A GUIDE TO HEALTHY PREGNANCY MANAGING AILMENTS AND FINDING SOLUTIONS

A_Guide_to_Healthy_Pregnancy

SAFE MEDICATION ADMINISTRATION DURING PREGNANCY

Sinem Tekin

Haseki Training and Research Hospital, Department of Gynecology and, İstanbul, Türkiye

Tekin S. Safe Medication Administration During Pregnancy. Çetin A, ed. A Guide To Healthy Pregnancy: Managing Ailments and Finding Solutions. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.83-96.

ABSTRACT

Pregnancy represents a crucial phase in which the development of the fetus and the health of the mother are deeply interrelated. The administration of pharmacologic agents during this period is a sensitive issue due to safety concerns for both fetal and maternal health. The use of medications during pregnancy is essential for managing acute maternal medical conditions; however, their potential effects on the fetus must be thoroughly assessed to ensure safety. In this process, the safe and effective use of drugs is critical to promote maternal health and minimize potential adverse effects on the fetus. This chapter has been written to guide clinicians in striking these two balances and providing maternal and fetal safe drug options. The concept of teratogenicity encompasses the potential adverse effects of a drug on fetal development. The teratogenic effects of drugs can be influenced by various factors such as genetic predisposition, dose, and duration of exposure. Many drugs that have been proven to be teratogenic are detailed in this section. The timing of drug use during pregnancy is also important; some drugs used during organogenesis can cause severe birth defects, while exposure during the fetal period can affect organ function. In addition, the risk-benefit balance of drugs used for temporary conditions such as nausea and vomiting, pain, infections, and for the treatment of chronic diseases such as hypertension and diabetes, and epilepsy, which are common during pregnancy, was evaluated in detail. In conclusion, drug use in pregnancy should be handled based on individualized treatment approaches, the principle of minimal effective dosage, and patient-physician collaboration. Staying updated on the latest scientific evidence regarding medication use during pregnancy is crucial to safeguarding the health of both the mother and the fetus. This article aims to provide evidence-based information on the safe use of medicines in pregnancy to guide healthcare professionals in making safe and effective treatment decisions and to best support maternal and fetal health.

Keywords: Drug use in pregnancy; Maternal-fetal health; Medication safety; Teratogenic drugs

Referanslar

  1. Yu X, Wu H, Yang Y, Wang F, Wang YL, Shao X. Placental Development and Pregnancy-Associated Diseases. Matern Med. 2022;4(1). [Crossref]
  2. Bérard A, Abbas-Chorfa F, Kassai B, et al. The French Pregnancy Cohort: Medication use during pregnancy in the French population. PLoS One. 2019;14(7):e0219095. [Crossref]  [PubMed]  [PMC]
  3. Bakker MK, Kölling P, van den Berg PB, de Walle HEK, de Jong van den Berg LTW. Increase in use of selective serotonin reuptake inhibitors in pregnancy during the last decade, a population-based cohort study from the Netherlands. Br J Clin Pharmacol. 2008;65(4):600-606. [Crossref]  [PubMed]  [PMC]
  4. Petersen I, Gilbert RE, Evans SJW, Man SL, Nazareth I. Pregnancy as a major determinant for discontinuation of antidepressants: an analysis of data from The Health Improvement Network. J Clin Psychiatry. 2011;72(7):979-985. [Crossref]  [PubMed]
  5. Dathe K, Schaefer C. The Use of Medication in Pregnancy. Dtsch Arztebl Int. 2019;116(46):783-790. [Crossref]  [PubMed]  [PMC]
  6. Adam MP, Polifka JE, Friedman JM. Evolving knowledge of the teratogenicity of medications in human pregnancy. Am J Med Genet Part C Semin Med Genet. 2011;157(3):175-182 [Crossref]  [PubMed]
  7. Cassina M, Salviati L, Di Gianantonio E, Clementi M. Genetic susceptibility to teratogens: State of the art. Reprod Toxicol. 2012;34(2):186-191. [Crossref]  [PubMed]
  8. Wenstrom KD, Johanning GL, Johnston KE, DuBard M. Association of the C677T methylenetetrahydrofolate reductase mutation and elevated homocysteine levels with congenital cardiac malformations. Am J Obstet Gynecol. 2001;184(5):806-807. [Crossref]  [PubMed]
  9. Wenstrom KD, Johanning GL, Owen J, Johnston KE, Acton S, Tamura T. Role of amniotic fluid homocysteine level and of fetal 5, 10-methylenetetrahydrafolate reductase genotype in the etiology of neural tube defects. Am J Med Genet. 2000;90(1):12-16. [Crossref]
  10. Dong J, Yin LL, Deng XD, et al. Initiation and duration of folic acid supplementation in preventing congenital malformations. BMC Med. 2023;21(1):292. [Crossref]  [PubMed]  [PMC]
  11. Patel MA, Aliporewala VM, Patel DA. Common Antifungal Drugs in Pregnancy: Risks and Precautions. J Obstet Gynecol India. 2021;71(6):577-582. [Crossref]  [PubMed]  [PMC]
  12. Dutta S. Human Teratogens and Their Effects: A Critical Evaluation. Int J Inf Res Rev. 2015;2(3):525-536. [Link]
  13. Czeizel AE. The estimation of human teratogenic/fetotoxic risk of exposures to drugs on the basis of Hungarian experience: a critical evaluation of clinical and epidemiological models of human teratology. Expert Opin Drug Saf. 2009;8(3):283-303. [Crossref]  [PubMed]
  14. Polifka JE, Friedman JM. Medical genetics: 1. Clinical teratology in the age of genomics. C Can Med Assoc J = J l'Association medicale Can. 2002;167(3):265-273. [Link]
  15. Winterstein AG, Ewig CLY, Wang Y, et al. Teratogenic Risk Impact and Mitigation (TRIM): Study Protocol for the Development of a Decision Support Tool to Prioritize Medications for Risk Mitigation. Drug Saf. Published online 2024. [Crossref]  [PubMed]  [PMC]
  16. Shojaei fard M, Malekzadeh S, Shariati M. A Review of the Teratogenic Factors Effect on Embryo. J Adv Biomed Sci. 2016;6(4). [Link]
  17. Denny KH, Faqi AS. Nonclinical Safety Assessment of Developmental and Reproductive Toxicology: Considerations for Conducting Fertility, Embryo--Fetal Development, and Prenatal and Postnatal Developmental Toxicology Studies. In: Faqi AS, ed. Developmental and Reproductive Toxicology. Springer New York; 2017:43-115. [Crossref]  [PubMed]
  18. Kille JW. Chapter 19 - Regulatory Toxicology. In: Faqi ASBTACG to T in NDD (Third E, ed. Academic Press; 2024:515-557. [Crossref]
  19. Alexander EK, Pearce EN, Brent GA, et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid®. 2017;27(3):315-389. [Crossref]  [PubMed]
  20. Pernia S, DeMaagd G. The New Pregnancy and Lactation Labeling Rule. P T. 2016;41(11):713-715. [PMC]
  21. Shrim A, Boskovic R, Maltepe C, Navios Y, Garcia-Bournissen F, Koren G. Pregnancy outcome following use of large doses of vitamin B6 in the first trimester. J Obstet Gynaecol J Inst Obstet Gynaecol. 2006;26(8):749-751. [Crossref]  [PubMed]
  22. Koren G, Clark S, Hankins GD V, et al. Maternal safety of the delayed-release doxylamine and pyridoxine combination for nausea and vomiting of pregnancy; a randomized placebo controlled trial. BMC Pregnancy Childbirth. 2015;15:59. [Crossref]  [PubMed]  [PMC]
  23. Etwel F, Faught LH, Rieder MJ, Koren G. The Risk of Adverse Pregnancy Outcome After First Trimester Exposure to H1 Antihistamines: A Systematic Review and Meta-Analysis. Drug Saf. 2017;40(2):121-132. [Crossref]  [PubMed]
  24. Abas MN, Tan PC, Azmi N, Omar SZ. Ondansetron compared with metoclopramide for hyperemesis gravidarum: a randomized controlled trial. Obstet Gynecol. 2014;123(6):1272-1279. [Crossref]  [PubMed]
  25. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. [Crossref]  [PubMed]
  26. Huybrechts KF, Hernández-Díaz S, Straub L, et al. Association of Maternal First-Trimester Ondansetron Use With Cardiac Malformations and Oral Clefts in Offspring. JAMA. 2018;320(23):2429-2437. [Crossref]  [PubMed]  [PMC]
  27. Picot C, Berard A, Grenet G, Ripoche E, Cucherat M, Cottin J. Risk of malformation after ondansetron in pregnancy: An updated systematic review and meta-analysis. Birth defects Res. 2020;112(13):996-1013. [Crossref]  [PubMed]
  28. Schrager NL, Parker SE, Werler MM. The association of nausea and vomiting of pregnancy, its treatments, and select birth defects: Findings from the National Birth Defect Prevention Study. Birth defects Res. 2023;115(3):275-289. [Crossref]  [PubMed]
  29. Scialli AR, Ang R, Breitmeyer J, Royal MA. A review of the literature on the effects of acetaminophen on pregnancy outcome. Reprod Toxicol. 2010;30(4):495-507. [Crossref]  [PubMed]
  30. Prenatal acetaminophen use and outcomes in children. Am J Obstet Gynecol. 2017;216(3):B14-B15. [Crossref]  [PubMed]
  31. Bloor M, Paech M. Nonsteroidal Anti-Inflammatory Drugs During Pregnancy and the Initiation of Lactation. Anesth Analg. 2013;116(5). [Crossref]  [PubMed]
  32. Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022. MMWR Recomm reports Morb Mortal Wkly report Recomm reports. 2022;71(3):1-95. [Crossref]  [PubMed]  [PMC]
  33. ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018;131(2):e49-e64. [Crossref]  [PubMed]
  34. 15. Management of Diabetes in Pregnancy: Standards of Care in Diabetes-2024. Diabetes Care. 2024;47(Suppl 1):S282-S294. [Crossref]  [PubMed]  [PMC]
  35. Byatt N, Deligiannidis KM, Freeman MP. Antidepressant use in pregnancy: a critical review focused on risks and controversies. Acta Psychiatr Scand. 2013;127(2):94-114. [Crossref]  [PubMed]  [PMC]
  36. Mitchell AA, Gilboa SM, Werler MM, Kelley KE, Louik C, Hernández-Díaz S. Medication use during pregnancy, with particular focus on prescription drugs: 1976-2008. Am J Obstet Gynecol. 2011;205(1):51.e1-8. [Crossref]  [PubMed]  [PMC]
  37. Jordan S, Morris JK, Davies GI, et al. Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants in Pregnancy and Congenital Anomalies: Analysis of Linked Databases in Wales, Norway and Funen, Denmark. PLoS One. 2016;11(12):e0165122. [Crossref]  [PubMed]  [PMC]
  38. Reis M, Källén B. Combined use of selective serotonin reuptake inhibitors and sedatives/hypnotics during pregnancy: risk of relatively severe congenital malformations or cardiac defects. A register study. BMJ Open. 2013;3(2). [Crossref]  [PubMed]  [PMC]
  39. Grigoriadis S, VonderPorten EH, Mamisashvili L, et al. Antidepressant exposure during pregnancy and congenital malformations: is there an association? A systematic review and meta-analysis of the best evidence. J Clin Psychiatry. 2013;74(4):e293-308. [Crossref]  [PubMed]
  40. Chisolm MS, Payne JL. Management of psychotropic drugs during pregnancy. BMJ. 2016;532:h5918. [Crossref]  [PubMed]
  41. Wang S, Yang L, Wang L, Gao L, Xu B, Xiong Y. Selective Serotonin Reuptake Inhibitors (SSRIs) and the Risk of Congenital Heart Defects: A Meta-Analysis of Prospective Cohort Studies. J Am Heart Assoc. 2015;4(5). [Crossref]  [PubMed]  [PMC]
  42. Petersen I, Evans SJ, Gilbert R, Marston L, Nazareth I. Selective serotonin reuptake inhibitors and congenital heart anomalies: comparative cohort studies of women treated before and during pregnancy and their children. J Clin Psychiatry. 2016;77(1):e36-42. [Crossref]  [PubMed]
  43. Bérard A, Iessa N, Chaabane S, Muanda FT, Boukhris T, Zhao JP. The risk of major cardiac malformations associated with paroxetine use during the first trimester of pregnancy: a systematic review and meta-analysis. Br J Clin Pharmacol.2016;81(4):589-604. [Crossref]  [PubMed]  [PMC]
  44. Huybrechts KF, Hernández-Díaz S, Patorno E, et al. Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations. JAMA psychiatry. 2016;73(9):938-946. [Crossref]  [PubMed]  [PMC]
  45. Jones I, Chandra PS, Dazzan P, Howard LM. Bipolar disorder, affective psychosis, and schizophrenia in pregnancy and the post-partum period. Lancet (London, England). 2014;384(9956):1789-1799. [Crossref]  [PubMed]
  46. Tinker SC, Reefhuis J, Bitsko RH, et al. Use of benzodiazepine medications during pregnancy and potential risk for birth defects, National Birth Defects Prevention Study, 1997-2011. Birth defects Res. 2019;111(10):613-620. [Crossref]  [PubMed]  [PMC]
  47. Wikner BN, Stiller CO, Bergman U, Asker C, Källén B. Use of benzodiazepines and benzodiazepine receptor agonists during pregnancy: neonatal outcome and congenital malformations. Pharmacoepidemiol Drug Saf. 2007;16(11):1203-1210. [Crossref]  [PubMed]
  48. ACOG Practice Bulletin: Clinical management guidelines for obstetrician-gynecologists number 92, April 2008 (replaces practice bulletin number 87, November 2007). Use of psychiatric medications during pregnancy and lactation. Obstet Gynecol. 2008;111(4):1001-1020. [Crossref]  [PubMed]
  49. Ulander VM, Stenqvist P, Kaaja R. Treatment of deep venous thrombosis with low-molecular-weight heparin during pregnancy. Thromb Res. 2002;106(1):13-17. [Crossref]  [PubMed]
  50. Stoffel NU, von Siebenthal HK, Moretti D, Zimmermann MB. Oral iron supplementation in iron-deficient women: How much and how often? Mol Aspects Med. 2020;75:100865. [Crossref]  [PubMed]
  51. Barry MJ, Nicholson WK, Silverstein M, et al. Folic Acid Supplementation to Prevent Neural Tube Defects: US Preventive Services Task Force Reaffirmation Recommendation Statement. JAMA. 2023;330(5):454-459. [Crossref]  [PubMed]
  52. Hacker AN, Fung EB, King JC. Role of calcium during pregnancy: maternal and fetal needs. Nutr Rev. 2012;70(7):397-409. [Crossref]  [PubMed]