Amniotic Fluid Embolism

Amniotic fluid embolism (AFE) is a life-threatening obstetric emergency characterized by sudden cardiorespiratory collapse and disseminated intravascular coagulation.

AFE occurs in 2-8 per 100,000 deliveries and is responsible for between 7.5% and 10% of maternal mortality in the United States. ^[1]

Steiner and Luschbaugh first described AFE in 1941, after they found fetal debris in the pulmonary circulation of women who died during labor. Data from the National Amniotic Fluid Embolus Registry suggest that the process is more similar to anaphylaxis than to embolism, and the term anaphylactoid syndrome of pregnancy has been suggested because fetal tissue or amniotic fluid components are not universally found in women who present with signs and symptoms attributable to AFE. ^[2]

The diagnosis of AFE has traditionally been made at autopsy when fetal squamous cells are found in the maternal pulmonary circulation; however, fetal squamous cells are commonly found in the circulation of laboring patients who do not develop the syndrome. The diagnosis is essentially one of exclusion based on clinical presentation. Other causes of hemodynamic instability should not be neglected.

The pathophysiology of amniotic fluid embolism (AFE) is incompletely understood. It was originally believed that fetal cells and debris occluded the pulmonary vasculature. ^[3] Fetal material is not always found in the maternal circulation in patients with AFE, and material of fetal origin is often found in women who do not develop AFE.  A study performed to investigate whether fetal squamous cells from amniotic fluid could obstruct the maternal pulmonary vasculature causing cardiopulmonary collapse, found that the mean cell count in amniotic fluid was 695 +/- 600 squamous cells per mL of fluid.  The adult lung contains 480 million alveoli with 280 billion pulmonary capillaries. They concluded that even if the entire volume of amniotic fluid were transferred to the maternal circulation, the available squamous cells would only obstruct 1 in 1 million pulmonary capillary segments resulting in clinically undetectable obstruction. ^[4]

Clark has proposed that fetal antigens enter the maternal circulation triggering a response similar to systemic inflammatory response syndrome (SIRS) with activation of the coagulation cascade leading to DIC and inflammatory mediated suppression of myocardial function. ^[5]

Benson et al ^[6] tested 2 hypotheses concerning the pathophysiology of AFE: (1) Clinical symptoms result from mast cell degranulation with the release of histamine and tryptase, or (2) Clinical symptoms result from activation of the complement pathway. Nine women with AFE were compared with 22 women with normal labors. Serum from patients with AFE was collected within 14 hours of symptom onset and frozen. Urine was collected within 12-24 hours after symptom onset. Control patients had complement levels measured on admission, during labor, and the day after delivery.  Six of the 9 women with AFE died, and all 9 required blood transfusions for disseminated intravascular coagulation (DIC). Seven women had no evidence of mast cell degranulation (ie, either urinary histamine or serum tryptase). Compared with postpartum control patients, complement levels in the AFE group were severely depressed. C3 in the AFE group was 44 compared with 117.2 in the postpartum group. C4 was 10.7 in the AFE group versus 29.4 in the postpartum group. These differences were statistically significant. This suggests that complement activation may play an important role in the pathophysiology of AFE.

Farrar and Gherman ^[7] reported the case of a 40-year-old multipara in active labor with acute onset of facial erythema, seizures, hypoxia, cardiac arrest, DIC, and ultimately death. Fetal squames and fibrin thrombi were found in the pulmonary tree at autopsy. Blood drawn 2 hours after symptom onset had a serum tryptase level of 4.7 ng/mL (normal < 1 ng/mL). Mast cell degranulation is a central aspect of anaphylaxis which releases large quantities of tryptase. Kobayashi et al has proposed that serum tryptase levels may support the diagnosis of AFE. ^[8]

A case reported by Marcus et al, ^[9] in which AFE developed after a spontaneous rupture of membranes. No increase in mast cells or degranulation in lung tissue was shown by Giemsa staining. Serum tryptase levels were 11.4 ng/mL (normal < 11.4 ng/mL).

As these studies show, the initiating event and the complete pathophysiology are poorly understood.  Progression usually occurs in 2 phases. In phase I, pulmonary artery vasospasm with pulmonary hypertension and elevated right ventricular pressure cause hypoxia. Hypoxia causes myocardial capillary damage and pulmonary capillary damage, left heart failure, and acute respiratory distress syndrome. Women who survive these events may enter phase II. This is a hemorrhagic phase characterized by massive hemorrhage with uterine atony and DIC; however, fatal consumptive coagulopathy may be the initial presentation.

Amniotic fluid embolism (AFE) is considered an unpredictable and unpreventable event with an unknown cause. In the national registry, 41% of patients had a history of allergies.

Reported risk factors for development of AFE include multiparity, advanced maternal age, male fetus, and trauma. In a retrospective review of a 12-year period encompassing 180 cases of AFE, of which 24 were fatal, medical induction of labor increased the risk of AFE. ^[10]  In the same study, AFE was positively associated with multiparity, cesarean section or operative vaginal delivery, abruption, placenta previa, and cervical laceration or uterine rupture. ^{[11, 12, 13, 14]}

Fong et al found that non-Hispanic blacks have more than twice the risk of developing AFE and also found a 25-fold higher risk of the condition in women with cerebrovascular disorders and a 70-fold greater risk in those with cardiac disease. In addition, the study, of 182 patients with AFE, found a strong association between AFE and renal disease, placenta previa, polyhydramnios, placental abruption, and eclampsia and with procedures such as amnioinfusion, classical cesarean delivery, and dilation and curettage. The risk of AFE was also found to rise with maternal age, with the greatest increase occurring after age 39. ^[1]

United States and international statistics

Incidence of amniotic fluid embolism (AFE) is estimated at 1 case per 8,000-30,000 pregnancies. The true incidence is unknown because of inaccurate diagnoses and inconsistent reporting of nonfatal cases.

In 2011, AFE was the leading cause of death during childbirth in Germany. ^[15]

In Australia, AFE is cited as the leading direct cause of maternal death. Estimates range from 1 in 8000 to 1 in 80000 deliveries. ^[16]

In the United Kingdom incidence is estimated at 1.9 per 100000 to 7.7 per 100000 deliveries. ^[17]

Race-, sex-, and age-related demographics

No racial or ethnic predilection has been thought to exist. However, a study by Fong et al suggested that non-Hispanic blacks have more than twice the risk of developing AFE. ^[1]

AFE only occurs in women.

Advanced maternal age may be a risk factor. No relationship to age has been found in the National Amniotic Fluid Embolus Registry; however, at least two studies have noted an increased incidence in women aged 30 years and older. ^{[18, 19]} One study by Fong et al indicated that the greatest risk increase occurs after age 39. ^[1]  Another study by Lisonkova et al on the associations between maternal age and severe maternal morbidity reported that woman 35 years of age and older had increased adjusted rates of amniotic fluid embolism (AOR = 8.0, 95% CI 2.7-23.7). ^[19]

Mortality/Morbidity

Note the following:

• Maternal mortality approaches 80%. However, it was 61% in the US national registry, which listed 46 cases.

• Amniotic fluid embolism (AFE) is the cause of 5-10% of maternal mortality in the United States.

• Of patients with AFE, 50% die within the first hour of onset of symptoms. Of survivors of the initial cardiorespiratory phase, 50% develop a coagulopathy.

• A population-based study using the California Office of Statewide Planning and Development database reviewed 1,094,248 deliveries over a 2-year period. Of 53 cases of AFE, 14 patients (26.4%) died and 35 patients (66%) developed DIC. ^[20]

• Maternal survival is uncommon, although the prognosis is improved with early recognition and prompt resuscitation. The United Kingdom AFE registry reported a mortality of 37%; of the women who survived AFE, 7% were neurologically impaired. ^[21]  

• Neonatal survival has been reported to be 79% in the US registry and 78% in the UK registry. The intact infant survival rate is 70%. Neurologic status of the infant is directly related to the time elapsed between maternal arrest and delivery.

• The risk of recurrence is unknown. Successful subsequent pregnancies have been reported. The recommendation for elective cesarean delivery during future pregnancies in an attempt to avoid labor is controversial.

Complications

Pulmonary edema is a common occurrence in survivors. Pay close attention to fluid input and output.

Left heart failure may occur. Some sources recommend inotropic support.

Treat DIC with blood components. Consider activated factor VIIa for severe hemorrhage. Bilateral uterine artery embolization has been successful in controlling blood loss in 2 reported cases.

The recurrence risk of AFE is unknown. Case reports exist of successful uneventful pregnancies after a pregnancy complicated by AFE. ^[22]