What is Amniotic Fluid Embolism (Anaphylactoid Syndrome of Pregnancy, AFE)?
Amniotic fluid embolism (AFE) is a serious medical emergency that happens during childbirth. It’s characterized by a sudden heart and lung failure and widespread abnormal blood clotting, or what is known as disseminated intravascular coagulation (DIC). Sometimes, AFE is also called the anaphylactoid syndrome of pregnancy. However, an AFE is different from a direct embolism or the presence of amniotic fluid itself. AFE can happen in 1 out of 8,000 to 80,000 childbirths globally, but the exact numbers are uncertain due to differences in diagnosis and reporting.
In the United States, AFE is the second highest cause of death in pregnant women during childbirth (peripartum) and the leading cause of sudden heart failure during this time. Its symptoms can come on suddenly and usually include a sudden heart and lung failure, a change in mental state, and severe blood clotting disorders. Survivors often have to deal with serious health problems, including issues with their heart, kidneys, brain, and lungs. In the US, AFE affects between 2.2 to 7.7 out of every 100,000 deliveries, contributing to 7.5% of deaths during childbirth. The death rate from AFE in developing countries is between 1.8 to 5.9 out of 100,000 deliveries, compared to 0.5 to 1.7 out of 100,000 deliveries in wealthier countries.
AFE was first identified in 1941 when researchers noticed fetal cells in the blood vessels of the lungs in women who died during labor. Data from the National Amniotic Fluid Embolism Registry indicates that AFE shares more similarities with severe allergic reactions, or anaphylaxis, than with a typical embolism. Interestingly, fetal tissue or components of amniotic fluid are not always found in women who show signs and symptoms of AFE. The diagnosis of AFE traditionally happened after death, and it was based on the presence of fetal skin cells in the mother’s blood vessels of the lungs. However, these cells can also be found in pregnant women in labor who do not develop AFE. So, the diagnosis of AFE is often made by ruling out other causes of instability in the body’s circulatory system.
What Causes Amniotic Fluid Embolism (Anaphylactoid Syndrome of Pregnancy, AFE)?
Amniotic fluid embolism (AFE) is an unpredictable complication affecting some pregnant people. Several factors can increase the risk of this happening. These may include the pregnant person’s age (especially if they are over 35 to 40 years old), carrying multiple children, carrying a male fetus, developing gestational diabetes, delivering the baby surgically, a condition where the amniotic fluid is too much (polyhydramnios), and extracting the placenta manually. Other risk factors include substance use, trauma, and certain underlying health conditions like asthma, heart disease, or cerebrovascular disorders.
Inducing labor can increase the danger of AFE, as can other pregnancy conditions like placenta previa (when the placenta covers the opening to the cervix), eclampsia (seizures in pregnancy), uterine rupture, fetal growth restriction, fetal death, placental abruption (when the placenta separates from the uterus wall), maternal kidney disease, heart disease after childbirth, and heavy bleeding after birth.
There is still a lot of research being done to pinpoint all the risk factors of AFE. For example, earlier studies suggested that having a cesarean delivery could increase the risk, but more recent studies have found no connection between cesarean delivery and AFE. One specific study observed 149 cases of AFE, 80 of which resulted in fatalities, and found that a natural vaginal delivery was 12 times more likely to result in AFE than a cesarean delivery. This study concluded that a cesarean section may actually lower the risk of a fatal AFE.
Amnioinfusion, a procedure where saline is injected into the amniotic cavity, was associated with a threefold increase in AFE risk, potentially due to the increased stretching of the uterus.
Another significant observation is that many people who had AFE reported having allergies. This observation is the reason for the condition’s other name, “anaphylactoid syndrome of pregnancy”. Around 8% of AFE cases are associated with in vitro fertilization pregnancies, which is higher than the overall rate of in vitro fertilization pregnancies.
A disorder called a placenta accreta spectrum (PAS) disorder has a very strong association with AFE, carrying a 10-times higher risk. The more severe the PAS, the higher the AFE incidence. AFE happens when amniotic fluid and fetal components enter the mother’s bloodstream, triggering severe tightening of the blood vessels in the lungs and the airways (pulmonary vasoconstriction and bronchoconstriction). This isn’t just caused by a physical blockage, but mainly from the body’s immune response to the foreign material, which activates some blood factors leading to a syndrome known as DIC (disseminated intravascular coagulation).
Risk Factors and Frequency for Amniotic Fluid Embolism (Anaphylactoid Syndrome of Pregnancy, AFE)
Amniotic fluid embolism (AFE) is a condition that affects pregnant women and can sometimes lead to death. Although the exact number of cases is uncertain due to misdiagnosis and underreporting, it’s estimated to happen in 1.9 to 6.1 out of every 100,000 births. It notably caused a high number of deaths during childbirth in Germany back in 2011, and also accounts for almost a quarter of maternal deaths in Japan. Australia has recognized AFE as the top direct cause of death in mothers, occurring in about 1 in 8,000 to 1 in 80,000 deliveries. In the UK, there are approximated 2 cases per 100,000 births, while in the United States, the rate is roughly 7.7 per 100,000 births.
AFE tends to occur during labour with about 70% of all cases happening at this stage. Roughly 19% of cases take place during cesarean sections, and around 11% after vaginal deliveries. Interestingly, AFE can even occur up to 48 hours after giving birth. There have also been a few unique cases reported where AFE happened after pregnancy termination, amniocentesis (a test done during pregnancy), following injections of a certain type of salt solution into the uterus to induce abortion, and in the early stages of pregnancy.
Signs and Symptoms of Amniotic Fluid Embolism (Anaphylactoid Syndrome of Pregnancy, AFE)
An amniotic fluid embolism (AFE) is a severe and often fatal condition that can occur during pregnancy or childbirth, typically in women of advanced age or those who have had multiple pregnancies. Other risk factors may include issues related to the placenta, such as accreta, abruption, or previa, as well as conditions like preeclampsia, gestational diabetes, excessive amniotic fluid (polyhydramnios), or procedures like amniocentesis or operations on the pregnant uterus. This condition usually occurs late in labor when the woman suddenly has trouble breathing and her blood pressure drops drastically.
- Shortness of breath
- Low blood pressure (hypotension)
- Agitation
- Anxiety
- Altered mental status
- A sense of doom
- Seizures possibly leading to cardiac arrest
- Massive bleeding
In many cases, amniotic fluid embolism results in unconsciousness, seizures, and even respiratory or cardiac arrest. Patients often display signs of severe lack of oxygen, low blood pressure, and bluish skin. A key identifying feature of AFE is a combination of low oxygen levels, low blood pressure, and issues related to blood clotting, although patients generally have a normal body temperature. Patients might also have minute bubbles in their retinal arteries, fast breathing, a unique heart murmur, and varying levels of bleeding. Notably, heavy bleeding from the uterus can worsen the situation. Usually, the initial bleeding happens via the vagina, but it can occur in surgical cuts too. Almost 83% of AFE patients experience a complete disorganization of the blood clotting system. Preliminary symptoms, such as breathing difficulty or agitation, often occur before the body goes into shock.
Testing for Amniotic Fluid Embolism (Anaphylactoid Syndrome of Pregnancy, AFE)
Amniotic fluid embolism (AFE) can be a challenging condition to diagnose. Basically, doctors consider it when a patient shows symptoms like difficulty breathing, feeling upset or confused, low blood pressure, heart problems, and issues with the blood’s ability to clot. These symptoms usually occur after events related to childbirth, like labor, the breaking of water, vaginal delivery, or a C-section. Sometimes, it can happen during or after an elective abortion, either using medication or surgery.
The doctor will assess your heart health during the cardiopulmonary resuscitation process. They may use echocardiography, which uses sound waves to create pictures of your heart. If your condition is stable, a special form of echocardiography called a transesophageal echocardiogram (TEE) might be suggested. This exam provides a close-up look at your heart from the inside. Significant findings that suggest AFE include swelling and sluggishness of the right side of the heart, blood leaking backward through the tricuspid valve, and an enlarged right atrium. Early stage blood clots might also be seen in the enlarged right heart chamber.
A key feature related to AFE is the bowing of the wall that separates the ventricles (pumping chambers) of the heart, which can cause blockage and inefficient heart function. This could make the heart look like the shape of the letter ‘D’.
As part of the diagnostic process, doctors will immediately gather blood samples for lab tests. These tests can provide a broader understanding of your health status, assess your body’s ability to clot, and indicate if you might need a blood transfusion.
Even with these tests, no single, definitive test for AFE exists. That’s why the diagnosis depends on careful consideration of your symptoms and test results. In 2016, the American Society for Maternal-Fetal Medicine created a set of standards that doctors use to diagnose AFE. They look for sudden issues with heart and lung function, or problems with blood clotting, all happening during labor or after the delivery of the placenta.
Still, some situations may not fit exactly into these standards, like when an AFE occurs during an elective termination of pregnancy. Even though the standards are not perfect, the intention is to have a consistent framework within the medical community when handling cases and conducting research related to AFE.
It’s important to note that key symptoms of AFE can include abnormalities in blood clotting, high blood pressure in the lungs, and neurological signs. Some experts suggested expanding the criteria to include alarming signs like seizures, agitation, anxiety, feeling of imminent death, confusion, and fainting. They recommend that further research be conducted in the future to substantiate these suggestions.
Treatment Options for Amniotic Fluid Embolism (Anaphylactoid Syndrome of Pregnancy, AFE)
Due to its infrequency, many maternity doctors may not have experience handling cases of amniotic fluid embolism (AFE), a rare but critical condition that can occur during childbirth. In order to improve coordination among healthcare practitioners, a checklist could be helpful in quickly and efficiently managing this urgent condition. The most immediate steps in treating a patient with AFE fall under the “ABC” principles: ensuring a clear airway, supporting breathing, and maintaining circulation.
Immediate and effective cardiopulmonary resuscitation (CPR), which involves chest compressions and ventilations, is a key part of AFE management. Defibrillator pads may be applied during CPR to provide a shock to the heart if the heart rhythm is irregular. After two minutes of CPR, there should be a pause to check the patient’s pulse and heart rhythm, as well every few minutes of giving chest compressions.
In cases where an intravenous line can’t be put in, a different type of access can be established in the upper part of the arm bone, to give fluids and medications. Should the heart rhythm persist, a medication called epinephrine may be given through this access every few minutes. If no circulation returns after about four minutes, steps should be taken in preparation for delivery of the baby. This could involve surgically delivering the baby if the fetus is at a stage of development considered viable, or old enough to potentially survive outside the womb.
AFE can often lead to an increase in pulmonary vascular resistance, which can result in right heart failure. This can be indicated by specific findings in a transthoracic echocardiogram (TTE), which is a type of heart ultrasound. Management of this heart failure may involve adjusting ventilator settings, avoiding too much fluid, and using specific medications like norepinephrine for blood pressure control and dobutamine or milrinone for heart support. A medication called epoprostenol is recommended for causing blood vessels to widen.
A state of excessive blood clotting can be managed by maintaining adequate levels of fibrinogen, a protein involved in clot formation, using a balanced ratio of packed red blood cells, platelets, and fresh frozen plasma. A medicine called tranexamic acid can be given promptly, as this drug prevents excessive breakdown of blood clots and is safe to use in cases of obstetrical bleeding or heavy bleeding during childbirth. If heart failure does not respond to medical management or CPR is prolonged, a treatment called extracorporeal membrane oxygenation (ECMO) may be considered, which provides extended cardiac and respiratory support.
Successfully delivering the baby as quickly as possible, a procedure also known as “resuscitative hysterotomy”, is a key part of AFE treatment. Given the urgency of this procedure, it is likely to be performed on site, as it is often not feasible to transport the patient to an operating room within the ideal time window of 1-2 minutes.
Aside from this, comprehensive maternal care includes maintaining an open airway, effective breathing, appropriate fluid management, and the careful use of vasopressors, which constrict blood vessels and increase blood pressure. Devices known as intra-arterial and central venous pressure lines are crucial for ongoing assessment and monitoring of the patient’s condition.
Severe right heart failure and increased pressure in the pulmonary arteries often accompany AFE. So, treatment often involves medications that support the heart, dilate the blood vessels in the lungs and reduce the load on the heart. In more severe cases, ECMO life support may be needed if heart function does not improve with medication.
After the delivery of the baby, managing bleeding, poor uterine contraction, and clotting problems is the next step. Blood products are used to increase blood volume and reduce the risk of overload.
Lab tests for clotting may be too slow for patients who are actively bleeding. Real-time tests at the bedside can offer faster, more relevant results for managing major bleeding during childbirth, as in AFE.
Doctors may also opt for several procedures to alleviate ongoing uterine bleeding. If severe and ongoing clotting problems occur, an emergency hysterectomy or surgical removal of the uterus may be the best course.
After the critical event, a debriefing is recommended to review what happened, identify areas for improvement, and offer emotional support to the patient, family, and medical providers. Reporting all cases of AFE to the international AFE registry can also help improve outcomes for future patients. Practice drills are valuable in preparing the healthcare team for these rare but urgent situations.
What else can Amniotic Fluid Embolism (Anaphylactoid Syndrome of Pregnancy, AFE) be?
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A simple way to understand AFE (amniotic fluid embolism) diagnosis is by following vigilance for reversible causes such as less blood volume (hypovolemia), low oxygen in the blood (hypoxemia), and cold body temperature (hypothermia). Diagnoses that need attention include heart attack (myocardial infarction), high potassium in the blood (hyperkalemia), and pressure in the chest cavity (tension pneumothorax).
For pregnant women experiencing severe problems with their heart and blood vessels at the time of delivery, followed by heavy bleeding, the following potential reasons should be considered:
- Blood clot in the lung (Pulmonary embolism)
- Heart weakness during pregnancy or after childbirth (Peripartum cardiomyopathy)
- Severe body infection (Septic shock)
- Tear in the main artery (Aortic dissection)
- Excessive magnesium in the blood (Magnesium toxicity)
- Air or cholesterol embolism
- Heart attack (Myocardial infarction)
- Air bubble in veins (Venous air embolism)
- Eclampsia
- Inhalation of foreign material(Aspiration)
- Negative reaction to anesthetic drugs
- Severe allergic reaction (Anaphylaxis)
- Blood loss causing bleeding disorders and shock
- Spread of spinal anesthetic to the head
It’s also important to realize that AFE may have similarities with pulmonary embolism (blood clot in the lungs) but it does not have continuous blood clotting disorder like in pulmonary embolism. Basic imaging of the heart can help in clarifying the diagnosis. For example, septic shock, usually shows symptoms of intense body reaction to infection before leading to sudden heart and blood vessels collapse. Heart attack, unless it’s the cause of the cardiac arrest, will show specific changes on ECG and increased heart enzymes. Air bubbles in veins often begin with wheezing, gasping, and chest pain before the collapse. Eclampsia may show high blood pressure, water retention, protein in urine, headaches, or seizures prior to the collapse. Allergic reactions should show symptoms like wheezing, shortness of breath, rash, hives, and a period of low blood pressure before heart and blood vessel failure. Anesthetic spread to the head would present with increased sensation level, upper body weakness, difficulty in speaking, swallowing problems, and slow heart rate.
What to expect with Amniotic Fluid Embolism (Anaphylactoid Syndrome of Pregnancy, AFE)
Amniotic Fluid Embolism (AFE), a rare but serious condition during pregnancy, is a leading cause of death among mothers in developed countries. Historically, the death rate was thought to be 61%, but recent data points to a lower figure, around 10%. Survival rates increase significantly with early intervention and effective treatment of any heart complications.
AFE is a serious condition. Sadly, it’s estimated that roughly 50% of patients die within the first hour of an AFE occurring, and about two-thirds within five hours. The highest death rate occurs within the first 12 hours. A study from California reports that 26.4% of affected pregnant patients died, and nearly two-thirds developed Disseminated Intravascular Coagulation (DIC), a condition that causes dangerous blood clots and bleeding.
Life after an AFE can be quite challenging. Survivors often face significant health deficits in brain function, lung efficiency, and heart health. The chance of an AFE occurring in future pregnancies is uncertain, but successful pregnancies after experiencing an AFE have been reported. Recommendations for choosing cesarean section delivery for future pregnancies as a way to reduce potential risks are still debated.
Newborn mortality rates related to AFE are around 30%, with surviving infants at an elevated risk for conditions such as Hypoxic-Ischemic Encephalopathy (brain damage caused by lack of oxygen), cerebral palsy, and cognitive disabilities. In some cases, pregnancies complicated by AFE result in stillbirths and neonatal deaths, with rates reaching between 10% and 40%. It’s also common for survivors to experience depression and post-traumatic stress disorder (PTSD).
However, there is some encouraging news. Initially, only 15% of survivors remained without brain damage, but recent data suggests this is improving, with estimates of up to 46% of survivors retaining normal brain function. This improvement is a direct result of advances in diagnosing and treating AFE and a greater understanding of how the condition develops. Early detection and intervention have not only improved the survival rate for mothers but have also led to better outcomes for newborns.
Possible Complications When Diagnosed with Amniotic Fluid Embolism (Anaphylactoid Syndrome of Pregnancy, AFE)
People who survive AFE (Amniotic Fluid Embolism) might face a range of serious health problems. These can include:
- Kidney failure
- Heart failure
- Prolonged lung failure leading to severe respiratory distress
- Heart attack
- Heart rhythm problems
- Heart muscle disease
- Fluid overload in the heart
- Poor functioning of the left side of the heart
- Extended blood clotting disorders
- Long-term lung failure
- Prolonged narrowing of the airways
- Liver failure
- Lung fluid overload due to heart problems
- Seizures
- Brain damage due to lack of oxygen
- Various mental or nerve-related disorders
In addition, babies born urgently because of maternal AFE have an increased risk of suffering from a condition called hypoxic-ischemic encephalopathy (HIE). This condition can significantly affect the child’s cognitive ability resulting in long-term seizure disorders, motor function problems, and developmental delays.
Preventing Amniotic Fluid Embolism (Anaphylactoid Syndrome of Pregnancy, AFE)
A Amniotic Fluid Embolism (AFE) is a very serious condition that often starts suddenly and without warning, making it difficult to predict or prevent. However, there are some strategies that may help reduce the risk of AFE. For instance, extra care should be taken during certain procedures, including the placement of a pressure catheter, a tube that measures blood pressure, and intraamniotic infusion therapy, a treatment involving injecting fluid into the amniotic sac that surrounds a baby in the womb. Furthermore, it’s recommended that doctors avoid cutting into the placenta, the organ that provides oxygen and nutrients to the baby, during a cesarean (C-section) delivery whenever possible.
There is a need for more research to identify who is most at risk for AFE. This condition often has long-term mental and physical health effects and only about 60% of women with AFE return to their previous level of health. Increased research could lead to a better understanding of the risk factors for AFE and help improve prevention strategies.
