REVIEW

URRENT
C
OPINION

Amniotic fluid embolism: despite progress,

challenges remain
Kathryn J. Balinger a, Melissa T. Chu Lam b, Heidi H. Hon a,
Stanislaw P. Stawicki a, and James N. Anasti b

Purpose of review
This article reviews the incidence, pathophysiology, risk factors, diagnosis, and management of amniotic
fluid embolism (AFE).
Recent findings
AFE is a leading cause of maternal morbidity and mortality despite an incidence of approximately 7 to 8
per 100 000 births. Recent reevaluation of AFE suggests that the presence of fetal tissue in maternal
circulation alone is not sufficient to cause the clinical syndrome, but rather an individuals response to this
fetal tissue. The anaphylactoid reaction associated with AFE shares many clinical and metabolic aspects
of septic shock. Acute dyspnea followed by cardiovascular collapse, coagulopathy, and neurological
symptoms, such as coma and seizures may all be associated with the clinical AFE syndrome. Specific
biochemical markers have been described, but are of limited clinical value because of the rapid
progression of the disease process. Treatment is based on an interdisciplinary approach that consists of a
combination of prompt, aggressive hemodynamic resuscitation, provision of end-organ support, correction
of hemostatic disorders, and delivery.
Summary
Although AFE cannot be prevented, early diagnosis and intervention may lead to better outcomes for both
the mother and the fetus. Clinical suspicion, traditional laboratory data, or intravascular cellular debris
(demonstrated only in 50% of patients) are insufficient to make a definitive diagnosis of AFE. An evolving
array of novel biomarkers may help differentiate AFE from other conditions, but none of them currently
provide sufficient early warning ability to make real-time impact on diagnosis and/or treatment of AFE.
Keywords
amniotic fluid embolism, diagnosis, management

INTRODUCTION
Amniotic fluid embolism (AFE) is an unpredictable
and rare occurrence that usually presents during
delivery or the immediate postpartum period. AFE
appears to involve an abnormal activation of
humoral and immunologic mechanisms leading
to a massive inflammatory reaction following the
entry into the maternal circulation of fetal antigens.
Although classically associated with delivery process, it has been described in the settings of abortion,
maternal trauma, amniocentesis, cervical lacerations, and manual removal of the placenta [17].
Despite its infrequent occurrence, AFE continues to
be one of the leading causes of maternal mortality in
the United States, and is estimated to be causative in
roughly 10% of maternal deaths in developed
countries [8].
Amniotic fluid embolism, as described by Meyer
in 1926 [8] was initially thought to be the result of
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physical obstruction of the maternal pulmonary

circulation by fetal material contained within the
amniotic fluid. In the 1940s, Steiner and Lushbaugh
[9] noted squamous cells or debris of presumed fetal
origin in the maternal pulmonary arterial circulation after reviewing the autopsies of 32 women who
died of obstetrical shock during labor. Up till the
mid-1980s, this definition of pulmonary embolism
by amniotic fluid remained largely unchallenged.
However, this mechanical etiology of AFE failed to
a

Department of Surgery and bDepartment of Obstetrics and Gynecology,

St. Lukes University Health Network, Bethlehem, Pennsylvania, USA
Correspondence to Stanislaw P. Stawicki, MD, FACS, Department of
Surgery, St. Lukes University Health Network, NW2-Administration,
Bethlehem, PA 18015, USA. Tel: +1 484 526 4426; fax: +484 526
3027; e-mail: stanislaw.stawicki@sluhn.org
Curr Opin Obstet Gynecol 2015, 27:398405
DOI:10.1097/GCO.0000000000000218
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Amniotic fluid embolism Balinger et al.

KEY POINTS
 AFE is a rare but potentially devastating syndrome that
manifests mainly during delivery or the immediate
postpartum period.
 Optimal clinical outcomes are achieved with prompt
identification and aggressive support measures that rely
on close collaboration involving multispecialty teams.
 Efforts to facilitate prompt diagnosis of AFE are
ongoing, with a number of potential biomarkers
under investigation.

stand up to closer experimental and clinical scrutiny

in the more recent period [10,11]. Although AFE
continues to be somewhat enigmatic, our ability to
understand it, diagnose it, and manage it effectively
is evolving. Optimization of clinical outcomes
involves clinical vigilance, early intervention, multidisciplinary collaboration, and team-based
approach. This review discusses the incidence, pathophysiology, risk factors, diagnosis, and management of this rare but potentially lethal condition.

INCIDENCE
The true incidence of AFE is difficult to determine
because of wide range of clinical presentations and
lack of standardized approaches to diagnosis [12]. In
an attempt to improve these estimates the prospective UK Obstetric Surveillance System was queried,
noting that the observed incidence of AFE was somewhere around 1.8 per 100 000 cases. However, their
results have been called into question by some.
A review by Conde-Agudelo and Romero [6]
found that large population-based studies
reported an incidence of combined fatal and
nonfatal AFE cases between 1 in 12 953 deliveries
in the United States and 1 in 56 500 in the
United Kingdom. Thus, an incidence of 1 in
40 000 deliveries seems to be a more reasonable
estimate. Other studies have shown an increased
incidence of AFE in women between the ages of 30
and 39 years, as well as those undergoing cesarean
delivery [13,14].

to be insufficient to cause AFE, and that the

individuals response to it may be the key pathophysiologic determinant [15]. This breach of the
maternal fetal physiologic barrier causes the activation of proinflammatory mediators and results in
a complex cascade of systemic reactions. As a result,
Clark et al. [16] proposed the term Anaphylactoid
Syndrome of Pregnancy an entity that has some
commonality with the systemic inflammatory
response syndrome. The most often suspected sites
of amniotic fluid entry are the endocervix and the
lower uterine segment, with endocervical veins,
uterine trauma sites, and the placental attachments
likely involved in the egress of fetal tissue [17].
A major mechanistic component of AFE was
thought to be the activation of mast cells and the
resultant physiologic response [8]. Recent studies
provide contradictory data on this point, with some
showing the lack of significant serum tryptase (a
serine protease released by mast cells) elevation in
AFE, whereas others suggesting that mast cell degranulation does take place in the lungs of patients
suffering from fatal AFE [8]. In 1982, Vercelloti et al.
[2], found that amniotic fluid could indeed activate
the complement. Tamura et al. [18,19] conducted a
study examining the role of complement activation
in AFE and showed that levels of C1 esterase inhibitor (C1INH) activity were decreased in patients with
AFE. C1INH not only decreases the activity of C1
esterase, but has also been shown to inhibit factor
XIIa, XIa, and kallikrein activities, which also appear
to participate in the pathogenesis of AFE. Furthermore, Chen et al. [20] described how amniotic fluid
was able to induce inflammation via neutrophil
activation and platelet neutrophil aggregation. It
remains unknown, however, what renders an individual susceptible to this anaphylactic shock [21].
Disseminated intravascular coagulation (DIC) is
considered one of the most common clinical manifestations in patients affected by AFE [22]. Factor XII
may be involved in its onset after activation by
contact surfaces [23,24], which in turn leads to
the initiation of the coagulation cascade, activation
of complement, as well as the kallikrein-kinin system. The kallikrein-kinin system generates bradykinin via proteolytic cleavage of high molecular
weight kininogen by the enzyme kallikrein. Bradykinin is known to have both vasodilatory effects and
the ability to increase vascular permeability [25 ].
Ultimately, vascular permeability is increased,
followed by vasoconstriction of pulmonary,
systemic and coronary vessels, bronchospasm, and
uterine hypertonus induced by inflammatory
mediators and catecholamines. Cardiac arrest and
pulmonary injury may develop, with some patients
experiencing severe DIC [13].
&

PATHOGENESIS AND
PATHOPHYSIOLOGY
AFE maybe a misnomer, since clinical observations,
animal studies and other experimental evidence
have put into question the embolic mechanism
[8]. Since the 1950s, it was noted that the presence of
fetal tissue in maternal circulation alone appears

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Table 1. Risk factors for amniotic fluid embolism
Fetal factors

Maternal factors

Obstetrical factors

Male gender

Advanced maternal age >35

Cesarean section

Placenta previa

Multiparity

Cervical laceration

Placenta accreta

Diabetes

Induction of labor

Placental abruption

Instrumental delivery: forceps and

vacuum-assisted vaginal deliveries

Fetal distress

Uterine rupture

Polyhydramnios

Eclampsia

Fetal macrosomia

Oxytocin use

Premature rupture of membranes

Intrauterine death

RISK FACTORS FOR AMNIOTIC FLUID

EMBOLISM
Numerous risk factors for AFE have been proposed.
Conditions such as cesarean section, placenta previa, abruption, and cervical lacerations have all been
cited [26]. Other factors may include advanced
maternal age [2], increased parity [27], male fetus,
induction of labor [28], instrumental delivery,
eclampsia [29], amnioinfusion [27], fetal distress,
and multiple pregnancies [6,30 ]. The overall rarity
of AFE makes defining clinically useful risk adjustments difficult. Table 1 provides an evidence-based
overview of risk factors for AFE.

distress. Ultimately, this late phase is marked by heart

failure, acute respiratory distress, and coagulopathy.
AFEs presentation is very similar to massive
placental abruption with a release of fetal tissue,
placental thromboplastin, or both, into maternal
circulation. What results is an anaphylactoid
response, in a way similar to septic shock. More

&

Phase 1: Initial insult

- Breach in maternal and fetal environments
a. Endocervical veins
b. Uterine trauma sites

CLINICAL MANIFESTATIONS OF
AMNIOTIC FLUID EMBOLISM
The AFE syndrome usually occurs during labor and
delivery, but can occur up to 48 h postpartum [6].
Three phases of this syndrome have been typically
described (Fig. 1). During the initial phase, transient
pulmonary and systemic hypertension is noted [7].
This phase usually occurs within the first 30 min and
results in hypoxemia because of ventilation perfusion mismatch associated with pulmonary hypertension. Concurrent myocardial injury may result,
which can be further exacerbated by mediators
associated with the amniotic fluid embolism itself
[31]. Mortality is particularly high during this acute
phase of AFE.
The second phase of the AFE syndrome is characterized by a profound depression of left ventricular
function with normalization of pulmonary arterial
pressures. Myocardial depression and hypoxia is
seen secondary to AFE-associated pulmonary injury
and/or cardiac arrest [32]. This may involve coronary
artery spasm and direct myocardial ischemia.
Pulmonary manifestations occur because of profound intrapulmonary shunting followed by lung
injury patterns consistent with acute respiratory
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c. Placental attachment site

Phase 2: Early phase

- Pulmonary vasoconstriction = hypoxemia
- Myocardial depression = myocardial injury

Phase 3: Late phase

- Heart failure
- Acute respiratory distress syndrome
- Coagulopathy

FIGURE 1. Proposed clinical phases of amniotic fluid

embolism.
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Amniotic fluid embolism Balinger et al.

Table 2. Clinical manifestations of amniotic fluid embolism
Organ system

Clinical manifestations

Respiratory

Respiratory arrest
Shortness of breath/dyspnea
Pulmonary edema
Acute respiratory distress syndrome
Cyanosis

Cardiac

Sudden cardiovascular collapse

Profound systemic hypotension
Cardiac dysrhythmias
Myocardial infarction

Hematologic

Disseminated intravascular coagulation

Hemorrhage

Neurological

Altered mental status

Seizures
Coma

specifically, there are three main subtypes of AFE

classical, anaphylactoid, and DIC. The classical subtype involves a respiratory arrest or distress; cardiac
arrest or ventricular dysfunction are seen mainly in
the anaphylactoid subtype; and massive bleeding is
associated with the DIC subtype [21]. Table 2 demonstrates common clinical manifestations of AFE, as
well as the associated organ systems that may
become affected.
Neurologic dysfunction is a potentially devastating long-term consequence for survivors of AFE.
This is thought to be a direct result of hypoxia
present during the initial insult. Up to 85% of
survivors may demonstrate some degree of permanent neurologic impairment [14].
As AFE can occurring during labor, maternal
systemic manifestations can have a direct effect
on fetal well-being. Alterations in fetal heart rate
may be seen with maternal hypoxia and present as
late decelerations or prolonged decelerations, which
in some cases can precede maternal signs and symptoms because of shunting of blood from the peripheral and splanchnic vascular beds towards the
central circulation [12].

If any of these clinical manifestations occur during

labor, cesarean section, dilation and evacuation, or
within 30 min postpartum, AFE must be considered
[13].
Early nonspecific prodromal symptoms such as
anxiety, agitation, extremity paresthesias, and light
headedness can be present [6]. Fetal bradycardia can
also occur early at the onset of AFE. Uterine atony
has also been described [8].
Basic laboratory assessments, such as arterial
blood gas, comprehensive blood count to assess
for leukocytosis, hemoglobin and platelets, comprehensive metabolic panel, and coagulation profile
should be obtained. Arterial blood gases will help
determine the adequacy of ventilation and the
degree of hypoxemia. Prolongation of prothrombin
time and a drop in fibrinogen and platelets may be
indicative of DIC. Cardiac enzymes may be elevated.
Other adjuncts to diagnosis which may be more
useful for monitoring and treatment optimization
include electrocardiogram, chest radiography,
transthoracic or transesophageal echocardiogram,
and thromboelastography [6,7]. Electrocardiogram
may show tachycardia with a right ventricular strain
pattern, ST and T wave abnormalities, and cardiac
arrhythmias with severe cardiovascular collapse.
Chest radiography abnormalities may include diffuse areas of opacity. Transesophageal echocardiogram may reveal pulmonary hypertension with
acute right ventricular failure and an obliterated left
ventricle [6].
In fatal cases, postmortem histopathologic and
histochemical analysis can lend further evidence,
and support the clinical diagnosis of AFE. Components of amniotic fluid can be determined with
hematoxylin-and-eosin, alcian-phloxine-martius
yellow (testing for mucin), cytokeratin AE1/AE3
(for squamous cells), ZnCp-1 (for meconium), and
C5aR stain (for complement activation) [3436]. It
has been noted, however, that only about 50% of
patients with AFE had detectable fetal debris present
in maternal circulation [6,37]. Other differential
diagnoses need to be considered as well, mainly
because of the rare occurrence of AFE and similarity
in manifestation (Table 3).

DIAGNOSTIC CONSIDERATIONS
Although the diagnosis of AFE is essentially one of
exclusion, clinical suspicion for this life threatening
syndrome must be high [33]. Most importantly,
vigilant clinical observation is critical to recognizing
the early signs/symptoms of AFE and making
the initial diagnosis. Usually one or more of the
following are present: acute severe hypotension,
acute hypoxemia or respiratory distress, severe
hemorrhage or coagulopathy, and/or cardiac arrest.

AMNIOTIC FLUID EMBOLISM:

BIOMARKERS
Although AFE is thought to have an inflammatory
based mechanism of disease, laboratory findings
often fail to provide definitive evidence for the
diagnosis of AFE. Some of the diagnostic tests
described include elevation of zinc coproporphyrin,
a component of meconium, and serum sialyl-Tn, a
fetal antigen present in both meconium and

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Womens health
Table 3. Differential diagnoses by organ system
Differential diagnoses

Table 4. Biomarkers currently utilized for the diagnosis of

amniotic fluid embolism
Current biomarkers

Respiratory

Zinc coproporphyrin

Pulmonary embolism

Characteristic component of
meconium and fetal urine

Air embolism

Elevated in AFE

Aspiration

Detected via high performance liquid

chromatography

Cardiac
Acute myocardial infarction

Sialosyl Tn antigen

Peripartum cardiomyopathy

Fetal antigen found in meconium and

amniotic fluid

Aortic dissection

Detected via TKH-2 monoclonal

antibody

Cardiac arrhythmia
Shock

Tryptase

Mast cell degranulation marker

Complement factors

Decreased C3 and C4 complement

Elevated in some AFE patients

Septic shock
Anaphylactic shock: drug induced

Possible complement activation

Obstetric
Cytokines

Postpartum hemorrhage

IL-6, IL-8, and tumor necrosis factor

Uterine rupture

Elevated in some AFE patients

Placental abruption

Nonspecific because can be present

in systemic inflammatory response
syndrome

Eclampsia
Insulin-like growth factor
binding protein 1

amniotic fluid. Decreased levels of C3, C3a, and C4

have also been found [3]. Insulin-like growth factor
is a protein synthesized by the decidua, which can
be measured in both the maternal serum and the
amniotic fluid. Ratios of approximately 150 exist
between amniotic fluid and maternal serum making
this marker potentially useful for diagnosis (Table 4)
[38 ,39].
Other novel and potentially viable biomarkers
have been described [38 ] and are outlined in
Table 5. A recent review evaluated the diagnostic
potential of using protein, lipid, and transcriptomic
profiles of extracellular vesicles [40]. These vesicles
are extruded into the maternal circulation early in
the course of AFE, at times even before clinical
manifestations are present, making them potentially useful in early diagnosis (and thus the ability
to institute early life-saving therapy). However, the
sensitivity and specificity of these tests remain poor,
limiting their wider use at this time.
&&

&&

CLINICAL MANGEMENT OF AMNIOTIC

FLUID EMBOLISM
The primary management of AFE involves prompt,
accurate diagnosis, followed by the provision of
optimized supportive care once the suspicion for
AFE is raised. After the airway is secured, adequate
intravenous access established, and hemodynamic
monitoring instituted, aggressive resuscitation with
fluids and vasopressors is started, as clinically indicated. Because DIC and hemorrhage may occur in a
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Embryonic development protein

synthesized in decidua
Detectable in amniotic fluid and
maternal serum

AFE, amniotic fluid embolism.

significant proportion of AFE cases, aggressive blood

and component replacements may become necessary. Recently, recombinant factor VIIa has been
tried in such scenarios, but was associated with
worse outcomes and thus is no longer recommended [41,42]. C1INH concentrates have been
shown to revert hereditary angioedema in C1INH
deficient patients; thus the administration of
C1INH may turn out to be a promising treatment
in some cases of AFE [1].
Prompt delivery improves the likelihood of good
outcome for the baby and should be undertaken
within  5 min of maternal cardiac arrest to decrease
fetal morbidity and improve maternal resuscitation
efforts by removing aorto-caval compression due to
the gravid uterus [43]. Phenylephrine and vasopressin may be appropriate during the early phase of
circulatory vasodilation. Milrinone can be useful for
right heart support as it has a positive effect on
inotropy, as well as a vasodilatory effect on the
pulmonary vasculature. Efficacy of antifibrinolytic
drugs, such as tranexamic acid or aminocaproic
acid is undetermined despite their use in the past.
Heparin and steroids have occasionally shown some
beneficial effects [1]. It has been postulated that
hemofiltration or plasma exchange may be effective
in selected cases [44].
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Amniotic fluid embolism Balinger et al.

Table 5. Investigational biomarkers for amniotic fluid embolism
New biomarkers
Activin A (transforming growth factor)

Characteristic of maternal serum, cord blood serum, and amniotic fluid

Increased with gestational age

Proopiomelanocortin

Characteristic of placental membrane

10 more concentrated in amniotic fluid than maternal serum
Inversely related to human chorionic gonadotropin
High concentrations at feto-maternal junction

Endothelin

Increased when amniotic fluid injected into circulation

Meconium stained amniotic fluid elicited greatest degree of endothelial injury

Procollagen type 1 N-terminal propeptide

Associated with fetal metabolism and development

>400 times more concentrated in amniotic fluid than maternal circulation

CK13 (Rab); CK10/13 (Mab)

Strongly expressed in squamous cells from maternal amniotic fluid

Brown cytoplasmic granules when immunostained

Refractory hypoxemia may be treated initially

with inhaled nitric oxide [45] or inhaled epoprostenol to produce pulmonary vasodilation. Sodium
bicarbonate, once used on cardiac arrest algorithms,
has also been proposed for pulmonary vasodilation
in patients unresponsive to advanced life support
measures, with right ventricular failure and acidosis
[46]. However, if this fails, extracorporeal membrane
oxygenation (ECMO) may be considered in a highly
selective fashion. Veno-venous ECMO intervention
is used for pulmonary support and veno-arterial
ECMO is used for cardiac support in addition to
pulmonary support. Other advanced therapeutic
strategies include intra-aortic balloon counterpulsation, cardiopulmonary bypass [47], intraoperative
cell salvage, uterine artery embolization, Bakri balloon (a silicone-based balloon device inserted into
the uterus and filled with fluid which then helps
tamponade endometrial bleeding), and the placement of nonpneumatic antishock garment [48].
Therapeutic hypothermia for 12 to 24 h anecdotally
showed promising results in the context of hypoxic
brain injury [48]. Once again, it is important to note
that because of the rare occurrence of AFE, clinical
data on each of the abovementioned treatments are
very limited. In a case report by Yao et al. [49], a
patient with late onset AFE and presenting with
hemoptysis 6 days after delivery, was treated with
lobectomy of the affected lung. A systematic algorithmic approach has been proposed in Figure 2.
To achieve optimal clinical outcomes, treatment
needs to ideally take place in the intensive care unit
and should involve a multidisciplinary team [50].
Survival has been said to be improved with the
provision of advanced maternal healthcare at tertiary hospitals. Although this complication is far
from preventable, better outcomes can be achieved

in the presence of an advanced, emergency obstetric

care system [51].

PROGNOSTIC CONSIDERATIONS
Although mortality from AFE has improved over the
past few decades, it continues to be unacceptably

High suspicion for AFE

Immediate action
- Protect airway
- 2x large bore IV
- Immediate lab work: including type and cross
- Consider vasopressors
- Contact operating room

EMERGENT C-section

Post operative care

- Intensive care unit
- Volume resuscitation
- Serial endpoints (lactate,ABG,VBG)
- Blood products as needed i.e. PRBC,FFP, platelets
- Consider vasopressors

FIGURE 2. Algorithm for management after diagnosis of

amniotic fluid embolism.

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Womens health

high, between 20 and 60% [12]. According to the US

registry data, as many as 56% of patients died from
AFE within the first 2 h [7]. Prognosis is more closely
linked to disease severity and occurrence of concomitant cardiac arrest than any specific treatment
modality. Most of the survivors display some degree
of neurologic impairment. The perinatal death rate
associated with AFE approximates 25% [52], with
only 50% of surviving neonates being neurologically intact [53]. The ability to identify AFE in its
earliest stages may help practitioners institute
aggressive therapeutic and supportive measures
more promptly. In order for this to be possible,
accurate diagnostic methods and specific biomarkers must be developed and implemented.

CONCLUSION
Although the incidence of AFE continues to be low
and the mortality has been decreasing over the past
few decades, this potentially devastating syndrome
remains a feared entity in both the obstetric and
critical care realms. Prompt identification and
aggressive supportive measures are the mainstay
of treatment and involve the interdisciplinary
efforts from multiple clinical specialty teams. There
is an acute need for better ways to diagnose AFE
early, with a number of promising biomarkers
currently in various stages of development and
investigation.
Acknowledgements
The authors would like to thank the Departments of
Surgery and Obstetrics/Gynecology at St. Lukes University Health Network.
Financial support and sponsorship
This work was supported by the Departments of Trauma/
Acute Care Surgery and Obstetrics and Gynecology,
St. Lukes University Health Network, Bethlehem,
Pennsylvania.
Conflicts of interest
There are no conflicts of interest.

REFERENCES AND RECOMMENDED

READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
&
of special interest
&& of outstanding interest
1. Kanayama N, Tamura N. Amniotic fluid embolism: pathophysiology and new
strategies for management. J Obstet Gynaecol Res 2014; 40:15071517.
2. Ito F, Akasaka J, Koike N, et al. Incidence diagnosis and pathophysiology of
amniotic fluid embolism. J Obstet Gynaecol 2014; 34:580584.
3. McDonnell NJ, Percival V, Paech MJ. Amniotic fluid embolism: a leading cause
of maternal death yet still a medical conundrum. Int J Obstet Anesth 2013;
22:329336.

404

www.co-obgyn.com

4. Fong A, Chau CT, Pan D, Ogunyemi DA. Amniotic fluid embolism: antepartum,
intrapartum and demographic factors. J Matern Fetal Neonatal Med 2015;
28:793798.
5. Kissko JM, Gaiser R. Amniotic fluid embolism. Anesthesiol Clin 2013;
31:609621.
6. Conde-Agudelo A, Romero R. Amniotic fluid embolism: an evidence-based
review. Am J Obstet Gynecol 2009; 201:445; e113.
7. Kramer MS, Rouleau J, Baskett TF, Joseph KS. Amniotic-fluid embolism and
medical induction of labour: a retrospective, population-based cohort study.
Lancet 2006; 368:14441448.
8. Benson MD. Current concepts of immunology and diagnosis in amniotic fluid
embolism. Clin Dev Immunol 2012; 2012:946576.
9. Steiner PE, Lushbaugh CC. Maternal pulmonary embolism by amniotic fluid as
a cause of obstetric shock and unexpected deaths in obstetrics. JAMA 1941;
117:12451254.
10. Stolte L, van Kessel H, Seelen J, et al. Failure to produce the syndrome of
amniotic fluid embolism by infusion of amniotic fluid and meconium into
monkeys. Am J Obstet Gynecol 1967; 98:694697.
11. Adamsons K, Mueller-Heubach E, Myers RE. The innocuousness of amniotic
fluid infusion in the pregnant rhesus monkey. Am J Obstet Gynecol 1971;
109:977984.
12. Clark SL. Amniotic fluid embolism. Obstet Gynecol 2014; 123 (2 Pt 1):337
348.
13. Thongrong C, Kasemsiri P, Hofmann JP, et al. Amniotic fluid embolism. Int J
Crit Illn Inj Sci 2013; 3:5157.
14. Moore J, Baldisseri MR. Amniotic fluid embolism. Crit Care Med 2005; 33
((10 Suppl)):S279S285.
15. Mallory GC, Blackburn N, Sparling HJ, Nickerson DA. Maternal pulmonary
embolism by amniotic fluid: report of three cases and discussion of the
literature. N Engl J Med 1950; 109:583587.
16. Clark SL, Hankins GD, Dudley DA, et al. Amniotic fluid embolism: analysis
of the national registry. Am J Obstet Gynecol 1995; 172 (4 Pt 1):1158
1167.
17. Tamura N, Nagai H, Maeda H, et al. Amniotic fluid embolism induces uterine
anaphylaxis and atony following cervical laceration. Gynecol Obstet Invest
2014; 78:6568.
18. Tamura N, Kimura S, Farhana M, et al. C1 esterase inhibitor activity in amniotic
fluid embolism. Crit Care Med 2014; 42:13921396.
19. Kocsis I, Gal J. C1 esterase inhibitor: a biomarker for amniotic fluid embolism?
Crit Care Med 2014; 42:15481549.
20. Chen KB, Chang SS, Tseng YL, et al. Amniotic fluid induces plateletneutrophil aggregation and neutrophil activation. Am J Obstet Gynecol
2013; 208:318327.
21. Tsunemi T, Oi H, Sado T, et al. An overview of AFE: past, present and future
directions. Open Womens Health J 2012; 6:49.
22. Levi M. Pathogenesis and management of peripartum coagulopathic calamities (disseminated intravascular coagulation and amniotic fluid embolism).
Thromb Res 2013; 131 (Suppl 1):S32S34.
23. Uszynski W, Zekanowska E, Uszynski M, et al. New observations on procoagulant properties of amniotic fluid: microparticles (MPs) and tissue factorbearing MPs (MPs-TF), comparison with maternal blood plasma. Thromb Res
2013; 132:757760.
24. Uszynski W, Zekanowska E, Uszynski M, Kieszkowski P. Activation contact
system (ACS) and tissue factor (TF) in human amniotic fluid: measurements of
ACS components and TF, and some implications on the pathophysiology of
amniotic fluid embolism. Thromb Res 2015; 135:699702.
25. Busardo FP, Frati P, Zaami S, Fineschi V. Amniotic fluid embolism patho&
physiology suggests the new diagnostic armamentarium: beta-tryptase and
complement fractions C3-C4 are the indispensable working tools. Int J Mol
Sci 2015; 16:65576570.
Good review for the understanding of the pathophysiological mechanism which
underlies AFE and the role of the immune system.
26. Thomson AJ, Greer IA. Non-haemorrhagic obstetric shock. Baillieres Best
Pract Res Clin Obstet Gynaecol 2000; 14:1941.
27. Main EK, McCain CL, Morton CH, et al. Pregnancy-related mortality in
California: causes, characteristics, and improvement opportunities. Obstet
Gynecol 2015; 125:938947.
28. Frati P, Foldes-Papp Z, Zaami S, Busardo FP. Amniotic fluid embolism: what
level of scientific evidence can be drawn? A systematic review. Curr Pharm
Biotechnol 2014; 14:11571162.
29. Kramer MS, Abenhaim H, Dahhou M, et al. Incidence, risk factors, and
consequences of amniotic fluid embolism. Paediatr Perinat Epidemiol
2013; 27:436441.
30. Fitzpatrick K, Tuffnell D, Kurinczuk J, Knight M. Incidence, risk factors,
&
management and outcomes of amniotic-fluid embolism: a population-based
cohort and nested case-control study. BJOG 2015. [Epub ahead of print]
A population-based cohort and nested case control study conducted using the
UKOSS. Risk factors for AFE were evaluated by comparing cases with a control
group of 3839 women.
31. Hosoya Y, Watanabe M, Terashima M, et al. Cardiac magnetic resonance
imaging in a patient with amniotic fluid embolism associated with severe
cardiopulmonary complications. Int Heart J 2013; 54:119122.
32. van Liempt SW, Stoecklein K, Tjiong MY, et al. Essentials in cardiac arrest
during cesarean section. Clin Pract 2015; 5:668.

Volume 27  Number 6  December 2015

Copyright 2015 Wolters Kluwer Health, Inc. All rights reserved.

Amniotic fluid embolism Balinger et al.

33. Clark SL. Amniotic fluid embolism. Clin Obstet Gynecol 2010; 53:322328.
34. Hikiji W, Tamura N, Shigeta A, et al. Fatal amniotic fluid embolism with typical
pathohistological, histochemical and clinical features. Forensic Sci Int 2013;
226:e16e19.
35. Yoneyama K, Sekiguchi A, Matsushima T, et al. Clinical characteristics of
amniotic fluid embolism: an experience of 29 years. J Obstet Gynaecol Res
2014; 40:18621870.
36. Wang J, Lai Q, Pan H, et al. Evaluation of specific marker CK13 and CK10/13
combined with APM staining for the diagnosis of amniotic fluid embolism and
aspiration. Forensic Sci Int 2014; 238:108112.
37. Lunetta P, Penttila A. Immunohistochemical identification of syncytiotrophoblastic cells and megakaryocytes in pulmonary vessels in a fatal case of
amniotic fluid embolism. Int J Legal Med 1996; 108:210214.
38. Stawicki SP, Papadimos TJ. Challenges in managing amniotic fluid embolism:
&&
an up-to-date perspective on diagnostic testing with focus on novel biomarkers and avenues for future research. Curr Pharm Biotechnol 2014;
14:11681178.
Comprehensive review of traditional and novel biomarkers as well as the future of
proteomics, lipidomics, and transcriptomics in the diagnosis of AFE.
39. Wernet A, Luton D, Muller F, Ducarme G. Use of insulin-like growth factor
binding protein-1 for retrospective diagnosis of amniotic fluid embolism in first
trimester. Arch Gynecol Obstet 2014; 289:461462.
40. Choi DM, Duffy BL. Amniotic fluid embolism. Anaesth Intensive Care 1995;
23:741743.
41. Leighton BL, Wall MH, Lockhart EM, et al. Use of recombinant factor VIIa in
patients with amniotic fluid embolism: a systematic review of case reports.
Anesthesiology 2011; 115:12011208.
42. Sadera G, Vasudevan B. Amniotic fluid embolism. J Obstet Anaest Crit Care
2015; 5:38.

43. Kaneko Y, Ogihara T, Tajima H, Mochimaru F. Continuous hemodiafiltration for

disseminated intravascular coagulation and shock due to amniotic fluid
embolism: report of a dramatic response. Intern Med 2001; 40:945947.
44. Trifonov I. Amniotic embolism: damocles sword or lifebelt? Akush Ginekol
(Sofiia) 2013; 52:4447.
45. Evans S, Brown B, Mathieson M, Tay S. Survival after an amniotic fluid
embolism following the use of sodium bicarbonate. BMJ Case Rep 2014;
2014.
46. Yuan SM. Indications for cardiopulmonary bypass during pregnancy and
impact on fetal outcomes. Geburtshilfe Frauenheilkd 2014; 74:5562.
47. Jelks A, Berletti M, Hamlett L, Hugin M. Nonpneumatic antishock garment
combined with bakri balloon as a nonoperative uterine sandwich for temporization of massive postpartum hemorrhage from disseminated intravascular
coagulation. Case Rep Obstet Gynecol 2015; 2015:124157.
48. Ocegueda-Pacheco C, Garcia JC, Varon J, Polderman KH. Therapeutic
hypothermia for cardiovascular collapse and severe respiratory distress after
amniotic fluid embolism. Ther Hypothermia Temp Manag 2014; 4:9698.
49. Yao J, Shao GG, Song W, et al. Surgical treatment of late-onset amniotic fluid
pulmonary embolism. J Obstet Gynaecol 2014; 34:209211.
50. Oi H, Naruse K, Koike N, et al. Predictor of mortality in patients with amniotic
fluid embolism. J Obstet Gynaecol Res 2014; 40:941945.
51. Mo X, Feng A, Liu X, Tobe RG. Amniotic fluid embolism (AFE) in China: are
maternal mortality and morbidity preventable? Intractable Rare Dis Res 2014;
3:9799.
52. Guillaume A, Sananes N, Akladios CY, et al. Amniotic fluid embolism: 10-year
retrospective study in a level III maternity hospital. Eur J Obstet Gynecol
Reprod Biol 2013; 169:189192.
53. Gist RS, Stafford IP, Leibowitz AB, Beilin Y. Amiotic fluid embolism. Anesth
Analg 2009; 108:15991602.

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