Asthma and Pregnancy

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)





• 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

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

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

Asthma and Pregnancy

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