Research Article
BibTex RIS Cite

Reliability of cardiovascular drug use in pregnancy with clinical pharmacology teratology risk analysis

Year 2019, Volume: 44 Issue: 3, 705 - 711, 30.09.2019
https://doi.org/10.17826/cumj.490997

Abstract

Purpose: Maternal cardiac disease is one of the major causes of non-obstetric maternal morbidity and mortality. In the treatment of cardiovascular diseases during pregnancy, it is important to prescribe the drugs that control maternal disease and to minimize potential drug-related risk to the fetus. The aim of this study is to evaluate the teratogenic safety of cardiovascular drugs in pregnancy.

Materials and Methods: We collected data of pregnant women who used drugs for cardiovascular disorders and admitted to our unit for drug analysis between 2014 and 2018. Teratology Information Service assessed the teratogenic risk of drugs. After delivery, a follow-up was conducted with families to obtain the presence of any congenital malformations or adverse neurodevelopmental effects in the infant. 

Results: Use of ramipril in the first six weeks of pregnancy resulted in spontaneous abortus at the 10th week. Use of warfarin in the first 12 weeks resulted in exitus at the postnatal fourth day. Telmisartan exposure in the first six weeks resulted in intrauterine death in the 18th gestational week.

Conclusion: Drugs acting on renin-angiotensin system should be discontinued when pregnancy is detected. Warfarin is contraindicated for use in pregnancy except mechanical heart valve pregnancies with high risk of thromboembolism, as it leads to coumarin embryopathy and nervous system anomalies in the first trimester exposures. Pregnant women should be directed to the teratogenic drug analysis and evaluated for possible increase in drug-related congenital malformation risks at early gestational period. Teratogenic risk counselling and follow-up ensures reliable data on drug safety during pregnancy.


References

  • 1. Fretts RC, Schmittdiel J, McLean FH, Usher RH, Goldman MB. Increased maternal age and the risk of fetal death. N Engl J Med. 1995 Oct 12;333(15):953-7. PubMed PMID: 7666913.
  • 2. Cunningham FG, Leveno KJ. Childbearing among older women--the message is cautiously optimistic. N Engl J Med. 1995 Oct 12;333(15):1002-4. PubMed PMID: 7666897.
  • 3. Kaplan YC, Karadaş B, Küçüksolak G, Ediz B, Demir Ö, Sozmen K, et al. Counselling pregnant women at the crossroads of Europe and Asia: effect of Teratology Information Service in Turkey. Int J Clin Pharm. 2017; 39(4):783-790. doi: 10.1007/s11096-017-0496-5.
  • 4. Roos-Hesselink JW, Ruys TP, Stein JI, Thilén U, Webb GD, Niwa K, et al. ; ROPAC Investigators. Outcome of pregnancy in patients with structural or ischaemic heart disease: results of a registry of the European Society of Cardiology. Eur Heart J. 2013 Mar;34(9):657-65. doi: 10.1093/eurheartj/ehs270. Epub 2012 Sep 11. PubMed PMID: 22968232.
  • 5. Balci A, Sollie-Szarynska KM, van der Bijl AG, Ruys TP, Mulder BJ, Roos-Hesselink JW, et al. ; ZAHARA-II investigators. Prospective validation and assessment of cardiovascular and offspring risk models for pregnant women with congenital heart disease. Heart. 2014 Sep;100(17):1373-81. doi: 10.1136/heartjnl-2014-305597. Epub 2014 Jul 17. PubMed PMID: 25034822.
  • 6. Loane M, Dolk H, Kelly A, Teljeur C, Greenlees R, Densem J; EUROCAT Working Group. 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; 91Suppl 1:S31-43. doi: 10.1002/bdra.20778.
  • 7. Barr M Jr. Teratogen update: angiotensin-converting enzyme inhibitors. Teratology. 1994 Dec;50(6):399-409. Review. PubMed PMID: 7778045.
  • 8. Oppermann M, Padberg S, Kayser A, Weber-Schoendorfer C, Schaefer C. Angiotensin-II receptor 1 antagonist fetopathy--risk assessment, critical time period and vena cava thrombosis as a possible new feature. Br J Clin Pharmacol. 2013 Mar;75(3):822-30. doi: 10.1111/j.1365-2125.2012.04388.x. PubMed PMID: 22816796; PubMed Central PMCID: PMC3575949.
  • 9. Weber MA, Schiffrin EL, White WB, Mann S, Lindholm LH, Kenerson JG, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014 Jan;16(1):14-26. doi: 10.1111/jch.12237. Epub 2013 Dec 17. PubMed PMID: 24341872.
  • 10. Pieper PG. Use of medication for cardiovascular disease during pregnancy. Nat Rev Cardiol 2015;12:718–729.
  • 11. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomström-Lundqvist C, Cífková R, De Bonis M, et al. ; ESC Scientific Document Group . 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018 Sep 7;39(34):3165-3241. doi: 10.1093/eurheartj/ehy340. PubMed PMID: 30165544.
  • 12. Perez-Aytes A, Marin-Reina P, Boso V, Ledo A, Carey JC, Vento M. Mycophenolate mofetil embryopathy: A newly recognized teratogenic syndrome. Eur J Med Genet. 2017 Jan;60(1):16-21. doi: 10.1016/j.ejmg.2016.09.014. Epub 2016 Sep 14. PubMed PMID: 27639443.
  • 13. Kang HH, Ahn KH, Hong SC, Kwon BY, Lee EH, Lee JS, Oh MJ, Kim HJ. Association of citalopram with congenital anomalies: A meta-analysis. Obstet Gynecol Sci. 2017 Mar;60(2):145-153. doi: 10.5468/ogs.2017.60.2.145. Epub 2017 Mar 16. PubMed PMID: 28344955; PubMed Central PMCID: PMC5364096.
  • 14. Orbach H, Matok I, Gorodischer R, Sheiner E, Daniel S, Wiznitzer A, et al. Hypertension and antihypertensive drugs in pregnancy and perinatal outcomes. Am J Obstet Gynecol. 2013 Apr;208(4):301.e1-6. doi: 10.1016/j.ajog.2012.11.011. Epub 2012 Nov 15. PubMed PMID: 23159698.
  • 15. Hassouna A, Allam H. Limited dose warfarin throughout pregnancy in patients with mechanical heart valve prosthesis: A meta-analysis. Interact Cardiovasc Thorac Surg 2014;18:797–806.
  • 16. Xu Z, Fan J, Luo X, Zhang WB, Ma J, Lin YB, et al. Anticoagulation regimens during pregnancy in patients with mechanical heart valves: A systematic review and meta-analysis. Can J Cardiol 2016;32:1248.e1–1248.e9.
  • 17. D’Souza R, Ostro J, Shah PS, Silversides CK, Malinowski A, Murphy KE, et al. Anticoagulation for pregnant women with mechanical heart valves: A systematic review and meta-analysis. Eur Heart J 2017;214:S351–S351.
  • 18. Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e691S-e736S. doi: 10.1378/chest.11-2300. PubMed PMID: 22315276; PubMed Central PMCID: PMC3278054.
  • 19. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, et al. ; ACC/AHA Task Force Members. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 10;129(23):2440-92. doi: 10.1161/CIR.0000000000000029. Epub 2014 Mar 3. Erratum in: Circulation. 2014 Jun 10;129(23):e650. PubMed PMID: 24589852.

Klinik farmakoloji teratoloji risk analizi ile gebelikte kardiyovasküler ilaç kullanımının güvenilirliği

Year 2019, Volume: 44 Issue: 3, 705 - 711, 30.09.2019
https://doi.org/10.17826/cumj.490997

Abstract

Amaç: Maternal kardiyak hastalık, non-obstetrik maternal morbidite ve mortalitenin ana nedenlerinden biridir. Hamilelik sırasında kardiyovasküler hastalıkların tedavisinde, maternal hastalığı kontrol eden ilaçların reçetelenmesi ve fetusa karşı potansiyel ilaca bağlı risklerin en aza indirilmesi önemlidir. Bu çalışmanın amacı gebelikte kardiyovasküler ilaçların teratojenik açıdan güvenilirliğini değerlendirmektir.

Gereç ve Yöntem: 2014-2018 yılları arasında kardiyovasküler hastalıklar sebebiyle ilaç kullanan ve ilaç analizi için birimimize başvuran gebelerin verilerini topladık. Teratoloji Bilgi Servisi ilaçların teratojenik riskini değerlendirdi. Doğumdan sonra, infantta olası konjenital malformasyon veya nörogelişimsel bozuklukları saptamak için ailelerle irtibata geçildi.

Bulgular: Hamileliğin ilk altı haftasında ramipril kullanımı 10. haftada spontan abortus ile sonuçlandı. İlk 12 haftada warfarin kullanımı postnatal dördüncü günde eksitusa neden oldu. İlk altı haftada telmisartan maruziyeti 18. gebelik haftasında intrauterin ölümle sonuçlandı.

Sonuç: Gebelik tespit edildiğinde renin-anjiyotensin sistemi üzerine etki eden ilaçlar kesilmelidir. Varfarin, birinci trimester maruziyetinde kumarin embriyopatisi ve sinir sistemi anomalilerine yol açtığı için, yüksek tromboembolizm riski taşıyan mekanik kalp kapakçığı olan gebeler dışında gebelikte kullanım için kontrendikedir. Gebe kadınlar teratojenik ilaç analizine yönlendirilmeli ve erken gebelik döneminde ilaçla ilişkili konjenital malformasyon risklerindeki olası artış için değerlendirilmelidir. Teratojenik risk danışmanlığı ve takibi, hamilelik sırasında ilaç güvenliği konusunda güvenilir veriler sağlar.

References

  • 1. Fretts RC, Schmittdiel J, McLean FH, Usher RH, Goldman MB. Increased maternal age and the risk of fetal death. N Engl J Med. 1995 Oct 12;333(15):953-7. PubMed PMID: 7666913.
  • 2. Cunningham FG, Leveno KJ. Childbearing among older women--the message is cautiously optimistic. N Engl J Med. 1995 Oct 12;333(15):1002-4. PubMed PMID: 7666897.
  • 3. Kaplan YC, Karadaş B, Küçüksolak G, Ediz B, Demir Ö, Sozmen K, et al. Counselling pregnant women at the crossroads of Europe and Asia: effect of Teratology Information Service in Turkey. Int J Clin Pharm. 2017; 39(4):783-790. doi: 10.1007/s11096-017-0496-5.
  • 4. Roos-Hesselink JW, Ruys TP, Stein JI, Thilén U, Webb GD, Niwa K, et al. ; ROPAC Investigators. Outcome of pregnancy in patients with structural or ischaemic heart disease: results of a registry of the European Society of Cardiology. Eur Heart J. 2013 Mar;34(9):657-65. doi: 10.1093/eurheartj/ehs270. Epub 2012 Sep 11. PubMed PMID: 22968232.
  • 5. Balci A, Sollie-Szarynska KM, van der Bijl AG, Ruys TP, Mulder BJ, Roos-Hesselink JW, et al. ; ZAHARA-II investigators. Prospective validation and assessment of cardiovascular and offspring risk models for pregnant women with congenital heart disease. Heart. 2014 Sep;100(17):1373-81. doi: 10.1136/heartjnl-2014-305597. Epub 2014 Jul 17. PubMed PMID: 25034822.
  • 6. Loane M, Dolk H, Kelly A, Teljeur C, Greenlees R, Densem J; EUROCAT Working Group. 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; 91Suppl 1:S31-43. doi: 10.1002/bdra.20778.
  • 7. Barr M Jr. Teratogen update: angiotensin-converting enzyme inhibitors. Teratology. 1994 Dec;50(6):399-409. Review. PubMed PMID: 7778045.
  • 8. Oppermann M, Padberg S, Kayser A, Weber-Schoendorfer C, Schaefer C. Angiotensin-II receptor 1 antagonist fetopathy--risk assessment, critical time period and vena cava thrombosis as a possible new feature. Br J Clin Pharmacol. 2013 Mar;75(3):822-30. doi: 10.1111/j.1365-2125.2012.04388.x. PubMed PMID: 22816796; PubMed Central PMCID: PMC3575949.
  • 9. Weber MA, Schiffrin EL, White WB, Mann S, Lindholm LH, Kenerson JG, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014 Jan;16(1):14-26. doi: 10.1111/jch.12237. Epub 2013 Dec 17. PubMed PMID: 24341872.
  • 10. Pieper PG. Use of medication for cardiovascular disease during pregnancy. Nat Rev Cardiol 2015;12:718–729.
  • 11. Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomström-Lundqvist C, Cífková R, De Bonis M, et al. ; ESC Scientific Document Group . 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018 Sep 7;39(34):3165-3241. doi: 10.1093/eurheartj/ehy340. PubMed PMID: 30165544.
  • 12. Perez-Aytes A, Marin-Reina P, Boso V, Ledo A, Carey JC, Vento M. Mycophenolate mofetil embryopathy: A newly recognized teratogenic syndrome. Eur J Med Genet. 2017 Jan;60(1):16-21. doi: 10.1016/j.ejmg.2016.09.014. Epub 2016 Sep 14. PubMed PMID: 27639443.
  • 13. Kang HH, Ahn KH, Hong SC, Kwon BY, Lee EH, Lee JS, Oh MJ, Kim HJ. Association of citalopram with congenital anomalies: A meta-analysis. Obstet Gynecol Sci. 2017 Mar;60(2):145-153. doi: 10.5468/ogs.2017.60.2.145. Epub 2017 Mar 16. PubMed PMID: 28344955; PubMed Central PMCID: PMC5364096.
  • 14. Orbach H, Matok I, Gorodischer R, Sheiner E, Daniel S, Wiznitzer A, et al. Hypertension and antihypertensive drugs in pregnancy and perinatal outcomes. Am J Obstet Gynecol. 2013 Apr;208(4):301.e1-6. doi: 10.1016/j.ajog.2012.11.011. Epub 2012 Nov 15. PubMed PMID: 23159698.
  • 15. Hassouna A, Allam H. Limited dose warfarin throughout pregnancy in patients with mechanical heart valve prosthesis: A meta-analysis. Interact Cardiovasc Thorac Surg 2014;18:797–806.
  • 16. Xu Z, Fan J, Luo X, Zhang WB, Ma J, Lin YB, et al. Anticoagulation regimens during pregnancy in patients with mechanical heart valves: A systematic review and meta-analysis. Can J Cardiol 2016;32:1248.e1–1248.e9.
  • 17. D’Souza R, Ostro J, Shah PS, Silversides CK, Malinowski A, Murphy KE, et al. Anticoagulation for pregnant women with mechanical heart valves: A systematic review and meta-analysis. Eur Heart J 2017;214:S351–S351.
  • 18. Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO. VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):e691S-e736S. doi: 10.1378/chest.11-2300. PubMed PMID: 22315276; PubMed Central PMCID: PMC3278054.
  • 19. Nishimura RA, Otto CM, Bonow RO, Carabello BA, Erwin JP 3rd, Guyton RA, et al. ; ACC/AHA Task Force Members. 2014 AHA/ACC Guideline for the Management of Patients With Valvular Heart Disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014 Jun 10;129(23):2440-92. doi: 10.1161/CIR.0000000000000029. Epub 2014 Mar 3. Erratum in: Circulation. 2014 Jun 10;129(23):e650. PubMed PMID: 24589852.
There are 19 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Research
Authors

Duygun Altıntaş Aykan 0000-0001-8224-4006

Yusuf Ergün 0000-0002-6169-8911

Publication Date September 30, 2019
Acceptance Date December 26, 2018
Published in Issue Year 2019 Volume: 44 Issue: 3

Cite

MLA Altıntaş Aykan, Duygun and Yusuf Ergün. “Reliability of Cardiovascular Drug Use in Pregnancy With Clinical Pharmacology Teratology Risk Analysis”. Cukurova Medical Journal, vol. 44, no. 3, 2019, pp. 705-11, doi:10.17826/cumj.490997.