Asthma history may indicate risk for exacerbations during pregnancy
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Women who experienced asthma exacerbations before pregnancy and more severe asthma at the start of pregnancy had a greater rate of exacerbations while pregnant, which can lead to poor pregnancy outcomes, according to a study.
Researcher Marleen Bokern, MSc, PhD candidate at London School of Hygiene and Tropical Medicine at University of London, and colleagues wrote their findings, published in The Journal of Allergy and Clinical Immunology: In Practice, could be used to develop a prediction rule and recommendations to optimize asthma management during pregnancy.
Previous studies have associated poorly controlled asthma and exacerbations with lower birth weight, preterm birth, preeclampsia, spontaneous abortion and congenital malformations, as well as increased risk for perinatal mortality and childhood asthma.
The researchers evaluated data of 1,461 women from Eastern Australia — all of whom were aged 18 years or older and had physician-diagnosed asthma — enrolled in the Asthma and Pregnancy Phase II Study (n = 84; 5.7%), the Managing Asthma in Pregnancy Study and Viral Exacerbations of Asthma in Pregnancy Study (n = 280; 19.2%), and the Breathing for Life Trial (n = 1,097; 75.1%) between 2004 and 2019.
Overall, 135 of these women (9.2%) experienced at least one severe asthma exacerbation during pregnancy, defined as worsening of asthma requiring hospitalization, ED presentation or a course of oral corticosteroids.
Women who experienced an exacerbation during pregnancy had significantly worse baseline asthma control as assessed by the Asthma Control Questionnaire (P = .001) and by the Global Initiative for Asthma assessment (P < .001). Also, asthma exacerbations in the 12 months before pregnancy were associated with more exacerbations during pregnancy (P < .001).
Women who demonstrated good inhaler technique (P = .016) and had a written action plan for their asthma (P < .001) before pregnancy experienced more frequent exacerbations as well, but these women may have already optimized their asthma management due to their more frequent or severe asthma, the researchers wrote.
Additionally, women who took more than 500 µg of inhaled corticosteroids (ICS) each day were more likely to experience exacerbations than women who did not use ICS or who used lower doses (P < .001).
In fact, higher doses of ICS were associated with the highest risk for exacerbations (adjusted OR = 3.2; 95% CI, 1.85-5.53), with higher ICS doses a likely proxy for more severe and/or uncontrolled asthma.
But despite this dosage and optimal management including a written asthma education plan and education, the researchers wrote, women with more severe asthma had more severe exacerbation during pregnancy.
The study further associated multiparity (P = .002) and gastrointestinal reflux (P = .044) with exacerbations. Pregnancy can induce or exacerbate gastrointestinal reflux disease, the researchers wrote, so women whose asthma is triggered by it may see their asthma exacerbated. Gastrointestinal reflux disease also may become a new trigger for women who previously didn’t experience it.
Based on these observations, researchers evaluated several models that could be used to predict asthma exacerbations during pregnancy. The model they found to be most predictive included reflux and food as triggers, forced expiratory volume in 1 second, history of asthma exacerbations, inhaler technique, possession of a written action plan, smoking status and ICS dose, with an area under the curve of 0.768 (95% CI, 0.705-0.832).
The researchers called current asthma severity and control and exacerbation history “important factors” associated with exacerbations that occur during pregnancy. They also called for more research into asthma triggers as risk factors for exacerbations, particularly food.
Before their models can be implemented in clinical practice, the researchers wrote, they must be validated.
“To increase applicability of the models in clinical practice, it would be useful to develop a prediction rule with a cut-off score for high, medium and low risk [for] exacerbations, and asthma management recommendations for each risk category,” they added. “Due to the potentially severe consequences of exacerbations for both mother and baby, this may help optimize asthma management during pregnancy.”
Perspective
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Michael S. Blaiss, MD
Women with frequent exacerbations during pregnancy are at a high risk for poor perinatal outcomes including preeclampsia, premature labor and birth, and low-birth-weight infants. Understanding the factors that increase the risk for asthma exacerbations during pregnancy may help the clinician better screen these women and prevent complications.
This prospective Australian study looked at numerous characteristics in more than 1,400 pregnant asthmatics to get clues on issues that trigger exacerbations during pregnancy. What they found are the same reasons for exacerbations that have been seen in asthmatic children, men and women who are not pregnant — the more baseline exacerbations a patient has and the more severe they are, and uncontrolled the asthma, the higher the risk is for continued and increased exacerbations.
Not surprisingly, the women who needed oral corticosteroids for their asthma during pregnancy had poorer baseline lung function and higher doses of ICS. Again, this points out that women with severe, uncontrolled asthma prior to pregnancy are more likely to have frequent issues with their asthma during pregnancy.
The relationship that did not make sense to me was between having a written asthma action plan and good inhaler technique and increased asthma exacerbations. You would think that these elements would relate to decreased asthma flareups. This may be due to the major flaw in this study, which is determination of adherence to treatment. It was assessed directly from the subject, with no objective measures.
Unfortunately, as we know, patients may not be very truthful about their degree of adherence to medications. This could explain why some women on high-dose ICS/long-acting beta agonists, with good inhaler technique and an action plan to follow, still suffered severe exacerbations.
We can’t say for sure that this applies to all patients. Data are mixed on the benefit of written asthma action plans in improving outcomes. Some of these women with frequent, severe exacerbations may require other treatments for optimal control, including biologics, and/or control of comorbidities such as gastroesophageal reflux, which worsens during pregnancy.
This study reinforces our need to aggressively manage and frequently follow women during pregnancy who have a history of frequent exacerbations, have poor lung function, are on high-dose ICS/long-acting beta agonists, and/or have severe, uncontrolled disease. It is not only important for the health of the mother, but also to ensure the best outcome for the pregnancy: a healthy newborn.
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