Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Review Article

The effect of antihypertensive drugs on the fetus

Journal of Human Hypertension volume 16, pages 293–298 (2002)Cite this article

Abstract

A critical review of the literature on the effects of antihypertensive drugs on the fetus in pregnant women is presented. The survey covers the alpha-adrenergic receptor agonists, beta-blockers including topical eye medications, alpha-beta blockers, calcium antagonists, diuretics, and angiotensin-converting enzyme (ACE) inhibitors. The lack of data on angiotensin II receptor blockers is noted although effects are considered to be similar to those reported with ACE inhibitors and therefore to be avoided. Analysis of the literature underscores that some antihypertensive drugs can be used safely at certain stages of pregnancy, while others are suspect and to be avoided at all costs. The lack of placebo-controlled studies on the treatment of severe hypertension in pregnancy due to ethical considerations is discussed against the background of the pressing need to treat these women despite the possible deleterious effects of antihypertensive drugs

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Working Group Report on High Blood Pressure in Pregnancy Am J Obstet Gynecol 1990; 163: 1691–1712 NIH publication N000–3029. Revised July 2000

  2. De Swiet M . Maternal blood pressure and birthweight (editorial) Lancet 2000; 355: 81

    Article  CAS  Google Scholar 

  3. Von Dadelszen P et al. Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: a meta-analysis Lancet 2000; 355: 87–92

    Article  CAS  Google Scholar 

  4. Sibai BM et al. Risk factors for preeclampsia abruption placental, and adverse neonatal outcomes among women with chronic hypertension N Engl J Med 1998; 338: 701–705

    Article  Google Scholar 

  5. Rey E, Couturier A . The prognosis of pregnancy in women with chronic hypertension Am J Obstet Gynecol 1994; 171: 410–416

    Article  CAS  Google Scholar 

  6. Montan S et al. Effects of methyldopa on uteroplacental and fetal hemodynamics in pregnancy-induced hypertension Am J Obstet Gynecol 1993; 168: 152–156

    Article  CAS  Google Scholar 

  7. Sibai BM . Treatment of hypertension in pregnant women N Engl J Med 1996; 335: 257–265

    Article  CAS  Google Scholar 

  8. Lindheimer MD . Hypertension in pregnancy Hypertension 1993; 22: 127–137

    Article  CAS  Google Scholar 

  9. Kirsten R, Nelson K, Kirsten D, Heintz B . Clinical pharmakokinetics of vasodilators – Part II Clin Pharmacokinet 1998; 35: 9–36

    Article  CAS  Google Scholar 

  10. Sibai MB et al. A comparison of no medication versus methyldopa or labetalol in chronic hypertension during pregnancy Am J Obstet Gynecol 1990; 162: 960–967

    Article  CAS  Google Scholar 

  11. Pickles CJ, Symonds EM, Pipkin FB . The fetal outcome in a randomized double blind controlled trial of labetalol versus placebo in pregnancy-induced hypertension Br J Obstet Gynecol 1989; 96: 38–43

    Article  CAS  Google Scholar 

  12. Pickles CJ, Broughton Pipkin F, Symonds EM . A randomized placebo controlled trial of labetalol in the treatment of mild to moderate pregnancy induced hypertension Br J Obstet Gynecol 1992; 99: 964–968

    Article  CAS  Google Scholar 

  13. Butters L, Kennedy S, Rubin PC . Atenolol in essential hypertension during pregnancy BMJ 1990; 301: 587–589

    Article  CAS  Google Scholar 

  14. Lip GYH et al. Effect of atenolol on birth weight Am J Cardiol 1997; 79: 1436–1438

    Article  CAS  Google Scholar 

  15. Magee LA, Omstein MP, von Dsadelszen P . Fortnightly review: management of hypertension in pregnancy BMJ 1999; 318: 1332–1336

    Article  CAS  Google Scholar 

  16. Lydakis C et al. Atenolol and fetal growth in pregnancies complicated by hypertension Am J Hypertens 1999; 12: 541–547

    Article  CAS  Google Scholar 

  17. Easterling TR et al. Prevention of preeclampsia a randomized trial of atenolol in hyperdynamicpatients before onset of hypertension. Obstet Gynecol 1999; 93: 725–733

    CAS  Google Scholar 

  18. Churchill D, Bayliss H, Beevers G . Fetal growth restriction Lancet 2000; 355: 1366–1367

    Article  CAS  Google Scholar 

  19. Magee L . Authors reply Lancet 2000; 355: 1367

    Article  Google Scholar 

  20. Magee LA et al. The generalizability of trial data; a comparison of beta blocker trial participants with a prospective cohort of women taking beta blockers in pregnancy Eur J Obstet Gynecol Reprod Biol 2001; 94: 205–210

    Article  CAS  Google Scholar 

  21. Wagebvoort AM et al. Topical timolol therapy in pregnancy: is it safe for the fetus? Teratology 1998; 58: 258–262

    Article  Google Scholar 

  22. Van Tetten GR . Cardiovascular effects of timolol in the anesthetized pregnant ewe and fetus Proc West Pharmacol Soc 1980; 23: 191–195

    Google Scholar 

  23. Kooner KS, Zimmerman TJ . Antiglaucoma therapy during pregnancy – Part I Ann Ophthalmol 1988; 20: 166–169

    CAS  PubMed  Google Scholar 

  24. Bourget P et al. Weak placental passages of prazosin (Alpress) during the third trimester of pregnancy J Gynecol Obstet Biol Reported Paris 1993; 22: 871–874

    CAS  Google Scholar 

  25. Hurst JA et al. Transverse limb deficiency, facial clefting and hypoxic renal damage: an association with treatment of maternal hypertension? Clin Dysmorphol 1995; 4: 359–363

    Article  CAS  Google Scholar 

  26. Kaler SG et al. Hypertrichosis and congenital anomalies associated with maternal use of minoxidil Pediatrics 1987; 79: 434–436

    CAS  PubMed  Google Scholar 

  27. Carlson RG, Feenstra ES . Toxicologic studies with the hypotensive agent minoxidil Toxicol Appl Pharmacol 1977; 39: 1–11

    Article  CAS  Google Scholar 

  28. Magee LA et al. The safety of calcium channel blockers in human pregnancy: A prospective, multicenter cohort study Am J Obstet Gynecol 1996; 174: 823–828

    Article  CAS  Google Scholar 

  29. Gruppo di studio Ipertensione in Gravidanze. Nifedipine versus expectant management in mild to moderate hypertension in pregnancy Br J Obstet Gynaecol 1998; 105: 718–722

  30. Sibai BM, Grossman RA, Grossman HG . Effects of diuretics on plasma volume in pregnancies with long term hypertension Am J Obstet Gynecol 1984; 150: 831–835

    Article  CAS  Google Scholar 

  31. Arias F, Zamora J . Antihypertensive treatment and pregnancy outcome inpatients with mild chronic hypertension Obstet Gynecol 1979; 53: 489–494

    CAS  PubMed  Google Scholar 

  32. Collins R, Yusuf S, Peto R . Overview of randomised trials of diuretics in pregnancy BMJ 1985; 290: 17–23

    Article  CAS  Google Scholar 

  33. Davidson D, Stalcup SA, Mellins RB . Captopril administration to the pregnant guinea pig inhibits fetal angiotensin converting enzyme activity Pediatr Res 1981; 15: 658

    Article  Google Scholar 

  34. Broughton-Pipkin F, Wallace CP . The effect of enalapril (MK421), an angiotensin converting enzyme inhibitor, on the conscious pregnant ewe and her foetus Br J Pharmacol 1986; 87: 533–542

    Article  CAS  Google Scholar 

  35. Broughton-Pipkin F, Symonds EM, Turner SR . The effect of captopril (SQ14,255) upon mother and fetus in the chronically cannulated ewe and in the pregnant rabbit J Physiol 1982; 323: 415–422

    Article  CAS  Google Scholar 

  36. Ferris TF, Weir EK . Effect of captopril on uterine blood flow and prostaglandin synthesis in the pregnant rabbit J Clin Invest 1983; 71: 809–815

    Article  CAS  Google Scholar 

  37. Fiocchi R et al. Captopril during pregnancy Lancet 1984; 2: 1153

    Article  CAS  Google Scholar 

  38. Coen G et al. Successful treatment of long lastingsevere hypertension with captopril during a twinpregnancy Nephron 1985; 40: 498–500

    Article  CAS  Google Scholar 

  39. Brent RL . Angiotensin-converting enzyme inhibitors, an embryopathic class of drugs with unique properties: information for clinical tetralogy counselors Tetralogy 1991; 43: 543–546

    CAS  Google Scholar 

  40. Guignard JP . Burgener F, Calame A Persistent anuria in a neonate: a side effect of captopril? J Pediatr Nephrol 1981; 2: 133

    Google Scholar 

  41. Scott AA, Purohit DM . Neonatal renal failure: a complication of maternal antihypertensive therapy Am J Obstet Gynecol 1989; 160: 1223–1224

    Article  CAS  Google Scholar 

  42. Rothberg AD, Lorenz R . Can captopril cause fetal and neonatal renal failure? Pediatr Pharmacol 1984; 4: 189–192

    CAS  Google Scholar 

  43. Cuniff C et al. Oligohydramnios sequence and renal tubular malformation associated with maternal enalapril use Am J Obstet Gynecol 1990; 162: 187–189

    Article  Google Scholar 

  44. Schubiger G, Flury G, Nussberger J . Enalapril for pregnancy induced hypertension: Acute renal failure in neonate Ann Intern Med 1988; 108: 215–216

    Article  CAS  Google Scholar 

  45. Barr M Jr, Cohen MM Jr . ACE inhibitor fetopathy and hypocalvaria: the kidney-skull connection Teratology 1991; 44: 485–495

    Article  CAS  Google Scholar 

  46. Duminy PC, Burger P du T . Fetal anbormality associated with the use of captopril during pregnancy. (Letter) S Afr Med J 1981; 60: 805

    CAS  PubMed  Google Scholar 

  47. Mheta N, Modi N . ACE inhibitors in pregnancy (Letter) Lancet 1989; 2: 96

    Article  Google Scholar 

  48. Kreft-Jais C et al. Angiotensin-converting enzyme inhibitors during pregnancy: a survey of 22patients given captopril and nine given enalapril Br J Obstet Gynecol 1988; 95: 420–422

    Article  CAS  Google Scholar 

  49. Kalter H, Warkany J . Congenital malformations: etiologic factors and their role in prevention N Engl J Med 1983; 308: 491–497

    Article  CAS  Google Scholar 

  50. Are ACE inhibitors safe in pregnancy? (editorial) Lancet 1989; 2: 482–483

  51. Shotan A et al. Risks of angiotensin converting enzyme inhibition during pregnancy: experimental and clinical evidence, potential mechanisms and recommendations for use Am J Med 1994; 96: 451–456

    Article  CAS  Google Scholar 

  52. Calhoun DA, Oparil S . High blood pressure in women Int J Fertil 1997; 42: 198–205

    CAS  Google Scholar 

  53. Lip GYH et al. Angiotensin converting enzyme inhibitors in early pregnancy Lancet 1997; 350: 1446–1447

    Article  CAS  Google Scholar 

  54. Forhead AJ et al. Changes in maternal and fetal renin-angiotensin system in response to angiotensin II type 1 receptor blockade and angiotensin converting enzyme inhibitor in pregnant sheep during late gestation Exp Phys 1997; 82: 761–776

    Article  CAS  Google Scholar 

  55. Spence SG et al. Toxicokinetic analysis of losartan during gestation and lactation in the rat Teratology 1996; 53: 245–252

    Article  CAS  Google Scholar 

  56. Lambot MA, Vermeylen D, Noel JC . Angiotensin II receptor inhibitors in pregnancy Lancet 2001; 357: 1619–1620

    Article  CAS  Google Scholar 

  57. Saji H, Yamanaka M, Hagiwara A, Ijiri R . Losartan and fetal toxic effects (Letter) Lancet 2001; 357: 363

    Article  CAS  Google Scholar 

  58. Hinsberger A, Wingen AM, Hoyer PF . (Letter) Lancet 2001; 357: 1620

    Article  CAS  Google Scholar 

  59. Chung NA, Lip GH, Beevers M, Beevers DG . Outcomes in women given valsortam early in pregnancy. (Letter) Lancet 2001; 357: 1620

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Chorley Hypertension Research Institute, Chaim Sheba Medical Center, Tel Hashomer and Sackler School of Medicine, Tel Aviv University, Israel

    T Rosenthal

  2. Department of Medicine, Division of Cardiovascular Disease, Vascular Biology and Hypertension Program, University of at Birmingham Alabama School of Medicine, Birmingham, AL, USA

    S Oparil

Authors
  1. T Rosenthal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S Oparil
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T Rosenthal.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rosenthal, T., Oparil, S. The effect of antihypertensive drugs on the fetus. J Hum Hypertens 16, 293–298 (2002). https://doi.org/10.1038/sj.jhh.1001400

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.jhh.1001400

Keywords

This article is cited by

Search

Advanced search

Quick links