• 1
    Foidart JM, Schaaps JP, Chantraine F, et al. Dysregulation of anti-angiogenic agents (sFlt-1, PLGF, and sEndoglin) in preeclampsia--a step forward but not the definitive answer. J Reprod Immunol 2009;82(2):10611.
  • 2
    George EM, Granger JP. Mechanisms and potential therapies for preeclampsia. Curr Hypertens Rep 2011;13(4):26975.
  • 3
    Lyall F, Robson SC, Bulmer JN. Spiral artery remodeling and trophoblast invasion in preeclampsia and fetal growth restriction: relationship to clinical outcome. Hypertension 2013;62(6):104654.
  • 4
    Konje JC, Howarth ES, Kaufmann P, Taylor DJ. Longitudinal quantification of uterine artery blood volume flow changes during gestation in pregnancies complicated by intrauterine growth restriction. BJOG 2003;110(3):3015.
  • 5
    Savvidou MD, Yu CK, Harland LC, et al. Maternal serum concentration of soluble fms-like tyrosine kinase 1 and vascular endothelial growth factor in women with abnormal uterine artery Doppler and in those with fetal growth restriction. Am J Obstet Gynecol 2006;195(6):166873.
  • 6
    Nevo O, Many A, Xu J, et al. Placental expression of soluble fms-like tyrosine kinase 1 is increased in singletons and twin pregnancies with intrauterine growth restriction. J Clin Endocrinol Metab 2008;93(1):28592.
  • 7
    Rana S, Karumanchi SA, Lindheimer MD. Angiogenic factors in diagnosis, management, and research in preeclampsia. Hypertension 2014;63(2):198202.
  • 8
    Gulmezoglu AM, Hofmeyr GJ. Bed rest in hospital for suspected impaired fetal growth. Cochrane Database Syst Rev 2000. URL [accessed on 05 February 2014].
  • 9
    Say L, Gulmezoglu AM, Hofmeyr GJ. Betamimetics for suspected impaired fetal growth. Cochrane Database Syst Rev 2001. URL [accessed on 05 February 2014].
  • 10
    Gulmezoglu AM, Hofmeyr GJ. Calcium channel blockers for potential impaired fetal growth. Cochrane Database Syst Rev 2000. URL [accessed on 05 February 2014].
  • 11
    Say L, Gülmezoglu AM, Hofmeyr GJ. Maternal oxygen administration for suspected impaired fetal growth. Cochrane Database Syst Rev 2003. URL [accessed on 05 February 2014].
  • 12
    Say L, Gulmezoglu AM, Hofmeyr GJ. Maternal nutrient supplementation for suspected impaired fetal growth. Cochrane Database Syst Rev 2003. URL [accessed on 05 February 2014].
  • 13
    Rumbold A, Duley L, Crowther CA, Haslam RR. Antioxidants for preventing pre-eclampsia. Cochrane Database Syst Rev 2008. URL [accessed on 05 February 2014].
  • 14
    Salles AM, Galvao TF, Silva MT, et al. Antioxidants for preventing preeclampsia: a systematic review. Scientific World Journal 2012;2012:243476. URL: [accessed on 13 May 2014].
  • 15
    Johal T, Lees CC, Everett TR, Wilkinson IB. The nitric oxide pathway and possible therapeutic options in pre-eclampsia. Br J Clin Pharmacol 2013. [accessed on 13 May 2014].
  • 16
    Makino Y, Izumi H, Makino I, Shirakawa K. The effect of nitric oxide on uterine and umbilical artery flow velocity waveform in pre-eclampsia. Eur J Obstet Gynecol Reprod Biol 1997;73(2):13943.
  • 17
    Martinez-Abundis E, Gonzalez-Ortiz M, Hernandez-Salazar F, Huerta JLMT. Sublingual isosorbide dinitrate in the acute control of hypertension in patients with severe preeclampsia. Gynecol Obstet Invest 2000;50(1):3942.
  • 18
    Manzur-Verastegui S, Mandeville PB, Gordillo-Moscoso A, 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):5805.
  • 19
    Lees C, Langford E, Brown AS, et al. The effects of S-nitrosoglutathione on platelet activation, hypertension, and uterine and fetal Doppler in severe preeclampsia. Obstet Gynecol 1996;88(1):149.
  • 20
    Everett TR, Wilkinson IB, Mahendru AA, et al. S-nitrosoglutathione improves haemodynamics in early-onset preeclampsia. Br J Clin Pharmacol 2014. [accessed on 13 May 2014].
  • 21
    Wareing M, Myers JE, O'Hara M, et al. Effects of a phosphodiesterase-5 (PDE5) inhibitor on endothelium-dependent relaxation of myometrial small arteries. Am J Obstet Gynecol 2004;190(5):128390.
  • 22
    Wareing M, Myers JE, O'Hara M, Baker PN. Sildenafil citrate (Viagra) enhances vasodilatation in fetal growth restriction. J Clin Endocrinol Metab 2005;90(5):25505.
  • 23
    Samangaya RA, Mires G, Shennan A, et al. A randomised, double-blinded, placebo-controlled study of the phosphodiesterase type 5 inhibitor sildenafil for the treatment of preeclampsia. Hypertens Pregnancy 2009;28(4):36982.
  • 24
    Samangaya RA, Wareing M, Skillern L, Baker PN. Phosphodiesterase Inhibitor Effect on Small Artery Function in Preeclampsia. Hypertens Pregnancy 2011;30(2):14452.
  • 25
    Stanley JL, Andersson IJ, Poudel R, et al. Sildenafil citrate rescues fetal growth in the catechol-O-methyl transferase knockout mouse model. Hypertension 2012;59(5):10218.
  • 26
    George EM, Palei AC, Dent EA, Granger JP. Sildenafil attenuates placental ischemia-induced hypertension. Am J Physiol Regul Integr Comp Physiol 2013;305(4):R397403.
  • 27
    von Dadelszen P, Dwinnell S, Magee LA, et al. Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118(5):6248.
  • 28
    David AL, Torondel B, Zachary I, et al. Local delivery of VEGF adenovirus to the uterine artery increases vasorelaxation and uterine blood flow in the pregnant sheep. Gene Ther 2008;15(19):134450.
  • 29
    Mehta V, Abi-Nader KN, Peebles DM, et al. Long-term increase in uterine blood flow is achieved by local overexpression of VEGF-A(165) in the uterine arteries of pregnant sheep. Gene Ther 2012;19(9):92535.
  • 30
    Wallace JM, Bourke DA, Aitken RP, et al. Relationship between nutritionally-mediated placental growth restriction and fetal growth, body composition and endocrine status during late gestation in adolescent sheep. Placenta 2000;21(1):1008.
  • 31
    Carr DJ, Aitken RP, Milne JS, et al. Fetoplacental biometry and umbilical artery Doppler velocimetry in the overnourished adolescent model of fetal growth restriction. Am J Obstet Gynecol 2012;207(2):141 e615.
  • 32
    Redmer DA, Aitken RP, Milne JS, et al. Influence of maternal nutrition on messenger RNA expression of placental angiogenic factors and their receptors at midgestation in adolescent sheep. Biol Reprod 2005;72(4):10049.
  • 33
    Carr D, Wallace JM, Aitken RP, et al. Uteroplacental adenovirus VEGF gene therapy increases fetal growth velocity in growth-restricted sheep pregnancies. Hum Gene Ther 2014;25(4):37584.
  • 34
    Carr DJ, Aitken RP, Milne JS, et al. Maternal delivery of Ad.VEGF gene therapy increases fetal growth velocity in an ovine paradigm of fetal growth restriction. Reprod Sci 2011;18(3 suppl):269A.
  • 35
    Mehta V, Boyd M, Martin J, et al. Local administration of Ad.VEGF-A165 to the uteroplacental circulation enhances fetal growth and reduces brain sparing in an FGR model of guinea pig pregnancy. Reprod Sci 2012;19(3):78A.
  • 36
    Royal College of Obstetrics and Gynaecology, Royal College of Radiologists, British Society of Interventional Radiology. Good Practice No. 6: The Role of Emergency and Elective Interventional Radiology in Postpartum Haemorrhage. London: RCOG, 2007.
  • 37
    Wang MJ, Cai WJ, Li N, et al. The hydrogen sulfide donor NaHS promotes angiogenesis in a rat model of hind limb ischemia. Antioxid Redox Signal 2010;12(9):106577.
  • 38
    Cindrova-Davies T, Herrera EA, Niu Y, et al. Reduced cystathionine gamma-lyase and increased miR-21 expression are associated with increased vascular resistance in growth-restricted pregnancies: hydrogen sulfide as a placental vasodilator. Am J Pathol 2013;182(4):144858.
  • 39
    Holwerda KM, Burke SD, Faas MM, et al. Hydrogen Sulfide Attenuates sFlt1-Induced Hypertension and Renal Damage by Upregulating Vascular Endothelial Growth Factor. J Am Soc Nephrol 2014;25(4):71725.
  • 40
    Costantine MM, Tamayo E, Lu F, et al. Using pravastatin to improve the vascular reactivity in a mouse model of soluble fms-like tyrosine kinase-1-induced preeclampsia. Obstet Gynecol 2010;116(1):11420.
  • 41
    Bauer AJ, Banek CT, Needham K, et al. Pravastatin attenuates hypertension, oxidative stress, and angiogenic imbalance in rat model of placental ischemia-induced hypertension. Hypertension 2013;61(5):110310.
  • 42
    Ofori B, Rey E, Berard A. Risk of congenital anomalies in pregnant users of statin drugs. Br J Clin Pharmacol 2007;64(4):496509.
  • 43
    Petersen EE, Mitchell AA, Carey JC, et al. Maternal exposure to statins and risk for birth defects: a case-series approach. Am J Med Genet A 2008;146A(20):27015.
  • 44
    Nanovskaya TN, Patrikeeva SL, Paul J, et al. Transplacental transfer and distribution of pravastatin. Am J Obstet Gynecol 2013;209(4):373 e15.
  • 45
    Kane AD, Herrera EA, Hansell JA, Giussani DA. Statin treatment depresses the fetal defence to acute hypoxia via increasing nitric oxide bioavailability. J Physiol 2012;590(Pt 2):32334.
  • 46
    Costantine MM, Cleary K. Pravastatin for the prevention of preeclampsia in high-risk pregnant women. Obstet Gynecol 2013;121(2 Pt 1):34953.
  • 47
    Martin JN, Jr., Perry KG, Jr., Roberts WE, et al. Plasma exchange for preeclampsia: II. Unsuccessful antepartum utilization for severe preeclampsia with or without HELLP syndrome. J Clin Apher 1994;9(3):15561.
  • 48
    Wang Y, Walli AK, Schulze A, et al. Heparin-mediated extracorporeal low density lipoprotein precipitation as a possible therapeutic approach in preeclampsia. Transfus Apher Sci 2006;35(2):10310.
  • 49
    Thadhani R, Kisner T, Hagmann H, et al. Pilot Study of Extracorporeal Removal of Soluble Fms-Like Tyrosine Kinase 1 in Preeclampsia. Circulation 2011;124(8):94050.
  • 50
    Royal College of Obstetricians and Gynaecologists. Green-top Guideline No. 7: Antenatal Corticosteroids to Reduce Neonatal Morbidity and Mortality. London: RCOG, 2010.
  • 51
    Doyle LW, Crowther CA, Middleton P, et al. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2009. URL [accessed on February 2014].
  • 52
    Australian Research Centre for Health of Women and Babies. Antenatal Magnesium Sulphate Prior to Preterm Birth for Neuroprotection of the Fetus, Infant and Child. Adelaide: ARCH, 2010.
  • 53
    American College of Obstetricians and Gynecologists Committee on Obstetric Practice Society for Maternal-Fetal Medicine. Committee Opinion No. 455: Magnesium sulfate before anticipated preterm birth for neuroprotection. Obstet Gynecol 2010;115(3):66971.
  • 54
    Altman D, Carroli G, Duley L, et al. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet 2002;359(9321):187790.
  • 55
    National Collaborating Centre for Women's and Children's Health. NICE Clinical Guideline 127. Hypertension in Pregnancy: the Management of Hypertensive Disorders During Pregnancy. London: RCOG, 2010.
  • 56
    American College of Obstetricians and Gynecologists Committee on Obstetric Practice Society for Maternal-Fetal Medicine. Committee Opinion No. 573: Magnesium sulfate use in obstetrics. Obstet Gynecol 2013;122(3):7278.
  • 57
    Royal College of Obstetricians and Gynaecologists. Green-top Guideline No. 31: The Investigation and Management of the Small-for-Gestation-Age Fetus. London: RCOG, 2014.
  • 58
    Reeves S, Bernstein I. Effects of maternal tobacco-smoke exposure on fetal growth and neonatal size. Expert Rev Obstet Gynecol 2008;3(6):71930.
  • 59
    Raisanen S, Sankilampi U, Gissler M, et al. Smoking cessation in the first trimester reduces most obstetric risks, but not the risks of major congenital anomalies and admission to neonatal care: a population-based cohort study of 1,164,953 singleton pregnancies in Finland. J Epidemiol Community Health 2014;68(2):15964.
  • 60
    McCowan LM, Dekker GA, Chan E, et al. Spontaneous preterm birth and small for gestational age infants in women who stop smoking early in pregnancy: prospective cohort study. BMJ (Clin Res Ed) 2009;338:b1081.
  • 61
    Suzuki K, Sato M, Zheng W, et al. Effect of maternal smoking cessation before and during early pregnancy on fetal and childhood growth. J Epidemiol 2014;24(1):606.
  • 62
    Robertson NJ, Faulkner S, Fleiss B, et al. Melatonin augments hypothermic neuroprotection in a perinatal asphyxia model. Brain 2013;136(Pt 1):90105.
  • 63
    Richter HG, Hansell JA, Raut S, Giussani DA. Melatonin improves placental efficiency and birth weight and increases the placental expression of antioxidant enzymes in undernourished pregnancy. J Pineal Res 2009;46(4):35764.
  • 64
    Lemley CO, Meyer AM, Camacho LE, et al. Melatonin supplementation alters uteroplacental hemodynamics and fetal development in an ovine model of intrauterine growth restriction. Am J Physiol Regul Integr Comp Physiol 2012;302(4):R45467.
  • 65
    Miller SL, Yawno T, Alers NO, et al. Antenatal antioxidant treatment with melatonin to decrease newborn neurodevelopmental deficits and brain injury caused by fetal growth restriction. J Pineal Res 2014;56(3):28394.
  • 66
    Alers NO, Jenkin G, Miller SL, Wallace EM. Antenatal melatonin as an antioxidant in human pregnancies complicated by fetal growth restriction--a phase I pilot clinical trial: study protocol. BMJ Open 2013;3(12):e004141.
  • 67
    Hobson SR, Lim R, Gardiner EE, et al. Phase I pilot clinical trial of antenatal maternally administered melatonin to decrease the level of oxidative stress in human pregnancies affected by pre-eclampsia (PAMPR): study protocol. BMJ Open 2013;3(9):e003788.
  • 68
    Bisseling TM, Maria Roes E, Raijmakers MT, et al. N-acetylcysteine restores nitric oxide-mediated effects in the fetoplacental circulation of preeclamptic patients. Am J Obstet Gynecol 2004;191(1):32833.
  • 69
    Chang EY, Barbosa E, Paintlia MK, et al. The use of N-acetylcysteine for the prevention of hypertension in the reduced uterine perfusion pressure model for preeclampsia in Sprague-Dawley rats. Am J Obstet Gynecol 2005;193(3 Pt 2):9526.
  • 70
    Roes EM, Raijmakers MT, Boo TM, et al. Oral N-acetylcysteine administration does not stabilise the process of established severe preeclampsia. Eur J Obstet Gynecol Reprod Biol 2006;127(1):617.
  • 71
    Hashimoto K, Pinkas G, Evans L, et al. Protective effect of N-acetylcysteine on liver damage during chronic intrauterine hypoxia in fetal guinea pig. Reprod Sci 2012;19(9):10019.
  • 72
    Wing DA, Powers B, Hickok D. U.S. Food and Drug Administration drug approval: slow advances in obstetric care in the United States. Obstet Gynecol 2010;115(4):82533.
  • 73
    Carter AM. Animal models of human placentation--a review. Placenta 2007;28 Suppl A:S417.
  • 74
    Carney EW, Ellis AL, Tyl RW, et al. Critical evaluation of current developmental toxicity testing strategies: a case of babies and their bathwater. Birth Defects Res B Dev Reprod Toxicol 2011;92(5):395403.
  • 75
    McCullough LB, Coverdale JH, Chervenak FA. A comprehensive ethical framework for responsibly designing and conducting pharmacologic research that involves pregnant women. Am J Obstet Gynecol 2005;193(3 Pt 2):9017.
  • 76
    Lyerly AD, Little MO, Faden RR. Pregnancy and Clinical Research. Hastings Cent Rep 2008;38(6):53.
  • 77
    Everett TR, Wilkinson IB, Lees CC. Drug development in preeclampsia: a ‘no go’ area? J Matern Fetal Neonatal 2012;25(1):502.