Anaphylactoid syndrome of pregnancy (ASP) remains a puzzling and deadly condition despite decades of recognition and research. It is a leading cause of maternal mortality,1 yet it likely has been overdiagnosed, with many unexplained peripartum maternal deaths historically attributed to ASP. The aim of this discussion is to shed light on more recent research and our current understanding of this life-threatening obstetric emergency.
Women with ASP may present with the classic triad of hypoxia, hypotension, and coagulopathy resulting in sudden cardiovascular collapse or cardiac arrest.2 In less typical cases, one or more of these signs may be blunted or absent. ASP usually occurs during labor or within minutes of delivery, either vaginal or cesarean. Patients may experience symptoms of anxiety, a sense of impending doom, confusion, or shortness of breath which are accompanied by abnormal vital signs (Table 1), loss of consciousness, or cardiopulmonary arrest.2,3 Seizures may also occur with this condition, which may be mistaken for eclampsia. Fetal heart rate (FHR) tracing and uterine contraction monitoring may reveal uterine tachysystole as a direct result of maternal catecholamine release; this initial shock reaction also includes shunting of uterine blood from the uterus and placenta to transiently maintain blood pressure and perfusion of maternal vital organs. Both of these processes result in signs of fetal hypoxia and FHR abnormalities, which often precede maternal cardiopulmonary manifestations.
Coagulopathy is also a major component of classic ASP, although some patients may expire before their clotting status can be assessed. Disseminated intravascular coagulation (DIC) can result in massive hemorrhage and may be detected clinically by bleeding from the vagina, during cesarean, or from the incision postoperatively, intravenous sites or the bladder (hematuria.) In the acute care setting, presence of coagulopathy may be the only clinical feature distinguishing ASP from massive pulmonary embolism; however, the latter occurs primarily in the postpartum period whereas ASP is primarily an intrapartum condition.
Etiology and mechanism
Most cases of ASP occur peripartum, during labor (70%) or within minutes of delivery (30%).4 Originally, it was hypothesized that fetal squamous cells entering the maternal circulation and obstructing the pulmonary vascular tree were responsible for the hemodynamic manifestations of this condition. This was based on autopsy reports of eight women who died during labor in whom such squamous cells were identified.5 Based on this presumed pathophysiologic mechanism, this syndrome was originally designated amniotic fluid embolism but it is now known as anaphylactoid syndrome of pregnancy (ASP). This is because we now have an improved understanding of the pathophysiology of the condition, based on recent research.2,4
Subsequent studies demonstrated presence of squamous cells in pregnant women with other conditions, and the clinical similarity of this condition to other manifestations of the systemic inflammatory response syndrome (SIRS) cast doubt upon the theory involving squamous cells.6 Recent evidence also demonstrates that an insufficient number of squamous cells exist in amniotic fluid to cause any significant obstruction of the pulmonary vasculature, even were the entire content of the term amniotic cavity infused into the maternal circulation.7
Because the clinical picture of ASP mimics an allergic or proinflammatory reaction, and it occurs at the time when fetal tissue is likely to enter the maternal circulation, it appears that the mechanism of ASP involves an abnormal host (maternal) immunological response to a common physiologic phenomenon. Specifically, fetal antigens enter the maternal circulation during labor or delivery and elicit a proinflammatory response driven by endogenous mediators including cytokines. This SIRS-like process may include pulmonary vasoconstriction, direct pulmonary injury and capillary leak (acute respiratory response syndrome) and depression of myocardial contractility. DIC and hemorrhage are downstream effects of systemic activation of inflammatory mediators and the coagulation cascade. Unfortunately, at present there are no identifiable clinical risk factors for pre-labor identification of at-risk maternal-fetal pairs nor are there any preventative measures for ASP.
The author reports no potential conflicts of interest with regard to this article.
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- Ecker JL, Solt K, Fitzsimons MG, MacGillivray TE. Case records of the Massachusetts General Hospital. Case 40-2012. A 43-year-old woman with cardiorespiratory arrest after a cesarean section. N Engl J Med. 2012;367:2528-36.
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- Clark SL, Pavlova Z, Greenspoon J, Horenstein J, Phelan JP. Squamous cells in the maternal pulmonary circulation. Am J Obstet Gynecol. 1986;154:104-6.
- Funk M, Damron A, Bandi V, Aagaard K, Szigeti R, Clark S. Pulmonary vascular obstruction by squamous cells is not involved in amniotic fluid embolism. Am J Obstet Gynecol. 2018;218:460-1.
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- Australasian Maternal Outcomes Surveillance System Amniotic fluid embolism. Available at: http://www.amoss.com.au/?q¼content/amniotic-fluid-embolism-afe. Accessed May 23, 2018.
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