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Asthma in pregnancy: Clinical course and physiologic changes

Asthma in pregnancy: Clinical course and physiologic changes
Authors:
Steven E Weinberger, MD, MACP, FRCP
Michael Schatz, MD, MS
Section Editors:
Anne E Dixon, BM, BCh
Charles J Lockwood, MD, MHCM
Deputy Editor:
Paul Dieffenbach, MD
Literature review current through: Jan 2024.
This topic last updated: Nov 30, 2021.

INTRODUCTION — Asthma is the most common pulmonary disease encountered during pregnancy, occurring in 3 to 8 percent of pregnant women [1-8]. Two questions about the interaction of asthma and pregnancy are raised by clinicians and patients alike:

●How does pregnancy affect asthma?

●How does asthma affect the outcomes of pregnancy?

The pathophysiology of asthma during pregnancy and the interrelationships of these two conditions will be reviewed here. The management of gestational asthma, the evaluation of dyspnea in pregnancy, and the changes in the respiratory system during pregnancy are discussed separately. (See "Management of asthma during pregnancy" and "Maternal adaptations to pregnancy: Dyspnea and other physiologic respiratory changes".)

RESPIRATORY PHYSIOLOGY DURING PREGNANCY — A review of maternal respiratory physiology during pregnancy is helpful in understanding the interrelationships between pregnancy and asthma. More detailed discussions of the normal physiologic changes in the cardiopulmonary system during pregnancy are presented separately. This review will emphasize those changes that directly impact or are influenced by co-existent asthma. (See "Maternal adaptations to pregnancy: Dyspnea and other physiologic respiratory changes" and "Maternal adaptations to pregnancy: Cardiovascular and hemodynamic changes" and "Maternal adaptations to pregnancy: Dyspnea and other physiologic respiratory changes", section on 'Physiologic pulmonary changes in pregnancy'.)

Maternal pulmonary function — The spirometric evaluation of asthma in pregnant patients is similar to that of non-pregnant patients, as airway mechanics do not change significantly during pregnancy. Forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC ratio, and peak expiratory flow are stable to slightly increased in pregnancy [9-14]. As in non-pregnant patients, the diagnosis of asthma can be confirmed by demonstrating reversible airflow limitation before and after bronchodilator inhalation or before and after initiation of empiric treatment for asthma [15]. The diagnosis of asthma and the pharmacologic treatment of asthma during pregnancy are discussed separately. (See "Asthma in adolescents and adults: Evaluation and diagnosis" and "Pulmonary function testing in asthma" and "Management of asthma during pregnancy".)

While spirometry is minimally affected by pregnancy, some pulmonary function test measurements do change (figure 1) [13,16]. Vital capacity (VC) and total lung capacity (TLC) are usually preserved due to increased mobility and flaring of the ribs and unimpaired diaphragmatic excursion, although TLC may decrease slightly in the last trimester [13,17]. Based on small case series, expiratory reserve volume (ERV), residual volume (RV), and functional residual capacity (FRC) decrease over the course of the second and third trimesters, presumably due to diaphragm elevation from the enlarging uterus [13,16,17].

Maternal airway hyperresponsiveness — Bronchoprovocation challenge is generally avoided during pregnancy, and pregnancy is a relative contraindication for methacholine challenge, so limited data are available about maternal airway hyperresponsiveness during pregnancy [15,18]. In a small prospective study of 16 asthmatic women, for example, the airways became less hyperreactive in most patients during pregnancy, as shown by measurements of the PC20 (ie, the dose of methacholine needed to produce a 20 percent fall in FEV1) (figure 2) [19]. These changes did not correspond to changes in the levels of estriol or progesterone. (See "Bronchoprovocation testing".)

Maternal arterial blood gases — Minute ventilation increases during pregnancy, presumably due to increased circulating levels of progesterone [20]. The increase in minute ventilation, which exceeds metabolic demands, lowers alveolar and arterial tension of carbon dioxide (PaCO2) while simultaneously increasing alveolar and arterial oxygen tension (PAO2 and PaO2). The resulting respiratory alkalosis induces secondary compensation through renal loss of bicarbonate. Thus, normal blood gases during pregnancy reveal a higher PaO2 (100 to 106 mmHg [13.1 to 14.1 kPa]) and a lower PaCO2 (28 to 30 mmHg [3.72 to 3.99 kPa]) than in the non-pregnant state, typically accompanied by a slightly alkalotic pH.

During an acute asthma exacerbation, any associated changes in blood gases are superimposed on the "normal" respiratory alkalosis of pregnancy. Thus, a PaCO2 >35 mmHg (4.66 kPa) or a PaO2 <70 mmHg (9.31 kPa) associated with acute asthma represent more severe compromise during pregnancy than in the non-gravid state.

Fetal oxygenation — Arterial oxygen tension PaO2 in the fetus is only about one-third to one-fourth the PaO2 in the adult [21]. The fetus normally thrives at this low oxygen level due to a number of compensations, such as fetal hemoglobin and changes in the oxyhemoglobin dissociation curve. However, fetal oxygenation may be threatened in a number of ways that are potentially relevant to gestational asthma. First, maternal hypoxemia directly reduces oxygen supply to the fetus. Second, hypocapnia and/or alkalosis itself may cause fetal hypoxia, although the exact mechanism is unclear. Finally, reduction in uterine blood flow (potentially due to exogenous or endogenous vasoconstrictors, dehydration, hypotension, or significant maternal alkalosis) may compromise fetal oxygenation.

It appears that the fetus can compensate for hypoxemia in a number of ways, including redistribution of circulation to vital organs, decreased gross body movements, and increasing tissue oxygen extraction. The exact level and duration of fetal hypoxemia that exceed these compensatory mechanisms are not defined in humans. A common response to chronic hypoxia is deferment of growth needs in favor of vital functions, resulting in a small for gestational age fetus.

EFFECTS OF PREGNANCY ON ASTHMA — The clinical effect of pregnancy on asthma is variable [1,8,9,22,23]. This was illustrated by a prospective study that followed 366 pregnancies in 330 asthmatic women [24]. Asthma worsened during pregnancy in 35 percent, improved in 28 percent, and was unchanged in 33 percent; 4 percent were uncertain about a change. However, a subsequent study in 308 pregnant women using an unsupervised machine learning approach suggested that asthma control remained the same in 60 percent of women and worsened in 40 percent [25]; this study did not identify a group of women whose asthma control improved during pregnancy. In women with well-controlled asthma at baseline, 23 percent experienced worsening of asthma during pregnancy, whereas 56 percent of women with poorly controlled asthma at baseline became worse during pregnancy.

General trends — Most studies suggest that asthma severity prior to pregnancy is a predictor of asthma severity during pregnancy [22,23,26]. The following additional trends were noted among 330 pregnant women with asthma [24]:

●In women who improved, the improvement was gradual as pregnancy progressed.

●In women whose asthma worsened, the increase in symptoms was most prominent between weeks 29 and 36 of gestation, although other studies have reported an increase in asthma exacerbations in weeks 14 to 24 [26,27].

●Asthma was generally less severe during the last four weeks of pregnancy.

●Substantial asthma symptoms were uncommon during labor and delivery.

●The course of asthma in successive pregnancies in an individual patient tended to be similar.

In a review of prescription databases, inhaled glucocorticoid use decreased during the first trimester, compared with prepregnancy, increased during the second trimester, and decreased again in the third trimester [28].

Acute exacerbations — Asthma exacerbations have been reported to occur in 20 to 45 percent of pregnant asthmatic patients with severe exacerbations in approximately 10 percent [23,29,30]. Being overweight or obese [31] and having excessive first trimester weight gain [32] have been identified as risk factors for asthma exacerbations during pregnancy. Other studies have shown that asthma exacerbations are more common and more severe in women with a previous exacerbation in the 12 months prior to pregnancy [30], more difficult to control asthma at baseline (require higher doses of inhaled glucocorticoids) [30], smoking during pregnancy [29], and anxiety during pregnancy [33]. These exacerbations are not uniformly distributed over the course of pregnancy. In one observational study that followed 504 pregnant asthmatic patients, exacerbations occurred most frequently during weeks 17 through 24 of pregnancy (figure 3) [27]. A similar observational study of 146 patients revealed a peak incidence of severe asthma exacerbations during weeks 14 through 24 of pregnancy and a peak incidence of mild asthma exacerbations during weeks 25 through 32 of pregnancy [26].

The reason for the unequal distribution of asthma exacerbations over the course of gestation is unclear, although it has been demonstrated that many women decrease or stop taking their asthma medication shortly after becoming aware of the pregnancy [34-37], which can lead to subsequent deterioration in asthma control. In particular, inadequate use of inhaled glucocorticoids may increase the risk of an asthma exacerbation [26,27]. In one of the prospective studies mentioned above, only 4 percent of women taking inhaled glucocorticoids continuously from the start of pregnancy developed an acute attack, compared with 17 percent of women who were not [27].

EFFECTS OF ASTHMA ON PREGNANCY — The available literature suggests that asthma may negatively impact various aspects of pregnancy, including perinatal mortality and several common complications of pregnancy. However, the effect of asthma on pregnancy should not be considered a contraindication to pregnancy for patients with asthma, as adequate therapy and good asthma control can minimize these complications.

Complications of pregnancy — A number of investigators have found that asthma during pregnancy is associated with an increased incidence of perinatal mortality and increased risks of spontaneous abortion, hyperemesis, uterine hemorrhage, preeclampsia, complicated labor, neonatal mortality, prematurity, hypertensive disorders, and low birthweight infants [38-50]. However, such associations have not been found in all studies [44,51-53]. One database study suggested that the risk of pregnancy loss, preterm delivery, and low birth weight was greater in women with nonatopic asthma compared to women with the allergic asthma phenotype [54]. The following large studies suggest a small but significant increase in the complications of pregnancy associated with asthma and asthma exacerbations:

●A study from the United Kingdom evaluated the outcome of 281,019 pregnancies: 37,585 pregnancies of women with asthma and 243,434 pregnancies of women without asthma [45]. The pregnancies of women with asthma were more likely to be associated with miscarriage (OR 1.10, 95% CI 1.06-1.13), antepartum hemorrhage (OR 1.20, 95% CI 1.08-1.34), postpartum hemorrhage (OR 1.38, 95% CI 1.21-1.57), anemia (OR 1.06, 95% CI 1.01-1.12), depression (OR 1.52, 95% CI 1.36-1.69), or cesarean delivery (OR 1.11, 95% CI 1.07-1.16). There were no differences in stillbirths, pregnancy termination, or most obstetrical complications (eg, placental abruption, preeclampsia, hypertension, diabetes). The outcomes of preterm births, low birth weight infants, and intrauterine growth restriction were not evaluated in this study.

●A retrospective cohort study examined the effect of asthma on 223,512 singleton pregnancies from 12 clinical centers in the United States [46]. After adjusting for maternal age, race/ethnicity, marital status, prepregnancy body mass index, smoking, alcohol use, comorbidities, and insurance status, women with asthma had higher odds of a number of complications of pregnancy, including preeclampsia (aOR 1.14, 95% CI 1.06-1.22), preterm birth (aOR, 1.17, 95% CI 1.12-1.23), and pulmonary embolism (aOR, 1.71, 95% CI 1.05-2.79).

●A systematic review and meta-analysis that did not include the two above studies found an increased risk of congenital malformations among women with asthma compared with control women without asthma (RR 1.11, 95% CI 1.02 to 1.21) [55]. However, the effect was only significant in the subcategory of retrospective studies without active asthma management. Use of bronchodilators, use of inhaled glucocorticoids, and asthma exacerbations were not associated with congenital malformation risk.

●In a population cohort study of 103,424 singleton pregnancies, asthma exacerbations were associated with higher odds of preeclampsia (OR 1.30, 95% CI 1.12–1.51) and pregnancy-induced hypertension (OR 1.17, 95% CI 1.02–1.33) in the mothers, and low birthweight (OR 1.14, 95% CI 1.00–1.31), preterm birth (OR 1.14, 95% CI 1.01–1.29), and congenital malformations (OR 1.21, 95% CI 1.05–1.39) in the babies [56].

Possible causes of adverse outcomes — Two possible causes for these adverse pregnancy outcomes have been suggested [57]:

●Hypoxia and other direct consequences of poorly controlled asthma – Direct consequences of asthma that could impair fetal oxygenation and uteroplacental blood flow include maternal hypoxemia, hypocapnia, and alkalosis, all of which can occur during an acute exacerbation of asthma. Markers of more severe or uncontrolled asthma are associated with adverse perinatal outcomes, as observed in the following reports:

•An observational series of 2123 pregnant women with asthma demonstrated that decreased gestational maternal forced expiratory volume in one second (FEV1) was associated with gestational hypertension and preterm birth compared to women with a normal FEV1 [58].

•Another series found a modest increased risk (OR 1.64, 95% CI 1.02-2.64) of congenital malformations in the infants of asthmatic women experiencing a severe exacerbation during the first trimester of pregnancy compared with infants of asthmatic mothers not experiencing an exacerbation [59]. No association was noted between moderate asthma exacerbations and congenital malformations.

•A large database study of 15,107 pregnancies found a correlation between markers of uncontrolled asthma and spontaneous abortion [49].

•A systematic review and meta-analysis found that asthma exacerbations and oral glucocorticoids during pregnancy were associated with an increased risk of low birth weight and preterm infants [60].

●Complications of asthma medications — Complications of medications used for the treatment of asthma are reviewed in detail elsewhere. (See "Management of asthma during pregnancy".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Asthma in adolescents and adults" and "Society guideline links: Respiratory disease in pregnancy".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)

●Basics topics (see "Patient education: Asthma and pregnancy (The Basics)")

●Beyond the Basics topics (see "Patient education: Asthma treatment in adolescents and adults (Beyond the Basics)" and "Patient education: Asthma and pregnancy (Beyond the Basics)" and "Patient education: Trigger avoidance in asthma (Beyond the Basics)" and "Patient education: How to use a peak flow meter (Beyond the Basics)" and "Patient education: Inhaler techniques in adults (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●The forced vital capacity (FVC), forced expiratory volume in one second (FEV1), FEV1/FVC ratio, and peak expiratory flow (PEF) do not change significantly during normal pregnancy. (See 'Maternal pulmonary function' above.)

●Residual volume (RV) and functional residual capacity (FRC) decrease during pregnancy, while total lung capacity (TLC) decreases only slightly in the last trimester (figure 1). (See 'Maternal pulmonary function' above.)

●Minute ventilation increases during pregnancy, associated with increased tidal volume, presumably due to increased circulating levels of progesterone. Thus, normal pregnancy is associated with a compensated respiratory alkalosis. (See 'Maternal arterial blood gases' above.)

●Arterial blood gases obtained during pregnancy normally reveal a higher arterial oxygen tension (PaO2) in the range of 100 to 106 mmHg (13.1 to 14.1 kPa) and a lower arterial carbon dioxide tension (PaCO2) in the range of 28 to 30 mmHg (3.72 to 3.99 kPa), compared with the non-pregnant state. (See 'Maternal arterial blood gases' above.)

●The diagnosis of asthma during pregnancy is based on the demonstration of reversible airflow obstruction by spirometry over time or in response to inhaled bronchodilator. However, bronchoprovocation challenge is usually avoided during pregnancy. (See 'Maternal pulmonary function' above and "Asthma in adolescents and adults: Evaluation and diagnosis" and "Pulmonary function testing in asthma".)

●In general, asthma worsens during pregnancy in approximately 30 to 40 percent of patients and either remains stable or improves in the remainder. However, asthma severity prior to pregnancy is related to asthma severity during pregnancy. (See 'Effects of pregnancy on asthma' above.)

●Asthma exacerbations affect 20 to 45 percent of pregnant asthmatic patients and tend to occur during the middle trimester. (See 'Acute exacerbations' above.)

●Gestational asthma is associated with a relatively small but statistically significant increase in pregnancy complications, such as perinatal mortality, preeclampsia, and preterm delivery. However, appropriate therapy and good asthma control probably minimize these complications. (See 'Effects of asthma on pregnancy' above and "Management of asthma during pregnancy".)

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Topic 555 Version 24.0

References

1 : Asthma during pregnancy: mechanisms and treatment implications.

2 : Pregnancy and asthma: recent developments.

3 : Asthma in pregnancy.

4 : Perinatal outcomes in women with asthma during pregnancy.

5 : General strategy for the management of bronchial asthma in pregnancy.

6 : Management of rhinitis and asthma in pregnancy.

7 : Asthma therapy during pregnancy.

8 : Asthma prevalence among pregnant and childbearing-aged women in the United States: estimates from national health surveys.

9 : Asthma in pregnancy.

10 : [Evaluation of respiratory tract function in healthy women in the last month of uncomplicated pregnancy].

11 : Changes in pulmonary function during pregnancy: a longitudinal cohort study.

12 : Asthma and pregnancy: a prospective study of 198 pregnancies.

13 : Pregnancy and the lung.

14 : Large airways function during normal pregnancy.

15 : Large airways function during normal pregnancy.

16 : RESPIRATORY AND ACID-BASE CHANGES DURING PREGNANCY.

17 : Pulmonary function in pregnancy. I. Serial observations in normal women.

18 : ERS technical standard on bronchial challenge testing: general considerations and performance of methacholine challenge tests.

19 : Improvement in airway responsiveness and asthma severity during pregnancy. A prospective study.

20 : Respiratory physiologic changes in pregnancy.

21 : Fetal oxygenation, assessment of fetal well-being, and obstetric management of the pregnant patient with asthma.

22 : The change of asthma course during pregnancy.

23 : Asthma morbidity during pregnancy can be predicted by severity classification.

24 : The course of asthma during pregnancy, post partum, and with successive pregnancies: a prospective analysis.

25 : Determining the Clinical Course of Asthma in Pregnancy.

26 : Severe asthma exacerbations during pregnancy.

27 : Acute asthma during pregnancy.

28 : Inhaled corticosteroid use during pregnancy among women with asthma: A systematic review and meta-analysis.

29 : The effect of cigarette smoking on asthma control during exacerbations in pregnant women.

30 : Factors Associated with Asthma Exacerbations During Pregnancy.

31 : Influence of Maternal Body Mass Index and Macrophage Activation on Asthma Exacerbations in Pregnancy.

32 : Excessive gestational weight gain in first trimester is a risk factor for exacerbation of asthma during pregnancy: A prospective study of 1283 pregnancies.

33 : Psychosocial variables are related to future exacerbation risk and perinatal outcomes in pregnant women with asthma.

34 : Cessation of asthma medication in early pregnancy.

35 : Management of asthma by pregnant women attending an Australian maternity hospital.

36 : Asthma during pregnancy: the experiences, concerns and views of pregnant women with asthma.

37 : A population analysis of prescriptions for asthma medications during pregnancy.

38 : Intrauterine growth is related to gestational pulmonary function in pregnant asthmatic women. Kaiser-Permanente Asthma and Pregnancy Study Group.

39 : Association between pregnancy-induced hypertension and asthma during pregnancy.

40 : Association of asthma diagnosis, severity, symptoms, and treatment with risk of preeclampsia.

41 : Maternal asthma and pregnancy outcomes: a retrospective cohort study.

42 : Risk of perinatal mortality associated with asthma during pregnancy.

43 : A meta-analysis of adverse perinatal outcomes in women with asthma.

44 : Pregnancy and birth outcomes in families with asthma.

45 : A comprehensive analysis of adverse obstetric and pediatric complications in women with asthma.

46 : Obstetric complications among US women with asthma.

47 : Asthma during pregnancy--a population based study.

48 : Neonatal health of infants born to mothers with asthma.

49 : Relationship between maternal asthma, its severity and control and abortion.

50 : Trends in and Maternal Outcomes of Delivery Hospitalizations of Patients With an Asthma Diagnosis.

51 : Asthma during pregnancy.

52 : Perinatal outcomes in the pregnancies of asthmatic women: a prospective controlled analysis.

53 : Influence of asthma in pregnancy on labor and the newborn.

54 : The Influence of Asthma and/or Hay Fever on Pregnancy: Data from the 1995 National Survey of Family Growth.

55 : The risk of congenital malformations, perinatal mortality and neonatal hospitalisation among pregnant women with asthma: a systematic review and meta-analysis.

56 : Effect of asthma exacerbation during pregnancy in women with asthma: a population-based cohort study.

57 : Asthma and pregnancy.

58 : Spirometry is related to perinatal outcomes in pregnant women with asthma.

59 : Asthma exacerbations during the first trimester of pregnancy and congenital malformations: revisiting the association in a large representative cohort.

60 : Effects of asthma severity, exacerbations and oral corticosteroids on perinatal outcomes.

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