Asthma and Pregnancy

Asthma in pregnancy-Questions

What is the effect of pregnancy on asthma? What is the effect of asthma on pregnancy? How is asthma managed?

Chronically During an exacerbation During Labor and Delivery

Which medications are safest? What is prognosis for mother and fetus?

Outline

Epidemiology Maternal respiratory changes Fetal oxygenation Maternal immunity Teratogenicity Lactation Management Answer the questions

Epidemiology

Asthma complicates 4% of pregnancies in US. Up to 10% of pregnant women have nonspecific airway hyper-responsiveness. Worldwide, asthma is one of the most common medical conditions complicating pregnancy. 10% of pregnant asthmatic patients seek urgent care at some time during their pregnancy.

Aim: to evaluate the relationship between asthma severity classification during pregnancy and gestational asthma exacerbations Schatz et al. JACI 2003
Prospective observational cohort study at 16 US centers 1739 pregnant asthmatic patients Classified as mild, moderate,or severe by NHLBI 1993 Endpoint: Exacerbation(Sxs resulting in a medical intervention)

Results - Schatz 2003 Initial asthma classification was related to subsequent morbidity during pregnancy
Exacerbations occurred in 13% initially mild, 26% moderate, 52% severe Morbidity of moderate and severe were similar 30% of initially mild, reclassified to m-s 23% of m-s reclassified as mild
Exac=exacerbations=hospitalizations, unscheduled visits, oral corticosteroid course

Pregnancy: maternal physiologic changes

Maternal respiratory changes

FVC, FEV1, PEF do not change significantly Thus spirometry (peak flow) is useful Jones Medical

Maternal respiratory changes

Physiologic compensated respiratory alkalosis

PCO2 32-34 mm Hg pO2 100-105 mm Hg ph 7.42 - 7.46

This alkalosis is observed in the 1st trimester

Physiologic dyspnea in pregnancy

By 30 weeks, 75% experience exertional dyspnea

Clinical consequences of physiologic changes

Changes of asthma are superimposed on the respiratory alkalosis of pregnancy Dyspnea has several possible sources

Hyperventilation of pregnancy experienced by 60%-75% qUpward pressure on diaphragm near term from asthma

and asthma other pathology

DDx of asthma during pregnancy

Mechanical obstruction Laryngeal dysfunction Chronic obstructive pulmonary disease Pulmonary edema Pulmonary embolism Amniotic fluid embolism Upper airway cough (sinusitis, rhinitis, reflux) Carcinoid symdrome

Clues to pathologic dyspnea

History, including time course

e.g., abrupt or paroxysmal dyspnea

Respiratory rate > 20/min pCO2 < 30 or > 35 Abnormal spirometry Alveolar-arterial oxygen difference > 25mmHg Abnormal TLC

What is the effect of asthma on pregnancy?

Fetal oxygenation physiology

Fetal paO2 @ (adult paO2) Fetal umbilical vein pO2 < maternal venous pO2 Compensation:

High fetal perfusion rate Increased blood flow Fetal hemoglobin has higher affinity for O2 Fetal hemoglobin levels are higher than adult values Shunts and streaming effects direct oxygenated blood to high-priority tissues and deoxygenated blood back to placenta

Asthma threatens fetal oxygenation through

Maternal hypoxia Alkalosis (unknown mechanism) Reduced uterine blood flow

e.g., exogenous or endogenous vasoconstrictors Dehydration Hypotension

Fetus compensates for pathologic hypoxia by

Redistributing blood flow Decreasing body movements Increasing oxygen extraction

Maternal immunity

Humoral immunity

Probably not significantly altered

IgG crosses the placenta Responses to vaccines adequate

Influenza Tetanus toxoid Haemophilus influenza Meningococcus Hepatitis

Cell-mediated immunity
Responses to virus, mycobacteria, fungi; cancer; delayed graft rejection; delayed hypersensitivity For the most part unchanged

Maternal immunity Clinical recommendations

Vaccinate for influenza

Most common infection causing morbidity No evidence of maternal/fetal risk from vaccination

Measles, varicella, rubella

Administer live viral vaccinations before conception

TB: ATS recommends delaying preventive therapy until after delivery except in recently infected pregnant women

Maternal immunity Allergy Clinical recommendations

Avoidance

of allergens & irritants Skin testing Immunotherapy

Teratogenesis and pregnancy

medication-induced congenital malformations

Major malformations:

2-4% of all newborns Another 2-4% recognized in 1st yr Radiation Maternal infection Ethanol Industrial chemicals Pharmacologic

Environmental teratogens:

1-5% of environmental causes are caused by medications

Type and severity of a teratogenetic effect depend upon

Medication

Dose Route Duration q Exposure 4 - 10 wks after onset of last menses associated with major organ malformation Exposure 2nd 3rd trimester associated with neurologic damage

Gestational age at time of exposure

Genetic make-up of mother & fetus Other environmental exposures

Teratogenicity and pregnancy

Approach with patients
Relatively few asthma medications have proved harmful during pregnancy. No asthma medication should be considered completely safe. Discuss consequences of inadequately controlled asthma for mother and fetus. Weigh risks/benefits of alternatives.

Potential for Toxicity - U. S. FDA

Medications to be avoided in pregnancy

Tetracyclines Iodine-containing cough medications Sulfonamides (late pregnancy & lactation) Quinolones Epinephrine (except in anaphylaxis) a-Adrenergics (except pseudoephedrine) Lithium Alcohol
NAEPP Working Group on Asthma and Pregnancy. NIH 1993

Medications used for obstetric reasons to be avoided in asthma

Beta-blockers 15-Methyl prostaglandin F2a, Transcervical or intraamniotic prostaglandin E2 Methylergonovine or ergonovine NSAIDs in aspirin-sensitive patients

Recommended medications

More medication recommendations

And more medication recommendations

Safety of systemic corticosteroids

Most data do not show adverse effects Steroids in a dose 10mg prednisone/day have been associated with increased risk of preeclampsia, lower birth weight, preterm birth Park-Wylie et al meta-analysis

6 cohort studies-no risk of total malformations 4 case-control studies-increased risk of oral clefts

BUT, uncontrolled maternal asthma is associated with preeclampsia, perinatal mortality, preterm births, low-birth weight infants The lowest effective dose.

LactationLess drug reaches the infant through breast feeding than reaches the fetus through the placenta

Breast feeding is generally recommended Majority of drugs pass into breast milk Fetus exposed to less than 2% of maternal dose Exposure can be minimized by scheduling drug dose just after feeding

Management of Asthma in Pregnancy

Make changes in Rx before conception Use preconception counseling as an opportunity to optimize asthma management in general and to make any changes in management appropriate to pregnancy. Optimize non-pharmacologic therapies

Avoidance allergens, irritants Consider peak flow monitoring

Monitor patients carefully and frequently Address psychosocial issues Experts in asthma & obstetrics should work as a team.

More comments relevant to management

Radiologic studies

Weigh benefits/risks/indication Shield maternal abdomen and pelvis, even for sinus or chest studies

Respiratory infections: the most common precipitant of asthma exacerbations in pregnancy Poor adherence is associated with poor control in pregnancy, especially in adolescents Under-treatment of asthma by physicians may lead to increased morbidity during pregnancy Monitor pts on corticosteriods for gestational diabetes and pre-eclampsia and intrauterine growth retardation

Evaluation of acute asthma

Signs of severe disease

HR>120 b/min in afebrile pregnant women is usually indicative of very poor control RR > 30 Pulsus paradoxus > 12 mm Hg

Pulse oximetry is helpful if PEFR>200 L/min or FEV1> 1.0L Pulse oximetry < 95% may be associated with a pO2 < 60 mmHg If pulse oximetry < 95%, get ABG

Initial treatment of acute asthma

O2, initially 3-4 L/min by nasal cannula

Maintain pO2> 70 mmHg Maintain O2sat >95%

Medication Adequate hydration Adequate glucose Evaluate for infection and other precipitants

Pharmacological management of acute asthma during pregnancy

Nebulized b2 - agonist bronchodilator

up to 3 doses q 20 minutes then every 1 - 2 hours thereafter until adequate response

Ipratropium by nebulizer 500 mcg in 2.5ml saline Intravenous methylprednisolone (with initial therapy in patients on regular corticosteroids and for those with poorresponse during the first hour of treatment)

1 mg/kg every 6 - 8 hrs taper as patient improves

Pharmacological management of acute asthma during pregnancy

Consider intravenous aminophylline (generally only if hospitalized) 6 mg/kg to load, the 0.5 mg/kg/hr, adjust to keep level between 8-12 mcg/ml. Consider subcutaneous terbutaline 0.25 mg if patient not responding to the above therapy. Consider IV magnesium sulfate.

Management of asthma during labor

Communicate ahead of time with obstetrician Continue antepartum therapy Treat any exacerbations For steroid-dependent patients:

100 mg hydrocortisone IV or IM on admission to L&D and q8 hr or until stable postpartum. Adrenal insufficiency has only rarely been reported in infants of mothers receiving glucocorticoids during pregnancy

Prognosis is excellent for both mother and infant if asthma is controlled

Several studies, e.g. Stenius-Aarniala et al, Apter et al, Schatz have shown that the overall perinatal prognosis for mother and child is comparable to the nonasthmatic population. In uncontrolled asthma risk of preeclampsia, perinatal mortality, preterm births, low-birth weight. Dombrowski et al. OB Gyn 2004 Objective: determine neonatal and maternal outcomes by asthma severity during pregnancy Multicenter prospective cohort study 4 years and 16 university hospital centers Fetal: No increase in preterm delivery or other adverse peri-natal outcomes except discharge diagnosis of neonatal sepsis in mild asthmatics. Maternal: C-section increased in those with m-s asthma

Maternal Smoking

But when medications are necessary: Use adequate doses to control symptoms & avoid hypoxia. Avoid recently introduced medication. Use the minimal dose necessary to control symptoms. Use the route of administration which will result in the lowest blood levels.

What is the effect of pregnancy on asthma?

1/3 get better, 1/3 get worse, and 1/3 stay the same.

Maternal hemodynamic changes during pregnancy

The Management of the Pregnant Asthmatic

Should not differ radically from the optimum management of the non-pregnant asthmatic. Will change as understanding of the pathophysiology of asthma and experience with newer medications increases. Should change in concert with changes in the principles of the management of asthma in general.

Other respiratory physiologic changes

Decreased ERV Decreased RV VC and TLC: No change DLCO In late pregnancy in supine

PEF, FEV1, pO2,are lower pCO2 is higher

And more comments

Rhinitis

Significant in 30% Especially in women with pre-existing rhinitis Therapeutic options depend on cause

Buffered saline Pseudoephedrine TNS Cromolyn Antihistamine