JSUR Journal

Introduction

Reports on Placenta Accretae Spectrum (PAS) disorder, one of the most critical pregnancy complications, have increased globally since the 1950s [1-4]. Severe PAS prevents physiological placental detachment after childbirth, which increases the risk of massive obstetric bleeding. PAS disorder was first described in women with previous manual placental removal or uterine curettage in the 1920 - 30s [1]. The primary predisposing factor today, in line with increasing cesarean section (CS) rates globally, is a placenta previa which covers the internal cervical os, or a lowlying anterior placenta in combination with a prior CS scar [27]. Several clinical diagnostic criteria for PAS have been applied, which has resulted in heterogenous study reports. In order to improve the diagnostic accuracy, the International Federation of Gynecology and Obstetrics (FIGO) presented standardized clinical and histological criteria for PAS in 2019 [4]. The histopathological criteria encompass Grade 1 (abnormally adherent placenta accreta), where no decidua is detected and placental trophoblasts attach directly to the superficial myometrium, Grade 2 (abnormally invasive placenta or increta), where trophoblasts invade into the uterine myometrium, and Grade 3 (abnormally invasive placenta or percreta), subdivided into Grade 3a, where invasion is limited to the uterine serosa, Grade 3b, with bladder invasion and Grade 3c, with invasion of other pelvic organs or tissues.

Women with a placenta previa or PAS disorder should be delivered by CS to avoid life-threatening bleeding, and in case of advanced PAS, CS is commonly planned with PPHE. The prevalence of PAS has been estimated according to various diagnostic criteria to 2 - 90 per 10 000 births in different regions of the world [7], The incidence of emergency PPHE in the Nordic countries was 3 - 5 per 10 000 births in 2009 - 12, where four out of 10 were performed because of PAS [7,8]. Advanced PAS disorder should be taken care of at a referral center with Multidisciplinary Care Team (MCT) management to improve clinical outcomes [3-7,9]. The Karolinska University Hospital is a tertiary referral center for high-risk obstetrics including advanced PAS disorders in the Stockholm Region, where approximately one third of the 105 - 110 0000 deliveries per year in Sweden take place [10].

The objective of this study was to compare maternal and neonatal outcomes between the years 2008 - 15 and 2016 - 22, before and after altered clinical guidelines for PAS in 2016. We hypothesized, that the new guidelines would result in improved clinical outcomes.

Material and Methods

A retrospective single-center cohort study of all women with severe PAS in need of CS with PPHE at the Karolinska University Hospital between Jan 1^st 2008 - Dec 31^st 2015 (n = 18) as compared to Jan 1^st 2016 - Dec 31^st 2022 (n = 40), before and after the introduction of structured clinical guidelines for women with predisposing factors for PAS. Data were retrieved from original electronic obstetric records (Obstetrix^® Cerner AB, Stockholm, Sweden) by identification of the World Health Organization (WHO) International Classification of Diseases (ICD)-10 codes placenta accreta/percreta O43.2A/B and CS with PPHE O82.2. Classification was made according to the FIGO histologic criteria [4]. Cases with classification according clinical criteria alone and cases that dis not necessitate PPHE were excluded. Some of this material was reported in Arnadottir B, et al. in Clin Surgery 2020.

Ethical approval was obtained from the Swedish Ethics Authority, January 19^th 2022, DNr 2021-05018. Since all data were retrieved in retrospect, were anonymized and presented on a group basis only, individual patient consent was not requested by the Ethics Authority.

Clinical Guidelines and Antepartum Care in 2008 - 15

In 2008 - 15, pregnant women in the Stockholm Region with suspected advanced PAS according to routine ultrasonud at 18 - 20 weeks Gestational Age (GA) or emergency ultrasound after vaginal bleeding were planned for CS with arrangements for PPHE at 35 - 38 weeks. Peroperative antibiotic prophylaxis was given at emergency surgery. The operation was performed by an obstetrician and a gynecologic surgical oncologist, mostly in a regular operating theatre, and only occasionally in a hybrid operating theatre. All women received uterotonics with oxytocin injection (Syntocinon^®, CD Pharma, Sweden) and less than half of the women received addition of metylergometrine (Methergin^®, Novartis, Sweden), prostaglandin F (karboprost, Prostinfenem^®, Pfizer AB, Sweden) and fibrinolytic inhibition with tranexamic acid (Cyklokapron^® Pfizer, Sweden). The postoperative care was admission to an intensive care unit (ICU) or a high-dependency postoperative unit, analgesia with intravenous and oral opioids, nonsteroidal antiinflammatory drugs (NSAID) and paracetamol, antithrombotic prophylaxis with low molecular weight heparin (LMWH, dalteparin, Fragmin^®, Pfizer AB, Sweden) for 1 - 2 weeks and return visit to an obstetrician within 4 - 6 weeks.

Clinical Guidelines and Antepartum Care in 2016 - 22

In 2016 - 22, pregnant women in the Stockholm Region with risk factors for PAS - a placenta previa or a low-lying anterior placenta in combination with a prior CS at routine ultrasound - were planned for diagnostic ultrasound at 24 - 28 weeks´ GA, performed by a fetal-medicine ultrasound specialist. Assessment criteria for PAS were loss of clear zone, intraplacental lacunae, hypervascularity, irregular bladder wall, thinning of the myometrium [11,12]. If signs of PAS were found, Magnetic Resonance Imaging (MRI) and a follw-up ultrasound at 32-34 weeks GA were performed [13,14]. All women were informed about the PAS diagnosis and probability of PPHE. MCT management with an anesthetist, a fetal-medicine ultrasound specialist, an interventional radiologist, a gynecologic surgical oncologist, midwife, neonatologist, obstetrician and a theatre nurse was initiated. Standardized perioperative protocols were initiated and strategies in case of an emergency situation were documented. Planned CS with arrangements for a PPHE was scheduled in a hybrid operative theatre at 34 - 36 weeks´ GA. Timing of surgery was individualized in case of bleeding, uterine contractions or ruptured fetal membranes. All women were admitted to the hospital the day before surgery and antibiotic prophylaxis was given 1-2 hours preoperatively [15,16]. The WHO Surgical Safety Checklist was applied routinely [17]. Large peripheral venous catheters were inserted and monitoring with continuous pulse oximetry, electrocardiography, and invasive blood pressure measurement was initiated. An introducer was inserted in one femoral artery after sterile wash, to allow for embolization of the uterine arteries or balloon catheterization of the aorta. Epidural Analgesia (EDA) was used during the CS. If antepartum diagnosis was made, a midline abdominal wall incision was made, followed by intraoperative ultrasound mapping of the placental demarcation to avoid transplacental incision. The infant was delivered through a corporal uterotomy and the umbilical cord was ligated close to the placenta. All women received oxytocin injection and 4 out of 5 women received combined uterotonics with metylergometrine, prostaglandin F and fibrinolytic inhibition with tranexamic acid. General anesthesia was used during the PPHE leaving the ovaries in situ, performed in by a gynecologic surgical oncologist and an obstetrician. Blood loss was quantified according to standardized routines after separate measurement of amniotic fluid, and weighing of surgical cloths. Intraoperative cell salvage with retransfusion of leukocyte filtered autologous blood to decrease allogenous transfusion was introduced at our hospital in December 2015 and was used in 2016-22 [18,19]. The postoperative care was admission to a high-dependency postoperative unit for at least 6 h and an ICU if needed, analgesia with EDA for 3 days followed by intravenous and oral analgesia with opiods, NSAID and paracetamol, antithrombotic prophylaxis with LMWH for 6 weeks, mobilization with assistance of a physiotherapist, psychosocial support and return visit to an obstetrician within 4-6 weeks.

Clinical Outcomes

We quantified the prevalence of CS with PPHE for advanced PAS per 10 000 births in the region, the proportions of antepartum diagnosis and planned surgery, early maternal and neonatal outcomes, length of ICU care and hospital stay.

Maternal Outcome: Early maternal outcome was perioperative blood loss during surgery and the following 24 hours, and composite morbidity within 42 days, according to the WHO definition of the postpartum period. Composite morbidity was ICU care for >24 h, transfusion of  ≥4 U of erythrocytes, coagulopathy (platelet count ≤100 x 10⁹/mL, prothrombin complex/international normalized ratio ≥1.2, or fibrinogen ≤2 g/L), ureteral injury, reoperation, intraabdominal infection, hospital readmission or death within 42 days (9).

Neonatal Outcome: Early neonatal outcome was low Birth Weight (BW) <2500 g, signs of asphyxia with Apgar score <7 at 5 min, and umbilical artery Base Excess (BE) less than -10 mmol/L, Neonatal Intensive Care Unit (NICU) admission, intrauterine death or neonatal death within 28 days.

Statistical Methods

Based on clinical observations in 2008 - 15, we assumed that antepartum diagnosis and rate of planned surgery would increase from 50 to 90%. If so, a sample size of (n = 17) in each group would be required when aiming at a significance level of 5% and 80% power. A two-tailed p-value <0.05 was considered significant. Continuous data were analyzed with Mann Whitney U-test and General Linear Model when appropriate, and categorical data with Chi²-test or Fisher´s exact test when appropriate or with Kruskal Wallis´test. Continuous data were presented as mean ± Standard Deviation (SD) when normally distributed or median ± range if not, and categorical data as numbers and percentages.

Results

The total CS rate in Sweden increased from 17.1% in 2008 to 19.1% in 2022, and the Stockholm Region CS rate increased from 20.4% to 21.9% between these years (10). The prevalence of CS with PPHE due to advanced PAS in the Stockholm Region increased threefold from 0.7 to 2.0 per 10 000 deliveries between the study periods 2008 - 15 and 2016 - 22. (Figure 1). Antepartum diagnosis increased from 67 to 95 % (p=0.05), and planned surgery from 44 to 78% (p=0.02) (Table 1).

Figure 1: Regional prevalence of women with advanced Placenta accrete spectrum (PAS) in need of peripartum hysterectomy (PPHE) in 2008 – 15 as compared to 2016 – 22.

In 2022, 29 206 deliveries took place in the Stockholm Region, which was 28% of the 103 840 deliveries in Sweden.

Source: Swedish Board of Health and Welfare, Medical Birth Register (10).

Abbreviations: BMI: Body Mass Index; D&C: Dilation and Curettage; ICU: Intensive Care Unit; PPROM: Preterm Prelabor Rupture of Fetal Membranes (pPROM).

Table 1: Maternal data. Statistical methods: Mann Whitney U-test and General Linear Model when appropriate¹; Chi²-test and Fisher´s exact test when appropriate², Kruskal-Wallis test³_.