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146 J Nippon Med Sch 2008; 75 (3)
―Original―
Risk Factors for Peripartum Blood Transfusion in Women
with Placenta Previa: A Retrospective Analysis
Atsuko Oya, Akihito Nakai, Hidehiko Miyake,
Ikuno Kawabata and Toshiyuki Takeshita
Division of Reproductive Medicine, Perinatology and Gynecologic Oncology, Graduate School of Medicine, Nippon Medical School
Abstract
Background: The incidence of placenta previa has been increasing. It is of a great
importance to determine the clinical risk factors for peripartum blood transfusion in women
with placenta previa in an effort to anticipate cases of severe hemorrhage.
Methods: A total of 129 consecutive cases of placenta previa (64 cases of complete
placenta previa and 65 cases of marginal placenta previa), including 43 cases requiring blood
transfusion, were retrospectively analyzed. Maternal and neonatal clinical data were examined
with univariate and multivariate logistic regression analyses for potential risk factors for
peripartum blood transfusion.
Results: The independent risk factors for blood transfusion were maternal age greater
than 34 years (adjusted odds ratio [OR]=3.7; 95% confidence interval [CI]=1.5
―
7.5, p<0.05),
history of having undergone dilatation and curettage more than once (adjusted OR=4.8; 95%
CI=1.1
―
26.2, p<0.05), and complete placenta previa (adjusted OR=2.6, 95% CI=1.2
―
5.9, p<0.05).
Body mass index, gravidity, parity, previous cesarean section, antepartum hemorrhage, use of
tocolytic agents, gestational age at delivery, preoperative anemia, emergent surgery, birth
weight, and Apgar score were not associated with the incidence of blood transfusion.
Conclusion: Risk factors for blood transfusion in women with placenta previa are
advanced maternal age, repeat dilatation and curettage, and complete placenta previa. Women
with placenta previa who are at risk for blood transfusion should be carefully managed with
sufficient preparation for blood transfusion.
(J Nippon Med Sch 2008; 75: 146
―
151)
Key words: placenta previa, cesarean section, risk factors, blood loss
Introduction
Placenta previa has recently been estimated to be
present in 0.28% to 2.0% of all deliveries, and its
incidence has been increasing with the rate of
cesarean section1. Placenta previa is thought to be
related to endometrial atrophy, a defect caused by
previous scarring or inflammation in the
endometrium, resulting in abnormally low
implantation of the placenta at the internal uterine
os with an abundant blood supply.
Correspondence to Atsuko Oya, MD, PhD, Department of Obstetrics and Gynecology, Nippon Medical School Tama
Nagayama Hospital, 1
―
7
―
1 Nagayama, Tama, Tokyo 206
―
8512, Japan
E-mail: oya-a@nms.ac.jp
Journal Website (http:!!www.nms.ac.jp!jnms!)
Blood Transfusion in Placenta Previa
J Nippon Med Sch 2008; 75 (3) 147
The rates of blood transfusion and cesarean
hysterectomy are increased with placenta previa
because of the often massive peripartum
hemorrhage2. The volume of hemorrhage during
surgery in cases of placenta previa is significantly
higher than in cases of normal placental
presentation, and the rate of blood transfusion is also
significantly increased from 2.3% to 15%3.Placenta
previa accreta is one of the most important risk
factors for severe hemorrhage, which can be fatal. In
the present study, we evaluated the incidence of and
associated risk factors for peripartum blood
transfusion in women with placenta previa.
Materials and Methods
A retrospective analysis was performed through
the review of the medical charts of women with
placenta previa who had given birth at Nippon
Medical School Tama Nagayama Hospital from
August 1993 through June 2007. Placenta previa was
diagnosed with serial transvaginal ultrasonographic
scans and confirmed within 1 week of delivery.
Twin gestations were excluded. Both complete and
marginal placenta previas were included. Complete
placenta previa was defined as complete coverage
by the placenta of the internal os, and marginal
placenta previa was defined as the edge of the
placenta reaching the internal os but not covering
it4. Informed consent was obtained from each
patient, and Institutional Review Board approval
was granted.
The subjects were divided into two groups:
patients who had received blood transfusion within
24 hours of surgery were designated as the blood
transfusion group, and those who did receive blood
transfusion were designated as the non-blood
transfusion group. Blood transfusion was considered
if the estimated volume of hemorrhage reached 30%
to 40% of the blood volume (1,500
―
2,000 mL). The
decision for transfusion was made by the attending
obstetrician or anesthesiologist with consideration of
the patients health status, the duration of
hemorrhage, and the effects of hemorrhage on vital
signs. Maternal demographic data and neonatal
outcomes were reviewed. In both groups, the
following factors were examined: maternal age at
the time of delivery, body mass index (BMI),
gravidity, parity, previous cesarean section, history
of dilatation and curettage (D&C), preoperative
hemoglobin and hematocrit, type of placenta previa
(complete or marginal), antepartum hemorrhage, use
of tocolytic agents on the day of surgery, gestational
age at delivery, mode of cesarean section
(emergency or elective), total volume of blood loss,
birth weight, and Apgar score at 5 minutes.
Antepartum hemorrhage was defined as
hemorrhage that occurred from 22 weeks gestation
to cesarean section. Tocolytic agents included
prophylaxis with magnesium sulfate or ritodrine.
The total volume of blood loss was defined as the
total volume of hemorrhage during the 24 hours of
cesarean delivery.
To examine the characteristics of both groups,
such variables as maternal age at the time of
delivery, BMI, gravidity, parity, preoperative
laboratory data, gestational age at the time of
delivery, blood loss, birth weight, and Apgar score
were analyzed with Students t-test.
For univariate and multivariate analyses, each
variable was subdivided into 2 or 3 categories.
Maternal age at delivery was divided into 3
categories: age <25 years, 25 to 34 years (reference),
and >34 years. BMI was divided into 2 categories:
<25 (reference) and !25. Gravidity was divided into
3 categories: 0 (reference), 1, and, !2. Parity was
divided into 3 categories: 0 (reference), 1, and !2. A
history of previous cesarean section was divided into
2 categories: a history of previous cesarean section
(reference) and no history of previous cesarean
section. A history of D&C was divided into 3
categories: no D&C (reference), 1 D&C, and !2
D&Cs. Gestational age at delivery was divided into 3
categories: <34 weeks, 34 to 36 weeks (reference),
and >36 weeks. Antepartum hemorrhage was
divided into 2 categories: those without hemorrhage
(reference) and those with hemorrhage. Use of
tocolytic agents on the day of surgery was divided
into 2 categories: no treatment with tocolytic agents
(reference) and treatment with tocolytic agents. The
type of placenta previa was divided into 2
categories: complete placenta previa and marginal
A. Oya, et al
148 J Nippon Med Sch 2008; 75 (3)
Table 1 Characteristics of subjects
p value
Non-blood transfusion groupBlood transfusion groupTotal
Variables n=86n=43n=129
<0.0014.5+/-31.15.3+/-34.25.0+/-32.1Maternal age at delivery (y)
0.32.7+/-23.32.3+/-23.92.6+/-23.6BMI
0.0181.09+/-0.951.53+/-1.511.28+/-1.14Gravidity
0.2240.75+/-0.650.97+/-0.840.84+/-0.71Parity
Pre-operative laboratory data
0.9780.9+/-10.81.1+/-10.81.0+/-10.8Hemoglobin (mg/dL)
0.9553.6+/-32.55.2+/-32.44.2+/-32.4Hematocrit (%)
0.0972.3+/-36.13.8+/-35.32.9+/-35.9Gestational age at delivery (w)
<0.001504+/-1,0272,537+/-2,5201,676+/-1,525Blood loss (mL)
0.807508+/-2,420663+/-2,448565+/-2,430Birth weight (g)
0.7621.7+/-8.31.9+/-8.41.8+/-8.3Apgar score
Data are expressed as mean +/- standard deviation.
placenta previa (reference). The mode of cesarean
section was divided into 2 categories: emergency
and elective cesarean section (reference).
The magnitude of the univariate associations
between potential risk factors and blood transfusion
was quantified with the use of odds ratios (ORs).
Logistic regression analysis was used to calculate
ORs with 95% confidence intervals (CIs).
For multivariate analysis, the independent
variables initially included were as follows: maternal
age at the time of delivery, gravidity, parity,
previous cesarean section, history of D&C, type of
placenta previa, and mode of cesarean delivery. For
the final model, all independent variables were
selected with a stepwise procedure (JMP, version 4;
SAS Institute, Tokyo, Japan). A probability value of
<0.05 was considered to indicate statistical
significance.
Results
From August 1993 through June 2007, 130 women
with placenta previa gave birth at Nippon Medical
School Tama Nagayama Hospital. One case of twin
gestation was excluded. Consequently, 129 cases
were included in the study. All deliveries were by
cesarean section. The study subjects were divided
into 2 groups: a blood transfusion group (n=43) and a
non-blood transfusion group (n=86). The volume of
blood transfused in the blood transfusion group was
1,335 1,569 mL (mean SD). In the blood
transfusion group, 7 patients with placenta previa
accreta were included; these patients underwent
cesarean hysterectomy under general anesthesia.
The other 122 patients underwent routine cesarean
section under regional anesthesia.
The characteristics of the 2 groups are shown in
Table 1. The 2 groups differed significantly in terms
of maternal age at the time of delivery, gravidity,
and the total volume of blood loss but not in terms
of BMI, parity, preoperative hemoglobin or
hematocrit, gestational age at the time of delivery,
neonatal birth weight, or Apgar score at 5 minutes.
Table 2 shows the univariate association analysis
of each clinical factor with blood transfusion.
Maternal age greater than 34 years, a history of 2 or
more D&Cs, and complete placenta previa were risk
factors for peripartum blood transfusion in patients
with placenta previa.
A multivariate logistic regression model was
developed with maternal age, gravidity, parity,
previous cesarean sections, history of D&C, type of
placenta previa, and mode of cesarean delivery. The
independent variables of the final model selected by
the stepwise procedure were as follows: maternal
age (3 categories), history of D&C (3 categories), and
type of placenta previa (2 categories). Table 3 shows
the results of multivariate logistic regression
analysis. The risk factors for blood transfusion
confirmed by multivariate logistic regression
analysis were maternal age greater than 34 years
(adjusted OR=3.7, 95% CI=1.5
―
7.5, p<0.05), history of
Blood Transfusion in Placenta Previa
J Nippon Med Sch 2008; 75 (3) 149
Table 2 Univariate association with blood transfusion
p value95% CICrude OR
Non-blood
transfusion group
Blood transfusion
group
Total
Variables
n=86n=43n=129
Maternal age at delivery (y)
0.9525.0
―
0.21.1( 75%)6( 25%)2( 6.2%)8<25
Reference1(75.9%)60(24.1%)19(61.2%)7925
―
34
0.0027.8
―
1.63.4(47.6%)20(52.4%)22(32.6%)42>34
BMI
Reference1(67.3%)66(32.7%)32( 76%)98<25
0.7712.6
―
0.51.1(64.5%)20(35.5%)11( 24%)31>24
Gravidity
Reference1(71.4%)35(28.6%)14( 38%)490
0.8372.3
―
0.40.9(73.3%)33(26.7%)12(34.9%)451
0.0645.9
―
1.02.4(51.4%)18(48.6%)17(27.1%)35>1
Parity
Reference1(66.7%)42(33.3%)21(48.8%)630
0.3781.6
―
0.30.7(74.5%)35(25.5%)12(36.4%)471
0.1336.4
―
0.82.2(47.4%)9(52.6%)10(14.7%)19>1
Previous cesarean section
0.3494.8
―
0.61.7(56.3%)9(43.7%)7(12.4%)16Yes
Reference1(68.1%)77(31.9%)36(87.6%)113No
History of D&C
Reference1( 71%)66( 29%)27(72.1%)930
0.4293.5
―
0.61.4( 63%)17( 37%)10(20.9%)271
0.03324.5
―
1.24.8(33.3%)3(66.7%)6( 7%)9>1
Type of placenta previa
0.0364.8
―
1.12.2(57.8%)37(42.2%)27(49.6%)64Complete
Reference1(75.4%)49(24.6%)16(50.4%)65Marginal
Antepartum hemorrhage
0.6841.9
―
0.40.9(71.2%)47(28.8%)19(51.2%)66Yes
Reference1(61.9%)39(38.1%)24(48.8%)63No
Tocolytic agent
0.8012.3
―
0.51.1(65.4%)36(34.5%)19(42.6%)55Yes
Reference1(67.6%)50(32.4%)24(57.4%)74No
Gestational age at delivery (w)
0.7453.6
―
0.41.2(61.1%)11(38.9%)7( 14%)18<34
Reference1(65.4%)34(34.6%)18(40.3%)5234
―
36
0.6451.8
―
0.40.8(69.5%)41(30.5%)18(45.7%)59>36
Mode of cesarean section
0.2172.2
―
0.51.1( 66%)33( 34%)17(38.8%)50Emergency
Reference1(67.1%)53(32.9%)26(61.2%)79Elective
OR=odds ratio; CI=confidence interval
2 or more D&Cs (adjusted OR=4.8, 95% CI=1.1
―
26.2,
p<0.05), and complete placenta previa (adjusted OR=
2.6, 95% CI=1.2
―
5.9, p<0.05).
Discussion
The risk factors for excessive blood loss during
cesarean section have previously been reported as a
function of various maternal diseases5,6. The risk
factors previously reported for blood transfusion
associated with cesarean section for various
indications, including placenta previa, are a lack of
prenatal care, grand multiparity, previous cesarean
section, general anesthesia, severe preoperative
hematocrit less than 25%, and placenta previa5,6.
Furthermore, although blood transfusion was not
specified, risk factors for excessive blood loss during
cesarean section have been reported to include
A. Oya, et al
150 J Nippon Med Sch 2008; 75 (3)
Table 3 Risk factors for blood transfusion in patient with placenta
previa: Results of multivariate logis
tic regression analysis
(n=129)
p value95%CIAdjusted ORVariables
Maternal age at delivery (y)
0.0047.5
―
1.53.7>34
History of D&C
0.04826.2
―
1.14.8>1
Type of placenta previa
0.0235.9
―
1.22.6Complete
OR=odds ratio; CI=confidence interval
maternal age greater than 34 years, leiomyoma, low-
lying placenta, placenta previa, placental abruption,
elevated BMI, and low and high birth weights7,8.
With respect to hemorrhage and placenta previa,
several studies involving ultrasonographic
examination of the placenta have generated useful
information about the prediction of bleeding. The
central part of a placenta overlapping the internal
os, a sponge-like echo in the uterine wall adjacent to
the placenta9, and a thick placental edge10 are
reported risk factors for severe hemorrhage.
Tuvolic11 has suggested that compared with
incomplete placenta previa, complete placenta previa
is related to a higher requirement for antepartum
and postpartum blood transfusions and a higher
frequency of postpartum hemorrhage and
hysterectomy. In agreement with these previous
reports, our results show that complete placenta
previa is an independent risk factor for blood
transfusion in women with placenta previa. The
elevated risk of placenta previa accreta is an
important risk factor for severe hemorrhage in
women with a complete placenta previa. However,
even in placenta previa without accreta, abundant
vascularization to a broad area of the lower segment
of the uterine with weak myometrial contractions
after removal of the placenta may significantly
increase the risk of hemorrhage.
Our study also found that maternal age greater
than 34 years and a history of 2 or more D&Cs are
independent risk factors for blood transfusion during
cesarean section for placenta previa. Although these
factors have not been identified in previous studies
as risk factors for blood transfusion in women with
placenta previa, maternal age and D&C have
previously been reported to affect the implantation
of the placenta and are known risk factors for
placenta accreta12,13. Of the 7 women older than 34
years with placenta previa acrreta in the present
study, 2 had undergone 2 or more D&Cs. In
contrast, repeat cesarean section is also a well-
known risk factor for placenta accreta12, but in the
present study a history of cesarean section was not
significantly associated with blood transfusion.
Frederiksen et al.14 have reported that neither
elective surgery nor emergent surgery affects the
risk of hemorrhage during surgery in women with
placenta previa. In agreement with this previous
report, our results show that emergent cesarean
section is not an independent risk factor for blood
transfusion in women with placenta previa. In
addition, our study shows that antepartum
hemorrhage is not an independent risk factor.
Therefore, neither antepartum hemorrhage nor
emergent surgery necessarily predict gross
hemorrhage during cesarean section. Even if no
hemorrhage occurs during gestation, the volume of
hemorrhage during cesarean section should not be
underestimated. Frederiksen et al.14 have also
reported that general anesthesia increases blood loss
during cesarean section in women with placenta
previa. In the present study, because general
anesthesia was used only in cases of placenta previa
accreta and regional anesthesia was used in other
cases, the affect of anesthesia on blood transfusion
was not analyzed.
Several studies have suggested the beneficial use
of tocolytic agents, such as ritodrine15 and
Blood Transfusion in Placenta Previa
J Nippon Med Sch 2008; 75 (3) 151
magnesium sulfate16, for prolonging pregnancy in
women with symptomatic placenta previa. Towers17
have reported that third-trimester preterm tocolysis
for several indications, including placenta previa,
does not increase the risk of blood transfusion. In
agreement with this previous report, our results
suggest that the use of tocolytic agents just before
cesarean section does not affect the risk of blood
transfusion. Tocolytic agents can thus be used when
antepartum hemorrhage occurs owing to uterine
contractions in women with placenta previa without
the attendant risk of blood transfusion during
cesarean section.
In summary, independent risk factors for
peripartum blood transfusion in women with
placenta previa are advanced maternal age, repeat
D&C, and complete placenta previa. Women at risk
should be carefully managed with sufficient
preparation for blood transfusion.
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(Received,
(Accepted,
November
March
12, 2007)
17, 2008)