This chapter should be cited as follows:
Lucidi A, D’Antonio F, Glob Libr Women's Med
ISSN: 1756-2228; DOI 10.3843/GLOWM.419183

The Continuous Textbook of Women’s Medicine Series – Obstetrics Module

Volume 18

Ultrasound in obstetrics

Volume Editors: Professor Caterina M (Katia) Bilardo, Amsterdam UMC, Amsterdam and University of Groningen, Groningen, The Netherlands
Dr Valentina Tsibizova, PREIS International School, Florence, Italy

Chapter

Anomalies of Placentation: Placenta Accreta Spectrum Disorders

First published: February 2025

AUTHORS

Alessandro Lucidi

Center for Fetal Care and High-Risk Pregnancy, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy

Francesco D’Antonio

Center for Fetal Care and High-Risk Pregnancy, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy

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OVERVIEW

Placenta previa and prior uterine surgery represent the most commonly reported risk factors for placenta accreta spectrum (PAS). Prenatal diagnosis is usually accomplished during the second and/or third trimester of pregnancy, although there is no consensus yet on the optimal gestational age of ultrasound examination to detect PAS and the number and type of imaging criteria to improve the overall diagnostic accuracy of ultrasound. This chapter explores the role of prenatal ultrasound in the three trimesters of pregnancy in identifying PAS disorders.

BACKGROUND

PAS disorders encompass a heterogeneous group of conditions characterized by abnormal trophoblastic tissue invasion of and adhesion to the myometrium and uterine serosa or even beyond extending to pelvic organs.¹

Depth and topography of placental invasion are the main determinants of surgical outcome in women affected by PAS disorders. The depth of invasion refers to the degree of trophoblastic infiltration through the myometrium and uterine serosa, with its most severe type, placenta percreta, carrying the highest risk of maternal mortality and morbidity.²

Although the natural history of PAS disorders has not been completely elucidated, placenta previa and prior Cesarean delivery or uterine surgery represent the main risk factors.³^,⁴

The relative risk of placenta previa increases with each prior Cesarean delivery from 4.5 for one to 7.4 for two, 6.5 for three and 44.9 for four or more when compared to that of vaginal delivery.⁵^,⁶ Similarly, in women with prior Cesarean delivery presenting with a placenta previa, the risk of PAS is 3%, 11%, 40%, 61% and 67% for first, second, third, fourth and fifth or more Cesarean delivery, respectively.¹ Nevertheless, PAS is not exclusively a consequence of previous Cesarean delivery and has also been reported in nulliparous women with a history of operative hysteroscopy, suction curettage and surgical endometrial ablation.³ In addition, any uterine pathology such as bicornuate uterus, adenomyosis, submucous fibroids or myotonic dystrophy, or any procedure causing surgical damage to the uterine wall integrity, such as myomectomy, has been associated with PAS.⁷

PAS disorders are among the most dangerous complications of pregnancy potentially leading to massive intrapartum hemorrhage and death.

Reducing maternal morbidity and mortality is among the highest priorities of the World Health Organization (WHO). In this context prenatal diagnosis of PAS disorders is fundamental because it has been reported to improve maternal outcome by allowing a preplanned treatment of these conditions in centers with a high level of surgical expertise.⁶

PAS is a progressive disorder and the ultrasound signs of disorders involving the placental bed, myometrial thickness, lacunae and the vascular features beneath and around the accretic area change with advancing gestation.⁸

FIRST-TRIMESTER SCREENING FOR PAS

In women with prior Cesarean section, ultrasound examination in the early first trimester is recommended to look for features of Cesarean scar pregnancy (CSP), a precursor of PAS. This can facilitate timely detection, counseling, management and referral.⁹

Misdiagnosis of CSP as miscarriage of an intrauterine pregnancy will lead to curettage, resulting in profuse bleeding and need for emergency surgical intervention.¹⁰

Although the most likely clinical evolution of CSP is towards severe hemorrhage requiring prompt surgical intervention, a variable proportion of CSP may evolve into PAS.¹¹

Low implantation of the gestational sac within or in close proximity to a Cesarean scar in the first trimester is associated with an increased incidence of placenta accreta in the third trimester. A meta-analysis including 551 at-risk pregnancies showed the detection of at least one ultrasound sign suggestive of PAS in 91.4% of women with confirmed PAS in the first trimester. The most common ultrasound feature in the first trimester of pregnancy was low implantation of the gestational sac close to a previous uterine scar (Figure 1), which was observed in 82.4% of cases. Anechoic spaces within the placental mass (lacunae) were observed in 46.0% and a reduced myometrial thickness in 66.8% (95% CI, 45.2–85.2%) of cases affected by PAS⁹ (Figure 1).

First-trimester ultrasound signs of placenta accreta spectrum disorder: (a) implantation of the gestational sac in the area of the prior Cesarean delivery scar (Cesarean scar pregnancy); (b) placental lacunae (arrows) and loss of the hypoechoic clear zone behind the placenta (arrowheads); (c) hypervascularization at the uterus–bladder interface. B, bladder; P, placenta; (d) three-dimensional ultrasound showing hypervascularization at the uterus–bladder interface with loss and irregularity of the retroplacental space.

In the early first trimester, from 6 to 8 weeks of gestation, the cross-over sign (COS) or relationship between the ectopic gestational sac and the endometrial line has been suggested to have the potential to stratify risk of evolution to PAS (Figure 2).¹² This sign is assessed as follows: in a sagittal view of the uterus, a straight line connecting the internal cervical os and the uterine fundus through the endometrium (endometrial line) is drawn; then, having identified the gestational sac, the superior-to-inferior (S–I) diameter perpendicular to the endometrial line is traced. According to the relationship between the endometrial line and the S–I diameter of the ectopic sac, the patients can be divided into two different groups:

COS-1 insertion: the gestational sac is implanted within the previous CS and more than or equal to two-thirds of the S–I diameter of the gestational sac is above the endometrial line towards the anterior uterine wall
COS-2 insertion: the gestational sac is implanted within the previous CS and less than two-thirds of the S–I diameter of the gestational sac is above the endometrial line. COS-2 cases can be divided into two different categories according to the presence (COS-2+) or not (COS-2−) of an intersection between the S–I diameter of the ectopic sac and the endometrial line.

COS-1 is associated with placenta percreta and increta, whereas COS-2+ is associated with placenta accreta.

The relationship between gestational sac position and Cesarean scar can be evaluated according to two other sonographic markers reported by Kaelin Agten et al. (implantation of the gestational sac on the scar vs in the niche of the CS)¹³ and Timor-Tritsch et al. (location of the center of the gestational sac below or above the midline of the uterus, that is the longitudinal line between the external cervical os and the fundus).¹⁰

COS-1 and implantation 'in the niche' and 'below the uterine midline' are associated with severe types of PAS in the third trimester of pregnancy. Conversely, COS-2, implantation 'on the scar' and 'above the uterine midline' are associated with less severe types of PAS.¹² When combining the three classifications, Cali et al. proposed 'high-risk-for-PAS triangle' formed by (a) the endometrial line, (b) Cesarean scar, and (c) the uterine midline (c). This area may enable an easy visual perception and application of the three methods to predict the risk for CS pregnancy and PAS disorder.¹⁴

Cross-over sign (COS) in Cesarean scar pregnancies in the early first trimester. Endometrial line (solid lines) and superoinferior diameter of the gestational sac (dashed lines) are shown.

At 11–14 weeks of pregnancy, low implantation of the gestational sac is not identifiable in the large majority of images; however, most of the classical ultrasonography signs of PAS, such as loss of the clear space, placental lacunae, bladder wall interruption and uterovesical hypervascularity, are present by this time.¹⁵^,¹⁶ In particular, these signs that were not present during the early first trimester, were identified at 11–14 weeks in 84.3% (loss of the clear space), 78.3% (placental lacunae), 75.9% (bladder wall interruption) and 51.8% (uterovesical hypervascularity) of the images in a recent study by D’Antonio et al.⁹ (Figure 1). In addition, signs of vascular invasion of the parametria were detected in none of the images from the early first trimester compared with 18.1% of images from the first trimester.⁹

SECOND-TRIMESTER SCREENING FOR PAS

The potential for PAS disorders should be considered in women with clinical risk factors as previously described. In the second trimester, multimodal ultrasound, including imaging with an adequately filled bladder, can achieve a high (>90%) positive predictive value for confirmed placenta previa with PAS disorder at delivery. The overall diagnostic accuracy of ultrasound in detecting the presence of PAS disorders is reported as: sensitivity 90.7% (95% confidence interval (CI) 87.2%−93.6%) and specificity 96.9% (95% CI 96.3%−97.5%).¹⁷

The sonographic signs most commonly reported to be associated with invasive placentation in the second trimester (Figure 3) comprise:

vascular lacunae within the placenta
loss of normal hypoechoic retroplacental zone
interruption of the bladder line and/or focal exophytic masses extending into the bladder space
color Doppler abnormalities (the presence of vessels visualized crossing the myometrium and extending from the placenta to the posterior bladder wall or to other organs, often running perpendicular to the myometrium).

Second-trimester ultrasound signs of placenta accreta spectrum disorder: (a) placental lacunae; (b) interruption of the retroplacental hypoechoic space (note that a correct assessment of the hypoechoic space requires a partially full bladder); (c) focal interruption of the retroplacental hypoechoic space with placental bulging; (d) lateral hypervascularization in the parametrial region; (e) and (f) multiple interruptions of the hypoechoic space on gray-scale and color Doppler ultrasound; (g) and (h) cervical lakes on gray-scale and color Doppler ultrasound.

The pathophysiology of placental lacunae is not clear, although their presence has been associated with an increased likelihood of invasive placentation.

The invasion of trophoblastic tissue through the myometrium and the absence of decidua basalis in invasive placentation progressively lead to a reduction in myometrial thickness and a loss of the hypoechoic space between the myometrium and the placenta.

Higher degrees of placental invasion lead to the destruction of the outer third of the myometrium and uterine serosa with subsequent involvement of the bladder. This condition may be diagnosed with ultrasound by examining the border between the bladder and myometrium (abnormalities of uterus–bladder interface), which is normally echogenic and smooth. Exophytic masses in the bladder are likely to be seen only with placenta percreta. Observation of this sign is a reliable ‘rule-in’ sign for making the diagnosis, but its absence does not exclude lesser degrees of placental adherence.

Color Doppler abnormalities such as abnormal blood vessels at the myometrium–bladder interface have the best combination of sensitivity and specificity (sensitivity 90.74%; specificity 87.68%).¹⁸

The prevalence of ultrasound signs suggestive of PAS through pregnancy has been reported by Calì et al..⁸ In this study, loss of the clear space was present in 84.3% of images from the first trimester, compared with 88.6% of those from the second trimester (P = 0.517), and bladder wall interruption was visible in 75.9% and 87.6% of images from the first and second trimesters, respectively (P = 0.052). Conversely, the increases in visualization of placental lacunae, uterovesical hypervascularity and vascular invasion of the parametria observed between the first and second trimesters of pregnancy were significant (all P < 0.001).

Di Pasquo et al.¹⁹ recently introduced a new ultrasound sign, intracervical lakes (ICL), defined as tortuous anechoic spaces within the cervix, which appeared to be hypervascular on color Doppler, using a pulsed-rate frequency <1.3 kHz. Presence of ICL seems to be an independent predictor of placenta percreta and its incorporation into ultrasound examination may increase the diagnostic accuracy for Cesarean hysterectomy and major postpartum hemorrhage in women with placenta previa or low-lying placenta.

THIRD-TRIMESTER ULTRASOUND

The diagnosis of a PAS disorder may be made at any stage in the third trimester, but there is no diagnostic advantage in delaying the examination if invasive placentation is suspected in the second trimester. Nevertheless, at this gestational age, prediction of placental invasion, topography and the use of a scoring or staging system may be helpful in order to identify women at high risk. This can help in individual risk stratification for PAS and enable multidisciplinary counseling, preoperative planning and timing of delivery.

A staging system has been proposed by Cali et al.¹⁴ based on the distribution of different ultrasound signs in women presenting with placenta previa as follows:

PAS0: Placenta previa with no ultrasound signs of invasion or placenta previa with placental lacunae but no evidence of abnormal uterine–bladder interface (loss of the clear zone and/or bladder wall interruption).

PAS1: Presence of at least two of the following ultrasound signs: placental lacunae, loss of the clear zone, bladder wall interruption

PAS2: PAS1 + uterovesical hypervascularity

PAS3: PAS1 or PAS2 + evidence of increased vascularity in the inferior part of the lower uterine segment extending into the parametrial region.

Based on this PAS scoring system, women in the higher PAS category demonstrated increased estimated blood loss, operative times, hospital stay, need for transfusion, prevalence of surgical complications and need for transfer to intenstive care unit.

Compared with PAS2 in which there was no case of parametrial invasion, PAS3 was associated with a significantly higher risk of severe hemorrhage and need for blood transfusion, probably because of invasion of S2 area and parametrium (Figure 2).

In addition, this staging system correlated with the International Federation of Gynecology and Obstetrics (FIGO) clinical grading system.²⁰

Another predictive model, called the 'placenta accreta index', combined the number of previous Cesarean sections and placental location, as well as sonographic signs, including reduced myometrial thickness, intraplacental lacunae and bridging vessels.²¹ This model was designed to help identify patients with clinically significant placental invasion requiring Cesarean hysterectomy.

Finally, a recent multicenter prospective study confirmed that, in patients with low-lying placenta or placenta previa in the third trimester, ultrasound may play a crucial role and should be used to guide management decisions and concentrate resources on patients with higher risk of clinically significant PAS.²² The ADoPAD study concluded that grayscale ultrasound has good diagnostic performance to identify pregnancies at low risk of PAS disorders in a high-risk population of patients with low-lying placenta or placenta previa. The probability of clinically significant PAS decreased from 21% to 11%, 9% and 5% when the uterine serosa–bladder wall interface was normal, when placental lacunae were absent and when the hypoechogenic retroplacental space was non-interrupted, respectively.²²

CONCLUSION

Placenta previa and prior uterine surgery represent the most commonly reported risk factors for PAS. Prenatal diagnosis is usually accomplished during the second and/or third trimester of pregnancy, although there is no consensus yet on the optimal gestational age at which to detect PAS and the number and type of imaging criteria which should be adopted in order to improve the overall diagnostic accuracy of ultrasound. However, prenatal diagnosis of PAS has been shown to be improved when a multiparametric prediction model, including ultrasound, maternal and pregnancy characteristics, is applied to women at risk. In this scenario, integrating findings from the first trimester with those from the second- and third-trimester scans, together with maternal and pregnancy characteristics, should theoretically improve the diagnostic accuracy of ultrasound in detecting the presence and severity of PAS.

PRACTICE RECOMMENDATIONS

Placenta previa and prior uterine surgery (especially Cesarean delivery) are the most significant risk factors for PAS. The severity of PAS depends on the depth and extent of placental invasion, with placenta percreta carrying the highest risk of maternal morbidity and mortality. PAS is a progressive disorder that can lead to life-threatening complications, including massive hemorrhage.
Early first-trimester ultrasound is recommended for women with prior Cesarean delivery to identify Cesarean scar pregnancy (CSP), a precursor to PAS. Key ultrasound signs in early pregnancy include low implantation of the gestational sac, placental lacunae and reduced myometrial thickness. The 'cross-over sign' (COS) and other sonographic markers can help stratify risk for PAS later in pregnancy.
PAS should be suspected in women with risk factors, and second-trimester ultrasound can achieve high diagnostic accuracy (>90%). Key ultrasound signs include vascular lacunae, loss of the retroplacental hypoechoic zone, bladder wall interruption, and abnormal blood flow on color Doppler. New signs, such as intracervical lakes (ICL), have been identified as potential predictors of placenta percreta.
Late pregnancy ultrasound focuses on assessing the extent of placental invasion and guiding preoperative planning. Staging systems like PAS0–PAS3 categorize patients based on ultrasound findings to predict surgical complexity, blood loss and the need for hysterectomy. The 'placenta accreta index' combines ultrasound markers with clinical history to predict the severity of PAS.
Early and accurate prenatal diagnosis of PAS improves maternal outcomes by allowing planned delivery in specialized centers with experienced surgical teams. Integration of first-, second- and third-trimester ultrasound findings with maternal history enhances diagnostic precision, facilitating individualized care and reducing maternal morbidity and mortality.

CONFLICTS OF INTEREST

The author(s) of this chapter declare that they have no interests that conflict with the contents of the chapter.

All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report.

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