Amniotic fluid embolism (AFE) is a catastrophic syndrome typically occurring during labor and delivery or immediately postpartum. Although presenting symptoms may vary, the most common clinical features include shortness of breath, altered mental status, followed by sudden cardiovascular collapse, disseminated intravascular coagulation (DIC), and often maternal death. The diagnosis remains clinical and involves a triad of sudden hypoxia and hypotension followed by coagulopathy with the exclusion of any other likely cause. The first case report of AFE was published in a 1926 Brazilian medical journal¹ and AFE was recognized as a syndrome in 1941, when two investigators in Chicago described fetal mucin and squamous cells during postmortem examination of the pulmonary vasculature in women who had unexplained obstetric deaths.² Since then, over 1000 studies, case reports, and series have been published in an attempt to elucidate the etiology, risk factors, pathogenesis, and treatment of this mysterious obstetric complication.

The reported incidence of AFE, including both fatal and nonfatal cases, ranges between 1 in 13,000 deliveries in the United States³ to 1 in 50,000 deliveries in the United Kingdom.⁴ Approximate maternal fatality rate and perinatal mortality associated with AFE are 13% to 30% and 9% to 44%, respectively in a study evaluating AFE cases in the United States and Europe (Conde-Agudelo, A 2009). The true incidence and mortality rates of AFE are confounded by several factors: (1) the clinical definition of AFE varies across reports, (2) the signs and symptoms of AFE overlap with other more common obstetrical complications such as hemorrhagic shock due to postpartum hemorrhage, (3) there is not a “gold standard” test for the diagnosis of AFE, (4) the diagnosis of AFE is to a great extent a diagnosis of exclusion, and (5) many of the population-based studies relying on hospital discharge diagnostic codes do not ascertain the clinical diagnosis of AFE from the medical record. In addition, there are several significantly differing international criteria for the diagnosis of AFE compounding the challenges of refining risk factors, diagnosis, pathophysiology, and prognosis. New proposed diagnostic criteria for the case definition of AFE were recently developed by the Society for Maternal Fetal Medicine and the Amniotic Fluid Embolism Foundation in order to improve the identification of true cases for the primary purpose of clinical research. Uniform diagnostic criteria for research reporting of AFE as proposed by the committee are summarized in Table 14-1.

There have also been wide variances in the published maternal mortality rates associated with AFE. In the US national registry examining 46 cases of AFE, the maternal mortality rate was 61%, with a neurologically intact maternal survival rate of 15% in cases which occurred in the late 1980s and early 1990s. More recent population-based studies have reported a decreased case fatality rate from AFE (Table 14-2); however, in series derived from administrative databases, there will likely be inclusion of cases which were not likely AFE, thus increasing the cited incidence and reducing the mortality estimates.^3-14 These improving survival statistics may in part reflect improvement in general and specialized medical care over the recent decades. However, AFE still remains a leading cause of maternal death in the United States.¹⁵ Fetal outcome is poor when AFE occurs before delivery. In the US registry report, the fetal survival rate approached 40%, though with up to half of surviving neonates developing neurologic abnormalities.⁵ As with the maternal mortality statistics, perinatal mortality rates appear to be improving as well over the last several decades.

Although the US national registry⁵ did not find any predictive maternal demographic risk factors for AFE, it was noted that 70% of cases occurred during labor, 19% were recorded during cesarean section, and 11% of cases occurred immediately following vaginal delivery. Other studies have also found an increased frequency of AFE in women who underwent cesarean delivery, with rates of cesarean between 20% and 60%.^10,16 Approximately 50% of these cases were associated with fetal distress, suggesting that amniotic fluid embolus and associated hypoxia preceded cesarean delivery. Rupture of membranes was a consistent finding among 78% of women in the US registry, with onset of symptoms occurring within 3 minutes of amniotomy in 11% of cases.⁵ Another study found maternal age (mean age 33 years) and multiparity (mean parity 2.6) to be associated with AFE.¹⁶ Conflicting data have been reported regarding the association of AFE with multiple gestations. The frequency of twin gestation in the national AFE registry was not increased from baseline population estimates, but was found to be approximately threefold higher in one retrospective analysis.¹⁶ Induction of labor has been associated with an increased relative risk of AFE in some^4,10 but not all studies.³ Whether this is cause-and-effect versus an association is not clear, nevertheless the increase in absolute risk would seem clinically small assuming there is a valid indication for induction of labor.

The pathogenesis of AFE is poorly understood. Early studies describe the histologic presence of amniotic fluid components in maternal lung tissue during postmortem examination in obstetric patients who had unexplained death.² This finding was followed by reports of amniotic fluid debris found in the maternal circulation in fatal and nonfatal cases of AFE.^17,18 It was hypothesized that embolism of amniotic fluid into the maternal venous circulation caused direct mechanical obstruction of the pulmonary venous circulation resulting in cor pulmonale. However, elements of amniotic fluid have been isolated in the blood of pregnant women who did not have clinical evidence of AFE^19,20 and not all women with “classic AFE” have fetal elements detected in maternal central venous blood or lung histology.⁵

Amniotic fluid contains various concentrations of fetal elements (eg, squamous epithelial cells, lanugo hair, vernix, mucin) and other elements which may incite vasoactive and procoagulant effects (eg, prostaglandins, platelet-activating factor). Possible mechanisms of disease include the direct effects of procoagulants and/or vasoactive substances found in amniotic fluid on maternal systems. Romero and colleagues hypothesize infection/sepsis as an etiology of AFE based on two cases of proposed AFE where supralethal maternal plasma tumor necrosis factor-alpha (TNF-α) levels were present prior to the clinical AFE event.²¹ Laboratory analyses of various substances found in amniotic fluid or thought to be involved in the pathophysiologic response (eg, zinc coproporphyrin, Sialyl Tn antigen, serum tryptase, complement C3 and C4) have been studied and reported, but to date, none appear reliable in predicting or diagnosing AFE.

Although AFE typically occurs during labor and delivery or immediately postpartum, rare cases of AFE have been reported after pregnancy termination, transabdominal amniocentesis, trauma, and saline amnioinfusion.^22-26 Classic presenting signs and symptoms of AFE include respiratory distress, altered mental status, profound hypotension, coagulopathy, and death.⁶ Historical studies have described the presenting symptom as primarily respiratory distress, whereas other studies describe the most common presenting symptom before delivery to be altered mental status. Seizure or seizure-like activity was reported as the initial symptom of 30% of patients involved in the US national registry, followed by dyspnea (27%), fetal bradycardia (17%), and hypotension (13%).⁵ Classic signs and symptoms are listed in Table 14-3. The interval between the onset of symptoms and collapse reportedly varies between almost immediately to over 4 hours later. Other signs and symptoms include nausea, vomiting, fever, chills, headache, and a sense of impending doom have even been described.

Clinical features of AFE include profound cardiovascular changes. According to the US national registry, all patients who had AFE experienced hypotension.⁵ Most women (93%) had some level of pulmonary edema or adult respiratory distress syndrome along with hypoxia. One explanation for these findings includes the possibility of severe bronchospasm related to the presence of fetal elements in the pulmonary vasculature; however, only 15% of patients were found to have bronchospasm. Transesophageal echocardiography and pulmonary artery catheterization studies have demonstrated transiently elevated pulmonary artery pressures in cases of AFE along with left ventricular dysfunction, supporting the notion that these pulmonary findings are consistent with cardiogenic shock. There have also been reports of isolated right ventricular dysfunction with high right-sided pressures and tricuspid regurgitation.^27-32 In several cases where transesophageal echocardiography was performed during the early course of AFE, left ventricular failure was secondary to impaired left ventricular filling caused by dilation of the right ventricle with deviation of the interventricular septum. Available evidence suggests that the hemodynamic response to AFE initially presents with increased pulmonary vascular resistance, and right ventricular failure followed by left ventricular dysfunction.²⁷ Progression to cardiac arrest can occur quickly with pulseless electrical activity, asystole and ventricular fibrillation and ventricular tachycardia. A summary of pulmonary artery catheter hemodynamic studies following AFE is presented in Table 14-4. Myocardial hypoxic injury may be related to decreased cardiac output and impaired filling, resulting in decreased coronary artery perfusion. This vasoconstriction is often followed by profound hypotension and shock, most likely resulting from cardiogenic or obstructive causes as described earlier. After initial survival, hypoxia relates more to noncardiogenic shock, whereby severe alveolar-capillary membrane leak leads to an increase in pulmonary edema and a decrease in oxygenation.²⁷ If the event occurs before delivery, electronic fetal monitoring may demonstrate decelerations or bradycardia as blood is shunted away from the uterus.