Placenta accreta spectrum disorders (PAS) refers to various grades of abnormal invasive placenta implantation. The epidemiology of PAS showed to be increasing, in parallel with the cesarean section (CS) rate and other uterine procedures. The pathogenesis of PAS results in series of maternal morbidity and mortality entailing from uterine rupture, postpartum hemorrhage, hysterectomy, to pelvic organ injury. Delicate perinatal preparations by multidisciplinary team are of great importance to improve maternal and fetal prognosis. Nevertheless, the paradox has been in PAS management, which is poor prognosis from over-estimation or under-estimation versus less evidence-based recommendation. PAS is challenging for both pregnant women and clinicians. It has been raised attention worldwide.
A case report was published by the New England Journal of Medicine last year,1 followed by the recommendation update of International Federation of Gynecology and Obstetrics2 and society of American Maternal-Fetal Medicine.3 Then International Society for Abnormally Invasive Placenta published guidelines in the American Journal of Obstetrics and Gynecology in 2019. With a modified Delphi technique (42 clinicians and basic science researchers from 13 countries) and best available evidence (case reports, case series, and retrospective cohort studies with small size, and regarded as methodologically flawed), twenty-one extensive topics have been discussed, most of which are related to management. Several recommendations have been made independently while consistently to existed other guidelines.
The rarity (0.79–3.11/1000 birth after prior cesarean) and heterogenicity of PAS have been concerned by all above academic organizations. In a systematic review4 of prevalence of PAS, there was considerable heterogeneity among studies with I2 value of 99.4%. The I2 statistic describes the percentage of variation across studies that is due to heterogeneity rather than chance, which is an intuitive and simple expression of the inconsistency of studies’ results. Meanwhile, the sample size of most current researches from China is relatively large, with potential of deep analysis to fulfill the gap. More prospective studies with targeted design are in urgent need.
The primary aim of this review is to compile some controversial topics and pursue related solutions.
First, the terminology of abnormal placenta implantation has been changing and inconsistent.
Pathologists describe different grade of adherent or invasive placenta as creta, vera, or adherenta. Given the fact that all the above could lead to failure of spontaneous separation during delivery, general nomenclature is suggested PAS. A retained placenta should be noted and do not included as PAS.
Even cesarean scar pregnancy (CSP) has been regarded as a stage of PAS given the shared pathology features. The terminology of CSP is “placental implantation within the scar of a previous cesarean delivery.” PAS is regarded as one of its complications, along with uterine rupture, severe hemorrhage, and preterm labor.
However, within the dehiscent scar or on the top of well-healed scar could behave different. A retrospective study5 included 17 cases diagnosed from 5 to 9 weeks, and based on first-trimester ultrasound, they were categorized as on the scar or in the niche groups. The myometrial thickness was related to gestational age at delivery. Muscle thickness was thinner (1 mm) that require hysterectomy than who did not (5 mm). Those less than 2 mm thickness is associated with morbidly adherent placenta. Those with CSP implanted on the scar compared to in the niche, and a myometrial thickness more than 4 mm could be good for expectant treatment.
The effects on clinics
During delivery, for suspected or even worse in unsuspected PAS, deep uterine disrupted vasculature causes rapid hemorrhage. Multiple blood and other blood products could be required in the peripartum period. Surgical complications during hysterectomy are technically difficult, and often hard to avoid injuries of urinary system.
The main neonatal complication is iatrogenic preterm birth, while vaginal bleeding or uterine rupture might present earlier and threaten maternal and neonatal lives.
Maternal death from PAS was reported to be 7% of cases.6 The maternal morbidity and mortality could be significantly moderated with prenatal diagnosis.7
Controversial topics and key issues for solutions
Recently several publications on PAS management argued the limitation of systematic review or meta-analysis, which were raised from limited number of retrospective non-randomized design, heterogeneity in details, and presence of confounding factors. The stratification of analysis based on location or severity of invasion was hard to achieve given the small sample size of studies, along with the progress of integrating surgical technique with aid of preoperative approaches.
Prediction (score and training)
The pre-delivery assessment of PAS remains to be tough with not highly accurate approach. Typical ultrasound characteristics (sub-placental vascularity, lacuna, bladder line, and loss of clear space) have been recommended primarily. Scoring models8,9 with ultrasonic characteristics has also been shown to be useful to predict postpartum bleeding. Chong et al. conducted a prospective study with 137 cases to verify the self-made scoring system, covering four accepted ultrasonic markers for placenta accrete, along with placental position, thickness, cervix morphology and blood sinus, and previous history of CS. The patients were then classified to three groups, those less than 5 (N1), 6–9 (N2), and more than 10 (N3). The higher score means severer and tends to suffer from hysterectomy. The prediction of three groups with pathological type showed to be highly consistent (87.6% for N1, 92% for N3).
Concerning the accuracy of subjective description, the proposal for standardized ultrasound descriptors has been raised by associated research groups.10 In this way, the data collected from different centers nationally or internationally could be shared and compared, and further fasten the solid evidence-based guidelines.
The risk factors other than ultrasound characteristics should be taken into consideration. Primary issues are previous CS-related (numbers/internal time/CS classification, emergency or during labor), or surgery related (anterior myomectomy, dilatation and curettage, previous hysteroscopic surgery, iatrogenic perforation of the uterus). While other factors, such as assisted reproductive technology, smoking, advanced maternal age, multiparity, and submucosal leiomyomas, have been noticed for their contributions to PAS. Although no routine scanning for PAS in practice, from 2013, UK introduced a targeted scanning protocol,11 which suggested those with a history of CS or presenting with placenta low-lying should be reviewed by an experienced sonographer. Based on their model, the most effective indicators were the presence of lacunae, obliteration of uteroplacental demarcation, and placenta previa. With implementation of such strategy, 90% of PAS could be detected and outcomes greatly improved. As far as China is concerned, the integration PAS with mid-term fetal anatomy screening is also feasible and tempting.
Based on analysis of 2219 PAS cases from multi-centers’ retrospective study, a scoring system combined ultrasound markers and maternal risk factors were generated (unpublished data). The maternal risk factors included “previous abortion or miscarriage (P = 0.027) and previous CSs (P < 0.001)”, which were related to the severity of PAS. The system could be used for predelivery diagnosis and maternal morbidity prediction, which was further validated with 67 cases for the accuracy of severe hemorrhage (area under the receiver– operating characteristics curve, ROC = 0.76, 95% CI: 0.62–0.91, P = 0.005) and hysterectomy (area under ROC = 0.98, 95% CI: 0.93–1.000, P = 0.023).
Magnetic resonance imaging (MRI) also plays a role in PAS assessment. The sensitivity and specificity ranged from 65% to 100%. It should be noted that the discrepancy could rooted from the strategy as the second-tier screening method. In conditions of posterior placenta, pregnancy complicated with obesity, or expected management from earlier trimester, the contribution of MRI is generally supported by international exports. The recent publication12 argued the identifiable benefit of MRI, in which an incorrect change in diagnosis in 17% and an incorrect confirmation of ultrasound in 21%. The utility of MRI as routine as an adjunct to ultrasound needs more prospective studies.
Meanwhile, even with all above applications of prenatal evaluations, there still occurred “missed cases” or underestimated cases. Palacios-Jaraquemada et al.13 have argued that the topography rather than the depth of invasion was more reliable in prediction of maternal morbidity. In general, risk model with detailed stratification is fundamental to standardize clinical treatment. The biomarkers, such as alpha-fetoprotein or human chorionic gonadotropin, so far have not been showed as valuable as other complications.
In case of planned delivery fails, there should be contingent strategy for emergency delivery. The transfer system is composed of two parts, involving patient-to-hospital or to centers of excellence with exports, in the settings of before or during delivery, or after delivery for further intense care and management.
With the development of Chinese economy, many business models have been validated to be convenient and efficient. Online to offline with application of WeChat (Chinese multi-purpose messaging, social media and mobile payment app) has been taken as example for emergent care model for PAS.14 Taking the advantage of the connection between caregivers and patients get closer, the timeline extended to before admission, and the rate of hysterectomy was decreased from 20.6% (45/218) to 14.9% (31/209) with fully prepared assembly.
The referral centers with multidisciplinary exports confront complicated cases with well preparation,15 and have been well described. In order to enhance the effectiveness of management, a large number of dedicated exports and resources should be ready for 24/7 service. And around delivery, a complicated general plan needs to be finalized. From placement of epidural catheters, interventional radiology, transfusion, or mechanical ventilation if needed. Detailed consents on massive transfusion, intensive care unit admission, or prolonged stay should be thoroughly discussed and counseled.
As the employment of conservative treatment may associated with high rate of repeated hysterectomy and major severe morbidity, it is common opinion among major academic societies worldwide that only carefully selected cases could be considered. In the past few decades, several methods have been applied both preoperatively and intraoperatively to reduce pelvic organ blood supplies. There is no significant difference of postpartum bleeding whether hysterectomy is performed or the uterus is successfully preserved.
Among them, the tourniquet compression16 and uterine compression suture during surgeries are widely applied in China. For prophylactic interventions, abdominal aortic balloon occlusion, which means preoperative placement of balloon catheters that are inflated after delivery of the baby, is more and more applied to reduce intraoperative and postpartum blood loss, especially in the subgroup of placenta percreta. Nonetheless, the effectiveness of this procedure is still doubtful for the risk of exacerbating collateral circulation bleeding, complicating vessel rupture, and thromboembolism.
In a multi-center retrospective study leading by Peking University First Hospital in China (unpublished data), maternal outcomes were compared between the conservative management with or without abdominal aortic balloon occlusion in placenta percreta cases. The sample size of 132 cases was relatively large. With propensity score-matched method applied to statistically evaluate causal effects, an observational study into a randomized study was achieved, and showed significant reduction in the rate of postpartum hemorrhage (68.9% vs. 87.9%, P < 0.001), blood loss (1805 vs. 3017 mL, P = 0.006), hysterectomy (8.3% vs. 65.2%, P < 0.001), and repeated surgery (1.5% vs. 12.1%, P < 0.001). Hence, Prophylactic AABO can significantly lower the rate of blood loss, hysterectomy, and repeated surgery. This procedure has not shown harmful effects toward neonatal outcomes.
PAS disorder is a multifactorial process that encompasses a heterogeneous group of conditions characterized by an abnormal invasion of trophoblastic tissue through the myometrium and uterine serosa. It endangers the life of both mother and child. Along with global scientists, research groups from Chinese society attach much attention to PAS. Combining existed evidences and conducting target-oriented prospective studies from multiple centers to intervene this critical crisis in obstetrics.
Conflicts of Interest
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