Safety of Performing Spirometry During Pregnancy: A Systematic Review

Highlights

What are the main findings?

• There are no studies examining the safety profile of spirometry during pregnancy.
• None of the studies which evaluated spirometry attempts by pregnant women reported any adverse events during the procedure

What are the implications of the main findings?

• Further studies are needed to evaluate the safety profile of spirometry during pregnancy.

Abstract

Introduction: It is estimated that up to 75% of pregnant women complain of dyspnea at some point during pregnancy. Asthma is the most common chronic pulmonary disease complicating pregnancy. Well controlled asthma does not affect pregnancy negatively. However, asthma exacerbations are linked with several adverse perinatal outcomes. As diligent treatment of asthma significantly reduces the number of asthma exacerbations, it is important to properly detect asthmatic patients among pregnant women in order to provide them with better care. The most efficient way to diagnose asthma is to perform spirometry with a reversibility test. There are no studies that have examined the safety of performing spirometry and, more specifically, a reversibility test, during pregnancy. Objectives: In this systematic review we aimed to review current available data regarding the safety of performing spirometry and a reversibility test during pregnancy. Patients and methods: For this systematic review, we searched PubMed, Scopus and Cochrane databases. We used the following search terms: (pregnancy); (spirometry); (lung function test); (pulmonary function test); (reversibility test); (post-bronchodilator challenge); (safety). Results: We collected reports of spirometry performed on pregnant women and analyzed them for complications that occurred during the procedure. Out of 13,594 records identified for the aforementioned search words, we included 78 documents that met the inclusion criteria. In total, the studies consisted of over 33,405 spirometry attempts performed by 10,617 pregnant women. Additionally, the reversibility test was conducted in nine studies. In all of the selected articles, there were no reports of adverse events occurring while performing spirometry. Conclusions: In this systematic review we aimed to summarize the current available data about the safety of performing spirometry during pregnancy. Several studies have investigated pulmonary function tests during pregnancy. No studies reported any adverse events that occurred while performing the procedure. In order to better characterize the safety profile of spirometry, including during pregnancy, further prospective studies systematically reporting on adverse symptoms during spirometry are required.

1. Introduction

Rationale: Dyspnea is one of the most common symptoms to be reported among pregnant women. It is estimated that up to 75% of pregnant women will complain of dyspnea at some point during pregnancy [1,2]. In majority, it comes from physiological adaptations the body undergoes in order to sustain a growing fetus. However, when dyspnea is accompanied by a cough or when it persists at rest and during the night further investigation is needed. Pulmonary function tests provide valuable findings to better understand the pathophysiology behind dyspnea. They help to establish a diagnosis of obstructive diseases, including asthma [3]. The prevalence of asthma during pregnancy varies depending on the population. American studies report that from 3 up to 8% of pregnant women have asthma [4]. A Danish study estimated that even up to 12% of pregnant women suffer from asthma [5]. Maternal asthma is linked with several adverse outcomes, both for the mother and the fetus [6,7,8,9]. For example, asthmatic women are more likely to develop preeclampsia, placenta previa and to undergo caesarean section, while for the infant, maternal asthma increases the risk of preterm birth, low birth weight, small-for-gestational age and congenital abnormalities [10,11,12]. As such, it is crucial to recognize pregnant women with asthma to provide better care and minimize the risk of adverse outcomes. In the past, pregnancy was considered a contraindication for lung function tests, and in current standards, late-term pregnancy remains a relative contraindication [13]. We therefore reviewed the published literature on the safety of performing spirometry during pregnancy.

Current guidelines for spirometry are based on a joint statement of American Thoracic Society and European Respiratory Society from 2019. In the report, late-term pregnancy is listed as one of the relative contraindications for spirometry testing. The reasoning behind this statement is linked to an increase in intra-thoracic or intra-abdominal pressure. There is, however, no source material to verify the origins of this annotation. The section on patient details lists age, height, weight and ethnicity as factors to be considered. There is no mention of pregnancy being a critical variable. Norms for the spirometry readings come from the European Respiratory Society Global Lung Function Initiative (GLI) document first published in 2012, later updated in 2022 [14]. In this paper, after reviewing 97,759 records obtained from healthy, non-smoking individuals, of which 55.3% were women, the reference ranges were established. The data were evaluated in relation to age, ethnicity and height. There is no mention of pregnancy being considered, either as a contraindication for the procedure or a variable affecting the spirometry result. Furthermore, a more general document considering pulmonary function tests as a whole was published by the two organizations in 2022 [15]. In this document pregnancy is mentioned only once, in a section addressing special considerations for lung volumes. It states that a pregnancy may affect lung volumes and therefore spirometry results obtained during pregnancy should be interpreted with caution. There is no elaboration on how pregnancy alters lung function. Linked source material leads to two papers. First, a research paper [16] detailing physiological and anatomical changes that a woman undergoes during pregnancy. Secondly, a cross-sectional study published in 2002 by McAuliffe et al. [17] which compares spirometry results obtained from women with singleton and twin pregnancy. There is no mention of the safety of performing spirometry while pregnant.

Objectives: To evaluate the safety of performing pulmonary function tests during pregnancy. We paid special attention to reports including the application of the reversibility test. Additionally, we searched for an answer to the question of whether multiple pregnancy poses a greater risk of adverse outcomes occurring during spirometry than a singleton pregnancy.

2. Materials and Methods

For this systematic review we followed the guidelines from the PRISMA 2020 statement (Supplementary Materials). The systematic review has not been registered in any database. Two independent investigators searched PubMed and Cochrane databases, Google Scholar, and forward and backward citations for studies published between the database search and 1 January 1970. We used the following search terms: (pregnancy); (spirometry); (lung function test); (pulmonary function test); (reversibility test); (post-bronchodilator challenge); (safety).

Eligibility criteria: We included documents reporting spirometry results obtained from pregnant individuals. We considered reports published in English, Polish, French, German and Spanish.

Selection process: First, we selected studies based on their titles, with eligibility criteria being on the topic of pulmonary function tests, pregnancy, asthma, or cystic fibrosis. Then, we skimmed through the abstracts of selected works and excluded those that did not involve spirometry being performed by pregnant women. Finally, we read through the full text of the remaining studies. We included studies for which full text was available online. We took note of any adverse events reported as occurring during the procedure. We counted the number of women tested and the number of spirometry tests performed. We paid special attention to studies involving the reversibility test.

All steps, including database search, study selection and study analysis, were performed independently by two investigators.

Study risk of bias assessment: The risk of bias in our study comes from the assumption that not reporting complications that might have happened during a pulmonary function test means that no complications occurred. The second limitation stems from the fact that the majority of studies we analyzed performed the objectives on otherwise healthy subjects, excluding patients with chronic illnesses, smokers or women with complicated pregnancies.

Effect measures: Safety, by the definition from the Merriam-Webster Dictionary, is ‘1: the condition of being safe from undergoing or causing hurt, injury, or loss’. In our review by safety we understood not experiencing any potential harms or risk, both to the mother and the fetus, during spirometry. Recognizing that there are a number of possible complications, we preemptively grouped them into categories based on the severity of the potential adverse events. The possible outcomes we suspected to occur were general complications that are expected to happen during procedure in otherwise healthy, non-pregnant subjects. These adverse events include:

• Respiratory alkalosis as a result of hyperventilation;
• Hypoxemia in a patient whose oxygen therapy has been interrupted;
• Chest pain;
• Fatigue;
• Paroxysmal coughing;
• Bronchospasm;
• Dizziness;
• Urinary incontinence;
• Increased intra-cranial pressure;
• Syncopal symptoms [18].

We propose a low-risk category for these complications that routinely occur even in the otherwise healthy population. Furthermore, we identified a high-risk category for adverse events that may require medical treatment or hospitalization.

Synthesis methods: Given the broadness of the subject investigated we categorized each document assessed for eligibility into a category as follows:

• Prospective longitudinal reports researching pulmonary function findings during the course of pregnancy;
• Cross-sectional studies examining women in groups of a certain trimester;
• Single spirometry measurement in a pregnant participant;
• Case reports.

In the first category we placed 28 studies. We recognized 19 prospective cross-sectional studies. There were 23 studies in which a single measurement of spirometry was performed, without dividing women into trimester groups. In the fourth category we found 8 case reports. We prepared graphs including the number of women participating in the study and the number of spirometry attempts obtained in the study. To meet the inclusion criteria, the study had to state the number of women involved in a study, gestational age they were examined in and the number of spirometry tests performed. It was not possible to conduct a meta-analysis as the studies we reviewed did not report any adverse events.

3. Results

For this analysis we identified nearly 14,000 results. After initial retrieval we screened 234 records, from which we excluded 41 based on being published before 1970 or being published in a different language than considered. Ultimately, 78 papers met the criteria for final inclusion in this analysis (Figure 1). There were no studies whose main objective was to examine the safety profile of spirometry during pregnancy.

We excluded studies that assessed pregnant women without performing a spirometry, review papers summarizing the topic of pregnancy-related dyspnea and retrospective studies examining historical findings, as there was no possibility for an adverse event to occur. We decided not to include papers that had no full text available. There were three studies that did not fit into any of the categories. One did not report the number of participants [19], the second paper examined remote spirometry [20], which raised concerns about whether the procedure was performed correctly and whether any adverse events would have been reliably reported in the absence of medical supervision. Finally, the third paper did not state the gestational age of the participants during testing and number of spirometry attempts obtained [21]. Further information available in Appendix A.

3.1. Prospective Longitudinal Studies

In our search we recognized twenty-eight prospective longitudinal studies that examined women throughout their pregnancy. In total 5973 women participated in those studies, with 27,688 spirometries performed. Thirteen studies examined women with asthma, three studies involved patients with cystic fibrosis and one study assessed women with cardiovascular diseases. Eleven studies were conducted in a healthy population, with consideration of smoking, parity and obesity as additional factors. Across reviewed longitudinal studies there were three papers where the reversibility test was performed. In total, 551 women underwent the examination. None of those studies reported any adverse events occurring during the procedure (Figure 2).

3.2. Prospective Cross-Sectional Studies

We found nineteen cross-sectional studies, in which participants were divided into groups based on the trimester they were examined in. Combined, there were 2158 women participating in those studies, with over 2188 procedures performed. There was one publication whose main objective was to evaluate pulmonary function by spirometry in women with high-risk pregnancies. It assessed 30 women with gestational diabetes and/or preeclampsia. The study did not report any adverse events to happen during spirometry in this population. One study from 2002 by McAuliffe et al. [17] compared singleton and twin pregnancies, examining 68 women with multiple pregnancies to 140 women with singleton pregnancies. None of the cross-sectional studies we considered mentioned having performed the reversibility test (Figure 3).

3.3. Studies with a Single Measurement of Spirometry

In our research we gathered twenty-three studies in which a single measurement of spirometry was performed on pregnant participants, without differentiating them by the trimester. Across those studies 2469 women were examined, with 3494 spirometry assessments performed. The difference in number comes from eight papers. First, a study that compared lung function tests in various positions, where each participant was examined sitting and standing [68]. Secondly, from the study that researched the impact of spinal anesthesia on respiratory function during caesarean section, where each participant performed baseline spirometry before induction of the anesthesia and shortly after [69]. We also included in this category a study that compared pulmonary function test results before and after implementing inspiratory muscle training and diaphragmatic breathing exercises for four weeks [70]. Lastly, five papers conducted a reversibility test, which gave two spirometry readings per participant. In nine of the studies women with asthma were examined; three studies involved participants with cystic fibrosis. Aside from the previously mentioned study examining women in late-term pregnancy there were two additional studies that performed lung function tests shortly before delivery by a caesarean section—a study by Lirk et al. [71] and a study by Kelly et al. [72] Another study that examined women in late-term pregnancy was a study by Çaltekin et al. [73] which assessed the relationship between maternal spirometry readings with umbilical cord blood gases values. Despite performing lung function tests in late-term pregnancy, no adverse effects were reported to happen during those procedures. Two studies researched lung function in women with preeclampsia—Roopnarinesingh et al. [74] and da Silva et al. [75] They did not report any adverse events to happen during spirometry. Among twenty-three considered single-measurement studies there were five which included performing the reversibility test on the participants. In these studies, 735 women were tested, and there was no report of complications happening while conducting the procedure (Figure 4).

3.4. Case Reports

For our analysis we considered eight case reports that mentioned performing pulmonary function tests on pregnant women. In these papers seventeen women were examined, with combined 38 spirometry assessments obtained. The first study involved a woman with infantile spinal muscular atrophy type II, the second study described a woman with a motor neurone disease. The third described a patient with alpha-1 antitrypsin deficiency. The fourth paper presented successful pregnancies in nine women with interstitial and restrictive lung disease. Two documents presented cases of women with Swyer–James–MacLeod syndrome. The seventh paper involved a patient with a chronic obstructive pulmonary disease, and finally, the eighth paper reported two cases of new onset asthma during pregnancy. In this last document there is a mention of the reversibility test being conducted. None of the papers reported any adverse events occurring during pulmonary function tests (Figure 5).

After an initial search we screened 234 papers regarding lung function tests among the pregnant population. Of these, we selected 78 documents that met the inclusion criteria for this analysis. After reviewing the material, we did not find any information on adverse events during spirometry. There are, however, two considerations that need to be acknowledged. Firstly, not reporting complications does not necessarily indicate that none occurred. It is possible that mild symptoms, which may occur even in healthy individuals, were not described. Secondly, many studies were conducted in otherwise healthy women. Thirty-eight studies were carried out in populations with an additional diagnosis. Twenty-three studies included women with asthma, six examined women with cystic fibrosis, one included patients with gastroesophageal reflux, and one considered women with a cardiopulmonary disease. Among case reports there were women with an infantile spinal muscular atrophy type II, with a motor neurone disease, alpha-1 antitrypsin deficiency, with Swyer–James–MacLeod syndrome, as well as patients with interstitial or restrictive lung diseases and with a chronic obstructive pulmonary disease. None of the papers reported any complication occurring during spirometry in pregnant women.

In the process of this systematic review, we did not find any studies whose main objective was to examine the safety profile of performing spirometry during pregnancy. Our interpretation of the gathered material comes with the assumption that not reporting any adverse events to happen during the procedure means that no serious complications occurred. This, however, creates lack of certainty in concluding that a spirometry is safe to conduct in a pregnant woman, highlighting the need for further research, with a prospective study evaluating any symptoms reported by a pregnant woman during spirometry.

4. Discussion

Spirometry is a valuable test offering insight into the possible pathomechanism of dyspnea reported by the patient. It is a safe, non-invasive procedure with a few potential complications. During the examination due to the forced exhalation there is an increase in intra-cranial, intra-thoracic and intra-abdominal pressure. As such, it may pose a risk to the thoracic and abdominal organs. This observation led to late-term pregnancy being a relative contraindication for performing spirometry as listed by the joint statement by the ERS/ATS [13]. In our systematic review we considered the question whether spirometry is safe to perform during pregnancy. We paid special attention to the use of the reversibility test. Additionally, we considered whether multiple pregnancies posed a greater risk of complications happening while performing lung function tests. We collected studies that examined pregnant women with a spirometry and found no reports of adverse events occurring while performing spirometry on a pregnant individual. Among studies included in this review we counted 33,405 spirometry procedures attempted by 10,617 women. These women included both healthy individuals and patients with preexisting conditions. As asthma is the main indicator for spirometry, whether to verify the diagnosis with a bronchodilator testing or to monitor a pre-established disease, studies conducted in women with asthma require special attention. Twenty-three papers considered for this review were conducted in women with asthma, ten of them presented longitudinal studies that monitored pregnant asthmatic women with spirometry during the course of their pregnancy. Nine studies included a bronchodilator challenge by the participants. In one of these papers there is explicit information that the reversibility test was performed 4 h after bronchodilator use; however, in the remaining studies no such information is provided. None of those studies reported any adverse events during the procedure. Nine studies conducted a reversibility test on the participants and none of them reported any adverse events during the procedure. In two studies women with a multiple pregnancy were examined. There was no mention of any complications occurring in that population while performing the spirometry. Among the studies considered for this review, there were 4596 women examined in the first trimester, 6540 women tested in the second trimester, and finally, 7388 women in the third trimester. A total of 5973 women participating in longitudinal studies were examined multiple times during pregnancy. Three studies researched the respiratory functions of women undergoing caesarean section. They included performing spirometry just before the operation, in a highly late-term pregnancy. The gestational age over a certain week was not the exclusion criteria for any of the studies. Conversely, twenty-three studies included women in late-term pregnancy, examining women in the gestational age of over 39 weeks pregnant. Two studies included patients with preeclampsia, one study researched women with high-risk pregnancies. None of these studies reported any adverse events during lung function testing.

We had identified several limitations. First, although the studies did not report any adverse events during the procedure, the safety of a spirometry and a reversibility test was not the primary objective of any of the studies. As such, there is a possibility that the documents did not include any complications that might have happened. Additionally, many of the studies excluded patients with preexisting conditions, obtaining results from otherwise healthy individuals who had a lower risk of adverse events. Similarly, multiple pregnancy was often an exclusion criterion for participation in a study. Therefore, it is not well evaluated whether a multiple pregnancy poses a greater risk of adverse events during spirometry.

The review process had some limitations. We included articles published only in English, Polish, French, German and Spanish; excluding other languages such as Chinese, Bulgarian, Slovak to name a few, of which there have been some papers available. We did not register our study in any databases.

Dyspnea is one of the most common complaints among pregnant women. The majority of these cases stem from the physiological changes that the female body undergoes to sustain a pregnancy. However, there is a significant percentage of women who suffer from asthma. If untreated, asthma can negatively impact the pregnancy, leading to a number of complications. Maternal asthma has been associated with infant complications such as low birth weight, small-for-gestational age, congenital abnormalities and increased infant hospital stay, as well as adverse maternal outcomes including preeclampsia, placenta previa, caesarean delivery and prolonged hospital stay [10,11,12]. Spirometry is a simple, non-invasive and widely available diagnostic test that helps to establish a diagnosis of asthma. Numerous studies have examined pregnant women using spirometry without reporting any complications occurring during the procedure. However, the safety of performing spirometry by a pregnant woman was not the objective of any of the studies. This suggests the need for further research prospectively reporting on adverse events that happen during spirometry.