# Presentation: 358596

##  Asthma, especially more severe asthma, may

** ****Asthma, especially more severe asthma, may**
**     ****increase the risk of:**
** ****Perinatal mortality**
** ****Low birth weight**** ****infants**
**Preterm births**
**Preeclampsia**

## Adverse Perinatal Outcomes in Asthmatic Women: Potential Mechanisms

- Poor asthma control
- Hypoxia
- Reduced uteroplacental blood flow due to hypocapnia, alkalosis, dehydration, hypertension
- Asthma medications

## The Effect of Asthma on Pregnancy:Relationship to Severity/Control

**Maternal and/or fetal deaths associated with severe asthma during pregnancy**
**Lower birth weight in infants of mothers hospitalized for asthma during pregnancy compared to mothers not requiring emergency therapy**
**Inverse relationship between mean maternal FEV****1 **** during pregnancy and incidence of infant low ponderal indices**

## Adverse Perinatal Outcomes in Asthmatic Women: Potential Mechanisms

- Poor asthma control
- Hypoxia
- Reduced uteroplacental blood flow due to hypocapnia, alkalosis, dehydration, hypertension
- Asthma medications

## Questions Regarding Asthma Medications during Pregnancy

- Which medications have not been associated with adverse effects?
- Which medications may be associated with adverse effects?
- Benefit-Risk:  Under what circumstances does the use of the medication appear to entail less risk than the untreated asthma?

## Inhaled Corticosteroids and Repeat Asthma Exacerbations During Pregnancy

**65 women**
**31 Group A (no inhaled **
**    ****steroids)**
**34 Group B (inhaled**
**    ****steroids)**
**55% reduction in Group **
**    ****B (OR = 3.6, p = 0.047)**
**    ****Wendel, et al 1996**

**R**
**E  **
**A  **
**D**
**M**
**I**
**S**
**S**
**I**
**O**
**N**
**S**

**                          ****I      I**
**       ****Group      A     B**

## Human Data on the Use of Medications During Pregnancy

**Experimental**
**To ****prove**** causation or lack of it**
**Usually not ethical**

**Observational**
**Will not ****prove ****causation or lack of it, but can   provide suspicion or reassurance**
**Cohort**
**Case control**

## Collaborative Perinatal Project

- Teratogenicity of drugs taken during the first four months of pregnancy
- 50,282 women in 12 U.S. centers
- 1959-65
- Pregnancies > 20 weeks gestation
- Total and selected specific malformations
- Relative risks > 1.5 “suggestive”
- Statistical significance reported

## Michigan Medicaid Study

- 229,101 completed pregnancies
- 1985 to 1992
- Total and selected specific congenital     	malformations
- Incidence of malformations in exposed compared to expected incidence (based on rate in unexposed)
- Published in Briggs, Freeman, and Yaffe (1994)

## Kaiser-Permanente, 1997

- 824 pregnant women with asthma
- 678 pregnant women without asthma
- 1978 to 1990
- Adjustment for
- Multiple medications
- Maternal age, parity, smoking, race, weight
- Maternal pulmonary function, acute asthmatic episodes

## Reassuring Human Data For Asthma Medications During Pregnancy

## Adverse Associations With Oral Corticosteroids During Pregnancy

- Oral clefts (3 - 6  fold increased risk)
- Lower infant birth weight (10 mg daily throughout pregnancy)
- Preeclampsia (independent association)

## Other  Medications

## ACAAI-ACOG Recommendations for the Pharmacologic Step Therapy of Chronic Asthma During Pregnancy

## ACUTE ASTHMA AMONG PREGNANT WOMEN PRSESENTING TO AN EDCydulka, et al: Am J Respir Crit Care Med 1999;160:887

## Asthma Medications During Pregnancy: Research PrioritiesControlled Observational Data

- Large cohort studies (multi-center, database, registry)
- appropriate control groups
- appropriate outcomes
- control for potential confounders
- Case-Control studies: specific malformations

## Asthma Medications During Pregnancy: Research PrioritiesOther Studies

- Pharmacokinetics/Pharmacodynamics of systemic corticosteroids during pregnancy
- Systemic absorption of inhaled medications during pregnancy compared to non-pregnant state
- Fetal penetration of medications

## Asthma Medications During Pregnancy ResearchCooperative Approach

- Government
- Industry
- Clinical Investigators
- Providers
- Professional Organizations
- Patients

## Asthma Medications During PregnancySummary

- Severe asthma may increase the risk of adverse perinatal outcomes
- Uncontrolled asthma appears to be a greater risk than asthma medications studied to date
- Based on the data available, consensus recommendations have been published
- Further studies will be necessary to test the hypothesis that following these recommendations leads to good outcomes