Adverse drug reactions reported during pregnancy and associated congenital disorders
Introduction: The main aim of this review is to bring forth the information about adverse drug events that take place because of the consumption of various sorts of medications during pregnancy and also to create awareness regarding birth defects. Not only the recognition of the unfavorable results of the drugs is difficult, but avoiding some of the medications, even during pregnancy, becomes out of the question. The non-inclusion of pregnant females in clinical trials is another factor adding to this problem. It was only after the thalidomide incidence when pharmacovigilance in pregnancy drew focus. Till today, many drugs have been reported to have severe outcomes on the developing fetus which have also had a great impact on their lives.
Methods: Several literary works from various platforms like Google Scholar, PubMed, The Lancet, American Journal of Perinatology, and many others concerning the adverse drug reactions during pregnancy and related fetal disadvantages were thoroughly reviewed.
Results: This review can cater us with a brief idea of the unpleasant results of antidepressants, antibacterials, antihypertensives, NSAIDs, and antithyroid drugs taken during the phase of pregnant nine months. Vaccines, on the other hand, are comparatively safe to use on preggers and are reported with no adverse results. Corona virus was also reported to cause serious illness in pregnant females. However, there were no reports of its vertical transmission. Drug exposure during pregnancy is not completely risk-free and can result in cardiac and CNS malformations, neural tube defects, and many other serious disorders.
Discussion: Numerous unpleasant reactions of the drugs on pregnant females and newborns have been unveiled. Nevertheless, many more such studies are obligatory for bringing forth new knowledge of the unfavorable outcomes of various drugs.
Aboubakr, M., Elbadawy, M., Soliman, A., & El-Hewaity, M. (2014). Embryotoxic and teratogenic effects of norfloxacin in pregnant female albino rats. Advances in pharmacological sciences, 2014.
Alabdulrazzaq, F., & Koren, G. (2012). Fetal safety of calcium channel blockers. Canadian Family Physician, 58(7), 746.
Alzamora, M. C., Paredes, T., Caceres, D., Webb, C. M., Valdez, L. M., & La Rosa, M. (2020). Severe COVID-19 during pregnancy and possible vertical transmission. American journal of perinatology, 37(08), 861-865.
Andersen, S. L., & Andersen, S. (2020). Antithyroid drugs and birth defects. Thyroid research, 13(1), 1-9.
Andersen, S. L., Olsen, J., Wu, C. S., & Laurberg, P. (2014). Severity of birth defects after propylthiouracil exposure in early pregnancy. Thyroid, 24(10), 1533-1540.
Anderson, K. N., Lind, J. N., Simeone, R. M., Bobo, W. V., Mitchell, A. A., Riehle-Colarusso, T., ... & Reefhuis, J. (2020). Maternal use of specific antidepressant medications during early pregnancy and the risk of selected birth defects. JAMA psychiatry, 77(12), 1246-1255.
Andersson, N. W., Olsen, R. H., & Andersen, J. T. (2021). Association between use of macrolides in pregnancy and risk of major birth defects: nationwide, register based cohort study. bmj, 372.
Bahat Dinur, A., Koren, G., Matok, I., Wiznitzer, A., Uziel, E., Gorodischer, R., & Levy, A. (2013). Fetal safety of macrolides. Antimicrobial agents and chemotherapy, 57(7), 3307-3311.
bDashraath, P., Wong, J. L. J., Lim, M. X. K., Lim, L. M., Li, S., Biswas, A., ... & Su, L. L. (2020). Coronavirus disease 2019 (COVID-19) pandemic and pregnancy. American journal of obstetrics and gynecology, 222(6), 521-531.
Chen, H., Guo, J., Wang, C., Luo, F., Yu, X., Zhang, W., ... & Zhang, Y. (2020). Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. The lancet, 395(10226), 809-815.
Cooper, W. O., Griffin, M. R., Arbogast, P., Hickson, G. B., Gautam, S., & Ray, W. A. (2002). Very early exposure to erythromycin and infantile hypertrophic pyloric stenosis. Archives of pediatrics & adolescent medicine, 156(7), 647-650.
Dashraath, P., Nielsen-Saines, K., Madhi, S. A., & Baud, D. (2020). COVID-19 vaccines and neglected pregnancy. The Lancet, 396(10252), e22.
Dathe, K., & Schaefer, C. (2019). The use of medication in pregnancy. Deutsches Ärzteblatt International, 116(46), 783.
Donovan, P. (2012). Hypertensive disorders of pregnancy.
Dubovicky, M., Belovicova, K., Csatlosova, K., & Bogi, E. (2017). Risks of using SSRI/SNRI antidepressants during pregnancy and lactation. Interdisciplinary toxicology, 10(1), 30.
Einarson A. (2010). Paroxetine use in pregnancy and increased risk of heart defects: Evaluating the evidence. Canadian family physician Medecin de famille canadien, 56(8), 767–768.
Fornasier, G., Francescon, S., Leone, R., & Baldo, P. (2018). An historical overview over Pharmacovigilance. International journal of clinical pharmacy, 40(4), 744-747.
Giles, M. L., Krishnaswamy, S., Macartney, K., & Cheng, A. (2019). The safety of inactivated influenza vaccines in pregnancy for birth outcomes: a systematic review. Human vaccines & immunotherapeutics, 15(3), 687-699.
Goldberg, O., Moretti, M., Levy, A., & Koren, G. (2015). Exposure to nitrofurantoin during early pregnancy and congenital malformations: a systematic review and meta-analysis. Journal of Obstetrics and Gynaecology Canada, 37(2), 150-156.
Hansen, C., Andrade, S. E., Freiman, H., Dublin, S., Haffenreffer, K., Cooper, W. O., ... & Davis, R. (2016). Trimethoprim–sulfonamide use during the first trimester of pregnancy and the risk of congenital anomalies. Pharmacoepidemiology and drug safety, 25(2), 170-178.
Holdiness, M. R. (1987). Teratology of the antituberculosis drugs. Early human development, 15(2), 61-74.
Hviid, A., & Svanström, H. (2009). Antibiotic use and intussusception in early childhood. Journal of antimicrobial chemotherapy, 64(3), 642-648.
Kahaly, G. J., Bartalena, L., Hegedüs, L., Leenhardt, L., Poppe, K., & Pearce, S. H. (2018). 2018 European thyroid association guideline for the management of Graves’ hyperthyroidism. European thyroid journal, 7(4), 167-186.
Khalil, A., Von Dadelszen, P., Draycott, T., Ugwumadu, A., O’Brien, P., & Magee, L. (2020). Change in the incidence of stillbirth and preterm delivery during the COVID-19 pandemic. Jama, 324(7), 705-706.
Khan, M. S. I., Nabeka, H., Akbar, S. M. F., Al Mahtab, M., Shimokawa, T., Islam, F., & Matsuda, S. (2020). Risk of congenital birth defects during COVID-19 pandemic: Draw attention to the physicians and policymakers. Journal of Global Health, 10(2).
Kharbanda, E. O., Vazquez-Benitez, G., Romitti, P. A., Naleway, A. L., Cheetham, T. C., Lipkind, H. S., ... & Datalink, V. S. (2017). First trimester influenza vaccination and risks for major structural birth defects in offspring. The Journal of pediatrics, 187, 234-239.
Kim, J. H., & Scialli, A. R. (2011). Thalidomide: the tragedy of birth defects and the effective treatment of disease. Toxicological sciences, 122(1), 1-6.
Kozer, E., Nikfar, S., Costei, A., Boskovic, R., Nulman, I., & Koren, G. (2002). Aspirin consumption during the first trimester of pregnancy and congenital anomalies: a meta-analysis. American journal of obstetrics and gynecology, 187(6), 1623-1630.
Li, P., Qin, X., Tao, F., & Huang, K. (2020). Maternal exposure to sulfonamides and adverse pregnancy outcomes: A systematic review and meta-analysis. Plos one, 15(12), e0242523.
Li, X., Liu, G. Y., Ma, J. L., & Zhou, L. (2015). Risk of congenital anomalies associated with antithyroid treatment during pregnancy: a meta-analysis. Clinics, 70, 453-459.
Louik, C., Kerr, S., & Mitchell, A. A. (2014). First‐trimester exposure to bupropion and risk of cardiac malformations. Pharmacoepidemiology and drug safety, 23(10), 1066-1075.
Mackin, D. W., & Walker, S. P. (2020). The historical aspects of vaccination in pregnancy. Best Practice & Research Clinical Obstetrics & Gynaecology.
Mallah, N., Tohidinik, H. R., Etminan, M., Figueiras, A., & Takkouche, B. (2020). Prenatal exposure to macrolides and risk of congenital malformations: a meta-analysis. Drug safety, 43(3), 211-221.
Moore, K. M., & Suthar, M. S. (2020). Comprehensive analysis of COVID-19 during pregnancy. Biochemical and Biophysical Research Communications.
Moretti, M. E., Caprara, D., Drehuta, I., Yeung, E., Cheung, S., Federico, L., & Koren, G. (2012). The fetal safety of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers. Obstetrics and Gynecology International, 2012.
Moro, P. L., Cragan, J., Lewis, P., & Sukumaran, L. (2017). Major birth defects after vaccination reported to the Vaccine Adverse Event Reporting System (VAERS), 1990 to 2014. Birth defects research, 109(13), 1057-1062.
Muanda, F. T., Sheehy, O., & Bérard, A. (2017). Use of antibiotics during pregnancy and the risk of major congenital malformations: a population based cohort study. British journal of clinical pharmacology, 83(11), 2557-2571.
Nakhai-Pour, H. R., & Bérard, A. (2008). Major malformations after first trimester exposure to aspirin and NSAIDs. Expert review of clinical pharmacology, 1(5), 605-616.
Nezvalová-Henriksen, K., Wood, M., Spigset, O., & Nordeng, H. (2016). Association of prenatal ibuprofen exposure with birth weight and gestational age: A population-based sibling study. PloS one, 11(12), e0166971.
Ofori, B., Oraichi, D., Blais, L., Rey, E., & Bérard, A. (2006). Risk of congenital anomalies in pregnant users of non‐steroidal anti‐inflammatory drugs: A nested case‐control study. Birth Defects Research Part B: Developmental and Reproductive Toxicology, 77(4), 268-279.
Olesen, C., De Vries, C. S., Thrane, N., MacDonald, T. M., Larsen, H., Sørensen, H. T., & Group, T. E. (2001). Effect of diuretics on fetal growth: a drug effect or confounding by indication? Pooled Danish and Scottish cohort data. British journal of clinical pharmacology, 51(2), 153-157.
Oyebode, F., Rastogi, A., Berrisford, G., & Coccia, F. (2012). Psychotropics in pregnancy: safety and other considerations. Pharmacology & therapeutics, 135(1), 71-77.
Payne, J. L., & Meltzer-Brody, S. (2009). Antidepressant use during pregnancy: current controversies and treatment strategies. Clinical obstetrics and gynecology, 52(3), 469.
Podymow, T., & August, P. (2008). Update on the use of antihypertensive drugs in pregnancy. Hypertension, 51(4), 960-969.
Polen, K. N., Rasmussen, S. A., Riehle‐Colarusso, T., Reefhuis, J., & National Birth Defects Prevention Study. (2013). Association between reported venlafaxine use in early pregnancy and birth defects, national birth defects prevention study, 1997–2007. Birth Defects Research Part A: Clinical and Molecular Teratology, 97(1), 28-35
Rasmussen, S. A., Kelley, C. F., Horton, J. P., & Jamieson, D. J. (2021). Coronavirus disease 2019 (COVID-19) vaccines and pregnancy: what obstetricians need to know. Obstetrics and gynecology, 137(3), 408.
Santini-Oliveira M., Friedman R.K., Veloso V.G., Cunha C.B., Pilotto J.H., Marins L.M., João E.C., Torres T.S., Grinsztejn B. (2014). Incidence of antiretroviral adverse drug reactions in pregnant women in two referral centers for HIV prevention of mother-to-child-transmission care and research in Rio de Janeiro, Brazil. Braz. J. Infect. Dis. 18(4):372–378.
Scheller, N. M., Pasternak, B., Mølgaard-Nielsen, D., Svanström, H., & Hviid, A. (2017). Quadrivalent HPV vaccination and the risk of adverse pregnancy outcomes. New England journal of medicine, 376(13), 1223-1233.
Teratogenicity of first trimester ACE inhibitors. (2006). Archives of Disease in Childhood, 91(10), 840. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2066032/pdf/840.pdf/?tool=EBI accessed on 05/08/2021.
Wettach, C., Thomann, J., Lambrigger-Steiner, C., Buclin, T., Desmeules, J., & von Mandach, U. (2013). Pharmacovigilance in pregnancy: adverse drug reactions associated with fetal disorders. Journal of perinatal medicine, 41(3), 301-307.
Yakoob, M. Y., Bateman, B. T., Ho, E., Hernandez-Diaz, S., Franklin, J. M., Goodman, J. E., & Hoban, R. A. (2013). The risk of congenital malformations associated with exposure to β-blockers early in pregnancy: a meta-analysis. Hypertension, 62(2), 375-381.
Copyright (c) 2022 Manvi Suri, Jyoti Upadhyay
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.