Amniotic fluid embolism (AFE) remains a difficult condition to define, describe and understand, but it continues to be responsible for a significant proportion of maternal deaths [1, 2]. Even the name of the condition is disputed, with some preferring anaphylactoid syndrome of pregnancy [3]. The term embolism almost implies an obstruction of the vessels as the mechanism of injury, when it is probably more complex than this, as will be discussed below. However, the condition is so widely known as AFE that it seems unlikely that the nomenclature will change.

The condition is rare – around one in 50 000 births in the UK [4]. It is only possible to obtain data from a large number of cases by interrogating large discharge databases, as has been done in the US [5] and Canada [6], or by having a specific system for collecting information on rare disorders, as has been used in the UK. The use of routine hospital databases for generating robust information on conditions such as AFE is fraught with difficulties. In order to research the condition, it is necessary to have a reasonable working definition as to what comprises a case. Importantly, it is almost a diagnosis of exclusion; if there is another condition that could explain the clinical presentation, it is more likely to be the cause. Therefore, in the course of investigation of a suspected case, several alternative diagnoses may be considered and the diagnosis of AFE subsequently discounted. However, the diagnosis may still be included in the codes attached to the woman’s admission in the hospital discharge database. Research on AFE using such discharge databases will therefore inevitably include large numbers of false-positive cases.

In the UK, AFE is researched through the UK Obstetric Surveillance System (UKOSS). The system is designed to study rare disorders using robust diagnostic criteria, to ensure specifically that false-positive cases are not included. The use of a strict case definition also ensures consistency and comparability of studies over time and between countries. For a number of specified rare disorders, reporters (including anaesthetists) in all maternity units in the UK report to a centralised system whether they have had a case each month, and then data are collated to allow study of the condition [7]. Importantly, reports are required each month, either negative or positive, and this ‘active negative surveillance’ system helps ensure high rates of case identification. The criteria for defining cases of AFE used by UKOSS are shown in Table 1. These criteria have broadened the definition from that first used in the US national registry [8]. In particular, there is no specified time in relation to birth included, as some cases do present later than the 30 min used in the US registry. However, it is more specific in excluding the women who present with bleeding and then collapse. Whilst, for the attending clinicians, ascribing an adverse outcome to AFE may be attractive, as the outcome may seem less avoidable, the bleeding of AFE is due to coagulopathy and is likely to develop at least alongside the cardiorespiratory signs and usually after them, rather than being the initial presentation.

Table 1.   UK Obstetric Surveillance System criteria for defining cases of amniotic fluid embolism.
EitherIn the absence of any other clear cause
Acute maternal collapse with one or more of the following features:
• Acute fetal compromise
• Cardiac arrhythmias or arrest
• Coagulopathy
• Convulsion
• Hypotension
• Maternal haemorrhage
• Premonitory symptoms, e.g. restlessness, numbness, agitation, tingling
• Shortness of breath
Excluding women with maternal haemorrhage as the first presenting feature in whom there was no evidence of early coagulopathy or cardiorespiratory compromise
OrWomen in whom the diagnosis was made at post-mortem examination by finding fetal squames or hair in the lungs

The epidemiology of the condition has advanced [4–6]. The incidence in the largest studies still varies and this may be due to differences in methodology. The incidence is reported to be much higher in North America (around 1:15 000) compared to the UK (1:50 000). Case fatality for women seems to have improved to around 20%. However, the infant fatality remains around 10%. Risk factors are now more clearly identified. Age over 35 years increases the risk, whilst being younger than 20 years old protects. Ethnic minority groups (Black women specifically) may be at increased risk.

The obstetric factors associated with AFE are more difficult to disentangle. The North American papers [5, 6] identify associations with other disorders such as eclampsia. However, the concern is that this may be due to over-reporting because the systems used in population cohort studies do not allow precision with regard to the diagnosis. This may be a factor in the higher incidence reported when this study methodology is used, compared with case registers or survey systems such as UKOSS that allow closer scrutiny of the clinical condition. There appears to be an association with induction of labour – nearly a doubling of risk [5, 6]. If there was no induction of labour, an estimated 35% of cases of AFE may be avoided [4], but the risk is still very small. Operative birth is associated with an increased risk but it remains unclear whether this is cause or effect. Collapse will lead to caesarean section and separating the confounding factors is difficult. In the UK study, 56% of women collapsed before birth and 44% after; 80% of those with collapse before birth had a caesarean section. However, there was an eightfold increase in the odds of a caesarean section in those who collapsed after the birth of the baby, implying some causal relationship with caesarean section [4].

Unfortunately, not a great deal has changed in our understanding of the pathophysiology in the last 10 years. Animal models have not been helpful [9, 10]. Whilst anaphylaxis has been considered, the evidence is contradictory [11]. The haemodynamic changes seem to be variable; there is only a mild to moderate elevation in pulmonary artery pressure but there is evidence of left ventricular dysfunction or failure [12–14]. Clark et al. [12] reconciled the pulmonary hypertension and left ventricular failure by suggesting a biphasic model. Acute onset of profound pulmonary hypertension leading to profound hypoxia may be responsible for neurological damage and early fatalities, but this was not a sustained feature. In survivors of this early phase, pulmonary hypertension resolved, being replaced by left ventricular failure. Whether the condition that arises is as a result of occlusive, direct toxic effects, or by triggering a cascade effect through a humoral mechanism, remains unclear [15].

The clinical presentation is classically of collapse with significant cardiorespiratory decompensation, followed by massive haemorrhage associated with profound coaguloapthy around the time of birth. However, the UK triennial report on maternal mortality [1] identified that 11 of 17 women who died had had premonitory symptoms and this was also found in 18 of 60 women in the UKOSS study [4]. These symptoms include restlessness, agitation, numbness and tingling. Whilst these may not be uncommon symptoms in the obstetric population, they should raise the index of suspicion if they arise. Unexplained acute fetal compromise was also a feature in around 20% of cases and can precede maternal deterioration. This has led to the suggestion that when there has been acute fetal compromise for no apparent reason, close monitoring of maternal condition for a period of time after the birth, perhaps with pulse oximetry, may allow earlier identification of the woman who may otherwise deteriorate unnoticed [16].

There is no specific antemortem diagnostic test. Even the presence of fetal squames in the maternal circulation can occur in other conditions [17]. The coagulopathy is often so profound that simply placing blood in a glass tube shows it will not clot, but formal testing is usually part of the battery of tests used to explore the differential diagnosis. Management of women with suspected AFE is supportive. Hypoxia may be profound, requiring early invasive ventilation. The general principles of cardiovascular support for haemorrhagic (or non-haemorrhagic) shock apply, often against a background of profound coagulopathy. Cardiopulmonary resuscitation should include reduction of aortocaval compression through manual displacement or tilt, placement of the hands higher on the chest and early intubation (because of the increased risk aspiration). No return of spontaneous circulation within 5 min is an indication to empty the uterus, if delivery has not already been achieved. This increases the efficacy of cardiac compressions and improves the chances for both the woman and the fetus. Correction of arrhythmias may be necessary. Fluids, vasopressors and inotropes may all be required to reverse profound systemic hypotension. Invasive monitoring will be required but if possible, some correction of the coagulopathy should be attempted first and ultrasound used to facilitate insertion. Care should be used in the interpretation of central venous pressures because of the possibility of pulmonary hypertension. There is evidence from the non-obstetric population that the use of pulmonary artery flotation catheters does not improve survival, and especially in the presence of profound coagulopathy, alternative methods for monitoring cardiac output should be considered. The majority of deaths now are in women who do not survive the acute phase: only three of the 12 women who died in the UK series reached the intensive care unit [4]. Those who do survive will almost certainly require level-3 care and so will need transfer to an intensive care unit.

Once the initial phase has passed, good supportive care is likely to lead to a good outcome. Recombinant factor VIIa was used in the management of coagulopathy in 14 cases in the UK series, with 13 survivors [4]. Plasma exchange was described 20 years ago as a treatment [18] and was used in seven cases – all of whom survived. This aims to remove fragments of red cells and/or substances that mediate the adverse effects of AFE. However, the good outcome with these treatments may well reflect the fact that the woman has survived the initial insult, and whilst these treatments may be of benefit, there is likely to be an overestimate of their success in cases of AFE. Hysterectomy is required in about 25% of women, either because of a persistently atonic uterus or because it is not possible to correct the coagulopathy in the face of continuing haemorrhage. Some women suffer cerebral injury even if they survive, and this leads to long-term morbidity.

Amniotic fluid embolism continues to be an important cause of maternal death from direct obstetric causes. It remains unpredictable and probably unpreventable; the latest figures suggest that there has been no significant change in the death rate from AFE in the UK [1]. Why one woman develops the symptoms and signs when amniotic fluid enters her circulation, whereas other women do not, remains difficult to establish. Improvements in outcome will probably come from improved resuscitation and supportive techniques. Continuing to gather information on women who survive and those who die, through systems such as UKOSS and other members of the International Network of Obstetric Survey Systems (INOSS) [19], may improve understanding further, as individual clinicians cannot ever gather enough personal experience to be informed as to the best way to manage this rare condition. The maternal death enquiry for 2006–2008 will be published in March 2011 and is awaited with interest as to further knowledge about this difficult condition.

Competing interests

  1. Top of page
  2. Competing interests
  3. References

All authors are members of the UKOSS Steering Group and DT is Central Obstetric Assessor of the Maternal Death Enquiry of the Centre for Maternal and Child Enquiries. We thank all clinicians who report cases to UKOSS and support our continuing understanding of rare disorders.


  1. Top of page
  2. Competing interests
  3. References
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