Research

Obstetrics

for whom it is important to obtain regular

folate supplementation. Because these
women may become pregnant during or
shortly after discontinuation of OC use,
such a Metafolin-fortified OC might potentially reduce the risk for an NTD
pregnancy.

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CLINICAL IMPLICATIONS

In the absence of clinical data, the current study provides insight related to the
potential benefit of ways to raise folate
levels in women of reproductive age,
even while food fortification is in place.

The use of Metafolin-fortified oral contraceptives might potentially reduce the

incidence of neural tube defects by increasing red blood cell folate levels in
women using oral contraceptives. f

Anesthetic management as a risk factor for postpartum

hemorrhage after cesarean deliveries
Chuen-Chau Chang, MD, MPH, PhD; I-Te Wang, MD; Yi-Hua Chen, PhD; Herng-Ching Lin, PhD
OBJECTIVE: This population-based study aimed to compare the

RESULTS: Women who received general anesthesia had a higher rate

risk of postpartum hemorrhage (PPH) for patients who underwent

cesarean section delivery (CS) with general vs spinal/epidural
anesthesia.
STUDY DESIGN: We identified 67,328 women who had live singleton
births by CS by linking the Taiwan National Health Insurance Research
Dataset and the national birth certificate registry. Multivariate logistic
regression was carried out to explore the relationship between anesthetic management type and PPH.

of PPH than women who received epidural anesthesia (5.1% vs 0.4%).

The odds of PPH in women who had CS with general anesthesia were
8.15 times higher (95% confidence interval, 6.4310.33) than for
those who had CS with epidural anesthesia, after adjustment was made
for the maternal and fetal characteristics.
CONCLUSION: The odds that women will experience cesarean PPH with
general anesthesia are approximately 8.15 times higher than for
women who undergo CS with epidural anesthesia.

Cite this article as: Chang C-C, Wang I-T, Chen Y-H, et al. Anesthetic management as a risk factor for postpartum hemorrhage after cesarean deliveries. Am J
Obstet Gynecol 2011;205:462.e1-7.

B ACKGROUND AND O BJECTIVE

Despite great advances in medical therapies and surgical techniques in recent decades, postpartum hemorrhage
(PPH) remains an important medical issue for both developing and developed
countries. Its impact deserves further
scrutiny.
Anesthetic management of cesarean
section delivery (CS), which includes
general anesthesia and spinal/epidural
anesthesia, rarely has been studied for
the risks that are associated with PPH

From the Department of Anesthesiology (Dr

Chang), the Department of Obstetrics and
Gynecology (Dr Wang), the School of Public
Health (Dr Chen), and the School of Health
Care Administration (Dr Lin), Taipei
Medical University, Taipei, Taiwan.
The authors report no conflict of interest.
0002-9378/free
2011 Mosby, Inc. All rights reserved.
doi: 10.1016/j.ajog.2011.06.068

462

and that are based on a limited number

of cases from single hospital datasets. In
this study, we set out to compare the risk
of PPH after CS for those women who
receive general vs spinal/epidural anesthesia, with the use of a 1-year nationwide dataset. We hypothesized that
women who received general anesthesia
would be at higher risk for PPH, compared with those women who received
epidural anesthesia, because adverse
uterine contractions and platelet function might be associated with general
anesthesia.

M ATERIALS AND M ETHODS

This study linked 2 nationwide population-based datasets. The first was the
Taiwan National Health Insurance Research Dataset, which is available to scientists in Taiwan for research purposes.
The second was the national birth certificate registry supervised by the Ministry
of the Interior, Taiwan. The mothers
unique personal identification numbers

American Journal of Obstetrics & Gynecology NOVEMBER 2011

provided links between the Taiwan National Health Insurance Research Dataset
and birth certificate data, with assistance
from the Bureau of Health Promotion,
Department of Health, Taiwan.
We identified 204,610 women who
were pregnant and used prenatal care
services from January 1, 2005, through
December 31, 2005. Of these, 69,533
women had live singleton births by CS
and were included in our study. Ultimately, 67,328 women were included:
2433 women received general anesthesia,
and 64,895 women received spinal/epidural anesthesia.
In this study, the independent variable
of interest was treated as a dichotomous
category according to whether a woman
had received general anesthesia during
delivery. The outcome variable was
whether a woman had hemorrhaged
within 24 hours of delivery (ICD-9-CM
codes 666.1, 666.10, 666.12, and 666.14).
To assess the independent effect of different modes of anesthetic management on

Obstetrics

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PPH, we adjusted for a number of potential confounders that had been identified
in previous studies in the regression modeling that included the mothers age and
fetal parity.

Research

TABLE

Adjusted odds ratios for postpartum hemorrhage

Postpartum hemorrhage
Variable

Odds ratio

95% CI

P value

Method of anesthesia

.....................................................................................................................................................................................................................................

R ESULTS
Mothers who received general anesthesia
had a higher rate of PPH than those who
received spinal/epidural anesthesia (5.1%
vs 0.4%; P .001). The Table shows that
the odds ratio of PPH was 8.15 (95%
confidence interval [CI], 6.4310.33;
P .001) for patients who received general anesthesia vs those who received
spinal/epidural anesthesia after adjustment for the mothers age and parity and
whether a mother had complications of
placental abruption, placenta previa without hemorrhage, overdistended uterus,
pregnancy-induced hypertension, prolonged labor, myoma, previous myomectomy, placenta accreta, and previous or
emergent CS.

General

8.15

Epidural or spinal

1.00

6.4310.33

.001

.....................................................................................................................................................................................................................................
..............................................................................................................................................................................................................................................

Maternal characteristics

.....................................................................................................................................................................................................................................

Age, y

............................................................................................................................................................................................................................

20

0.49

0.122.05

.330

20-24

0.83

0.531.29

.408

25-29

1.00

30-34

1.38

1.061.79

.016

34

1.92

1.452.54

.001

............................................................................................................................................................................................................................
............................................................................................................................................................................................................................
............................................................................................................................................................................................................................
............................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................

Placenta previa without hemorrhage

1.33

0.842.09

.223

Overdistended uterus

0.32

0.052.30

.258

Pregnancy-induced hypertension

0.99

0.641.55

.974

Prolonged labor

0.78

0.551.10

.161

Placenta abruption

0.44

0.161.23

.117

Myoma

1.48

0.782.82

.234

Previous myomectomy

0.99

0.382.58

.987

Placenta accreta

1.58

0.366.94

.546

.....................................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................

C OMMENT
Although people of Asian and Southeast
Asian ethnicity have been associated
with increased risk for PPH, we observed
a PPH prevalence of only 0.6%, which is
a low figure on a worldwide scale. Effects
of anesthetic management on PPH have
been explored to only a limited degree.
In a study that was based on 4837 women
who underwent CS that was stratified according to whether the CS was elective
and blood loss levels, general anesthesia
was associated with higher odds of PPH
than spinal/epidural anesthesia, with adjusted odd ratios that ranged from 2.79
(95% CI, 1.88 4.10) to 4.81 (95% CI,
2.34 9.35), respectively. The large sample size not only represents the general
population that underwent CS in Taiwan but also provides sufficient statistical power to detect differences between
patients who received different anesthetic interventions. We were able to
identify an even larger adjusted odds ratio of 8.15 (95% CI, 6.4310.33).
The plausible mechanisms by which
general anesthesia carries a higher risk of
PPH than spinal/epidural anesthesia

.....................................................................................................................................................................................................................................

Cesarean section delivery

............................................................................................................................................................................................................................

Emergent

9.51

7.5711.95

Previous

0.78

0.591.02

.001

............................................................................................................................................................................................................................

.067

..............................................................................................................................................................................................................................................

Fetal characteristics

.....................................................................................................................................................................................................................................

Parity, n

............................................................................................................................................................................................................................

1.00

1.19

0.901.58

.216

1.85

1.342.54

.001

............................................................................................................................................................................................................................
............................................................................................................................................................................................................................
.....................................................................................................................................................................................................................................

Gestational age, wk

............................................................................................................................................................................................................................

37

1.00

37

1.39

............................................................................................................................................................................................................................

0.991.97

.060

..............................................................................................................................................................................................................................................

CI, confidence interval.

Chang. Anesthetic management and postpartum hemorrhage. Am J Obstet Gynecol 2011.

might be classified into 2 categories.

First, many drugs that are used for general anesthesia exert a suppressive effect
on uterine contraction. Yet, the myometrial activity of local anesthetics that are
used in spinal/epidural anesthesia and
include prilocaine, Ultracaine, procaine, lidocaine, bupivacaine, and ropivacaine has been demonstrated to be
nonmonotonic.

The second category of mechanisms

that might explain the higher risk of PPH
that is associated with general anesthetics is the property of suppressing platelet
function and hemostasis. These speculative mechanisms of PPH deserve further
study before sound conclusions can be
drawn.
Spinal/epidural anesthesia has been
contraindicated relatively for women

NOVEMBER 2011 American Journal of Obstetrics & Gynecology

463

Research

Obstetrics

who are at risk for major hemorrhage because of concerns about hemodynamic
instability and the need to resuscitate an
awake patient. Our study, which demonstrates increased odds that general anesthesia is associated with PPH with an OR
of 8.15, suggests that the decision to use
general anesthesia should be reconsidered by clinicians who formulate anesthesia plans for hemorrhage-prone patients who undergo CS.
Although our population-based datasets allow us to identify all PPHs and provide significant statistical power to distinguish small differences in outcomes
between the 2 modes of anesthesia, this
study has limitations. The database did
not contain information regarding maternal characteristics (such as blood disorders and body mass index) that would
not be identified in the administrative
claims database unless the patient was
undergoing active medical management

464

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of such conditions. On the other hand,
PPH remains a clinical diagnosis without
a universal definition.
The use of retrospective data does not
guarantee randomized allocation between
groups. The choice of anesthesia techniques could be influenced by the presence
of or concern about bleeding. Finally, with
this study design, although a correlation
might be established, causality cannot be
confirmed until more prospective randomized studies are performed.
The odds that women will experience
cesarean PPH with general anesthesia
were approximately 8.15 times higher
than for women who received spinal/
epidural anesthesia. This finding supports previously proposed methods of
anesthetic management of obstetric
hemorrhage and provides evidence for
the evolving concept of the use of regional anesthesia for high-risk patients
who undergo CS.

American Journal of Obstetrics & Gynecology NOVEMBER 2011

CLINICAL IMPLICATIONS

Overall risk for postpartum hemorrhage after cesarean section delivery in

Taiwan is 0.6%; women were approximately 8.15 times more likely to experience cesarean postpartum hemorrhage
with general anesthesia than were
women who received spinal/epidural
anesthesia.
The decision to use general anesthesia
should be reconsidered by clinicians
who formulate anesthetic plans for
hemorrhage-prone patients who undergo cesarean section delivery.
Our finding supports previously proposed methods of anesthetic management of obstetric hemorrhage and
provides evidence for the evolving
concept of the use of regional anesthesia for high-risk patients who undergo
cesarean section delivery.
f