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Anaphylaxis during pregnancy and delivery

Anaphylaxis during pregnancy and delivery
Literature review current through: Jan 2024.
This topic last updated: Nov 02, 2023.

INTRODUCTION — Anaphylaxis is defined clinically as "a serious allergic or hypersensitivity reaction that is rapid in onset and may cause death" [1]. In pregnancy, it can be catastrophic for both parent and fetus [2]. This topic will review issues specific to anaphylaxis during pregnancy, delivery, and early breastfeeding.

PREVALENCE — The lifetime prevalence of anaphylaxis in the general population is estimated as 0.05 to 2 percent [3-6]. Data regarding the prevalence among pregnant women are limited. A prospective study from the United Kingdom reported 1.6 cases per 100,000 pregnancies (95% CI 1.1-2.2) [7]. Retrospective studies have found rates of 2.6 to 3.8 per 100,000 pregnancies [8-10]. Risk factors for anaphylaxis during pregnancy were found to be cesarean delivery and a personal history of allergy [10].

CLINICAL MANIFESTATIONS — Observations about anaphylaxis during pregnancy, delivery, and breastfeeding are largely derived from case reports and small series [2,8,11-13]. The clinical manifestations of anaphylaxis do not appear to be altered by pregnancy. (See "Anaphylaxis: Emergency treatment".)

The term "anaphylactoid" is no longer recommended for use, and anaphylactic and anaphylactoid reactions do not need to be distinguished with respect to diagnosis and acute treatment [1,6].

Presentation in the pregnant patient — Anaphylaxis may present with any combination of approximately 40 symptoms and signs (table 1). Only a few symptoms and signs may be present. Two or more organ systems are typically involved. In pregnant patients, it is particularly important to recognize symptoms and signs that involve the uterus and fetus (figure 1) [1,2].

The most common symptoms and signs of anaphylaxis are:

Cutaneous symptoms, including flushing, itching, urticaria, and angioedema (including periorbital edema and conjunctival swelling).

Respiratory symptoms, including nasal discharge, nasal congestion, change in voice quality, sensation of throat closure or choking, cough, wheeze, and dyspnea.

Gastrointestinal symptoms, including nausea, vomiting, diarrhea, and crampy abdominal pain.

Cardiovascular symptoms, including dizziness, tachycardia, hypotension, and collapse.

Anaphylaxis may also present with vulvar and/or vaginal itching, uterine cramping, and lower back pain, presumably as a result of degranulation of mast cells in the walls of the vagina and uterus, which are rich in these cells. Pregnant women have been reported to have contractions following severe allergic reactions and anaphylaxis [2,14]. Symptoms related to reproductive organs generally occur along with symptoms in other organ systems, rather than alone.

Fetus — Maternal immunoglobulin E (IgE) does not normally cross the placenta, and, in resource-abundant countries where parasites are not endemic, fetal blood usually does not contain significant amounts of allergen-specific IgE [11]. However, maternal anaphylaxis can lead to fetal hypoxemia, acidosis, hypoxic ischemic encephalopathy, and death if uterine blood flow and maternal oxygenation are significantly compromised. (See 'Consequences' below.)

TRIGGERS — In a systematic review, beta-lactam antibiotics, latex, and anesthetic agents were the most common triggers [15]. However, any agent that can trigger anaphylaxis in the nonpregnant state can potentially trigger it in a susceptible pregnant person [2,8,12,14].

Antibiotics — Antibiotics administered before cesarean delivery for prophylaxis against surgical-site infection or during labor for prophylaxis against early-onset group B streptococcal infection are the most commonly reported triggers of anaphylaxis during pregnancy [7,12,13,16-23]. These medications include penicillin [12,23], ampicillin [18,20,21], cefazolin [19,22], and ceftriaxone [16].

Anesthetic agents — Medications used for neuraxial and general anesthesia can cause anaphylaxis [24,25]. Neuromuscular blocking agents, such as suxamethonium, are the most common causes. In a study of anaphylaxis-related mortality in the obstetrical setting from France [26], suxamethonium was a suspected cause in all five pregnant women whose deaths were attributed to anaphylaxis. (See "Perioperative anaphylaxis: Clinical manifestations, etiology, and management", section on 'Neuromuscular-blocking agents'.)

Local anesthetics used for neuraxial anesthesia can cause vasovagal responses, tachycardia, lightheadedness, metallic taste, and perioral numbness, but these signs and symptoms are more likely the result of accidental intravascular injection rather than an immune-mediated reaction. Anaphylactic reactions to local anesthetics are extremely rare, and true allergic reactions account for less than 1 percent of all drug reactions to local anesthetics. The most common immune-mediated reaction to local anesthetics is a delayed hypersensitivity reaction or contact dermatitis [27,28]. (See "Perioperative anaphylaxis: Clinical manifestations, etiology, and management", section on 'Etiologies' and "Allergic reactions to local anesthetics".)

Oxytocin — Anaphylaxis to synthetic oxytocin (eg, Pitocin, Syntocinon [brand names]) has been reported [29-37]. Positive-immediate (read at 20 minutes) [33], delayed (read at five days) [32], and negative [31] skin tests to oxytocin have been described in these patients. In some cases, the reactions may have been due to concurrent latex exposure [35,36], and, in another case, symptoms may have been attributable to chlorbutol, an "inactive" ingredient in the oxytocin preparation [37].

Intravenous iron — Intravenous iron is sometimes preferable to oral preparations. The safety of intravenous iron preparations has greatly improved because high-molecular-weight iron dextran is no longer available in most of the world. Administration of iron dextran was associated with anaphylaxis and shock, including fatal events. The availability of intravenous iron formulations with improved safety profiles has lowered the threshold at which many clinicians would consider prescribing intravenous iron. (See "Anemia in pregnancy", section on 'Intravenous iron' and "Treatment of iron deficiency anemia in adults", section on 'Oral versus IV iron'.)

Laminaria — Osmotic dilators are used in pregnancy for gradual cervical dilation. Laminaria japonica is a type of osmotic dilator derived from seaweed; it has rarely been associated with anaphylaxis. Conversely, Dilapan-S is a synthetic osmotic dilator made from a polyacrylate-based hydrogel; it has not been associated with hypersensitivity reactions [38].

Misoprostol — Misoprostol is a synthetic prostaglandin E1 that causes dissolution of collagen bundles and an increase in the submucosal water content of the cervix, resulting in a cervical state that is associated with greater success when labor is induced with oxytocin. Prostaglandins also cause the uterus to contract and may initiate labor. Anaphylaxis following buccal misoprostol administration has been reported [37].

Natural rubber latex — Sensitization to latex appears to occur more frequently in females than in males, and obstetric and gynecologic procedures are common settings for latex anaphylaxis in females in their reproductive years [39,40]. As noted above, oxytocin and vasopressin may potentiate the effects of latex hypersensitivity in obstetric patients, and homology between latex and oxytocin and vasopressin may play a role [41]. (See "Latex allergy: Epidemiology, clinical manifestations, and diagnosis".)

RhD immunoglobulin G (anti-D) — Hypersensitivity reactions, including features of anaphylaxis, have occasionally been reported after administration of anti-D immunoglobulin to pregnant women. However, careful evaluation of three cases of suspected anti-D immunoglobulin reactions suggested other causes for their reactions or loss of sensitivity since all three patients were eventually able to tolerate the drug [42]. The investigators proposed using a skin test and drug challenge protocol in patients with suspected anti-D immunoglobulin sensitivity.

Breastfeeding — Breastfeeding has been implicated as a trigger of anaphylaxis in several case reports, sometimes in association with the administration of nonsteroidal antiinflammatory drugs, which are also potential anaphylaxis triggers [43-47]. The mechanism underlying breastfeeding anaphylaxis is unclear. Skin testing with oxytocin and breast milk were performed in some of the cases described above, with negative results [43,45]. Changing levels of progesterone and/or prolactin were suggested as possible predisposing factors [45].

Other — As in nonpregnant individuals, venom from stinging Hymenoptera insects (eg, honey bees, yellowjackets, hornets, wasps, or ants, including fire ants) and ingestion of foods (eg, shellfish, peanuts, or tree nuts) can cause anaphylaxis during pregnancy [48-51]. (See "Bee, yellow jacket, wasp, and other Hymenoptera stings: Reaction types and acute management" and "Seafood allergies: Fish and shellfish".)

Some patients have no obvious trigger and are considered to have idiopathic anaphylaxis. (See "Idiopathic anaphylaxis".)

DIAGNOSIS — The clinical diagnosis of anaphylaxis during pregnancy is similar to the diagnosis in nonpregnant patients and is based on a meticulous history and physical examination. Diagnostic criteria for anaphylaxis have been defined and validated and can be applied to pregnant patients (table 2 and figure 1) [1,2]. (See "Anaphylaxis: Emergency treatment".)

Laboratory tests — In some but not all patients, the clinical diagnosis of anaphylaxis can be confirmed by an elevated serum total tryptase level measured in a blood sample drawn shortly after the onset of symptoms. Blood for serum tryptase is optimally obtained 15 minutes to three hours after symptom onset. Any elevation in serum tryptase provides evidence of mast cell activation and thus supports a diagnosis of anaphylaxis, although elevated tryptase levels have also been reported in amniotic fluid embolism [52]. However, in some patients with anaphylaxis, (eg, those with food-triggered anaphylaxis or those who are normotensive), elevations in tryptase generally do not occur. A normal tryptase level cannot be used to refute the diagnosis of anaphylaxis [2,6,53].

The serum tryptase assay is standardized (in contrast to the histamine assay) and is widely available in clinical laboratories, although results can seldom be obtained on an urgent basis. The interpretation of tryptase levels and other tests that can support the diagnosis of anaphylaxis are reviewed in detail separately. (See "Laboratory tests to support the clinical diagnosis of anaphylaxis".)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of anaphylaxis during pregnancy includes all of the disorders that can mimic aspects of anaphylaxis in nonpregnant individuals (table 3), as well as some disorders unique to pregnancy, labor, and delivery (table 4) [2]. The differential diagnosis of anaphylaxis is reviewed in more detail separately. (See "Differential diagnosis of anaphylaxis in adults and children".)

Other causes of laryngeal edema — Laryngeal obstruction, a frequent and potentially life-threatening symptom of anaphylaxis, must be differentiated from the laryngeal edema associated with preeclampsia, as well as that caused by laryngopathia gravidarum.

Preeclampsia – Laryngeal edema associated with hypertension and proteinuria after 20 weeks gestation suggests preeclampsia. Most cases are asymptomatic and noted at intubation before cesarean delivery. However, difficulty breathing has been described in case reports. (See "Preeclampsia: Clinical features and diagnosis".)

Laryngopathia gravidarum – Laryngopathia gravidarum refers to the changes in laryngeal function observed in pregnancy. In the acute type, symptoms of dyspnea, hoarseness, sore throat, and painful swallowing occur just prior to delivery, and laryngeal examination reveals edema. In the chronic form, the symptoms are similar but begin earlier in pregnancy and persist [54]. (See "Recognition and management of allergic disease during pregnancy", section on 'Urticaria and angioedema'.)

Hereditary angioedema – Laryngeal obstruction also occurs in hereditary angioedema (HAE), but laryngeal stridor usually develops over hours rather than minutes. In addition, patients often have a history of recurrent unexplained abdominal pain or episodes of cutaneous swelling. There may also be a family history of HAE. Urticaria (hives) and itching are not present in HAE but are common features of anaphylaxis. (See "Hereditary angioedema: Epidemiology, clinical manifestations, exacerbating factors, and prognosis" and "Hereditary angioedema (due to C1 inhibitor deficiency): Pathogenesis and diagnosis".)

Other causes of hypotension — Hypotension may be a prominent feature of severe anaphylaxis and must be differentiated from other causes of hypotension during pregnancy, such as neuraxial block (epidural or spinal), hemorrhage, and amniotic fluid embolism [2]. In hypotensive patients with minimal vaginal bleeding, the possibility of internal hemorrhage should be excluded, especially after operative delivery. The sudden onset of skin symptoms and signs (such as pruritus, urticaria, and angioedema) or respiratory symptoms and signs (such as stridor or wheezing) in addition to hypotension strongly supports a diagnosis of anaphylaxis.

Amniotic fluid embolism syndrome — Amniotic fluid embolism syndrome is an important cause of acute cardiovascular collapse during pregnancy and can be difficult to distinguish clinically from anaphylaxis. This entity is reviewed briefly here and described in detail separately. (See "Amniotic fluid embolism".)

Suggested criteria for amniotic fluid embolism syndrome include one or more of the clinical findings of sudden-onset cardiovascular collapse, respiratory distress, or disseminated intravascular coagulation during pregnancy and absence of other medical explanations for the clinical course.

Bronchospasm is characteristic of anaphylaxis rather than amniotic fluid embolism [55], while large volume blood loss should raise suspicion for amniotic fluid embolism. Coagulopathy and/or disseminated intravascular coagulation are more often associated with amniotic fluid embolism, although activation of both the contact system and the coagulation system can also occur in anaphylaxis [53,56].

Amniotic fluid embolism has been termed "anaphylactoid syndrome of pregnancy" by some authors [57]. The proposed mechanism is a non-IgE-mediated reaction to fetal antigens, leading to mast cell degranulation and release of histamine and tryptase. An elevated beta-tryptase level was reported in one fatal case [52]. Complement activation has also been suggested as a possible mechanism [58]. Blood tests for sialyl-Tn may also be helpful in diagnosis, as this is a possible marker for severe amniotic fluid embolism and appears to be predictive for life-threatening or fatal episodes [55]. Tryptase levels may be increased in amniotic fluid.

CONSEQUENCES — Case reports and small series of anaphylaxis during pregnancy generally show good maternal outcomes, although maternal morbidity (eg, abnormal kidney function or kidney failure, increased liver enzymes, disseminated intravascular coagulation, severe hypotension, acute respiratory distress syndrome) and death have been reported [7,12,13,16,26,27,48-50,59,60].

In contrast, available reports suggest that the fetus/neonate is at risk of neurologic damage and/or death, even when the maternal outcome is favorable [2].

Maternal blood passing through the uteroplacental interface releases oxygen as a function of the magnitude of the partial pressure of oxygen (PO2) difference between the fetal and maternal circulation. The uterine artery is nearly completely dilated to maximize blood flow and oxygen delivery to the fetus. The fetus can compensate for decreased blood flow by increasing oxygen uptake, redistributing circulation to vital organs (brain, heart, adrenal glands, placenta), decreasing gross body movements, and increasing tissue oxygen extraction. However, eventually these compensatory mechanisms can be exceeded, resulting in fetal hypoxemia and acidosis [61,62].

Maternal anaphylaxis affects the fetus in several ways:

Maternal hypoxemia directly reduces the oxygen supply for the fetus.

Maternal hypotension reduces uterine perfusion, which in turn reduces oxygen supply to the fetus.

Maternal alkalosis decreases uterine blood flow by vasoconstriction and increases the affinity of maternal hemoglobin for oxygen, which reduces the oxygen supply for the fetus.

As a result, anaphylaxis may lead to fetal asphyxia or death [61,62]. Neonates may develop rigidity of the extremities, seizure-like movements, brain damage, and/or hypoxic encephalopathy, potentially leading to long-term neurodevelopmental morbidity or death. In most cases, the risk of these consequences can be reduced or eliminated with early recognition of maternal anaphylaxis and prompt administration of epinephrine [27]. (See "Etiology and pathogenesis of neonatal encephalopathy".)

MANAGEMENT

The pregnant patient — With a few modifications, the medical management of anaphylaxis during pregnancy is the same as in nonpregnant patients. Prompt administration of epinephrine is critical. The dosing and route of administration of epinephrine may vary according to the setting:

In the ambulatory or emergency department setting, intramuscular injection of epinephrine is the safest and most effective means of delivery. A brief overview of anaphylaxis treatment is provided in the table (table 5) [2]. A more detailed presentation of the diagnosis and treatment of anaphylaxis is found elsewhere. (See "Anaphylaxis: Emergency treatment", section on 'Immediate management'.)

In the operative setting, epinephrine is usually given by intravenous bolus or infusion, using the more dilute preparation intended for intravenous infusion (table 6). (See "Perioperative anaphylaxis: Clinical manifestations, etiology, and management", section on 'Initial management'.)

Measures specific to pregnant patients — There are three modifications to the management of anaphylaxis that are important in pregnant patients [2]:

Positioning the patient on their left side to prevent compression of the aortocaval vessels by the gravid uterus.

Maintaining a minimum maternal systolic blood pressure of 90 mmHg to maintain adequate uteroplacental perfusion.

Monitoring the fetal heart rate to assess the fetal status in response to maternal treatment. (See 'Fetal monitoring' below and 'Emergency cesarean delivery' below.)

Overviews of management in pregnant patients are provided (figure 2 and table 7).

Epinephrine — Epinephrine is considered the drug of choice in the treatment of anaphylaxis in both nonpregnant and pregnant patients [15,63]. No alternative drug more completely treats the physiologic manifestations of anaphylaxis.

The correct dosing and administration of epinephrine are discussed in more detail separately [2,63-67]. (See "Anaphylaxis: Emergency treatment", section on 'Epinephrine' and "Anaphylaxis: Emergency treatment", section on 'Dosing and administration' and "Perioperative anaphylaxis: Clinical manifestations, etiology, and management", section on 'Management'.)

After the epinephrine injection, ambulatory patients should not suddenly sit upright or stand, as this can lead to cardiac arrest due to the empty inferior vena cava/empty ventricle syndrome [64].

Even though epinephrine has the potential to reduce uterine blood flow through alpha-adrenergic-mediated blood vessel vasoconstriction [12], evidence of fetal harm in humans is limited and confounded by the disease state necessitating epinephrine administration.

Infant deaths and neurologic abnormalities have been associated with maternal epinephrine treatment of anaphylaxis during pregnancy. However, these adverse outcomes are likely due to fetal asphyxia related to severe anaphylaxis itself rather than to epinephrine treatment. Furthermore, healthy infants have been delivered to a number of pregnant women who were treated with epinephrine for anaphylaxis, including one patient who received a continuous intravenous epinephrine infusion for 3.5 hours to treat refractory anaphylaxis during labor [20]. Moreover, perinatal deaths or infant neurologic abnormalities have occurred in women with anaphylaxis who were not treated with epinephrine, as described previously.

A few case reports have suggested ephedrine by the intravenous route as an alternative to epinephrine during anaphylaxis in pregnancy [12]. Ephedrine is a noncatechol sympathomimetic with alpha- and beta-adrenergic effects. However, it is a less potent vasoconstrictor and bronchodilator than epinephrine, and its administration has been associated with increased fetal distress and acidosis when compared with other vasopressors [68,69]. Additionally, intravenous formulations of ephedrine are not universally available. Thus, epinephrine remains the recommended agent to treat anaphylaxis during pregnancy.

Supplemental oxygen — Supplemental oxygen, 8 to 10 liters by facemask, up to 100 percent, should be administered (table 7 and figure 2) [2]. Supplemental oxygen is important because epinephrine, like other alpha-1 adrenergic vasoconstrictors, can potentially worsen the ventilation/perfusion ratio [68].

Fluid resuscitation — Adequate intravascular volume repletion is important to treat hypotension and maintain uteroplacental perfusion (table 7) [2]. (See "Anaphylaxis: Emergency treatment".)

The patient should be placed on their left side to prevent added positional hypotension resulting from compression of the aortocaval vessels by the gravid uterus.

Impending or existing hypotension must be promptly reversed with large volumes of intravenous fluids, preferably crystalloid (eg, normal [isotonic] saline) [70]. In nonpregnant adults with anaphylaxis, 1 to 2 liters of normal saline may be needed in the first 30 minutes of treatment. The rate of infusion should be titrated against blood pressure, cardiac rate and function ascertained by continuous noninvasive monitoring, and urine output. Glucose-containing solutions should be avoided, as these fluids can result in a large glucose bolus, which can reduce umbilical cord pH and can cause neonatal hypoglycemia.

A minimum systolic blood pressure of 90 mmHg should be maintained to ensure adequate placental perfusion and fetal oxygenation since uterine blood flow is not autoregulated.

Other measures — Adjunctive treatments for anaphylaxis include inhaled bronchodilators, H1 antihistamines, H2 antihistamines, and glucocorticoids [71-73]. (See "Anaphylaxis: Emergency treatment".)

Bronchodilators – A selective beta2-adrenergic agonist, such as albuterol, may be administered by nebulizer and facemask if wheezing and/or coughing are prominent symptoms.

Systematic reviews of H1 antihistamines, H2 antihistamines, and glucocorticoids in anaphylaxis have failed to identify any randomized, controlled trials that meet the inclusion criteria. These medications can be used as add-on treatments in anaphylaxis but should not replace epinephrine and should not be given as initial treatment or sole treatment in anaphylaxis [70-72].

H1 antihistamines – H1 antihistamines treat itching and hives, but these agents do not prevent or relieve upper or lower airway obstruction and do not prevent or relieve shock and therefore should not be used as initial or sole treatment. The safety of H1 antihistamines in pregnancy was affirmed in a meta-analysis that examined the association between antihistamine use and major congenital malformations [74]. In this review of 24 controlled studies, including over 200,000 first trimester exposures, exposure to H1 antihistamines was associated with a lower risk of malformations (odds ratio [OR] 0.76, 95% CI 0.60-0.94). In most cases, the H1 antihistamines were being taken to treat nausea and vomiting of pregnancy.

Diphenhydramine (50 mg intravenously) can be given to decrease hives and itching if a parenteral agent is desired. No second-generation H1 antihistamine is available in a parenteral formulation.

Among oral agents, the second-generation H1 antihistamines, cetirizine and loratadine, are preferred over other oral H1 antihistamines for use in pregnancy because of reassuring pregnancy safety data and because second-generation agents are significantly less likely to impair central nervous system function and cause sedation or other adverse effects [75]. Loratadine (and other nonimpairing, nonsedating H1 antihistamines) are minimally excreted in breast milk [76].

H2 antihistamines – H2 antihistamines, in combination with H1 antihistamines, decrease skin symptoms and signs but are not lifesaving [70].

Glucocorticoids – A glucocorticoid (eg, methylprednisolone 1 mg/kg intravenously every eight hours for two or three doses) can be administered to patients with severe anaphylaxis to reduce the risk of protracted anaphylaxis, although efficacy is unproven, and doses are extrapolated from asthma treatment [72].

Fetal monitoring — In addition to continuous electronic monitoring of the patient's heart rate, blood pressure, electrocardiogram, and oxygenation, we suggest continuous electronic fetal heart monitoring of potentially viable fetuses in pregnancies complicated by anaphylaxis. Fetal heart rate monitoring can be a more sensitive assessment of maternal cardiorespiratory status than parental vital signs, as parental hemodynamic stability does not guarantee that placental perfusion and fetal oxygenation are optimal [2]. (See "Intrapartum fetal heart rate monitoring: Overview".)

Nonreassuring fetal heart rate patterns (category II and III fetal heart rate tracings) during anaphylaxis are managed by correcting parental hypotension and/or hypoxemia with aggressive medical management of the pregnant patient. However, achieving stable parental hemodynamic status does not guarantee appropriate placental perfusion and fetal oxygenation, so the abnormal pattern may persist and necessitate cesarean delivery [27] (see 'Emergency cesarean delivery' below). If the abnormal fetal heart rate pattern resolves, it has been recommended that continuous fetal monitoring be continued for 48 to 72 hours following anaphylaxis [60].

Emergency cesarean delivery — Emergency cesarean delivery should be considered in the setting of a nonreassuring fetal heart rate tracing that is unresponsive to parental and fetal resuscitative interventions [2]. (See "Intrapartum category I, II, and III fetal heart rate tracings: Management", section on 'General approach'.)

Cesarean delivery can have beneficial parental effects because emptying the uterus when the fundus reaches or exceeds the level of the umbilicus reduces aortocaval compression and increases cardiac output. In the case of maternal cardiac arrest, the goal is delivery of the fetus within five minutes of arrest (see "Sudden cardiac arrest and death in pregnancy", section on 'Delivery as part of the resuscitation process'). However, the potential benefits of emergency cesarean delivery in patients with anaphylaxis refractory to medical treatment need to be balanced against the potential parental risks of surgery in an unstable patient with hypoxemia, and/or hypotension [2]. In addition, the potential benefits should be balanced against neonatal morbidity and mortality secondary to prematurity when the gestation is remote from term [2].

Refractory anaphylaxis — Patients with anaphylaxis that is not responding completely to initial management should be admitted to an intensive care unit without delay. There are no published prospective studies on the optimal management of anaphylaxis with hypotension refractory to initial treatment with epinephrine and intravenous fluid resuscitation.

Anaphylactic shock displays features of both distributive (vasodilatory) and hypovolemic shock. The management of severe forms of these types of shock is discussed separately. A systematic review of crystalloids versus colloids in fluid resuscitation based on mortality data from randomized, controlled trials in more than 20,000 critically ill surgical patients has revealed that colloid administration does not correlate with increased survival in distributive shock [70]. (See "Sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis" and "Hypovolemic shock in children in resource-abundant settings: Initial evaluation and management" and "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Vasopressors' and "Treatment of severe hypovolemia or hypovolemic shock in adults".)

PREVENTION — Strategies for the prevention of anaphylaxis during pregnancy primarily involve identification, confirmation, and avoidance of the specific allergen triggers to which the patient is sensitive, including foods, medications, insect stings, and natural rubber latex. This begins with a thorough medical history, as described below. Patients with histories of reactions to latex or agents that may be required during pregnancy (eg, beta-lactam antibiotics, local anesthetics, or neuromuscular blocking drugs) should be referred to an allergy specialist for evaluation, ideally before pregnancy, so that testing and challenge procedures can be done, if needed [2]. Most allergists defer noncritical skin testing in pregnant patients until after delivery.

Patients with drug allergies — Pregnant patients should be questioned carefully about past adverse drug reactions. Specific questions that help uncover important information about past reactions are reviewed separately. (See "An approach to the patient with drug allergy", section on 'Clinical history'.)

Patients with a history of adverse reactions to penicillins who need these drugs can be managed in several ways:

If this history is obtained in advance, referral to an allergy specialist should be arranged. Skin testing and graded challenge have traditionally been avoided during pregnancy because of the small but definite risk that the procedure can induce a systemic allergic reaction. However, two studies of 136 and 220 pregnant women who underwent penicillin testing concluded that penicillin allergy skin testing and challenge was safe during pregnancy [77,78]. In exceptional circumstances, desensitization has also been safely performed in pregnant women [79,80]. One scenario in which this is indicated is the need to administer penicillin to a penicillin-allergic pregnant woman for treatment of syphilis and prevention of congenital syphilis [81]. (See "Syphilis in pregnancy", section on 'Role of nonpenicillin regimens'.)

Another situation in which possible penicillin allergy in a pregnant patient requires careful consideration is the need to treat following a positive culture for group B Streptococcus. This is discussed in detail separately. (See "Prevention of early-onset group B streptococcal disease in neonates", section on 'Patients with penicillin allergy'.)

If referral to an allergist or skin testing is not possible, an antibiotic that does not cross-react with the suspect culprit antibiotic should be given. (See "Prevention of early-onset group B streptococcal disease in neonates", section on 'Patients with penicillin allergy'.)

Patients with natural rubber latex allergy — Pregnant patients should be questioned about possible latex allergy and about past reactions to common latex-containing objects [82]. These objects include latex gloves, balloons, condoms, pacifiers, teethers, bottle nipples, and adhesives for hair extensions. Objects commonly used in medical procedures include latex gloves, balloon-tipped catheters (eg, used during barium enema examination, pulmonary artery catheterization), and dental cofferdams. (See "Latex allergy: Epidemiology, clinical manifestations, and diagnosis".)

The management of patients with latex allergy primarily involves the provision of care in a latex-free environment. (See "Latex allergy: Management".)

Patients with insect sting allergy — Patients with possible systemic allergic reactions to insect stings (eg, honey bees, yellowjackets, hornets, and wasps ) should be evaluated by an allergy specialist to see if they are candidates for immunotherapy with standardized stinging insect venom (VIT). VIT involves a series of subcutaneous injections with standardized insect venoms administered over a period of three to five years. It significantly reduces the patient's risk of anaphylaxis or other systemic reactions to stinging insect venom and provides protection for years after injections are discontinued [2,83].

Tests for VIT and initiation of VIT are not typically performed during pregnancy due to the small but definite risk of anaphylaxis during the initial dose escalation. However, if a patient becomes pregnant while receiving maintenance VIT, when doses are not changing, it may be safely continued [2]. VIT is discussed separately. (See "Hymenoptera venom immunotherapy: Efficacy, indications, and mechanism of action", section on 'Pregnant women'.)

Emergency preparedness — Pregnant patients who are at risk of anaphylaxis in the community setting should be counseled to take the following precautions [2]:

Carry one or more epinephrine autoinjectors at all times. Patients should be trained in how to use an epinephrine autoinjector correctly and when to use it [67]. (See "Prescribing epinephrine for anaphylaxis self-treatment" and "Patient education: Using an epinephrine autoinjector (Beyond the Basics)".)

Carry an anaphylaxis emergency action plan at all times. This document should be developed with input from the patient and should describe the importance of prompt intramuscular injection of epinephrine, laying the patient on their left side, and calling 911 or emergency medical services (Anaphylaxis Emergency Action Plan - English) (Anaphylaxis Emergency Action Plan - Spanish).

Obtain a medical identification bracelet or necklace listing their known allergies and any relevant comorbidities (eg, asthma, cardiovascular conditions, mastocytosis, or idiopathic mast cell activation syndrome).

Provide all of their health care providers with documentation of known allergies and any relevant comorbidities.

In addition, referral to an allergy specialist should be arranged. The immediate and long-term care of patients with anaphylaxis is presented in detail elsewhere. (See "Anaphylaxis: Emergency treatment", section on 'Follow-up care' and "Anaphylaxis: Confirming the diagnosis and determining the cause(s)".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Anaphylaxis".)

SUMMARY AND RECOMMENDATIONS

Prevalence – Anaphylaxis is not common during pregnancy. However, it is important to recognize it rapidly and treat it effectively as the parental hypoxia and hypotension that can result may be catastrophic to both parent and fetus. (See 'Introduction' above.)

Clinical manifestations – Anaphylaxis may present with various combinations of up to 40 potential symptoms and signs (table 1). Common features include pruritus (sometimes involving the vagina and vulva), urticaria, angioedema, bronchospasm, tachycardia, and hypotension. In pregnant patients, anaphylaxis may also induce lower back pain, uterine cramping, nonreassuring fetal heart rate, and preterm labor (figure 1). Fetal asphyxia, hypoxic ischemic encephalopathy, or death can occur. (See 'Clinical manifestations' above.)

Etiologies – Triggers of anaphylaxis in pregnancy include those that typically induce it in community settings (eg, foods, drugs, or insect stings) and those that are specifically encountered in medical settings, including labor and delivery, such as latex, antibiotics, and neuromuscular blocking drugs. Rarely, breastfeeding may also trigger anaphylaxis. (See 'Triggers' above.)

Diagnosis and differential diagnosis – The diagnosis of anaphylaxis in pregnancy is based on the clinical history and on physical signs (table 2). It is sometimes confirmed by laboratory tests, such as an elevated serum total tryptase level. However, a tryptase level that is within normal limits cannot be used to refute the diagnosis. (See 'Diagnosis' above and 'Differential diagnosis' above.)

Impact on the fetus – Parental hypoxemia and hypotension in anaphylaxis are associated with a high risk of fetal asphyxia or death, even when the parental outcome is favorable. (See 'Consequences' above.)

Importance of epinephrine – Medical management of anaphylaxis in a pregnant patient is similar to that in the nonpregnant patient and involves prompt intramuscular or intravenous injection of epinephrine, adequate supplemental oxygen, and intravenous fluid resuscitation (table 7 and figure 2). The fetal heart rate should be monitored if the fetus has reached a viable gestational age. (See 'Management' above.)

Prevention – Prevention of anaphylaxis during pregnancy begins with a careful history to uncover any past allergic reactions that may provide clues about potential allergies to foods, medications, insect stings, latex, or other allergens. Patients with past anaphylaxis should prepare for a potential recurrence (ie, epinephrine autoinjector, anaphylaxis emergency action plan, and medical identification). (See 'Prevention' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges F Estelle R Simons, MD, FRCPC, who contributed to earlier versions of this topic review.

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Topic 393 Version 24.0

References

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