alone. The univariate accuracy for each of the classic blinded evaluation of ultrasound signs to diagnose PAS
signs individually and each of the novel signs individually compares favorably with the most recently published
ranged from 77% to 95% and 17% to 94%, respectively, blinded evaluation, in which Bowman et al.16 found
in the diagnosis of any type of PAS and placenta accreta that the sensitivity, specificity, positive predictive value,
alone. The presence of classic signs suggestive of PAS negative predictive value, accuracy and false-positive
should provide a warning that PAS is possible or likely, rate were 53.5%, 88.0%, 82.1%, 64.8%, 64.8%
while the lack of these signs should be reassuring. and 5.6%, respectively. Agreement between blinded
Although the novel signs are generally not as good at reviewers in our study was almost perfect (κ ≥ 0.81)
predicting individually, they may provide incremental for four signs (lacunae, bladder-wall interruption,
value when combined with the classic signs. The subplacental hypervascularity and irregular PMI) and
diagnostic performance in our study was similar to that substantial (κ ≥ 0.61) for three signs (myometrial
reported in the literature on PAS14 . A systematic review, thinning, small lacunae and non-tapered placental edge),

© 2021 International Society of Ultrasound in Obstetrics and Gynecology. Ultrasound Obstet Gynecol 2022; 59: 465–473.
472
demonstrating that detection of these ultrasound signs
of PAS is reliable. Agreement between reviewers for
the remaining two ultrasound signs was moderate to
poor, suggesting that vascular PMI and placental bladder
bulge may not be helpful in any diagnostic rubric
for PAS.
The development of the novel signs stemmed from our
clinical findings in several individual cases of PAS. In
particular, lacunae may form owing to increased jets of
blood from spiral arteries into the intervillous space that
impact upon villous trees and produce regression, leaving
larger spaces between villi. We studied small lacunae
because they could be precursors of large lacunae seen
later in gestation or they may be found when placenta
accreta is present, as opposed to placenta increta or
percreta. We have demonstrated that these novel signs
have reasonable accuracy in detecting PAS. It is important
to note that this study was completed before the recent
publication of the Society for Maternal–Fetal Medicine
PAS Ultrasound Marker Task Force17 , and the novel signs
are distinctly different from the more well known signs
described by the task force.
Univariate diagnostic performance characteristics
showed that the negative predictive value of each clas-
sic sign was above 90%. Clinicians should be reassured
about the absence of PAS when these signs are absent
in the population of women with placenta previa or
low-lying placenta in the mid-trimester. Another finding
is that the false-positive rate for the presence of at least
one classic sign was low (17%), which suggests that the
use of classic signs for diagnosis will not lead to a high
rate of unwarranted intervention. Also, small placental
lacunae had the highest negative predictive value, with
96% for PAS and 97% for placenta accreta alone, sug-
gesting that examination of the body of the placenta for
this sign may be clinically helpful.
Our findings show that when more than one sign is
present in any individual patient, there is an increased risk
of PAS18–20 . This culminated in a 94% rate of PAS when
three or more classic signs were seen. This information
is likely to be clinically useful in both patient counseling
and preparation for safe delivery.
With regard to the diagnosis of PAS with the clinical
finding of difficulty in removing the placenta, we believe
that this allowed the inclusion of some cases of placenta
accreta that would otherwise have been missed with the
use of only histopathological criteria, since there are no
reliable pathological signs of placenta accreta in these
clinical circumstances.
All our findings are particularly significant given
the inclusion of low-risk nulliparous women (55%
of our cohort), which allowed us to include women
with placenta accreta only, which may be associated
with pregnancies following curettage and not necessarily
Cesarean delivery. The lack of low-risk women in previous
studies assessing the association between ultrasound
signs and PAS has been highlighted as critical in the
literature17 .
© 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Skupski et al.
We suggest as the next step in the evaluation of PAS
the completion of a carefully designed prospective study
that would allow the inclusion of both low- and high-risk
women, collect second- and third-trimester images, train
all participating sonographers, reviewers and pathologists
in the consistent acquisition and interpretation of
findings (including intracervical lakes21 ) prior to the
start of patient recruitment and attempt to provide
histopathological examination of every placenta that was
deemed to be difficult to remove. This type of design will
provide the most generalizable results for the production
of a useful clinical diagnostic algorithm.
Strengths of this study include a relatively large number
of PAS cases, allowing the range of imaging characteristics
in both PAS and non-PAS cases to be determined. In
addition, independent and blinded review of images by
three board-certified maternal–fetal medicine providers
and the requirement for at least two reviewers to agree on
a finding allowed us to establish the reliability of the signs.
Another strength is the inclusion of low-risk women,
enhancing the generalizability of our findings. An addi-
tional strength is that we evaluated the diagnostic ability
of both classic and novel signs for all PAS types combined
and for each individual type of PAS. A limitation of our
study is the retrospective cohort design, which allowed
us to determine associations but not the true prospective
diagnostic ability. Moreover, different protocols for
image acquisition at each center could have led to
false-negative findings for some of the ultrasound signs.
In addition, a significant amount of missing demographic
and outcome data limited our ability to determine some
associations.
Conclusions
Abnormal placentation leads to physiological and
blood-flow derangement, which result in changes
detectable on sonographic imaging, known as classic signs
of PAS. Our study has confirmed the diagnostic ability of
the classic signs. We have also described novel signs of
PAS that could be visualized owing to the improved reso-
lution of transvaginal ultrasound, and demonstrated their
incremental value when used in combination with the
classic signs. The improved ability to suspect and detect
PAS during ultrasound imaging allows proper referral to
specialist centers, preparation for delivery by a multi-
disciplinary team and decreased maternal–fetal medicine
morbidity and mortality.
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SUPPORTING INFORMATION ON THE INTERNET
The following supporting information may be found in the online version of this article:
Table S1 Number of cases with placenta accreta spectrum disorders according to site
© 2021 International Society of Ultrasound in Obstetrics and Gynecology.
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