Professional Documents
Culture Documents
Placenta Accreta
Spectrum and
Postpartum
Hemorrhage
MAHMOUD ABDELWAHAB, MD,
and MICHAEL CACKOVIC, MD
Department of Obstetrics and Gynecology, The Ohio State
University College of Medicine, Columbus, Ohio
Abstract: Placenta accreta spectrum is a group of trophoblastic invasion to the deep layers
disorders involving abnormal trophoblastic invasion of endometrium and myometrium that
to the deep layers of endometrium and myometrium.
Placenta accrete spectrum is one of the major causes of prevent normal completion of the third
severe maternal morbidity, with increasing incidence stage of labor or manual delivery of the
in the past decade mainly secondary to an increase in placenta during cesarean delivery. PAS is
cesarean deliveries. Severity varies depending on the one of the major causes of severe maternal
depth of invasion, with the most severe form, known morbidity.1,2
as percreta, invading uterine serosa or surrounding
pelvic organs. Diagnosis is usually achieved by ultra- The incidence of PAS has been increas-
sound, and MRI is sometimes used to assess invasion. ing in modern obstetrics, mainly secon-
Management usually involves a hysterectomy at the dary to an increase in rates of cesarean
time of delivery. Other strategies include delayed deliveries and a decline in the rate of
hysterectomy or expectant management. operative deliveries throughout the
Key words: placenta accreta spectrum, cesarean hys-
terectomy, delayed hysterectomy United States. The incidence was esti-
mated to be 1 in thousands in the 1970-
1980s, making it a rare encounter.3 A
national study estimated the incidence to
Introduction be 1 in 272 patients between 1998 and
Placenta accreta spectrum (PAS) is a 2011, which is more than a 10-fold
group of disorders involving abnormal increase, with potentially higher rates
present now.1,4
Correspondence: Mahmoud Abdelwahab, MD, Division
of Maternal-Fetal Medicine, Department of Obstetrics RISK FACTORS
and Gynecology, The Ohio State University College of
Medicine, Columbus, OH. E-mail: Mahmoud. The most important risk factors for PAS
Abdelwahab@osumc.edu are previous cesarean deliveries and pla-
The authors declare that they have nothing to disclose. centa previa. With one cesarean delivery,
www.clinicalobgyn.com | 1
Copyright r 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
2 Abdelwahab and Cackovic
the rate of PAS is estimated to be 0.3% factor given the increasing rates of IVF.13
versus 6.7% with 5 or more cesarean Pregnancy following uterine artery embo-
deliveries.1,5 Rate of PAS in patients with lization may also be associated with an
placenta previa is estimated to be 3% in increased risk for PAS.14
the absence of previous cesarean deliv-
eries. A synergistic relationship exists PATHOGENESIS
between previous cesarean deliveries and The exact mechanism of abnormal
placenta previa when it comes to the risk trophoblastic invasion leading to PAS is
of PAS. The absence of endometrial re- poorly understood. A previous insult to
epithelization following trauma by cesar- the endometrial-myometrial interface,
ean delivery allows for deep trophoblastic which fails to limit trophoblastic invasion,
invasion when implantation happens is the most accepted hypothesis.1,6 This
close to the scar.6 The clinical presenta- theory stems from the fact that multiple
tion of 1 previous cesarean delivery and uterine surgeries are one of the major risk
placenta previa, the risk of PAS is esti- factors for PAS. However, PAS can rarely
mated to be 11%. While risk is 40% with 2 happen in the absence of uterine surgeries,
previous cesarean deliveries, 60% with 3 which contradicts the simplicity of this
previous cesarean deliveries, and 67% if hypothesis.
more than 3 previous cesarean deliveries.7 Differential gene expression has been
Double-layered uterine closure has been reported in the literature in PAS patients.
suggested to reduce the risk of PAS. DOC4, a gene involved in some cancer
Single-layer closure with the incorpora- progression, is 3 times more expressed in
tion of endometrium in the myometrial invasive placentas compared with normal
closure or strangulation of tissue by lock- placentas. Higher expression of the B2M
ing sutures has been associated with gene has also been demonstrated, which is
weaker scars in some reports.8 However, involved in the function of the MHC 1
studies have failed to prove the superior- complex, with potential immune modu-
ity of double-layer closure over single- lating function.15 That can be one of the
layer closure to reduce the chance of explanations for the exaggerated immune
PAS.9 Interestingly the presence of a tolerance to the invasive placenta. Differ-
low-lying placenta within 2 cm from the ent genes have been reported to be either
cervix was not found to be associated with up or downregulated in PAS patients,
increased risk for PAS in the presence of with many of the upregulated genes being
previous cesarean deliveries.10 associated with cellular proliferation and
Other uterine surgeries have been asso- tissue invasion, including COL17A1,
ciated with an increased risk of PAS, MMP12, and FSTL3.16 The mechanism
including myomectomy, dilation and cur- by which the expression of those genes is
ettage, and endometrial ablation.11 PAS altered is unknown.
rate was reported to be 23% following
endometrial ablation.12 PAS has been GRADING
described in the absence of uterine sur- Traditionally PAS was graded into 3
geries as well. Some nonsurgical risk categories, placenta accreta, increta, and
factors include previous endometritis, ute- percreta. Increta refers to placenta
rine anomalies, adenomyosis, submucous extending to deep myometrial tissue and
fibroids, and assisted reproductive percreta refers to an extension to or
techniques.11 The rate of PAS has been beyond uterine serosa. In 2019, a more
estimated to increase by 13-fold following descriptive grading system was published
in vitro fertilization (IVF) procedures, by FIGO, similar to oncologic gradings,
making it an important contributing risk in an attempt to standardize how PAS is
www.clinicalobgyn.com
Copyright r 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Placenta Accreta Spectrum and Postpartum Hemorrhage 3
described and reported across different one specific sign/finding has not been
centers. (Table 1). identified as diagnostic. The presence of
Grade 1 is described as abnormal risk factors is one of the most important
invasion to deep decidual layers and indicators to diagnose PAS antenatally.
superficial myometrial layers without However, PAS can happen in the absence
deep myometrial invasion. Clinically, it of risk factors, and caution should be
presents with failure to deliver the placen- taken for delivery planning once risk
ta without obvious macroscopic features factors have been identified. Despite
of PAS at the time of laparotomy. Grade ultrasonography being the standard of
2 is equivalent to the term increta, where care for diagnosing PAS, considerable
the placenta extends to deep myometrial interobserver variation in the inter-
tissue but not to uterine serosa. Grade 3 pretation of the ultrasound images has
involves an extension to the uterine serosa been reported.23 A standardized reporting
(3a), urinary bladder (3b), or other pelvic system has been suggested in the literature
organs (3c).17 to reduce interobserver variability.24
A recently published study supports (Table 2).
that the use of the FIGO classification Some of the ultrasound findings
system at the time of laparotomy corre- include: Greyscale suggestive findings
lates accurately with histopathological include the loss of clear zone underneath
examination.18 Supporting the use of the placental bed, myometrial thinning
FIGO as a standard grading system <1 mm, and abnormal placental lacunae
for PAS. that are large or irregular. Findings
suggestive of extrauterine spread can
DIAGNOSIS OF PAS be seen too, including interruption of
Antenatal diagnosis of PAS is crucial to the bladder wall and placental bulge into
optimize the management and reduce surrounding organs (Fig. 1). Color Dop-
maternal morbidity and mortality. How- pler is also helpful in the diagnosis,
ever, the diagnosis remains challenging, uterovesical hypervascularity, subpla-
one-third to one-half of PAS patients are cental hypervascularity, bridging vessels
not diagnosed antenatal, even in special- with vessels running perpendicular in the
ized obstetric imaging units.19–21 myometrium towards bladder or other
Two-dimensional ultrasonography organs is very suggestive. (Fig. 2).1,24
remains the primary tool for antenatal The rail sign has been described in the
detection of PAS. The sensitivity of literature as a sign of deep villous
ultrasonography is reported as 90.7% in invasion. It is defined as 2 parallel neo-
the literature, with a specificity of vascularization over the uterovesical
96.9%.22 There are several key ultrasound junction connected by perpendicular
findings that are suggestive of PAS, but vessels.25
www.clinicalobgyn.com
Copyright r 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
4 Abdelwahab and Cackovic
www.clinicalobgyn.com
Copyright r 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Placenta Accreta Spectrum and Postpartum Hemorrhage 5
www.clinicalobgyn.com
Copyright r 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
6 Abdelwahab and Cackovic
www.clinicalobgyn.com
Copyright r 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Placenta Accreta Spectrum and Postpartum Hemorrhage 7
inhibits rapidly dividing cells and the hysterectomy date was estimated to be
trophoblasts are no longer rapidly divid- 23%, which is similar to patients opting
ing after delivery, the benefit from its use for expectant management.51
is questionable. A case of maternal mor- The surgical approach for delayed hys-
tality was reported following methotrex- terectomy has traditionally been a lapa-
ate administration post-delivery for PAS, rotomy. However, recently minimally
secondary to maternal sepsis and acute invasive delayed hysterectomy techniques
kidney injury.44 Methotrexate is currently have been described with encouraging
not recommended to have a role in outcomes including less blood loss and
expectant management for PAS.1,50 faster recovery.52
Care for PAS patients should be indi-
DELAYED HYSTERECTOMY vidualized based on the grade of PAS,
Delayed hysterectomy is becoming the expertise of providers, and patient wishes
primary recommendation for the man- for future fertility or uterus preservation.
agement of PAS patients in several cen- Hysterectomy at the time of cesarean
ters across the United States. This delivery remains the most widely used
technique involves planning delivery at approach for the management of PAS
34 to 35 weeks, mapping the placenta in most centers. However, in patients
intraoperative, and placing the uterine where immediate hysterectomy carries
incision away from the placental bed, significant risks secondary to extensive
and then the placenta is left in place after invasion, the approach of delayed hyster-
delivery. Hysterotomy is then closed, and ectomy should be considered. Detailed
the hysterectomy is performed 4 to 6 counseling before delivery is advised
weeks later. The hypothesis is to allow in cases where extensive accreta’s are
for regression of the congested pelvic suspected.
vessels and involution of the uterus, so
the hysterectomy is associated with less
blood loss and maternal morbidities.48
The protocol that has been suggested References
for delayed hysterectomy involves hospi-
tal admission for 7 days, with 72 hours of 1. Gynecologists ACoOa, Medicine SfM-F. Obstet-
ric Care Consensus No. 7: Placenta Accreta
broad-spectrum antibiotics, and daily Spectrum. Obstet Gynecol. 2018;132:e259–e275
CBCs. Patients are discharged home with 2. Usta IM, Hobeika EM, Musa AA, et al. Placenta
close follow-up after this observation previa-accreta: risk factors and complications. Am J
period if there is no bleeding, signs of Obstet Gynecol. 2005;193(3Pt2):1045–1049; (In eng).
infection, or elevated white blood cell 3. Wu S, Kocherginsky M, Hibbard JU. Abnormal
placentation: twenty-year analysis. Am J Obstet
count. Patients are only discharged if they Gynecol. 2005;192:1458–1461; (In eng).
live close to the hospital and have reliable 4. Mogos MF, Salemi JL, Ashley M, et al. Recent
transportation to attend outpatient fol- trends in placenta accreta in the United States and
low-up appointments. Patients then its impact on maternal-fetal morbidity and health-
receive weekly outpatient visits, with a care-associated costs, 1998-2011. J Matern Fetal
Neonatal Med. 2016;29:1077–1082; (In eng).
hysterectomy planned 4 to 6 weeks later 5. Marshall NE, Fu R, Guise JM. Impact of multiple
after preoperative MRI.48 Delayed hys- cesarean deliveries on maternal morbidity: a system-
terectomy has been shown to be associ- atic review. Am J Obstet Gynecol. 2011;205:262.
ated with less operative time, less blood e1–8; (In eng).
loss, and less transfusion of blood 6. Jauniaux E, Collins S, Burton GJ. Placenta
accreta spectrum: pathophysiology and evi-
products.48 The rate of unscheduled hys- dence-based anatomy for prenatal ultrasound
terectomy secondary to bleeding or infec- imaging. Am J Obstet Gynecol. 2018;218:75–87;
tion before the scheduled delayed (In eng).
www.clinicalobgyn.com
Copyright r 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
8 Abdelwahab and Cackovic
7. Silver RM, Landon MB, Rouse DJ, et al. Maternal placenta accreta. Am J Obstet Gynecol.
morbidity associated with multiple repeat cesarean 2014;211:177.e1–7; (In eng).
deliveries. Obstet Gynecol. 2006;107:1226–1232; 21. Thurn L, Lindqvist PG, Jakobsson M, et al.
(In eng). Abnormally invasive placenta-prevalence, risk
8. Bujold E. The optimal uterine closure technique factors and antenatal suspicion: results from a
during cesarean. N Am J Med Sci. 2012;4: large population-based pregnancy cohort study in
362–363; (In eng). the Nordic countries. BJOG. 2016;123:
9. Sumigama S, Sugiyama C, Kotani T, et al. 1348–1355; (In eng).
Uterine sutures at prior caesarean section and 22. Comstock CH. Re: Prenatal identification of
placenta accreta in subsequent pregnancy: a case- invasive placentation using ultrasound: system-
control study. BJOG. 2014;121:866–874; discus- atic review and meta-analysis. F D’Antonio, C
sion 875.; (In eng). Iacovella and A Bhide Ultrasound Obstet Gynecol
10. Twickler DM, Lucas MJ, Balis AB, et al. Color 2013; 42: 509-517 Ultrasound Obstet Gynecol.
flow mapping for myometrial invasion in women 2013;42:498; (In eng).
with a prior cesarean delivery. J Matern Fetal 23. Bowman ZS, Eller AG, Kennedy AM, et al.
Med. 2000;9:330–335; (In eng). Interobserver variability of sonography for pre-
11. Jauniaux E, Chantraine F, Silver RM, et al. Panel diction of placenta accreta. J Ultrasound Med.
FPADaMEC. FIGO consensus guidelines on 2014;33:2153–2158; (In eng).
placenta accreta spectrum disorders: Epidemiol- 24. Alfirevic Z, Tang AW, Collins SL, et al. Group
ogy. Int J Gynaecol Obstet. 2018;140:265–273; (In A-hIAE. Pro forma for ultrasound reporting in
eng). suspected abnormally invasive placenta (AIP): an
12. Kohn JR, Shamshirsaz AA, Popek E, et al. international consensus. Ultrasound Obstet Gyne-
Pregnancy after endometrial ablation: a system- col. 2016;47:276–278; (In eng).
atic review. BJOG. 2018;125:43–53; (In eng). 25. Shih JC, Kang J, Tsai SJ, et al. The “rail sign”: an
13. Salmanian B, Fox KA, Arian SE, et al. In vitro ultrasound finding in placenta accreta spectrum
fertilization as an independent risk factor for indicating deep villous invasion and adverse out-
placenta accreta spectrum. Am J Obstet Gynecol. comes. Am J Obstet Gynecol. 2021;225:292.
2020;223:568.e1–568.e5; (In eng). e1–292.e17; (In eng).
14. Jitsumori M, Matsuzaki S, Endo M, et al. Obstet- 26. Abdel Moniem AM, Ibrahim A, Akl SA, et al.
ric outcomes of pregnancy after uterine artery Accuracy of three-dimensional multislice view
embolization. Int J Womens Health. 2020;12: Doppler in diagnosis of morbid adherent placen-
151–158; (In eng). ta. J Turk Ger Gynecol Assoc. 2015;16:126–136;
15. McNally L, Zhou Y, Robinson JF, et al. Up- (In eng).
regulated cytotrophoblast DOCK4 contributes to 27. Shih JC, Palacios Jaraquemada JM, Su YN, et al.
over-invasion in placenta accreta spectrum. Proc Role of three-dimensional power Doppler in the
Natl Acad Sci U S A. 2020;117:15852–15861; (In antenatal diagnosis of placenta accreta: compar-
eng). ison with gray-scale and color Doppler techni-
16. Chen B, Wang D, Bian Y, et al. Systematic ques. Ultrasound Obstet Gynecol. 2009;33:
identification of hub genes in placenta accreta 193–203; (In eng).
spectrum based on integrated transcriptomic and 28. Abinader RR, Macdisi N, El Moudden I, et al.
proteomic analysis. Front Genet. 2020;11:551495; First-trimester ultrasound diagnostic features of
(In eng). placenta accreta spectrum in low-implantation
17. Jauniaux E, Ayres-de-Campos D, Langhoff-Roos pregnancy. Ultrasound Obstet Gynecol. 2022;59:
J, et al. Panel FPADaMEC. FIGO classification 457–464; (In eng).
for the clinical diagnosis of placenta accreta 29. Doulaveris G, Ryken K, Papathomas D, et al.
spectrum disorders. Int J Gynaecol Obstet. Early prediction of placenta accreta spectrum in
2019;146:20–24; (In eng). women with prior cesarean delivery using trans-
18. Aalipour S, Salmanian B, Fox KA, et al. Placenta vaginal ultrasound at 11 to 14 weeks. Am J Obstet
Accreta Spectrum: Correlation between FIGO Gynecol MFM. 2020;2:100183; (In eng).
Clinical Classification and Histopathologic Find- 30. Varghese B, Singh N, George RA, et al.
ings. Am J Perinatol. 2021.; (In eng). Magnetic resonance imaging of placenta accreta.
19. Jauniaux E, Bhide A, Kennedy A, et al. FIGO Indian J Radiol Imaging. 2013;23:379–385; (In
consensus guidelines on placenta accreta spec- eng).
trum disorders: Prenatal diagnosis and screening. 31. Einerson BD, Rodriguez CE, Silver RM, et al.
Int J Gynaecol Obstet. 2018;140:274–280; (In Accuracy and Interobserver Reliability of Mag-
eng). netic Resonance Imaging for Placenta Accreta
20. Bowman ZS, Eller AG, Kennedy AM, et al. Spectrum Disorders. Am J Perinatol. 2021;38:
Accuracy of ultrasound for the prediction of 960–967; (In eng).
www.clinicalobgyn.com
Copyright r 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Placenta Accreta Spectrum and Postpartum Hemorrhage 9
32. Einerson BD, Rodriguez CE, Kennedy AM, et al. surgery: a systematic review of the use of resusci-
Magnetic resonance imaging is often misleading tative endovascular balloon occlusion of the aorta
when used as an adjunct to ultrasound in the (REBOA) in cases of morbidly adherent placenta.
management of placenta accreta spectrum disor- Eur J Trauma Emerg Surg. 2018;44:519–526; (In
ders. Am J Obstet Gynecol. 2018;218:618.e1–618. eng).
e7; (In eng). 43. Tsurukiri J, Akamine I, Sato T, et al. Resuscita-
33. Gyamfi-Bannerman C. pubs@smfm.org SfM- tive endovascular balloon occlusion of the aorta
FMSEa. Society for Maternal-Fetal Medicine for uncontrolled haemorrahgic shock as an
(SMFM) Consult Series #44: Management of adjunct to haemostatic procedures in the acute
bleeding in the late preterm period. Am J Obstet care setting. Scand J Trauma Resusc Emerg Med.
Gynecol. 2018;218:B2–B8; (In eng). 2016;24:13; (In eng).
34. Shamshirsaz AA, Fox KA, Salmanian B, et al. 44. Sentilhes L, Ambroselli C, Kayem G, et al.
Maternal morbidity in patients with morbidly Maternal outcome after conservative treatment
adherent placenta treated with and without a of placenta accreta. Obstet Gynecol. 2010;115:
standardized multidisciplinary approach. Am J 526–534; (In eng).
Obstet Gynecol. 2015;212:218.e1–9; (In eng). 45. Marcellin L, Delorme P, Bonnet MP, et al.
35. Silver RM, Barbour KD. Placenta accreta spec- Placenta percreta is associated with more frequent
trum: accreta, increta, and percreta. Obstet Gyne- severe maternal morbidity than placenta accreta.
col Clin North Am. 2015;42:381–402; (In eng). Am J Obstet Gynecol. 2018;219:193.e1–193.e9;
36. Belfort MA, Shamshiraz AA, Fox K. Minimizing (In eng).
blood loss at cesarean-hysterectomy for placenta 46. Matsuzaki S, Yoshino K, Endo M, et al. Con-
previa percreta. Am J Obstet Gynecol. 2017;216: servative management of placenta percreta. Int J
78.e1–78.e2; (In eng). Gynaecol Obstet. 2018;140:299–306; (In eng).
37. Morlando M, Collins S. Placenta accreta spec- 47. Sentilhes L, Kayem G, Ambroselli C, et al.
trum disorders: challenges, risks, and manage- Fertility and pregnancy outcomes following con-
ment strategies. Int J Womens Health. 2020;12: servative treatment for placenta accreta. Hum
1033–1045; (In eng). Reprod. 2010;25:2803–2810; (In eng).
38. Tam Tam KB, Dozier J, Martin JN. Approaches 48. Zuckerwise LC, Craig AM, Newton JM, et al.
to reduce urinary tract injury during management Outcomes following a clinical algorithm allowing
of placenta accreta, increta, and percreta: a for delayed hysterectomy in the management of
systematic review. J Matern Fetal Neonatal Med. severe placenta accreta spectrum. Am J Obstet
2012;25:329–334; (In eng). Gynecol. 2020;222:179.e1–179.e9; (In eng).
39. Crocetto F, Esposito R, Saccone G, et al. Use of 49. Ramoni A, Strobl EM, Tiechl J, et al. Conserva-
routine ureteral stents in cesarean hysterectomy tive management of abnormally invasive placen-
for placenta accreta. J Matern Fetal Neonatal ta: four case reports. Acta Obstet Gynecol Scand.
Med. 2021;34:386–389; (In eng). 2013;92:468–471; (In eng).
40. Al-Khan A, Guirguis G, Zamudio S, et al. Pre- 50. Fox KA, Shamshirsaz AA, Carusi D, et al.
operative cystoscopy could determine the severity Conservative management of morbidly adherent
of placenta accreta spectrum disorders: An obser- placenta: expert review. Am J Obstet Gynecol.
vational study. J Obstet Gynaecol Res. 2019;45: 2015;213:755–760; (In eng).
126–132; (In eng). 51. Gatta LA, Lee PS, Gilner JB, et al. Placental
41. Chen M, Liu X, You Y, et al. Internal Iliac artery uterine artery embolization followed by delayed
balloon occlusion for placenta previa and sus- hysterectomy for placenta percreta: a case series.
pected placenta accreta: a randomized controlled Gynecol Oncol Rep. 2021;37:100833; (In eng).
trial. Obstet Gynecol. 2020;135:1112–1119; (In 52. Rupley DM, Tergas AI, Palmerola KL, et al.
eng). Robotically assisted delayed total laparoscopic
42. Manzano-Nunez R, Escobar-Vidarte MF, Nar- hysterectomy for placenta percreta. Gynecol
anjo MP, et al. Expanding the field of acute care Oncol Rep. 2016;17:53–55; (In eng).
www.clinicalobgyn.com
Copyright r 2023 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.