Ultrasound Obstet Gynecol 2013; 42: 509–517
Published online 2 October 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/uog.13194
Prenatal identification of invasive placentation using
ultrasound: systematic review and meta-analysis
F. D’ANTONIO, C. IACOVELLA and A. BHIDE
Fetal Medicine Unit, Division of Developmental Sciences, St George’s University of London, London, UK
K E Y W O R D S: invasive placental implantation; placenta accreta; prenatal diagnosis; ultrasound
ABSTRACT
Objective The accuracy of prospective sonographic
prenatal detection of invasive placentation is unclear.
The objective of this study was to conduct a systematic
review and meta-analysis to assess the performance of
ultrasound in at-risk women for prenatal identification of
invasive placentation.
Methods MEDLINE, EMBASE, The Cochrane Database
of Systematic Reviews, Database of Abstracts of Reviews
of Effects (DARE) and The Cochrane Central Register of
Controlled Trials (CENTRAL) were searched using the
search terms ‘placenta accreta’, ‘placenta increta’, ‘pla-
centa percreta’, ‘ultrasound’, ‘magnetic resonance imaging
(MRI)’, ‘invasive placenta’ and ‘infiltrative placenta’. Two
authors independently abstracted data from the articles.
Sensitivity, specificity, positive and negative likelihood
ratios (LR+ and LR–), the diagnostic odds ratio (DOR)
and their 95% CIs for each study were calculated. For-
est plots and summary receiver–operating characteristics
curves were produced. Between-study heterogeneity was
explored both graphically and statistically. The MOOSE
(meta-analysis of observational studies in epidemiology)
guidelines were followed.
Results Twenty-three studies involving 3707 pregnancies
at risk for invasive placentation were included. The overall
performance of ultrasound for the antenatal detection of
invasive placentation was as follows: sensitivity, 90.72
(95% CI, 87.2–93.6)%; specificity, 96.94 (95% CI,
96.3–97.5)%; LR+, 11.01 (95% CI, 6.1–20.0); LR–,
0.16 (95% CI, 0.11–0.23); and DOR, 98.59 (95% CI,
48.8–199.0). Among the different ultrasound signs, color
Doppler had the best predictive accuracy (sensitivity,
90.74 (95% CI, 85.2–94.7)%; specificity, 87.68 (95%
CI, 84.6–90.4)%; LR+, 7.77 (95% CI, 3.3–18.4); LR–,
0.17 (95% CI, 0.10–0.29); and DOR, 69.02 (95% CI,
22.8–208.9)).
Correspondence to: Dr Amar Bhide, Fetal Maternal Medicine Unit, St George’s University of London, London SW17 0RE, UK (e-mail:
abhide@sgul.ac.uk)
All authors contributed equally to the manuscript.
Accepted: 31 July 2013
Copyright  2013 ISUOG. Published by John Wiley & Sons Ltd.
Conclusions Ultrasound has a high accuracy for prenatal
diagnosis of disorders of invasive placentation in high-
risk women. The use of color Doppler improves the test
performance. Copyright  2013 ISUOG. Published by
John Wiley & Sons Ltd.
INTRODUCTION
Morbidly adherent placenta is a spectrum of conditions
characterized by an abnormal adherence of the placenta
to the implantation site. Three major variants of adherent
placentation can be recognized according to the degree of
trophoblastic invasion through the myometrium and the
uterine serosa: placenta accreta, placenta increta and pla-
centa percreta. Placenta accreta probably represents the
most common variant of abnormally adherent placenta,
and all varieties of invasive placentation are associated
with a significant increase in maternal morbidity, espe-
cially due to blood loss, damage to local organs, need for
urgent hysterectomy and postoperative complications1 .
Placenta previa and previous uterine surgery represent the
major risk factors for invasive placentation2 – 6 . Prena-
tal diagnosis of invasive placentation is associated with a
reduced risk of maternal complications such as peripartum
blood loss, need for transfusions and rate of hysterectomy,
as it allows a preplanned treatment of the condition7 – 13 .
Several terms are used to describe morbidly adherent
placenta; ‘invasive placentation’ is the term used in this
manuscript to include placenta accreta and its variants.
Ultrasonography is usually employed as the primary
modality for antenatal diagnosis of invasive placentation.
Prenatal magnetic resonance imaging is reported to
be complementary to ultrasound, as it may help in
diagnosing invasive placentation, especially in those cases
in which ultrasound is not conclusive, to assess the
degree of invasion (i.e. ambiguous ultrasound findings,
SYSTEMATIC REVIEW
510
posterior placenta previa)14,15 . The performance of
antenatal ultrasound and of different sonographic signs
is not consistent across published studies. This is most
probably owing to a combination of limited sample size,
retrospective design and variability of inclusion criteria
and definition of invasive placentation.
The aim of this review was to systematically assess
the performance of ultrasound in the prenatal diagnosis
of placenta accreta and its variants and to explore the
role of the different specific ultrasound signs in predicting
disorders of invasive placentation.
METHODS
Search strategy
This review was performed according to a protocol
designed a priori and recommended for systematic reviews
and meta-analyses16 – 18 . MEDLINE, EMBASE and The
Cochrane Library including The Cochrane Database of
Systematic Reviews (CDSR), Database of Abstracts of
Reviews of Effects (DARE) and The Cochrane Central
Register of Controlled Trials (CENTRAL) were searched
electronically on 7th February 2013, utilizing combina-
tions of the relevant medical subject heading (MeSH)
terms, keywords and word variants for ‘placenta accreta’,
‘placenta increta’, ‘placenta percreta’, ‘ultrasound’,
‘magnetic resonance imaging (MRI)’, ‘invasive placenta’
and ‘infiltrative placenta’ (Table S1 online). The search
and selection criteria were restricted to the English
language. Reference lists of relevant articles and reviews
were hand-searched for additional reports.
Study selection
Studies were assessed according to the following criteria:
population, outcome, prenatal diagnosis of placenta
accreta by ultrasound and study design. In this review, the
general term ‘invasive placentation’ will refer to placenta
accreta and its variants (increta/percreta). For the purpose
of this study, invasive placentation was defined based
on histopathological diagnosis of trophoblastic invasion
through the myometrium or clinical assessment of
abnormal adherence/evidence of gross placental invasion
at the time of surgery in the absence of histopathological
evidence. The overall sensitivity and specificity of prenatal
ultrasound in the diagnosis of invasive placentation and
the predictive value of various sonographic signs were
noted.
The sonographic signs included in this review were
the ones most commonly reported to be associated with
invasive placentation and comprise: (1) vascular lacunae
within the placenta, (2) loss of normal hypoechoic retro-
placental zone, (3) interruption of the bladder line and/or
focal exophytic masses extending into the bladder space
and (4) color Doppler abnormalities such as abnormal
blood vessels at the myometrium–bladder interface14 .
Interruption of the bladder line and the presence of
exophytic masses extending into the bladder space were
Copyright  2013 ISUOG. Published by John Wiley & Sons Ltd.
D’Antonio et al.
considered together and labeled as ‘abnormalities of the
uterus–bladder interface’. When multiple color Doppler
signs were reported and their overall presence in positive
and negative cases could not be extrapolated, only the one
showing the best predictive performance was included. In
cases in which the overall performance of ultrasound and
the number of imaging criteria used to diagnose invasive
placentation were not stated, the sign showing the best
predictive value was used as a surrogate for the final
diagnosis.
Prospective and retrospective cohorts, case–control
studies, case reports and case series were analyzed. Only
studies reporting a prospective diagnosis of invasive
placentation and/or the evaluation of single ultrasound
signs in the second and/or third trimesters of pregnancy
and studies for which the number of true positives,
false positives, true negatives and false negatives were
available were included in the final analysis. Opinion
articles and studies carried out only in the first trimester
of pregnancy were excluded. Case reports and case series
with fewer than five cases and larger case series with a
lack of information on false negatives were also excluded
in order to avoid publication bias.
We decided to exclude several published reports. Some
reported the inclusion criterion ‘suspicion of accreta’ on
routine ultrasound. This is problematic, since there are no
objective criteria for this condition. No information was
given on how many accreta cases were missed because
of a lack of suspicion on routine ultrasound. Absence of
definition of ‘accreta’ also led to exclusion.
Data extraction and quality assessment
Two reviewers (F.D., C.I.) independently extracted data.
Inconsistencies were discussed by the reviewers and
consensus reached. For those articles in which targeted
information was not reported but the methodology was
such that the information might have been recorded
initially, the authors were contacted requesting the data.
The quality of the studies was assessed using the revised
tool for the quality assessment of diagnostic accuracy
studies (QUADAS-2)19 . Each item is scored ‘yes’ or ‘no’,
or ‘unclear’ if there is insufficient information to make an
accurate judgment18 .
Statistical analysis
Meta-DiSc 1.4 (http://www.hrc.es/investigacion/metadisc_
en.htm; Hospital Universitario Ramón y Cajal, Madrid,
Spain) was used to analyze the data20 . Heterogeneity
was identified using Cochran’s Q test and the I2 statistic,
in which P < 0.05 and I2 ≥ 50% indicate significant
heterogeneity20,21 . According to the results of hetero-
geneity testing, we chose an appropriate statistical model
(random or fixed effects model) to pool the sensitivity,
specificity, positive likelihood ratio (LR+), negative
likelihood ratio (LR–) and diagnostic odds ratio (DOR).
Pooled sensitivity, specificity, LR+, LR– and DOR were
calculated according to reconstructed 2 × 2 tables22 – 25 .
Ultrasound Obstet Gynecol 2013; 42: 509–517.
Prenatal identification of invasive placentation 511

The DOR is defined as the ratio of the odds of the test R E S U LT S

being positive if the subject has a disease relative to the
odds of the test being positive if the subject does not have
the disease (and is also related to the likelihood ratios as:
LR+/LR–)26 . Additionally, summary receiver–operating
characteristics (sROC) curves were plotted. The area
under the curve (AUC) and the Q* index were also
computed to evaluate the overall performance of the
diagnostic test accuracy. The AUC of an sROC curve is
a measure of the overall performance of a diagnostic test
in accurately differentiating those cases with and those
without the condition of interest. The Q* index is defined
by the point at which sensitivity and specificity are equal,
which is closest to the ideal top-left corner of the sROC
space. Both values range between 0 and 1, with higher
values indicating better test performance27 .
General characteristics of the studies
The search yielded 447 possible citations; of these, 360
were excluded by reviewing the title or the abstract, as
they did not meet the selection criteria. The remaining 87
full-text manuscripts were retrieved, and 23 studies were
included in the final analysis. These 23 studies included
3707 pregnancies at risk for invasive placentation, mainly
based on the presence of anterior placenta and a history of
uterine surgery. The incidence of invasive placentation in
this review was 9.3%. A summary of the included studies
is given in Table 1.
Quality assessment based on QUADAS guidelines was
conducted on all 23 studies included for systematic review
(Figure 1). Most of the studies were of high quality and

Table 1 Characteristics of studies included in the systematic review

Diagnostic Women Invasive

Study Trimester Reference criteria scanned placentation
Reference design Inclusion criteria at scan standard (n) (n) (n)

Cali (2013)38 Prosp PP, previous uterine surgery 2–3 Path ≥2 187 41
Fishman (2011)44 Retro PP 3 Path ≥2 154 23
Esakoff (2011)45 Retro PP 3 Path ? 108 19
Hamada (2011)30 Prosp PP and/or previous CS 3 Path ≥2 70 5
Mansour (2011)41 Prosp PP, previous uterine surgery 3 Surg ≥2 35 15
Lim (2011)42 Retro Previous CS and/or third-trimester bleeding 2–3 Path ≥1 13 9
El Behery (2010)46 Prosp PP, previous CS or uterine surgery 3 Path, Surg ≥1 35 7
Shih (2009)37 Prosp PP and/or previous CS or uterine surgery 3 Path ≥1 170 39
Chou (2009)47 Retro PP, previous CS 2–3 Path ? 44 6
Wong (2008)52 Retro PP and/or previous CS or uterine surgery 2–3 Path, Surg ≥2 66 9
Masselli (2008)39 Retro PP, previous CS 2–3 Path ≥2 50 12
Dwyer (2008)40 Retro PP and/or previous CS or uterine surgery ? Path, Clin ≥2 32 15
Miura (2008)48 Prosp PP and/or previous CS 3 Path ≥4 12 4
Japaraj (2007)49 Prosp PP, previous CS 3 Path, Surg ≥1 21 7
Warshak (2006)43 Retro PP and/or previous uterine CS, uterine surgery 1–2–3 Path ≥2 453 39
Yang (2006)31 Retro PP, previous CS 2,3 Path ≥1 51 23
Comstock (2004)28 Prosp Low anterior placenta, previous CS 2–3 Path ≥1 2002 15
Moodley (2004)50 Prosp PP 3 Path, Surg ≥2 30 3
Chou (2000)34 Retro PP and/or previous CS or uterine surgery 2–3 Path ? 80 17
Twickler (2000)35 Prosp PP, previous CS 3 Path, Surg ≥1 20 10
Levine (1997)36 Prosp PP, previous CS or uterine surgery 3 Path, Surg ≥2 19 7
Lerner (1995)51 Prosp PP, previous CS 3 Path ≥2 21 5
Finberg (1992)32 Prosp PP, previous CS 2–3 Path, Surg ≥2 34 15

Only first author of each study is shown. Clin, clinical findings; CS, Cesarean section; Path, pathology; PP, placenta previa; Prosp,
prospective; Retro, retrospective; Surg, surgical findings; ?, not stated.

(a) (b)
Flow and timing Reference standard

Reference standard Index test

Index test
Patient selection

Patient selection 0 20 40 60 80 100

Proportion (%)
0 10 20 30 40 50 60 70 80 90 100
Proportion (%)

Figure 1 Summary of results of Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool for articles included in the present
analysis. Proportion of studies with low ( ), high ( ) or unclear ( ): (a) risk of bias; (b) concerns regarding applicability.

Copyright  2013 ISUOG. Published by John Wiley & Sons Ltd. Ultrasound Obstet Gynecol 2013; 42: 509–517.
512 D’Antonio et al.

there was an overall low risk of bias and low concern sROC for the performance of prenatal ultrasound for the
regarding the applicability of the studies19 . As there detection of invasive placenta is shown in Figure 4, while
was evidence of significant heterogeneity between the the corresponding values for specific ultrasound signs are
studies included, a random effects model was used. The reported in Figure 5 and in Table 2.
heterogeneity test results for sensitivity and specificity are The AUC for diagnostic accuracy was 0.956 (standard
illustrated in Figures 2 and 3. error (SE), 0.011) for ultrasound overall, 0.889 (SE,
0.032) for presence of placental lacunae, 0.884 (SE,
0.049) for loss of the hypoechoic space between the
Diagnostic accuracy placenta and the myometrium, 0.934 (SE, 0.037) for
The overall performance of ultrasound for the antenatal abnormalities at the level of the uterus–bladder interface
detection of invasive placentation was as follows: and 0.948 (SE, 0.020) for color Doppler abnormalities
sensitivity, 90.72 (95% CI, 87.2–93.6)%; specificity, (Figure 5). Among the different ultrasound signs, color
96.94 (95% CI, 96.3–97.5)%; LR+, 11.01 (95% CI, Doppler had the best predictive accuracy (sensitivity,
6.1–20.0); LR–, 0.16 (95% CI, 0.11–0.23); and DOR, 90.74 (95% CI, 85.2–94.7)%; specificity, 87.68 (95%
98.59 (95% CI, 48.8–199.0) (Table 2 and Figure 2). The CI, 84.6–90.4)%; LR+, 7.77 (95% CI, 3.3–18.4); LR–,
0.17 (95% CI, 0.10–0.29); and DOR, 69.02 (95% CI,
22.8–208.9)).
Sensitivity (95% CI)
38
CALI
1.00 (0.91–1.00)
HAMADA30
0.60 (0.15–0.95)
MANSOUR41 0.87 (0.60–0.98) DISCUSSION
Fishman44 0.91 (0.72–0.99)
Esakoff45 0.89 (0.67–0.99)
Lim42
EL BEHERY46
0.67 (0.30–0.93) The findings from this review show that prenatal
1.00 (0.59–1.00)
SHIH37 1.00 (0.91–1.00) ultrasound has predictive accuracy in diagnosing invasive
Chou47 1.00 (0.54–1.00)
Masselli39 0.92 (0.62–1.00) placentation in a population at high risk. Among the
MIURA48 1.00 (0.40–1.00)
Dwyer40 0.93 (0.68–1.00) sonographic signs of invasive placentation, color Doppler
Wong52 0.89 (0.52–1.00)
JAPARAJ49
43 1.00 (0.59–1.00) had the best combination of sensitivity and specificity.
Warshak 0.77 (0.61–0.89)
Yang31 0.87 (0.66–0.97) Quality assessment of the studies showed that the study
COMSTOCK28
MOODLEY
50 1.00 (0.78–1.00)
0.67 (0.09–0.99)
quality was generally high, high sensitivity and specificity
35
TWICKLER
Chou34
1.00 (0.69–1.00)
0.82 (0.57–0.96)
being seen in both retrospective and prospective studies.
36
LEVINE 0.86 (0.42–1.00) Women who had had previous uterine surgery and
LERNER51 1.00 (0.48–1.00)
32
FINBERG 0.93 (0.68–1.00) placenta previa were assessed for invasive placentation.
The prevalence of invasive placentation was 9.3% in this
Pooled sensitivity = 0.91 (0.87–0.94) review. This prevalence is heavily influenced by the largest
Chi-square = 43.56; df = 22 (P = 0.0040)
Inconsistency (I-square) = 49.5% study, of over 2000 women, in which the prevalence of
0 0.2 0.4 0.6 0.8 1.0
Sensitivity
invasive placentation was much lower (0.75%)28 . This
was most probably owing to the fact that the authors
Specificity (95% CI)
38 1.00 (0.98–1.00)
included women with previous Cesarean section and
CALI
HAMADA
30 0.98 (0.92–1.00) low-lying placenta detected in the second trimester of
MANSOUR41 0.80 (0.56–0.94)
Fishman 44
1.00 (0.97–1.00) pregnancy, not all of which may have continued to be
Esakoff45 0.91 (0.83–0.96)
Lim42 0.50 (0.07–0.93) low-lying in the third trimester. If we exclude this study,
46
EL BEHERY 0.79 (0.59–0.92)
SHIH
37
0.85 (0.78–0.91) the pooled prevalence of invasive placentation was 19.3%.
47
Chou 1.00 (0.91–1.00)
Masselli
39
1.00 (0.91–1.00) We think this figure represents a more realistic estimation
48
MIURA
Dwyer 40
0.63 (0.24–0.91)
0.71 (0.44–0.90)
of invasive placentation in women with a low placenta
Wong52 0.98 (0.91–1.00) in the third trimester who had had a previous Cesarean
JAPARAJ49 1.00 (0.77–1.00)
Warshak43
31
0.96 (0.94–0.98) delivery.
Yang 0.79 (0.59–0.92)
COMSTOCK
50
28
0.99 (0.99–0.99) Prenatal diagnosis of invasive placentation has been
MOODLEY 0.93 (0.76–0.99)
TWICKLER
35
0.60 (0.26–0.88) shown to reduce the rate of maternal morbidity, as it
34
Chou 0.97 (0.89–1.00)
LEVINE
36
0.92 (0.62–1.00) allows planned management of the condition through
LERNER51 0.94 (0.70–1.00) the use of interventional radiology techniques or a
FINBERG32 0.79 (0.54–0.94)
conservative surgical approach saving the uterus8 – 13,29 .
Conservative surgical approach often involves the use
Pooled specificity = 0.97 (0.96–0.97)
Chi-square = 203.19; df = 22 (P = 0.0000)
of a fundal/classical incision to deliver the baby
0 0.2 0.4 0.6 0.8 1.0 Inconsistency (I-square) = 89.2% without disturbing the placenta. Complications from the
Specificity
placement of vascular occlusive balloons have also been
reported. It is important that prenatal diagnosis of invasive
Figure 2 Forest plots of overall sensitivity and specificity of placentation is accurate and the false-positive rate of the
ultrasonography in the prenatal diagnosis of invasive placentation
according to the current analysis. Only first author’s name is given diagnosis is kept to a minimum.
for each reference; names of authors of prospective studies are in The overall values of sensitivity and specificity for the
capitals and names of authors of retrospective studies are in ultrasound diagnosis of invasive placentation reported
capital/lower-case letters. in this review are based on a number of sonographic

Copyright  2013 ISUOG. Published by John Wiley & Sons Ltd. Ultrasound Obstet Gynecol 2013; 42: 509–517.
Prenatal identification of invasive placentation 513

(a) Sensitivity (95% CI) Specificity (95% CI)

38 38
Cali 0.73 (0.57–0.86) Cali 0.86 (0.80–0.91)
41 41
Mansour 0.87 (0.60–0.98) Mansour 0.81 (0.58–0.95)
30 30
Hamada 0.60 (0.15–0.95) Hamada 0.71 (0.58–0.81)
46 46
El Behery 0.86 (0.42–1.00) El Behery 0.93 (0.76–0.99)
37 37
Shih 0.54 (0.37–0.70) Shih 0.85 (0.77–0.90)
48 48
Miura 1.00 (0.40–1.00) Miura 0.25 (0.03–0.65)
52 52
Wong 49 0.78 (0.40–0.97) Wong 49 0.39 (0.26–0.52)
Japaraj 0.86 (0.42–1.00) Japaraj 1.00 (0.77–1.00)
31 31
Yang 0.87 (0.66–0.97) Yang 0.79 (0.59–0.92)
28 28
Comstock 0.80 (0.52–0.96) Comstock 1.00 (1.00–1.00)
35 35
Twickler 1.00 (0.69–1.00) Twickler 0.70 (0.35–0.93)
51 51
Lerner 1.00 (0.48–1.00) Lerner 0.94 (0.70–1.00)
32 32
Finberg 0.93 (0.68–1.00) Finberg 0.53 (0.29–0.76)

Pooled sensitivity = 0.77 (0.71–0.83) Pooled specificity = 0.95 (0.94–0.96)

Chi-square = 27.02; df = 12 (P = 0.0077) Chi-square = 482.24; df = 12 (P = 0.0000)
0 0.2 0.4 0.6 0.8 1.0 Inconsistency (I-square) = 55.6% 0 0.2 0.4 0.6 0.8 1.0 Inconsistency (I-square) = 97.5%
Sensitivity Specificity

(b) Sensitivity (95% CI) Specificity (95% CI)

Cali
38
0.90 (0.77–0.97) Cali38 0.81 (0.73–0.87)
Mansour41 0.87 (0.60–0.98) Mansour41 0.81 (0.58–0.95)
30 30
Hamada 0.60 (0.15–0.95) Hamada 0.98 (0.92–1.00)
El Behery46 1.00 (0.59–1.00) El Behery46 0.89 (0.72–0.98)
37 37
Shih 0.44 (0.28–0.60) Shih 0.95 (0.90–0.98)
Wong52 1.00 (0.66–1.00) Wong52 0.35 (0.23–0.49)
48
Miura48 1.00 (0.40–1.00) Miura 0.25 (0.03–0.65)
Japaraj49 0.43 (0.10–0.82) Japaraj49 1.00 (0.77–1.00)
28 28
Comstock 0.60 (0.32–0.84) Comstock 0.99 (0.99–1.00)
Finberg32 0.13 (0.02–0.40) Finberg32 0.79 (0.54–0.94)

Pooled sensitivity = 0.66 (0.58–0.74) Pooled specificity = 0.96 (0.95–0.97)

Chi-square = 61.10; df = 9 (P = 0.0000) Chi-square = 339.28; df = 9 (P = 0.0000)
0 0.2 0.4 0.6 0.8 1.0 Inconsistency (I-square) = 85.3% 0 0.2 0.4 0.6 0.8 1.0 Inconsistency (I-square) = 97.3%
Sensitivity Specificity

(c) Sensitivity (95% CI) Specificity (95% CI)

Cali
38
0.71 (0.54–0.84) Cali38 0.99 (0.96–1.00)
46 46
El Behery 0.43 (0.10–0.82) El Behery 0.96 (0.82–1.00)
47 47
Chou 1.00 (0.54–1.00) Chou 1.00 (0.91–1.00)
37 37
Shih 0.18 (0.08–0.34) Shih 1.00 (0.97–1.00)
Wong52 0.11 (0.00–0.48) Wong52 1.00 (0.94–1.00)
Japaraj
49
0.57 (0.18–0.90) Japaraj49 1.00 (0.77–1.00)
Comstock
28
0.20 (0.04–0.48) Comstock28 1.00 (1.00–1.00)
35
Twickler35 0.90 (0.55–1.00) Twickler
32
0.70 (0.35–0.93)
32 Finberg
Finberg 0.80 (0.52–0.96) 1.00 (0.52–1.00)

Pooled sensitivity = 0.50 (0.41–0.58) Pooled specificity = 1.00 (0.99–1.00)

Chi-square = 58.34; df = 8 (P = 0.0000) Chi-square = 34.04; df = 8 (P = 0.0000)
0 0.2 0.4 0.6 0.8 1.0 Inconsistency (I-square) = 86.3% 0 0.2 0.4 0.6 0.8 1.0 Inconsistency (I-square) = 76.5%
Sensitivity Specificity

(d) Sensitivity (95% CI) Specificity (95% CI)

38
38 Cali 1.00 (0.98–1.00)
Cali 0.90 (0.77–0.97) Mansour41 0.90 (0.68–0.99)
Mansour41 0.67 (0.38–0.88) El Behery46 0.96 (0.76–0.99)
46
El Behery 0.86 (0.42–1.00) Chou
47
1.00 (0.91–1.00)
47
Chou 1.00 (0.54–1.00) Shih37 0.85 (0.78–0.91)
37
Shih 1.00 (0.91–1.00) Wong52 0.41 (0.28–0.56)
52
Wong 0.88 (0.47–1.00) Miura
48
0.50 (0.16–0.84)
48
Miura 49 1.00 (0.40–1.00) Japaraj
49
1.00 (0.77–1.00)
Japaraj 1.00 (0.59–1.00) Moodley50 0.85 (0.66–0.96)
Moodley50 0.67 (0.09–0.99) Chou 34
0.97 (0.89–1.00)
34
Chou 0.82 (0.57–0.96) Twickler
35
0.60 (0.26–0.88)
Twickler35 1.00 (0.69–1.00) Lerner51 0.94 (0.70–1.00)
Lerner51 1.00 (0.48–1.00)

Pooled specificity = 0.88 (0.85–0.90)

Pooled sensitivity = 0.91 (0.85–0.95)
Chi-square = 134.64; df = 11 (P = 0.0000)
Chi-square = 23.21; df = 11 (P = 0.0165)
0 0.2 0.4 0.6 0.8 1.0 Inconsistency (I-square) = 91.8%
0 0.2 0.4 0.6 0.8 1.0 Inconsistency (I-square) = 52.6%
Specificity
Sensitivity

Figure 3 Forest plots of sensitivity and specificity of specific ultrasound signs in the prenatal diagnosis of invasive placentation according to
the current analysis: (a) placental lacunae, (b) loss of retroplacental clear space, (c) bladder-border abnormalities and (d) color Doppler
abnormalities.

criteria. We hypothesize that reduction in the number of
sonographic criteria needed to label a scan as suggestive
of invasive placentation may increase the sensitivity but is
likely to reduce the specificity of the test. Conversely, an
increase in the number of criteria needed to label a case
as positive would reduce sensitivity but would improve
specificity.
Assessment of individual signs should be viewed with
caution. Observation of one sign is likely to increase the
chance of detecting others, since the signs are not looked
for in isolation. In this review, we found a sensitivity
of 77.43 (95% CI, 70.9–83.1)% and a specificity
of 95.02 (95% CI, 94.1–95.8)% for the presence of
lacunae. The pathophysiology of placental lacunae is not

Copyright  2013 ISUOG. Published by John Wiley & Sons Ltd. Ultrasound Obstet Gynecol 2013; 42: 509–517.
514 D’Antonio et al.

Table 2 Pooled values for sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR–) and diagnostic odds ratio (DOR) for
ultrasound overall and the different ultrasound signs in the identification of invasive placentation

Studies Patients Sensitivity Specificity LR+ LR– DOR

Diagnostic method (n) (n) (95% CI) (%) (95% CI) (%) (95% CI) (95% CI) (95% CI)

Ultrasound (overall) 23 3707 90.72 96.94 11.01 0.16 98.59

(87.2–93.6) (96.3–97.5) (6.1–20.0) (0.11–0.23) (48.8–199.0)
Placental lacunae 13 2725 77.43 95.02 4.52 0.29 24.32
(70.9–83.1) (94.1–95.8) (2.5–8.1) (0.20–0.43) (9.13–64.8)
Loss of hypoechoic space 10 2633 66.24 95.76 5.64 0.38 21.98
(58.3–73.6) (94.9–96.5) (2.3–14.1) (0.20–0.69) (6.8–70.6)
Abnormalities of uterus– 9 2579 49.66 99.75 30.56 0.51 93.70
bladder interface (41.4–58.0) (99.5–99.9) (8.1–115.5) (0.34–0.77) (35.5–247.5)
Color Doppler 12 714 90.74 87.68 7.77 0.17 69.02
abnormalities (85.2–94.7) (84.6–90.4) (3.3–18.4) (0.10–0.29) (22.8–208.9)

1.0 myometrium, which is normally echogenic and smooth14 .

Exophytic masses in the bladder are likely to be seen only
0.9
with placenta percreta. Observation of this sign is a reli-
0.8 able ‘rule-in’ sign for making the diagnosis, but its absence
does not exclude lesser degrees of placental adherence.
0.7
Many reported series on invasive placentation are
0.6 retrospective in nature and few were blinded. With the
Sensitivity

benefit of hindsight, it may be easier to spot signs in

0.5
0.4
0.3
0.2
0.1
0 placenta with invasive placentation. The results are only
0 0.2 0.4 0.6 0.8
1 − Specificity
Figure 4 Summary receiver–operating characteristics curve (—)
with 95% CI (---) for ultrasonography in the prenatal diagnosis of
invasive placentation (area under the curve ± SE = 0.956 ± 0.011;
Q* ± SE = 0.898 ± 0.015). Size of data points is proportional to
study size.
clear, although their presence has been associated with
an increased likelihood of invasive placentation30 – 34 .
Lacunae may be present even in women with placenta
previa without myometrial invasion30 . The invasion
of trophoblastic tissue through the myometrium and
the absence of decidua basalis in invasive placentation
progressively lead to a reduction in myometrial thick-
ness and a loss of the hypoechoic space between the
myometrium and the placenta35 . The low sensitivity of
this ultrasound sign may arise because the lower uterine
segment appears as a thin line during the late third
trimester on conventional transabdominal ultrasound,
and evaluation of the interface between the myometrium
and the placenta may be difficult.
Higher degrees of placental invasion lead to the
destruction of the outer third of the myometrium and
uterine serosa with subsequent involvement of the blad-
der. This condition may be diagnosed with ultrasound
by examining the border between the bladder and
images on prenatal ultrasound. Most series included
in the current review were prospective. The rest were
also prospectively conducted, but ultrasound signs were
examined retrospectively. The availability, not only of
true positives but also of true and false negatives,
gives us confidence in the observed results. However,
the results are not applicable to fundal or posterior
1.0
applicable to women with placenta previa and a history
of a Cesarean delivery or uterine surgery. This is the
reason for low scores for generalizability observed in the
quality assessment. Low anterior placenta with invasive
placentation poses the biggest challenge to the surgeon.
Entry into the uterus for delivery of the baby is affected
by the presence of the placenta. It is impossible not
to disturb the placenta at conventional lower segment
Cesarean delivery. We argue that the group of anterior
placenta previa with a previous Cesarean section forms the
largest group amongst women with invasive placentation,
the group most likely to experience complications and
the group in whom prenatal diagnosis is likely to have
the biggest impact. Abnormalities on color Doppler and
presence of abnormal vessels performed best as predictors
of disorders of invasive placentation in high-risk women.
However, this is not an objective criterion, and needs to
be clarified.
In conclusion, the results of this study show that
among the different ultrasound signs the presence of
abnormal vasculature on color Doppler ultrasound has
the best combination of sensitivity and specificity, and
that abnormality of the uterus–bladder interface has the
best specificity for the prediction of invasive placentation.
The presence of placental lacunae and loss of the clear
space between the placenta and the myometrium does
not perform as well. In women with a low anterior

Copyright  2013 ISUOG. Published by John Wiley & Sons Ltd. Ultrasound Obstet Gynecol 2013; 42: 509–517.
Prenatal identification of invasive placentation 515

(a) 1.0 (b) 1.0

0.9 0.9

0.8 0.8

0.7 0.7

0.6 0.6

Sensitivity
Sensitivity

0.5 0.5

0.4 0.4

0.3 0.3

0.2 0.2

0.1 0.1

0 0
0 0.2 0.4 0.6 0.8 1.0 0 0.2 0.4 0.6 0.8 1.0
1 − Specificity 1 − Specificity

(c) 1.0 (d) 1.0

0.9 0.9

0.8 0.8

0.7 0.7

0.6 0.6
Sensitivity
Sensitivity

0.5 0.5

0.4 0.4

0.3 0.3

0.2 0.2

0.1 0.1

0 0
0 0.2 0.4 0.6 0.8 1.0 0 0.2 0.4 0.6 0.8 1.0
1 − Specificity 1 − Specificity

Figure 5 Summary receiver–operating characteristics curves (—) with 95% CI (---) for specific ultrasound signs in the prenatal diagnosis of
invasive placentation: (a) placental lacunae (area under the curve (AUC) ± SE = 0.889 ± 0.032; Q* ± SE = 0.820 ± 0.034), (b) loss of
retroplacental clear space (AUC = 0.884 ± 0.049; Q* = 0.815 ± 0.050), (c) bladder-border abnormalities (AUC = 0.934 ± 0.037;
Q* = 0.870 ± 0.045) and (d) color Doppler abnormalities (AUC = 0.948 ± 0.020; Q* = 0.888 ± 0.027). Size of data points is proportional to
study size. indicates two overlapping data points.

placenta who have had uterine surgery, third-trimester
ultrasound is highly sensitive and specific in diagnosing
invasive placentation prenatally. In women with previous
Cesarean section and low anterior placenta detected in the
third trimester, the prevalence of invasive placentation
is roughly one in five. Future research should be
directed at developing objective criteria for color Doppler
abnormalities and for determining the best surgical
technique for delivery.
ACKNOWLEDGMENTS
We would like to thank Ms Tiffany Hoare, NHS liaison
librarian, St George’s University of London, for her help
with the literature search. We would also like to thank
Prof. Palacios-Jaquaremada, Dr Cali, Dr Wong and Dr
Mansour for their contribution to this systematic review
in terms of additional data supplied and support.
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SUPPORT ING IN F O R M AT I O N O N T H E I N T E R N E T
The following supporting information may be found in the online version of this article:
Table S1 Search strategy using MEDLINE, EMBASE, Cinahl and The Cochrane Library (since inception)
including The Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of
Effects (DARE) and The Cochrane Central Register of Controlled Trials (CENTRAL)

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