idiopathic anaphylaxis information center

a resource for people with ia and other mast cell disorders

Pregnancy and idiopathic anaphylaxis

Can you carry a fetus to term with IA?

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Photograph of a pregnant woman, from Wikimedia Commons

Of the many holes in the medical literature on idiopathic anaphylaxis (IA), the one that seems most glaring to me is the issue of pregnancy. More women than men develop IA, and most women develop the disease in their fertile years. Reference [Greenberger PA. Idiopathic anaphylaxis. Immunol Allergy Clin N Am. 2007; Vol. 27: p. 280.]. So why hasn't attention been paid to the potentially devastating effects of unexplained, uncontrolled anaphylaxis on the life of both an expectant mother and her fetus?

To give you some idea of how terrifying the prospect of an unexpected pregnancy can be to a woman diagnosed with IA, here's one example of how the question has been posed to me:

I’ve been diagnosed with IA for years, but recently I’ve had attacks so bad that I was hospitalized. Last time, it took 18 hours to get it under control. By that time my heart rate was 155, my BP was stable but low (90/60), my hands were blue, my face red/purple, and I was so hot you could have fried an egg on my face. I am emotionally wasted from the stress of these attacks. I’m in a serious relationship, and I’m scared about what would happen if I became pregnant. Does anyone know if you can carry a baby to term with IA?

The answer to her question is Yes, but this is one of those good news/bad news situations. The good news: Yes, I know women with idiopathic anaphylaxis (IA) who have delivered healthy, full-term infants. The bad news: I know of one case in which a mother with IA lost her fetus after having anaphylaxis.

Unfortunately, there have been no published studies of pregnancy among women who have IA, despite what Zeiss [Zeiss CR. Foreward. In: Patterson R, ed. Idiopathic anaphylaxis. Providence, RI: OceanSide Publications; 1997; xiii: “They {Patterson's group at Northwestern} have explored every aspect of this disease in over thirty publications covering a 15 year period of investigation.”] has said to the contrary.

However, there have been studies on pregnancy among women with mastocytosis [another mast cell-related disease in which a person has too many normal or abnormal mast cells], studies on the occurrence of anaphylaxis during pregnancy, and studies of pregnancy with other autoimmune diseases, like thyroiditis [inflammation of the thyroid gland]. Based on those articles and a passing comment by an IA specialist, I can provide at least some useful information.

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Pregnancy and mastocytosis

In 1995, Donahue, Upton and Golichowski [Donahue JG, Upton JB, Golichowski AM. Cutaneous mastocytosis complicating pregnancy. Obstet Gynecol. 1995; 85(5, Pt 2):813–815] reported on the pregnancy of a woman with Telangiectasia macularis eruptiva perstans (TEMP), a rare form of cutaneous [pertaining to the skin] mastocytosis. The authors point out, “Histamine ... has been shown to increase pregnant myometrial [the smooth muscle layer of the wall of the uterus] contractility.... Patients with mastocytosis may be expected to have uterine irritability, preterm labor, and associated symptoms.” The patient’s symptoms required the use of both antihistamines and tocolytics [medications used to suppress premature labor], but she was able to carry the pregnancy to term.

In 2000, Worobec, Akin, Scott and Metcalfe [Worobec AS, Akin C, Scott LM, Metcalfe DD. Mastocytosis complicating pregnancy. Obstet Gynecol. 2000; 95(3):391–395] published a review of their experience with pregnant female mastocytosis patients. Their conclusion:

A subset of women with mastocytosis might have had exacerbated mastocytosis during and after pregnancy, but labor and delivery progressed normally. Infants were born generally healthy and were without mastocytosis. Thus there appears to be no absolute contraindication to pregnancy for women with mastocytosis, although women should be aware that the choice to have a child is not without some added risk. Reference [Worobec AS, Akin C, Scott LM, Metcalfe DD. Mastocytosis complicating pregnancy. Obstet Gynecol. 2000; 95(3):391].
Photograph of Dr. Mariana Castells of Brigham and Women's Hospital in Boston, Massachusetts

In that same article they included an interesting factoid: Mast cells have both estrogen and progesterone receptors — which may come as no surprise to those of us who have pre- or peri-menstrual exacerbation of our mast cell activation symptoms. Also, mast cells are present in both the myometrium and placenta. Reference [Worobec AS, Akin C, Scott LM, Metcalfe DD. Mastocytosis complicating pregnancy. Obstet Gynecol. 2000; 95(3):391].

In a 2004 article on mastocytosis, Dr. Mariana Castells [Castells M. Mastocytosis: classification, diagnosis, and clinical presentation. Allergy Asthma Proc. 2004; 25(1):33–6] (pictured on right) notes:

Limited studies are available on patients with mastocytosis and pregnancy. From 8 women with ISM [indolent systemic mastocytosis — the most common systemic form of the disease] who delivered 11 healthy children, 1/3 had mild exacerbations of their symptoms during pregnancy. No adverse reactions during anesthesia were observed and no complications occurred during labor and delivery.... Women with mastocytosis are fertile and pregnancy or delivery does not aggravate mast cell-mediated symptoms in most cases. Reference [Castells M. Mastocytosis: classification, diagnosis, and clinical presentation. Allergy Asthma Proc. 2004; 25(1):35].
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Pregnancy and anaphylaxis

In reviewing the literature on the more general topic of anaphylaxis and pregnancy, lack of oxygen or reduction in blood flow to the fetus are the primary ways that the fetus is affected by its mother’s anaphylaxis. As Wig [Wig J. Anaphylaxis in pregnancy. 2nd Annual Conf of Assn of Obstetric Anaesthesiologists. Chandigarh, India: Postgrad Inst of Med Ed & Research. SEP 2009] notes, “Maternal anaphylaxis has been associated with fetal distress, brain injury, as well as neonatal death.”

However, again, the good news is that, “Maternal anaphylaxis and the associated fetal distress may resolve totally with prompt and aggressive medical management, without maternal or fetal compromise.” And again, the bad news is that, “Alternatively, fetal or neonatal death may occur despite maternal survival, presumably because of diminished uteroplacental perfusion [blood circulation through tissues] as a result of the rapidity and severity of the episode or inadequate treatment.” Reference [Schatz M, Zeiger RS, Falkoff R, Chambers C, Macy E, Mellon MH. Asthma and allergic diseases during pregnancy. In: Adkinson NF, Bochner BS, et al., eds. Middleton's Allergy: Principles and Practice. 7th ed. Philadelphia, PA: Saunders-Elsevier. 2008; 2:1433–1446.].

By the way, another interesting factoid: Did you know that the act of breast-feeding has, on rare occasion, been associated with anaphylaxis? Two different women had anaphylaxis upon breast-feeding within the first to third day after giving birth. The good news is that, in both cases, the problem resolved itself within a day or two. Reference [Schatz M, Zeiger RS, Falkoff R, Chambers C, Macy E, Mellon MH. Asthma and allergic diseases during pregnancy. In: Adkinson NF, Bochner BS, et al., eds. Middleton's Allergy: Principles and Practice. 7th ed. Philadelphia, PA: Saunders-Elsevier. 2008; 2:1433–1446.].

Something that anyone with a mast cell-related disease should be aware of is that a woman can have laryngeal edema — swelling in her throat — as a symptom of preeclampsia [an uncommon, potentially serious complication of pregnancy that includes increasing hypertension, proteinuria, and edema]. Since laryngeal swelling or obstruction can also be a symptom of anaphylaxis, the pregnant woman with IA or mastocytosis needs to be aware that swelling in her throat could be a symptom of either condition. Reference [Schatz M, Zeiger RS, Falkoff R, Chambers C, Macy E, Mellon MH. Asthma and allergic diseases during pregnancy. In: Adkinson NF, Bochner BS, et al., eds. Middleton's Allergy: Principles and Practice. 7th ed. Philadelphia, PA: Saunders-Elsevier. 2008; 2:1433–1446.].

Map of USA highlighting Texas, (Public domain map courtesy of [http://www.lib.utexas.edu/ The General Libraries, The University of Texas at Austin], modified to highlight state boundaries. {{GFDL}}), from Wikimedia Commons

In the most recently published large study of anaphylaxis during pregnancy, in Texas public hospitals Mulla, Ebrahim and Gonzalez [Mulla ZD, Ebrahim MS, Gonzalez JL. Anaphylaxis in the obstetric patient: Analysis of a statewide hospital discharge database. Ann Allergy Asthma Immuno. 2010; 104(1):55-59] found a total of 19 cases of maternal anaphylaxis, which came out to 2.7 cases per 100,000 deliveries. They report: “The typical offending agents of anaphylaxis in the pregnant woman are as follows (in descending order of frequency): antibiotics (usually β-lactams), latex, succinylcholine, laminaria, and insect stings.” More specifically, they note, “Penicillins and cephalosporins were the anaphylactic trigger in 11 of the patients. Five patients were emergent admissions. There were no maternal deaths. Most of the patients (14 [74%]) delivered by cesarean section.”

What is even more interesting about that huge Texas study [Mulla ZD, Ebrahim MS, Gonzalez JL. Anaphylaxis in the obstetric patient: Analysis of a statewide hospital discharge database. Ann Allergy Asthma Immuno. 2010; 104(1):55-59], is that all 19 pregnant women who had anaphylaxis seem to have been reacting to a specific allergen. Some proportion of them could have had a mast cell-related disease, but the authors do not suggest that any of the women had idiopathic anaphylaxis. A woman with IA contemplating pregnancy can take at least a little comfort from that.

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Pregnancy and thyroid problems

Photograph of a mother with her newborn child, from Wikimedia Commons

Because IA is considered an autoimmune disease and thyroid problems are not uncommon among people with IA, it’s important to consider how thyroid problems may impact pregnancy.

Neale, Cootauco and Burrow [Neale DM, Cootauco AC, Burrow G. Thyroid disease in pregnancy. Clin Perinatol. 2007; 34:543] point out: "The physiologic changes of pregnancy can mimic thyroid disease or cause a true remission or exacerbation of underlying disease. In addition, thyroid hormones are key players in fetal brain development." And as with IA, the authors recommend that, "Preferably, thyroid disease should be controlled before conception." Reference [Neale DM, Cootauco AC, Burrow G. Thyroid disease in pregnancy. Clin Perinatol. 2007; 34:546].

Hyperthyroidism, most often due to Graves’ disease, occurs in only 0.2% of pregnancies. Neale, et al., tell us that:

Symptoms of hyperthyroidism include tachycardia, nervousness, tremors, heat intolerance, weight loss, goiter, frequent stools, excessive sweating, palpitations, and hypertension. Although some of these signs and symptoms mimic normal physiologic changes of pregnancy, a thyroid function test will differentiate thyroid disease from normal pregnancy. Reference [Neale DM, Cootauco AC, Burrow G. Thyroid disease in pregnancy. Clin Perinatol. 2007; 34:546].

Of course, for some of us with IA, all of those symptoms — except for nervousness, goiter, and hypertension — are frequent symptoms. This is a good example of why it’s even more important for a woman with IA to work closely with her medical care team during pregnancy!

A medical emergency that affects only 10% of pregnant women who have hyperthyroidism is a thyroid storm. Neale, et al. [Neale DM, Cootauco AC, Burrow G. Thyroid disease in pregnancy. Clin Perinatol. 2007; 34:549], note that a thyroid storm is suspected, "...When patients present with a combination of fever, change in mental status, seizures, nausea, diarrhea, and cardiac arrhythmias." Because this condition is associated with a high risk of maternal heart failure, it must be taken seriously and treated immediately.

Hypothyroidism is another thyroid condition that affects 0.1–0.3% of pregnancies. One problem is that the symptoms of hypothyroidism can be masked by the hypermetabolic [increased rate of metabolism] state of pregnancy. However, untreated hypothyroidism can increase “rates of miscarriage, preeclampsia [pregnancy complication that causes hypertension, proteinuria, and edema], placental abruption [sudden, premature, partial or total detachment of the placenta from its normal uterine location], growth restrictions, prematurity, and stillbirths.” Reference [Neale DM, Cootauco AC, Burrow G. Thyroid disease in pregnancy. Clin Perinatol. 2007; 34:550].

Even after giving birth, the potential for thyroid problems does not disappear. Postpartum thyroiditis occurs in 6% to 9% of women who have no history of thyroid disease. In fact, some research shows a relationship between postpartum depression and postpartum thyroiditis. Reference [Neale DM, Cootauco AC, Burrow G. Thyroid disease in pregnancy. Clin Perinatol. 2007; 34:553].

Meanwhile, 60% of women who have Graves’ disease during their reproductive years develop it after giving birth. Reference [Neale DM, Cootauco AC, Burrow G. Thyroid disease in pregnancy. Clin Perinatol. 2007; 34:554].

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Pregnancy and IA

In 1997, in the only book [Patterson R, ed. Idiopathic anaphylaxis. Providence, RI: OceanSide Publications; 1997] ever devoted to the subject of IA, Dr. Roy Patterson devoted one paragraph to the subject of “Pregnancy and IA.” Here is what he wrote, in its entirety:

“When a diagnosis of IA is made in a patient who could become pregnant, measures should be taken to avoid pregnancy until the IA is in a state of remission and the patient is off prednisone. If control of IA is required, prednisone is indicated and the antihistamine of choice would be diphenhydramine [sold as Benadryl®]. Reference [Patterson R, ed. Idiopathic anaphylaxis. Providence, RI: OceanSide Publications; 1997; p. 67].”

The problem with Patterson’s advice is that his idea that IA could reliably be put into remission by a course of prednisone has not been borne out by the experience of most people who have IA. Control of the condition is a more realistic goal than is remission, and if that control can be established without the use of corticosteroids, that is probably better for the pregnant patient. However, I would certainly agree with Patterson that pregnancy should be avoided, if possible, until the condition is well-controlled.

As for the safest H1 antihistamine to take during a pregnancy, in a 2002 chapter on this subject, Schatz [Schatz M. H1-Antihistamines in pregnancy and lactation. In: Simons FER. Histamine and H1-Antihistamines in Allergic Disease. 2nd, revised and expanded ed. New York: Marcel Dekker, Inc.; 2002; 421–436] sums up the research this way:

Vector drawing of a pill bottle by Kevin Dufendach, from Wikimedia Commons
“More recently, we have recommended chlorpheniramine [sold under a number of brand-names, including Chlor-Trimeton® in the US and Chlor-Triptolon® in Canada], based on duration of availability, animal study results, and the quantity and quality of reassuring human data.... If chlorpheniramine is not effective or well tolerated, tripelennamine [sold as Pyribenzamine® by Novartis] was suggested as an alternative. First-generation drugs such as diphenhydramine [sold as Benadryl®] and hydroxyzine [aka Atarax], for which human experience during pregnancy is large but for which animal and/or human data have raised some concerns regarding congenital malformations, would be considered after the first trimester. Diphenhydramine should be used at any time in the pregnancy if injectable antihistamine therapy is indicated, since there is no equally effective parenteral [any medication not given by mouth] substitute.” Reference [Schatz M. H1-Antihistamines in pregnancy and lactation. In: Simons FER. Histamine and H1-Antihistamines in Allergic Disease. 2nd, revised and expanded ed. New York: Marcel Dekker, Inc.; 2002; p. 431].

So, since chlorpheniramine is one of the safest antihistamines — and also happens to provide some measure of mast cell-stabilization — it may be the best control medicine for the first trimester, if not for the entire pregnancy.

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Summary

To summarize what I've learned from the sources I've found:

Photograph of a mother with her newborn child, from Wikimedia Commons
  • Whether you are diagnosed with IA or mastocytosis, having your disease under control is your first priority. Work with your allergist, immunologist or other mast-cell specialist to control your attacks before you conceive, and plan to work closely with him or her throughout your pregnancy.

  • The best choice for an H1 antihistamine, especially in the first trimester, may be chloripheniramine. It can be sedating, but it has a long track record of safety and it can also help to stabilize your mast cells to some extent.

  • Be very careful about taking antibiotics during the pregnancy. While any kind of infection can increase your tendency to have anaphylaxis, antibiotics are the medication most likely to trigger anaphylaxis within the general population. Work with your doctor to find medications that both you and your baby can tolerate.

  • Avoid anything that you feel has triggered exacerbations of your mast cell-related symptoms in the past. You may have to be very careful about where you go and what you do while you are pregnant, but doing so may help you to give birth to a healthy, full-term baby.

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Page last updated: May 16, 2011

 
All information contained in this site is one layperson's interpretation of medical journal articles, textbooks, seminars, presentations, and other materials. Nothing that is stated here should carry more weight than the informed and considered opinions of your own highly trained and qualified medical caregivers. The author of this site is not a doctor and has absolutely no authority to prescribe or diagnose.

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