1 Management and Outcomes of Placenta Accreta Spectrum (PAS) at Tertiary

2 Hospital in Bali: Descriptive Case Series Study

3
4 OOO

5
xxx
6
7
8 Abstract
9Background: There are 3 variants of abnormal placentation: placenta accreta, placenta increta,
10and placenta percreta. The lack of data and review studies on Placenta Accreta Spectrum (PAS)
11in Indonesia including Bali, make it difficult for clinicians to diagnose and predict morbidity that
12may occur.
13Objectives: To describe the management and outcomes of placenta accreta, increta, and
14percreta in tertiary Hospital, Bali - Indonesia
15Methods: Prospective case identification of 41 pregnancy cases with placenta adhesive from
162018-2020 at Tertiary Hospital, OOO Hospital- Bali Indonesia.
17Results: There was 1 case with primigravida who had an adhesive placenta (2.6%), 4 cases
18(10.5%) had PAS without a history of prior cesarean section, twenty cases (52.6%) had PAS
19without prior curettage procedure. Thirty-two cases (84.2%) had anterior placenta implantation
20and only 6 cases (15.8%) had posterior placenta implantation, median PAI (placenta accrete
21index) score in this study was 6 (1.25-10). All cases were managed by elective cesarean
22hysterectomy, with the median blood loss in all cases was 2,000 ml (400 - 13,300 ml). Bladder
23rupture as a complication during surgery found in 11 cases (28.9 %), Re-laparotomy was
24performed in 3 cases (7.9%), 12 cases (31.6%) required a postoperative blood transfusion, and
2528 cases (73.7%) required intensive postoperative care at ICU/ HCU.
26Conclusions: Antenatal history taking and ultrasound examination are needed to predict the
27evidence of Placenta Accreta Spectrum (PAS). Once PAS diagnosis is confirmed it should be
28managed by multidisciplinary approach to reduce either maternal and perinatal morbidity or
29mortality.
30
31Keywords: Placenta accreta spectrum, Management, Outcome
32Background

33 In some patients, the placenta grows morbidly adhered inside the wall of the uterus,

34and occasionally continues to grow outside of the uterus and invade into surrounding organs,

35this condition is called Placenta Accreta Spectrum (PAS). The placenta accreta spectrum

36depending on the depth of its invasion was divided into placenta accreta, increta, and percreta.1

37 Placenta accreta was first described in 1937 by Irving and Hertig as histopathological

38term as the ‘abnormal adherence of the afterbirth in whole or in parts to the underlying uterine

39wall in the partial or complete absence of decidua’ . The incidence of PAS has increased world

40widely from 1 in 2500 pregnancies to 1 in 500 pregnancies, due to rise in caesarean sections

41rate. This have increased maternal dan fetal morbidity and mortality. 1,2

42 The main risk factor for placenta accreta is a history of previous cesarean delivery,

43particularly when accompanied by a coexisting placenta previa. This finding is of particular

44concern in the context of increasing rates of cesarean delivery and older maternal age at giving

45birth.3 Many studies have observed factors that may be contributed to the increase risk in PAS,

46for example, shorter intervals between previous caesarean section and current pregnancy,

47multiparity, placenta praevia, assisted reproduction techniques, submucosal leiomyomas,

48smoking, and hypertension disease.2,3

49 Diagnosis of PAS can be achieved during pregnancy by ultrasound and/or magnetic

50resonance imaging. Several prenatal ultrasound features of PAS were the disappearance of the

51normal retroplacental interface (clear zone), extreme thinning of the myometrium, and vascular

52changes of the placenta (lacunae) and placental bed (hypervascularity). 1 Prenatal diagnosis

53have reduced maternal morbidity and mortality as it allows planning and timing surgery,
54arrangement for interventional radiology, availability of blood products and cell salvage, plan

55for most appropriate surgery technique.2

56

57Methods

58This study included all women identified as having placenta accreta, increta, or percreta who

59delivered from January 2018 until December 2020 at OOO Hospital. The PAS diagnosis in all

60cases has been confirmed postnatally by histopathology examination of their placenta.

61Microsoft Excel and SPSS software were used to collect and identify all cases who came to

62Obstetrics and Gynecology Emergency Department or Outpatient Clinic at OOO Hospital from

63January 2018 until December 2020. All samples will be followed until delivery and recorded in 1

64sheet for data tabulation.

65 Descriptive analysis was used to analyze the characteristics, management, and maternal

66outcomes of the cases which were suspected of having placenta accreta, increta, or percreta

67antenatally. All data were analyzed using SPSS 26.0.

68

69Results

70Distribution of research data showed that the median of age group was 33.5 (23-44), 11 cases

71were above 35 years old (28.9%) and 27 cases were under 35 years old (71.1%), most of the

72cases of PAS in this study was in the third pregnancy as many as 17 cases (44.7%) and only 1

73case was the first pregnancy, four cases (10, 5%) had placenta accreta without a history of

74previous cesarean section (CS), and 20 cases (52.6%) also had placenta accreta without a

75history of the previous curettage. From the histopathology examination results, 35 cases were
76appropriate with the diagnosis of PAS, three cases loss of follow-up, and there was only one

77case was misdiagnosed and normal pathology result was obtained (Table1).

78

79Table 1. Distribution Data of Placenta Accreta Spectrum Case Series

Variable f %
Age* Median of age 33.5 (23-44)
  >35 years old 11 28.9
  ≤ 35 year old 27 71.1
Total 38 100

Gravida* 1 1 2.6
  2 5 13.2
  3 17 44.7
  4 10 26.3
  5 2 5.3
  6 1 2.6
  7 2 5.3
  Total 38 100
   
History of CS * No 4 10.5
1 13 34.2
2 19 50
>2 2 5.3
Total 38 100

History of Curettage* No 20 52.6

1 15 39.5
  2 3 7.9
Total 38 100

Pathology ** Accreta 8 21.1

Increta 17 44.7
Percreta 9 23.7
Not Adhesive 1 2.6
Total 35 92.1
80*Percentage of the individual with complete data.

81**A total of 89.7% (35/38) of cases with 3 missing data

82

83Thirty-eight cases in this study have been done ultrasound diagnostic antenatally, 32 cases

84(84.2%) had anterior placental implantation and only 6 cases (15.8%) had posterior placental

85implantation, based on the presence of placental lacunae, 12 cases (31.6%) had grade 2

86placental lacunae and 18 cases (47.4%) had grade 3 placental lacunae. Besides, 12 cases (31.6%)

87implanted placenta lost their retroplacental clear space and 20 cases (52.6%) showed

88disruption of the bladder on ultrasound examination, and from myometrial thickness

89measurement, 16 cases (42.1%) had a myometrial thickness < 1mm, 18 cases (47.4%) had a

90myometrial thickness of 1-3 mm and 4 cases (10.5%) had a myometrial thickness above 3 mm,

91and almost 84.2% of cases (32 cases) showed a bridging vessel feature, and a median PAI score

92in this study samples were 6 (1.25-10) (Table 2).

93

94Table 2. Ultrasound features noted in women who had placenta accreta, increta, or percreta

95suspected before delivery

Number (%) of cases suspected prior

to delivery, diagnosed by

ultrasound* (n = 38)
Location of Placenta*

Anterior 32 (84.2)

Posterior 6(15.8)

Ultrasound features noted*

Placental lacunae

Grade 2 12(31.6)
 Grade 3 18(47.4)

Loss of retroplacental clear space 12(31.6)

Disruption of bladder 20(52.6)

Myometrial thickness

<1 mm 16(42.1)

1-3mm 18(47.4)

>3mm 4(10.5)

Bridging Vessel 32(84.2)

PAI (Placenta Accreta Index) Median Score* 6 (1.25-10)
96*Percentage of the individual with complete data.

97

98All of the cases in this study were managed by elective cesarean hysterectomy, with the median

99blood loss in all cases was 2,000 ml (400 -13,300 ml), with complications of bladder perforation

100during surgery in 11 cases (28.9 %) and relaparotomy was performed due to active bleeding in

101the abdomen or vagina after cesarean hysterectomy in 3 cases (7.9%), and only 12 cases

102(31.6%) required postoperative blood transfusion with a median of PRC given was 2.5 bags (250

103cc/bag), none of the cases in this study received TC or FFP transfusion. From 38 cases in the

104study, only 10 cases (26.3%) did not require intensive postoperative care and the remaining 28

105cases (73.7%) required intensive postoperative care at ICU/ HCU with a median length of stay in

106intensive care unit was 1 day (0-3).

107

108Table 3. Peripartum management and maternal outcomes for placenta accreta, increta, or

109percreta which has been suspected antenatally

Peripartum management/maternal outcome
Mode of Delivery*

CS 0(0)

Caesarean hysterectomy 38 (100)

Conservative surgery 0(0)

Median estimated total blood loss in ml (range)** 2.000 (400 -13.300)

Estimated total blood loss (ml)**

<1000 10 (26.3)

1000-2500 16 (42.1)

>2500 11 (28.9)
Bladder perforation*

Yes 11(28.9)

No 27(71.1)
Re-laparotomy*

Yes 3 (7.9)

No 35 (92.1)
Blood transfusion*

Yes 12 (31.6)

No 26 (68.4)
Blood products are given*

Median units of packed red cells transfused (range) 2.5(0-9)

Median units of platelets transfused (range) 0(0-10)

Median units of fresh frozen plasma transfused (range) 0(0-5)

Admission to ICU/HCU in days*

 No 10 (26.3)

1 14 (36.8)

2 4 (10.5)

3 10 (26.3)

The median duration of stay in ITU/HDU in days (range) 1 (0-3)

110*Percentage of the individual with complete data

111** Percentage of the individual with incomplete data 37 sample

112

113

114Discussion

115Outcomes of Placenta Accreta Spectrum are improved when delivered in centers that have

116multidisciplinary expertise and experience in the care of this pathology (maternal and fetal

117medicine; gynecologist; gynecology oncologist; vascular, trauma and urology surgery;

118transfusion medicine; intensive care, neonatologists, interventional radiologists and

119anesthesiologists).1,2 Most of these cases were referral cases from many district hospital around

120Bali, due to OOO Hospital as the only tertiary hospital in Bali.

121This study showed that the median age who had PAS was 33.5 (Range 23-44) years old. While a

122study by Zhong et al. have present 21 patients with median age 28 (range 23-33) years old. Fifty

123percent of our cases had 2 times the previous cesarean section, and four patients had placenta

124accreta without a history of previous cesarean section. This study also found that 47.4% (18/38)

125cases had a history of curettage. Meanwhile study by Zhong et al., from 21 patients with

126placenta accreta had previous cesarean sections (4/21), previous curettage (15/21), or uterine
127malformations (7/21).4 The 14 cohort studies included 3889 pregnancies presenting with

128placenta previa or low-lying placenta and 1 or more prior cesarean deliveries were screened for

129placenta accreta, there were 328 cases of placenta previa with accreta (8.4%), of which 298

130(90.9%) were diagnosed prenatally by ultrasound. One study found that 75% of placenta

131accreta cases were suspected on antenatal ultrasound; Many of those diagnosed had risk

132factors such as a previous cesarean delivery, uterine curettage, or a Müllerian anomaly, and

13390% were diagnosed as having a placenta previa. The incidence of placenta previa with accreta

134was 4.1% in women with 1 prior cesarean and 13.3% in women with ≥2 previous cesarean

135deliveries.1 Another study found that previous curettage was one of the risk factors for

136developing placenta accreta in 71,4% (15/21).4

137 In our study, we found that 84.2 % (32/38) cases had anterior placental location on

138ultrasound examination. Morgan et al also found a total of 86 pathology-confirmed placenta

139accreta spectrum, 59% of cases had anterior placental implantation. Anterior placenta accreta

140histologically and clinically appears to have the severe disease than the posterior placenta

141accreta. Placenta accreta spectrum with posterior placental location is associated with delayed

142diagnosis, surgical complications.5

143 Transvaginal ultrasound between 11 and 14 weeks of gestational age in women with

144prior cesarean delivery can identify at least 3 of 4 cases of placenta accreta spectrum.

145Assignment of the Placenta Accreta Index may help predict individual patient risk for the

146morbidly adherent placenta.6 From this study found that the median score of PAI from 34 cases

147of 35 cases was 6 (1.25-10), only 1 case misdiagnosed with placenta adhesive. A study from

148Sefty M. et. al among 21 placenta previa patients with a history of prior cesarean section,
14910(47.6%) of them histopathologically proven as abnormally invasive placenta. Placenta accreta

150index score four can be used as a cut-off value for prediction of placental invasion in patients

151with placenta previa.7 With statistical analysis accuracy values obtained PAIS and

152histopathological findings in a patient with placenta previa is 0.762 (good). 7

153 Several prenatal ultrasound features of the placenta accreta spectrum were reported

154over the last 35 years, principally the disappearance of the normal uteroplacental interface

155(clear zone), extreme thinning of the underlying myometrium, and vascular changes within the

156placenta (lacunae) and placental bed (hypervascularity). 1 From this study we found the sign of

157bladder disruption from antenatal ultrasound was 84,2% (32/34). This sign may arise as a direct

158result of villous invasion into the muscle of the posterior wall of the bladder. Myometrial

159thinning to <1 mm, or to where the myometrium becomes undetectable on ultrasound, has

160been used as a prenatal diagnostic sign for placenta adhesive. 1 Lacunae of ≥ Grade 1+ has

161sensitivity, specificity, positive predictive value, and negative predictive value of diagnosing

162adherent placenta were 86.9%, 78.6%, 76.9%, and 88.0% respectively. When lacunae of ≥ Grade

1632+ were considered, the sensitivity, specificity, positive predictive value, and negative predictive

164value of diagnosing placenta increta or percreta were 100%, 97.2%, 93.8%, and 100%,

165respectively and no hysterectomy was performed in any case in which lacunae were absent. 1

166This study found that 16 cases (42.1%) have a myometrial thickness < 1mm.

167 From this study, it was found that there was a bridging placental vessel in 32 cases

168(84.2%). A study conducted by Rac et. Al, 2015, found that from 184 gravidas, 54 (29%) had

169invasion confirmed on hysterectomy specimen. All sonographic parameters were associated

170with placental invasion (P <0.001). Assignment of the Placenta Accreta Index may help predict

171individual patient risk for the morbidly adherent placenta. 6

172 From this study, all patients (38 cases) were born by elective cesarean hysterectomy at

17337 weeks' gestation. Antenatal diagnosis is associated with decreased maternal hemorrhagic

174morbidity. Delivery at 34 0/7 –35 6/7 weeks of gestation is suggested as the preferred

175gestational age for scheduled cesarean delivery or hysterectomy. The most generally accepted

176approach to PAS is caesarean hysterectomy with placenta left in situ after delivery of the fetus.

177Caesarean hysterectomy is probably the preferable treatment and conservative management

178should only be used in highly selected cases and in places where such facilities are available. 8

179Delayed interval hysterectomy is an expectant approach for minimizing the degree of

180hemorrhage and tissue damage, where patient’s future fertility is not a consideration. 9

181 Caesarean hysterectomy is associated with maternal morbidity, including life-

182threatening hemorrhage, infection, bladder or bowel injury, and intensive care unit (ICU)

183admission.10 The median blood loss in accreta cases with cesarean hysterectomy in this case

184group was 2,000 ml (400 -13,300ml), this is largely determined by the experience of the

185operator who performed the surgery and preparations to anticipate complications that may

186occur. From another study, the estimated mean blood loss from placenta accreta with cesarean

187hysterectomy was 1416 ± 699 mL. The average blood loss is 3000-5000 mL, and up to 90% of

188the patients require a blood transfusion. 10 The median expected blood loss at the time of

189cesarean hysterectomy for patients with placenta accreta has been reported to be 3 liters and

190the mean transfusion requirement of 5 bags of packed red blood cells. 8 Patients with placenta

191percreta had significantly more blood loss (P= 0.02) and longer operative time (P= 0.007)
192compared with those with placenta accreta and increta. 10 As many as 90% of women with

193placenta accreta require a blood transfusion, and 40% require more than 10 bags of packed red

194blood cells.10 This study found that the median PRC given was 2.5 bags (0-9 bags) while the

195median TC requirement was 0 (0-10) and the FFP was 0 (0-5). Surgery complication found in

196this study were 11 cases (28.9%) had a perforation in the bladder, 3 cases (7.9%) had to

197undergo relaparotomy after cesarean hysterectomy due to intraabdominal and vaginal

198bleeding.

199 From this study, there were only 10 cases (26.3) who did not require intensive care after

200surgery (cesarean hysterectomy). with the median length of stay in the ICU was 1 day (range 0-

2013). One study from Mitrick et al stated that prenatal diagnosis of placenta accrete spectrum

202resulted in lower ICU admission rates (23 versus 43%) and four patients from all samples (8.5%)

203required ICU admission after surgery with length of stay was 5.2 days. 10

204

205Conclusions

206Antenatal history taking and ultrasound examination are needed to predict the evidence of

207Placenta Accreta Spectrum (PAS). Once PAS diagnosis is confirmed it should be managed by a

208multidisciplinary approach to reduce either maternal and perinatal morbidity or mortality.

209

210Conflict of Interests

211No potential conflict of interest relevant to this article was reported.

212

213Acknowledgments
214We would like to thank the director and the Head of the Obstetrics and Gynecologic

215department of OOO General Hospital and ### University Hospital for their support in this

216research study.
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