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  • Synonyms
  • Signs & Symptoms
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  • Complete Report

Amniotic Fluid Embolism


Last updated: June 27, 2019
Years published: 2019


NORD gratefully acknowledges Irene A. Stafford, MD, Assistant Professor, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Baylor College of Medicine/ Texas Children’s Hospital, and the AFE Foundation, for assistance in the preparation of this report.

Disease Overview

Amniotic fluid embolism (AFE) is an extremely rare, but life-threatening complication that affects pregnant women shortly before, during, or immediately following labor and childbirth. Most instances occur during labor. In this disorder, it is hypothesized that a pregnant woman has a severe, allergic reaction to amniotic fluid or other fetal material such as fetal cells, which enter the mother’s bloodstream. Amniotic fluid is contained within the amniotic sac. This fluid supports, cushions, and protects a developing fetus. Amniotic fluid embolism is unpredictable and no risk factors have been identified. AFE can cause a severe, rapid decline in the mother’s health. For years, some researchers believed that the amniotic fluid and fetal cells cause obstruction within the mother’s blood vessels, but now most researchers believe that the mother’s immune system reacts to the amniotic fluid and fetal cells causing an overwhelming immune system response, which ends up harming the mother and the fetus. Breathing problems, cardiac arrest, and excessive bleeding are some of the life-threatening complications that can occur. Researchers and physicians do not fully understand why amniotic fluid or fetal cells entering the mother’s bloodstream causes this reaction in some women. Amniotic fluid embolism is a medical emergency that develops suddenly and rapidly and can be fatal. Early recognition and prompt supportive treatment are essential.

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  • anaphylactoid syndrome of pregnancy
  • AFE
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Signs & Symptoms

The signs and symptoms of amniotic fluid embolism often develop rapidly. Nonspecific symptoms including headaches, chest pain, cough, sweating, nausea, and vomiting have been reported as early signs. Other common initial symptoms include difficulty breathing or shortness of breath (dyspnea), abnormally rapid breathing (tachypnea), low blood pressure (hypotension), an abnormally rapid heartbeat (tachycardia), bluish discoloration of the skin and mucous membranes due to a lack of oxygen (cyanosis) in the blood, and a deficiency in the amount of oxygen reaching the tissues of the body (hypoxia). There may be rapidly high blood pressure in the blood vessels of the lungs (pulmonary hypertension) and sudden narrowing of blood vessels (vasospasm).

Breathing problems can progress to acute respiratory failure a severe, life-threatening complication where damage and fluid leakage into the lungs makes breathing difficult or impossible. Some affected women experience increasing cardiac rhythm abnormalities, low blood pressure, shock, and/or the abrupt loss of heat function despite no underlying heart disease (cardiac arrest). Cardiac arrest can cause gasping breath, no breathing, or complete unresponsiveness in the affected individual. Affected women may experience an altered mental status including anxiety or confusion, seizures, or coma.

Most women develop a condition called disseminated intravascular coagulation (DIC). In DIC, blood clotting factors, specialized proteins that help the blood to clot, are used up or broken down. Without these clotting factors, an affected woman cannot create blood clots to stop bleeding. There may be bleeding from the uterus and from puncture sites, such as the site of an intravenous needle or an epidural catheter. In rare instances, severe bleeding (hemorrhaging) may be the first sign of amniotic fluid embolism.

Doctors may note a condition called nonreassuring fetal status. This term means that the fetus is not doing as well as would normally be expected. The fetus may not be getting enough oxygen and there may be an abnormally slow heart rate. Nonreassuring fetal status is an assessment of fetal health given late in the pregnancy or during delivery. In the event that an AFE occurs during pregnancy, the infant must be expeditiously delivered as a life saving measure for both the mother and fetus.

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Amniotic fluid embolism is a condition that occurs because there is systemic reaction similar to that found in an allergic response to amniotic fluid or fetal cells or fetal tissue debris by the pregnant mother. The amniotic fluid and other material enters the mother’s bloodstream, most likely due to small tears in the lower part of the uterus, the part of the cervix that forms a canal connecting the vagina to the uterus (endocervix), or because of damage or abnormality affecting the placenta. The cervix is the narrow passage that forms the lower end of the uterus. The placenta is the organ that joins or connects the developing fetus to the mother. The placenta allows the transfer of oxygen and nutrients from the mother to the fetus.

How amniotic fluid or fetal cells cause an allergic reaction in some women and not others is not completely understood. Originally, researchers believed that amniotic fluid had an embolic effect, which means that the amniotic fluid formed clots (emboli) in the mother’s blood vessels, most likely the blood vessels of the lungs. That is where the disorder’s name, amniotic fluid embolism, came from. While amniotic fluid or fetal cells may contribute to some mechanical obstruction, amniotic fluid dissolves in fluid (soluble) and the fetal cells or tissue debris that can also enter the mother’s blood are usually too small an amount to cause a clot to form. Researchers now believe that this is an immune-mediated disorder, and that the symptoms are caused by the mother’s immune system, which reacts to the amniotic fluid or fetal cells as foreign substances. This immune response causes an overwhelming inflammatory response in the mother’s body that damages healthy tissue and structures, which ultimately is believed to cause the signs and symptoms. The process more closely resembles anaphylactic shock than it does an embolic event.

Although many potential risk factors have been discussed, no risk factors for amniotic fluid embolization have been conclusively proven to increase a woman’s risk of developing this disorder. Most studies have been inconsistent or contradictive in regard to risk factors. The onset of amniotic fluid embolism cannot be predicted or anticipated by doctors nor can the disorder be prevented

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Affected populations

Amniotic fluid embolism is a rare complication that occurs just before, during, or immediately after birth. The number of women who have experienced this complication is unknown. Amniotic fluid embolism is a rare disorder. Rare disorders often go unrecognized or misdiagnosed, making it difficult to determine their true frequency in the general population. Estimates have ranged from 1 in 8,000 to 1 in 80,000 pregnancies.

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A diagnosis of amniotic fluid embolism is based upon identification of characteristic clinical symptoms only. To date, there are no diagnostic assays, imaging studies or pathologic markers that have been validated for the diagnosis of AFE. Prompt diagnosis and early, aggressive advanced life support techniques are essential in assuring the best possible outcomes in amniotic fluid embolism. There is a lack of internal consensus in the medical community as to diagnostic criteria for this disorder, although there have been proposed diagnostic criteria for the research reporting of AFE (Clark SL, 2016). The diagnosis is made by identifying characteristic symptoms and excluding other possible causes of the signs and symptoms (diagnosis of exclusion).

Clinical Testing and Workup
A variety of different tests can be ordered to assist in the management of amniotic fluid embolism. These tests include a full blood count, which can reveal low levels of hemoglobin or high levels of certain heart enzymes. Blood coagulation tests can be run that will show low platelet and fibrinogen levels and increased prothrombin time and activated partial thromboplastin time (APTT). Platelets are specialized red blood cells that help the blood to clot. Fibrinogen is a specialized protein found in blood. It is a type of clotting factor that is essential in helping the blood to clot. Prothrombin time and APTT are tests that determine how long it takes the blood to clot. Prothrombin and APTT times are prolonged, which means the blood is taking longer to clot than normal. This happens because in amniotic fluid embolism the clotting factors are used up or broken down rapidly and a woman’s blood cannot clot.

Two different tests may be used to show low oxygen levels – continuous pulse oximetry and arterial blood gas (ARG). Continuous pulse oximetry is a simple test in which a small sensor is attached to a person’s fingertip or an earlobe to measure how much oxygen is in a person’s blood. A doctor may take a small blood sample to perform an ARG, which can assess both oxygen and carbon dioxide levels.

A chest x-ray may show fluid in the lungs, a prominent pulmonary artery, or enlargement of the heart (cardiomegaly). An electrocardiogram, an echo or echocardiography, is a test that uses high frequency sound waves to create pictures of the heart. This test can show right heart strain and abnormalities of the heart rhythm as well as dysfunction of the right or left upper chamber of the heart (ventricular dysfunction). A finding on echocardiography that is specifically characteristic of AFE is right heart strain followed by elevated pulmonary pressures and resultant left sided failure. An electrocardiogram can also measure the electrical activity of the heart and can reveal abnormal electrical patterns.

Sometimes, doctors would take a sample of pulmonary blood to look for the fetal squamous cells, which were believed to be covered with white blood cells called neutrophils and fetal debris like fetal tissue or cells. This was once considered diagnostic of amniotic fluid embolism, but is no longer considered conclusive evidence of the disorder as this finding is not specific to this disorder.

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Standard Therapies

Amniotic fluid embolism is a medical emergency. Treatment is aggressive and supportive. A team of specialists is required to treat affected individuals. This team will include specialists in treating pain and in managing care of a patient before, during and after surgery (anesthesiologists); physicians who specialize in pregnancy, childbirth and a woman’s reproductive system (obstetricians); obstetricians who specialize in maternal and fetal health (maternal-fetal medicine specialists); physicians who specialize in the diagnosis and treatment of blood disorders (hematologists); and physicians who specialize in the treatment of critically ill patients (intensivists).

Specific therapeutic procedures and interventions may vary, depending upon numerous factors, such as the severity of the disorder; the presence or absence of certain symptoms; whether the patient is conscious, breathing, etc.; an individual’s age and general health; the health and status of the fetus; and/or other elements. The Society for Maternal-Fetal Medicine has published recommendations for the treatment of amniotic fluid embolism (Society for Maternal-Fetal Medicine, 2016 et al.).

Initially, physicians will work to stabilize a woman’s breathing and heart function. If an affected woman is unconscious, they may receive cardiopulmonary resuscitation (CPR). An affected woman may receive supplemental oxygen to make up for a lack of oxygen in the blood or tissues. This can require the insertion of a breathing tube to help with breathing and the use of a machine to assist with breathing (mechanical ventilation).

Sometimes, doctors will insert a small, thin tube called a catheter into the main artery of the lungs (pulmonary artery catheter). This catheter can be used to monitor blood pressure. A central venous catheter may be placed into a large vein and used to deliver medications, draw blood, given blood transfusions, or give fluids or nutrients.

Some women may receive medications to help the heart function better, or to help reduce fluid accumulation in the lungs or around the heart. Medications that cause the blood vessels to narrow, called vasopressors may be given to treat low blood pressure (hypotension) and improve the amount of blood the heart pumps out (cardiac output). Medications that change the speed or force of muscle contractions, called inotropic medications, may also be given to help improve cardiac output. Medications may also be given to help maintain the muscle tone of the uterus. Sometimes, there is a loss of muscle tone called uterine atony.

Some women will require blood transfusions to replace lost blood and to replace clotting factors that are essential to help the blood clot. Most patients require activation of hospital specific massive transfusion protocols as women who have suffered an AFE require multiple component therapy.

Immediate delivery of the fetus is required for the health of the fetus. Decreasing the aorto-caval compression may improve maternal resuscitation.

Psychosocial support for the entire family is essential as well. Some women survive amniotic fluid embolism with no long-term complications of the condition. However, there is a risk of long-term complications including neurological problems because of a lack of oxygen to the brain.

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Clinical Trials and Studies

Researchers are studying whether specific biomarkers for amniotic fluid embolism may be identified and used to help with diagnosis. Biomarkers are substances that can be detected and measured in a person and when detected at certain levels indicate a specific disorder or condition is or may be present. More research is necessary to determine whether there are specific biomarkers that can be used to detect amniotic fluid embolism.

There are several other treatment methods that have been discussed in the medical literature that have been tried in individual patients or small series of patients. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. More research is necessary to determine the long-term safety and effectiveness of various treatments for amniotic fluid embolism proposed in the medical literature.

The AFE Foundation along with the Baylor College of Medicine maintains an international patient registry of women with amniotic fluid embolism. In collaboration with Wayne State University, a biorepository of samples from women and their offspring are being collected to further understand this elusive disease. A registry is a special database that contains information about individuals with a specific disorder or group of conditions. The collection of data about rare disorders may enable researchers to increase the understanding of such disorders, expand the search for treatments, and accelerate clinical trials into specific treatment options. For more information, visit:

Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

Some current clinical trials also are posted on the following page on the NORD website:

For information about clinical trials sponsored by private sources, contact:

For information about clinical trials conducted in Europe, contact:

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Clark SL, Romero R, Dildy GA, et al. Proposed diagnostic criteria for the case definition of amniotic fluid embolism in research studies. Am J Obstet Gynecol. 2016;215:408-412. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5072279/

Society for Maternal-Fetal Medicine (SMFM). Pacheco LD, Saade G, Hankins GD, Clark SL. Amniotic fluid embolism: diagnosis and management. Am J Obstet Gynecol. 2016;215;B16-24. https://www.ajog.org/article/S0002-9378(16)00474-9/pdf

West M. Amniotic fluid embolism: a historical perspective in diagnosis and management. BJOG. 2016;123:110. https://obgyn.onlinelibrary.wiley.com/doi/full/10.1111/1471-0528.13528

Clark SL. Amniotic fluid embolism. Obstet Gynecol. 2014;123:337-348. https://www.ncbi.nlm.nih.gov/pubmed/24402585

Gist RS, Stafford I, Leibowitz AB, Beilin Y. Amniotic fluid embolism. Anesth Analg. 2009;108:1599-1602. https://journals.lww.com/anesthesia-analgesia/Fulltext/2009/05000/Amniotic_Fluid_Embolism.38.aspx

Benson MD. Amniotic fluid embolism mortality rate. J Obstet Gynaecol Res. 2017;43:1714-1718. https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1111/jog.13445

Conde-Agudelo A, Romero R. Amniotic fluid embolism: an evidence-based review. Am J Obstet Gynecol. 2009;201:445.e1-445.13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3401570/

Rudra A, Chatterjee S, Sengupta S, Nandi B, Mitra J. Amniotic fluid embolism. Indian J Crit Care Med. 2009;13:129-135. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823093/

Dedhia JD, Mushsambi MC. Amniotic fluid embolism. Continuing Education in Anaesthesia Critical Care & Pain. 2007;7:152-156. https://academic.oup.com/bjaed/article/7/5/152/534887

Moore LE. Amniotic Fluid Embolism. Emedicine Journal. Updated: May 13, 2019. Available at: https://emedicine.medscape.com/article/253068-overview Accessed June 5, 2019.

Moldenhauer JS. Amniotic Fluid Embolism. Merck Manual Online Professional Version website. Updated June 2018. https://www.merckmanuals.com/professional/gynecology-and-obstetrics/abnormalities-and-complications-of-labor-and-delivery/amniotic-fluid-embolism Accessed June 5, 2019.

Mayo Clinic for Medical Education and Research. Amniotic fluid embolism. Nov. 09, 2018. Available at: https://www.mayoclinic.org/diseases-conditions/amniotic-fluid-embolism/symptoms-causes/syc-20369324 Accessed June 5, 2019.

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