Birth Outcomes in Women Who Have Taken Adalimumab in Pregnancy: A Prospective Cohort Study

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2019 Oct 19

PMID 31626646

Citations 24

Authors

Christina D Chambers

Diana L Johnson

Ronghui Xu

Yunjun Luo

Janina Lopez-Jimenez

Margaret P Adam

Stephen R Braddock

Luther K Robinson

Keith Vaux

Kenneth Lyons Jones

Affiliations

Soon will be listed here.

Abstract

Background: Information is needed on the safety of adalimumab when used in pregnancy for the treatment of certain autoimmune diseases.

Methods And Findings: Between 2004 and 2016, the Organization of Teratology Information Specialists Research Center at the University of California San Diego conducted a prospective controlled observational cohort study in 602 pregnant women who had or had not taken adalimumab. Women in the adalimumab-exposed cohort had received at least one dose of the drug in the first trimester for the treatment of rheumatoid arthritis or Crohn's Disease (N = 257). Women in the disease comparison cohort had not used adalimumab in pregnancy (N = 120). Women in the healthy comparison cohort had no rheumatic or inflammatory bowel diseases (N = 225). Women and their infants were followed to one year postpartum with maternal interviews, medical records abstraction, and physical examinations. Study outcomes were major structural birth defects, minor defects, spontaneous abortion, preterm delivery, pre and post-natal growth deficiency, serious or opportunistic infections and malignancies. 42/602 (7.0%) of pregnancies were lost-to-follow-up. 22/221 (10.0%) in the adalimumab-exposed cohort had a live born infant with a major birth defect compared to 8/106 (7.5%) in the diseased unexposed cohort (adjusted odds ratio 1.10, 95% confidence interval [CI] 0.45 to 2.73). Women in the adalimumab-exposed cohort were more likely to deliver preterm compared to the healthy cohort (adjusted hazard ratio [aHR] 2.59, 95% CI 1.22 to 5.50), but not compared to the diseased unexposed cohort (aHR 0.82, 95% CI 0.66 to 7.20). No significant increased risks were noted with adalimumab exposure for any other study outcomes.

Conclusions: Adalimumab exposure in pregnancy compared to diseased unexposed pregnancies was not associated with an increased risk for any of the adverse outcomes examined. Women with rheumatoid arthritis or Crohn's Disease were at increased risk of preterm delivery, irrespective of adalimumab exposure.

Citing Articles

Trends in medications for autoimmune disorders during pregnancy and factors for their discontinuation: a population-based study.

Mainbourg S, Sheehy O, Gorgui J, Vinet E, Berard A BMC Pregnancy Childbirth. 2024; 24(1):765.

PMID: 39563243 PMC: 11575194. DOI: 10.1186/s12884-024-06932-y.

SARS-CoV-2 in Pregnancy, Birth and Puerperium. Guideline of the DGGG and DGPM (S2k-Level, AWMF Registry Number 015/092, March 2022).

Pecks U, Agel L, Doubek K, Hagenbeck C, Jennewein L, von Kaisenberg C Geburtshilfe Frauenheilkd. 2024; 83(5):517-546.

PMID: 39258218 PMC: 11384259. DOI: 10.1055/a-2003-5983.

Outcomes of Continuation vs Discontinuation of Adalimumab Therapy During Third Trimester of Pregnancy in Inflammatory Bowel Disease.

Truta B, Canner J, Fang S, Efron J, Safar B Gastro Hep Adv. 2024; 1(5):785-791.

PMID: 39131851 PMC: 11307739. DOI: 10.1016/j.gastha.2022.04.009.

Mechanisms underlying the therapeutic effects of in treating recurrent spontaneous abortion based on network pharmacology and molecular docking.

Zheng W, Lei M, Yao Y, Zhan J, Zhang Y, Zhou Q Front Mol Biosci. 2024; 11:1282100.

PMID: 38872917 PMC: 11170108. DOI: 10.3389/fmolb.2024.1282100.

Elevated cord levels of ustekinumab following its use in the treatment of Crohn's disease in pregnancy.

Keating N, Walker C, Lally D, OBrien C, Corcoran S, Ryan B Obstet Med. 2024; 17(1):47-49.

PMID: 38660328 PMC: 11037200. DOI: 10.1177/1753495X221135201.

References

Norgaard M, Larsson H, Pedersen L, Granath F, Askling J, Kieler H . Rheumatoid arthritis and birth outcomes: a Danish and Swedish nationwide prevalence study. J Intern Med. 2010; 268(4):329-37. DOI: 10.1111/j.1365-2796.2010.02239.x. View

Chambers C, Johnson D, Robinson L, Braddock S, Xu R, Lopez-Jimenez J . Birth outcomes in women who have taken leflunomide during pregnancy. Arthritis Rheum. 2010; 62(5):1494-503. PMC: 3633589. DOI: 10.1002/art.27358. View

Weber-Schoendorfer C, Oppermann M, Wacker E, Bernard N, Beghin D, Cuppers-Maarschalkerweerd B . Pregnancy outcome after TNF-α inhibitor therapy during the first trimester: a prospective multicentre cohort study. Br J Clin Pharmacol. 2015; 80(4):727-39. PMC: 4594709. DOI: 10.1111/bcp.12642. View

Namazy J, Blais L, Andrews E, Scheuerle A, Cabana M, Thorp J . Pregnancy outcomes in the omalizumab pregnancy registry and a disease-matched comparator cohort. J Allergy Clin Immunol. 2019; 145(2):528-536.e1. DOI: 10.1016/j.jaci.2019.05.019. View

Broms G, Granath F, Ekbom A, Hellgren K, Pedersen L, Sorensen H . Low Risk of Birth Defects for Infants Whose Mothers Are Treated With Anti-Tumor Necrosis Factor Agents During Pregnancy. Clin Gastroenterol Hepatol. 2015; 14(2):234-41.e1-5. DOI: 10.1016/j.cgh.2015.08.039. View

Xu R, Luo Y, Chambers C . Assessing the effect of vaccine on spontaneous abortion using time-dependent covariates Cox models. Pharmacoepidemiol Drug Saf. 2012; 21(8):844-50. DOI: 10.1002/pds.3301. View

Bharti B, Lee S, Lindsay S, Wingard D, Jones K, Lemus H . Disease Severity and Pregnancy Outcomes in Women with Rheumatoid Arthritis: Results from the Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Project. J Rheumatol. 2015; 42(8):1376-82. DOI: 10.3899/jrheum.140583. View

Xu R, Hou J, Chambers C . The impact of confounder selection in propensity scores when applied to prospective cohort studies in pregnancy. Reprod Toxicol. 2018; 78:75-80. DOI: 10.1016/j.reprotox.2018.04.003. View

LUBCHENCO L, HANSMAN C, Boyd E . Intrauterine growth in length and head circumference as estimated from live births at gestational ages from 26 to 42 weeks. Pediatrics. 1966; 37(3):403-8. View

10.

Patrick A, Schneeweiss S, Brookhart M, Glynn R, Rothman K, Avorn J . The implications of propensity score variable selection strategies in pharmacoepidemiology: an empirical illustration. Pharmacoepidemiol Drug Saf. 2011; 20(6):551-9. PMC: 3123427. DOI: 10.1002/pds.2098. View

11.

Julsgaard M, Brown S, Gibson P, Bell S . Adalimumab levels in an infant. J Crohns Colitis. 2012; 7(7):597-8. DOI: 10.1016/j.crohns.2012.10.009. View

12.

Chambers C, Johnson D, Xu R, Luo Y, Louik C, Mitchell A . Safety of the 2010-11, 2011-12, 2012-13, and 2013-14 seasonal influenza vaccines in pregnancy: Birth defects, spontaneous abortion, preterm delivery, and small for gestational age infants, a study from the cohort arm of VAMPSS. Vaccine. 2016; 34(37):4443-9. DOI: 10.1016/j.vaccine.2016.06.054. View

13.

Irvine E, Zhou Q, Thompson A . The Short Inflammatory Bowel Disease Questionnaire: a quality of life instrument for community physicians managing inflammatory bowel disease. CCRPT Investigators. Canadian Crohn's Relapse Prevention Trial. Am J Gastroenterol. 1996; 91(8):1571-8. View

14.

Bruce B, Fries J . The Stanford Health Assessment Questionnaire: a review of its history, issues, progress, and documentation. J Rheumatol. 2003; 30(1):167-78. View

15.

Boyd H, Basit S, Harpsoe M, Wohlfahrt J, Jess T . Inflammatory Bowel Disease and Risk of Adverse Pregnancy Outcomes. PLoS One. 2015; 10(6):e0129567. PMC: 4471220. DOI: 10.1371/journal.pone.0129567. View

16.

Stephansson O, Larsson H, Pedersen L, Kieler H, Granath F, Ludvigsson J . Crohn's disease is a risk factor for preterm birth. Clin Gastroenterol Hepatol. 2010; 8(6):509-15. DOI: 10.1016/j.cgh.2010.02.014. View

17.

Correa-Villasenor A, Cragan J, Kucik J, OLeary L, Siffel C, Williams L . The Metropolitan Atlanta Congenital Defects Program: 35 years of birth defects surveillance at the Centers for Disease Control and Prevention. Birth Defects Res A Clin Mol Teratol. 2004; 67(9):617-24. DOI: 10.1002/bdra.10111. View

18.

Pham-Huy A, Sadarangani M, Huang V, Ostensen M, Castillo E, Troster S . From mother to baby: antenatal exposure to monoclonal antibody biologics. Expert Rev Clin Immunol. 2018; 15(3):221-229. DOI: 10.1080/1744666X.2019.1561282. View

19.

Wallenius M, Salvesen K, Daltveit A, Skomsvoll J . Rheumatoid arthritis and outcomes in first and subsequent births based on data from a national birth registry. Acta Obstet Gynecol Scand. 2013; 93(3):302-7. DOI: 10.1111/aogs.12324. View

20.

Vinet E, De Moura C, Pineau C, Abrahamowicz M, Curtis J, Bernatsky S . Serious Infections in Rheumatoid Arthritis Offspring Exposed to Tumor Necrosis Factor Inhibitors: A Cohort Study. Arthritis Rheumatol. 2018; 70(10):1565-1571. DOI: 10.1002/art.40536. View