Amniotic fluid embolism is a rare obstetric emergency, estimated to occur in 2 to 6/100,000 pregnancies. It usually occurs during late pregnancy but may occur during termination of a 1st- or 2nd-trimester pregnancy.
Although mortality estimates vary widely (from about 20 to 90%), the syndrome clearly poses a significant risk, and of women who die suddenly during labor, amniotic fluid embolism is one of the most likely causes (1 General references Amniotic fluid embolism is a clinical syndrome of hypoxia, hypotension, and coagulopathy that results from entry of fetal antigens into the maternal circulation. Amniotic fluid embolism is a... read more , 2 General references Amniotic fluid embolism is a clinical syndrome of hypoxia, hypotension, and coagulopathy that results from entry of fetal antigens into the maternal circulation. Amniotic fluid embolism is a... read more ). Survival depends on early recognition and immediate institution of treatment.
1. Clark SL: Amniotic fluid embolism. Obstet Gynecol 123:337-348, 2014. doi: 10.1097/AOG.0000000000000107
2. Society for Maternal-Fetal Medicine (SMFM), Pacheco LD, Clark SL, Klassen M, Hankins GD: Amniotic fluid embolism: Principles of early clinical management. Am J Obstet Gynecol 222 (1):48–52, 2020. 222(1):48-52. doi: 10.1016/j.ajog.2019.07.036
The long-standing term amniotic fluid "embolism" implies a primarily mechanical, obstructive disorder, as occurs in thromboembolism or air embolism. However, because amniotic fluid is completely soluble in blood, it cannot cause obstruction. Furthermore, the minor amounts of fetal cells and tissue debris that may accompany the amniotic fluid into the maternal circulation are too small to mechanically obstruct enough of the pulmonary vascular tree to cause the marked hemodynamic changes that occur in this syndrome.
Instead, it is currently thought that exposure to fetal antigens during delivery activates proinflammatory mediators, which trigger an overwhelming inflammatory cascade and release of vasoactive substances (eg, norepinephrine) similar to the systemic inflammatory response syndrome (SIRS) that occurs in sepsis and septic shock Sepsis and Septic Shock Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection. In septic shock, there is critical reduction in tissue perfusion; acute failure... read more .
The inflammatory response causes organ damage, particularly to the lungs and heart, and triggers the coagulation cascade, resulting in disseminated intravascular coagulation Disseminated Intravascular Coagulation (DIC) Disseminated intravascular coagulation (DIC) involves abnormal, excessive generation of thrombin and fibrin in the circulating blood. During the process, increased platelet aggregation and coagulation... read more (DIC). The resulting maternal hypoxia and hypotension have profound adverse effects on the fetus.
Because maternal exposure to fetal antigens is likely fairly common during labor and delivery, it is not clear why only a few women develop amniotic fluid embolism. It is thought that different fetal antigens in varying amounts probably interact with unknown maternal susceptibility factors.
Many factors are associated with increased risk of amniotic fluid embolism, but evidence is inconsistent. As with exposure to fetal antigens, many of the risk factors are commonplace or at least much more likely than amniotic fluid embolism, and there is no good pathophysiologic understanding of why only a few women with risk factors develop the syndrome. Nonetheless, risk is generally thought to be increased by the following:
Amniotic fluid embolism usually manifests during and shortly after labor and delivery. The first sign may be sudden cardiac arrest. Other patients suddenly develop dyspnea and have tachycardia, tachypnea, and hypotension. Respiratory failure Overview of Respiratory Failure Acute respiratory failure is a life-threatening impairment of oxygenation, carbon dioxide elimination, or both. Respiratory failure may occur because of impaired gas exchange, decreased ventilation... read more , with significant cyanosis, hypoxia and pulmonary crackles, often quickly follows.
Coagulopathy manifests as bleeding from the uterus and/or sites of incisions and venipuncture.
Uterine hypoperfusion causes uterine atony and fetal distress.
The mortality rate is very high.
Diagnosis of amniotic fluid embolism is suspected when the classic triad develops during labor or immediately after delivery:
Diagnosis of amniotic fluid embolism is clinical and by excluding other causes of the following:
Sudden cardiac arrest in young women (eg, coronary artery dissection, congenital heart disease Overview of Congenital Cardiovascular Anomalies Congenital heart disease is the most common congenital anomaly, occurring in almost 1% of live births (1). Among birth defects, congenital heart disease is the leading cause of infant mortality... read more )
Acute respiratory failure (pulmonary embolism Pulmonary Embolism (PE) Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more , pneumonia Overview of Pneumonia Pneumonia is acute inflammation of the lungs caused by infection. Initial diagnosis is usually based on chest x-ray and clinical findings. Causes, symptoms, treatment, preventive measures, and... read more )
Coagulopathy (eg, sepsis Sepsis and Septic Shock Sepsis is a clinical syndrome of life-threatening organ dysfunction caused by a dysregulated response to infection. In septic shock, there is critical reduction in tissue perfusion; acute failure... read more , postpartum hemorrhage Postpartum Hemorrhage Postpartum hemorrhage is blood loss of > 1000 mL or blood loss accompanied by symptoms or signs of hypovolemia within 24 hours of birth. Diagnosis is clinical. Treatment depends on etiology... read more , uterine atony)
Autopsy may detect fetal squamous cells and hair in the pulmonary circulation, but this finding does not confirm the diagnosis. Fetal cells are sometimes detected in patients who do not have the amniotic fluid embolism.
Treatment of amniotic fluid embolism is supportive. It includes transfusion of red blood cells (as needed to replace lost blood) and fresh frozen plasma and clotting factors (as needed to reverse the coagulopathy) plus ventilatory and circulatory support, with inotropic drugs as needed. Recombinant factor VIIa should not be used routinely but may be given to women who continue to bleed heavily despite use of other clotting factors.
The Society for Maternal-Fetal Medicine has provided a concise checklist for the immediate management of amniotic fluid embolism to help obstetric practitioners respond rapidly and efficiently (1 Treatment reference Amniotic fluid embolism is a clinical syndrome of hypoxia, hypotension, and coagulopathy that results from entry of fetal antigens into the maternal circulation. Amniotic fluid embolism is a... read more ).
Immediate operative delivery can improve maternal outcome and can be critical for survival of a fetus that is a viable gestational age.
1. Combs CA, Montgomery DM, Toner LE, Dildy GA: Society for Maternal-Fetal Medicine special statement: Checklist for initial management of amniotic fluid embolism. Am J Obstet Gynecol S0002-9378 (21)00001-6, 2021. doi: 10.1016/j.ajog.2021.01.001
Amniotic fluid embolism typically occurs during labor and delivery and causes a triad of hypoxia, hypotension, and coagulopathy.
The disorder is not a mechanical embolic phenomenon but is probably a biochemical response in which exposure to fetal antigens triggers an overwhelming inflammatory response in the mother.
Mortality is high, and patients require immediate aggressive respiratory and hemodynamic support and replacement of clotting factors.
Immediate delivery is necessary for survival of a fetus that is a viable gestational age; it can also improve maternal outcome.