2. What I Will talk about ? 1
• NORMAL PHYSIOLOGY DURING PREGNANCY
• EFFECTS OF PREGNANCY ON ASTHMA
• EFFECTS OF ASTHMA ON PREGNANCY
Complications
causes of adverse outcomes
3. What I Will talk about ? 2
• OVERVIEW OF MEDICATIONS IN PREGNANCY
• GENERAL CARE
• SAFETY OF SPECIFIC MEDICATIONS
• OVERVIEW OF ASTHMA MANAGEMENT IN PREGNANCY
Chronic asthma
Acute exacerbations
4. INTRODUCTION
• Asthma is one of the most common medical
conditions encountered during pregnancy,
occurring in 3 - 8 % of pregnant women.
Namazy JA, Schatz M. Pregnancy and asthma: recent developments. Curr Opin Pulm Med
2005; 11:56.
Liccardi G, Cazzola M, Canonica GW, et al. General strategy for the management of bronchial
asthma in pregnancy. Respir Med 2003; 97:778.
Tan KS, Thomson NC. Asthma in pregnancy. Am J Med 2000; 109:727.
Dombrowski MP, Schatz M, Wise R, et al. Asthma during pregnancy. Obstet Gynecol 2004;
103:5.
5.
6. Normal Physiology
Pregnancy Changes
IncreasedTV
Decreased ERV and RV and FRC
Intact FEV1
Less than normal PCo2
Above normal PO2
7.
8. 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?
9. Effects of Pregnancy on
Asthma
• Two prospective studies (1998) of more than 500 women
1/3 aggravate
1/3 improve
1/3 does not change
10. • BA severity correlated with asthma morbidity during
pregnancy
• Mild asthma 13% had exacerbation
• Moderate 26 % had exacerbation
• Severe 50% had exacerbation
11. Most studies suggest that asthma severity prior to
pregnancy is related to asthma severity during pregnancy.
• The following additional trends have been noted :
1. Asthma was generally less severe during the last 4w of
pregnancy.
2. In women who improved, the improvement was gradual
as pregnancy progressed.
3. In women whose asthma worsened, the increase in
symptoms was most prominent between w 29 - 36 of
gestation.
4. Substantial asthma symptoms were uncommon during
labor and delivery.
5. The course of asthma in successive pregnancies in an
individual patient tended to be similar
12. Effects of Asthma on
Pregnancy
• Controversial results in terms of preeclampsia, cesarean
delivery, prematurity, IUGR, and perinatal mortality rate
• Generally unless there is severe disease, asthma has
relatively minor effects on pregnancy outcome
13. Effects of Asthma on
Pregnancy
• A prospective study by Dombrowski (2000), preterm delivery among
pregnancies complicated by asthma compared to non-asthmatic
controls.
the majority of women enrolled with severe asthma showed an
increase of preterm labor by two fold.
• Bracken (2003) found preterm delivery only slightly increased with
asthma while IUGR increased with severity of asthma.
15. A study of 36,985 subjects asthmatic 15 -20 %
increased risk of perinatal mortality, preeclampsia,
preterm deliveries, or low birth weight infants compared
to non-asthmatic women
These risks are increased 30 - 100 % those with more
severe asthma
Asthma is not associated with risk of congenital
malformations
Use of anti-asthmatic drugs during pregnancy. Congenital malformations in the
infants.Källén B, Otterblad Olausson P Eur J Clin Pharmacol. 2007;63(4):383.
16. Potential adverse effects of
Asthma Medication
•Miscarriage
•Fetal death
•Congenital malformation (especially first trimester exposure)
•Reduced fetal growth
•Impaired function of developing organs, such as the central nervous
system or kidney
•Reduced uteroplacental blood flow
•Increased risk of preterm delivery
•Drug related side effects in the newborn
Outcomes of pregnancy in asthmatic women Schatz, M, Dombrowski, M
Immunol Allergy Clin North Am. 2000; 20:715.
17. Possible causes of adverse
outcomes
• Direct consequences impair fetal oxygenation and
uteroplacental blood flow
• Diminished pulmonary function during pregnancy .
18. • An observational series of 2123 pregnant women with
asthma demonstrated that decreased gestational
maternal (FEV1) was associated with gestational
hypertension and preterm birth compared to women
with a normal FEV1.
Systemic effects of salbutamol and salmeterol in patients with asthma.
Bennett JA, Smyth ET, Pavord ID, Wilding PJ, Tattersfield AE
Thorax. 1994;49(8):771
19.
20. What I Will talk about ? 2
• GENERAL CARE
Monitoring lung function ,Smoking cessation ,Environmental
control & Patient education
• SAFETY OF SPECIFIC MEDICATIONS
• OVERVIEW OF MEDICATIONS IN PREGNANCY
• OVERVIEW OF ASTHMA MANAGEMENT IN PREGNANCY
21. Management
The Expert Panel Report of the Working Group on Asthma and
Pregnancy stressed the following four important components of
effective therapy :
1. Objective monitoring of maternal lung function and fetal well–
being as a guide to therapy
2. Proper control of environmental and other triggers for asthma
3. Patient education
4. Pharmacologic therapy
NAEPP expert panel report. Managing asthma during pregnancy:
recommendations for pharmacologic treatment-2004 update.
National Heart, Lung, and Blood Institute, National Asthma Education and
Prevention Program Asthma and Pregnancy Working Group
J Allergy Clin Immunol. 2005;115(1):34.
22. GENERAL CARE
The two primary goals of asthma management:
• Prevention of acute episodes should prevent potentially
harmful acute hypoxia, hypocapnia, alkalosis, and
dehydration.
• Optimization of chronic maternal pulmonary function should
reduce the potential for chronic hypoxia, maternal symptoms,
as well as the likelihood of acute episodes.
23.
24. Patient Education
• Understanding that asthma control is important to fetal
well being.
• Reduction of triggers.
• Understanding of basic medical management including
self monitoring
25. Environmental control
• Avoiding exposure to allergens and to nonspecific airway
irritants such as tobacco smoke, dust, and environmental
pollutants.
• Particular allergens of concern are from pets and
antigens from household dust mites.
26. Smoking cessation
It is critical for the pregnant asthmatic woman to discontinue smoking
during pregnancy [2].
1- Predispose the patient to asthma exacerbations, bronchitis or
sinusitis necessitate an increased need for medication [1].
2-Increase perinatal morbidity to the baseline risk of uncontrolled
maternal asthma [3].
(1)Murphy VE, Clifton VL, Gibson PG. The effect of cigarette smoking on asthma control during
exacerbations in pregnant women. Thorax 2010; 65:739.
(2)Newman RB, Momirova V, Dombrowski MP, et al. The effect of active and passive household
cigarette smoke exposure on pregnant women with asthma. Chest 2010; 137:601
(3)Schatz M, Zeiger RS, Hoffman CP. Intrauterine growth is related to gestational pulmonary
function in pregnant asthmatic women. Kaiser-Permanente Asthma and Pregnancy Study
Group. Chest 1990; 98:389.
27. Follow-up
• By clinicians experienced in managing asthma is essential.
• Regular medication at least monthly.
• All pregnant patients should have access to their clinician
(effective communication exists among the clinician
managing the asthma, the patient, and the obstetrician).
28.
29. Objective Measures for
Accurate Monitoring
• FEV1 is best single measure of pulmonary function but
requires a spirometer.
• PEFR is inexpensive as it is measured by peak flow ,
Self-monitoring of PEFR aids in detecting early signs of
deterioration in lung function.
31. OVERVIEW OF MEDICATIONS
IN PREGNANCY
Two important considerations arise with the use of any
medication in pregnancy:
• Are there potential adverse effects of the medication on the
developing fetus?
• Does pregnancy alter the metabolism or the bioavailability of
the medication?
32.
33.
34. SAFETY OF SPECIFIC
MEDICATIONS
• Experience with many of the medications used to treat
asthma suggests minimal or no known adverse effects for
their use during pregnancy.
• Most drugs used in the treatment of asthma fall into
categories B or C .
35.
36. Overview
• Cohort studies are reassuring and show a lack of adverse
effects on human pregnancy outcomes with the following
drugs :
Albuterol
Metaproterenol
Theophylline
Cromolyn sodium
Beclomethasone
Budesonide
37. Cont.
• Data regarding the use of oral glucocorticoids during
pregnancy have not been totally reassuring.
• These include drugs with
-Reassuring animal studies (formoterol , salmeterol ,
ipratropium , nedocromil , zafirlukast, and montelukast)
-Non-reassuring animal studies (zileuton).
38. Inhaled beta-adrenergic agonists
• The majority of reports provide reassurance regarding the use
of inhaled beta-agonists during pregnancy
• Clinical experience is greater with the older agents (eg,
albuterol) than with the newer ones (eg, formoterol,
salmeterol).
39. Short-acting beta-adrenergic agonists
SABA
• In animal studies, some of the SABAs have been teratogenic
when given in high doses, but there has been no clear
evidence of teratogenicity in humans.
• In a study of 259 pregnant asthmatic women, for example, no
adverse effects on the fetus were noted with the use of an
inhaled SABA (primarily metaproterenol) when compared with
control subjects, even though 180 of the women used these
agents during the first trimester .
Schatz M, Zeiger RS, Harden KM, et al. The safety of inhaled beta-agonist
bronchodilators during pregnancy. J Allergy Clin Immunol 1988; 82:686.
40. • Cardiac defects was noted in a cohort study that examined the
effect of exposure to bronchodilator therapy during pregnancy
[1].
• SABA use is a marker for poorly-controlled asthma and more
frequent exacerbations, which may independently contribute
to the development of congenital anomalies [2].
1 Otterblad Olausson P. Use of anti-asthmatic drugs during pregnancy. 3. Congenital
malformations in the infants. Eur J Clin Pharmacol 2007; 63:383.
2 Blais L, Forget A. Asthma exacerbations during the first trimester of pregnancy
and the risk of congenital malformations among asthmatic women. J Allergy Clin
Immunol 2008; 121:1379.
41. LABA
These findings are preliminary; clinicians should
continue with the goal of minimizing use of SABAs
in both pregnant and non-pregnant patients.
42. Long-acting beta-adrenergic agents
LABA
• Clinical experience with LABAs during pregnancy is less
extensive than with SABAs.
• Salmeterol is not expected to increase the risk of congenital
anomalies, based on data from animal studies and limited
human experience .
• Animal studies are also reassuring for formoterol, although
data from human pregnancies is very limited .
Wilton LV, Shakir SA. A post-marketing surveillance study of formoterol (Foradil): its
use in general practice in England. Drug Saf 2002; 25:213.
The use of newer asthma and allergy medications during pregnancy. The American
College of Obstetricians and Gynecologists (ACOG) and The American College of
Allergy, Asthma and Immunology (ACAAI). Ann Allergy Asthma Immunol 2000; 84:475.
43. LABA
• Given these findings, continuation of a LABA during
pregnancy is reasonable if a LABA has been needed to
achieve asthma control before pregnancy .
Schatz M, Dombrowski MP. Clinical practice. Asthma in pregnancy.
N Engl J Med 2009; 360:1862.
44. Epinephrine
• May cause vasoconstriction in the uteroplacental circulation.
• Working Group on Pregnancy and Asthma recommended that
epinephrine generally be avoided during pregnancy except in
the setting of anaphylaxis .
National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program
Asthma and Pregnancy Working Group. NAEPP expert panel report. Managing asthma during
pregnancy: recommendations for pharmacologic treatment-2004 update. J Allergy Clin
Immunol 2005; 115:34.
45. Systemic Glucocorticoids
• Several potential areas of concern have been raised
Congenital malformations (primarily cleft palate),
Preeclampsia,
Gestational diabetes,
Low birth weight,
& neonatal adrenal insufficiency.
46. Glucocorticoids
A few studies exist in which systemic glucocorticoids were used
for the management of asthma during pregnancy .
Some showed a slightly increased risk of prematurity and a
slightly higher risk of low birth weight (less than 2500 g).
Bracken MB, Triche EW, Belanger K, et al. Asthma symptoms, severity, and drug therapy: a prospective study of effects on
2205 pregnancies. Obstet Gynecol 2003; 102:739.
Schatz M, Dombrowski MP, Wise R, Momirova V, Landon M, Mabie W, Newman RB, Hauth JC, ay DL, Maternal-Fetal Medicine Units Network, The
National Institute of Child Health and Development, National Heart, Lung and Blood Institute
J Allergy Clin Immunol. 2004;113(6):1040.
47. Systemic glucocorticoids
• Congenital malformations
Data from animal studies in several species suggest that high
dose may lead to cleft palate.
Meta-analysis of the four case-control studies revealed an association
of oral clefts in infants of mothers used oral glucocorticoid.
Pregnancy outcome after first trimester exposure to corticosteroids:
Gur C, Diav-Citrin O, Shechtman S, Arnon J, Ornoy A
Reprod Toxicol. 2004;18(1):93
48. In a cohort study, 311 pregnancies with systemic
glucocorticoid use for various indications during 1st
trimester compared with those of 790 controls without
teratogenic exposure; the rate of major anomalies did not
differ significantly between the groups .
No oral cleft abnormalities were noted in the
glucocorticoid group.
Gur C, Diav-Citrin O, Shechtman S, et al. Pregnancy outcome after first trimester
exposure to corticosteroids: a prospective controlled study. Reprod Toxicol 2004; 18:93.
49. Preterm birth and low birth
weight
• A large, prospective, cohort study of 2123 pregnant
women with asthma recruited from 16 centers in the
USA (12-1994 – 02- 2000 ) oral glucocorticoid use was
significantly associated with preterm birth (odds ratio
1.54, 95% CI of 1.02 to 2.33) and low birth weight (odds
ratio 1.80, 95% CI of 1.13 to 2.88) .
• The authors did not evaluate the relationship between
these effects and the dose or duration of therapy.
Schatz M, Dombrowski MP, Wise R, Momirova V, Landon M, Mabie W, Newman RB, Hauth JC,
ay DL, Maternal-Fetal Medicine Units Network, The National Institute of Child Health and
Development, National Heart, Lung and Blood Institute
J Allergy Clin Immunol. 2004;113(6):1040.
50. Inhaled Steroid
• The safety of these medicines was best assessed in a
registry-based cohort study of 2014 Swedish women who
used inhaled budesonide during early pregnancy .
• Based largely upon these findings, budesonide is
currently the only inhaled glucocorticoid with a
pregnancy category B rating.
Källén B, Rydhstroem H, Aberg A. Congenital malformations after the use of inhaled budesonide in early pregnancy.
Obstet Gynecol 1999; 93:392.
National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program Asthma and
Pregnancy Working Group. NAEPP expert panel report. Managing asthma during pregnancy: recommendations for
pharmacologic treatment-2004 update. J Allergy Clin Immunol 2005; 115:34
51. Inhaled Steroid
• The rate of congenital malformations was not different from
that of the general population (3.8 Vs 3.5 %). Additional data
from the Swedish Medical Birth Registry reported no clinically
significant effects of inhaled budesonide on fetal mortality,
gestational age, or fetal growth .
Norjavaara E, de Verdier MG. Normal pregnancy outcomes in a population-based
study including 2,968 pregnant women exposed to budesonide. J Allergy Clin
Immunol 2003; 111:736
52. Inhaled Steroid
• A study of 13,280 pregnancies in women with asthma
confirmed that low to moderate doses of inhaled
glucocorticoids were NOT associated with an increased risk of
congenital malformations.
but
the use of high doses (>1000 mcg/day) during the 1st trimester
63 % increase in risk of all congenital malformations .
Blais L, Beauchesne MF, Lemière C, Elftouh N. High doses of inhaled
corticosteroids during the first trimester of pregnancy and congenital
malformations. J Allergy Clin Immunol 2009; 124:1229.
53. Inhaled Steroid
Two randomized controlled trials support the efficacy of inhaled
glucocorticoids during pregnancy.
• One study - 84 pregnant women who were managed with or
without inhaled beclomethasone after discharge following an
asthma hospitalization Use of this medication significantly
decreased the rate of readmission for asthma (12 Vs 33 %),
and no adverse events or outcomes were reported.
Wendel PJ, Ramin SM, Barnett-Hamm C, et al. Asthma treatment in pregnancy:
a randomized controlled study. Am J Obstet Gynecol 1996; 175:150.
54. Inhaled Steroid
• A more recent study compared inhaled beclomethasone to
theophylline in the management of moderate asthma during
pregnancy .
• Although exacerbation rates were similar in the two groups,
pulmonary function was better in the beclomethasone group
and fewer patients in the beclomethasone group discontinued
therapy due to side effects.
Dombrowski MP, Schatz M, Wise R, et al. Randomized trial of inhaled
beclomethasone dipropionate versus theophylline for moderate asthma
during pregnancy. Am J Obstet Gynecol 2004; 190:737.
55. Anticholinergic agents
• Fetal tachycardia can occur with the systemic administration
of atropine to the mother. But the minimal chronotropic effect
of inhaled ipratropium in the mother suggests that the inhaled
preparation should have negligible chronotropic effects on the
fetus.
• Gestational animal studies are also reassuring for ipratropium.
• Inhaled ipratropium, the most commonly used drug in this
category, is felt to be safe during pregnancy .
National Asthma Education and Prevention Program Expert Panel Executive Summary Report: Guidelines for the
Diagnosis and Management of Asthma - Update on Selected Topics 2002. National Institutes of Health, National Heart,
Lung, and Blood Institute, Publication No. 02-5075, 2002. www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf
(Accessed on March 1, 2006).
56. Methylxanthines
• Extensive clinical experience suggests that theophylline
and its ethylenediamine complex, aminophylline, do not
increase the risk of adverse effects during pregnancy .
Stenius-Aarniala B, Riikonen S, Teramo K. Slow-release theophylline in pregnant asthmatics.
Chest 1995; 107:642.
Neff RK, Leviton A. Maternal theophylline consumption and the risk of stillbirth. Chest 1990;
97:1266.
57. Methylxanthines
• Inhaled glucocorticoids have been shown to be more effective
than theophylline for persistent asthma in non-pregnant
patients and at least as effective as theophylline with fewer
side effects in pregnant patients .
• Theophylline could be considered as an add-on therapy to
inhaled glucocorticoids for pregnant women if needed .
Dombrowski MP, Schatz M, Wise R, et al. Randomized trial of inhaled beclomethasone dipropionate versus
theophylline for moderate asthma during pregnancy. Am J Obstet Gynecol 2004; 190:737.
National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program Asthma and
Pregnancy Working Group. NAEPP expert panel report. Managing asthma during pregnancy:
recommendations for pharmacologic treatment-2004 update. J Allergy Clin Immunol 2005; 115:34.
58. Alterations in drug metabolism
Two changes of potential clinical importance in the bioavailability and metabolism of
theophylline during pregnancy.:
1. Decreased binding to albumin results in an increased proportion of free drug in the
circulation the total (free plus bound) theophylline concentration falls target
plasma levels during pregnancy are 8 to 12 rather than 10 to 15 micrograms/mL.
2. Clearance of theophylline appears to decrease during the 3rd trimester, reduction
in the maintenance dose .
With an IV aminophylline infusion during the 3rd trimester, for example, the loading dose
of 5 to 6 mg/kg is unchanged, but the maintenance infusion rate is decreased from 0.9
mg/kg/hr to approximately 0.5 mg/kg/hr; the dose is then adjusted to maintain the
desired plasma level of 8 to 12 micrograms/mL.
Connelly TJ, Ruo TI, Frederiksen MC, Atkinson AJ Jr. Characterization of theophylline binding to serum
proteins in pregnant and nonpregnant women. Clin Pharmacol Ther 1990; 47:68.
Carter BL, Driscoll CE, Smith GD. Theophylline clearance during pregnancy. Obstet Gynecol 1986; 68:555.
59. • Like SABA&LABA, theophylline can also inhibit uterine
muscle contraction in vitro.
• This effect is presumably mediated by an inhibitory
action of increased c AMP (due to theophylline-induced
phosphodiesterase inhibition) on uterine smooth muscle,
but has not been shown to be clinically important.
60. Leukotriene Modifiers
• Little experience with use in pregnancy
• Given orally for maintence not effective in acute setting
• Often used in conjunction with oral corticosteroids to
obtain minimal steroid dose.
• Ducharme in 2002 reviewed all randomized trials
conducted through 2001
• Concluded these agents only slightly improved control
61. Leukotriene modifiers
• The first prospective, controlled study of the use of
leukotriene receptor antagonists in pregnancy followed 96
women taking these medications
122 women taking SABAs only, and 346 women without
asthma
No increase in major birth defects or adverse outcomes was
detected in the offspring of patients receiving these
medications.
Bakhireva LN, Jones KL, Schatz M, et al. Safety of leukotriene receptor antagonists in pregnancy.
J Allergy Clin Immunol 2007; 119:618..
62. Leukotriene modifiers
• A subsequent study with similar design described 180
montelukast-exposed pregnancies compared to 180 disease
matched controls and 180 pregnancies in non-asthmatic
women.
did not appear to increase the baseline rate of major
malformations.
• Larger studies are needed to detect small increases in adverse
pregnancy outcomes or rare birth defects.
Sarkar M, Koren G, Kalra S, et al. Montelukast use during
pregnancy: a multicentre, prospective, comparative study of
infant outcomes. Eur J Clin Pharmacol 2009; 65:1259
63. Leukotriene Modifiers
1. Animal data on zafirlukast have shown no teratogenicity .
2. No adequate and well–controlled studies of zileuton
animal studies have not been reassuring .
3. Use of montelukast In preference to the other leukotriene
modifiers, and would reserve this agent for add-on therapy
to inhaled glucocorticoids, especially in patients who had a
good response to this medication prior to pregnancy .
National Heart, Lung, and Blood Institute, National Asthma Education and
Prevention Program Asthma and Pregnancy Working Group. NAEPP expert
panel report. Managing asthma during pregnancy: recommendations for
pharmacologic treatment-2004 update. J Allergy Clin Immunol 2005; 115:34.
64. Immunotherapy
• The initiation of allergen immunotherapy is not recommended
during pregnancy based upon risk-benefit considerations . The
risk of systemic reactions.
• Allergen immunotherapy can be continued during pregnancy
in patients already receiving it .
Breathing for Two. A Guide to Asthma During Pregnancy. Asthma &
Allergy Network Mothers of Asthmatics (AANMA), 2003.
66. Acute Exacerbation
The most common cause of asthma
exacerbation
Discontinuation of drugs
Viral infections
67.
68.
69.
70. SUMMARY
• BA worsens during pregnancy in a third of patients, improves
in a third, and is unchanged in a third.
• Severity prior to pregnancy is related to asthma severity
during pregnancy.
• Asthma exacerbations affect 20 to 36 % of pregnant asthmatic
patients and tend to occur during the middle trimester.
71. • Gestational asthma is associated with a relatively small but
statistically significant increase in pregnancy complications,
such as perinatal mortality, preeclampsia, and preterm
delivery.
• Appropriate therapy and good asthma control probably
minimize these complications.
