Gebe olguların ilaç-ilaç etkileşimleri ve teratojenik riskler açısından retrospektif analizi

Year 2025, Volume: 17 Issue: 1, 10 - 20, 27.03.2025

Metin Deniz Karakoç

https://doi.org/10.18521/ktd.1478663

Abstract

Amaç: Gebelerde teratojenik riskler sıkça tartışılan bir konudur ancak polifarmasi ve ilaç-ilaç etkileşimleri (İİE) hakkında çok az bilgi mevcuttur. Çalışmanın amacı, gebelik sırasında meydana gelen polifarmasi durumunu, İİE ve teratojenik risk profillerini belirlemektir.
Metod: 2023 yılı süresince gebelikte ilaç kullanım öyküsü nedeniyle farmakoloji konsültasyonuna yönlendirilen kadınları kapsayan retrospektif bir kohort çalışması yapıldı. İİE araştırması Micromedex ve Medscape online sorgu modülleri kullanılarak gerçekleştirildi.
Bulgular: 113 gebenin toplamda 24 farklı farmakolojik gruptan 71 farklı etken madde içeren ilaç kullandığı bulundu. Birey başına kullanılan ilaçların ortalamasının 2,97 olduğu saptandı. Sırasıyla ağrı kesiciler, antibiyotikler ve mide asidi inhibitörlerinin en çok kullanılan ilaçlar olduğu belirlendi. Kadınların %11,6'sında bir komorbidite olduğu ve en sık kardiyovasküler hastalıklara sahip oldukları belirlendi. Gebelerin %28,3'ünde ciddi veya orta derecede İİE olduğu tespit edildi. Teratojenik açıdan özellikle riskli olan D ve X kategorisindeki ilaç oranının %40,8 olduğu saptandı.
Sonuç: Teratojenik etkilerin yanı sıra, polifarmasi ve İİE de gebelerde önemli risk faktörleridir. Gebelikte reçete edilen ilaçlar, özellikle komorbiditeleri olan kadınlar üzerindeki fayda ve zararları konusunda kanıtlara halen kritik derecede ihtiyaç bulunmaktadır.

Keywords

Polifarmasi, teratojenite, ilaç etkileşimleri, komorbiditeler, gebelik

Retrospective Analysis of Pregnant Cases in Terms of Drug-Drug interactions and Teratogenic risks

Abstract

Objective: While teratogenic risks in pregnant women are frequently discussed, polypharmacy and drug-drug interactions (DDI) are topics with little known information. The aim of this study is to determine the polypharmacy status, DDI, and teratogenic risk profile during pregnancy.
Method: A retrospective cohort study was conducted covering the year 2023 on pregnant women who were referred for pharmacology consultation due to a history of drug use. Investigation of DDI was performed through the Micromedex and Medscape online query modules.
Results: It was found that 113 pregnant women used a total of 71 different active ingredient drugs from 24 diverse pharmacological groups. The average number of drugs used per individual was 2.97. Analgesics, antibiotics, and gastric acid inhibitors were the most used medications, respectively. 11.6% of the women had a comorbidity, and cardiovascular diseases were the most common. It was determined that 28.3% of women had a serious or moderate DDI. The rate of drugs in categories D and X, which are particularly risky in terms of teratogenicity, was found to be 40.8%.
Conclusion: In addition to teratogenic effects, polypharmacy and DDI are also significant risk factors in pregnant women. There is still a crucial need for evidence on the medications prescribed in pregnancy, how it specifically affects women with comorbidities, and related benefits and harms.

Keywords

Polypharmacy, teratogenicity, drug interactions, comorbidities, pregnancy

Ethical Statement

Pamukkale University Non-invasive Clinical Research Ethics Committee (Permission no: E.462180)

Supporting Institution

No support was received from any person or institution for the study.

References

• 1. Webster WS, Freeman JA. Prescription drugs and pregnancy. Expert Opin Pharmacother. 2003;4(6):949-61.
• 2. Andrade SE, Raebel MA, Morse AN, Davis RL, Chan KA., Finkelstein JA, et al. Use of prescription medications with a potential for fetal harm among pregnant women. Pharmacoepidemiol Drug Saf. 2006;15(8):546-54.
• 3. Lupattelli A, Spigset O, Twigg MJ, Zagorodnikova K, Mårdby AC, Moretti ME, et al. Medication use in pregnancy: a cross-sectional, multinational web-based study. BMJ Open. 2014;4(2):e004365.
• 4. Costa DB, Coelho HL, Santos DB. Use of medicines before and during pregnancy: prevalence and associated factors. Cad Saude Publica. 2017;33(2):e00126215.
• 5. Addis A, Sharabi S, Bonati M. Risk classification systems for drug use during pregnancy: are they a reliable source of information?. Drug Saf. 2000;23(3):245-53.
• 6. Ulusoy KG. Evaluation of pregnant women who applied to a university hospital for drug use during pregnancy: case series. Sakarya Med J. 2020;10(3):459-66.
• 7. Yuan S, Liu J, Larsson SC. Smoking, alcohol and coffee consumption and pregnancy loss: a Mendelian randomization investigation. Fertil Steril. 2021;116(4):1061-67.
• 8. Wu P, Chew-Graham CA, Maas AH, Chappell LC, Potts JE, Gulati M, et al. Temporal changes in hypertensive disorders of pregnancy and impact on cardiovascular and obstetric outcomes. Am J Cardiol. 2020;125(10):1508-16.
• 9. Thunbo MØ, Vendelbo JH, Volqvartz T, Witte DR, Larsen A, Pedersen LH. Polypharmacy in polymorbid pregnancies and the risk of congenital malformations-a systematic review. Basic Clin Pharmacol Toxicol. 2022;130(3):394-414.
• 10. Judistiani RTD, Pratiwi AE, Wahyudi K, Gunawan A, Rahmawati A, Ruslami R. Medication use and associated factors among Indonesian pregnant women: a cross-sectional study. J Multidiscip Healthc. 2023;16:4173-79. 11. Ayele Y, Mekuria AN, Tola A, Mishore KM, Geleto FB. Prescription drugs use during pregnancy in Ethiopia: a systematic review and meta-analysis. SAGE Open Med. 2020;8:2050312120935471.
• 12. Subramanian A, Azcoaga-Lorenzo A, Anand A, Phillips K, Lee SI, Cockburn N. et al. Polypharmacy during pregnancy and associated risk factors: a retrospective analysis of 577 medication exposures among 1.5 million pregnancies in the UK, 2000-2019. BMC Med. 2023;21(1):21.
• 13. Cascorbi I. Drug interactions-principles, examples and clinical consequences. Dtsch Arztebl Int. 2012;109(33-34):546-56.
• 14. Gnjidic D, Johnell K. Clinical implications from drug-drug and drug-disease interactions in older people. Clin Exp Pharmacol Physiol. 2013;40(5):320-25.
• 15. Ferracini AC, Rodrigues AT, Visacri MB, Stahlschmidt R, Silva NMOD, Surita FG, et al. Potential drug interactions and drug risk during pregnancy and breastfeeding: an observational study in a women's health intensive care unit. Rev Bras Ginecol Obstet. 2017;39(6):258-64.
• 16. Pessoa TL, Clemente Junior WS, Costa TXD, Bezerra PKDV, Martins RR. Drug interactions in maternal intensive care: prevalence, risk factors, and potential risk medications. Einstein (Sao Paulo). 2019;17(3):eAO4521.
• 17. Yang T, Walker MC, Krewski D, et al. Maternal characteristics associated with pregnancy exposure to FDA category C, D, and X drugs in a Canadian population. Pharmacoepidemiol Drug Saf. 2008;17(3):270-7.
• 18. Kao LT, Chen YH, Lin HC, Chung SD. Prescriptions for category D and X drugs during pregnancy in Taiwan: a population-based study. Pharmacoepidemiol Drug Saf. 2014;23(10):1029-34.
• 19. Gagne JJ, Maio V, Berghella V, Louis DZ, Gonnella JS. Prescription drug use during pregnancy: a population-based study in Regione Emilia-Romagna, Italy. Eur J Clin Pharmacol. 2008;64(11):1125-32.
• 20. van Gelder MM, van Rooij IA, Miller RK, Zielhuis GA, de Jong-van den Berg LT, Roeleveld N. Teratogenic mechanisms of medical drugs. Hum Reprod Update. 2010;16(4):378-94.
• 21. Pham A, Polic A, Nguyen L, Thompson JL. Statins in Pregnancy: Can We Justify Early Treatment of Reproductive Aged Women?. Curr Atheroscler Rep. 2022;24(8):663-70.
• 22. Abadie RB, Keller CL, Jones NT, Mayeux EL, Klapper RJ, Anderson L, et al. Review of Teratogenic Effects of Leflunomide, Accutane, Thalidomide, Warfarin, Tetracycline, and Angiotensin-Converting Enzyme Inhibitors. Cureus. 2023;15(12):e50465.
• 23. Tomson T, Battino D, Perucca E. Teratogenicity of antiepileptic drugs. Curr Opin Neurol. 2019;32(2):246-52.
• 24. International Commission on Radiological Protection. Pregnancy and medical radiation. Ann ICRP. 2000;30(1):iii-43.
• 25. Kulaga S, Zargarzadeh AH, Bérard A. Prescriptions filled during pregnancy for drugs with the potential of fetal harm. BJOG. 2010;117(3):373.
• 26. de Waard M, Blomjous BS, Hol MLF, Sie SD, Corpeleijn WE, van Goudoever JHB, et al. Medication use during pregnancy and lactation in a Dutch population. J Hum Lact. 2019;35(1):154-64.
• 27. Carmo TA, Nitrini SM. Drug prescription for pregnant women: a pharmacoepidemiological study. Cad Saude Publica. 2004;20(4):1004-13.
• 28. Adam MP, Polifka JE, Friedman JM. Evolving knowledge of the teratogenicity of medications in human pregnancy. Am J Med Genet C Semin Med Genet. 2011;157C(3):175-82.
• 29. Lurie Y, Bar M, Levdov IA, Tkachenko D, Bentur Y, Kurnik D. Adherence with prescription drugs in pregnant and breastfeeding women consulting with the Israel Poison Information Center Teratology Service. Clin Toxicol (Phila). 2021;59(6):457-63.
• 30. Kuperman AA, Koren O. Antibiotic use during pregnancy: how bad is it?. BMC Med. 2016;14(1):91.
• 31. Bookstaver PB, Bland CM, Griffin B, Stover KR, Eiland LS, McLaughlin M. A Review of antibiotic use in pregnancy. Pharmacotherapy. 2015;35(11):1052-1062.
• 32. Ying XH, Bao DN, Jiang HY, Shi YD. Maternal non-steroidal anti-inflammatory drug exposure during pregnancy and risk of miscarriage: a systematic review and meta-analysis. Eur J Clin Pharmacol. 2022;78(2):171-80.
• 33. Molenaar NM, Bais B, Lambregtse-van den Berg MP, Mulder CL, Howell EA, Fox NS, et al. The international prevalence of antidepressant use before, during, and after pregnancy: A systematic review and meta-analysis of timing, type of prescriptions and geographical variability. J Affect Disord. 2020;264:82-89.
• 34. Eke AC, Saccone G, Berghella V. Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and risk of preterm birth: a systematic review and meta-analysis. BJOG. 2016;123(12):1900-07.
• 35. Wang XY, Ying XH, Jiang HY. Antidepressant use during pregnancy and the risk for gestational diabetes: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2023;36(1):2162817.
• 36. Morales DR, Slattery J, Evans S, Kurz X. Antidepressant use during pregnancy and risk of autism spectrum disorder and attention deficit hyperactivity disorder: systematic review of observational studies and methodological considerations. BMC Med. 2018;16(1):6.
• 37. Tanguay N, Abdelouahab N, Simard MN, Séguin JR, Marc I, Herba CM, et al. Antidepressants use during pregnancy and child psychomotor, cognitive and language development at 2 years of age-results from the 3D cohort study. Front Pharmacol. 2023;14:1252251.