Clinical aspects and antenatal diagnosis of invasive placenta: a review of ten-years’ experience of a multi-profile hospital in Lithuania

Background. Invasive placenta is a rare obstetrical pathology that is life-threatening to mother and child. It is important to diagnose this pathology as early as possible and to plan further optimal care of patients in order to minimize life-threatening complications. The aim of this study was to analyze the frequency of cases of invasive placenta, the peculiarities of their clinical manifestation in women who gave birth from 2006 to 2015, to evaluate diagnostic and treatment options of this pathology, and to review their changes when the level of services provided by the institution changes. Materials and methods. A retrospective study was performed of the ten-year period of 2006 to 2015. The study consisted of examining the data of medical records of a group of 14 women. Results. The incidence of invasive placenta at the secondary level hospital was 1/2170 births, 1:934 births at the tertiary level. There were only three patients (21.4%) diagnosed with invasive placenta during pregnancy at Vilnius University Hospital Santaros Klinikos Obstetrics and Gynaecology Centre. Before the surgery, pre-occlusive balloons were ushered into the internal iliac artery and inflated to reduce bleeding after the newborn delivery. The amount of blood loss in the whole group ranged from 1000 to 6500 ml (avg. 3130.7 ml). Radical treatment was given to eleven patients. Conclusion. Invasive placenta is a life-threatening condition. Tertiary-level hospitals have a greater capacity for antenatal diagnostics. Timely diagnosis of placental invasion and evaluation of the level of the myometrium damage before delivery is instrumental in planning patient care and preparing for delivery and operation.


INTRODUCTION
Invasive placenta is the term used to describe the condition when the whole or part of the placenta grows into the uterine wall and fails to detach from it during the delivery. It often leads to life-threatening complications such as severe bleeding, a caesarean section with possible hysterectomy, and even serious pelvic injuries.
Histologically, placental invasion is identified by trophoblast invasion into the myometrium through a decidua basalis defect. The most serious form of this condition is placenta percreta, when placenta grows through the uterine muscle and serosa layer or even overgrows the adjacent pelvic organs such as the bladder. The presence of placental overgrowth into uterine muscular layer without the infringement of the serosa layer is called placenta increta. A minor invasion is described as placenta accreta. Also, this term is often used as a general term to describe all these conditions (1).
Such an abnormal attachment of the placenta to the uterine wall is a life-threatening obstetric complication that causes excessive bleeding during pregnancy, delivery, or after it. It may also cause other serious complications such as disseminated intravascular coagulation (DIC), acute insufficiency of functions of kidneys and other organs, infectious complications, acute respiratory distress syndrome (ARDS), and fertility loss. Due to this pathology, the fatality rate is at 7% high.
Because of invasive placenta, has to be completed earlier. Life-saving surgical interventions such as hysterectomy or ligation of major pelvic blood vessels has to be used, transfusion of blood products has to be performed. Participation of a multidisciplinary team is required (2)(3)(4).
Early diagnosis of invasive placenta allows planning further care of the patient and preparation for possible surgery. Unfortunately, most of the cases are determined at the delivery when placental expulsion fails (2,3).
Vilnius University Hospital Santaros Klinikos is a multi-profile hospital. Until 2013, the Obstetric and Neonatal Department was part of the Central Branch of this hospital. It was a secondary-level hospital department. The Obstetrics and Gynaecology Centre was established in 2013, and since then the Department of Obstetrics, including the Perinatology Centre, has been providing tertiary-level functions. This offered a unique opportunity to examine the frequency of invasive placental pathology, peculiarities of its clinical course, and diagnostic and treatment options in one place, depending on the hospital level.
This study aims to analyze the frequency of cases of invasive placenta and peculiarities of its clinical manifestation in women who gave birth at a multi-profile hospital during a ten-year period (2006 to 2015), to evaluate diagnostic of this pathology and options of its treatment, and to review their changes resulting from the change in the level of services provided by the institution.

MATERIALS AND METHODS
A retrospective study of cases from a ten-year period, 2006 to 2015, was performed. The data of medical records of clinically diagnosed and histologically approved diagnosis of invasive placenta were investigated. The group consisted of 14 women.
The research was performed in accordance with the World Medical Association Declaration of Helsinki.

RESULTS
During the study period (2006 to 2015) at Vil nius University Hospital Santaros Klinikos Hospital, invasive placenta was diagnosed to 14 women: four women who gave birth at the Central Branch before 2013 and ten women who were treated at the Obstetrics and Gynaecology Centre from 2013 to 2015. During the period of investigation, 18,021 women gave birth: 8682 gave birth at the Central Branch before 2013 and 9339 at the Obstetrics and Gynaecology Centre from 2013 to 2015. Thus, the incidence of invasive placenta at the secondary-level hospital was 1/2170 births, and 1/934 births at the tertiary level.
The data of the investigated women is briefly presented in Table. Characteristics of the investigated women The women's age ranged from 29 to 45 years (avg. 35.4). For two women (14.3%), it was the first pregnancy, three women had from one to three abortions. For three women it was the first delivery and 11 were multiparous. Five patients (35.7%) had experienced caesarean section. The first caesarean Table. Data of the investigated women and neonatal data   Parameter  Case  1  2  3  4  5  6  7  8  9  10  11  12  13  14  Year  2006 2007 2010 2012 2013  2014  2015  Hospital  Secondary B  Tertiary  Age, year  29  36  31  38  33  32  32  33  40  45  36  39  35  37  Pregnancy  I  IV  III  I  II  II  III  V  III  VIII  III  III  X  IV  Delivery  I  IV  III  I  I  II  III  III  II  III  II  III  VII  III  Gestational  age, weeks  40  37  38  38  39  41  32  32  40  40  35  20  21  20 Previous caesarean delivery Apgar score at 5 min 9 8 10 10 9 10 8 8 10 9 9 Abbreviations: VD -vaginal delivery, CS -caesarean section, + -patient was indicated with a complication, R -radical treatment, S -sparing treatment, TH -total hysterectomy, SH -subtotal hysterectomy, M -a male newborn, F -a female newborn was performed for two women and the second caesarean for three patients. Two women had abnormal placental period in the past. All patients had one-foetus pregnancies. Duration of pregnancy with invasive placenta was from 20 to 41 weeks. Three women (21.4%) had complications of invasive placenta at 20th-21st week of pregnancy. These pregnancies resulted in abortion due to massive haemorrhage. Three patients (21.4%) gave birth prematurely at 32nd-35th (avg. 33rd) week of pregnancy. Other patients gave birth on time. Four of them gave birth before 2013, when the hospital was a secondary-level hospital. From 2013, pregnancy losses of patients before 22 weeks or premature delivery due to invasive placenta were five out of ten (50%). The average duration of pregnancy in the study group was 33.8 weeks.

Antenatal diagnosis
There were only three patients (21.4%) diagnosed with invasive placenta during pregnancy at the Obstetrics and Gynaecology Centre. All these patients were treated at the centre's tertiary-level hospital in 2015. In these patients, invasive placenta was not found or suspected at the outpatient department. They all arrived at the tertiary level hospital in a matter of urgency due to abdominal pain of varying intensity and/or bleeding from the uterus; one of the patients lost consciousness. All patients had had caesarean sections in the past: two had two caesarean sections, one -four caesarean sections. All patients were diagnosed with invasive placenta after ultrasound examination (Figs. 1, 2) and confirmed with magnetic resonance imaging (MRI) (Figs. 3-6).

Clinical manifestation
Eleven patients (78.6%) were diagnosed with invasive placenta when complications developed during the delivery or after it. Complications developed to two patients in the late period postpartum due to retained placenta: one patient had sepsis and profuse bleeding (nine days after delivery), another had profuse bleeding with DIC syndrome (30 days after delivery). Two patients (20th and 32nd weeks of pregnancy) were diagnosed with a uterine rupture due to placental invasion, manifesting with acute abdominal expressions and massive internal bleeding. The uterus of one of the patients is shown in Fig. 7. The remaining nine patients had profuse bleeding due to invasive placenta during the delivery or the caesarean section. the removal of ovaries and fallopian tubes, two women underwent subtotal hysterectomy without removal of ovaries and fallopian tubes.
In three cases, a caesarean hysterectomy was performed: one patient was diagnosed with invasive placenta antenatally and in two patients the placental invasion was revealed during surgery. No attempt was made to remove the placenta in either of the three patients and it was left in situ (Figs. 7,8). Surgery was carefully planned in advance for the patients whose diagnosis was established antenatally. It was performed by a multidisciplinary team of the tertiary-level hospital. Pre-occlusive balloons (Fig. 9) were ushered into the internal iliac artery before the surgery and inflated to reduce bleeding after a newborn delivery.
Hysterectomy was performed in six patients who gave birth naturally, in the period after the delivery. Two patients underwent surgery due to heavy bleeding within 45 min and 1 h 52 min after the delivery of a newborn, respectively. The other two were operated on due to heavy bleeding when All the patients had lost more blood than usual. The amount of blood loss in the whole group ranged from 1000 to 6500 ml (avg. 3130.7 ml). The women who gave birth naturally lost from 1200 to 5670 ml (avg. 2847.1 ml) of blood; those who underwent a caesarean section lost from 1000 to 6500 ml (avg. 2925.0 ml). The women who had complications of invasive placenta before 22 weeks of pregnancy lost from 1700 to 6000 ml (avg. 4066.7 ml) of blood.

Treatment
A radical treatment was given to eleven patients: nine women had total hysterectomy without One patient, who received sparing treatment, became pregnant two years later and gave birth again. She did not suffer a placental invasion during her next pregnancy, delivered a healthy newborn on time, and did not experience any complications during pregnancy and after.

Hospital admission time
Total hospital admission time of patients treated for invasive placenta was from 5 to 74 days (avg. 13.29). The admission time after delivery or a caesarean section was from 5 to 16 days (avg. 8.21). Nine patients required treatment in the intensive care unit. The intensive care unit admission time varied from 17 h 30 min to 378 h 29 min (avg. 90 hours).

Neonatal data
There were four male and nine female infants born in a group of 11 newborns. The ratio of boys and girls was 1:2.25. Infant birth weight was from 2000 to 4120 g (avg. 2931.36), height from 42 to 55 cm (avg. 49.27). The Apgar score at 1 minute was from 6 to 9 (avg. 8.18); two newborns were given 6 points, and one 7 points. At 5 minutes, Apgar scores ranged from 8 to 10 (avg. 9.09).

Prospects for future fertility
Uterus-sparing treatment was selected for three patients. The diagnosis was not established before the delivery for either of these patients and invasive placenta was diagnosed during the delivery or postpartum. In all these cases the placental invasion was partial. In two cases, part of the damaged myometrium was removed during the caesarean section. However, continuing bleeding from the uterus raised the suspicion of the invasion of placenta. The diagnosis was verified by ultrasound and MRI (Fig. 10). Selective embolization of the ascending branch of the right uterine artery and the uterine curettage in ultrasound control were selected. All the patients received adequate treatment and there were no complications.

DISCUSSION
This placental pathology was first described in 1930. The existence of this pathology was even questioned at that time as it was extremely rare. However, cases of invasive placenta have been increasing in recent decades: from 1/4027 pregnancies in 1970 to 1/533 pregnancies in 1982 to 2002. According to our research data, the frequency of invasive placenta in secondary-level hospitals was 1:2170 pregnancies, and in tertiary-level hospitals 1:934 pregnancies (1,5).
In most cases, abnormal placental attachment is associated with uterine scars after previous surgeries, such as caesarean section, myomectomy, and placenta praevia. The risk is higher if placenta implants itself in the uterine scar area (6).
It is important to note that invasive placenta may occur to patients who did not have a caesarean section before. In our group, only 35.7% of women had caesarean sections in the past. Risk factors of placenta accreta also include previous intrauterine infections, maternal age (over 35 years), many previous pregnancies (more than six), cervical dilation and curettage, ablation of endometrium, submucous myomas, hypertensive conditions, smoking (7). The average age in the study group was over 35 years old; eight patients (57%) were older than 35 years old; 14.28% of the investigated women were pregnant more than 6 times; 35.7% of women had several risk factors.
It is very important to determine the diagnosis of invasive placenta before the delivery. Unfortunately, only about 30% of cases are determined at the antenatal stage and in 70% of cases the diagnosis is established upon the emergence of complications (2). Invasive placenta results in 38% of cases of intense postpartum bleeding. Such bleeding causes other serious complications: DIC, acute insufficiency of the kidney function, infectious complications, ARDS, and fertility loss. Transfusion of blood products (1,4,5) has to be performed. The mortality rate is high -7%. We succeeded in avoiding death cases in our research group (100% survival).
Early diagnosis allows planning further patient care and treatment and proper preparation for a surgery and possible massive bleeding. This can reduce the blood loss and the need for the transfusion of blood products (3,8).
The diagnosis is usually established by ultrasound and additional MRI. Histological examination is necessary to confirm the final diagnosis (9).
Transvaginal and transabdominal ultrasonography are complementary methods, especially when placenta praevia is present. Findings of ultrasound examination leading to the suspicion of the invasion of placenta depend on the stage of pregnancy (9). In the first trimester of pregnancy, it is implantation of the gestational sac in the lower segment of the uterus or in the uterine scar area, multiple irregular vascularization areas in the place of placentation. After detection of these symptoms, it is appropriate to repeat ultrasound examination at a later period (32 weeks) and test specifically for the symptoms of placental invasion.
During the second and the third pregnancy trimesters placental invasion presents itself as an irregular lacunae shape in the manifestation of the placenta. During the Doppler scan, a turbulent blood flow in placental lacunae is recorded, thinning of retroplacental hypoechogenic line or its absence, uneven thinning of the myometrium, intervention of placental tissue into the rear wall of the bladder with uneven thinning of the uterine and bladder gap, and bright blood flow (9,10). The presence of lacunae (irregular vascular areas resembling "Swiss cheese" in the area of placental implantation) in the placenta and an increase in their number during the 15th-20th weeks of pregnancy are very important prognostic signs of placenta accreta (sensitivity of 79% and positive predictive value 92%). The more lacunae are present, the more likely the placental invasion into the surrounding tissue. The finberg scale is used: evaluated by grade 0 when no lacunae are seen, grade 1 when one to three small lacunae are present, grade 2 when four to six larger or more irregularly shaped lacunae are detected, and grade 3 when lacunae are present all over the placenta (11).
Criteria of placental invasion of the Doppler scan are: abnormal hypervascularization of tissue (the myometrium and the bladder gap), enlarged diffusion lacunae throughout the area of the placenta, that reach the myometrium and the cervix, low-resistance arterial blood flow, enlarged venous-type flow blood vessels, locally extinct vascular tone in the hypoechogenic subplacental gap. It is highly important to identify the pathological blood flow between the uterus and the bladder wall. This is one of the best indicators for invasive placenta diagnostics, which has high sensitivity and specificity of this parameter (12).
The sources of literature indicate that evaluating the entire whole of risk factors (condition after two or more caesarean surgeries, placenta on the front wall of the scar area), ultrasound findings, and calculation of the index of placenta accreta increase the possibility of detecting placental invasion to 96% (11).
In doubtful cases, MRI can be useful and complement the antenatal diagnosis (13). In our group, MRI was used in all the cases when placental invasion was suspected at the antenatal stage after ultrasound examination. In all cases, MRI confirmed the diagnosis. In one case MRI was also used after natural delivery when an invasion of leftover placental fragments was suspected clinically and by ultrasound.
MRI examination helps to evaluate the topography and placental invasion and can be useful in planning surgical treatment. MRI is now described as an examination that better predicts topography and placental tissue invasion, the possible damage to the adjacent organs, urethral involvement in this process. Helps to optimize the tactics of maternal care and treatment (14).

Tactics in prenatal diagnosis of placental invasion
After an ultrasound examination at the 20th week of pregnancy, when placenta previa is present and placental ingrowth is suspected, another ultrasound examination is recommended at the 32nd week of pregnancy. The diagnosis is adjusted during ultrasound examination; a further plan of pregnancy and delivery care is made (15).
A woman with a suspected placenta accreta is recommended to give birth at a tertiary-level hospital due to the potential danger of this condition and life-threatening bleeding. All the patients in the study group, who were diagnosed with invasive placenta before delivery, gave birth at a tertiary-level hospital. Only when patients were not diagnosed before delivery, they gave birth at a secondary-level hospital. The best treatment of placenta accreta is to start the evaluation of risk factors at the antenatal stage and, if circumstances allow, to confirm the diagnosis and develop a plan for further care. A multidisci-plinary team of experienced obstetrician-gynaecologists, anaesthesiologists, surgeons, interventional radiologists and urologists must be involved (5). Such tactics was used in our group with all the necessary personnel, services and equipment reserves of a tertiary-level hospital.
Optimal treatment of abnormal placental attachment has not been established yet. When ingrown or overgrown placenta is diagnosed, the usual method of treatment is a hysterectomy during the caesarean section (5). This surgery is associated with high morbidity and mortality of women, especially if it is performed urgently. As presented in a systematic review, the frequency of complications after urgent hysterectomy is 56% and the mortality rate is 3%. Surgery can be complicated by a damage to the urinary tract, profuse bleeding, and infection caused by invasive placenta. This risk can be reduced with preventive antibiotics at the early post-operative period. Neither methotrexate, nor artery embolization reduce this risk and should not be administered routinely (3,16,17).
If it is difficult to separate placenta from the uterus, separation should not be attempted during surgery. If the necessity of a hysterectomy arises, placenta should be left in situ, the uterine cavity should be closed with a few sutures, and an ordinary hysterectomy (usually subtotal, but if bleeding from the cervix does not stop, it can be total) performed (3,18).
It is proved that both general and regional anaesthesia are safe in the case of placenta accreta, therefore it should be decided individually which to administer. If surgery is planned, it is recommended to put on compression stockings before surgery and wear them throughout the admission period. Antibiotics are administered for the prophylaxis of infection, repeating the dose every 2-3 hours or if the volume of blood lost reaches or exceeds 1.5 l. Cystoscopy may be performed before surgery for the prophylaxis of urinary tract damage, during which the urinary tract may be stented. Blood components and coagulation factors should be prepared and ready to use in case of a possible blood transfusion (5).
In order to reduce blood loss during surgery, balloon occlusion of internal iliac arteries can be used (19). Such auxiliary method had a positive effect in our unit.
There are some data about other methods applied to staunch bleeding: bimanual compression or even aortic compression, balloon tamponade, the B-Lynch suture, vertical compression sutures, and inverse sewing of the cervical lip above the bleeding placenta (20)(21)(22)(23). The B-Lynch suture was ineffective in our study group.
A conservative treatment method was first described in 1986 (24). This treatment strategy aims to preserve the uterus and fertility. It can be applied when the patient is especially concerned about the preservation of the uterus and when the conditions are favourable: stable hemodynamics, normal coagulative state, accessible and safe blood transfusion, and good intensive care.
Ligature on the cord close to the placental surface may be attached after the delivery; placental tissue is left in situ. In order to reduce the size of the placenta, resection of part of the placenta is possible in order to maintain stable hemodynamics and prevent life-threatening bleeding. Compression sutures, selective arterial embolization and/or balloon occlusion, ligation of uterine arteries and/or the hypogastric artery (for spontaneous placental involution by stopping of the blood flow) are also used for the transfusion of blood components and uterotonic during the delivery. Blood loss-controlling methods such as vascular embolization, ligation, or balloon arterial occlusion can be applied during surgery (25,26). Our hospital no longer applies conservative tactics for large-area placental invasion. In the case of partial invasion, resection of the damaged myometrium was selected in two cases and abrasion of the uterus after the delivery with embolization of blood vessels in one case.
Possible complications of conservative tactics include a failure of the procedure, heavy bleeding prevention control at vascular anastomoses, thromboembolism and ischemic reperfusion damages at lower extremities, in particular due to the prolonged occlusion of the internal iliac artery and sudden embolization in the pelvic organs that may result in ovarian necrosis, chronic pelvic pain, sexual dysfunction, and bladder ischemia. Infectious complications are also possible. Complications may develop a few weeks or months after delivery, therefore, the woman should be regularly monitored after the delivery in order to detect possible complications in time (27,28). No complications developed in our study group of carefully selected patients with the uterus-preserving tactics applied.
Preservation of the uterus requires a multidisciplinary effort that includes interventional radiologists. The ability to ensure haemostasis during surgery is a major determining factor in the preservation of the uterus.
According to the Royal College of Obstetricians and Gynaecologists (RCOG), conservative treatment will hardly be successful when woman is already bleeding and is just a waste of valuable time (17).

Prognosis
There are no sufficient data to provide an accurate forecast for other pregnancies. The likelihood of a recurrence of invasive placenta can reach 28.6%, bleeding after the delivery 9.0% (29). One patient in our group became pregnant again and gave birth to a full-term newborn after conservative treatment. Placental invasion did not recur.

Drawbacks of the paper
The research covers a relatively long period during which diagnosis and management of invasive placenta underwent significant changes. Therefore it cannot be unambiguously determined whether the larger number of cases in our study in recent years reflects the absolute increased incidence of this condition, or it can be associated with better diagnostics.

CONCLUSIONS
Invasive placenta is a life-threatening condition. A tertiary-level hospital has a greater capacity of antenatal diagnostics. The options of planning patient care and preparation for delivery and operation largely depend on a timely diagnosis of the placental invasion and evaluation of the level of myometrium damage before the delivery. Patients must be advised, monitored and give birth at a highest level hospital, where necessary resources are ensured: a multidisciplinary team, accessible and safe blood transfusion, and twenty-four-hour intensive care.