Incidence of New Asthma in Pregnancy and Associated Risk Factors: A 10-Year Nationwide Population-Based Study

Asthma is a common and significant public health issue, and is one of the most serious complications during pregnancy.1, 2, 3 Pregnancy is also an important risk factor for asthma exacerbations.1 Asthma symptoms worsen in approximately one-third of pregnant women with asthma.4 Exacerbation and poor symptom control during pregnancy are associated with worse outcomes for both mothers and babies.2 Thus, aggressive treatment is important to avoid fetal hypoxia during pregnancy.1, 5 If asthma is well controlled throughout pregnancy, there is little to no increased risk of adverse maternal or fetal complications.6 Thus, all pregnant women with asthma should be considered at high risk for frequent exacerbations,3 and monthly monitoring is recommended for asthmatic women during pregnancy.7

Because pregnancy is a major risk factor for asthma flare-ups, some patients may experience their first asthma symptoms and/or exacerbation during pregnancy. Unexpected asthma flare-up in such patients can become severe and potentially lead to pregnancy complications.8 Kim et al.8 reported that 12.6% of pregnant women with asthma had no history of asthma for 1 year before pregnancy, and that the rate of hospitalization for asthma exacerbation was about 2.7 times higher in those patients than in pregnant women previously diagnosed with asthma.

This study evaluated the epidemiology of newly diagnosed asthma during pregnancy and the associated risk factors among previously nonasthmatic women.

During the 4-year study period (2012–2015), 1,381,845 women who had no asthma before pregnancy gave birth (Fig. 1); 7.5% (n = 103,126) of them required OCS treatment for asthma flare-ups during pregnancy, among whom 18.6% required hospitalization and/or ER visits (16.3% and 12.1%, respectively). The frequency of asthma flare-up did not vary by the pregnancy trimester.

Fig. 1
Flowchart of the study design.

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Advanced maternal age, primiparity, and multi-fetal pregnancy were risk factors for asthma flare-ups during pregnancy (Table 1). The analysis of maternal age as a continuous variable produced similar results (odd ratio [OR], 1.632; 95% confidence interval [CI], 1.198–1.824; P < 0.0001), as did a subgroup analysis by age, but statistical significance was found only for women in their 30s except among those with rhinitis (Supplementary Table S1). The risk of asthma exacerbation was higher for multi- than single-fetal pregnancies (OR, 3.338; 95% CI, 3.226–3.454; P < 0.001) after adjustment for age, delivery season, and year. Comorbidities including rhinitis, urticaria, GERD and neuropsychiatric disorders were identified as significant risk factors.

Table 1
Characteristics of the study population

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Two nested case-control studies (1:3 matching for age and year and season of delivery in one study and for same variables and additionally rhinitis severity in the other) yielded similar results (Supplementary Tables S2 and S3). The same results were obtained in sensitivity analysis of 1,073,030 women with a first (or only) pregnancy, including the same number of primiparous pregnancies as in the original analysis but fewer (by 36.9%; 463,222 vs. 772,037 cases) multiparity pregnancies, but with a higher OR of primiparity (Supplementary Table S4).

Supplementary Fig. S1 shows the ROC curve obtained with the risk factors including age, parity, fetus, and rhinitis for predicting asthma flare-ups. The sensitivity was 0.53 and the specificity was 0.69, with an AUC of 0.638 and 33.7 years as the optimal age cutoff.

Fig. 2 shows the incidence of an asthma flare-up for the entire study population according to the identified risk factors using 34 years as the optimal age cutoff from ROC curve analysis. Among those with moderate-to-severe rhinitis regardless of the number of fetuses, 23.0% of pregnant women ≥ 34 years of age and 24.3% of those < 34 years of age experienced asthma flare-ups during pregnancy. In those ≥ 34 years of age with primiparity and multi-fetal pregnancy regardless of rhinitis status, 22.7% experienced asthma flare-ups requiring OCS treatment during pregnancy, compared to only 3.5% of those < 34 years of age.

Fig. 2
Proportion of pregnant women with asthma flare-up during pregnancy according to age, rhinitis, and pregnancy characteristics.
^*Annual hospital visits for rhinitis.

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Cesarean section was more common in pregnant women with asthma flare-ups, but preterm labor, placenta previa, preeclampsia, and gestational diabetes mellitus did not differ between the two groups (Table 2). During the 3-year period following giving birth, only 9.0% of patients with an asthma flare-up during pregnancy visited a hospital for asthma.

Table 2
Adverse pregnancy outcomes according to the presence of asthma flare-up

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Among pregnant women who had not been diagnosed with asthma for at least 4 years prior to pregnancy, 7.5% experienced an asthma flare-up during pregnancy, including 18.6% who suffered a severe asthma exacerbation. The incidence rate of asthma for Korean adults 20–40 years of age was determined to be ~0.4% in 2012.14

In women with previously diagnosed asthma, asthma worsens during pregnancy in 16.5%–50%, and about 20% experience severe exacerbations, including OCS treatment, hospitalization, or ER visits.2, 15, 16 Ali et al.5 reported that 5% of patients with clinically stable asthma experience asthma exacerbation during pregnancy, while women with well controlled asthma and no history of asthma exacerbation before pregnancy are at low risk of exacerbation (0.5%).5 However, in our study population, a substantial proportion of women with no recent history of asthma experienced asthma exacerbation during pregnancy.

Moderate-to-severe rhinitis was a major risk factor for asthma flare-ups. Because this study included only women who had no history of asthma over 4 years and the study population was very large, strong bias (asthma treatment and adherence to asthma medication)2, 6 was avoided in the evaluation of the effects of individual and pregnancy-related factors on asthma flare-up during pregnancy. Rhinitis is a well-known risk factor both for asthma development and exacerbation. The nasal symptoms of patients with rhinitis can be exacerbated during pregnancy,17, 18 and worsening rhinitis can trigger a flare-up of hidden or subclinical asthma during pregnancy.17, 18 A previous study reported significant concordance between rhinitis and asthma in terms of clinical course during pregnancy.10 However, asthma before pregnancy may be underdiagnosed among rhinitis patients. Thus, screening for asthma symptoms before pregnancy, patient education, and close monitoring of asthma symptoms during pregnancy are necessary in women with moderate-to-severe rhinitis.

Primiparity and multiple fetuses were risk factors for asthma development in older pregnant women although the AUC using multiple risk factors was not adequate to predict asthma flare-ups. There are a few reports of a relationship between the age of pregnant women and asthma flare-up, but these studies have a limited number of subjects15 or uncontrolled biases such as asthma control status before pregnancy.19 Also in our subgroup analyses, the small number of patients may explain our finding that primiparity and multi-fetal pregnancy were not significant risk factors among women in their 40s. Birth rates among women of advanced maternal age (age > 35 years) have continued to increase.20, 21 An advanced maternal age is associated with an increased risk of maternal and fetal complications due to aging-related biological factors such as changes in hormone levels20, 21 and less efficient adaptation of the maternal cardiovascular system to pregnancy,21 which may also trigger asthma flare-ups during pregnancy. Advanced maternal age is a risk factor for multiple gestations due to multiple ovulations in older age21 and the high rates of advanced reproductive technology use in older women. The incidence of multifetal gestation has increased over the past several decades,22 and multifetal pregnancy is a risk factor for other pregnancy complications, maybe due to greater hormonal changes and oxygen requirement in multifetal pregnancy.22, 23, 24 Meanwhile, there have been few studies with very small populations regarding parity.10

This study had several limitations. First, asthma was not confirmed by diagnostic tests, which were not available in our claims data. Because dyspnea in pregnancy is common and there are many differential diagnoses for pregnant women, including GERD,3 a strict definition consisting of OCS treatment and three separate hospital visits for asthma was used to exclude other conditions. Second, enrolled participants without asthma for more than 4 years before pregnancy may nonetheless have had a history of asthma before the cutoff date, such as when they were young. Nonetheless, our findings demonstrate the importance of asthma screening and monitoring for all pregnant women, regardless of their asthma history, and particularly for those with risk factors, despite the conclusions in previous studies for patients with stable asthma.5 Third, our analysis did not consider the severity of other comorbidities including urticaria, GERD, or neuropsychiatric disorders. However, not only was rhinitis the strongest risk factor but its prevalence was very high in both cases and controls, thus justifying a further analysis according to the severity of rhinitis. The prevalence of other comorbidities was relatively low and the severity of each disease could not be easily classified. In addition, there were no data about known triggers for asthma symptoms such as smoking4, 15 and obesity.25, 26 Finally, only 9.0% of patients continued asthma treatment after giving birth. However, besides well-known poor adherence to asthma treatment in general population, asthma newly developed during pregnancy among nonasthmatics in our study and it is reported that the severity of asthma usually returns to baseline after delivery.4

A substantial proportion of women without a history of asthma experienced asthma exacerbation during pregnancy. Multi-fetal pregnancy as primiparity at an older age and moderate-to-severe rhinitis across all age groups were risk factors for asthma flare-ups during pregnancy. Because asthma exacerbations can endanger the mother and fetus, screening for asthma before pregnancy and close monitoring of asthma symptoms during pregnancy are needed for women with these risk factors.

Supplementary Table S1

Results of subgroup analysis by age

Supplementary Table S2

Nested case-control study with matching for age and year and season of delivery

Supplementary Table S3

Nested case-control study with matching for age, year and season of delivery, and annual frequency of hospital visits for rhinitis

Supplementary Table S4

Characteristics of the study population in a sensitivity study with first or only pregnancy during study period

Supplementary Fig. S1

Receiver operating characteristic curve used to predict asthma flare-up during pregnancy.