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Anaphylaxis-induced premature uterine contractions: a case report and literature review

BMC Pregnancy and Childbirth volume 24, Article number: 197 (2024) Cite this article

Abstract

Background

Preterm labor is caused by multiple etiologies, including intra-amniotic infection and/or intra-amniotic inflammation, vascular disorders, cervical disease, decidual senescence, and breakdown of maternal–fetal tolerance. Accumulating evidence in vivo and in vitro has shown that an allergic reaction, including anaphylaxis, can induce preterm uterine contractions. This report describes a case of a pregnant woman who developed anaphylaxis and regular uterine contractions after the ingestion of a strawberry-coated biscuit. We also review the mechanism of allergic reaction (hypersensitivity)-induced preterm labor.

Case presentation

A 31-year-old woman (gravida 1, para 0) at 30+2 weeks of gestation was admitted to the labor and delivery unit with regular uterine contractions and anaphylactic symptoms after she ingested a strawberry-coated biscuit as a snack. The uterine contractions resolved after the treatment of anaphylaxis by administering antihistamines and epinephrine. The patient subsequently delivered at 39+3 weeks of gestation. The amniotic fluid profile showed no infection or inflammation. A postpartum skin-prick test confirmed a positive type 1 hypersensitivity reaction to the strawberry-coated biscuit.

Conclusions

We report a case of anaphylaxis-induced uterine contractility in which uterine contractions subsided after the treatment of anaphylaxis. The absence of intra-amniotic infection and/or intra-amniotic inflammation and the cause of the anaphylaxis were confirmed. Our findings indicate that maternal allergic reactions may be one of the mechanisms of preterm labor.

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Background

Preterm birth is the leading cause of neonatal mortality globally [1,2,3,4,5,6,7]. Multiple pathological mechanisms, such as intra-amniotic inflammation, intra-amniotic infection, vascular disorders, cervical disease, decidual senescence, and breakdown of maternal–fetal tolerance, lead to spontaneous preterm delivery [1, 8,9,10,11]. Among these mechanisms, intra-amniotic infection and/or intra-amniotic inflammation is causally linked to preterm delivery [10, 12,13,14,15,16,17]. Accumulating evidence has shown that a maternal allergic reaction, including anaphylaxis, can induce preterm uterine contractions, which resolve after treatment of the allergic reaction, and the patient subsequently delivers at term gestation [18, 19]. The mechanism responsible for uterine contractions is thought to be myometrial contractility induced by degranulation of mast cells (effector cells of type 1 hypersensitivity) [18]. Anaphylaxis is a rare complication of pregnancy with an incidence rate ranging from 1.6 to 2.7/100,000 deliveries [20,21,22,23]. Common causes of anaphylaxis during pregnancy include the use of antibiotics and food allergies [21, 23]. This condition is associated with maternal hypotension and hypoxemia, which are potentially life-threatening to the mother and fetus [23]. Anaphylaxis is initially managed by immediate improvement of the maternal airway, eliminating causative agents, and administering drugs, such as anti-histamines, epinephrine, glucocorticoids, and vasopressors [19,20,21,22,23]. These drugs can be used safely without major side effects in pregnancy.

We report a case of a pregnant woman who developed systemic anaphylaxis and regular uterine contractions after ingestion of a strawberry-coated biscuit. Her uterine contractions subsided after the administration of antihistamines and epinephrine without the administration of tocolytic agents. Subsequently, she delivered uneventfully at term (39+3 weeks’ gestation). No intra-amniotic infection or intra-amniotic inflammation was associated with the uterine contractions. The cause of anaphylaxis was confirmed at postpartum. We also discuss the mechanism of anaphylaxis implicated in preterm labor.

Case presentation

A 31-year-old gravida 1, para 0, Thai woman at 30+2 weeks of gestation presented to the labor and delivery unit with regular uterine contractions together with an acute onset of generalized hives, pruritus, flushing, and swollen lips. Her antenatal care had been unremarkable. Prior to this pregnancy, she had several episodes of urticaria, but she had never investigated the cause of the rash. Six hours before hospital admission, she developed nasal and throat itching, tightness in the chest, shortness of breath, nausea, and vomiting. She also developed swollen lips and tongue, and an itchy, urticarial rash that began at her face and trunk and radiated to the upper and lower extremities (Fig. 1). These symptoms occurred suddenly after snacking on a strawberry-coated biscuit. She also reported an episode of regular abdominal cramping every 3 minutes. Her physician administered chlorpheniramine 10 mg intravenously and referred the patient to our hospital because of the presentation of preterm uterine contractions.

Fig. 1
figure 1

Urticarial rash on the patient’s abdomen. Photo courtesy of Dr. Piya Chaemsaithong, with permission

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At the labor and delivery unit (6 hours after the onset of symptoms), the patient complained of shortness of breath and abdominal cramps. Her vital signs showed tachycardia with a heart rate of 120 beats/minute and tachypnea with a respiratory rate of 24 breaths/minute. Her blood pressure was 100/60 mmHg. At a physical examination, inspiratory and expiratory wheezing in both lungs was observed. Facial swelling, erythema, edema, and a generalized pruritic erythematous maculopapular rash at the chest wall and abdomen and over both extremities were also observed (Fig. 1). The size of her uterus was appropriate for gestational age with the presence of regular uterine contractions occurring every 3 minutes and 40 seconds with moderate intensity (Fig. 2). A digital examination showed a closed cervical os with no effacement. The fetal heart rate status was reassuring, as shown by a baseline fetal heart rate of 140 beats/minute. An ultrasonographic examination revealed a single fetus appropriate for gestational age, the amniotic fluid and placenta appeared normal, and the patient’s cervical length was 30.2 mm.

Fig. 2
figure 2

External fetal monitoring. Uterine contractions occurred every 3 minutes and 40 seconds with moderate intensity

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The patient was diagnosed with anaphylaxis and threatened preterm labor. To treat her anaphylaxis, intravenous chlorpheniramine 10 mg, intramuscular epinephrine (1:1000) 0.5 mg, and intravenous dexamethasone 5 mg were administered. Two hours after the administration of epinephrine, the patient still had uterine contractions. A digital examination was performed and the cervical os was closed with 50% effacement. Therefore, preterm labor was diagnosed. Preterm labor syndrome is associated with intra-amniotic inflammation and/or intra-amniotic infection. Therefore, the patient was counseled about amniocentesis (under the IRB approval protocol COA. MURA2021/254). Written informed consent was obtained from the patient before collecting specimens. Second doses of intramuscular epinephrine (1:1000) 0.5 mg and intravenous dexamethasone 5 mg were administered to remedy the persistent dyspnea and wheezing. Her dyspnea and uterine contractions improved within 1 hour after administering the second doses of epinephrine and dexamethasone (Fig. 3). The maculopapular rash and swelling subsided within a few days.

Fig. 3
figure 3

Resolved uterine contractions after antihistamine and epinephrine administration

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At the admission (6 hours after the onset of symptoms), her maternal white blood cell (WBC) count was 16,580 cells/mm3 (neutrophils: 84.2%, lymphocytes: 5.9%, and monocytes: 6.9%). An amniotic fluid analysis showed a WBC count of 105 cells/mm3 (polymorphonuclear cells: 46%, mononuclear cells: 54%). Hematoxylin and eosin staining for a cell differential was not performed. Amniotic fluid Gram staining, culture, and 16S ribosomal RNA gene polymerase chain reaction results were negative for microorganisms, and the amniotic fluid interleukin-6 concentration was within the normal range (0.41 ng/mL; cut-off > 2.6 ng/mL). These negative findings were consistent with no finding of intra-amniotic infection or intra-amniotic inflammation. The pregnancy progressed uneventfully, and the patient subsequently had a vaginal delivery of a female neonate weighing 3,480 g at 39+3 weeks of gestation. The neonate’s Apgar score was 9, 10 and had no complication.

Three months after the delivery, the patient experienced similar symptoms (i.e., tightness in the chest and a maculopapular rash) after ingesting another snack of the same brand. The cause of the allergy was investigated. A skin-prick test result at 6 months after the delivery showed a positive wheal and flare for a strawberry-coated biscuit.

Discussion

This report suggests that maternal anaphylaxis can induce the onset of preterm uterine contractions, and these can be resolved by the administration of antihistamine agents, adrenergic drugs, and steroids. Although several reports have described the association between an allergic reaction and uterine contractions, only a few investigations proved the cause of allergy [18, 19]. Additionally, none of these reports determined the status of intra-amniotic infection and/or intra-amniotic inflammation, which is frequently observed in women presenting with symptoms of preterm labor.

Anaphylaxis during pregnancy

Anaphylaxis occurring during pregnancy is a rare event with an incidence of approximately 3.8/100,000 hospitalizations [20,21,22]. The mortality rate of anaphylaxis is approximately 0.09/100,000 live births [23]. According to diagnostic criteria amended by the World Allergy Organization in 2020 [24], anaphylaxis is a clinical diagnosis based on the criteria shown in Table 1.

Table 1 Diagnostic criteria of anaphylaxis [24]
Full size table

A recent systematic review and meta-analysis of 47 pregnant women with anaphylaxis showed that the most common clinical manifestations are hypotension and tachycardia (100%), followed by urticaria (57%) [22]. In addition, anaphylaxis is more commonly observed during the period of labor (approximately 80%) than prior to the onset of labor. Antibiotics, anesthetic drugs, latex, oxytocin, misoprostol, and rubber contained in a Foley catheter are common allergens. Anaphylaxis can be associated with a 3.2% (95% confidence interval: 0.4–11) maternal mortality rate and a 14.3% (95% confidence interval: 4.8–30.3) neonatal encephalopathy rate [21]. Nevertheless, approximately half of the reported cases were solely diagnosed based on clinical symptoms and allergological tests without a proven allergen [22]. In the current case, the criteria of anaphylaxis were met. Therefore, we concluded that the anaphylaxis induced preterm uterine contractions. Indeed, uterine contractions are recognized as a manifestation of anaphylaxis and, importantly, the cause of anaphylaxis can be proven after delivery.

Allergy as a mechanism of disease of preterm labor

Evidence supportive of an allergic reaction (hypersensitivity) as one of the mechanisms implicated in preterm labor has been reported as follows.

  1. 1.

    In 1910, Schultz reported that the exposure of a specific allergen to a sensitized guinea pig induced contractions of the ileum [25]. Subsequently, a contractile response was demonstrated in the uterus of the sensitized guinea pig [26]. The “Schultz-Dale phenomenon” was then characterized by a standard technique in which antigen-induced contractions of the smooth muscles in vitro induced anaphylactic hypersensitivity [27]. Schultz-Dale anaphylactic contractions have been shown in the uterus of the guinea pig [28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46], rat [44, 47,48,49], mouse [50, 51], and human [52]. The Schultz-Dale experiment was later demonstrated in human myometrial strips collected from women with an allergy to ragweed. In addition, a higher frequency and intensity of myometrial contractions were observed in pregnant donors and then compared with non-pregnant donors [53]. Moreover, preincubation of myometrial strips in human serum led to the sensitization of the myometrial strips of non-allergic women, and this was mediated by immunoglobulin E [53].

  2. 2.

    Mast cells, which are the effector cells of an allergic reaction, have been found in the uterus [54]. Furthermore, histamine and prostaglandins produced by mast cell degranulation can induce myometrial contractility [54, 55].

  3. 3.

    Pharmacological degranulation of mast cells with a compound called “48/80” induces myometrial contractility [56,57,58]. Histamine and serotonin induce myometrial contractions in a dose-dependent manner [53, 54, 59, 60]. Diphenhydramine, chlorpheniramine, and antihistamine agents partially suppress myometrial contractility of sensitized myometrium strips challenged with an allergen, suggesting a histamine receptor-mediated mechanism [61, 62]. In addition, pre-treatment with cromolyn, which is a mast cell stabilizer, inhibits myometrial contractility, suggesting a role of mast cells, especially degranulation, in myometrial contractions [61, 62].

  4. 4.

    Incubation of myometrial strips from sensitized and non-sensitized rats with an anti- immunoglobulin E antibody increases myometrial contractility [56].

  5. 5.

    A challenge with ovalbumin results in an increase in the uterine tone of non-pregnant guinea pigs sensitized with ovalbumin [56,57,58].

  6. 6.

    The autopsy report of a guinea pig, performed immediately after its death caused by anaphylactic shock, showed increased uterine contractility [25].

  7. 7.

    Eosinophils identified in the amniotic fluid were found to represent the majority of WBCs in a subset of women with preterm labor [63]. Eosinophil-rich inflammation is associated with allergic diseases, such as asthma, atopic dermatitis (eczema), and allergic rhinitis [64,65,66,67,68]. Additionally, patients with an increase in amniotic fluid eosinophils (WBC count differential containing > 20% of eosinophils) are at an increased risk of preterm delivery. However, some patients with eosinophils detected in samples of amniotic fluid deliver at term and show no evidence of complications [63].

  8. 8.

    Preterm labor and delivery can be induced in a guinea pig model of type I hypersensitivity [18]. In addition, a study showed that pretreatment with a histamine H1 receptor antagonist (ketotifen) to ovalbumin-sensitized guinea pigs increased the duration of gestation and prevented preterm labor and delivery [61].

  9. 9.

    Previous studies showed that guinea pigs that were sensitized with chicken egg ovalbumin were at greater risk to deliver a preterm pup than those challenged with normal saline [18, 61].

  10. 10.

    Prior studies have suggested an association between patients with an allergic disease, such as asthma or allergic rhinitis, and increased preterm delivery [69,70,71].

  11. 11.

    Several case reports have shown that exposure to an allergen can induce uterine contractions and that these contractions are ameliorated after the treatment of anaphylaxis together with the standard treatment of preterm labor pain [22, 72,73,74]. Collectively, type I hypersensitivity reactions can induce preterm labor and delivery.

Type I hypersensitivity reactions and uterine contractions in humans

A systematic review of clinical studies reported 31 cases of uterine contractions induced by anaphylaxis [19]. A total of 29% (9/31) of these cases were in pregnant women, of whom seven of nine of these women presented with an allergic reaction and preterm uterine contractions. Three cases were anaphylactic [73, 75]. Table 2 shows reported cases of type I hypersensitivity-induced preterm uterine contractions.

Table 2 Summary of cases with type I hypersensitivity-induced premature uterine contractions
Full size table

The first case of uterine contractions induced by hypersensitivity or anaphylaxis during pregnancy was reported in 1984 [72]. A pregnant woman at 29 weeks of gestation developed erythema of the palms and urticarial areas on the face and abdomen, uterine contractions every 3 to 4 minutes, and maternal hypotension. Fetal heart rate tracing showed repetitive late decelerations. After the administration of diphenhydramine and ephedrine, the uterine contractions and the late decelerations of fetal heart rate were resolved. The patient underwent cesarean delivery at term because of a failure to progress in labor. The newborn had an Apgar score of 9-9, a birthweight of 3780 g, and a normal neurological exam [72]. The second case was an anaphylactic reaction in response to a wasp sting in a woman at 27 weeks of gestation, followed by preterm delivery at 35 weeks of gestation [73]. Three patients were diagnosed with mastocytosis, which is characterized by an abnormal accumulation of mast cells in several organs. These patients experienced pruritic urticaria pigmentosa and preterm uterine contractions at mid-gestation, which were resolved by the administration of intravenous pheniramine maleate, hydroxyzine hydrochloride, and imipramine hydrochloride. All patients eventually delivered at near term or at term gestation without complications [76,77,78].

Subsequently, Romero et al described a pregnant woman at 31 weeks of gestation with an episode of spontaneous preterm labor and a generalized pruritic maculopapular rash after the ingestion of shellfish [18]. Preterm labor subsided after the treatment of antihistamines and steroids. The patient eventually delivered at 40 weeks of gestation. Recently, Tsuzuki et al reported a pregnant woman at 25 weeks of gestation who presented with anaphylactic symptoms (i.e., dyspnea, generalized itchy rash, and regular uterine contractions) after consuming buckwheat noodles. Such symptoms subsided after the administration of epinephrine, antihistamine, and methylprednisolone. A healthy, neurologically intact neonate was delivered at term. Skin-prick and challenge test results of the mother confirmed a buckwheat allergy [75].

In this report, we describe the fourth case of pregnancy with anaphylaxis-induced preterm uterine contractions. Anaphylaxis is generally diagnosed based on clinical criteria, which were met in this patient (acute onset of skin and laryngeal involvement), even though tryptase concentrations were not measured in the samples of serum and amniotic fluid. Strengths of this report are the confirmation of the cause of the allergic status post-delivery and the finding that the patient’s uterine contractions were not associated with intra-amniotic inflammation or intra-amniotic infection. Notably, an analysis of the types of cells in amniotic fluid by a flow cytometer or hematoxylin and eosin staining would be useful because a high number of eosinophils might be associated with type 1 hypersensitivity, including anaphylaxis, which can induce preterm labor [63].

Conclusions

We report a case of anaphylaxis-induced uterine contractions for which treatment of the anaphylaxis was followed by the resolution of uterine contractions. This evidence highlights a maternal allergic reaction as one of the mechanisms of preterm labor.

Availability of data and materials

All data generated or analyzed for this case report are included in this published article.

Abbreviations

WBC:

White blood cell

References

  1. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008;371:75–84.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Iams JD, Romero R, Culhane JF, Goldenberg RL. Primary, secondary, and tertiary interventions to reduce the morbidity and mortality of preterm birth. Lancet. 2008;371:164–75.

    Article  PubMed  Google Scholar 

  3. Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, et al. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ. 2010;88:31–8.

    Article  PubMed  Google Scholar 

  4. Chawanpaiboon S, Vogel JP, Moller AB, Lumbiganon P, Petzold M, Hogan D, et al. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Lancet Glob Health. 2019;7:e37-46.

    Article  PubMed  Google Scholar 

  5. Lee AC, Blencowe H, Lawn JE. Small babies, big numbers: global estimates of preterm birth. Lancet Glob Health. 2019;7:e2-3.

    Article  PubMed  Google Scholar 

  6. Chawla D, Agarwal R. Preterm births and deaths: from counting to classification. Lancet Glob Health. 2022;10:e1537-8.

    Article  CAS  PubMed  Google Scholar 

  7. Dhaded SM, Saleem S, Goudar SS, Tikmani SS, Hwang K, Guruprasad G, et al. The causes of preterm neonatal deaths in India and Pakistan (PURPOSe): a prospective cohort study. Lancet Glob Health. 2022;10:e1575-81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Romero R, Espinoza J, Kusanovic JP, Gotsch F, Hassan S, Erez O, et al. The preterm parturition syndrome. BJOG. 2006;113(Suppl 3):17–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Romero R. Prenatal medicine: the child is the father of the man. 1996. J Matern Fetal Neonatal Med. 2009;22:636–9.

    Article  PubMed  Google Scholar 

  10. Romero R, Dey SK, Fisher SJ. Preterm labor: one syndrome, many causes. Science. 2014;345:760–5.

    Article  CAS  PubMed  PubMed Central  ADS  Google Scholar 

  11. Jung E, Romero R, Yeo L, Chaemsaithong P, Gomez-Lopez N. Intra-amniotic infection/inflammation and the fetal inflammatory response syndrome. In: Polin R, Abman SH, Rowitch DH, Benitz W, editors. Fetal and neonatal physiology, 6th ed. Elsevier: Amsterdam, Netherlands; 2022.

  12. Schultes V, Deutzmann R, Jaenicke R. Complete amino-acid sequence of glyceraldehyde-3-phosphate dehydrogenase from the hyperthermophilic eubacterium Thermotoga maritima. Eur J Biochem. 1990;192:25–31.

    Article  CAS  PubMed  Google Scholar 

  13. Gomez R, Romero R, Edwin SS, David C. Pathogenesis of preterm labor and preterm premature rupture of membranes associated with intraamniotic infection. Infect Dis Clin North Am. 1997;11:135–76.

    Article  CAS  PubMed  Google Scholar 

  14. Goncalves LF, Chaiworapongsa T, Romero R. Intrauterine infection and prematurity. Ment Retard Dev Disabil Res Rev. 2002;8:3–13.

    Article  PubMed  Google Scholar 

  15. Kim CJ, Romero R, Chaemsaithong P, Chaiyasit N, Yoon BH, Kim YM. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance. Am J Obstet Gynecol. 2015;213(4 Suppl):S29-52.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Jung E, Romero R, Yeo L, Diaz-Primera R, Marin-Concha J, Para R, et al. The fetal inflammatory response syndrome: the origins of a concept, pathophysiology, diagnosis, and obstetrical implications. Semin Fetal Neonatal Med. 2020;25:101146.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Gomez-Lopez N, Galaz J, Miller D, Farias-Jofre M, Liu Z, Arenas-Hernandez M, et al. The immunobiology of preterm labor and birth: intra-amniotic inflammation or breakdown of maternal-fetal homeostasis. Reproduction. 2022;164:R11-45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Romero R, Kusanovic JP, Munoz H, Gomez R, Lamont RF, Yeo L. Allergy-induced preterm labor after the ingestion of shellfish. J Matern Fetal Neonatal Med. 2010;23:351–9.

    Article  PubMed  PubMed Central  Google Scholar 

  19. D’Astous-Gauthier K, Graham F, Paradis L, Des Roches A, Begin P. Beta-2 agonists may be superior to epinephrine to relieve severe anaphylactic uterine contractions. J Allergy Clin Immunol Pract. 2021;9:1232–41.

    Article  CAS  PubMed  Google Scholar 

  20. Tacquard C, Chassard D, Malinovsky JM, Saucedo M, Deneux-Tharaux C, Mertes PM, et al. Anaphylaxis-related mortality in the obstetrical setting: analysis of the French National Confidential Enquiry into Maternal Deaths from 2001 to 2012. Br J Anaesth. 2019;123:e151-3.

    Article  PubMed  Google Scholar 

  21. McCall SJ, Bonnet MP, Ayras O, Vandenberghe G, Gissler M, Zhang WH, et al. Anaphylaxis in pregnancy: a population-based multinational European study. Anaesthesia. 2020;75:1469–75.

    Article  CAS  PubMed  Google Scholar 

  22. Simionescu AA, Danciu BM, Stanescu AMA. Severe anaphylaxis in pregnancy: a systematic review of clinical presentation to determine outcomes. J Pers Med. 2021;11:1–13.

  23. McCall SJ, Bunch KJ, Brocklehurst P, D’Arcy R, Hinshaw K, Kurinczuk JJ, et al. The incidence, characteristics, management and outcomes of anaphylaxis in pregnancy: a population-based descriptive study. BJOG. 2018;125:965–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cardona V, Ansotegui IJ, Ebisawa M, El-Gamal Y, Fernandez Rivas M, Fineman S, et al. World allergy organization anaphylaxis guidance 2020. World Allergy Organ J. 2020;13:100472.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Schultz WH. Physiological studies in anaphylaxis: the reaction of smooth muscle of the guinea pig sensitized with horse serum. J Pharmacol Exp Ther. 1910;1:549–67.

  26. Dale H. The anaphylactic reaction of plain muscle in the guinea-pig. J Pharmacol Exp Ther. 1913:167–223.

  27. Chand N, Eyre P. The Schultz-Dale reaction: a review. Agents Actions. 1978;8:171–84.

    Article  CAS  PubMed  Google Scholar 

  28. Kendall Alexander, HL, Holmes, JA. The effects of formaldehyde on smooth muscle contraction in anaphylaxis: studies in bacterial metabolism. J Inf Dis. 1927:137–42.

  29. Schild HO. Reaction of the guinea-pig’s uterus immersed in a histamine solution to histamine and anaphylaxis. J Physiol. 1936;86:51–2.

    CAS  Google Scholar 

  30. Schild HO. Histamine release in anaphylactic shock from various tissues of the guinea-pig. J Physiol. 1939;95:393–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kulka AM. Studies on antibody antigen mixtures. II. The effect on normal living excised tissue and its dependence on the presence of free antibody in the mixture. J Immun. 1943;46:235–8.

    Article  Google Scholar 

  32. Kabat EA, Coffin GS, Smith DJ. A quantitative study of passive anaphylaxis in the guinea pig. J Immunol. 1947;56:377–84.

    Article  CAS  PubMed  Google Scholar 

  33. Swineford O Jr, Reynolds RJ. Studies in bacterial allergy. IV. The transitory nature of desensitization of the passively sensitized guinea pig uterus with a bacterial hapten, with a note on 95 per cent O2-5 per cent CO2 as an aerating mixture. J Allergy. 1951;22:156–9.

  34. Mongar JL, Schild HO. A comparison of the effects of anaphylactic shock and of chemical histamine releasers. J Physiol. 1952;118:461–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Makari JG. Detection of soluble carcinoma antigen by use of the Schultz-Dale test. Am J Pathol. 1955;31(581):1291–5.

    Google Scholar 

  36. Makari JG. Use of Schultz-Dale test for detection of specific antigen in sera of patients with carcinoma. Br Med J. 1955;2:1291–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Mongar JL, Schild HO. Inhibition of the anaphylactic reaction. J Physiol. 1957;135:301–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Sanyal RK, West GB. 5-Hydroxytryptamine and anaphylactic shock. Nature. 1957;180:1417.

    Article  CAS  PubMed  ADS  Google Scholar 

  39. Burrows D. Schultz-Dale test for detection of specific antigen in sera of patients with carcinoma. Br Med J. 1958;1:368–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Fink MA, Gardner CE. Anaphylaxis in guinea pig: improbability of release of serotonin in the Schultz-Dale reaction. Proc Soc Exp Biol Med. 1958;97:554–7.

    Article  CAS  PubMed  Google Scholar 

  41. McEwen LM. The Schultz-Dale anaphylactic test for carcinoma antigen. Br Med J. 1959;2:615–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Mota I. Effect of antigen and octylamine on mast cells and histamine content of sensitized guinea-pig tissues. J Physiol. 1959;147:425–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Boreus LO. Quantitative differences between guinea-pig ileum and uterus in the Schultz-Dale reaction. Acta Physiol Scand. 1961;52:320–7.

    Article  CAS  PubMed  Google Scholar 

  44. Boreus LO, Westerholm B. 5-Hydroxytryptamine in the Schultz-Dale reaction. Acta Physiol Scand. 1962;56:17–25.

    Article  CAS  PubMed  Google Scholar 

  45. Dale MM. The applicability of anaphylactic tests in studies of antigen mixtures. II. The discriminatory capacity of the tests. Immunology. 1965;8:444–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Aronson AS. The Schultz-Dale reaction of the depolarized guinea-pig uterus. Br J Pharmacol. 1968;34:523–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kellaway CH. The anaphylactic reaction of the isolated uterus of the rat. Br J Exp Pathol. 1930;11:72–80.

    CAS  PubMed Central  Google Scholar 

  48. Suden CT. Reactions of rat uterus excised and in situ to histamine and anaphylaxis. Am J Physiol. 1934;108:416–23.

    Article  CAS  Google Scholar 

  49. Sanyal RK, West GB. Anaphylactic shock in the albino rat. J Physiol. 1958;142:571–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Fink MA, Rothlauf MV. In vitro anaphylaxis in the sensitized mouse uterus. Proc Soc Exp Biol Med. 1955;90:477–80.

    Article  CAS  PubMed  Google Scholar 

  51. Fink MA. Anaphylaxis in the mouse: possible relation of the Schultz-Dale reaction to serotonin release. Proc Soc Exp Biol Med. 1956;92:673–5.

    Article  CAS  PubMed  Google Scholar 

  52. Tollackson KA, Frick OL. Response of human smooth muscle in Schultz-Dale experiments. J Allergy. 1966;37:195–203.

    Article  CAS  PubMed  Google Scholar 

  53. Garfield RE, Irani AM, Schwartz LB, Bytautiene E, Romero R. Structural and functional comparison of mast cells in the pregnant versus nonpregnant human uterus. Am J Obstet Gynecol. 2006;194:261–7.

    Article  CAS  PubMed  Google Scholar 

  54. Rudolph MI, Reinicke K, Cruz MA, Gallardo V, Gonzalez C, Bardisa L. Distribution of mast cells and the effect of their mediators on contractility in human myometrium. Br J Obstet Gynaecol. 1993;100:1125–30.

    Article  CAS  PubMed  Google Scholar 

  55. Padilla L, Reinicke K, Montesino H, Villena F, Asencio H, Cruz M, et al. Histamine content and mast cells distribution in mouse uterus: the effect of sexual hormones, gestation and labor. Cell Mol Biol. 1990;36:93–100.

    CAS  PubMed  Google Scholar 

  56. Garfield RE, Bytautiene E, Vedernikov YP, Marshall JS, Romero R. Modulation of rat uterine contractility by mast cells and their mediators. Am J Obstet Gynecol. 2000;183:118–25.

    Article  CAS  PubMed  Google Scholar 

  57. Bytautiene E, Vedernikov YP, Saade GR, Romero R, Garfield RE. Endogenous mast cell degranulation modulates cervical contractility in the guinea pig. Am J Obstet Gynecol. 2002;186:438–45.

    Article  PubMed  Google Scholar 

  58. Bytautiene E, Vedernikov YP, Saade GR, Romero R, Garfield RE. IgE-independent mast cell activation augments contractility of nonpregnant and pregnant guinea pig myometrium. Int Arch Allergy Immunol. 2008;147:140–6.

    Article  CAS  PubMed  Google Scholar 

  59. Cruz MA, Gonzalez C, Acevedo CG, Sepulveda WH, Rudolph MI. Effects of histamine and serotonin on the contractility of isolated pregnant and nonpregnant human myometrium. Gynecol Obstet Invest. 1989;28:1–4.

    Article  CAS  PubMed  Google Scholar 

  60. Bytautiene E, Vedernikov YP, Saade GR, Romero R, Garfield RE. Effect of histamine on phasic and tonic contractions of isolated uterine tissue from pregnant women. Am J Obstet Gynecol. 2003;188:774–8.

    Article  CAS  PubMed  Google Scholar 

  61. Bytautiene E, Romero R, Vedernikov YP, El-Zeky F, Saade GR, Garfield RE. Induction of premature labor and delivery by allergic reaction and prevention by histamine H1 receptor antagonist. Am J Obstet Gynecol. 2004;191:1356–61.

    Article  CAS  PubMed  Google Scholar 

  62. Willets JM, Taylor AH, Shaw H, Konje JC, Challiss RA. Selective regulation of H1 histamine receptor signaling by G protein-coupled receptor kinase 2 in uterine smooth muscle cells. Mol Endocrinol. 2008;22:1893–907.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Romero R, Kusanovic JP, Gomez R, Lamont R, Bytautiene E, Garfield RE, et al. The clinical significance of eosinophils in the amniotic fluid in preterm labor. J Matern Fetal Neonatal Med. 2010;23:320–9.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Martin LB, Kita H, Leiferman KM, Gleich GJ. Eosinophils in allergy: role in disease, degranulation, and cytokines. Int Arch Allergy Immunol. 1996;109:207–15.

    Article  CAS  PubMed  Google Scholar 

  65. Fulkerson PC, Rothenberg ME. Targeting eosinophils in allergy, inflammation and beyond. Nat Rev Drug Discov. 2013;12:117–29.

    Article  CAS  PubMed  Google Scholar 

  66. Wechsler ME, Munitz A, Ackerman SJ, Drake MG, Jackson DJ, Wardlaw AJ, et al. Eosinophils in health and disease: a state-of-the-art review. Mayo Clin Proc. 2021;96:2694–707.

    Article  CAS  PubMed  Google Scholar 

  67. Dunn JLM, Rothenberg ME. 2021 year in review: spotlight on eosinophils. J Allergy Clin Immunol. 2022;149:517–24.

    Article  CAS  PubMed  Google Scholar 

  68. Lombardi C, Berti A, Cottini M. The emerging roles of eosinophils: implications for the targeted treatment of eosinophilic-associated inflammatory conditions. Curr Res Immunol. 2022;3:42–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kramer MS, Coates AL, Michoud MC, Dagenais S, Moshonas D, Davis GM, et al. Maternal asthma and idiopathic preterm labor. Am J Epidemiol. 1995;142:1078–88.

    Article  CAS  PubMed  Google Scholar 

  70. Liu S, Wen SW, Demissie K, Marcoux S, Kramer MS. Maternal asthma and pregnancy outcomes: a retrospective cohort study. Am J Obstet Gynecol. 2001;184:90–6.

    Article  CAS  PubMed  Google Scholar 

  71. Kojima R, Yokomichi H, Akiyama Y, Ooka T, Miyake K, Horiuchi S, et al. Association between preterm birth and maternal allergy considering IgE level. Pediatr Int. 2021;63:1026–32.

    Article  CAS  PubMed  Google Scholar 

  72. Klein VR, Harris AP, Abraham RA, Niebyl JR. Fetal distress during a maternal systemic allergic reaction. Obstet Gynecol. 1984;64(3 Suppl):15S-7S.

    Article  CAS  PubMed  Google Scholar 

  73. Habek D, Cerkez-Habek J, Jalsovec D. Anaphylactic shock in response to wasp sting in pregnancy. Zentralbl Gynakol. 2000;122:393–4.

    CAS  PubMed  Google Scholar 

  74. Shingai Y, Nakagawa K, Kato T, Fujioka T, Matsumoto T, Kihana T, et al. Severe allergy in a pregnant woman after vaginal examination with a latex glove. Gynecol Obstet Invest. 2002;54:183–4.

    Article  PubMed  Google Scholar 

  75. Tsuzuki Y, Narita M, Nawa M, Nakagawa U, Wakai T. Management of maternal anaphylaxis in pregnancy: a case report. Acute Med Surg. 2017;4:202–4.

    Article  PubMed  Google Scholar 

  76. Donahue JG, Lupton JB, Golichowski AM. Cutaneous mastocytosis complicating pregnancy. Obstet Gynecol. 1995;85:813–5.

    Article  CAS  PubMed  Google Scholar 

  77. Kehoe SL, Bathgate SL, Macri CJ. Use of a doula for labor coaching in a patient with indolent systemic mastocytosis in pregnancy. Obstet Gynecol. 2006;107:514–6.

    Article  PubMed  Google Scholar 

  78. Madendag IC, Madendag Y, Tarhan I, Altinkaya SO, Danisman N. Mastocytosis in pregnancy. Taiwan J Obstet Gynecol. 2010;49:192–6.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank Maureen McGerty, M.A. (NICHD/NIH/DHHS), for her critical reading of the manuscript and for editorial support. We also thank Ellen Knapp, PhD, from Edanz (https://edanz.com/ac) for editing a draft of this manuscript.

Funding

Open access funding provided by Mahidol University This report was funded by the Specific League Funds from Mahidol University, Ramathibodi Funding Research RF-65048 and RF_65100 (Dr. Piya Chaemsaithong) and by the Faculty of Medicine Ramathibodi Hospital, Mahidol University (Decentralized funding for CNMI, RF_65090 and Ramathibodi funding ID 3158) (Dr. Pisut Pongchaikul).

This research was also supported, in part, by the Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services (NICHD/NIH/DHHS); and, in part, by federal funds from NICHD/NIH/DHHS (Contract No. HHSN275201300006C). Dr. Roberto Romero has contributed to this work as part of his official duties as an employee of the United States Federal Government. Dr. Romero provided intellectual input but did not have access to identifiable data.

The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand

    Puntabut Warintaksa, Waranyu Lertrat, Threebhorn Kamlungkuea & Piya Chaemsaithong

  2. Pregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S, Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, 20892, USA

    Roberto Romero

  3. Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, 48109, USA

    Roberto Romero

  4. Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, 48824, USA

    Roberto Romero

  5. Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital Mahidol University, Samut Prakan, 10540, Thailand

    Pornpun Vivithanaporn, Paninee Mongkolsuk, Rapeewan Settacomkul & Pisut Pongchaikul

  6. Integrative Computational BioScience Center, Mahidol University, Nakhon Pathom, 73170, Thailand

    Pisut Pongchaikul

  7. Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool, L69 3BX, UK

    Pisut Pongchaikul

Authors
  1. Puntabut Warintaksa
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  2. Waranyu Lertrat
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  3. Roberto Romero
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  4. Pornpun Vivithanaporn
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  5. Paninee Mongkolsuk
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  6. Threebhorn Kamlungkuea
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  7. Rapeewan Settacomkul
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  8. Pisut Pongchaikul
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  9. Piya Chaemsaithong
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Contributions

Substantial contributions to sample collection, patient management, original draft preparation, and finalization of the manuscript: P.W. Conceptualization and finalization of the manuscript: R.R. Sample collection and patient care: W.L, T.K. Substantial contributions to laboratory assessment and finalization of the manuscript: P.V., P.M., R.S., P.P. Conceptualization, sample collection, patient management, original draft preparation, obtain funding and finalization: P.C. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Roberto Romero, Pisut Pongchaikul or Piya Chaemsaithong.

Ethics declarations

Ethics approval and consent to participate

The collection and use of the materials for research purposes were approved by the Human Research Ethics Committee, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (COA. MURA2021/254). All data were collected from the patient after obtaining written informed consent. All methods were carried out in accordance with relevant guidelines and regulations.

Consent for publication

Written informed consent for the photographs and their subsequent publication in this case report was obtained from the patient.

Competing interests

The authors declare no competing interests.

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Warintaksa, P., Lertrat, W., Romero, R. et al. Anaphylaxis-induced premature uterine contractions: a case report and literature review. BMC Pregnancy Childbirth 24, 197 (2024). https://doi.org/10.1186/s12884-024-06297-2

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Keywords

BMC Pregnancy and Childbirth

ISSN: 1471-2393

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