asthma and pregnancy michael schatz, md, ms chief, department of allergy kaiser-permanente medical...
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Asthma and Pregnancy
Michael Schatz, MD, MS
Chief, Department of Allergy
Kaiser-Permanente Medical Center
San Diego, CA
Disclosures
• Investigator-initiated Research Support– Aerocrine
– Genentech
– GlaxoSmithKline
– Merck
• Research Consultant– Amgen
– GlaxoSmithKline
– Merck
Asthma and Pregnancy
• Most common potentially serious medical problem to complicate pregnancy
• May increase the risk of perinatal complications
• The risks of uncontrolled asthma appear to be greater than the risks of asthma medications
• Aggressive asthma management similar to non-pregnant patients is recommended
Asthma and Pregnancy: Clinically Relevant Questions
• Does asthma control make a difference?
• Are asthma medications safe during pregnancy?
• What are the barriers to asthma control during pregnancy?
• What is the role of exhaled nitric oxide in asthma management during pregnancy?
Relationship to Asthma Control
• Case reports—severe exacerbations associated with• Maternal and/or fetal deaths• Severe infant neurologic disease
• Studies• Parameters of asthma control
• Symptoms• FEV1
• Exacerbations• Outcomes affected
• Low birth weight/SGA• Preterm birth• Congenital malformations (one study)
.
Relationship Between FEV1 During Pregnancy and Prematurity
Outcome Mean FEV1 < 80 % (n = 354)
Mean FEV1 80 % (n = 1769)
Preterm < 32 weeks
5.1 % 3.0 %
Preterm < 37 weeks
21.2 % 15.3 %
Low birth weight
17.6 % 12.9 %
Schatz.. Am J Obstet Gynecol 2006; 194:120
The Relationship of Asthma Exacerbations During Pregnancy to Infant Low Birth Weight
Murphy. Thorax 2006; 61:169
Asthma Severity/Control and Congenital Malformations
• Canadian administrative database study• 4344 pregnancies of asthmatic women• Incidence of malformations
– 9.2 % total– 6.0 % major
• Odd Ratio (95 % CI) for patients with first trimester exacerbations– Total 1.48 (1.04-2.09)– Major 1.32 (0.86-2.04)
Blais. J Allergy Clin Immunol 2008; 121:1379
Conclusions Regarding Asthma Control
• Better control (based on symptoms, pulmonary function, exacerbations) associated with improved outcomes– LBW– Preterm – SGA– Congenital malformations
• Relationship can’t be proven by RCTs (random assignment to controlled versus not controlled)
Asthma and Pregnancy: Clinically Relevant Questions
• Does asthma control make a difference?
• Are asthma medications safe during pregnancy?
• What are the barriers to asthma control during pregnancy?
• What is the role of exhaled nitric oxide in asthma management?
Asthma Medications and Prematurity/Fetal Growth
Study SABA ICS Oral CS
Number exposed
Schatz, 1997 (Kaiser)
488* 149* 130 (↑ pre-eclampsia)
Bracken, 2003 (Yale)
529* 176* 52 (↑ preterm)
Schatz, 2004 (MFMU)
1753* 722* 185 (↑ preterm and LBW)
* No increased risk
Congenital Malformations
• Total malformations– Background risk of 3-5 %
• Increased risk of specific malformations– Drugs are generally associated with an
increased risk of specific, rather than total malformations
– Most studies have inadequate power for specific malformations
– Confounding by control/severity still possible
Specific Congenital Malformations and Bronchodilators
• Albuterol or bronchodilators (primarily albuterol)– Cardiac– Gastroschisis– Cleft lip/palate
• LABA– Cardiac
Kallen, 2007; Lin, 2008; Lin, 2009; Munsie, 2011; Eltonsy, 2011
Congenital Malformations and Corticosteroids
• Inhaled– No significant increase in Swedish Medical Birth
Registry study• 11,487 total• 10,013 budesonide
– Increased total malformations in high dose users versus other users in one database study
• Oral– Increased oral clefts in case control studies– Not confirmed in recent cohort study
Kallen, 2007; Blais, 2009; Park-Wylie, 2000 ; Hvid, 2011
Asthma Medications: Conclusions
• Asthma medications (other than prednisone) not likely to be the cause of prematurity or reduced fetal growth
• Bronchodilators, oral corticosteroids, and possibly high dose inhaled corticosteroids have been associated with certain birth defects
• Confounding by indication (more severe disease and exacerbations) may explain these associations
Asthma and Pregnancy: Clinically Relevant Questions
• Does asthma control make a difference?
• Are asthma medications safe during pregnancy?
• What are the barriers to asthma control during pregnancy?
• What is the role of exhaled nitric oxide in asthma management?
Barriers to Asthma Control
• Smoking– Associated with increased exacerbations
• Clinician undertreatment– Documented in ED
• Adherence– Substantial proportion of women reduce
medications– Common cause of exacerbations
• Viral infections– Most common cause of exacerbations
Murphy, 2010; Cydulka, 1999; McCallister, 2011; Enriquez, 2006; Murphy, 2005
Asthma and Pregnancy: Clinically Relevant Questions
• Does asthma control make a difference?
• Are asthma medications safe during pregnancy?
• What are the barriers to asthma control during pregnancy?
• What is the role of exhaled nitric oxide in asthma management?
Exhaled Nitric Oxide (eNO) and Pregnancy
• Mean levels of eNO were not different in asthmatic pregnant versus non-pregnant women
• Mean ACT scores were not different in asthmatic pregnant versus non-pregnant women
• Levels of eNO were modestly (r = 0.30) but significantly (p = 0.02) correlated with ACT scores in pregnant asthmatic women
Tamasi. J Asthma 2009; 46:786
Managing Asthma in Pregnancy (MAP) Study
• Double blind parallel group RCT• 220 pregnant asthmatic women• Algorithm based on eNO and ACQ
– Inhaled corticosteroid increased with inadequate control and high eNO
– Formoterol increased with inadequate control and low eNO
– Inhaled corticosteroid decreased with adequate control and low eNO
Powell. Lancet 2011; 378:983
Incidence of Exacerbations Over Time
FENO group: rate = 0.288
0 5 10 15 20 250
25
50
75 Control group: rate = 0.615
Time (weeks)
Exa
cerb
atio
ns IRR = 0.499
SE = 0.107p = 0.001
Comparison of Treatment Profiles
0
10
20
30
40
50
60
70
80
ICS LABA
%
Control
FENO
Comparison of ICS Doses
1 2 3 4 5 6500
600
700
800
900Control group
FENO group
p=0.043
Visit
Me
an
ICS
Do
se
(ug
/da
y)
Conclusions
• Asthma control during pregnancy makes a difference
• Asthma medications appear to have few risks during pregnancy, and those risks that have been identified may be due to confounding
• There are barriers that need to be addressed to improve asthma control during pregnancy
• eNO may allow more targeted and more effective management of asthma during pregnancy