Teratogenic evaluation of drugs used by pregnant patients with gastrointestinal system diseases

Aim: Drug use may be necessary in pregnant women due to chronic diseases or digestive disorders. However, safety of the use of many medications during pregnancy remains limited. The purpose of this study is to evaluate the safety of digestive system drugs during pregnancy.Material and Methods: In this observational study, we collected data of pregnant women who used gastrointestinal agents between 2014 and 2018. Data regarding the medications, exposure to other agents and co-morbidities were documented. Our Teratology Information Service assessed the teratogenic risk of drugs. To investigate the pregnancy outcomes, a follow-up was conducted on the women after delivery to obtain whether there had been any major and/or minor congenital malformations and/or adverse neurodevelopmental effects in the infant.Results: Twelve pregnant women (age 27-34 years), whose gestational age were between 4 and 24 weeks at admission time, were followed up. Among patients, one woman with ulcerative colitis used azathioprine; two women with hepatitis B using tenofovir; three women with nausea and abdominal pain used metoclopramide, hyoscine, ondansetron; six women with dyspepsia and gastritis used alginic acid, antacids, lansoprazole, rabeprazole, pantoprazole, trimebutine, alverine and pancreatin. After delivery, no congenital anomalies were detected. Two infants had low birth weights for gestational age, and one was born preterm.Conclusion: Data in our study contributes to the literature on safety of gastrointestinal system medications in pregnancy. This permits decreasing the number of potential elective terminations related to the concerns about digestive system drugs.

PDF

___

Dathe K, Schaefer C. Drug safety in pregnancy: the German Embryotox institute. Eur J Clin Pharmacol 2018;74:171-9.
Spielmann K, Kayser A, Beck E, et al. Pregnancy outcome after anti-migraine triptan use: A prospective observational cohort study. Cephalalgia 2018;38:1081-92.
Kaplan YC, Karadaş B, Küçüksolak G, et al. Counselling pregnant women at the crossroads of Europe and Asia: effect of Teratology Information Service in Turkey. Int J Clin Pharm 2017;39783-90.
De Santis M, Straface G, Carducci B, et al. Risk of drug-induced congenital defects. Eur J Obstet Gynecol Reprod Biol 2004;117:10-9.
Loane M, Dolk H, Kelly A, et al; Paper 4: EUROCAT statistical monitoring: identification and investigation of ten year trends of congenital anomalies in Europe. Birth Defects Res A Clin Mol Teratol 2011;91:31-43.
Githens Jh, Rosenkrantz Jg, Tunnock Sm. Teratogenic effects of azathioprine (imuran).J Pediatr 1965;66:959-61.
Azathioprine.Reprotox. http://www.micromedexsolutions.com/micromedex2/librarian/CS/524F03/ND_PR/evidencexpert/ND_P/evidencexpert/DUPLICATIONSHIELDSYNC/739220/ND_PG/evidencexpert/ND_B/evidencexpert/ND_AppProduct/evidencexpert/ND_T/evidencexpert/PFActionId/evidencexpert.
Davison JM, Dellagrammatikas H, Parkin JM. Maternal azathioprine therapy and depressed haemopoiesis in the babies of renal allograft patients. Br J Obstet Gynaecol 1985;92:233-9.
Durst JK, Rampersad RM. Pregnancy in women with solid-organ transplants: a review. Obstet Gynecol Surv 2015;70:408-18.
Flint J, Panchal S, Hurrell A, et al. BSR and BHPR Standards, Guidelines and Audit Working Group. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford) 2016;55:1693-7.
Hahn BH, McMahon MA, Wilkinson A, et al; American college of rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken) 2012;64:797-808.
Cleary BJ, Kallen B. Early pregnancy azathioprine use and pregnancy outcome. Birth Defects Res A Clin Mol Teratol 2009;85:647-54.
Williams PL, Crain MJ, Yildirim C, et al; Congenital anomalies and in utero antiretroviral exposure in human immunodeficiency virus-exposed uninfected infants. JAMA Pediatr 2015;169:48-55.
Tenofovir disoproxil fumarate: Drug information. https://www.uptodate.com/contents/tenofovir-disoproxil-fumarate-drug-information?search=tenofovir&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#F225420 access date 07.06.2018
Terrault NA, Bzowej NH, Chang KM, et al; AASLD guidelines for treatment of chronic hepatitis B. Hepatology 2016;63:261-83.
Hodgkinson R, Glassenberg R, Joyce TH 3rd, et al. Comparison of cimetidine (Tagamet) with antacid for safety and effectiveness in reducing gastric acidity before elective cesarean section. Anesthesiology 1983;59:86-90.
Witter FR, King TM, Blake DA. The effects of chronic gastrointestinal medication on the fetus and neonate. Obstet Gynecol 1981;58:79-84.
Gill SK, O’Brien L, Einarson TR, et al. The safety of proton pump inhibitors (PPIs) in pregnancy: a meta-analysis. Am J Gastroenterol 2009;104:1541-6.
Pasternak B, Hviid A. Use of proton-pump inhibitors in early pregnancy and the risk of birth defects. N Engl J Med 2010;363:2114-23.
rsenault MY, Lane CA, MacKinnon CJ, et al. The management of nausea and vomiting of pregnancy. J Obstet Gynaecol Can 2002;24:817-31.
Boelig RC, Barton SJ, Saccone G, Kelly AJ, et al. Interventions for treating hyperemesis gravidarum. Cochrane Database Syst Rev 2016;11:CD010607.
Matthews A, Haas DM, O’Mathúna DP, et al. Interventions for nausea and vomiting in early pregnancy. Cochrane Database Syst Rev 2014;21:CD007575.
Magee LA, Mazzotta P, Koren G. Evidence-based view of safety and effectiveness of pharmacologic therapy for nausea and vomiting of pregnancy (NVP). Am J Obstet Gynecol 2002;186:256-61.
Badell ML, Ramin SM, Smith JA. Treatment options for nausea and vomiting during pregnancy. Pharmacotherapy 2006;26:1273-87.
McParlin C, O’Donnell A, Robson SC, et al. Treatments for hyperemesis gravidarum and nausea and vomiting in pregnancy: a systematic review. JAMA 2016;316:1392-401.
Seto A, Einarson T, Koren G. Pregnancy outcome following first trimester exposure to antihistamines: meta-analysis. Am J Perinatol 1997;14:119-24.
Mazzotta P, Magee LA. A risk-benefit assessment of pharmacological and nonpharmacological treatments for nausea and vomiting of pregnancy. Drugs 2000;59:781-800.
Gilboa SM, Strickland MJ, Olshan AF, Use of antihistamine medications during early pregnancy and isolated major malformations. Birth Defects Res A Clin Mol Teratol 2009;85:137-50.
Li Q, Mitchell AA, Werler MM, et al. Assessment of antihistamine use in early pregnancy and birth defects. J Allergy Clin Immunol Pract 2013;1:666-74.