The Unexpectedly Critically Ill Gravida

The process of labor and delivery is considered to be a joyous event in women’s lives, and most of the time it is. However, practitioners have to be aware of potential complications that can have dire adverse outcomes, causing maternal morbidity and mortality as well as severe consequences for the baby.

In considering such complications, physicians usually think of women who have serious underlying comorbidities. However, the three complications discussed here – amniotic fluid embolism, ruptured uterus, and peripartum cardiomyopathy – are conditions that can happen to otherwise young, healthy women. Fortunately these complications are rare. However, when they do happen, early recognition and prompt intervention are critical to optimizing the outcome. This means we must continually keep a high index of suspicion for all such complications so that we are ready in the event that labor and delivery does not proceed normally.

Amniotic Fluid Embolism

This complication is a leading cause of maternal morbidity and mortality in the United States and other developed countries. It should be considered in any patient who has sudden, unheralded cardiopulmonary collapse followed by profuse hemorrhage associated with disseminated intravascular coagulation (DIC).

While the hallmark presentation of amniotic fluid embolism (AFE) is this profound cardiopulmonary collapse with severe hemorrhage, it is important to note that published definitions of the condition state that coagulopathy may occur in isolation. In a 2011 review, Dr. Michael Benson points out that at least six case reports have described coagulopathy alone as the sole clinical sign of AFE (Clin. Dev. Immunol. 2012:946576 Epub 2011 Sept. 29 [doi:10.1155/2012/946576]).

AFE is a diagnosis of exclusion, and one that is based on symptoms and clinical presentation rather than on laboratory testing or histopathologic examination. There is broad consensus that a clinical diagnosis of AFE can be made based on one or more of four key signs/symptoms (in the absence of other medical conditions or explanations): cardiovascular collapse (hypotension and/or cardiac arrest); respiratory distress; DIC; and coma and/or seizures.

The condition can occur suddenly and unpredictably at any point during labor and delivery or in the immediate postpartum period. It also has been reported to occur as late as 48 hours after delivery.

Pulmonary thromboembolism often may be suspected, and indeed, it is part of the differential diagnosis. Patients with thrombotic pulmonary embolism do not usually develop the classic DIC type of coagulopathy, however, while patients with AFE are coagulopathic and often hemorrhage profusely.

The incidence of AFE has been difficult to determine. The authors of a 2009 evidence-based review of AFE reported that the estimated incidence based on large population-based studies is 1 in 15,200 deliveries in North America and 1 in 53,800 deliveries in Europe (Am. J. Obstet. Gynecol. 2009;201:445.e1-13). The incidence in an Australian population-based cohort was recently reported to be 3.3 per 100,000 deliveries (BJOG 2010;117:1417-21).

Other published reports and reviews have described an extremely broad range of estimated incidence. For instance, a report in the journal Anesthesia and Analgesia, published by the International Anesthesia Research Society, stated that AFE may occur between 1 in 8,000 and 1 in 80,000 deliveries (Anesth. Analg. 2009;108:1599-602).

The pathophysiology of AFE also is poorly understood, causing us great uncertainty as to why some apparently stable patients undergo such a profound, life-threatening collapse. When AFE was first described more than 70 years ago, it was thought to result from amniotic fluid entering the maternal circulation and obstructing the pulmonary blood flow – thus the name "amniotic fluid embolism." However, research over the decades has consistently discounted this view. As Dr. Benson states, current thinking has shifted away from embolism and toward a maternal immune response to the fetus.

Investigators have suggested possible immunologic mechanisms such as complement activation and reactions similar to anaphylaxis, but more research needs to be done. In the meantime, we must recognize that the name AFE probably does not accurately reflect what actually occurs in these patients.

Management is usually first directed at getting the patient through the initial cardiovascular insults – often hypotension and cardiac arrest – and at treating hypoxia and rapidly correcting maternal hemodynamic instability. Significant teamwork is required for the mother and baby to survive – and to survive neurologically intact. Anesthesia is needed for development and control of the airway, for instance, and critical care is essential for inotropic support. Cardiology also must be involved, as continuous cardiac, respiratory, and blood pressure monitoring – and aggressive respiratory and circulatory support – are key.

The nursing staff also can play a critical role in preventing subsequent pulmonary edema by keeping meticulous records of the intake and output of fluids. The overwhelming insult of AFE to the heart and lungs leaves patients at high risk of developing pulmonary edema, and meticulous record-keeping can help ensure that these patients are not overloaded.

Aggressive blood replacement also is required to reverse the coagulopathy associated with AFE. Transfusion of packed red blood cells is a priority, but fresh frozen plasma, platelets, and cryoprecipitate also should be available for prompt administration.

There have been promising reports of the use of recombinant factor VIIa (rVIIa) for treating hemorrhage in patients with AFE in recent years, but a recent review of case reports of AFE from 2003 to 2009 suggests that the procoagulant may actually worsen outcomes (Anesthesiology 2011;115:1201-8). Indeed, unlike patients with other types of postpartum hemorrhaging, women with AFE have high circulating tissue factor concentrations. Recombinant factor VIIa can combine with tissue factor and form intravascular clots, resulting in thrombosis of major organs.

If the patient is undelivered and has cardiac arrest, an emergency cesarean section is indicated. Prompt delivery during the resuscitation process not only increases the chances of perinatal survival without neurological sequelae, but also improves the maternal resuscitation effort. We have a 4-minute window for delivery from the time the code is called to avoid neurologic injury to the fetus and optimize outcomes for the mother. This 4-minute principle was adopted by the American Heart Association in 1986, and its clinical use has been supported by 20 years of published case reports since then (Am. J. Obstet. Gynecol. 2005;192:1916-21).

Although outcomes with AFE may be improving somewhat, AFE still causes significant morbidity and mortality. Investigators in the Australian AFE cohort study, for instance, recently reported maternal and perinatal fatality rates of 35% and 32%, respectively. These rates were similar to those from the U.K. Obstetric Surveillance System, according to the authors (BJOG 2010;117:1417-21).

Ruptured Uterus

In an effort to reduce rates of cesarean deliveries, obstetricians are swinging back once again to encouraging more women to attempt vaginal birth after cesarean delivery (VBAC). Because the rates of uterine rupture are higher in women who attempt VBAC, our index of suspicion should be acute for any woman who is laboring after having had a prior cesarean delivery. We also must do everything we can to assess a patient’s risks of failed VBAC resulting in emergency cesarean section and uterine rupture.

The American College of Obstetricians and Gynecologists (ACOG) now recommends that most women with one previous cesarean delivery and with a low transverse incision be counseled about VBAC and offered a trial of labor. ACOG points out in its 2010 practice bulletin on VBAC that in several large studies, the uterine rupture rate after a trial of labor in such women was approximately 0.5-0.9%.

The College also says that many women previously considered to be at high risk may now be considered candidates for a trial of labor after cesarean section (TOLAC). Among the conditions that are no longer necessarily contraindications for attempted VBAC: two previous low transverse cesarean deliveries; suspected fetal macrosomia; twin gestations; more than one previous cesarean delivery; a previous low vertical incision; gestation beyond 40 weeks; and even external cephalic version for breech presentation (Obstet. Gynecol. 2010;116:450-63).

The ACOG bulletin addresses the importance of counseling, and mentions the possible utility of a nomogram developed for predicting the chance of successful VBAC for individual patients. The tool incorporates six variables that are ascertainable at the first prenatal visit, including maternal age, body mass index, and history of vaginal delivery (Obstet. Gynecol. 2007;109:806-12). The tool, a calculator of sorts, was developed through research by the National Institute of Child Health and Development’s (NICHD’s) Maternal-Fetal Medicine Units Network, and is also available at http://www.bsc.gwu.edu/mfmu/vagbirth.html.

Such individualized risk assessment is critical. Another model for assessing risk and informing discussions with individual patients is one developed in the United Kingdom by Dr. Gordon C. S. Smith at Cambridge University and his associates (PLoS Med. 2005:2:e252). These investigators documented that women with a predicted cesarean section risk (an unsuccessful trial of labor) of less than 20% using their model had a minimal incidence of uterine rupture of 2.0 per 1,000, while those deemed to have a high risk of cesarean delivery – defined as greater than 40% – had an incidence of uterine rupture of 9.1 per 1,000.

However small it is in absolute terms, there is an inherent risk of the uterine incision rupturing during an attempt at labor after a previous cesarean section. Indicative of this inherent risk are recommendations by the authors of numerous studies, as well as ACOG, for VBAC to be attempted in facilities with staff available for emergency care. When the fetus is actually extruded through the incision and into the abdominal cavity, there is significant risk of severe maternal and perinatal morbidity and mortality secondary to blood loss and hypoxia.

Signs and symptoms of possible uterine rupture include the following: a change in fetal heart rate pattern from normal to a category 3 heart rate tracing; unexplained vaginal bleeding; frequent epidural dosing or pain that is not alleviated with epidural anesthesia already in place; and loss of uterine tone with an intrauterine pressure catheter (IUPC) in place. If an IUPC is flushed and the patient still has abnormal readings, a diagnosis of uterine scar disruption should be entertained.

In addition to prompt recognition, rapid delivery and blood replacement are key to improving outcomes. The coagulopathy in patients with a ruptured uterus is dilutional rather consumptive, so these patients require replacement not only of packed red blood cells but also of clotting factors and other blood products. As with other types of obstetric hemorrhage, blood loss is usually in excess of the amount perceived.

A recent population-based registry study of 94 identified uterine ruptures after previous cesarean section found that almost half of the mothers diagnosed with uterine rupture after TOLAC (versus during elective or emergency prelabor cesarean section) developed moderate postpartum hemorrhage, while 15% developed severe postpartum hemorrhage and 4% needed peripartum hysterectomy (BJOG 2010;117:809-20).

Perinatal complications occurred in 48 of the 81 (59%) ruptures that occurred after attempted VBAC. In nine (19%) cases, the outcomes were serious (three deaths, three cases of severe asphyxia, and three cases of posthypoxic encephalopathy). To reduce the risk of iatrogenic uterine scar disruption, care should be taken in choosing the appropriate method of induction.

Peripartum Cardiomyopathy

This complication is characterized by the development of heart failure due to significant left ventricular (LV) systolic dysfunction. It is a diagnosis of exclusion. Patients present with the same signs and symptoms characterizing other forms of heart failure secondary to LV dysfunction, and other causes of heart disease and forms of heart failure must be ruled out.

This relatively uncommon myocardial complication can occur up to 5-6 months after delivery, but it usually occurs early in the postpartum period, with about 75% of cases presenting within the first month after delivery (Postgrad. Med. J. 2011;87:34-9). Most patients who are diagnosed during pregnancy present in the third trimester.

Various potential etiologies have been proposed – from viral myocarditis and abnormal hormonal regulation, to excessive prolactin production and an abnormal immune response to pregnancy – but its exact cause is still unknown.

Its incidence in the United States may be increasing. According to a recent review by Dr. Uri Elkayam, the incidence is estimated at approximately 1 in 3,200 deliveries, with a significantly higher incidence (up to 16-fold higher in one study) in African American women (J. Am. Coll. Cardiol. 2011;58:659-70).

Rates as high as 1 in 300 in Haiti and 1 in 100 in a small region of sub-Saharan Africa have also been reported in recent years, according to another review by Dr. Meredith Cruz and her associates (Obstet. Gynecol. Clin. N. Am. 2010;37:283-303).

Certainly, we must all be aware that certain ethnic groups and populations – most notably women of African descent – appear to be more at risk. Pregnancy-related hypertension and preeclampsia also are often cited as risk factors, as are multiparity, obesity, and older maternal age.

Diagnosis requires a high index of suspicion and vigilance, especially because many of the symptoms – shortness of breath, increased peripheral edema, and exhaustion, for instance – are similar to typical symptoms of a normal pregnancy. The diagnosis should be strongly considered in any woman who has nocturnal dyspnea. Chest pain, nocturnal cough, new regurgitant murmurs, pulmonary crackles, increased jugular venous pressure, or hepatomegaly also should raise suspicions, according to the review by Dr. Cruz and her associates.

The timing of delivery in patients diagnosed during pregnancy depends on the maternal status. If the mother is responding to medical management and is stable enough with regard to cardiovascular status to tolerate her heart failure, then induction of labor can be scheduled for or considered at 37 weeks’ gestation. If she is unstable or her LV function is poor or worsening, then early delivery should be considered.

Vaginal delivery often is preferable so that the potential risks associated with anesthesia and surgical delivery, such as clots or infection, can be avoided. Sometimes, however, cesarean delivery may be the only option. For a woman who is laboring, it is important to shorten the second stage of labor, with either low forceps or a vacuum device, in order to minimize pushing and ventricular work.

Management requires teamwork with cardiology, intensive care, anesthesiology, and nursing. After delivery, during a patient’s postpartum fluid shift, she should be managed in a critical care unit or another closely observed setting.

The management of peripartum cardiomyopathy – during pregnancy or afterward – is aimed at improving symptoms, slowing the progression of LV dysfunction and heart failure, and preventing arrhythmias and thromboembolism – both common complications.

Diuretics, nitrates, and hydralazine are often indicated and are safe in pregnancy, as is use of the beta-blocker metoprolol and either unfractionated heparin or low-molecular weight heparin for anticoagulation. (Anticoagulants are almost always indicated.) Nonpharmacologically, the focus is on reducing fluid and salt intake and on monitoring electrolyte levels and addressing any imbalances.

On the research front, animal studies and now preliminary data from a very small number of women with acute severe peripartum cardiomyopathy suggest that bromocriptine, an inhibitor of prolactin, may have a favorable effect on outcomes (Circulation 2010;121:1465-73).

Reported mortalities from the disease have ranged as high as 18%-56%, according to the Cruz review. On the other hand, many women will have a full recovery and a normalization of LV function. Dr. Elkayam concludes in his review that a normalization of LV function may occur in more than 50% of women with peripartum cardiomyopathy, mostly within 2-6 months after diagnosis.

Subsequent pregnancy is contraindicated in women who do not have a resolution of LV dysfunction, and even when LV function normalizes, there is a risk of recurrent and persistent dysfunction in a subsequent pregnancy.

Dr. Whiteman is associate professor and interim director of the division of maternal-fetal medicine at the University of South Florida, Tampa. She said she has no relevant financial disclosures.

The process of labor and delivery is considered to be a joyous event in women’s lives, and most of the time it is. However, practitioners have to be aware of potential complications that can have dire adverse outcomes, causing maternal morbidity and mortality as well as severe consequences for the baby.

In considering such complications, physicians usually think of women who have serious underlying comorbidities. However, the three complications discussed here – amniotic fluid embolism, ruptured uterus, and peripartum cardiomyopathy – are conditions that can happen to otherwise young, healthy women. Fortunately these complications are rare. However, when they do happen, early recognition and prompt intervention are critical to optimizing the outcome. This means we must continually keep a high index of suspicion for all such complications so that we are ready in the event that labor and delivery does not proceed normally.

Amniotic Fluid Embolism

This complication is a leading cause of maternal morbidity and mortality in the United States and other developed countries. It should be considered in any patient who has sudden, unheralded cardiopulmonary collapse followed by profuse hemorrhage associated with disseminated intravascular coagulation (DIC).

While the hallmark presentation of amniotic fluid embolism (AFE) is this profound cardiopulmonary collapse with severe hemorrhage, it is important to note that published definitions of the condition state that coagulopathy may occur in isolation. In a 2011 review, Dr. Michael Benson points out that at least six case reports have described coagulopathy alone as the sole clinical sign of AFE (Clin. Dev. Immunol. 2012:946576 Epub 2011 Sept. 29 [doi:10.1155/2012/946576]).

AFE is a diagnosis of exclusion, and one that is based on symptoms and clinical presentation rather than on laboratory testing or histopathologic examination. There is broad consensus that a clinical diagnosis of AFE can be made based on one or more of four key signs/symptoms (in the absence of other medical conditions or explanations): cardiovascular collapse (hypotension and/or cardiac arrest); respiratory distress; DIC; and coma and/or seizures.

The condition can occur suddenly and unpredictably at any point during labor and delivery or in the immediate postpartum period. It also has been reported to occur as late as 48 hours after delivery.

Pulmonary thromboembolism often may be suspected, and indeed, it is part of the differential diagnosis. Patients with thrombotic pulmonary embolism do not usually develop the classic DIC type of coagulopathy, however, while patients with AFE are coagulopathic and often hemorrhage profusely.

The incidence of AFE has been difficult to determine. The authors of a 2009 evidence-based review of AFE reported that the estimated incidence based on large population-based studies is 1 in 15,200 deliveries in North America and 1 in 53,800 deliveries in Europe (Am. J. Obstet. Gynecol. 2009;201:445.e1-13). The incidence in an Australian population-based cohort was recently reported to be 3.3 per 100,000 deliveries (BJOG 2010;117:1417-21).

Other published reports and reviews have described an extremely broad range of estimated incidence. For instance, a report in the journal Anesthesia and Analgesia, published by the International Anesthesia Research Society, stated that AFE may occur between 1 in 8,000 and 1 in 80,000 deliveries (Anesth. Analg. 2009;108:1599-602).

The pathophysiology of AFE also is poorly understood, causing us great uncertainty as to why some apparently stable patients undergo such a profound, life-threatening collapse. When AFE was first described more than 70 years ago, it was thought to result from amniotic fluid entering the maternal circulation and obstructing the pulmonary blood flow – thus the name "amniotic fluid embolism." However, research over the decades has consistently discounted this view. As Dr. Benson states, current thinking has shifted away from embolism and toward a maternal immune response to the fetus.

Investigators have suggested possible immunologic mechanisms such as complement activation and reactions similar to anaphylaxis, but more research needs to be done. In the meantime, we must recognize that the name AFE probably does not accurately reflect what actually occurs in these patients.

Management is usually first directed at getting the patient through the initial cardiovascular insults – often hypotension and cardiac arrest – and at treating hypoxia and rapidly correcting maternal hemodynamic instability. Significant teamwork is required for the mother and baby to survive – and to survive neurologically intact. Anesthesia is needed for development and control of the airway, for instance, and critical care is essential for inotropic support. Cardiology also must be involved, as continuous cardiac, respiratory, and blood pressure monitoring – and aggressive respiratory and circulatory support – are key.

The nursing staff also can play a critical role in preventing subsequent pulmonary edema by keeping meticulous records of the intake and output of fluids. The overwhelming insult of AFE to the heart and lungs leaves patients at high risk of developing pulmonary edema, and meticulous record-keeping can help ensure that these patients are not overloaded.

Aggressive blood replacement also is required to reverse the coagulopathy associated with AFE. Transfusion of packed red blood cells is a priority, but fresh frozen plasma, platelets, and cryoprecipitate also should be available for prompt administration.

There have been promising reports of the use of recombinant factor VIIa (rVIIa) for treating hemorrhage in patients with AFE in recent years, but a recent review of case reports of AFE from 2003 to 2009 suggests that the procoagulant may actually worsen outcomes (Anesthesiology 2011;115:1201-8). Indeed, unlike patients with other types of postpartum hemorrhaging, women with AFE have high circulating tissue factor concentrations. Recombinant factor VIIa can combine with tissue factor and form intravascular clots, resulting in thrombosis of major organs.

If the patient is undelivered and has cardiac arrest, an emergency cesarean section is indicated. Prompt delivery during the resuscitation process not only increases the chances of perinatal survival without neurological sequelae, but also improves the maternal resuscitation effort. We have a 4-minute window for delivery from the time the code is called to avoid neurologic injury to the fetus and optimize outcomes for the mother. This 4-minute principle was adopted by the American Heart Association in 1986, and its clinical use has been supported by 20 years of published case reports since then (Am. J. Obstet. Gynecol. 2005;192:1916-21).

Although outcomes with AFE may be improving somewhat, AFE still causes significant morbidity and mortality. Investigators in the Australian AFE cohort study, for instance, recently reported maternal and perinatal fatality rates of 35% and 32%, respectively. These rates were similar to those from the U.K. Obstetric Surveillance System, according to the authors (BJOG 2010;117:1417-21).

Ruptured Uterus

In an effort to reduce rates of cesarean deliveries, obstetricians are swinging back once again to encouraging more women to attempt vaginal birth after cesarean delivery (VBAC). Because the rates of uterine rupture are higher in women who attempt VBAC, our index of suspicion should be acute for any woman who is laboring after having had a prior cesarean delivery. We also must do everything we can to assess a patient’s risks of failed VBAC resulting in emergency cesarean section and uterine rupture.

The American College of Obstetricians and Gynecologists (ACOG) now recommends that most women with one previous cesarean delivery and with a low transverse incision be counseled about VBAC and offered a trial of labor. ACOG points out in its 2010 practice bulletin on VBAC that in several large studies, the uterine rupture rate after a trial of labor in such women was approximately 0.5-0.9%.

The College also says that many women previously considered to be at high risk may now be considered candidates for a trial of labor after cesarean section (TOLAC). Among the conditions that are no longer necessarily contraindications for attempted VBAC: two previous low transverse cesarean deliveries; suspected fetal macrosomia; twin gestations; more than one previous cesarean delivery; a previous low vertical incision; gestation beyond 40 weeks; and even external cephalic version for breech presentation (Obstet. Gynecol. 2010;116:450-63).

The ACOG bulletin addresses the importance of counseling, and mentions the possible utility of a nomogram developed for predicting the chance of successful VBAC for individual patients. The tool incorporates six variables that are ascertainable at the first prenatal visit, including maternal age, body mass index, and history of vaginal delivery (Obstet. Gynecol. 2007;109:806-12). The tool, a calculator of sorts, was developed through research by the National Institute of Child Health and Development’s (NICHD’s) Maternal-Fetal Medicine Units Network, and is also available at http://www.bsc.gwu.edu/mfmu/vagbirth.html.

Such individualized risk assessment is critical. Another model for assessing risk and informing discussions with individual patients is one developed in the United Kingdom by Dr. Gordon C. S. Smith at Cambridge University and his associates (PLoS Med. 2005:2:e252). These investigators documented that women with a predicted cesarean section risk (an unsuccessful trial of labor) of less than 20% using their model had a minimal incidence of uterine rupture of 2.0 per 1,000, while those deemed to have a high risk of cesarean delivery – defined as greater than 40% – had an incidence of uterine rupture of 9.1 per 1,000.

However small it is in absolute terms, there is an inherent risk of the uterine incision rupturing during an attempt at labor after a previous cesarean section. Indicative of this inherent risk are recommendations by the authors of numerous studies, as well as ACOG, for VBAC to be attempted in facilities with staff available for emergency care. When the fetus is actually extruded through the incision and into the abdominal cavity, there is significant risk of severe maternal and perinatal morbidity and mortality secondary to blood loss and hypoxia.

Signs and symptoms of possible uterine rupture include the following: a change in fetal heart rate pattern from normal to a category 3 heart rate tracing; unexplained vaginal bleeding; frequent epidural dosing or pain that is not alleviated with epidural anesthesia already in place; and loss of uterine tone with an intrauterine pressure catheter (IUPC) in place. If an IUPC is flushed and the patient still has abnormal readings, a diagnosis of uterine scar disruption should be entertained.

In addition to prompt recognition, rapid delivery and blood replacement are key to improving outcomes. The coagulopathy in patients with a ruptured uterus is dilutional rather consumptive, so these patients require replacement not only of packed red blood cells but also of clotting factors and other blood products. As with other types of obstetric hemorrhage, blood loss is usually in excess of the amount perceived.

A recent population-based registry study of 94 identified uterine ruptures after previous cesarean section found that almost half of the mothers diagnosed with uterine rupture after TOLAC (versus during elective or emergency prelabor cesarean section) developed moderate postpartum hemorrhage, while 15% developed severe postpartum hemorrhage and 4% needed peripartum hysterectomy (BJOG 2010;117:809-20).

Perinatal complications occurred in 48 of the 81 (59%) ruptures that occurred after attempted VBAC. In nine (19%) cases, the outcomes were serious (three deaths, three cases of severe asphyxia, and three cases of posthypoxic encephalopathy). To reduce the risk of iatrogenic uterine scar disruption, care should be taken in choosing the appropriate method of induction.

Peripartum Cardiomyopathy

This complication is characterized by the development of heart failure due to significant left ventricular (LV) systolic dysfunction. It is a diagnosis of exclusion. Patients present with the same signs and symptoms characterizing other forms of heart failure secondary to LV dysfunction, and other causes of heart disease and forms of heart failure must be ruled out.

This relatively uncommon myocardial complication can occur up to 5-6 months after delivery, but it usually occurs early in the postpartum period, with about 75% of cases presenting within the first month after delivery (Postgrad. Med. J. 2011;87:34-9). Most patients who are diagnosed during pregnancy present in the third trimester.

Various potential etiologies have been proposed – from viral myocarditis and abnormal hormonal regulation, to excessive prolactin production and an abnormal immune response to pregnancy – but its exact cause is still unknown.

Its incidence in the United States may be increasing. According to a recent review by Dr. Uri Elkayam, the incidence is estimated at approximately 1 in 3,200 deliveries, with a significantly higher incidence (up to 16-fold higher in one study) in African American women (J. Am. Coll. Cardiol. 2011;58:659-70).

Rates as high as 1 in 300 in Haiti and 1 in 100 in a small region of sub-Saharan Africa have also been reported in recent years, according to another review by Dr. Meredith Cruz and her associates (Obstet. Gynecol. Clin. N. Am. 2010;37:283-303).

Certainly, we must all be aware that certain ethnic groups and populations – most notably women of African descent – appear to be more at risk. Pregnancy-related hypertension and preeclampsia also are often cited as risk factors, as are multiparity, obesity, and older maternal age.

Diagnosis requires a high index of suspicion and vigilance, especially because many of the symptoms – shortness of breath, increased peripheral edema, and exhaustion, for instance – are similar to typical symptoms of a normal pregnancy. The diagnosis should be strongly considered in any woman who has nocturnal dyspnea. Chest pain, nocturnal cough, new regurgitant murmurs, pulmonary crackles, increased jugular venous pressure, or hepatomegaly also should raise suspicions, according to the review by Dr. Cruz and her associates.

The timing of delivery in patients diagnosed during pregnancy depends on the maternal status. If the mother is responding to medical management and is stable enough with regard to cardiovascular status to tolerate her heart failure, then induction of labor can be scheduled for or considered at 37 weeks’ gestation. If she is unstable or her LV function is poor or worsening, then early delivery should be considered.

Vaginal delivery often is preferable so that the potential risks associated with anesthesia and surgical delivery, such as clots or infection, can be avoided. Sometimes, however, cesarean delivery may be the only option. For a woman who is laboring, it is important to shorten the second stage of labor, with either low forceps or a vacuum device, in order to minimize pushing and ventricular work.

Management requires teamwork with cardiology, intensive care, anesthesiology, and nursing. After delivery, during a patient’s postpartum fluid shift, she should be managed in a critical care unit or another closely observed setting.

The management of peripartum cardiomyopathy – during pregnancy or afterward – is aimed at improving symptoms, slowing the progression of LV dysfunction and heart failure, and preventing arrhythmias and thromboembolism – both common complications.

Diuretics, nitrates, and hydralazine are often indicated and are safe in pregnancy, as is use of the beta-blocker metoprolol and either unfractionated heparin or low-molecular weight heparin for anticoagulation. (Anticoagulants are almost always indicated.) Nonpharmacologically, the focus is on reducing fluid and salt intake and on monitoring electrolyte levels and addressing any imbalances.

On the research front, animal studies and now preliminary data from a very small number of women with acute severe peripartum cardiomyopathy suggest that bromocriptine, an inhibitor of prolactin, may have a favorable effect on outcomes (Circulation 2010;121:1465-73).

Reported mortalities from the disease have ranged as high as 18%-56%, according to the Cruz review. On the other hand, many women will have a full recovery and a normalization of LV function. Dr. Elkayam concludes in his review that a normalization of LV function may occur in more than 50% of women with peripartum cardiomyopathy, mostly within 2-6 months after diagnosis.

Subsequent pregnancy is contraindicated in women who do not have a resolution of LV dysfunction, and even when LV function normalizes, there is a risk of recurrent and persistent dysfunction in a subsequent pregnancy.

Dr. Whiteman is associate professor and interim director of the division of maternal-fetal medicine at the University of South Florida, Tampa. She said she has no relevant financial disclosures.

The process of labor and delivery is considered to be a joyous event in women’s lives, and most of the time it is. However, practitioners have to be aware of potential complications that can have dire adverse outcomes, causing maternal morbidity and mortality as well as severe consequences for the baby.

In considering such complications, physicians usually think of women who have serious underlying comorbidities. However, the three complications discussed here – amniotic fluid embolism, ruptured uterus, and peripartum cardiomyopathy – are conditions that can happen to otherwise young, healthy women. Fortunately these complications are rare. However, when they do happen, early recognition and prompt intervention are critical to optimizing the outcome. This means we must continually keep a high index of suspicion for all such complications so that we are ready in the event that labor and delivery does not proceed normally.

Amniotic Fluid Embolism

This complication is a leading cause of maternal morbidity and mortality in the United States and other developed countries. It should be considered in any patient who has sudden, unheralded cardiopulmonary collapse followed by profuse hemorrhage associated with disseminated intravascular coagulation (DIC).

While the hallmark presentation of amniotic fluid embolism (AFE) is this profound cardiopulmonary collapse with severe hemorrhage, it is important to note that published definitions of the condition state that coagulopathy may occur in isolation. In a 2011 review, Dr. Michael Benson points out that at least six case reports have described coagulopathy alone as the sole clinical sign of AFE (Clin. Dev. Immunol. 2012:946576 Epub 2011 Sept. 29 [doi:10.1155/2012/946576]).

AFE is a diagnosis of exclusion, and one that is based on symptoms and clinical presentation rather than on laboratory testing or histopathologic examination. There is broad consensus that a clinical diagnosis of AFE can be made based on one or more of four key signs/symptoms (in the absence of other medical conditions or explanations): cardiovascular collapse (hypotension and/or cardiac arrest); respiratory distress; DIC; and coma and/or seizures.

The condition can occur suddenly and unpredictably at any point during labor and delivery or in the immediate postpartum period. It also has been reported to occur as late as 48 hours after delivery.

Pulmonary thromboembolism often may be suspected, and indeed, it is part of the differential diagnosis. Patients with thrombotic pulmonary embolism do not usually develop the classic DIC type of coagulopathy, however, while patients with AFE are coagulopathic and often hemorrhage profusely.

The incidence of AFE has been difficult to determine. The authors of a 2009 evidence-based review of AFE reported that the estimated incidence based on large population-based studies is 1 in 15,200 deliveries in North America and 1 in 53,800 deliveries in Europe (Am. J. Obstet. Gynecol. 2009;201:445.e1-13). The incidence in an Australian population-based cohort was recently reported to be 3.3 per 100,000 deliveries (BJOG 2010;117:1417-21).

Other published reports and reviews have described an extremely broad range of estimated incidence. For instance, a report in the journal Anesthesia and Analgesia, published by the International Anesthesia Research Society, stated that AFE may occur between 1 in 8,000 and 1 in 80,000 deliveries (Anesth. Analg. 2009;108:1599-602).

The pathophysiology of AFE also is poorly understood, causing us great uncertainty as to why some apparently stable patients undergo such a profound, life-threatening collapse. When AFE was first described more than 70 years ago, it was thought to result from amniotic fluid entering the maternal circulation and obstructing the pulmonary blood flow – thus the name "amniotic fluid embolism." However, research over the decades has consistently discounted this view. As Dr. Benson states, current thinking has shifted away from embolism and toward a maternal immune response to the fetus.

Investigators have suggested possible immunologic mechanisms such as complement activation and reactions similar to anaphylaxis, but more research needs to be done. In the meantime, we must recognize that the name AFE probably does not accurately reflect what actually occurs in these patients.

Management is usually first directed at getting the patient through the initial cardiovascular insults – often hypotension and cardiac arrest – and at treating hypoxia and rapidly correcting maternal hemodynamic instability. Significant teamwork is required for the mother and baby to survive – and to survive neurologically intact. Anesthesia is needed for development and control of the airway, for instance, and critical care is essential for inotropic support. Cardiology also must be involved, as continuous cardiac, respiratory, and blood pressure monitoring – and aggressive respiratory and circulatory support – are key.

The nursing staff also can play a critical role in preventing subsequent pulmonary edema by keeping meticulous records of the intake and output of fluids. The overwhelming insult of AFE to the heart and lungs leaves patients at high risk of developing pulmonary edema, and meticulous record-keeping can help ensure that these patients are not overloaded.

Aggressive blood replacement also is required to reverse the coagulopathy associated with AFE. Transfusion of packed red blood cells is a priority, but fresh frozen plasma, platelets, and cryoprecipitate also should be available for prompt administration.

There have been promising reports of the use of recombinant factor VIIa (rVIIa) for treating hemorrhage in patients with AFE in recent years, but a recent review of case reports of AFE from 2003 to 2009 suggests that the procoagulant may actually worsen outcomes (Anesthesiology 2011;115:1201-8). Indeed, unlike patients with other types of postpartum hemorrhaging, women with AFE have high circulating tissue factor concentrations. Recombinant factor VIIa can combine with tissue factor and form intravascular clots, resulting in thrombosis of major organs.

If the patient is undelivered and has cardiac arrest, an emergency cesarean section is indicated. Prompt delivery during the resuscitation process not only increases the chances of perinatal survival without neurological sequelae, but also improves the maternal resuscitation effort. We have a 4-minute window for delivery from the time the code is called to avoid neurologic injury to the fetus and optimize outcomes for the mother. This 4-minute principle was adopted by the American Heart Association in 1986, and its clinical use has been supported by 20 years of published case reports since then (Am. J. Obstet. Gynecol. 2005;192:1916-21).

Although outcomes with AFE may be improving somewhat, AFE still causes significant morbidity and mortality. Investigators in the Australian AFE cohort study, for instance, recently reported maternal and perinatal fatality rates of 35% and 32%, respectively. These rates were similar to those from the U.K. Obstetric Surveillance System, according to the authors (BJOG 2010;117:1417-21).

Ruptured Uterus

In an effort to reduce rates of cesarean deliveries, obstetricians are swinging back once again to encouraging more women to attempt vaginal birth after cesarean delivery (VBAC). Because the rates of uterine rupture are higher in women who attempt VBAC, our index of suspicion should be acute for any woman who is laboring after having had a prior cesarean delivery. We also must do everything we can to assess a patient’s risks of failed VBAC resulting in emergency cesarean section and uterine rupture.

The American College of Obstetricians and Gynecologists (ACOG) now recommends that most women with one previous cesarean delivery and with a low transverse incision be counseled about VBAC and offered a trial of labor. ACOG points out in its 2010 practice bulletin on VBAC that in several large studies, the uterine rupture rate after a trial of labor in such women was approximately 0.5-0.9%.

The College also says that many women previously considered to be at high risk may now be considered candidates for a trial of labor after cesarean section (TOLAC). Among the conditions that are no longer necessarily contraindications for attempted VBAC: two previous low transverse cesarean deliveries; suspected fetal macrosomia; twin gestations; more than one previous cesarean delivery; a previous low vertical incision; gestation beyond 40 weeks; and even external cephalic version for breech presentation (Obstet. Gynecol. 2010;116:450-63).

The ACOG bulletin addresses the importance of counseling, and mentions the possible utility of a nomogram developed for predicting the chance of successful VBAC for individual patients. The tool incorporates six variables that are ascertainable at the first prenatal visit, including maternal age, body mass index, and history of vaginal delivery (Obstet. Gynecol. 2007;109:806-12). The tool, a calculator of sorts, was developed through research by the National Institute of Child Health and Development’s (NICHD’s) Maternal-Fetal Medicine Units Network, and is also available at http://www.bsc.gwu.edu/mfmu/vagbirth.html.

Such individualized risk assessment is critical. Another model for assessing risk and informing discussions with individual patients is one developed in the United Kingdom by Dr. Gordon C. S. Smith at Cambridge University and his associates (PLoS Med. 2005:2:e252). These investigators documented that women with a predicted cesarean section risk (an unsuccessful trial of labor) of less than 20% using their model had a minimal incidence of uterine rupture of 2.0 per 1,000, while those deemed to have a high risk of cesarean delivery – defined as greater than 40% – had an incidence of uterine rupture of 9.1 per 1,000.

However small it is in absolute terms, there is an inherent risk of the uterine incision rupturing during an attempt at labor after a previous cesarean section. Indicative of this inherent risk are recommendations by the authors of numerous studies, as well as ACOG, for VBAC to be attempted in facilities with staff available for emergency care. When the fetus is actually extruded through the incision and into the abdominal cavity, there is significant risk of severe maternal and perinatal morbidity and mortality secondary to blood loss and hypoxia.

Signs and symptoms of possible uterine rupture include the following: a change in fetal heart rate pattern from normal to a category 3 heart rate tracing; unexplained vaginal bleeding; frequent epidural dosing or pain that is not alleviated with epidural anesthesia already in place; and loss of uterine tone with an intrauterine pressure catheter (IUPC) in place. If an IUPC is flushed and the patient still has abnormal readings, a diagnosis of uterine scar disruption should be entertained.

In addition to prompt recognition, rapid delivery and blood replacement are key to improving outcomes. The coagulopathy in patients with a ruptured uterus is dilutional rather consumptive, so these patients require replacement not only of packed red blood cells but also of clotting factors and other blood products. As with other types of obstetric hemorrhage, blood loss is usually in excess of the amount perceived.

A recent population-based registry study of 94 identified uterine ruptures after previous cesarean section found that almost half of the mothers diagnosed with uterine rupture after TOLAC (versus during elective or emergency prelabor cesarean section) developed moderate postpartum hemorrhage, while 15% developed severe postpartum hemorrhage and 4% needed peripartum hysterectomy (BJOG 2010;117:809-20).

Perinatal complications occurred in 48 of the 81 (59%) ruptures that occurred after attempted VBAC. In nine (19%) cases, the outcomes were serious (three deaths, three cases of severe asphyxia, and three cases of posthypoxic encephalopathy). To reduce the risk of iatrogenic uterine scar disruption, care should be taken in choosing the appropriate method of induction.

Peripartum Cardiomyopathy

This complication is characterized by the development of heart failure due to significant left ventricular (LV) systolic dysfunction. It is a diagnosis of exclusion. Patients present with the same signs and symptoms characterizing other forms of heart failure secondary to LV dysfunction, and other causes of heart disease and forms of heart failure must be ruled out.

This relatively uncommon myocardial complication can occur up to 5-6 months after delivery, but it usually occurs early in the postpartum period, with about 75% of cases presenting within the first month after delivery (Postgrad. Med. J. 2011;87:34-9). Most patients who are diagnosed during pregnancy present in the third trimester.

Various potential etiologies have been proposed – from viral myocarditis and abnormal hormonal regulation, to excessive prolactin production and an abnormal immune response to pregnancy – but its exact cause is still unknown.

Its incidence in the United States may be increasing. According to a recent review by Dr. Uri Elkayam, the incidence is estimated at approximately 1 in 3,200 deliveries, with a significantly higher incidence (up to 16-fold higher in one study) in African American women (J. Am. Coll. Cardiol. 2011;58:659-70).

Rates as high as 1 in 300 in Haiti and 1 in 100 in a small region of sub-Saharan Africa have also been reported in recent years, according to another review by Dr. Meredith Cruz and her associates (Obstet. Gynecol. Clin. N. Am. 2010;37:283-303).

Certainly, we must all be aware that certain ethnic groups and populations – most notably women of African descent – appear to be more at risk. Pregnancy-related hypertension and preeclampsia also are often cited as risk factors, as are multiparity, obesity, and older maternal age.

Diagnosis requires a high index of suspicion and vigilance, especially because many of the symptoms – shortness of breath, increased peripheral edema, and exhaustion, for instance – are similar to typical symptoms of a normal pregnancy. The diagnosis should be strongly considered in any woman who has nocturnal dyspnea. Chest pain, nocturnal cough, new regurgitant murmurs, pulmonary crackles, increased jugular venous pressure, or hepatomegaly also should raise suspicions, according to the review by Dr. Cruz and her associates.

The timing of delivery in patients diagnosed during pregnancy depends on the maternal status. If the mother is responding to medical management and is stable enough with regard to cardiovascular status to tolerate her heart failure, then induction of labor can be scheduled for or considered at 37 weeks’ gestation. If she is unstable or her LV function is poor or worsening, then early delivery should be considered.

Vaginal delivery often is preferable so that the potential risks associated with anesthesia and surgical delivery, such as clots or infection, can be avoided. Sometimes, however, cesarean delivery may be the only option. For a woman who is laboring, it is important to shorten the second stage of labor, with either low forceps or a vacuum device, in order to minimize pushing and ventricular work.

Management requires teamwork with cardiology, intensive care, anesthesiology, and nursing. After delivery, during a patient’s postpartum fluid shift, she should be managed in a critical care unit or another closely observed setting.

The management of peripartum cardiomyopathy – during pregnancy or afterward – is aimed at improving symptoms, slowing the progression of LV dysfunction and heart failure, and preventing arrhythmias and thromboembolism – both common complications.

Diuretics, nitrates, and hydralazine are often indicated and are safe in pregnancy, as is use of the beta-blocker metoprolol and either unfractionated heparin or low-molecular weight heparin for anticoagulation. (Anticoagulants are almost always indicated.) Nonpharmacologically, the focus is on reducing fluid and salt intake and on monitoring electrolyte levels and addressing any imbalances.

On the research front, animal studies and now preliminary data from a very small number of women with acute severe peripartum cardiomyopathy suggest that bromocriptine, an inhibitor of prolactin, may have a favorable effect on outcomes (Circulation 2010;121:1465-73).

Reported mortalities from the disease have ranged as high as 18%-56%, according to the Cruz review. On the other hand, many women will have a full recovery and a normalization of LV function. Dr. Elkayam concludes in his review that a normalization of LV function may occur in more than 50% of women with peripartum cardiomyopathy, mostly within 2-6 months after diagnosis.

Subsequent pregnancy is contraindicated in women who do not have a resolution of LV dysfunction, and even when LV function normalizes, there is a risk of recurrent and persistent dysfunction in a subsequent pregnancy.

Dr. Whiteman is associate professor and interim director of the division of maternal-fetal medicine at the University of South Florida, Tampa. She said she has no relevant financial disclosures.