European Journal of Obstetrics & Gynecology and Reproductive Biology 187 (2015) 20–24

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European Journal of Obstetrics & Gynecology and

Reproductive Biology
journal homepage: www.elsevier.com/locate/ejogrb

A prior placenta accreta is an independent risk factor for post-partum

hemorrhage in subsequent gestations
Adi Vinograd a, Tamar Wainstock b, Moshe Mazor c, Salvatore Andrea Mastrolia d,
Ruthy Beer-Weisel c, Vered Klaitman c, Doron Dukler c, Batel Hamou c,
Neta Benshalom-Tirosh c, Ofir Vinograd a, Offer Erez c,*
a
School of Medicine, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel
b
Department of Epidemiology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel
c
Department of Obstetrics and Gynecology, Soroka University Medical Center, School of Medicine, Ben Gurion University of the Negev, Beer Sheva, Israel
d
Department of Obstetrics and Gynecology, Azienda Ospedaliera-Universitaria Policlinico di Bari, School of Medicine, University of Bari ‘‘Aldo Moro’’,
Bari, Italy

A R T I C L E I N F O A B S T R A C T

Article history: Objective: The rate of placenta accreta, a life threatening condition, is constantly increasing, mainly due
Received 25 November 2014 to the rise in the rates of cesarean sections. This study is aimed to determine the effect of a history of
Received in revised form 4 January 2015 placenta accreta on subsequent pregnancies.
Accepted 13 January 2015
Study design: A population based retrospective cohort study was designed, including all women who
delivered at our medical center during the study period. The study population was divided into two
Keywords: groups including pregnancies with: (1) a history of placenta accreta (n = 514); and (2) control group
Blood transfusion
without placenta accreta (n = 239,126).
GEE model
Maternal complication
Results: (1) A history of placenta accreta is an independent risk factor for postpartum hemorrhage
Neonatal mortality (adjusted OR 4.1, 95% CI 1.5–11.5) as were placenta accreta (adjusted OR 22.0, 95% CI 14.0–36.0) and
Placenta previa placenta previa (adjusted OR 7.6, 95% CI 4.4–13.2) in the current pregnancy, and a prior cesarean section
Previous cesarean section (adjusted OR 1.7, 95% CI 1.3–2.2); (2) in addition, placenta accreta in a previous pregnancy is associated
with a reduced rate of mild preeclampsia in future pregnancies (1.8% vs. 3.4%, RR 0.51, 95% CI 0.26–0.98);
(3) however, in spite of the higher rate of neonatal deaths in the study group, a history of placenta accreta
was not an independent risk factor for total perinatal mortality (adjusted OR 1.0, 95% CI 0.5–1.9) after
adjusting for confounders.
Conclusion: A history of placenta accreta is an independent risk factor for postpartum hemorrhage. This
should be taken into account in order to ensure a safety pregnancy and delivery of these patients.
ß 2015 Elsevier Ireland Ltd. All rights reserved.

Introduction (PPH) [4,5] and peripartum hysterectomies [6–11], multisystem

Placenta accreta complicates 0.3% of pregnancies in the United
States [1,2]. The incidence of placenta accreta has tripled since the
1980s, mainly due to the steep rise in the rate of cesarean sections
[2,3], especially in the presence of placenta previa. Placenta
accreta is associated with increased maternal morbidity and
mortality, being the most severe and life threatening complica-
tions represented by intraoperative or postpartum hemorrhage
* Corresponding author at: Acting Director, Maternal Fetal Medicine Unit,
Department of Obstetrics and Gynecology ‘‘B’’, Soroka University Medical Center,
School of Medicine, Faculty of Health Sciences, Ben Gurion University of the Negev,
P.O. Box 151, Beer Sheva 84101, Israel. Tel.: +972 8 6400061; Fax: +972 8 6403294.
E-mail address: erezof@bgu.ac.il (O. Erez).
organ failure and maternal death [4,5].
The principal goal in women with placenta accreta is to
minimize the morbidity and potential damage to the uterus
and reproductive tract, in order to preserve future fertility.
This is reached in 78.4% of women, with a severe maternal
morbidity rate of 6% (associated to severe intrauterine
synechiae, recurrent placenta accreta, placenta previa in
following pregnancies and postpartum hemorrhage), while in
the remaining cases hysterectomy is not avoidable [9,12]. How-
ever, this success does not come without a price, since there is
18–28% of recurrence rate of placenta accreta in subsequent
pregnancies [9,12,13].
Moreover, due to the low incidence of placenta accreta, there is
a lack of large scale population based studies that aim to define the

http://dx.doi.org/10.1016/j.ejogrb.2015.01.014
0301-2115/ß 2015 Elsevier Ireland Ltd. All rights reserved.
 A. Vinograd et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 187 (2015) 20–24
long term effects of placenta accreta on future pregnancies in the
absence of recurrent disease.
Thus, the aim of the present study is to determine the maternal
and perinatal outcomes in women with placenta accreta in
a previous pregnancy, who were successfully managed expectantly.
Materials and methods
This population based retrospective cohort study, included
239,640 deliveries of 90,247 women who delivered at Soroka
University Medical Center from 1988 until 2010, and was aimed to
determine the maternal and perinatal outcomes in women with
placenta accreta in a previous pregnancy, who were successfully
managed expectantly. Women having a fetus with chromosomal
abnormalities or congenital anomalies were excluded. Data were
collected from an electronic database that included demographic,
obstetric and general information about the mother and fetus of
all the deliveries at our medical center. Placenta accreta was
diagnosed according to clinical definition (abnormal adherence of
the placenta to the uterine wall) and pathologic examination of the
placenta (direct apposition of placental villi to the myometrium)
and was coded accordingly in the database (ICD-9 code 66702).
Two groups were created: (1) pregnancies following an event
of placenta accreta (n = 514); and (2) normal pregnancies
(n = 239,126) as a control group.
Patients were defined as multipara (2–5 deliveries) and grand-
multipara (6 or more deliveries), according to parity. Hypertension
was defined as blood pressure above 140/90 mmHg in two
separate measurement four to six hours apart. Severe hypertension
was defined as blood pressure above 160/110 mmHg. Preeclamp-
sia was determined as the presence of hypertension and
proteinuria of more than 300 mg at 24-h urine collection or at
least +1 in dipstick; its severity was defined according to the
severity of hypertension and/or one of the following +3 proteinuria
by dipstick, thrombocytopenia 100,000, elevated liver enzymes,
persistent headache and/or blurred vision [14]. Gestational
hypertension was defined as hypertension developed after
20 weeks of gestation without proteinuria. Placenta accreta was
diagnosed according to surgeons’ and physicians’ diagnosis as well
as pathological examination of the placentas; the ICD-9 that was
used to identify the patients in our database was 66,702.
Gestational diabetes was diagnosed according to 100 g oral
glucose tolerance test and was classified according to White’s
classification [15].
Small for gestational age (SGA) was defined as birth weight
<the 10th percentile, adequate for gestational age (AGA) as birth
weight from 10th to 90th percentile, and large for gestational age
(LGA) as birth weight >90th percentile according to regional
growth curves [16]. Prelabor rupture of membranes (PROM) was
defined as rupture of the chorioamniotic membranes before the
onset of labor. Preterm delivery was defined as delivery prior to
Table 1
Background characteristics of the deliveries in the study population by study groups.
Variables History of placenta accreta, n = 514
Ethnicity
Jews 231 (44.9)
Bedouins 283 (55.1)
Maternal age 30.29  5.46
Gravidity 4 (1–13)
Parity 5 (1–14)
LOPC 44 (8.6)
Smoking 5 (1.0)
ART 6 (1.2)
Data is presented as number (percentage), median (range) or mean  standard deviation. LOPC, lack of prenatal care; ART, assisted reproductive technology; n/a, not available.
21
37 weeks of gestation. Uterine rupture was diagnosed in case of a
complete tear of the uterine wall including the visceral peritoneum
with establishment of a direct communication between the uterine
and abdominal cavities. Dehiscence was defined as an opening
of the previous cesarean scar with intact visceral peritoneum and
no direct communication between the uterine and abdominal
cavities.
Postpartum fever was diagnosed as maternal temperature
>38 8C that developed at least 24 h after delivery recorded in two
different measurements at least four hours apart or one measure-
ment of maternal temperature of >38.5 8C regardless the time after
delivery. Postpartum hemorrhage was considered as amount of
bleeding that exceeds 500 mL following vaginal delivery or 1000 mL
following cesarean delivery. Endometritis was defined as postpar-
tum maternal fever with clinical signs of tenderness above the
uterine fundus or during cervical manipulation, foul vaginal
discharge and positive endometrial culture. Wound infection was
defined according to either clinical signs of infection or positive
wound culture. Wound dehiscence was the spontaneous opening of
cesarean section wound including the abdominal fascia.
T-test was used for continuous normally distributed variables
and Mann–Whitney for non-normally distributed variables. Chi-
square test was used to compare categorical variables. Multivariate
logistic models were created to estimate the risk for PPH, total
perinatal mortality, and postpartum death (either including or
excluding birth weight). Logistic regression was employed for the
dichotomous outcomes. Since some women appear a number of
times in the database (due to a multiple number of deliveries),
we used generalized estimation equation (GEE) models in which
every woman constitutes a cluster in the model.
Results
The rate of history of placenta accreta in our population was
0.2% (514/239,640 deliveries). The demographic characteristics
and obstetrical history of the study population are presented in
Table 1. Bedouins were more likely to deliver following an episode
of placenta accreta than Jews (RR 0.80, 95% CI 0.67–0.95, P = 0.01).
Women with a history of placenta accreta were older and had
higher gravidity and parity than the control group (P < 0.001, for
all comparisons).
The overall rate of hypertensive disorders during pregnancy
was lower among patients with a history of placenta accreta than
in those in the control group (6.9% vs. 10.2%). This difference was
especially prominent in patients with mild preeclampsia (RR 0.51,
95% CI 0.26–0.98). Women with a history of placenta accreta had a
higher rate of blood products transfusion during the subsequent
pregnancies and deliveries than those in the control group (3.3% vs.
1.5%, RR 2.27, 95% CI 1.39–3.68) (Table 2).
Women with a history of placenta accreta had significantly
higher rate of PPH (2.1% vs. 0.6%, RR 3.78, 95% CI 2.07–2.88,
No history of placenta accreta, n = 239,126 P-value RR (95% CI)
120,849 (50.1) 0.01 0.80 (0.67–0.95)
118,277 (49.5)
28.55  5.83 0.02 n/a
3 (0–17) <0.001 n/a
3 (1–17) <0.001 n/a
20,285 (8.7) 0.9 0.98 (0.72–1.34)
2634 (1.1) 0.8 0.88 (0.37–2.13)
6114 (2.5) 0.1 0.45 (0.2–1.01)
22 A. Vinograd et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 187 (2015) 20–24

Table 2
Obstetric characteristics during pregnancy and delivery in the study groups.

Variables History of placenta accreta, No history of placenta accreta, RR (95%CI)

n = 514 n = 239,126

Cesarean section 84 (16.3) 34,036 (14.2) 1.17 (0.93–1.49)

Diabetes 31 (6.0) 13,945 (5.8) 1.04 (0.72–1.49)
Hypertension 20 (3.9) 13,533 (5.7) 0.67 (0.43–1.06)
Mild preeclapsia 9 (1.8) 8112 (3.4) 0.51 (0.26–0.98)
Severe preeclapsia 6 (1.2) 2578 (1.1) 1.08 (0.48–2.43)
Placenta previa 4 (0.8) 964 (0.4) 1.94 (0.72–5.19)
Meconium 70 (13.6) 35,547 (14.9) 0.90 (0.70–1.16)
Blood product transfusion 17 (3.3) 3552 (1.5) 2.27 (1.39–3.68)
Hysterectomy 1 (0.2) 106 (0.04) 4.4 (0.6–31.5)
Placental abruption 3 (0.6) 1567 (0.7) 0.89 (0.29–2.77)

Data is presented as number (percentage).

Table 3
Clinical characteristics during post-partum period in the study groups.

Variables History of placenta accreta, No history of placenta accreta, P-value RR (95%CI)

n = 514 n = 239,126

Anemia 222 (43.2) 66,802 (27.9) <0.001 1.96 (1.65–2.34)

Wound infection 1 (0.2) 295 (0.1) 0.6 1.58 (0.22–11.26)
Postpartum hemorrhage 11 (2.1) 1377 (0.6) <0.001 3.78 (2.07–2.88)
Postpartum fever 0 972 (0.4) 0.1 n/a
Infection 0 19 (0.01) 0.8 n/a

Data is presented as number (percentage).

P < 0.001) as well as anemia (43.2% vs. 27.9%, RR 1.96, 95% CI 1.65–
2.34, P < 0.001) compared to the control group (Table 3).
A history of placenta accreta was significantly associated with
an increased rate of very low birth weight (VLBW) neonates (2.7%
vs. 1.1%, RR 2.5, 95% CI 1.47–4.26, P < 0.001), postpartum death
(1.4% vs. 0.3%, RR 4.24, 95% CI 2.005–8.97, P < 0.001), and total
perinatal mortality (2.2% vs. 1.1%, RR 2.26, 95% CI 1.24–4.11,
P = 0.006) (Table 4). In addition, the rate of overall and early
preterm birth was elevated in women with a history of placenta
accreta.
In order to determine the risk factors for PPH and especially the
role of a history of placenta accreta, we performed a GEE model
(Table 5). After adjusting for maternal and obstetrical character-
istics, we found that a history of placenta accreta is an independent
risk factor for PPH (adj. OR = 4.1, 95% CI 1.5–11.5). Additional
independent risk factors are placenta accreta (adj. OR = 22.0, 95% CI
14.0–36.0) and placenta previa (adj. OR = 7.6, 95% CI 4.4–13.2) in the
current pregnancy, history of cesarean sections (adj. OR = 1.7, 95% CI
1.3–2.2), as well as Jewish origin (adj. OR = 1.3, 95% CI 1.0–1.6). Of
interest, maternal age, parity and fertility treatments were not
independently associated with PPH.
In the study of the association between perinatal mortality and
a history of placenta accreta the model testing total perinatal
mortality as the independent factor revealed no independent
association between the two factors (Table 6). We then studied
the association between neonatal death and a history of placenta
accreta (Table 7), but only gestational age at delivery, the delivery
of an SGA neonate, maternal ethnicity, and placenta accreta at the
index pregnancy were independently associated with neonatal
death.
Comments
The principal findings of the study are: (1) a history for placenta
accreta is an independent risk factor for PPH in following
pregnancies, even without an evidence for placenta accreta in
the current pregnancy (OR = 4.1, P = 0.007); and (2) placenta
accreta in a previous pregnancy is associated with a reduced rate of

Table 4
Neonatal complications in the study groups.

Variables History of placenta accreta, No history of placenta accreta, P-value RR (95%CI)

n = 514 (0.2%) n = 239,126 (99.8%)

Gender
Male 279 (54.3) 121,926 (51.0) 0.1 1.14 (0.96–1.36)
Female 235 (45.7) 117,200 (49.0)

Malpresentation 41 (8.0) 14,508 (6.1) 0.1 1.34 (0.97–1.85)

VLBW 14 (2.7) 2650 (1.1) <0.001 2.5 (1.47–4.26)
IUGR 9 (1.8) 4624 (1.9) 1 0.90 (0.47–1.75)
SGA 17 (3.3) 12,334 (5.2) 0.1 0.63 (0.39–1.02)
Apgar 1 < 7 34 (6.6) 14,709 (6.2) 0.7 1.08 (0.76–1.53)
Apgar 5 < 7 17 (3.3) 6455 (2.7) 0.4 1.23 (0.76–2.00)
APD 4 (0.8) 1381 (0.6) 0.6 1.35 (0.50–3.62)
IPD 0 136 (0.1) 0.6 0.98 (0.98–0.98)
PPD 7 (1.4) 776 (0.3) <0.001 4.24 (2.005–8.97)
Total perinatal mortality 11 (2.2) 2293 (1.1) 0 2.26 (1.24–4.11)
Preterm delivery (37) 58 (11.3) 21,194 (8.9) 0.1 1.31 (0.99–1.72)
Early preterm birth (34) 17 (3.3) 5027 (2.1) 0.1 1.59 (0.98–2.58)
Gestational age (weeks) 38.82  2.913 38.37  3.643 0.3 n/a

Data is presented as number (percentage) or standard deviation. VLBW, very low birth weight; IUGR, intrauterine growth restriction; APD, antepartum death; IPD,
intrapartum death; PPD, postpartum death; n/a, not available.
 A. Vinograd et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 187 (2015) 20–24 23

Table 5 Table 7
Risk factors for postpartum hemorrhage; GEE multivariate logistic model. Risk factors for postpartum death; GEE multivariate logistic model.

Co-variates Adj. OR 95% CI Co-variates Adj. OR 95% CI

Placenta accreta 22.0 14.0–36.0 Placenta accreta 2.26 1.19–4.33

History of placenta accreta 4.1 1.5–11.5 History of placenta accreta 1.87 0.97–3.58
History of cesarean section 1.7 1.3–2.2 History of cesarean section 0.99 0.77–1.29
Placenta previa 7.6 4.4–13.2 Parity 1.03 0.98–1.08
Any fertility treatment 1.4 0.8–2.4 Maternal age (years) 1 0.98–1.02
Maternal age 0.99 0.97–1.02 Gestation age at delivery (weeks) 0.66 0.64–0.67
SGA < 10th 2.15 1.72–2.68
Ethnicity
Bedouins 1.3 1.0–1.6 Ethnicity
Jews Bedouins 0.69 0.56–0.86
Jews
Parity 1.01 0.95–1.07
Model c-statistics: 92.3%, P < 0.01.
Model c-statistics: 59.1, P < 0.001.

mild preeclampsia in future pregnancies (1.8% vs. 3.4%, RR 0.51,
95% CI 0.26–0.98).
Previously, there are numerous reports on the association
between placenta accreta and maternal hemorrhage in the ongoing
pregnancy [4,5]. This association is mainly due to either retained
placental tissue that prevents the uterus from contractions or as
a result of the trauma to the uterus during the removal of the
adherent placenta [17]. Moreover, the finding that a history of
placenta accreta is an independent risk factor for PPH is novel.
A similar result was recently published by Kabiri et al. [18],
based on pregnancies obtained from 268 women that were divided
in two groups (patients with a history of placenta accreta in
previous pregnancies and controls; RR 3.29, 95% CI 1.43–7.53,
P < 0.001). However, the authors performed a match cohort study
and did not adjust for confounding factors.
The fact that a history of placenta accreta is an independent risk
factor for PPH even in the absence of recurrent placenta accreta
deserves further discussion. This association implies that the
mechanisms leading to placenta accreta may also be involved in
the process underlying to PPH in subsequent pregnancies. In vitro
studies bring evidence of differences in the potential of trophoblast
invasion following decidual injury [19]. Of interest, there is a
difference in decidual leukocyte population between patients who
delivered spontaneously or had a cesarean section [19]. These
findings suggest that surgical manipulation may alter the decidual
ecosystem in women with a history of placenta accreta. Thus, these
changes may be also relevant to the physiologic hemostatic
mechanisms of the decidua predisposing the affected women for
PPH. This assumption awaits further study.
The finding of a lower rate of hypertensive disorders during
pregnancy in women with a history of placenta accreta is novel in
our cohort. Some of the major obstetrical syndromes, including
pre-eclampsia, pre-eclampsia with fetal growth restriction,
intrauterine growth restriction, pre-term premature rupture of
the fetal membranes [20] and pre-term birth [21] have been
associated with defective deep placentation. The pathogenesis of
Table 6
Risk factors for perinatal mortality; GEE multivariate logistic model.
Co-variates Adj. OR
Placenta accreta 2.9
History of placenta accreta 1.05
History of cesarean section 0.69
Parity 1.11
Maternal age (years) 1.004
Gestation age at delivery (weeks) 0.87
Birthweight (g) 0.998
Ethnicity
Bedouins 0.68
Jews
Model c-statistics: 57.5, P < 0.001.
defective deep placentation is frequently related to defective
trophoblast invasion [22]. Our findings may suggest that placentas
of patient with a history of placenta accreta may have better
implantation and trophoblast invasiveness. Evidence in support of
this view can be derived from the study by McMahon et al. [23]
who assessed the activity of the antiangiogenic molecule soluble
fms-like tyrosine kinase (sFLT-1) on trophoblast invasion. sFLT-1
irreversibly binds to circulating VEGF, a potent angiogenic growth
factor, preventing its interaction to the endothelial cell receptor
and the expression of its physiologic activity [24]. Indeed, in
humans, a syndrome associated with treatment with VEGF inhi-
bitors characterized by hypertension, proteinuria, and cerebral
edema, in some ways similar to preeclampsia, has been described
[25]. Human and animal studies [23,26–29] support the effect of an
overexpression of sFLT-1 in the pathogenesis of preeclampsia. In
contrast to the pathogenesis of preeclampsia the characteristic
invasiveness of trophoblast of patients with placenta accreta
include a lower expression of sFLT-1 at maternal–fetal interface
than that observed in normal placentation [23]. Overall the
epidemiologic data presented in the current manuscript, the
tendency of placenta accreta to reoccur, along with the existing in
vitro evidence [19], support the assumption that trophoblast of
women who had placenta accreta in the past, is more invasive and
thus associated with less hypertensive disorders of pregnancy.
Nevertheless, since when we adjusted for other risk factor a prior
placenta accreta did not have a protective effect against
preeclampsia suggest that this association should be treated with
caution and targeted studies may be needed to address this
question appropriately.
The univariate analysis demonstrated an association between
a history of placenta accreta and total perinatal mortality,
especially postpartum death. However, we tested this association
in the multivariate models and it was insignificant as long as birth
weight was included in the model, becoming significant if it was
excluded (Supplementary Table S1). This tendency may imply
that the major cause of the neonatal death might be related to
prematurity and very low birth weight that were more prevalent
in the study group. Overall it seems that in our cohort these
findings are more related to sequel of prematurity rather the
history of placenta accreta.
95% CI
The strength of the current study is the large dataset of
1.7–4.87 deliveries that enable us to study even rare complications in
0.59–1.9
sufficient power. Nevertheless, the pitfalls of our study include its
0.6–0.81
1.09–1.14 retrospective design and the fact that it is based on a dataset with
0.99–1.02 its inherent limitations (for example data regarding the extent of
0.85–0.88 placental invasiveness were not retrievable. As a consequence the
0.998–0.998 proportions of women with placenta accreta, increta or precreta
are not available for the present study).
0.60–0.77 In conclusion, the pathogenesis of PPH in patients with history
of placenta accreta or recurrence of this pathology is not
completely understood.
24 A. Vinograd et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 187 (2015) 20–24
Moreover, as we found, even the simple history of placenta
accreta without recurrent disease, is associated with an increased
risk of obstetric complications in future pregnancies. These
complications, as in the case of PPH, might be life threatening
without a proper and immediate treatment. For this reason
adequate counseling of the patient and increased awareness of the
obstetrician attending these deliveries are needed in order to
manage possible complications such as massive PPH. In addition,
efforts should be made to achieve a safe prevention of the primary
cesarean delivery as a way to reduce the incidence of placental
abnormalities, thus, preventing the morbidity associated with an
invasive placentation [30].
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.ejogrb.2015.01.
014.
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