rEViEW artiClE Postpartum Haemorrhage in the Developing World A Review of Clinical Management Strategies ABSTRACT: The developing world is disproportionately burdened with high rates of maternal mortality. Despite widespread reduction in maternal deaths due to improved antepartum, intrapartum, and postpartum care in developed nations, mortality rates are persistently high in many countries unable to provide advanced medical care. Postpartum haemorrhage accounts for a substantial proportion of maternal deaths in developing countries. This review addresses the clinical management strategies aimed at the prevention and treatment of postpartum haemorrhage that are effective in low- resource settings. The review was conducted by searching the English-language medical literature using MEDlINE (1950 - Feb 2009) and the online search engine Google Scholar. Four relevant strategies were identified in the literature: active management of the third stage of labour (AMSTl), the use of uterotonic agents including misoprostol, accurate measurement of blood loss, and internal and external compression techniques. Despite known intervention options, additional research on effective management strategies and their implementation is needed to address postpartum haemorrhage in countries of the developing world. INTRODUCTION
nations disproportionately burdened by maternal
Healthy mothers are the focus of United Nations’ Fifth
Millennium Development Goal, with the aim of
Maternal mortality can be conceptualised as a direct
lowering maternal mortality ratios by 75% between
result of obstetrical complication leading to death, or
1990 and 2015 (1). Despite reduction in maternal
indirectly from a previously existing disease for which
deaths amongst transitional and developed countries,
pregnancy exacerbates the pathology or contributes to
maternal mortality remains a significant cause of death
increased severity of illness. Direct causes account for
for women of reproductive age in the developing world.
the great majority of maternal deaths in the developing
This fact is exemplified by statistics collected by the
world (3). A systematic review conducted by the WHO
WHO, which show that 99% of the world’s half-million
found that postpartum haemorrhage is the leading cause
annual maternal deaths occur in developing countries
of maternal mortality in Africa and Asia, accounting for
(2). Lifetime risk of maternal death is as high as one in
up to half of the total number of deaths in these regions
six for women living in the world’s poorest nations, a
(4). Overall, postpartum haemorrhage accounts for an
figure in sharp contrast to a risk of one in 30,000 for
estimated 25% of maternal mortality worldwide (2).
women in Northern Europe (3). Substantial progress is
Hypertensive disorders such as eclampsia were
required before the targets of Goal No. 5 are met, and
identified as the leading causes of death in Latin
increasingly this progress must be seen within the
America and the Caribbean; other prevalent causes ofmaternal mortality include sepsis, obstructed labour,and complications with abortion (2).
*To whom correspondence should be addressed:John W. Snelgrove
This review addresses the question of which clinical
management strategies are effective in treating
postpartum haemorrhage in the developing world.
Relevance of management options to the low-resource
settings characteristic of developing countries is
and accurate blood loss estimation, and compression
especially considered. While equally important health
infrastructure and policy interventions are necessary todecrease maternal mortality in developing countries
Active Management of the Third Stage of Labour
(2,3), these are not the focus of this review.
Active management of the third stage of labour
pharmacological treatment directed at reducing the risk
A search of the available English-language medical
of postpartum haemorrhage. This management strategy
literature was undertaken using MEDLINE (1950-Feb.
is in contrast to “expectant” management of the third
2009) and an online search engine, Google Scholar.
stage of labour, whereby therapeutic intervention to aid
Terms used in searches included combinations of
in the expulsion of the placenta is not performed.
“maternal mortality”, “postpartum haemorrhage/
Modalities of treatment in AMTSL include the
hemorrhage”, “labor/labour complications”, and
administration of a uterotonic agent, umbilical cord
“developing countries.” Abstracts from potentially
traction, fundal massage, and may or may not include
relevant publications were read for content and included
early cord clamping (10). A large randomised
in the review if they addressed the clinical management
controlled trial found evidence that AMSTL reduced the
of postpartum haemorrhage in a developing country or
odds of postpartum haemorrhage by half compared to
non-active delivery of the placenta (OR=0.50, 95%CI0.34-0.73) (11). These findings were reflected in a
ClINICAl MANAGEMENT OF POSTPARTUM
retrospective cohort study with historical controls
HAEMORRHAGE
conducted in a developing country, which found a
Postpartum haemorrhage is defined as blood loss of
significant reduction in incidence of postpartum
more than 500 mL within 24 hours of vaginal delivery.
haemorrhage after implementation of AMSTL
Blood loss may be associated with retained or adherent
management (10). The evidence is in favour of AMTSL
placenta, trauma to tissue and vessels during delivery,
as a relatively inexpensive and effective management
uterine atony, or coagulopathies such as fibrinolysis and
modality for controlling postpartum haemorrhage in
afibrinogenaemia (5). The known risk factors for
developing countries, providing the technique is
postpartum haemorrhage include prolonged third stage
performed appropriately. Evidence from a Cochrane
of labour, multiple delivery, fetal macrosomia,
Review (12) on active versus expectant management is
episiotomy, and previous history of postpartum
consistent with this recommendation: significantly
haemorrhage (6,7). Postpartum haemorrhage may have
reduced odds of postpartum haemorrhage were
a predilection toward certain ethnicities; however, this
observed with the use of AMSTL in the meta-analysis
is not a consistent finding. In a low-resource setting,
of Khan and colleagues (11), which focussed on the
advanced maternal age and low parity have been shown
developing world. Side effects of nausea, vomiting, and
to associate with a higher risk of haemorrhage (8).
raised blood pressure were more strongly associated
Importantly, postpartum haemorrhage may occur in
with AMSTL than expectant management, though these
obstetrical patients with an absence of known risk
were considered less adverse than the higher risk of
postpartum haemorrhage found with expectant
The clinical management of postpartum haemorrhage
has not been systematically assessed with respect to thereduction of maternal mortality in the context of
developing countries. Indeed, maternal mortality has
Uterotonic agents are administered during active
been used as a primary outcome in only a few
management of the third stage of labour to promote
randomised controlled trials, largely because of the
uterine contractions and the expulsion of placental
unethical nature of withholding care that is obviously
tissue (10,12,13,15,19). Regarding the appropriate
life-saving, but also as a result of the necessary sample
choice of uterotonic agent, oxytocin is favoured for the
size requirements to show an effect on mortality (9).
medical management of postpartum haemorrhage,
Fortunately, clinical management strategies to prevent
based on a large, multicentre randomised controlled
or reduce blood loss due to postpartum haemorrhage
trial conducted by the WHO (13). This study showed
have been more broadly considered in the literature (9-
that oxytocin is associated with significantly less risk of
27). This review identified four management strategies
haemorrhage (3% versus 4% incidence in the oxytocin
relevant to the topic of postpartum haemorrhage in
and misoprostol groups respectively, p<0.001) and
developing countries: the active management of the
fewer side effects than misoprostol (13). This result is
third stage of labour, the use of uterotonic agents, early
consistent with a Cochrane systematic review, which
assessed 37 trials from both developed and developing
similar collection system used in Tanzania provides a
nations and concluded that oxytocin is more effective
consistent measure of blood loss with the use of kanga,
than misoprostol against postpartum haemorrhage and
a type of blanket with standard dimensions that is used
associated sequelae (14). Smaller randomised
regionally in East Africa and holds approximately 250
controlled trials conducted specifically in developing
mL of blood when soaked (23). The effectiveness of
countries found significant evidence of reduced
blood loss estimation using these techniques has not
postpartum haemorrhage risk with misoprostol
been established empirically with respect to postpartum
compared to placebo (15,16), and some reported no
haemorrhage outcomes. However, standardised,
difference when compared to oxytocin (17,18). The
accurate measurement tools would theoretically allow
above studies concluded that misoprostol is effective as
birth attendants to more easily recognise postpartum
a uterotonic agent to prevent and treat postpartum
haemorrhage in a systematic way, resulting in
opportunities for intervention and appropriate
The choice of uterotonic agent for treatment of
management. Although these approaches have been
postpartum haemorrhage in developing countries must
described in only a handful of studies, they demonstrate
be considered in the context of both expense and
the importance of solutions that are regionally
thermostability. Costly or heat-labile preparations
acceptable and relevant—such as calibrated measures in
requiring refrigeration may be difficult or impossible to
Tanzania based on the amount of blood absorbed by a
use in low-resource settings (17,18). Misoprostol is a
relatively inexpensive, thermostable uterotonic agentwhich can be administered orally, rectally, or vaginally
External and Internal Compression
(16-19). This makes it a likely candidate for effective
Blood loss resulting from postpartum haemorrhage
medical prevention and management of postpartum
may be managed with the use of compression
haemorrhage in the developing world despite the
techniques suited or adapted to use in low-resource
therapeutic advantage provided by oxytocin, which is
settings. Abdominal compression of the aorta may
more expensive, heat-labile, and requires IV or IM
decrease blood loss in severe postpartum haemorrhage
administration (19). Given that oxytocin may provide
if performed correctly (24). This manoeuvre is easy to
an advantage over misoprostol and is associated with
perform and requires little equipment, thus it would
fewer side-effects, its use in areas with refrigeration
present fewer barriers to implementation in developing
capability and adequate financing is favoured over
countries than many other therapies. However, there is
misoprostol in settings where AMSTL is the norm
a dearth of evidence showing that abdominal
(13,14,19). However, in low-resource settings,
compression of the aorta significantly reduces negative
misoprostol should be considered as an alternative
outcomes associated with postpartum haemorrhage
primary treatment for postpartum haemorrhage.
specifically. Intrauterine tamponade with the use of acondom and rubber catheter has been suggested as an
Early and Accurate Estimation of Blood Loss
affordable alternative to blood loss management in
Not surprisingly, the severity of clinical outcomes for
severe postpartum haemorrhage refractory to uterotonic
postpartum haemorrhage correlates with the amount of
therapy. The evidence for this technique is based on
blood lost, and for this reason, the early and accurate
several series of case reports, the largest of which
estimation of blood loss is vitally important to the
involved 23 obstetric patients and was conducted in
clinical management of the postpartum bleeding patient
(20). Low-resource settings may not have access tostandardised blood collection tools, however, novel
DISCUSSION
approaches developed to estimate blood loss may
The proper management of postpartum haemorrhage
provide effective alternatives. For example, Patel and
is an essential component of obstetric care and a
colleagues describe the effectiveness of an inexpensive
necessary step in the goal to reduce worldwide maternal
blood collection drape used in India to estimate blood
mortality. The literature is replete with evidence for
loss against visual assessment alone. Estimates based
best practices and appropriate therapies, particularly
on the drape correlated well with photospectrometry
with respect to uterotonic agents and active
and were more accurate than visual assessment alone,
management of the third stage of labour. However, the
which tended to underestimate the amount of blood lost
interventions predominantly identified in the research
(21). This suggests the tool provides an appropriate
and clinical settings of developed countries may not be
measurement that can be easily and inexpensively made
feasible in the low-resource settings characteristic of the
in low-resource settings. Geller and colleagues indicate
developing world (9, 22, 26). Strategies that prevent
that this system is now used in eight countries (22). A
and treat postpartum haemorrhage must be readily
accessible, affordable, and have uncomplicated storage
mothers experiencing complications with pregnancy
requirements in order to be effective in countries with
and delivery. The authors describe three potential
limited healthcare financing and infrastructure. A ready
delays to treatment, the first being a delay in the
example of this phenomenon is the suggested use of
patient’s or family’s recognition of the need to seek care
misoprostol as a uterotonic agent in the absence of
(3). This can be further explained as discordance
resources that make the provision of the superior
between actual and perceived risk, the latter being
therapy (oxytocin) possible. An urgent need for the
partly constituted by attitudes and cultural beliefs such
uptake of technologies proven to work in developing
as, for example, the benefit or normalcy of bleeding
countries has been identified. Furthermore, continued
during delivery (29). Added to this “first delay” would
research into the effectiveness of postpartum
be a family’s inability to afford care in settings that lack
haemorrhage interventions in the context of low-
publically funded healthcare. Uncoordinated referral
resource settings is required to better understand the
systems and barriers at the community level—including
clinical management of this obstetrical complication.
physical, financial, or cultural—comprise the second
These needs extend beyond postpartum haemorrhage to
delay, while delay in receiving effective interventions is
include the other direct and indirect causes of maternal
cited as the third (3). As mentioned previously, this
mortality in the developing world. Contextually
review focuses on clinical management strategies, akin
appropriate strategies to manage hypertensive disorders
to the interventions necessary to avoid the “third delay”.
(e.g. eclampsia), sepsis, obstructed labour, and
Nonetheless, the extent to which appropriate
complications related to abortion have been identified
management may improve clinical outcomes is limited
but still require implementation to be effective against
by factors described by delays “one” and “two”.
Socioeconomic inequalities predispose women from
This review identified four clinical management
poorer backgrounds to increased risk of death during
strategies for postpartum haemorrhage, however a fifth
childbirth, as does the lower social status women hold
clinical consideration needs also to be addressed,
in many communities of the developing world (3, 29).
although it is not specific to reduced postpartum
Additionally, healthcare systems in developing
haemorrhage alone: the presence of skilled birth
countries may not be able to provide comprehensive
attendants during delivery. These healthcare workers
care to patients as a result of limited access to resources.
and midwives possess (at least theoretically) a
In an ecological analysis of Latin American and
minimum skill set necessary to take a detailed history,
Caribbean countries, Cruz found an inverse association
provide antenatal care, perform a vaginal exam, time
between donor blood availability and both maternal
and assess uterine contractions, and otherwise manage
mortality ratios and risk of death due to postpartum
normal labour and recognise the need to refer in the
haemorrhage (30). Social and cultural inequalities,
presence of complications (27). The availability of
along with issues concerning the accessibility and
skilled birth attendants during delivery may be an
comprehensiveness of healthcare, are the antecedents of
important step toward maternal mortality reduction, as
maternal mortality in developing nations. These
suggested by ecological data from the WHO (28).
upstream factors need to be considered alongside
clinical management and intervention in the pursuit of
recommendations regarding skilled attendance at birth.
Intrapartum care is largely dependent on setting,transportation, and the availability of referral networks
SUMMARy OF RECOMMENDATIONS
to manage complications (9). Additionally, the lack of
This review identified several evidence-based
a clear definition regarding the practice scope of skilled
recommendations for the prevention and management
birth attendants continues to confuse their role in
of postpartum haemorrhage in developing countries.
providing healthcare. Despite these areas of ambiguity,
Broadly, these recommendations relate to AMSTL,the
Graham and colleagues note the positive impact
use of uterotonic therapy, the use of compression
attendants may have on reducing maternal mortality, so
techniques, and the accurate measurement of blood loss.
long as specific skill sets are mastered and adequate
These recommendations and their level of evidence are
access to equipment and referral services is available
Recommendations Based on Level A Evidence
In considering only the clinical management of
1. AMTSL should be practised by clinicians to reduce risk
postpartum haemorrhage, this review necessarily takes
a narrow view of the causes of maternal mortality.
2. Oxytocin should be used as a uterotonic agent in settings
Ronsmans and colleagues describe the other levels at
where the appropriate storage and administration of this
which delays in access to care can prove fatal to
3. In the absence of available oxytocin, misoprostol is an
14. Gülmezoglu AM, Forna F, Villar J, Hofmeyr GJ. Prostaglandins
effective uterotonic agent and should be used to help
for preventing postpartum haemorrhage. Cochrane Database of
prevent postpartum haemorrhage (17-19).
15. Walraven G, Blum J, Dampha Y, Sowe M, Morison L, Winikoff
Recommendations Based on Level B Evidence
B, et al. Misoprostol in the management of the third stage of
1. Intrauterine tamponade with condom and catheter may be
labour in the home delivery setting in rural Gambia: Arandomised controlled trial. BJOG: Int J Obstet Gynaecol.
used to control severe postpartum haemorrhage refractory
Derman RJ, Kodkany BS, Goudar SS, Geller SE, Naik VA,
Recommendations Based on Level C Evidence
Bellad MB, et al. Oral misoprostol in preventing postpartumhaemorrhage in resource-poor communities: a randomised
1. Accurate estimation of blood loss should be standardised
controlled trial. Lancet. 2006;368:1248-1253.
using a blood collection drape (21-23).
17. Lokugamage AU, Sullivan KR, Niculescu I, Tigere P,
2. Abdominal compression of the aorta may decrease blood
Onyangunga F, El-Refaey H, et al. A randomized study
loss in severe postpartum haemorrhage (24).
comparing rectally administered misoprostol versusSyntometrine combined with an oxytocin infusion for thecessation of primary post partum hemorrhage. Acta Obstet
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John Snelgrove (MD 2011) is a medical student at the University of Western Ontario. He previously studied
at McMaster University in the Bachelor of Health Sciences program and holds a MSc in social epidemiology
from University College London in the U.K.
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SCHOOL OF BIOSCIENCES EXAMINATION MARK SCHEME Module Code: Module Name: Gene Manipulation Date: May/June 2004 With all questions some marks (approx. 20%) for each question are given for communication skills(planning, correct punctuation, good spelling, English usage and standard of scientific English, correctpresentation of Latin names); originality and creativity in the development