Asthma and pregnancy-Nelson - World Allergy Organization

Asthma and pregnancy-Nelson - World Allergy Organization

Asthma and PregnancyHarold S Nelson, MDProfessor of MedicineNational Jewish Health, andUniversity of Colorado School of MedicineDenver, Colorado, USA

Reported Complications ofPregnancy due to Asthma Preterm labor Preterm delivery Small for gestational age Low birth weight Preeclampsia Gestational diabetes Congenital malformations Fetal or neonatal deathBracken MB, et al. Obstet Gynecol 2003;102:739-52

Reported Complications of Pregnancydue to Asthma in 8 Recent ProspectiveStudies (n = 4411) Preterm labor (if asthma severe or on OCS) Small for gestational age (Only with dailysymptoms) Preeclampsia (only with daily symptoms) Gestational diabetes (only if asthma severe) Cesarean section (Moderate/severe asthmaor elective) Congenital malformations (No) Fetal or neonatal death (No)Dombrowski MP. Obstet Gynecol 2006;108:667-81

Effect of Maternal Moderate tot Severeasthma on Perinatal Outcomes.F Firoozi, et al. Respir Med 2010;104:1278-87 From 3 Canadian databases informationobtained on 1274 pregnancies in asthmaticwomen. Distribution of asthma severities andincidence of small for gestational age babieswere:Prevalence SGA- mild 82.6% 13.8%- moderate 12.4% 17.4% Sig- severe 5.0%. 19.5% Sig

Pregnancy and Asthma“The ultimate goal of asthma therapy duringpregnancy is to maintain adequateoxygenation of the fetus by prevention ofhypoxic episodes in the mother”Dombrowski MP. Obstet Gynecol 2006;108:667-81

Pregnancy and Pulmonary Function The enlarging uterus elevates the diaphragmabout 4 cm with reduction in FRC, but not inflows. Progesterone-mediated stimulation of therespiratory center produces a 50% increasein minute ventilation Shortness of breath at rest or with mildexertion is common.Dombrowski MP. Obstet Gynecol 2006;108:667-81

The Effect of Pregnancy on Asthma Conventional notion is that asthma in onethirdgets better, in one third stays the sameand in one-third gets worse. In a large prospective study 23% improvedand 30% became worse. Asthma more likely to deteriorate in severeasthma (52-65%) than mild asthma (8-13%).Schatz M et al. JACI 2003;112:283-8Murphy V, et al Obstet Gynecol 2005;106:1045-4

The Asthma Exacerbations inPregnancy A prospective observational study of asthmain pregnancy included 873 with mild asthma,814 with moderate asthma 52 with severeasthma and 881 non-asthmatic controls.ExacerbationsHospitalizationsMild asthma 13% 2.3%Moderate 25% 6.9%Severe 52% 26.9%Louik C, et al. Ann Allergy Asthma Immunol 2010;105:110-7

The Effect of Asthma Exacerbations inPregnancy on the Fetus From 3 Canadian databases information obtained on4,344 pregnancies of asthmatic women. Exacerbations in first trimester included oralcorticosteroids, emergency department or hospitaladmission. With exacerbations OR for malformation in baby 1.48(CI 1.04-2.09) for any and 1.32 (CI .86-2.04) formajor. Exacerbation increases risk for low birth weight baby(OR 2.54)Blais & Forget. JACI 2008;121:1379-84.Murphy VE Thorax 2006;61:169-76

Pregnancy and the use ofInhaled Corticosteroids The NAEPP Working Group reviewed 10studies including 6,113 patients who tookinhaled corticosteroids during pregnancy. There was no evidence linking inhaledcorticosteroid use and increases in:- Congenital malformations- Adverse perinatal outcomesDombrowski MP. Obstet Gynecol 2006;108:667-81

Pregnancy and the use ofInhaled Beta-Adrenergic Agonists The NAEPP Working Group reviewed 6studies including 1,599 patients who tookinhaled beta-agonists during pregnancy. Additional a prospective study examinedbeta-agonist use in 1,828 patients. There was no evidence of adverse pregnancyoutcomes with inhaled beta-agonist use.Dombrowski MP. Obstet Gynecol 2006;108:667-81

Pregnancy and the use ofOral Corticosteroids The NAEPP Working Group reviewed 8 studiesof patients who took oral corticosteroids duringpregnancy. OC use during the first trimester was associatedwith a 3-fold increased risk for isolated cleft lip OC use in patients who have asthma wasassociated with increased risk for preeclampsia,preterm delivery and low birth weight, perhapsrelated to uncontrolled asthmaDombrowski MP. Obstet Gynecol 2006;108:667-81

Pregnancy and the use ofTheophylline, LTRA, Cromolyn Cromolyn is considered without significantadverse reactions. Leukotriene receptor antagonists are CategoryB for pregnancy, but there is not extensivereported experience. Theophylline has frequent side effects, but wasfound safe in a review by the NAEPP of studiesin 600 women.Dombrowski MP. Obstet Gynecol 2006;108:667-81

Pregnancy and theTreatment of Rhinitis Intranasal corticosteroids are the most effectivetreatment. Oral or intranasal antihistamines are generallyconsidered safe. Oral decongestants in the first trimester have beenreported to be associated with gastroschisis. Howeverthe Swedish Birth Register found no increasedmalformations (OR 0.96) with their use in >4,000pregnancies.Dombrowski MP. Obstet Gynecol 2006;108:667-81Killien & Olausson AJOG 2006;194:480-5

Maternal Conditions as Risk Factors forAsthma in the Child Dietary Factors:- Low intake vitamin D & vitamin E- Intake of Mediterranean diet, oily fish and dairyproducts reported to be protective. Acetaminophen in 2nd and 3rd trimester a risk. Exposure to household cleaning products a risk Use of antibiotics in pregnancy a risk Cesarean section delivery a risk Maternal smoking a risk Farm exposure protectiveDombrowski MP. Obstet Gynecol 2006;108:667-81Killien & Olausson AJOG 2006;194:480-5

Epigenetic Contributions toAsthma Phenotypes Early environmental exposures(particularly in utero) play a key role inactivating or silencing genes by alteringDNA and histone methylation, histoneacetylation and chromatin structure. These changes are passed on to somaticdaughter cells and are heritable acrossgenerations.Martino and Prescott. Allergy2010;65:7-5

Consequences of Low VitaminD Vitamin D insufficient leads to dysfunctionalT cell regulation with lack of down regulationof Th1 and Th2. Vitamin D participates in TLR signaling;deficiency may predispose to increasedrespiratory tract infections.AA Litonjua & ST Weiss. JACI 2007;120:1031-5C Camargo. Curr Allergy Asthma Reports 2009 (in press)

Consequences of Low VitaminD Viral infections in infancy are a risk forschool age asthma. In two birth cohort studies low maternalvitamin D was associated with increased riskof wheezing at age 3 and 5 with populationattributable risk of > 40%.AA Litonjua & ST Weiss. JACI 2007;120:1031-5C Camargo. Curr Allergy Asthma Reports 2009 (in press)

Maternal Vitamin D intake DuringPregnancy is Inversely Associated withAsthma and Allergic Rhinitis in 5-yearoldChildren.M Erkkola, et al. Clin Exp Allergy 2009;39:875-82 Finnish birth cohort (n = 1669).- Food frequency questionnaire duringpregnancy- Children assessed at age 5-years. Maternal intake of vitamin D in foodnegatively associated with risk in offspring of:- Asthma (HR 0.80)- Allergic rhinitis (HR 0.85)

Household Chemicals, PersistentWheezing, and Lung Function:Effect Modification by Atopy?J Henderson, et al. Eur Respir J 2008;31:547-54 Objective: Assess the effects of maternaluse of domestic chemicals duringpregnancy on wheezing and lung functionin children age up to 8.5 years. Maternal composite household chemicalexposure score (CHCE) derived duringpregnancy.

Household Chemicals, PersistentWheezing, and Lung Function:Effect Modification by Atopy? CHCE score was associated with:- Early (< 18 months) and Intermediate (18-36 months) persistent and Late (>30 month)wheezing in non-atopic children.- Decrements in FEV1 and FEF25-75%. Effects may result from prenataldevelopment effects or post-natal irritanteffects.J Henderson, et al. Eur Respir J 2008;31:547-54

Odds Ratio for Wheezing Phenotypes byCHCE Z-ScoreLOWIOPIOTEOPEOTLate-onset wheezeIntermediate onsetpersistent.Intermediate onsettransientEarly onset persistentEarly onset transientNever wheeze0.0 1.0 2.5J Henderson, et al.Eur Respir J2008;31:547-54Non-Atopic

Risk of Asthma with AcetaminophenUse in Adulthood: Nurses’ HealthStudyBarr et al. Am J Respir Crit Care Med 2004;169:836-41 Prospective study (1990-6) of 48,028nurses, mean age 57 years. > 14 days/month versus no useassociated with OR 1.62 for developmentof physician diagnosed asthma

Prenatal Acetaminophen Exposureand Risk of Wheeze at Age 5 years inan Urban, Low-Income CohortM Perzanowski, et al. thorax 2009 Prenatal acetaminophen use predictedwheezing and atopy at age 5-years in aminority, New York cohort (n = 301)none 1d 2-4d ≥5d pwheezing 1.0 1.06 1.95 2.26

Prenatal Acetaminophen Exposure and Riskof Wheeze at Age 5 years According toGlutathione S Transferase Polymorphism The association of prenatalacetaminophen exposure and currentwheezing (OR 2.08) & atopy (OR 1.96) atage 5 years was limited to children withGSTP1 AG or GG alleles.GSTT1 (present vs.. null) associatedwith seroatopy (p < 0.001)M Perzanowski, et al. thorax 2009

Association Between Acetaminophen Use,Wheezing age 5 years, and GSTP1 PolymorphismsPrevalence of wheeze age 5 years70%60%50%40%30%20%10%0%n =GSTP1-01 AA(31%), Trend P=0.65GSTP1-01 AG/GG (68%), Trend P _ 5PerzanowskiThorax 2010Reported days prenatal acetaminophen exposure

Asthma and Pregnancy Pregnancy has little effect on well-controlledasthma. Well-controlled asthma has little effect on theoutcome of pregnancy. The drugs required to control asthma have nodeleterious effect on the outcome ofpregnancy Many conditions during pregnancy can effectthe likelihood of the offspring developingasthma and atopy.

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