Review outlines safe asthma, allergy treatments during pregnancy
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Patient education and treatment can safely reduce the risks that women with asthma and other allergic diseases face during pregnancy, according to a review published in Allergy.
Birgit Pfaller, MD, of Karl Landsteiner University of Health Sciences in Krems, Austria, and colleagues noted that a shift in type 2 mechanisms during pregnancy may contribute to deterioration of asthma control and aggravation of chronic rhinosinusitis, and asthma along with other allergic diseases like allergic rhinitis, food allergy, Hymenoptera allergy or atopic dermatitis can affect up to 30% of women of childbearing age.
Asthma management
Uncontrolled asthma during pregnancy increases the risks for preeclampsia, caesarean delivery, preterm delivery, low birth weight and babies who are small for their gestational age, as well as for early-onset and more pronounced asthma in the offspring, according to Pfaller and colleagues.
Data suggest that asthma exacerbation — occurring at a range of 13% to 52% during pregnancy — is proportional to the disease’s severity. Most of these exacerbations happen during the second and beginning of the third trimesters. Asthma-related symptoms decrease during the final weeks of pregnancy, with exacerbations rarely occurring during labor.
The researchers recommended that pregnant women with asthma enroll in an asthma management program that regularly monitors their disease activity. Also, these programs can reassess inhaler use and techniques to improve medication adherence and self-management.
Further, the researchers recommended a stepwise approach such as the Global Initiative for Asthma guidelines to improve risk control and symptom reduction.
Inhaled short-acting beta-agonists, inhaled corticosteroids (ICS), inhaled long-acting beta-agonists (LABAs), leukotriene receptor antagonists (LTRAs), inhaled tiotropium bromide, oral steroids and biologics are among the most common medications for asthma management.
Inflammation-based management with inhaled steroids may reduce asthma exacerbations and improve pregnancy outcomes. Also, although it isn’t preferred, the researchers wrote, theophylline might be an alternative add-on treatment for asthma during pregnancy. Theophylline crosses the placenta, so careful titration and regular monitoring of dose levels are advised.
Clinicians also have used systemic corticosteroids as maintenance therapy to treat severe asthma during pregnancy, in addition to short courses to treat exacerbations.
Among inhaled therapeutics, the researchers called albuterol/salbutamol the preferred and most studied beta-agonist for asthma treatment. The researchers also expected LBAs to have a similar safety profile. Fluticasone and budesonide are preferred for ICS treatment, which should not be halted during periconceptional care or pregnancy.
LTRAs have not shown any associations with major congenital malformations or adverse perinatal outcomes, although the researchers advised clinicians to discuss recent black box warnings about mental health side effects related to montelukast during the counselling process.
When conventional asthma treatment approaches are poorly tolerated or ineffective, the researchers recommended biologics, which include the IgG1 isotypes omalizumab (Xolair; Genentech, Novartis), benralizumab (Fasenra, AstraZeneca) and mepolizumab (Nucala, GlaxoSmithKline), and the IgG4 isotypes dupilumab (Dupixent, Sanofi) and reslizumab (Cinqair, Teva). Although animal data on biologics are reassuring, the researchers wrote, published human data are rare. So, clinicians should consider biologics during pregnancy after informed and shared decision-making.
Other allergic diseases
Noting 54 studies assessing their use during pregnancy, the researchers recommended nonsedating, second-generation antihistamines for treatment during pregnancy and cited their safety, particularly regarding congenital malformations.
When it comes to sublingual immunotherapy, there are no unfavorable outcomes with maintenance therapy, the researchers said. But clinicians should avoid initiating allergen-specific immunotherapies or dose-increase steps during pregnancy due to the rare but existing risk for treatment-associated anaphylaxis.
The researchers also reviewed immunosuppressants and said women who were using azathioprine before pregnancy may continue it, but risks for prematurity and other adverse pregnancy outcomes have been reported. Cyclosporine can be considered as well, as long as maternal blood pressure and kidney function are watched.
The researchers additionally recommended following the proposed stepwise approach from the European Task Force on Atopic Dermatitis for treating atopic dermatitis.
When moisturizers are not sufficient for managing atopic dermatitis, the researchers continued, first-line treatment should use topical corticosteroids, which present no increased risk for congenital malformations. Mild to moderate topical corticosteroids are preferred over very potent corticosteroids.
Pregnant women with allergic rhinitis or chronic rhinosinusitis can safely receive the same treatment as the general population, the researchers wrote, adding that corticosteroid nasal sprays are the most effective single maintenance therapy. They also said that budesonide can be the first choice for nasal application.
When anaphylaxis occurs among pregnant women, as in the general population, it must be recognized early, and epinephrine must be administrated immediately. Also, pregnant women should be positioned on their left side so the gravid uterus does not compress the aortocaval vessels. Systolic blood pressure must be kept higher than 90 mm Hg to maintain adequate uteroplacental perfusion. Fetal heart rate and status must be monitored during treatment.
Plus, the researchers recommended that clinicians provide patients with an anaphylaxis emergency plan and refresh and assess their information about allergen avoidance and long-term prevention during every clinic visit.
Contraindications for asthma and allergy disease treatment include methotrexate, which inhibits DNA synthesis, and mycophenolate mofetil, which is a purine synthesis inhibitor.
Overall, the researchers called preparedness, awareness and education the cornerstones of preconception counseling, and regular monitoring is key. Discussions with patients also are opportunities for re-education, they continued, about the benefits and risks of pharmacologic treatment.
Perspective
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Jennifer Namazy, MD
One-third of asthmatic pregnant women see their asthma get worse during pregnancy, but it’s almost impossible to figure out who that third is going to be. It’s important to focus on asthma control and have a plan in place, even in the planning stages of pregnancy. It’s also important to follow these women closely during pregnancy because there can be subtle changes in symptoms and lung function testing that can indicate whether a woman is starting to have her airway compromised.
Babies born to mothers with uncontrolled asthma have a higher risk for being premature, or having a smaller birth weight, largely because they can’t receive adequate oxygenation during development. But if we manage these patients well early on in pregnancy, and even before pregnancy, studies have shown we can improve those outcomes.
The authors of this review understand that education is important.
One of the biggest risks comes from the fact that when a woman realizes she’s pregnant, and she has asthma, she’s going to start thinking about the medications that she’s on and whether they will affect her baby. That’s completely understandable.
Many women either stop or reduce the medication they use during pregnancy. They tend to rely on a rescue inhaler rather than on a controller medication such as a steroid. These are the kinds of opportunities where you must educate your patients and come to some informed decision-making together. It’s important for medical professionals to have a dialogue with their pregnant patients so they can understand the risk of using medication vs. the risk of untreated medical conditions such as asthma.
The authors also did a great job in stressing that there are not a lot of safety data available for medications that are commonly used for asthma and allergies. Pregnant women for the most part are excluded from clinical trials. As a result, we just don’t have a lot of safety information for pregnant women for most available medications.
That’s why the Vaccines and Medications in Pregnancy Surveillance System (VAMPSS) was created. In coordination with the American Academy of Asthma, Allergy & Immunology, VAMPSS includes a task force and an independent advisory committee including members from the CDC, NIH and other societies trying to collect safety information in a systematic fashion to fill in these knowledge gaps and answer questions relatively quickly about the safety of medications.
Health care providers who take care of pregnant patients should engage with organizations such as MotherToBaby, which provides information about the use of medications during pregnancy. They also should enroll their patients in these ongoing studies when appropriate.
We need more information about women who are taking these medicines during pregnancy. The more information we have, the better informed conversations we can have with pregnant patients. We especially should focus on adherence and barriers to control, such as the fear of taking medicines, smoking and obesity, all of which can influence symptom control during pregnancy.
In the meanwhile, this review can help any medical professional who might see pregnant patients. It provides an overview of common allergic diseases and of the safety of commonly used medications based on the data that we have now. It’s a useful resource for providers.
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