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Amniotic Fluid Embolism

  • Author: Lisa E Moore, MD, FACOG; Chief Editor: Carl V Smith, MD  more...
Updated: Sep 14, 2015


Amniotic fluid embolism (AFE) is a rare obstetric emergency in which it is postulated that amniotic fluid, fetal cells, hair, or other debris enter the maternal circulation, causing cardiorespiratory collapse.

In 1941, Steiner and Luschbaugh described AFE for the first time 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.[1]

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. In a patient who is critically ill, a sample obtained by aspiration of the distal port of a pulmonary artery catheter that contains fetal squamous cells is considered suggestive of but not diagnostic of AFE syndrome.[2] 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 poorly understood. Based on the original description, it was theorized that amniotic fluid and fetal cells enter the maternal circulation, possibly triggering an anaphylactic reaction to fetal antigens. However, 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.

Benson et al[3] 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[4] 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).

A case reported by Marcus et al,[5] in which AFE developed after a spontaneous rupture of membranes, demonstrated no increase in mast cells or degranulation in lung tissue as shown by Giemsa staining. Serum tryptase levels were 11.4 ng/mL (normal < 11.4 ng/mL).

The initiating event is poorly understood. However, usually during labor or other procedure, amniotic fluid and debris, or some as yet unidentified substance, enters the maternal circulation; this may trigger a massive anaphylactic reaction, activation of the complement cascade, or both. 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.[6]  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.[7, 8, 9]

The aforementioned study by Fong et al indicated 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.[10]



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.

The international incidence of AFE is similar to that of the United States.

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.[10]

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 one study has noted an increased incidence in women aged 30 years and older.[11] The aforementioned study by Fong et al indicated that the greatest risk increase occurs after age 39.[10]




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. [12]
  • 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 womene who survived AFE, 7% were neurologically impaired. [13]  
  • 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.


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.

Contributor Information and Disclosures

Lisa E Moore, MD, FACOG Professor, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine

Lisa E Moore, MD, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Medical Association, Society for Maternal-Fetal Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

John G Pierce, Jr, MD Associate Professor, Departments of Obstetrics/Gynecology and Internal Medicine, Medical College of Virginia at Virginia Commonwealth University

John G Pierce, Jr, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, Association of Professors of Gynecology and Obstetrics, Christian Medical and Dental Associations, Medical Society of Virginia, Society of Laparoendoscopic Surgeons

Disclosure: Nothing to disclose.

Chief Editor

Carl V Smith, MD The Distinguished Chris J and Marie A Olson Chair of Obstetrics and Gynecology, Professor, Department of Obstetrics and Gynecology, Senior Associate Dean for Clinical Affairs, University of Nebraska Medical Center

Carl V Smith, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Institute of Ultrasound in Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Society for Maternal-Fetal Medicine, Council of University Chairs of Obstetrics and Gynecology, Nebraska Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

John J Kavanagh, Jr, MD Chief, Professor, Department of Internal Medicine, Section of Gynecological and Medical Therapeutics, MD Anderson Cancer Center, University of Texas Medical School at Houston

John J Kavanagh, Jr, MD is a member of the following medical societies: American Association for the Advancement of Science, Society of Gynecologic Oncology, American Association for Cancer Research, American Association for the History of Medicine, American College of Physicians, American Federation for Medical Research, American Medical Association, Southern Medical Association, Texas Medical Association

Disclosure: Nothing to disclose.

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