UOG Journal Club: November 2013 Prenatal identification of invasive placentation using ultrasound: systematic review and meta-analysis F. D'Antonio, C. Iacovella and A. Bhide Link to free-access article: http://onlinelibrary.wiley.com/doi/10.1002/uog.13194/abstract

1. UOG Journal Club: November 2013
Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
F. D’Antonio, C. Iacovella and A. Bhide
Volume 42, Issue 5, Date: November 2013, pages 509-517
Journal Club slides prepared by Dr Leona Poon
(UOG Editor for Trainees)

2. •
Morbidly adherent placenta is associated with a significant increase in
maternal morbidity (Oyelese and Smulian, 2006).
•
Three major variants can be recognized according to the degree of
trophoblastic invasion through the myometrium and serosa:
•
Placenta accreta (most common)
•
Placenta increta
•
Placenta percreta
•
Prenatal diagnosis of invasive placentation has been shown to reduce
risk of maternal complications (Eller et al, 2009; Warshak et al, 2010).
•
Ultrasound is the primary modality for prenatal diagnosis, and MRI
can be complementary to ultrasound.
Oyelese Y, Smulian JC. Obstet Gynecol 2006;107;927-41.
Eller AG et al. BJOG 2009;116:648-54.
Warshak CR et al. Obstet Gynecol 2010;115:65-9.

3. Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
D’Antonio et al., UOG 2013
Objective
To conduct a systematic review and meta-analysis
to assess the performance of ultrasound in at-risk women for
prenatal identification of invasive placentation

4. Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
D’Antonio et al., UOG 2013
Methodology
Study selection
• Invasive placentation was defined based on histopathological
diagnosis of trophoblastic invasion, or clinical assessment of abnormal
adherence at time of surgery.
• Sonographic signs included:
(1)vascular lacunae within placenta
(2)loss of normal hypoechoic retroplacental zone
(3)interruption of bladder line and/or focal exophytic masses extending
into bladder space
(4)color Doppler abnormalities such as abnormal blood vessels at
myometrial-bladder interface.

5. Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
D’Antonio et al., UOG 2013
Methodology
Eligibility criteria
• Studies reporting a
prospective diagnosis of
invasive placentation and/or the
evaluation of single ultrasound
signs in the 2nd and 3rd
trimesters.
• Studies for which the number
of true +ve, false +ve, true –ve
and false –ve outcomes were
available.
Data extraction
• Two reviewers independently
extracted data.
• Quality of studies was
assessed using the revised tool
for quality assessment of
diagnostic accuracy studies
(QUADAS-2).

6. Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
D’Antonio et al., UOG 2013
Methodology
• Meta-DiSc 1.4 was used to analyze the data.
• Heterogeneity between studies: Cochran’s Q test and I2 statistic.
• P < 0.05 and I2 > 50% indicate significant heterogeneity.
• Random or fixed effects models were used according to
heterogeneity in order to pool the sensitivity, specificity, positive
likelihood ratio (LR+), LR- and diagnostics odds ratio (DOR).
• ROC or summary ROC curves were plotted, AUC and the Q* index
were computed to evaluate overall performance of diagnostic
accuracy.

7. Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
D’Antonio et al., UOG 2013
Results
477 potentially appropriate studies from
electronic search
360 studies were excluded by reviewing
the title or abstract, as they did not meet
the selection criteria
87 potentially appropriate studies for inclusion
in meta-analysis
64 studies were further excluded
23 studies (including 3707 pregnancies at risk
for invasive placentation) were included in the
final analysis

8. Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
D’Antonio et al., UOG 2013
Results
(a)
Proportion of studies with low
(b)
Summary of results of the QUADAS tool
, high or unclear risk of bias (a) or concerns regarding applicability (b)
Quality assessment based on QUADAS guidelines demonstrated that
most studies were of high quality, low risk of bias and low
concern regarding the applicability of the studies.

9. Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
D’Antonio et al., UOG 2013
Results
Forest plots of overall sensitivity and specificity of ultrasonography
in the prenatal diagnosis of invasive placentation according to the current analysis
Prevalence of invasive placentation is 9.3%

10. Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
D’Antonio et al., UOG 2013
Results
Pooled values for sensitivity, specificity, LR+, LR- and DOR
for overall ultrasound and the different ultrasound signs
in the identification of invasive placenta
Studies Patients Sensitivity Specificity
LR+
(n)
(n)
(95% CI) (%) (95% CI) (%) (95% CI)
23
3707
90.7
96.9
11.0
(87.2-93.6)
(96.3-97.5) (6.1-20.0)
Placenta lacunae
13
2725
77.4
95.0
4.5
(70.9-83.1)
(94.1-95.8)
(2.5-8.1)
Loss of hypoechoic
10
2633
66.2
95.8
5.6
space
(58.3-73.6)
(94.9-96.5) (2.3-14.1)
Abnormalities of
9
2579
49.7
99.8
30.6
uterus-bladder interface
(41.4-58.0)
(99.5-99.9) (8.1-115.5)
LR(95% CI)
0.2
(0.1-0.2)
0.3
(0.2-0.4)
0.4
(0.2-0.7)
0.5
(0.3-0.8)
DOR
(95% CI)
98.6
(48.8-199.0)
24.3
(9.1-64.8)
22.0
(6.8-70.6)
93.7
(35.5-247.5)
Color Doppler
abnormalities
0.2
(0.1-0.3)
69.0
(22.8-208.9)
Diagnostic
method
Ultrasound (overall)
12
714
90.7
(85.2-94.7)
87.7
(84.6-90.4)
7.8
(3.3-18.4)

11. Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
D’Antonio et al., UOG 2013
Results
sROC curves of placental lacunae (blue),
loss of retroplacental clear space (green),
bladder-border abnormalities (yellow) and
color-Doppler abnormalities (red) in prenatal
diagnosis of invasive placentation.
Among the different ultrasound
signs, color Doppler had the best
predictive accuracy:
• Sensitivity 90.7% (95%CI 85.2-94.7)
• Specificity 87.7% (95%CI 84.6-90.4)
• LR+ 7.77 (95%CI 3.3-18.4)
• LR- 0.17 (95%CI 0.10-0.29)
• DOR 69.02 (95%CI 22.8-208.9)

12. Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
D’Antonio et al., UOG 2013
Discussion
•
Prenatal ultrasound has high predictive accuracy in diagnosing
invasive placentation in women at high risk.
•
Among the sonographic signs of invasive placentation, color Doppler
had the best combination of sensitivity and 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.
•
The authors hypothesize that:
•
A reduction in the number of sonographic criteria for invasive placentation may
increase sensitivity but is likely to reduce specificity.
•
An increase in the number of sonographic criteria for invasive placentation would
reduce sensitivity but would improve specificity.

13. Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
D’Antonio et al., UOG 2013
Discussion
•
The low sensitivity of placental lacunae may arise because the lower
uterine segment appears as a thin line during the late 3rd trimester on
conventional transabdominal ultrasound, so evaluation of the interface
between the myometrium and the placenta may be difficult.
•
Higher degrees of placental invasion lead to penetration of the
bladder. This condition may be diagnosed with ultrasound by
examining the border between the bladder and myometrium, which is
normally echogenic and smooth.
•
Exophytic masses in the bladder are likely to be seen only with
placenta percreta – this observation is a reliable ‘rule-in’ sign but its
absence does not exclude lesser degrees of placental adherence.

14. Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
D’Antonio et al., UOG 2013
Limitations
1. Some reported series were prospectively conducted but ultrasound
signs were retrospectively examined. With the benefit of hindsight, it
might have been easier to spot signs in images on prenatal
ultrasound.
2. Results from this review are only applicable to women with anterior
placenta praevia and a history of a Cesarean delivery or uterine
surgery, but not applicable to women with fundal or posterior placenta
with invasive placentation.
3. 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.

15. Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
D’Antonio et al., UOG 2013
Conclusions
•
Among the different ultrasound signs, the presence of abnormal
vasculature on color Doppler ultrasound has the best combination of
sensitivity and specificity.
•
Abnormality of the uterus-bladder interface has the best specificity.
•
The presence of placental lacunae and loss of the clear space
between the placenta and myometrium do not perform as well.
•
In women with a low anterior placenta who have had uterine surgery,
3rd trimester ultrasound is highly sensitive and specific in diagnosing
invasive placentation prenatally.
•
Future research should be directed at developing objective criteria for
color Doppler abnormalities and for determining the best surgical
technique for delivery.

16. Prenatal identification of invasive placentation using ultrasound:
systematic review and meta-analysis
D’Antonio et al., UOG 2013
Discussion points
•
Is there a need to set up a multi-disciplinary clinic for the prenatal
diagnosis and subsequent management of invasive placentation?
•
If yes, should all women with an anterior low-lying placenta and previous
history of Cesarean delivery or uterine surgery be referred to this clinic?
•
How should we develop the objective criteria for the diagnosis of invasive
placentation (i.e. color Doppler abnormalities), thus allowing objective
structured training of fetal medicine subspecialists?