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Hypertension in Pregnancy: Natural History and Treatment Options

  • Blood Pressure Monitoring and Management (J Cockcroft, Section Editor)
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Abstract

Hypertensive disorders of pregnancy affect approximately 5–10 % of all maternities and are major contributors of maternal and neonatal morbidity and mortality worldwide. This group of disorders encompasses chronic hypertension, as well as conditions that arise de novo in pregnancy: gestational hypertension and pre-eclampsia. The latter group is thought to be part of the same continuum but with arbitrary division. Research into the aetiology of hypertension in pregnancy have largely been focused on pre-eclampsia, with a majority of studies exploring either pregnancy-associated factors such as placental-derived or immunologic responses to pregnancy tissue, or maternal constitutional factors such as cardiovascular health and endothelial dysfunction. The evidence base for the pathophysiology and progression of hypertensive disorders in pregnancy, particularly pre-eclampsia, is reviewed. Clinical algorithms and pharmacological agents for the management of hypertension in pregnancy are summarised, with a brief focus on post-partum considerations and long-term health implications. Novel therapeutic options for the management of pre-eclampsia are also explored.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Say L et al. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2(6):e323–33.

    PubMed  Google Scholar 

  2. Lindheimer MD et al. ASH position paper: hypertension in pregnancy. J Clin Hypertens (Greenwich). 2009;11(4):214–25.

    Google Scholar 

  3. Lo JO, Mission JF, Caughey AB. Hypertensive disease of pregnancy and maternal mortality. Curr Opin Obstet Gynecol. 2013;25(2):124–32.

    PubMed  Google Scholar 

  4. Foo L, Bewley S, Rudd A. Maternal death from stroke: a thirty year national retrospective review. Eur J Obstet Gynecol Reprod Biol. 2013;171(2):266–70.

    PubMed  Google Scholar 

  5. Chapman AB et al. Temporal relationships between hormonal and hemodynamic changes in early human pregnancy. Kidney Int. 1998;54(6):2056–63.

    CAS  PubMed  Google Scholar 

  6. Duvekot JJ et al. Early pregnancy changes in hemodynamics and volume homeostasis are consecutive adjustments triggered by a primary fall in systemic vascular tone. Am J Obstet Gynecol. 1993;169(6):1382–92.

    CAS  PubMed  Google Scholar 

  7. Mahendru AA et al. Maternal cardiovascular changes from pre-pregnancy to very early pregnancy. J Hypertens. 2012;30(11):2168–72.

    CAS  PubMed  Google Scholar 

  8. Hibbard JU, Shroff SG, Lang RM. Cardiovascular changes in preeclampsia. Semin Nephrol. 2004;24(6):580–7.

    PubMed  Google Scholar 

  9. MacGillivray I, Rose GA, Rowe B. Blood pressure survey in pregnancy. Clin Sci. 1969;37(2):395–407.

    CAS  PubMed  Google Scholar 

  10. Fujime M et al. Central aortic blood pressure and augmentation index during normal pregnancy. Hypertens Res. 2012;35(6):633–8.

    PubMed  Google Scholar 

  11. Simmons LA, Gillin AG, Jeremy RW. Structural and functional changes in left ventricle during normotensive and preeclamptic pregnancy. Am J Physiol Heart Circ Physiol. 2002;283(4):H1627–33.

    CAS  PubMed  Google Scholar 

  12. Robson SC et al. Haemodynamic changes during the puerperium: a Doppler and M-mode echocardiographic study. Br J Obstet Gynaecol. 1987;94(11):1028–39.

    CAS  PubMed  Google Scholar 

  13. Chung E, Leinwand LA. Pregnancy as a cardiac stress model. Cardiovasc Res. 2014;101(4):561–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Lees MM et al. The circulatory effects of recumbent postural change in late pregnancy. Clin Sci. 1967;32(3):453–65.

    CAS  PubMed  Google Scholar 

  15. Yoder SR, Thornburg LL, Bisognano JD. Hypertension in pregnancy and women of childbearing age. Am J Med. 2009;122(10):890–5.

    PubMed  Google Scholar 

  16. Brown MA, Gallery ED. Volume homeostasis in normal pregnancy and pre-eclampsia: physiology and clinical implications. Baillieres Clin Obstet Gynaecol. 1994;8(2):287–310.

    CAS  PubMed  Google Scholar 

  17. Mustafa R et al. A comprehensive review of hypertension in pregnancy. J Pregnancy. 2012;2012:105918.

    PubMed  PubMed Central  Google Scholar 

  18. Ward K et al. A molecular variant of angiotensinogen associated with preeclampsia. Nat Genet. 1993;4(1):59–61.

    CAS  PubMed  Google Scholar 

  19. Schroeder BMO, . American College of Obstetricians and Gynecologists. ACOG practice bulletin on diagnosing and managing preeclampsia and eclampsia. Am Fam Physician. 2002;66(2):330–1.

  20. NICE, National Institute for Health and Clinical Excellence: (CG62) Antenatal care, routine care for the healthy pregnant woman. 2008, RCOG Press: Royal College of Obstetricians & Gynaecologists.

  21. Brown MA et al. Ambulatory blood pressure monitoring in pregnancy: what is normal? Am J Obstet Gynecol. 1998;178(4):836–42.

    CAS  PubMed  Google Scholar 

  22. Churchill D, Beevers DG. Differences between office and 24-hour ambulatory blood pressure measurement during pregnancy. Obstet Gynecol. 1996;88(3):455–61.

    CAS  PubMed  Google Scholar 

  23. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol, 2000. 183(1): p. S1-S22.

  24. NICE, National Institute for Health and Clinical Excellence: (CG107) Hypertension in pregnancy: the management of hypertensive disorders during pregnancy. 2011: London.

  25. Paruk F, Moodley J. Untoward effects of rapid-acting antihypertensive agents. Best Pract Res Clin Obstet Gynaecol. 2001;15(4):491–506.

    CAS  PubMed  Google Scholar 

  26. Redman, C., Hypertension, in medical disorders in obstetric practice. M.d. Swiet, Editor. 2002, Blackwell Publishing Company. p. 159–197.

  27. Valensise HNG, Vasapollo B. Pre-eclampsia: one name, two conditions—the case for early and late disease being different. Fetal Mat Med Rev. 2014;24:32–7.

    Google Scholar 

  28. Ferrazzi EST, Aupont JE. The evidence for late-onset pre-eclampsia as a maternogenic disease of pregnancy. J Fetal Mat Med Rev. 2013;24(1):18–31.

    Google Scholar 

  29. Huppertz B. Placental origins of preeclampsia: challenging the current hypothesis. Hypertension. 2008;51(4):970–5.

    CAS  PubMed  Google Scholar 

  30. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005;365(9461):785–99.

    PubMed  Google Scholar 

  31. Levine RJ et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006;355(10):992–1005.

    CAS  PubMed  Google Scholar 

  32. Levine RJ et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350(7):672–83.

    CAS  PubMed  Google Scholar 

  33. Xiong X et al. Impact of preeclampsia and gestational hypertension on birth weight by gestational age. Am J Epidemiol. 2002;155(3):203–9.

    PubMed  Google Scholar 

  34. Brosens I et al. The “Great Obstetrical Syndromes” are associated with disorders of deep placentation. Am J Obstet Gynecol. 2011;204(3):193–201.

    PubMed  Google Scholar 

  35. Burton GJ et al. Rheological and physiological consequences of conversion of the maternal spiral arteries for uteroplacental blood flow during human pregnancy. Placenta. 2009;30(6):473–82.

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Hunkapiller NM et al. A role for Notch signaling in trophoblast endovascular invasion and in the pathogenesis of pre-eclampsia. Development. 2011;138(14):2987–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Cobellis L et al. Distribution of Notch protein members in normal and preeclampsia-complicated placentas. Cell Tissue Res. 2007;330(3):527–34.

    CAS  PubMed  Google Scholar 

  38. Sahin Z et al. Distribution of Notch family proteins in intrauterine growth restriction and hypertension complicated human term placentas. Acta Histochem. 2011;113(3):270–6.

    CAS  PubMed  Google Scholar 

  39. Staff AC, Dechend R, Pijnenborg R. Learning from the placenta: acute atherosis and vascular remodeling in preeclampsia-novel aspects for atherosclerosis and future cardiovascular health. Hypertension. 2010;56(6):1026–34. An interesting paper which presents several possible hypotheses linking placental and maternal pre-disposing risk factors acting in synergy to produce the phenotype of pre-eclampsia.

    CAS  PubMed  Google Scholar 

  40. Chatzizisis YS et al. Role of endothelial shear stress in the natural history of coronary atherosclerosis and vascular remodeling: molecular, cellular, and vascular behavior. J Am Coll Cardiol. 2007;49(25):2379–93.

    CAS  PubMed  Google Scholar 

  41. Staff AC, Dechend R, Redman CW. Review: preeclampsia, acute atherosis of the spiral arteries and future cardiovascular disease: two new hypotheses. Placenta. 2013;34(Suppl):S73–8.

    PubMed  Google Scholar 

  42. Sheppard BL, Bonnar J. The ultrastructure of the arterial supply of the human placenta in pregnancy complicated by fetal growth retardation. Br J Obstet Gynaecol. 1976;83(12):948–59.

    CAS  PubMed  Google Scholar 

  43. Prins JR et al. Preeclampsia is associated with lower percentages of regulatory T cells in maternal blood. Hyper Pregnancy. 2009;28(3):300–11.

    Google Scholar 

  44. Wallace K et al. CD4+ T-helper cells stimulated in response to placental ischemia mediate hypertension during pregnancy. Hypertension. 2011;57(5):949–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Gilbert JS et al. Pathophysiology of hypertension during preeclampsia: linking placental ischemia with endothelial dysfunction. Am J Physiol Heart Circ Physiol. 2008;294(2):H541–50.

    CAS  PubMed  Google Scholar 

  46. Krauss T et al. Circulating endothelial cell adhesion molecules as diagnostic markers for the early identification of pregnant women at risk for development of preeclampsia. Am J Obstet Gynecol. 1997;177(2):443–9.

    CAS  PubMed  Google Scholar 

  47. Roberts JM, Taylor RN, Goldfien A. Endothelial cell activation as a pathogenetic factor in preeclampsia. Semin Perinatol. 1991;15(1):86–93.

    CAS  PubMed  Google Scholar 

  48. Wang A, Rana S, Karumanchi SA. Preeclampsia: the role of angiogenic factors in its pathogenesis. Physiology (Bethesda). 2009;24:147–58.

    Google Scholar 

  49. Mutter WP, Karumanchi SA. Molecular mechanisms of preeclampsia. Microvasc Res. 2008;75(1):1–8.

    CAS  PubMed  Google Scholar 

  50. Thadhani R et al. Pilot study of extracorporeal removal of soluble Fms-like tyrosine kinase 1 in preeclampsia. Circulation. 2011;124(8):940–U178.

    CAS  PubMed  Google Scholar 

  51. Li Z et al. Recombinant vascular endothelial growth factor 121 attenuates hypertension and improves kidney damage in a rat model of preeclampsia. Hypertension. 2007;50(4):686–92.

    CAS  PubMed  Google Scholar 

  52. Izumi H et al. Gestational changes in endothelium-dependent vasorelaxation in human umbilical artery. Am J Obstet Gynecol. 1994;170(1 Pt 1):236–45.

    CAS  PubMed  Google Scholar 

  53. Nathan L, Cuevas J, Chaudhuri G. The role of nitric oxide in the altered vascular reactivity of pregnancy in the rat. Br J Pharmacol. 1995;114(5):955–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Crane MS, Rossi AG, Megson IL. A potential role for extracellular nitric oxide generation in cGMP-independent inhibition of human platelet aggregation: biochemical and pharmacological considerations. Br J Pharmacol. 2005;144(6):849–59.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Kubes P, Suzuki M, Granger DN. Nitric-oxide—an endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci U S A. 1991;88(11):4651–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Savvidou MD et al. Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre-eclampsia. Lancet. 2003;361(9368):1511–7.

    CAS  PubMed  Google Scholar 

  57. Khalil A et al. Maternal hemodynamics at 11–13 weeks’ gestation and risk of pre-eclampsia. Ultrasound Obstet Gynecol. 2012;40(1):28–34.

    CAS  PubMed  Google Scholar 

  58. Valensise H et al. Early and late preeclampsia: two different maternal hemodynamic states in the latent phase of the disease. Hypertension. 2008;52(5):873–80.

    CAS  PubMed  Google Scholar 

  59. Melchiorre, K., et al., Maternal cardiovascular impairment in pregnancies complicated by severe fetal growth restriction. Hypertension. 60(2): p. 437-43.

    CAS  PubMed  Google Scholar 

  60. Duvekot JJ et al. Severely impaired fetal growth is preceded by maternal hemodynamic maladaptation in very early-pregnancy. Acta Obstetricia Et Gynecol Scandinav. 1995;74(9):693–7.

    CAS  Google Scholar 

  61. Ayuk PT, Matijevic R. Placental ischaemia is a consequence rather than a cause of pre-eclampsia. Med Hypotheses. 2006;67(4):792–5.

    PubMed  Google Scholar 

  62. Everett, T.R. and C.C. Lees, Beyond the placental bed: placental and systemic determinants of the uterine artery Doppler waveform. Placenta. 33(11): p. 893–901.

    CAS  PubMed  Google Scholar 

  63. Harrington K et al. Changes observed in Doppler studies of the fetal circulation in pregnancies complicated by pre-eclampsia or the delivery of a small-for-gestational-age baby. I. Cross-sectional analysis. Ultrasound Obstet Gynecol. 1995;6(1):19–28.

    CAS  PubMed  Google Scholar 

  64. Albaiges G et al. One-stage screening for pregnancy complications by color Doppler assessment of the uterine arteries at 23 weeks’ gestation. Obstet Gynecol. 2000;96(4):559–64.

    CAS  PubMed  Google Scholar 

  65. Lees C et al. Individualized risk assessment for adverse pregnancy outcome by uterine artery Doppler at 23 weeks. Obstet Gynecol. 2001;98(3):369–73.

    CAS  PubMed  Google Scholar 

  66. Verlohren, S., et al., Uterine artery Doppler, birthweight and timing of preeclampsia onset: providing insights into the dual etiology of late-onset preeclampsia. Ultrasound Obstet Gynecol, 2014.

  67. Magnussen EB et al. Prepregnancy cardiovascular risk factors as predictors of pre-eclampsia: population based cohort study. Br Med J. 2007;335(7627):978–81.

    CAS  Google Scholar 

  68. Irgens HU et al. Long term mortality of mothers and fathers after pre-eclampsia: population based cohort study. Br Med J. 2001;323(7323):1213–6.

    CAS  Google Scholar 

  69. Ray JG et al. Cardiovascular health after maternal placental syndromes (CHAMPS): population-based retrospective cohort study. Lancet. 2005;366(9499):1797–803.

    PubMed  Google Scholar 

  70. Mongraw-Chaffin ML, Cirillo PM, Cohn BA. Preeclampsia and cardiovascular disease death: prospective evidence from the child health and development studies cohort. Hypertension. 2010;56(1):166–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Smith GC, Pell JP, Walsh D. Pregnancy complications and maternal risk of ischaemic heart disease: a retrospective cohort study of 129,290 births. Lancet. 2001;357(9273):2002–6.

    CAS  PubMed  Google Scholar 

  72. Talaulikar V, A.S., HELLP syndrome, in hypertensive disease in pregnancy. G.S. Arulkumaran S, Fernandez E, Editor. 2014, Jaypee Brothers Medical Publishers Ltd: India. p. 88–95.

  73. Ananth CV. Chronic hypertension and risk of placental abruption: is the association modified by ischemic placental disease? Am J Obstet Gynecol. 2007;197(3):273 e1–7.

    Google Scholar 

  74. Haelterman E et al. Effect of uncomplicated chronic hypertension on the risk of small-for-gestational age birth. Am J Epidemiol. 1997;145(8):689–95.

    CAS  PubMed  Google Scholar 

  75. Walfisch A et al. Teratogenicity of angiotensin converting enzyme inhibitors or receptor blockers. J Obstet Gynaecol. 2011;31(6):465–72.

    CAS  PubMed  Google Scholar 

  76. Piper JM, Ray WA, Rosa FW. Pregnancy outcome following exposure to angiotensin-converting enzyme inhibitors. Obstet Gynecol. 1992;80(3 Pt 1):429–32.

    CAS  PubMed  Google Scholar 

  77. Rosa FW et al. Neonatal anuria with maternal angiotensin-converting enzyme inhibition. Obstet Gynecol. 1989;74(3 Pt 1):371–4.

    CAS  PubMed  Google Scholar 

  78. Kincaid-Smith P, Bullen M, Mills J. Prolonged use of methyldopa in severe hypertension in pregnancy. Br Med J. 1966;1(5482):274–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Ananth CV et al. Influence of hypertensive disorders and cigarette smoking on placental abruption and uterine bleeding during pregnancy. Br J Obstet Gynaecol. 1997;104(5):572–8.

    CAS  PubMed  Google Scholar 

  80. Romero-Arauz JF. [Progression of gestational hypertension to preeclampsia]. Ginecol Obstet Mex. 2014;82(4):229–35.

    PubMed  Google Scholar 

  81. Anumba DO, Lincoln K, Robson SC. Predictive value of clinical and laboratory indices at first assessment in women referred with suspected gestational hypertension. Hyper Pregnancy. 2010;29(2):163–79.

    CAS  Google Scholar 

  82. Villar J et al. Preeclampsia, gestational hypertension and intrauterine growth restriction, related or independent conditions? Am J Obstet Gynecol. 2006;194(4):921–31.

    PubMed  Google Scholar 

  83. Buchbinder A et al. Adverse perinatal outcomes are significantly higher in severe gestational hypertension than in mild preeclampsia. Am J Obstet Gynecol. 2002;186(1):66–71.

    PubMed  Google Scholar 

  84. Steer PJ et al. Maternal blood pressure in pregnancy, birth weight, and perinatal mortality in first births: prospective study. BMJ. 2004;329(7478):1312.

    PubMed  PubMed Central  Google Scholar 

  85. Al Khaja KAJ et al. Drug treatment of hypertension in pregnancy: a critical review of adult guideline recommendations. J Hypertens. 2014;32(3):454–63. A comprehensive review which covered 25 national/international guidelines for the management of arterial hypertension in adults, and extracted data pertaining to pharmacological management of hypertension in pregnancy, with a focus on drug safety for the fetus.

    CAS  PubMed  Google Scholar 

  86. Mutch LM et al. Hypertension during pregnancy, with and without specific hypotensive treatment. II. The growth and development of the infant in the first year of life. Early Hum Dev. 1977;1(1):59–67.

    CAS  PubMed  Google Scholar 

  87. Cockburn J et al. Final report of study on hypertension during pregnancy: the effects of specific treatment on the growth and development of the children. Lancet. 1982;1(8273):647–9.

    CAS  PubMed  Google Scholar 

  88. el-Qarmalawi AM et al. Labetalol vs. methyldopa in the treatment of pregnancy-induced hypertension. Int J Gynaecol Obstet. 1995;49(2):125–30.

    CAS  PubMed  Google Scholar 

  89. Huisjes HJ, Hadders-Algra M, Touwen BC. Is clonidine a behavioural teratogen in the human? Early Hum Dev. 1986;14(1):43–8.

    CAS  PubMed  Google Scholar 

  90. Chobanian AV et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA. 2003;289(19):2560–72.

    CAS  PubMed  Google Scholar 

  91. Butters L, Kennedy S, Rubin PC. Atenolol in essential hypertension during pregnancy. BMJ. 1990;301(6752):587–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Lip GY et al. Effect of atenolol on birth weight. Am J Cardiol. 1997;79(10):1436–8.

    CAS  PubMed  Google Scholar 

  93. Yakoob MY et al. The risk of congenital malformations associated with exposure to beta-blockers early in pregnancy: a meta-analysis. Hypertension. 2013;62(2):375–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Sorensen HT et al. The risk of limb deficiencies and other congenital abnormalities in children exposed in utero to calcium channel blockers. Acta Obstet Gynecol Scand. 2001;80(5):397–401.

    CAS  PubMed  Google Scholar 

  95. Danielsson BR et al. Digital defects induced by vasodilating agents: relationship to reduction in uteroplacental blood flow. Teratology. 1989;40(4):351–8.

    CAS  PubMed  Google Scholar 

  96. Scott Jr WJ et al. Cardiovascular alterations in rat fetuses exposed to calcium channel blockers. Reprod Toxicol. 1997;11(2–3):207–14.

    CAS  PubMed  Google Scholar 

  97. Brown MA et al. Efficacy and safety of nifedipine tablets for the acute treatment of severe hypertension in pregnancy. Am J Obstet Gynecol. 2002;187(4):1046–50.

    CAS  PubMed  Google Scholar 

  98. Impey L. Severe hypotension and fetal distress following sublingual administration of nifedipine to a patient with severe pregnancy induced hypertension at 33 weeks. Br J Obstet Gynaecol. 1993;100(10):959–61.

    CAS  PubMed  Google Scholar 

  99. Papatsonis DN et al. Calcium channel blockers in the management of preterm labor and hypertension in pregnancy. Eur J Obstet Gynecol Reprod Biol. 2001;97(2):122–40.

    CAS  PubMed  Google Scholar 

  100. Ben-Ami M, Giladi Y, Shalev E. The combination of magnesium sulphate and nifedipine: a cause of neuromuscular blockade. Br J Obstet Gynaecol. 1994;101(3):262–3.

    CAS  PubMed  Google Scholar 

  101. Ales K. Magnesium plus nifedipine. Am J Obstet Gynecol. 1990;162(1):288.

    CAS  PubMed  Google Scholar 

  102. Magee LA et al. Therapy with both magnesium sulfate and nifedipine does not increase the risk of serious magnesium-related maternal side effects in women with preeclampsia. Am J Obstet Gynecol. 2005;193(1):153–63.

    CAS  PubMed  Google Scholar 

  103. Vasilakis-Scaramozza C et al. Antihypertensive drugs and the risk of congenital anomalies. Pharmacotherapy. 2013;33(5):476–82.

    CAS  PubMed  Google Scholar 

  104. Cooper WO et al. Major congenital malformations after first-trimester exposure to ACE inhibitors. N Engl J Med. 2006;354(23):2443–51.

    CAS  PubMed  Google Scholar 

  105. Quan A. Fetopathy associated with exposure to angiotensin converting enzyme inhibitors and angiotensin receptor antagonists. Early Hum Dev. 2006;82(1):23–8.

    CAS  PubMed  Google Scholar 

  106. Alwan S, Polifka JE, Friedman JM. Angiotensin II receptor antagonist treatment during pregnancy. Birth Defects Res A Clin Mol Teratol. 2005;73(2):123–30.

    CAS  PubMed  Google Scholar 

  107. Groves TD, Corenblum B. Spironolactone therapy during human pregnancy. Am J Obstet Gynecol. 1995;172(5):1655–6.

    CAS  PubMed  Google Scholar 

  108. Spinnato JA, Sibai BM, Anderson GD. Fetal distress after hydralazine therapy for severe pregnancy-induced hypertension. South Med J. 1986;79(5):559–62.

    CAS  PubMed  Google Scholar 

  109. Paterson-Brown S et al. Hydralazine boluses for the treatment of severe hypertension in pre-eclampsia. Br J Obstet Gynaecol. 1994;101(5):409–13.

    CAS  PubMed  Google Scholar 

  110. Davis RL et al. Risks of congenital malformations and perinatal events among infants exposed to calcium channel and beta-blockers during pregnancy. Pharmacoepidemiol Drug Saf. 2011;20(2):138–45.

    PubMed  Google Scholar 

  111. Olsen KS, Beier-Holgersen R. Hemodynamic collapse following labetalol administration in preeclampsia. Acta Obstet Gynecol Scand. 1992;71(2):151–2.

    CAS  PubMed  Google Scholar 

  112. Magee LA et al. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ. 2003;327(7421):955–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Vigil-De Gracia P et al. Severe hypertension in pregnancy: hydralazine or labetalol. a randomized clinical trial. Eur J Obstet Gynecol Reprod Biol. 2006;128(1–2):157–62.

    CAS  PubMed  Google Scholar 

  114. Duley L, Henderson-Smart DJ, Meher S. Drugs for treatment of very high blood pressure during pregnancy. Cochrane Database Syst Rev. 2006;3:CD001449.

    Google Scholar 

  115. Firoz T et al. Oral antihypertensive therapy for severe hypertension in pregnancy and postpartum: a systematic review. BJOG. 2014;121(10):1210–8. discussion 1220.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Rumbold AR et al. Vitamins C and E and the risks of preeclampsia and perinatal complications. N Engl J Med. 2006;354(17):1796–806.

    CAS  PubMed  Google Scholar 

  117. Poston L et al. Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial. Lancet. 2006;367(9517):1145–54.

    CAS  PubMed  Google Scholar 

  118. Conde-Agudelo, A., et al., Supplementation with vitamins C and E during pregnancy for the prevention of preeclampsia and other adverse maternal and perinatal outcomes: a systematic review and metaanalysis. American Journal of Obstetrics and Gynecology, 2011. 204(6).

    Google Scholar 

  119. Basaran A, Basaran M, Topatan B. Combined vitamin C and E supplementation for the prevention of preeclampsia: a systematic review and meta-analysis. Obstet Gynecol Surv. 2010;65(10):653–67.

    PubMed  Google Scholar 

  120. Romero R, Garite TJ. Unexpected results of an important trial of vitamins C and E administration to prevent preeclampsia. Am J Obstet Gynecol. 2006;194(5):1213–4.

    CAS  PubMed  Google Scholar 

  121. Banerjee S, Chambers AE, Campbell S. Is vitamin E a safe prophylaxis for preeclampsia? Am J Obstet Gynecol. 2006;194(5):1228–33.

    CAS  PubMed  Google Scholar 

  122. Ramsay B et al. A nitric oxide donor improves uterine artery diastolic blood flow in normal early pregnancy and in women at high risk of pre-eclampsia. Eur J Clin Invest. 1994;24(1):76–8.

    CAS  PubMed  Google Scholar 

  123. Manzur-Verastegui S et al. Efficacy of nitroglycerine infusion versus sublingual nifedipine in severe pre-eclampsia: a randomized, triple-blind, controlled trial. Clin Exp Pharmacol Physiol. 2008;35(5–6):580–5.

    CAS  PubMed  Google Scholar 

  124. Cetin A et al. The effect of glyceryl trinitrate on hypertension in women with severe preeclampsia, HELLP syndrome, and eclampsia. Hyper Pregnancy. 2004;23(1):37–46.

    CAS  Google Scholar 

  125. Lees C et al. The efficacy and fetal-maternal cardiovascular effects of transdermal glyceryl trinitrate in the prophylaxis of pre-eclampsia and its complications: a randomized double-blind placebo-controlled trial. Ultrasound Obstet Gynecol. 1998;12(5):334–8.

    CAS  PubMed  Google Scholar 

  126. Schleussner E et al. Impact of the nitric oxide-donor pentaerythrityl-tetranitrate on perinatal outcome in risk pregnancies: a prospective, randomized, double-blinded trial. J Perinat Med. 2014;42(4):507–14.

    CAS  PubMed  Google Scholar 

  127. de Belder A et al. Treatment of HELLP syndrome with nitric oxide donor. Lancet. 1995;345(8942):124–5.

    PubMed  Google Scholar 

  128. Lees C et al. The effects of S-nitrosoglutathione on platelet activation, hypertension, and uterine and fetal Doppler in severe preeclampsia. Obstet Gynecol. 1996;88(1):14–9.

    CAS  PubMed  Google Scholar 

  129. Everett TR et al. S-Nitrosoglutathione improves haemodynamics in early-onset pre-eclampsia. Br J Clin Pharmacol. 2014;78(3):660–9. A well-designed trial demonstrating the potential use of nitric oxide donors as a novel therapeutic option for the treatment of pre-eclampsia.

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Hernandez-Diaz S, Toh S, Cnattingius S. Risk of pre-eclampsia in first and subsequent pregnancies: prospective cohort study. BMJ. 2009;338:b2255.

    PubMed  PubMed Central  Google Scholar 

  131. Basso O, Christensen K, Olsen J. Higher risk of pre-eclampsia after change of partner. an effect of longer interpregnancy intervals? Epidemiology. 2001;12(6):624–9.

    CAS  PubMed  Google Scholar 

  132. Hargood JL, Brown MA. Pregnancy-induced hypertension: recurrence rate in second pregnancies. Med J Aust. 1991;154(6):376–7.

    CAS  PubMed  Google Scholar 

  133. Trogstad L et al. Recurrence risk of preeclampsia in twin and singleton pregnancies. Am J Med Genet A. 2004;126A(1):41–5.

    PubMed  Google Scholar 

  134. Facchinetti F et al. L-arginine infusion reduces blood pressure in preeclamptic women through nitric oxide release. J Soc Gynecol Investig. 1999;6(4):202–7.

    CAS  PubMed  Google Scholar 

  135. Cindrova-Davies T. The therapeutic potential of antioxidants, ER chaperones, NO and H2S donors, and statins for treatment of preeclampsia. Front Pharmacol. 2014;5:119.

    PubMed  PubMed Central  Google Scholar 

  136. Fox KA. Effects of pravastatin on mediators of vascular function in a mouse model of soluble Fms-like tyrosine kinase-1-induced preeclampsia. Am J Obstet Gynecol. 2011;205(4):366 e1–5.

    Google Scholar 

  137. Kumasawa K et al. Pravastatin induces placental growth factor (PGF) and ameliorates preeclampsia in a mouse model. Proc Natl Acad Sci U S A. 2011;108(4):1451–5.

    CAS  PubMed  Google Scholar 

  138. Ahmed A et al. A new mouse model to explore therapies for preeclampsia. PLoS One. 2010;5(10):e13663.

    PubMed  PubMed Central  Google Scholar 

  139. Redecha P et al. Pravastatin prevents miscarriages in mice: role of tissue factor in placental and fetal injury. Blood. 2009;113(17):4101–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  140. NICE, National Institute for Health & Clinical Excellence: (CG37) Routine post-natal care of women and their babies. 2006.

  141. Cantwell R. Saving mothers’ lives: reviewing maternal deaths to make motherhood safer: 2006–2008. The eighth report of the confidential enquiries into maternal deaths in the United Kingdom. BJOG. 2011;118 Suppl 1:1–203.

    PubMed  Google Scholar 

  142. Podymow T, August P, Umans JG. Antihypertensive therapy in pregnancy. Semin Nephrol. 2004;24(6):616–25.

    PubMed  Google Scholar 

  143. Redman CWG, Kelly JG, Cooper WD. The excretion of enalapril and enalaprilat in human breast-milk. Eur J Clin Pharmacol. 1990;38(1):99.

    CAS  PubMed  Google Scholar 

  144. Lunell NO, Kulas J, Rane A. Transfer of labetalol into amniotic fluid and breast milk in lactating women. Eur J Clin Pharmacol. 1985;28(5):597–9.

    CAS  PubMed  Google Scholar 

  145. Bramham K et al. Postpartum management of hypertension. BMJ. 2013;346:f894. An easy-to-read review summarising post-partum management of hypertension in pregnancy, including algorithms for in-patient and out-patient management and breast feeding considerations.

    PubMed  Google Scholar 

  146. Duley L et al. Antiplatelet agents for preventing pre-eclampsia and its complications. Cochrane Database Syst Rev. 2007;2:CD004659.

    Google Scholar 

  147. van Rijn BB et al. Cardiovascular disease risk factors in women with a history of early-onset preeclampsia. Obstet Gynecol. 2013;121(5):1040–8.

    PubMed  Google Scholar 

  148. Bellamy L et al. Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis. BMJ. 2007;335(7627):974.

    PubMed  PubMed Central  Google Scholar 

  149. Melchiorre K et al. Preeclampsia is associated with persistent postpartum cardiovascular impairment. Hypertension. 2011;58(4):709–15. An important paper reporting on post-partum cardiac impairments in women with pre-eclampsia, which raises important considerations of longer term cardiovascular risk implications.

    CAS  PubMed  Google Scholar 

  150. McDonald SD et al. Cardiovascular sequelae of preeclampsia/eclampsia: a systematic review and meta-analyses. Am Heart J. 2008;156(5):918–30.

    PubMed  Google Scholar 

  151. Hannaford P, Ferry S, Hirsch S. Cardiovascular sequelae of toxaemia of pregnancy. Heart. 1997;77(2):154–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Mahendru AA et al. A longitudinal study of maternal cardiovascular function from preconception to the postpartum period. J Hypertens. 2014;32(4):849–56.

    CAS  PubMed  Google Scholar 

  153. Meah V, C.J., Stohr E, Maternal cardiac twist pre-pregnancy: potential as a novel marker of pre-eclampsia. Fetal and Maternal Medicine Review, 2013: p. 1–7.

  154. Mosca L et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women–2011 update: a guideline from the American Heart Association. Circulation. 2011;123(11):1243–62.

    PubMed  PubMed Central  Google Scholar 

  155. Senter C, Appelle N, Behera SK. Prescribing exercise for women. Curr Rev Musculoskelet Med. 2013;6(2):164–72.

    PubMed  PubMed Central  Google Scholar 

  156. ACOG. ACOG committee opinion no. 267. Exercise during pregnancy and the post-partum period. Obstet Gynecol. 2002;99:171–3.

    Google Scholar 

  157. Magnus P et al. Recreational physical activity and the risk of preeclampsia: a prospective cohort of Norwegian women. Am J Epidemiol. 2008;168(8):952–7.

    PubMed  PubMed Central  Google Scholar 

  158. Marcoux S, Brisson J, Fabia J. The effect of leisure time physical activity on the risk of pre-eclampsia and gestational hypertension. J Epidemiol Community Health. 1989;43(2):147–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  159. Saftlas AF et al. Work, leisure-time physical activity, and risk of preeclampsia and gestational hypertension. Am J Epidemiol. 2004;160(8):758–65.

    PubMed  Google Scholar 

  160. Vollebregt KC et al. Does physical activity in leisure time early in pregnancy reduce the incidence of preeclampsia or gestational hypertension? Acta Obstet Gynecol Scand. 2010;89(2):261–7.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, Hammersmith Campus, Du Cane Road, London, W12 0NN, UK

    L. Foo & C. C. Lees

  2. Queen Charlotte’s & Chelsea Hospital, Imperial NHS Healthcare Trust, Du Cane Road, London, W12 0HS, UK

    J. Tay

  3. Clinical Pharmacology Unit, University of Cambridge, Level 6 ACCI Building, Addenbrooke’s Hospital, Cambridge, CB2 0QQ, UK

    C. M. McEniery & I. B. Wilkinson

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  1. L. Foo
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  2. J. Tay
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  3. C. C. Lees
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  4. C. M. McEniery
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Conflict of Interest L. Foo, J. Tay, C.C. Lees, C.C. McEniery and I.B. Wilkinson declare that they have no conflicts of interest.

Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Blood Pressure Monitoring and Management

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Foo, L., Tay, J., Lees, C.C. et al. Hypertension in Pregnancy: Natural History and Treatment Options. Curr Hypertens Rep 17, 36 (2015). https://doi.org/10.1007/s11906-015-0545-1

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