Screening At First Trimester And Clinical Study Of Prenatal Ultrasound Staging System For Placenta Accreta Spectrum Disorders

IntroductionPlacenta accreta（PA）was first described by obstetricians Irving and Hertig in1937.There are several different terminologies for placenta accreta in different literatures,such as adhesive placenta disease（APD）,abnormally invasive placenta（AIP）,morbidly adherent placenta（MAP）,invasive placenta（IP）,etc..The terms are confused,so it is necessary to standardize the diagnostic terminology.Bhide et al.also called for the standardization of the diagnostic terminology for placenta accreta.Placenta accreta spectrum（PAS）disorders were first proposed by Luke et al..In order to standardize terminology and facilitate academic exchanges,the International Federation of Gynecology and Obstetrics（FIGO）recommended that the disorders such as the villi simply adhere to the myometrium,the villi invade the myometrium and the villi invade the full thickness of the myometrium be included in PAS.PAS is classified into three categories according to the depth of the placental trophoblast invading the myometrium:placenta creta（PC）,placenta increta（PI）and placenta percreta（PP）.In this study,we refer to all the cases as PAS disorders.The incidence of PAS disorders is increasing in many middle and high-income countries around the world.Prior cesarean section and placenta previa are the main risk factors,and high rate of cesarean section has also increased the incidence of placenta previa.Study showed that more than 90%of pregnant women diagnosed with PAS have a placenta previa.Because PAS can cause catastrophic bleeding,especially in pregnant women with placenta percreta,as a result,emergency postpartum hysterectomy is required in most cases.And sometimes more serious complications such as bladder fistula,ureteral injury,pulmonary embolism,and diffuse intravascular coagulation（DIC）,acute respiratory distress syndrome（ARDS）,renal failure,and even death are occurred,so prenatal diagnosis is an important basis for clinical management.Prenatal diagnosis methods for PAS include ultrasound imaging,magnetic resonance imaging（MRI）and serum markers.Ultrasound imaging is a preferred,promising and effective screening tool for PAS disorders.Prenatal diagnosis of PAS can reduce the incidence of perioperative complications,especially the risk of surgical bleeding,and prenatal ultrasound diagnosis has become the key to improving the outcomes of PAS.Although MRI has been widely employed in the diagnosis for PAS,has yet to clearly demonstrate a signifcant improvement in management or pregnancy outcomes.At present,many professional institutions around the world,including the Royal College of Obstetrics and Gynecology（RCOG）,recommend MRI only as an aid to ultrasound imaging.In recent years,many scholars have devoted themselves to studying the prediction of maternal serological indicators for obstetric comorbidities and complications,such as miscarriage,premature delivery,intrauterine fetal death,preeclampsia,intrauterine growth restriction（IUGR）and PAS disorders.The main indicators that can predict PAS are alpha-fetoprotein（AFP）,pregnancy associated plasma protein A（PAPP-A）human chorionic gonadotropin（HCG）,creatine kinase（CK）and cell-free fetal DNA（cff DNA）etc..Since prior cesarean section is an independent risk factor of PAS disorders,pregnant women with the prior cesarean section are the high-risk population of PAS.The first part of this study is to predict the possibility of PAS in high-risk groups by ultrasound screening the high-risk population of PAS at pregnancy 11～13⁺⁶weeks,and provide basis for subsequent clinical follow-up and management.Serum markers are not the specific indicators for screening PAS disorders,and it is difficult to detect and screen in general population.However,the maternal serological indicators testing has less trauma,and it’s repeatable,which can combine with imaging examinations in high-risk populations to identify pregnant women at risk of PAS.The second part of this study aims to explore the predictive value of serum PAPP-A and freeβHCG at11～13⁺⁶ weeks of pregnancy for the occurrence of PAS in high-risk population,and provide new ideas for the prenatal diagnosis of PAS.Previous studies on prenatal diagnosis of PAS focused on the accuracy of diagnosis,and few studies evaluated the risk stratification of prenatal ultrasound staging.FIGO proposed a clinical staging system for PAS to describe and classify different levels of PAS during delivery in2018.The third part of this study aims to establish a ultrasound staging system for PAS based on the characteristics of prenatal ultrasound signs.To explore the correlation between prenatal PAS ultrasound staging system and surgical outcome,the degree of invasion,and the FIGO clinical staging for PAS.PartⅠUltrasound screening at first trimester for placenta accrete spectrum disordersAims:To investigate the high-risk population of placental accreta spectrum disorders by ultrasound screening of women with prior cesarean section at 11～13⁺⁶ weeks of pregnancy,and to explore the value of ultrasound imaging in screening placental accreta spectrum disorders at first trimester.Materials and methods:1.A prospective study was conducted on pregnant women who were undergoing routine examinations in our hospital from October 2016 to October 2019 at 11～13+6weeks of pregnancy.Two groups of the cases were enrolled,the first group included4528 cases of pregnant women with prior cesarean section,and the other group included 827 cases were randomly selected without cesarean section.2.Basic clinical data and related medical history of all cases in detail were recorded.All cases were routinely examined by ultrasound at 11～13⁺⁶ weeks of gestation,and the results of ultrasound examination were recorded.According to the cesarean section,the cases were divided into two groups:the experimental group with cesarean section and the control group without cesarean section.The patients in the experimental group were classified into two groups according to the placental position,the relationship between uterine scar and placenta,which included high-risk group and low-risk group.3.After screening at 11～13⁺⁶ weeks,the low-risk group and the control group underwent regular obstetric follow-up in accordance with routine procedures.Ultrasound imaging characteristics and related clinical data were recorded,and the ultrasound images were saved for subsequent retrospective analysis.The high-risk group was monitored closely,and the content of the follow-up focused on the ultrasound signs related to the PAS.Ultrasound signs and related data were recorded in detail,and the ultrasound images were stored for retrospective analysis.Ultrasound images characteristics were analyzed by two experienced ultrasound diagnosis doctors,and the analytical results were recorded.4.All cases were followed up until delivery.The PAS disorders were diagnosed by histopathology or clinical intraoperative conditions.Results:1.The average age of the high risk group was higher than those of control group（P<0.05）and low risk group（P<0.05）,and there was no significant difference in the average age between control group and low risk group（P>0.05）.The number of cesarean sections in high risk group was higher than those of low risk group（P<0.05）.High risk group had higher pregnancy times than low risk group and control group（P<0.05）;Low risk group had higher pregnancy times than control group（P<0.05）.All cases in the three groups were not combined with uterine malformations.There was no significant difference in the history of uterine and uterine cavity surgery among the three groups（P>0.05）.2.107 subjects were diagnosed with PAS postpartum in high risk group,which accounted for 31.2%（107/343）and included 37 subjects with placenta creta（PC）,25subjects with placenta increta（PI）and 45 subjects with placenta percreta（PP）.All of the subjects were complicated with placenta previa or low placenta.3 subjects were diagnosed with PAS after delivery in low risk group,which accounted for 0.072%（3/4143）.Of which 1 subject conceived by in vitro fertilization（IVF）was diagnosed with PC;1 subject had a history of uterine cavity surgery was diagnosed with PC;1with PI was was diagnosed as an angular pregnancy at first trimester.1 subject with PC in control group was diagnosed as an angular pregnancy at first trimester,which accounted for 0.13%（1/784）.To compare the incidence of PAS in high risk group,low risk group and control group,the results showed that the incidence of PAS in high risk group was significantly higher than those of low risk group and control group（P<0.05）.There was no significant difference in the incidence of PAS between low risk group and control group（P>0.05）.3.7 cases with placental lacunae,5 cases with loss of the hypoechoic clear zone between placenta and myometrium,5 cases with uterovescical hypervascularity,and 7cases with anterior myometrial thinning（less than<5mm）at 11～13⁺⁶ weeks of pregnancy out of 111 cases diagnosed with PAS.Conclusions:Ultrasound screening at 11～13⁺⁶ weeks of pregnancy can screen high-risk group of PAS.It is extremely important to reduce the occurrence of serious complications by frequently following up and managing in the high-risk group of PAS.PartⅡSignificance of serum screening for aneuploidy at first trimester in the diagnosis of placental accrete spectrum disordersAims:To explore the application value of serum PAPP-A and freeβHCG in the prediction and diagnosis of PAS at 11～13⁺⁶ weeks of pregnancy.Materials and methods:1.Pregnant women who were referred for routine screening for ultrasonography at 11～13⁺⁶ weeks of gestation in our hospital from October 2016 to October 2019were enrolled in the study if they had prior cesarean section and with placenta previa or low placenta.A total of 343 cases were enrolled in this study.2.According to the results of ultrasound screening at 11～13⁺⁶ weeks of gestation and the diagnosis results of PAS after delivery,343 subjects were classified into PAS group,normal control group,placenta previa group and low placenta group.3.2～3m L of peripheral venous blood was drawn after a routine ultrasound examination at 11～13⁺⁶ weeks of pregnancy in all subjects.The serum PAPP-A and freeβHCG values were tested and compared with postpartum diagnosis results of PAS.The serum PAPP-A and freeβHCG levels of PAS group,normal control group,placenta previa group and low placenta group were compared.The levels of serum PAPP-A and freeβHCG among PC,PI and PP were compared.4.To construct a receiver operating characteristic（ROC）curve,calculate the area under curve（AUC）,and obtain the best diagnostic cutoff values of PAPP-A and freeβHCG to predict the PAS.Results:1.343 cases combined with cesarean section and placenta previa or low placenta were diagnosed at 11～13⁺⁶ weeks of pregnancy.During the ultrasound following-up,the placentas migrated upward（n=151）as the gestational age increasing and became the normal placenta position.Of these 151 cases,none of them were combined with PAS,and they were classified as normal control group.192 cases were eventually combined with placenta previa or low placenta,and 107 were diagnosed with PAS after delivery,which were classified as the PAS case group.Among the 107 PAS cases,47 cases with PA,25 cases with PI and 35 cases with PP.85 cases with placenta previa but without PAS were classified as the placenta previa group（n=51）and low placenta group（n=34）.2.The PAPP-A value of PAS group was significantly higher than those of control group,placenta previa group and low placenta group（P<0.05）.There was no difference in PAPP-A among normal group,placenta previa group and low placenta group（P>0.05）.FreeβHCG in PAS group was higher than those in normal group,placenta previa group and low placenta group（P<0.05）.There was no difference in freeβHCG between normal control group,placenta previa group and low placenta group（P>0.05）.3.The comparison of serum PAPP-A andβHCG levels in different types of PAS groups showed that the PAPP-A level of PP group was higher than those of PC group and PI group（P<0.05）.There was no difference in PAPP-A level between PC group and PI group（P>0.05）.TheβHCG level of PP group was higher than those of the PC group.There were no difference in freeβHCG between PI group and PC group,and no difference between PC group and PP group（P>0.05）.4.ROC curve analysis results showed that the diagnostic cut-off value of serum PAPP-A is 1.32,AUC is 0.941,the sensitivity is 86%,the specificity is 94.5%,and the diagnostic cut-off value of serum freeβHCG is 1.16,AUC is 0.876,the sensitivity is 66.4%,the specificity is 95.3%.Conclusions:Serum PAPP-A and freeβHCG can predict the possibility of occurrence of PAS in high-risk population at 11～13⁺⁶ weeks of pregnancy,which has important clinical significance for pregnancy management,and provides a new method for clinical diagnosis for PAS.PartⅢClinical study of prenatal ultrasound staging system for placenta accrete spectrum disordersAims:To develop a prenatal ultrasound staging system for PAS in pregnant women with placenta previa or low placenta,and to evaluate its correlation with surgical outcome,the degrees of PAS invasion,and the clinical staging for PAS disorders proposed by the International Federation of Gynecology and Obstetrics（FIGO）.Materials and methods:1.A retrospective analysis of prospectively was carried out on the pregnant women who were pregnant at 11～13⁺⁶ weeks from October 2016 to October 2019 for a routine check-up.Cases of pregnant women with prior cesarean section and prenatal diagnosis of placenta previa or low placenta were selected as the research objects.A total of 192 eligible pregnant women were enrolled.2.The ultrasound examination results and clinical basic characteristics of 192cases were analyzed.To established a prenatal ultrasound staging system for PAS disorders based on the characteristics of ultrasound images signs,and to compare the ultrasound staging system for PAS disorders with the surgical outcome,which included:general condition of the newborns,estimated blood loss,operation time,occurrence of surgical complications,length of hospital stay and admission to the intensive care unit（ICU）.3.To evaluate the correlation between the ultrasound staging system for PAS disorders and the depth of placental invasion,PC,PI and PP were included.4.To compare the correlation between the ultrasound staging for PAS disorders and the clinical staging proposed by FIGO.Results:1.Two experienced ultrasound diagnosis doctors separately performed ultrasound staging for PAS disorders based on ultrasound images signs of the 192 cases in this study.The difference between the two ultrasound staging results was not statistically significant（P>0.05）.The final results of ultrasound staging for PAS disorders were as follows:103 cases of PAS0,accounting for 53.6%（103/192）,32 cases of PAS1,accounting for 16.7%（32/192）,21 cases of PAS2,accounting for 10.9%（21/192）,36cases of PAS3,accounting for 18.8%（36/192）.2.Comparison of ultrasound staging for PAS and surgical outcome（1）General conditions of newborns No neonatal complications occurred in the newborns,and the Apgar score（1min,10min）of all the newborns were not statistically significant（P>0.05）.In comparison of newborn birth weight,PAS0 had the largest weight and PAS3 had the smallest weight.The differences amomg all the groups were statistically significant（P<0.05）.（2）Mean operation time Mean operation time was longer in women with PAS3compared with those with PAS0,PAS1,or PAS2（P<0.05）.PAS3 had the longest mean operation time and PAS0 had the shortest mean operation time.（3）Estimated bleeding loss（EBL）The EBL in PAS3 was significantly higher than PAS0,PAS1 and PAS2（P<0.05）.（4）Postoperative complications No postoperative complications occurred in PAS0,PAS1 and PAS2;3 cases complications occurred in PAS3,accounting for 8.3%（3/36）.（5）Hospital stay Women with PAS3 had longer hospital stay compared with those with PAS0,PAS1 or PAS2（P<0.05）.PAS3 had the longest hospital stay and PAS0 had the shortest hospital stay.（6）ICU admission PAS0,PAS1 or PAS2 were not transferred to ICU for treatment;4 cases of PAS3 were transferred to ICU,accounting for 11.1%（4/36）,while only PAS3 was associated with admission to the ICU（P<0.005）.3.The correlation between ultrasound staging and the degress of placental invasionAmong the 192 cases,85 cases without PAS,accounting for 44.3%（85/192）;107 cases were combined with PAS,accounting for 55.7%（107/192）,including PC（n=37）,PI（n=25）,and PP（n=45）.The comparative analysis of the ultrasound staging system for PAS and the depth of placental invasion showed that PAS0 included 17.5%（18/103）with PC and 82.6%（85/103）with normal adhesions;PAS1 included 59.4%（19/32）with PC,40.6%（13/32）with PI;PAS2 included 57.1%（12/21）with PI,42.9%（9/21）with PP;PAS3 were all with PP（36/36）.4.The correlation between ultrasound staging and clinical staging for PASCorrelation analysis between the ultrasound grading system and the FIGO clinical staging system for PAS disorder showed that:All women with PAS0 on ultrasound were classified as having Grade-1（n=85）and Grade-2（n=18）according to the FIGO grading system.Of the women presenting with PAS1 on ultrasound,9.3%（3/32）were classified as having Grade-2,68.8%（22/32）were classified as having Grade-3 and 21.9%（7/32）were classified as having Grade-4 according to the FIGO grading system.All women with PAS2（n=21）were categorized as having Grade-5and all those with PAS3（n=36）as having Grade-6 according to the FIGO system for PAS.Conclusions:1.The ultrasound staging system for PAS is related to the surgical outcome and can predict the surgical outcome.2.The ultrasound staging for PAS is related to the depth of placental invasion and can predict the depth of placental invasion.3.The ultrasound staging system for PAS has a good correlation with FIGO clinical staging for PAS,which can provide a basis for clinical treatment.