American Journal of Obstetrics & Gynecology
Volume 195, Issue 1 , Pages 149-153, July 2006

Cessation of asthma medication in early pregnancy

  • Rachel Enriquez, PhD

      Affiliations

    • Departments of Medicine
    • Divisions of Allergy, Pulmonary, and Critical Care Medicine
    • ,
  • Pingsheng Wu, PhD

      Affiliations

    • Departments of Medicine
    • Divisions of Allergy, Pulmonary, and Critical Care Medicine
    • ,
  • Marie R. Griffin, MD, MPH

      Affiliations

    • Departments of Medicine
    • Preventive Medicine
    • General Internal Medicine
    • Center for Education and Research on Therapeutics, Vanderbilt University School of Medicine
    • Mid-South Geriatric Research Education and Clinical Center and Clinical Research Center of Excellence, Veterans Affairs Tennessee Valley Health Care System, Nashville, TN
    • ,
  • Tebeb Gebretsadik, MPH

      Affiliations

    • Biostatistics
    • ,
  • Ayumi Shintani, MPH, PhD

      Affiliations

    • Biostatistics
    • ,
  • Ed Mitchel, MS

      Affiliations

    • Preventive Medicine
    • ,
  • Kecia N. Carroll, MD, MPH

      Affiliations

    • Pediatrics
    • ,
  • Tina V. Hartert, MD, MPH

      Affiliations

    • Departments of Medicine
    • Divisions of Allergy, Pulmonary, and Critical Care Medicine
    • Corresponding Author InformationReprint requests: Tina V. Hartert, MD, MPH, Center for Lung Research, Center for Health Services Research, T-1218 MCN, Vanderbilt University School of Medicine, Nashville, TN 37232-2650.

Received 3 October 2005; received in revised form 6 January 2006; accepted 14 January 2006. published online 24 April 2006.

Article Outline

Objective

The objective of the study was to determine whether women alter their use of asthma medications during pregnancy.

Study design

Weekly asthma medication use was determined from prescription claims data in a cohort of 112,171 pregnant women aged 15 to 44 years who were continuously enrolled in the Tennessee Medicaid program prior to their singleton pregnancy and who delivered a singleton birth during 1995 to 2001. Change in asthma medication use was evaluated using generalized estimating equation analyses.

Results

Women with asthma significantly (P ≤ 0.0005) decreased their asthma medication use from 5 to 13 weeks of pregnancy. During the first trimester, there was a 23% decline in inhaled corticosteroid prescriptions, a 13% decline in short-acting beta-agonist prescriptions, and a 54% decline in rescue corticosteroid prescriptions.

Conclusions

Utilization of all categories of asthma medications decreased in early pregnancy, with the largest declines occurring for inhaled and rescue corticosteroids.

Key words: Asthma, Pregnancy, Medicaid database, Drug utilization, Guidelines

 

Asthma is one of the most common chronic medical conditions complicating pregnancy, affecting up to 8% of pregnant women.1, 2, 3, 4, 5 Adverse maternal and neonatal outcomes have been described among women with more severe asthma or asthma requiring hospital care.3, 6, 7, 8, 9, 10, 11, 12, 13 Studies of inhaled asthma medication use during pregnancy have not identified risks to mother or fetus, and national guidelines recommend the continued use of appropriate asthma medications.5, 10, 11, 12, 14, 15 Patterns of use of asthma medications during pregnancy, however, have not been studied. A pharmaceutical company–sponsored national survey found that 39% of women with asthma reported discontinuing their asthma medication, reducing their dosage, or both during pregnancy, and 82% of women using inhaled corticosteroids reported they would be concerned about birth defects if they became pregnant.16 However, there have been no studies to date examining how women manage their asthma medication during pregnancy.

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Material and methods 

We conducted a cohort study of 8149 pregnant women with asthma drawn from a population of 112,171 white and black pregnant women aged 15 to 44 years, with singleton gestations, enrolled in the Tennessee Medicaid program during 1995 to 2001, and with at least 180 days of continuous enrollment prior to their last menstrual period (LMP). These requirements captured 48% of deliveries to mothers enrolled in Medicaid and approximately 21% of all births to Tennessee residents from 1995 to 2001. Nonblack or white women and women outside the 15- to 44-year age range were too few to study.

Data were obtained from linked Tennessee Medicaid database and vital records files, which were developed for studying medication use and pregnancy outcomes among pregnant women enrolled in the Tennessee Medicaid Program.17, 18 Demographic variables were obtained from Tennessee birth certificates and Tennessee Medicaid enrollment files. Birth certificates include the date of the last maternal menstrual period, which was used to estimate week of pregnancy for 92.6% of subjects. When LMP was not available on the birth certificate, LMP was imputed as median gestational age in weeks for infants of the same race, birth weight, and birth year (7.35%) or assigned a gestation period of 270 days (0.05%).

Asthma-specific medication use was determined using Tennessee Medicaid pharmacy claims files, which included prescriptions filled and the number of days supplied as previously described.19 For all inhalers, days supply was set at 30 days. For each week from 20 weeks prior to LMP through the last full week of pregnancy, women were categorized as current users in the week if the days' supply of their prescription included at least 1 day in that week; otherwise they were categorized as nonusers. Rescue corticosteroid use was defined as a single prescription of at least 3 days' supply, with each new course separated by at least 7 days. Terbutaline was excluded because of its use for preterm labor, and dexamethasone, betamethasone, and hydrocortisone were excluded because these medications may have been used in pregnant women at risk for preterm labor during the study years to prevent infant respiratory distress syndrome.

Mothers with an International Classification of Diseases, Ninth Revision diagnosis code of 493 (asthma) in any of the 9 diagnostic fields for inpatient, other hospital care (23 hour observation), or outpatient physician visit claims and/or women with 2 prescriptions for any short-acting beta-agonist or a single prescription for any other asthma medication from the 180 days prior to LMP through their date of delivery were considered to have asthma. In previous studies, this definition was validated by chart reviews and found to be highly sensitive and specific.4, 19

A longitudinal data set was created for the analysis, which classified each subject as a user or nonuser of medication by week of pregnancy. The prevalence of medication use was computed dividing the total number of users by the total numbers of women in the cohort for the corresponding week. We a priori hypothesized that we would observe a drop in asthma medication use after the recognition of pregnancy.

To test this hypothesis, we applied the following 2 approaches for data analysis. First, we estimated medication usage at 3 times (from 20 weeks prior to LMP through 5 weeks after LMP, at 13 weeks after LMP, and at 26 weeks after LMP) and calculated the percent change in medication usage. Second, we compared linear regression slopes between 20 weeks prior to LMP and 5 weeks after LMP to a period between 6 and 13 weeks after LMP and again from 6 to 13 weeks after LMP and a slope from 14 to 26 weeks after LMP. We applied generalized estimating equations method for both approaches to account for within-person correlation. For the first approach, indicator variables for time periods were used in generalized estimating equations regression. For the second approach, regression slopes were calculated for 2 time periods in which a positive or negative slope indicates an increase or decrease in medication rates. A difference between 2 slopes was compared statistically by including a cross-product term of weeks of pregnancy and a variable indicating 2 periods. P value for the interaction term was presented as P value for trend shift.20 Statistical analyses were performed using SAS (version 8.2, SAS Institute, Cary, NC).

The protocol was approved by the Institutional Review Boards of Vanderbilt University and the Tennessee Department of Health.

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Results 

The study cohort consisted of 8149 pregnant women with asthma. Mean maternal age was 24 ± 5 years, 67.9% were white, 39.1% were married, and 38.2% smoked. Overall, 83% of women used any asthma medication, 30% used inhaled anti-inflammatory agents, 77% used inhaled beta-agonists, and 28% used rescue corticosteroids during the study period. On average, in any single week prior to pregnancy 19% of women were users of any asthma medication, 5% used inhaled anti-inflammatory agents, 18% used inhaled beta-agonists, and 2% were users of rescue corticosteroids.

The Figure illustrates the average use of inhaled anti-inflammatory agents (Figure, A), short-acting beta-agonists (Figure, B), and rescue corticosteroids (Figure, C) by week of pregnancy. There was a distinct drop in the mean use of all 3 classes of asthma medications from weeks 6 to13 of pregnancy. Similar results were seen for all classes of asthma medications during the same time period, although the largest drops occurred for inhaled anti-inflammatory agents and rescue corticosteroids. At 13 weeks of pregnancy, use of inhaled anti-inflammatory agents dropped by 22.9% with 95% confidence interval (CI) of 13.9 to 31.0 (P value for trend shift = .0005), short-acting beta-agonist use fell by 13.2% with 95% CI of 9.0 to 17.2 (P value for trend shift < .0001), and rescue corticosteroid use decreased by 54.3% with 95% CI of 41.6 to 64.2 (P value for trend shift < .0001), compared with the average rate between 20 weeks prior to LMP and 5 weeks after LMP (Table I, Table II).

  • View full-size image.
  • Figure. 

    Asthma medication utilization by week of pregnancy from 20 weeks prior to LMP to last full week of pregnancy or 40 weeks' gestation. The bar on the right margin is standardized to a 1% change to facilitate comparisons. A, Prevalence of inhaled anti-inflammatory use by week. B, Prevalence of short-acting beta-agonist use by week. C, Prevalence of rescue (oral) corticosteroid use by week.

Table I. Percent drop in asthma medication use during early pregnancy and estimated medication use among women with asthma enrolled in TennCare
MedicationPercent drop in medication use from 5 to 13 wk of pregnancy (95% CI)Average percent using between 20 wk prior to LMP to 5 wk of pregnancyPercent using at 13 wk after LMP
Inhaled corticosteroids22.9 (13.9-31.0)4.73.7
Short acting beta-agonists13.2 (9.0-17.2)17.715.4
Rescue (oral) corticosteroids54.3 (41.6-64.2)1.70.8
Table II. Trend shift in asthma medication use for 2 time periods, –20 weeks to 5 weeks after pregnancy and 6 weeks to 13 weeks
MedicationSlope 1 (−20 to 5 wk LMP) (95% CI)Slope 2 (6-13 wk LMP) (95% CI)Δ slope∗P value for Δ slope∗
Inhaled corticosteroids0.0021 (−0.011 to 0.016)−0.036 (−0.055 to 0.018)0.039.0002
Short acting beta-agonists0.0014 (−0.004 to 0.0065)−0.025 (−0.034 to 0.016)0.027<.0001
Rescue (oral) corticosteroids−0.0007 (−0.023 to 0.021)−0.084 (−0.12 to 0.049)0.084<.0001

∗Δ slope = (slope 1 − slope 2).

At 26 weeks of pregnancy, only use of short beta-agonists had a statistically significant rebound of 6.9% (95% CI 1.6-12.4, P = .01), compared with the average rate between 6 weeks and 12 weeks after LMP. However, for all classes of asthma medication, there were significant increases in the slope from 6 to 13 weeks and 14 to 26 weeks after LMP.

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Comment 

The results of this study suggest that women on Medicaid decrease and/or stop asthma medications during early pregnancy despite national guidelines recommending continued use.5 We observed a 23% drop in use of inhaled corticosteroids, a 13% drop in beta-agonist use, and a 54% drop in rescue corticosteroid use. These results are similar to results of a survey among women receiving asthma case management from a managed care organization, which found that 39% of women discontinued or reduced asthma medication use during pregnancy, and in that study 33% of these women did so without discussing it with their doctor.16 The sharp drop in asthma prescriptions in our study population began 6 weeks following the LMP, a time when women often recognize that they are pregnant, but precedes the first prenatal care visit. The decrease in asthma medication use continued throughout the first trimester, a period when more than 60% of Medicaid recipients initiate prenatal care.21

On average, only 5% of women with asthma were classified as current users of inhaled corticosteroids in each week prior to pregnancy, which suggests low overall use of controller asthma medication in this cohort. However, prior to recognition of pregnancy, medication use was stable; therefore, it is unlikely that women in this cohort stopped medication in anticipation of becoming pregnant. Furthermore, about half of U.S. pregnancies are unplanned, and the rate of unplanned pregnancies in Medicaid populations is higher.22, 23

The most dramatic decrease in asthma medication use during early pregnancy was prescriptions for inhaled anti-inflammatory agents and rescue corticosteroids, with a 23% and 54% decrease, respectively, during the first trimester of pregnancy. This is consistent with findings that some patients and, potentially, providers may have concerns about the safety of anti-inflammatory agents, which may lead to undertreatment of asthma symptoms among women who were adequately treated.24, 25

Because oral corticosteroid therapy has been shown to have adverse effects on pregnancy, including associations with cleft lip when given in the first trimester, reduced intrauterine growth, and possible associations with preterm birth and pre-eclampsia, patients and providers may be reluctant to use oral corticosteroids.26, 27 Although beta-agonist use also dropped in early pregnancy, mean use was actually significantly higher during later pregnancy than prior to pregnancy.

Use of inhaled and rescue corticosteroids also rebounded in the second trimester, although usage remained lower than prepregnancy levels. Although physicians may be encouraging women to continue appropriate asthma medications at obstetric care visits, women and practitioners may also preferentially use short-acting beta-agonists, or asthma control may become worse, leading to preferential increased use of short-acting beta-agonists.

Several limitations of this study should be considered. This study was limited to the Tennessee Medicaid population, in which there is low overall asthma drug use,19 and the results may not be generalizable to other populations; however, the focus of this analysis is on medication use patterns among women who were prescribed and filled asthma medications. Additional data from a cross-sectional survey suggest that this phenomenon occurs in other populations as well.16 Current use of medication was inferred by the filling of a prescription. The medication could be filled, but not taken, and therefore, this could overestimate medication use. However, filling a prescription is the first step in taking a medication, and refilling a chronic medication likely indicates its use.

Additionally, this analysis may underestimate medication use among those with mild asthma or those with inadequately treated disease who had no encounters with the medical system for asthma and no medications prescribed during the study period. Most women will not recognize they are pregnant until a missed menstrual cycle; therefore, we evaluated asthma medication use from 6 weeks after LMP to the end of the first trimester. The analysis represents prevalent users before and after pregnancy and may not represent the same women starting and stopping medications. In addition, short-acting beta-agonists are used as needed and may not require monthly refills, and the decrease in beta-agonist utilization could be underestimate or overestimated.

With these administrative data, we were unable to determine why women stopped or decreased their asthma medications. The decrease in asthma medication use during pregnancy could reflect improved asthma control during the first trimester and need for less medication; however, studies of asthma during pregnancy suggest that a larger proportion of pregnant women experience a worsening of asthma than experience improvement.28 Additionally, the decrease in medication use was seen in not only rescue medications but also chronic asthma (inhaled anti-inflammatory) agents.

Our data suggest that women with asthma stop and/or decrease asthma medications in early pregnancy. The reasons for this could not be elucidated in this study; however, women and physicians may be concerned about the safety of asthma medications during pregnancy. Several cohort studies suggest that appropriate use of inhaled corticosteroids and beta-agonists do not harm pregnant women or the developing fetus, and controlling asthma may improve pregnancy outcomes3, 5, 10, 11, 12, 14, 15; the Guidelines on Asthma during Pregnancy, published by the National Heart, Lung, and Blood Institute, emphasize continuing treatment of asthma throughout pregnancy.5 However, this study reveals a reduction in medication prescriptions filled in early pregnancy in a population that should have an increase in medication use as physician contacts increase.

This work highlights the need to reinforce to women of child-bearing age, and their health care providers, the importance of controlling asthma with appropriate medication use throughout pregnancy.

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 Supported in part by research grants UO1 HL 72471, MO1 RR00095, and KO8 AI01582, Agency for Healthcare Research and Quality, Centers for Education and Research Grant U18-HS10384, Geriatric Research Education and Clinical Center, Department of Veterans Affairs, and the Food and Drug Administration FD-U-000073.

PII: S0002-9378(06)00105-0

doi:10.1016/j.ajog.2006.01.065

American Journal of Obstetrics & Gynecology
Volume 195, Issue 1 , Pages 149-153, July 2006

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