The morbidity of PA shows an increasing trend year by year, which has become one of the major causes leading to perinatal hysterectomy, postpartum hemorrhage and maternal death. However, the pathogenic mechanism of PA remains unclear, which may be related to decidua dysplasia, enhanced invasiveness of trophoblasts and changed placental angiogenesis . The high risk factors for PA include advanced age, history of cesarean section, history of intrauterine operation, history of multiple pregnancies and births and placenta previa. In this study, the general data of patients with PA were statistically analyzed. As a result, age, gravidity, induced abortion times, history of cesarean section, history of intrauterine operation and with/without placenta previa were the important factors for PA occurrence, among which, gravidity and placenta previa were the independent risk factors.
Accurate prenatal evaluation and prediction of PA type and severity can reduce the occurrence of adverse pregnancy outcome of PA, so as to make adequate preoperative preparation. Multidisciplinary (obstetricians with PA management experience, anesthesiology, neonatology and ultrasonography) cooperation and sufficient preparation of blood source can reduce the potential maternal and neonatal morbidity and mortality rates . 3D ultrasound flow imaging can provide quantitative reference based on the 3D structure and blood flow perfusion at the lesion site, which is commonly used in the clinical diagnosis of PA . However, there is no uniform standard for diagnosis at present, which makes it impossible to effectively predict the PA severity. In addition, the presence of artifact may lead to a certain rate of misdiagnosis. Serological indexes combined with 3D ultrasound flow imaging can provide a new direction for the clinical diagnosis of PA severity.
Alpha fetoprotein (AFP) and β-human chorionic gonadotropin (β-hCG): AFP is the most commonly seen globulin in fetal serum, which is used to evaluate the placenta barrier function. β-hCG is produced by the trophoblasts, which mainly enter the maternal blood, but its content is relatively low in placental tissue. Its detection rate is high and stable in the second trimester of pregnancy, which can reflect the activity of trophoblasts . Some research discovers that the risk of PA increases significantly when the AFP or free β-hCG (fβ-hCG) level is ≥ 2.5 MOM in the second trimester of pregnancy, and the increase amplitude is related to the severity of PA [10, 11]. This study discovered that the serum AFP and β-hCG levels in PA patients were higher than those of non-PA group. Besides, inter-group analysis among PA groups suggested that, the serum AFP and β-hCG levels in patients increased with the increase in PA severity. These results indicate that serum AFP and β-hCG levels are valuable in the diagnosis of placenta accreta. It is possible that, due to decidua developmental defect in PA patients, the trophoblasts invade the myometrium, at this time, AFP in fetal blood enters the maternal circulation, leading to the increased serum AFP levels in pregnant women. The reason for the abnormal increase of β-hCG may be that when PA occurs, placental villi cannot form a good exchange of maternal and infant nutrients with the uterine basement membrane, resulting in hypoxia of placental tissue, resulting in excessive secretion of β-hCG, and finally the increase of its level.
Soluble Fms-like tyrosinekinase (sFlt) is the soluble form of VEGFR-1, which is selectively expressed in placental tissues and is a kind of placenta-specific protein . sFlt-1 can irreversibly bind to VEGF, thus suppressing the physiological function of VEGF. In addition, it exerts the anti-angiogenic activity, which induces endothelial cell dysfunction, and breaks the vascular wall permeability and integrity . It is also speculated that sFlt-1 may play an important role in enhancing the excessive invasion of trophoblasts and vascular remodeling, and this series of changes may be secondary to the endometrial-myometrial injury microenvironment of PA patients . It was found in this work that, the peripheral blood sFlt-1 levels in PA patients were apparently reduced compared with non-PA group, in particular for placenta percreta. Such result was consistent with the PA serological index research results obtained by Schwickert et al. . The analysis of the reason is that VEGF and sFlt-1 in normal pregnant women in the third trimester are in a relatively stable state. When the expression of VEGF increases and sFlt-1 decreases, it promotes the formation and development of placental blood vessels in pregnant women, and then promotes the occurrence and development of PA.
Creatine kinase (CK) mainly exists in the muscle and brain tissue of human body, which is a kinase related to intercellular energy transfer and muscle contraction. When PA occurs, the villi of the placenta invade the Uterine basal layer and damage the muscle cells, CK in the cells is released into the blood, which can elevate the serum CK level After the damage of muscle cells . In this study, the serum CK level was positively correlated with the PA degree, which might serve as the serological index for the prenatal diagnosis of PA. However, the diagnostic value of serum CK in PA remains controversial [6, 15].
3D ultrasound flow imaging can evaluate placenta angiogenesis from the perspectives of VI, FI and VFI, and assess placenta status from the level of blood supply. The VI, FI and VFI values increase in the case of PA, and the increase amplitudes are positively related to the PA degree. But ultrasound imaging can hardly display the placenta when it is located in the posterior wall, and is subject to the experience of the diagnostic physician. According to our research results, the VI, FI and VFI values in PA groups were higher than those in non-PA group. This was mainly because that, a large amount of new blood vessels were formed in the case of PA, which manifested as the elevated VI, FI and VFI values, but only the difference in VFI value was of statistical significance, and it might be related to our low sample size. ROC curve analysis suggested that, serum AFP, β-hCG, sFlt-1, CK and 3D ultrasound VFI value had the greatest AUC values in predicting PA, which might provide reference for the clinical diagnosis and disease evaluation of PA.
Due to the small sample size of the data analyzed in this study, the results of the study may lack corresponding convincing. In the future, studies with a larger sample size are needed to further widely apply the studied indicators to clinical diagnosis.