The safety of asthma medications during pregnancy and lactation: Clinical management and research priorities

Asthma is one of the most common underlying diseases in women of reproductive age that can lead to potentially serious medical problems during pregnancy and lactation. A group of key stakeholders across multiple relevant disciplines was invited to take part in an effort to prioritize, strategize, and mobilize action steps to fill important gaps in knowledge regarding asthma medication safety in pregnancy and lactation. The stakeholders identified substantial gaps in the literature on the safety of asthma medications used during pregnancy and lactation and prioritized strategies to fill those gaps. Short-term action steps included linking data from existing complementary study designs (US and international claims data, single drug pregnancy registries, case-control studies, and coordinated systematic data systems). Long-term action steps included creating an asthma disease registry, incorporating the disease registry into electronic health record systems, and coordinating care across disciplines. The stakeholders also prioritized establishing new infrastructures/collaborations to perform research in pregnant and lactating women and to include patient perspectives throughout the process. To address the evidence gaps, and aid in populating product labels with data that inform clinical decision making, the consortium developed a plan to systematically obtain necessary data in the most efficient and timely manner. Asthma is one of the most common underlying diseases in women of reproductive age that can lead to potentially serious medical problems during pregnancy and lactation. A group of key stakeholders across multiple relevant disciplines was invited to take part in an effort to prioritize, strategize, and mobilize action steps to fill important gaps in knowledge regarding asthma medication safety in pregnancy and lactation. The stakeholders identified substantial gaps in the literature on the safety of asthma medications used during pregnancy and lactation and prioritized strategies to fill those gaps. Short-term action steps included linking data from existing complementary study designs (US and international claims data, single drug pregnancy registries, case-control studies, and coordinated systematic data systems). Long-term action steps included creating an asthma disease registry, incorporating the disease registry into electronic health record systems, and coordinating care across disciplines. The stakeholders also prioritized establishing new infrastructures/collaborations to perform research in pregnant and lactating women and to include patient perspectives throughout the process. To address the evidence gaps, and aid in populating product labels with data that inform clinical decision making, the consortium developed a plan to systematically obtain necessary data in the most efficient and timely manner. Asthma affects 3% to 10% of women of reproductive age in the United States and is one of the most common underlying health conditions that can complicate pregnancy and lactation.1National Center for Health Statistics. Summary Health Statistics Tables for U.S. Adults: National Health Interview Survey, 2018. Available at: https://www.cdc.gov/nchs/nhis/shs/tables.htm. Accessed January 8, 2021.Google Scholar In addition, there are substantial inequities in the burden of asthma in pregnancy by race and ethnic group.2Centers for Disease Control and PreventionCurrent asthma prevalence by race and ethnicity (2016-2018).https://www.cdc.gov/asthma/most_recent_national_asthma_data.htmDate accessed: January 8, 2021Google Scholar Asthma is associated with increased risk of maternal morbidity and perinatal complications including spontaneous abortion, gestational diabetes, hypertensive disorders of pregnancy, preterm delivery, fetal growth restriction, antepartum and postpartum bleeding, and congenital anomalies.3Murphy V.E. Namazy J.A. Powell H. Schatz M. Chambers C. Attia J. et al.A meta-analysis of adverse perinatal outcomes in women with asthma.BJOG. 2011; 118: 1314-1323Crossref PubMed Scopus (208) Google Scholar, 4Murphy V.E. Wang G. Namazy J.A. Powell H. Gibson P.G. Chambers C. et al.The risk of congenital malformations, perinatal mortality and neonatal hospitalisation among pregnant women with asthma: a systematic review and meta-analysis.BJOG. 2013; 120: 812-822Crossref PubMed Scopus (90) Google Scholar, 5Wang G. Murphy V.E. Namazy J. Powell H. Gibson P.G. Chambers C. et al.The risk of maternal and placental complications in pregnant women with asthma: a systematic review and meta-analysis.J Matern-Fetal Neonat Med. 2014; 27: 934-942Crossref PubMed Scopus (55) Google Scholar The mechanisms underlying these are likely multifactorial, but an important element appears to be asthma control. Unfortunately, asthma medication nonadherence is common in pregnancy and has implications for disease activity.6Cydulka R.K. Emerman C.L. Schreiber D. Molander K.H. Woodruff P.G. Camargo Jr., C.A. Acute asthma among pregnant women presenting to the emergency department.Am J Respir Crit Care Med. 1999; 160: 887-892Crossref PubMed Scopus (107) Google Scholar, 7Kim S. Kim J. Park S.Y. Um H.Y. Kim K. Kim Y. et al.Effect of pregnancy in asthma on health care use and perinatal outcomes.J Allergy Clin Immunol. 2015; 136: 1215-1223.e1211-6Abstract Full Text Full Text PDF PubMed Scopus (28) Google Scholar, 8Matsui D. Adherence with drug therapy in pregnancy.Obstetr Gynecol Int. 2012; 2012796590Crossref PubMed Google Scholar, 9Murphy V.E. Gibson P. Talbot P.I. Clifton V.L. Severe asthma exacerbations during pregnancy.Obstetr Gynecol. 2005; 106: 1046-1054Crossref PubMed Scopus (182) Google Scholar, 10Murphy V.E. Gibson P.G. Talbot P.I. Kessell C.G. Clifton V.L. Asthma self-management skills and the use of asthma education during pregnancy.Eur Respir J. 2005; 26: 435-441Crossref PubMed Scopus (80) Google Scholar Many women report that concerns about medication safety are reasons for discontinuing appropriate therapies.11van Trigt A.M. Waardenburg C.M. Haaijer-Ruskamp F.M. de Jong-van den Berg L.T. Questions about drugs: how do pregnant women solve them?.Pharm World Sci. 1994; 16: 254-259PubMed Google Scholar The maternal need for medication is also frequently cited as a reason for early termination of breast-feeding, based on lack of data confirming safety for the infant.12Odom E.C. Li R. Scanlon K.S. Perrine C.G. Grummer-Strawn L. Reasons for earlier than desired cessation of breastfeeding.Pediatrics. 2013; 131: e726-e732Crossref PubMed Scopus (279) Google Scholar In 2015, the US Food and Drug Administration (FDA) introduced the Pregnancy and Lactation Labeling Rule, a new system that removed the pregnancy letter ratings (A, B, C, D, X) from all prescribing information for drugs approved after June 30, 2001, replacing the letters with a narrative summary of animal and human gestational safety data and clinical considerations. The intent is to provide the prescriber and patient with important safety and risk information about the use of a prescription product during pregnancy and lactation. More than 1500 drug labelings have been converted to the Pregnancy and Lactation Labeling Rule format since 2015. However, there has been a growing awareness that many prescription products lack good quality clinical pregnancy and lactation safety information, including most asthma medications. The revised prescribing information highlights a critical need for high-quality human safety data to inform the use of asthma medications during pregnancy and lactation. In November 2019, the National Heart, Lung, and Blood Institute and the Office of Research on Women’s Health in the Office of the Director, of the National Institutes of Health, and the US Food and Drug Administration Office of Women’s Health hosted a workshop titled “The Safety of Asthma Medications during Pregnancy and Lactation: Research Priorities and Methodology.” A group of key stakeholders across multiple relevant disciplines was invited to take part in an effort to prioritize, strategize, and mobilize action steps on gaps in knowledge regarding asthma medication safety in pregnancy and lactation. Stakeholder representatives included academic researchers, obstetric/maternal-fetal medicine specialists, regulatory and other federal agencies, the pharmaceutical industry, clinicians, patient advocacy groups, and patients. The conference was developed in response to recommendations of the Department of Health and Human Service’s Task Force on Research Specific to Pregnant Women and Lactating Women pursuant to the 21st Century Cures Act. The workshop proceedings are summarized in this article. Substantial gaps in the literature on the safety of asthma medications used during pregnancy and lactation were identified and strategies prioritized to fill those gaps. Recommended short-term actions include linking data from existing complementary study designs (US and international claims data, single drug pregnancy registries, case-control studies, and coordinated systematic data systems). Proposed long-term actions include creating an asthma disease registry, incorporating the disease registry into electronic health record systems, and coordinating care across disciplines. The stakeholders also prioritized establishing new infrastructures and collaborations to increase research in pregnant and lactating women and to include patient perspectives throughout the process. Recommended pharmacologic management of asthma during pregnancy follows a stepwise approach (Table I), based on the determination of asthma control. Medication is typically stepped up for uncontrolled asthma, after issues such as avoidance of environmental triggers, inhaler technique, and medication adherence are optimized. The available safety data for asthma medications in pregnancy are generally reassuring for several older and commonly used asthma medications, such as inhaled corticosteroids and short-acting beta agonists (Table II).Table ISteps in asthma therapy during pregnancyStepPreferred controller medicationAlternative controller medication1None—2Low-dose ICSLTRA, theophylline, or cromolyn3Medium-dose ICS or low-dose ICS plus LABALow-dose ICS plus LTRA or theophylline4Medium-dose ICS plus LABAMedium-dose ICS plus either LTRA or theophylline5High-dose ICS plus LABAMedium-dose ICS plus LABA plus tiotropium; consider adding omalizumab for patients with allergy or adding other asthma biologics (anti–IL-5, anti–IL-5Rα, anti–IL-4Rα) for appropriate candidates6High-dose ICS plus LABA plus oral prednisoneConsider adding omalizumab for patients with allergy or adding other asthma biologics (anti–IL-5, anti–IL-5Rα, anti–IL-4Rα) for appropriate candidatesICS, Inhaled corticosteroid; LABA, long-acting β-agonist; LTRA, leukotriene receptor antagonist.There are no randomized clinical trials of asthma biologics that intentionally included pregnant women.Data modified from Schatz and Dombrowski.13Schatz M. Dombrowski M.P. Asthma in pregnancy.N Engl J Med. 2009; 360: 1862-1869Crossref PubMed Scopus (75) Google Scholar Open table in a new tab Table IIHuman pregnancy summary safety data for selected asthma medicationsAdapted from Namazy et al.46Namazy J.A. Schatz M. Litonjua A.A. Severe asthma in pregnancy: special considerations.in: Difficult to treat asthma. Springer International Publishing, 2000: 243-264https://doi.org/10.1007/978-3-030-20812-7_13Google ScholarMedicationMajor birth defectsOther birth outcomesEvidence gaps and recommendationsLactationShort-acting beta agonists (any, primarily albuterol)No increase in major birth defects over expected among 1090 albuterol-exposed pregnancies in a claims database.14Briggs G.G. Freeman R.K. Towers C.V. Forinash A.B. Drugs in pregnancy and lactation: a reference guide to fetal and neonatal risk.11th ed. Wolters Kluwer, Philadelphia, Pa2017Google Scholar No increase in major birth defects in 1753 albuterol-exposed pregnancies compared with other asthmatic pregnancies.15Schatz M. Dombrowski M.P. Wise R. Momirova V. Landon M. Mabie W. et al.The relationship of asthma medication use to perinatal outcomes.J Allergy Clin Immunol. 2004; 113: 1040-1045Abstract Full Text Full Text PDF PubMed Scopus (156) Google ScholarModest increased risk in isolated cleft lip or cleft palate (odds ratios from 1.65 to 1.79) in albuterol-exposed pregnancies in case-control study of 2711 cases of oral clefts and 6482 controls.16Munsie J.W. Lin S. Browne M.L. Campbell K.A. Caton A.R. Bell E.M. et al.Maternal bronchodilator use and the risk of orofacial clefts.Hum Reprod. 2011; 26: 3147-3154Crossref PubMed Scopus (26) Google ScholarSeveral additional studies have suggested modest increased risks (odds ratios, <3) for specific birth defects such as any cardiac or gastroschisis, esophageal atresia, or omphalocele17Lin S. Munsie J.P. Herdt-Losavio M.L. Druschel C.M. Campbell K. Browne M.L. et al.Maternal asthma medication use and the risk of selected birth defects.Pediatrics. 2012; 129: e317-e324Crossref PubMed Scopus (39) Google Scholar, 18Lin S. Munsie J.P. Herdt-Losavio M.L. Bell E. Druschel C. Romitti P.A. et al.Maternal asthma medication use and the risk of gastroschisis.Am J Epidemiol. 2008; 168: 73-79Crossref PubMed Scopus (72) Google Scholar, 19Garne E. Hansen A.V. Morris J. Zaupper L. Addor M.C. Barisic I. et al.Use of asthma medication during pregnancy and risk of specific congenital anomalies: a European case-malformed control study.J Allergy Clin Immunol. 2015; 136: 1496-1502.e1497Abstract Full Text Full Text PDF PubMed Scopus (43) Google ScholarNo increase in preterm delivery, low birth weight, or small-for-gestational-age infants in 1828 pregnancies exposed to short-acting beta agonists compared with other asthmatic pregnancies15Schatz M. Dombrowski M.P. Wise R. Momirova V. Landon M. Mabie W. et al.The relationship of asthma medication use to perinatal outcomes.J Allergy Clin Immunol. 2004; 113: 1040-1045Abstract Full Text Full Text PDF PubMed Scopus (156) Google ScholarFirst patented in 1972, albuterol is one of the most commonly used asthma medications. Despite this, there is still a lack of evidence regarding its safety when used during pregnancy. There have been reports of associations with specific congenital defects. These observations may be a result of uncontrolled confounding by indicationNo published data. Poor bioavailability and low serum levels expected to produce low levels in milkAny inhaled corticosteroid (ICS) including beclomethasone, budesonide, flunisolide, fluticasone, triamcinoloneNo increased risk for major birth defects in 396 exposed compared with the general population.20Namazy J. Schatz M. Long L. Lipkowitz M.A. Lillie M.A. Voss M. et al.Use of inhaled steroids by pregnant asthmatic women does not reduce intrauterine growth.J Allergy Clin Immunol. 2004; 113: 427-432Abstract Full Text Full Text PDF PubMed Scopus (61) Google Scholar A meta-analysis of studies of inhaled steroids did not find increased risk of major birth defects overall21Rahimi R. Nikfar S. Abdollahi M. Meta-analysis finds use of inhaled corticosteroids during pregnancy safe: a systematic meta-analysis review.Hum Exp Toxicol. 2006; 25: 447-452Crossref PubMed Scopus (56) Google ScholarNo increased risks for preterm delivery, low birth weight, or pregnancy-induced hypertension in 396 exposed or in meta-analysis.22Sawicki E. Stewart K. Wong S. Paul E. Leung L. George J. Management of asthma by pregnant women attending an Australian maternity hospital.Austr N Z J Obstetr Gynaecol. 2012; 52: 183-188Crossref PubMed Scopus (43) Google Scholar,23Rejnö G. Lundholm C. Gong T. Larsson K. Saltvedt S. Almqvist C. Asthma during pregnancy in a population-based study--pregnancy complications and adverse perinatal outcomes.PloS One. 2014; 9e104755Crossref PubMed Scopus (64) Google Scholar Higher doses of ICSs may be associated with an increased risk of low birth weight, preterm delivery, and small-for- gestational-age infants21Rahimi R. Nikfar S. Abdollahi M. Meta-analysis finds use of inhaled corticosteroids during pregnancy safe: a systematic meta-analysis review.Hum Exp Toxicol. 2006; 25: 447-452Crossref PubMed Scopus (56) Google ScholarBudesonide and fluticasone may be preferred if starting ICS during pregnancy. Other ICSs may be continued in patients who were well controlled by these agents before pregnancy, especially if it is thought that changing formulations may jeopardize asthma control. Adverse outcomes associated with higher doses of ICSs need further study because confounding by severity may explain this associationBudesonideNo increased risk for major birth defects overall or oral clefts among 2014 exposed in population-based Scandinavian register24Källén B. Rydhstroem H. Aberg A. Congenital malformations after the use of inhaled budesonide in early pregnancy.Obstetr Gynecol. 1999; 93: 392-395Crossref PubMed Scopus (211) Google ScholarNo increased risks for preterm birth, reduced birth weight or length, or stillbirths in 2968 exposed in population-based Scandinavian register25Norjavaara E. de Verdier M.G. Normal pregnancy outcomes in a population-based study including 2,968 pregnant women exposed to budesonide.J Allergy Clin Immunol. 2003; 111: 736-742Abstract Full Text Full Text PDF PubMed Scopus (179) Google ScholarSmall amounts excreted in 8 women with asthma using inhaled budesonide26Fält A. Bengtsson T. Kennedy B.M. Gyllenberg A. Lindberg B. Thorsoon L. et al.Exposure of infants to budesonide through breast milk of asthmatic mothers.J Allergy Clin Immunol. 2007; 120: 798-802Abstract Full Text Full Text PDF PubMed Scopus (21) Google ScholarFluticasoneNo increased risk of major congenital malformations overall in a cohort study of 1602 mother-infant pairs exposed to fluticasone compared with 3678 exposed to other ICSs, stratified by severity27Charlton R.A. Snowball J.M. Nightingale A.L. Davis K.J. Safety of fluticasone propionate prescribed for asthma during pregnancy: a UK population-based cohort study.J Allergy Clin Immunol Pract. 2015; 3: 772-779.e773Abstract Full Text Full Text PDF PubMed Scopus (19) Google ScholarNo increased risk of low birth weight, preterm birth, or small-for-gestational-age infants in retrospective database study of infants of 3190 mothers exposed to fluticasone compared with 608 mothers exposed to budesonide28Cossette B. Beauchesne M.F. Forget A. Lemiere C. Larivee P. Rey E. et al.Relative perinatal safety of salmeterol vs formoterol and fluticasone vs budesonide use during pregnancy.Ann Allergy Asthma Immunol. 2014; 112: 459-464Abstract Full Text Full Text PDF PubMed Scopus (27) Google ScholarNo published data. Poor bioavailability and low serum levels expected to produce low levels in milkLong-acting beta agonists (LABAs)No evidence of increased risk in major birth defects in 65 salmeterol-exposed pregnancies.29Wilton L.V. Pearce G.L. Martin R.M. Mackay F.J. Mann R.D. The outcomes of pregnancy in women exposed to newly marketed drugs in general practice in England.Br J Obstetr Gynaecol. 1998; 105: 882-889Crossref PubMed Scopus (120) Google Scholar In 1 analysis of a database, increased risks for major cardiac and major "other" birth defects were seen with first trimester exposure in 165 pregnancies.30Eltonsy S. Forget A. Blais L. Beta2-agonists use during pregnancy and the risk of congenital malformations.Birth Def Res A Clin Mol Teratol. 2011; 91: 937-947Crossref PubMed Scopus (35) Google Scholar However, in a later study from the same database, 841 pregnancies exposed to LABAs with low- or medium-dose ICSs showed no increased risk of major birth defects overall compared with pregnancies exposed to medium- to high-dose ICSs alone31Eltonsy S. Forget A. Beauchesne M.F. Blais L. Risk of congenital malformations for asthmatic pregnant women using a long-acting β₂-agonist and inhaled corticosteroid combination versus higher-dose inhaled corticosteroid monotherapy.J Allergy Clin Immunol. 2015; 135: 123-130Abstract Full Text Full Text PDF PubMed Scopus (36) Google ScholarNo difference in low birth weight, preterm birth, or small-for-gestational-age infants was noted in infants of mothers exposed to salmeterol vs formoterol in a retrospective database study28Cossette B. Beauchesne M.F. Forget A. Lemiere C. Larivee P. Rey E. et al.Relative perinatal safety of salmeterol vs formoterol and fluticasone vs budesonide use during pregnancy.Ann Allergy Asthma Immunol. 2014; 112: 459-464Abstract Full Text Full Text PDF PubMed Scopus (27) Google ScholarLimited observational data are available regarding the safety of LABA use during pregnancy. The benefits of the use of LABA appear to outweigh the risks as long as they are used concurrently with ICSsSalmeterol: No published data. Poor bioavailability and low serum levels expected to produce low levels in milkMontelukast/leukotriene receptor antagonist (LTRA)No increased risk of major birth defects overall in 74 and 180 exposed pregnancies.32Sarkar M. Koren G. Kalra S. Ying A. Smorlesi C. De Santis M. et al.Montelukast use during pregnancy: a multicentre, prospective, comparative study of infant outcomes.Eur J Clin Pharmacol. 2009; 65: 1259-1264Crossref PubMed Scopus (57) Google Scholar,33Bakhireva L.N. Jones K.L. Schatz M. Klonoff-Cohen H.S. Johnson D. Slymen D.J. et al.Safety of leukotriene receptor antagonists in pregnancy.J Allergy Clin Immunol. 2007; 119: 618-625Abstract Full Text Full Text PDF PubMed Scopus (76) Google Scholar No increased risk in major birth defects overall or specific birth defects in 1164 exposed pregnancies in claims study.34Nelsen L.M. Shields K.E. Cunningham M.L. Stoler J.M. Bamshad M.J. Eng P.M. et al.Congenital malformations among infants born to women receiving montelukast, inhaled corticosteroids, and other asthma medications.J Allergy Clin Immunol. 2012; 129: 251-254.e251-6Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar No increased risk in major birth defects in 1827 exposed pregnancies in Danish register study35Cavero-Carbonell C. Vinkel-Hansen A. Rabanque-Hernández M.J. Martos C. Garne E. Fetal exposure to montelukast and congenital anomalies: a population based study in Denmark.Birth Def Res. 2017; 109: 452-459Crossref PubMed Scopus (16) Google ScholarNo increased risk for reduced birth weight or shortened gestational age in 180 exposed when compared with other asthmatic patients.32Sarkar M. Koren G. Kalra S. Ying A. Smorlesi C. De Santis M. et al.Montelukast use during pregnancy: a multicentre, prospective, comparative study of infant outcomes.Eur J Clin Pharmacol. 2009; 65: 1259-1264Crossref PubMed Scopus (57) Google ScholarNo increased risk for preterm delivery, low birth weight, or preeclampsia in 1827 exposed compared with other treated asthmatic patients35Cavero-Carbonell C. Vinkel-Hansen A. Rabanque-Hernández M.J. Martos C. Garne E. Fetal exposure to montelukast and congenital anomalies: a population based study in Denmark.Birth Def Res. 2017; 109: 452-459Crossref PubMed Scopus (16) Google ScholarData on the use of LTRA during human pregnancy are limitedVery low levels in breast milk of 7 women given 10 mg dose—0.68% of weight-adjusted maternal dose36Datta P. Rewers-Felkins K. Baker T. Hale T.W. Transfer of montelukast into human milk during lactation.Breastfeed Med. 2017; 12: 54-57Crossref PubMed Scopus (3) Google ScholarSystemic corticosteroidsMeta-analysis of cohort studies showed no overall increased risk of major birth defects in pooled 535 exposed pregnancies; meta-analysis of 4 case-control studies showed an increased risk of ∼3-fold for oral clefts.37Park-Wyllie L. Mazzotta P. Pastuszak A. Moretti M.E. Beique L. Hunnisett L. et al.Birth defects after maternal exposure to corticosteroids: prospective cohort study and meta-analysis of epidemiological studies.Teratology. 2000; 62: 385-392Crossref PubMed Scopus (644) Google Scholar However, most recent and largest case-control study from US National Birth Defects Prevention Study showed no increased risk for oral clefts with first-trimester systemic steroid use for any indication in 2372 cases and 5922 controls38Skuladottir H. Wilcox A.J. Ma C. Lammer E.J. Rasmussen S.A. Werler M.M. et al.Corticosteroid use and risk of orofacial clefts.Birth Def Res A Clin Mol Teratol. 2014; 100: 499-506Crossref PubMed Scopus (58) Google ScholarPreterm delivery, low birth weight or reduced birth weight, preeclampsia, and gestational diabetes have all been reported to occur more frequently in women treated with systemic steroids in pregnancy; however, studies that attempted to control for underlying maternal disease and disease activity typically find the associated risks for these outcomes reduced or eliminated39Bandoli G. Palmsten K. Forbess Smith C.J. Chambers C.D. A review of systemic corticosteroid use in pregnancy and the risk of select pregnancy and birth outcomes.Rheum Dis Clin North America. 2017; 43: 489-502Abstract Full Text Full Text PDF PubMed Scopus (83) Google ScholarAdverse outcomes seen may be a result of severe asthma or the medication itself. These outcomes would be outweighed by the potential risks of a severe asthma exacerbation, which include maternal or fetal mortality. Oral corticosteroids are recommended when indicated for the management of severe asthma during pregnancyPrednisone: Amounts very low in breast milk; no adverse effects noted in breast-fed infants.40Katz F.H. Duncan B.R. Letter: entry of prednisone into human milk.N Engl J Med. 1975; 293: 1154Crossref PubMed Scopus (36) Google Scholar,41Constantinescu S. Pai A. Coscia L.A. Davison J.M. Moritz M.J. Armenti V.T. Breast-feeding after transplantation.Best Pract Res. 2014; 28: 1163-1173Crossref Scopus (52) Google Scholar High doses may cause temporary loss of milk supply42McGuire E. Sudden loss of milk supply following high-dose triamcinolone (Kenacort) injection.Breastfeed Rev. 2012; 20: 32-34PubMed Google Scholar,43Babwah T.J. Nunes P. Maharaj R.G. An unexpected temporary suppression of lactation after a local corticosteroid injection for tenosynovitis.Eur J Gen Pract. 2013; 19: 248-250Crossref PubMed Scopus (7) Google ScholarTiotropiumNo published human dataNo published data. Poor bioavailability and low serum levels expected to produce low levels in milkBiologicsContinue biologics in patients who are responding to them before pregnancy. Consider starting biologics during pregnancy in women who (1) are candidates for the therapy, and (2) who have severe asthma and are at risk of asthma exacerbations or oral corticosteroid use. Data are neededOmalizumab/anti-IgENo increased risk compared with general population for major birth defects overall in 169 exposed pregnancies enrolled in a registry.44Namazy J. Cabana M.D. Scheuerle A.E. Thorp J.M. Chen H. Carrigan G. et al.The Xolair Pregnancy Registry (EXPECT): the safety of omalizumab use during pregnancy.J Allergy Clin Immunol. 2015; 135: 407-412Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar Also when compared with a disease-matched unexposed cohort45Namazy J.A. Blais L. Andrews E.B. Scheuerle A.E. Cabana M.D. Thorp J.M. et al.Pregnancy outcomes in the omalizumab pregnancy registry and a disease-matched comparator cohort.J Allergy Clin Immunol. 2020; 145: 528-536.e521Abstract Full Text Full Text PDF PubMed Scopus (34) Google ScholarThe rates of prematurity (<37 wk gestation) and small for gestational age were not unlike those seen in other studies of severe pregnant asthmatic patientsContinue omalizumab in patients who are responding to it before pregnancy. Consider starting omalizumab during pregnancy in patients who (1) are candidates for this therapy and (2) have severe asthma and are at risk of asthma exacerbations or oral corticosteroid use. Consider omalizumab over other biologics in women who are candidates for more than 1 biologic due to some available human data. More data are neededNo published data. Large protein is likely destroyed in infant gastrointestinal tractMepolizumab/anti–IL-5No published human data/Pregnancy registry through mothertobaby.orgNo published data. Large protein is likely destroyed in infant gastrointestinal tractReslizumab/anti–IL-5No published human dataNo published data. Large protein is likely destroyed in infant gastrointestinal tractBenralizumab/anti–IL-5 receptorNo published human data/Pregnancy registry through mothertobaby.org ongoingNo published data. Large protein is likely destroyed in infant gastrointestinal tractDupilmuab/anti–IL-4 receptorNo published human data/Pregnancy registry through mothertobaby.org ongoingNo published data. Large protein is likely destroyed in infant gastrointestinal tract Open table in a new tab ICS, Inhaled corticosteroid; LABA, long-acting β-agonist; LTRA, leukotriene receptor antagonist. There are no randomized clinical trials of asthma biologics that intentionally included pregnant women. Data modified from Schatz and Dombrowski.13Schatz M. Dombrowski M.P. Asthma in pregnancy.N Engl J Med. 2009; 360: 1862-1869Crossref PubMed Scopus (75) Google Scholar However, many older and most newer medications, such as asthma biologics, have limited epidemiologic studies on human pregnancy available. Despite lack of such data, current recommendations are to continue biologics during pregnancy, especially if a woman has shown a significant response to treatment before pregnancy.47Pfaller B. Yepes-Nuñez J.J. Agache I. Akdis C.A. Alsalamah M. Bavbek S. et al.Biologicals in atopic disease in pregnancy: an EAACI position paper.Allergy. 2021; 76: 71-89Crossref PubMed Scopus (16) Google Scholar In addition, to minimize known maternal and fetal risks for poorly controlled asthma in pregnancy, providers may consider starting a biologic in a pregnant woman with severe asthma at risk for asthma exacerbations or need for oral corticostero