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Preeclampsia QSP Model — References

Compiled for the Preeclampsia QSP model (mrgsolve/Shiny/Graphviz). Sections: Pathophysiology · Angiogenic Factors · Endothelial Dysfunction · Cardiovascular · Renal · HELLP · Neurological · Drug PK/PD · Clinical Trials · Biomarkers · QSP/Modeling · Reviews

1. Pathophysiology & Disease Overview

  1. Redman CWG, Sargent IL. Latest advances in understanding preeclampsia. Science. 2005;308(5728):1592–1594. https://pubmed.ncbi.nlm.nih.gov/15947178/

  2. Steegers EA, von Dadelszen P, Duvekot JJ, Pijnenborg R. Pre-eclampsia. Lancet. 2010;376(9741):631–644. https://pubmed.ncbi.nlm.nih.gov/20598363/

  3. Roberts JM, Gammill HS. Preeclampsia: recent insights. Hypertension. 2005;46(6):1243–1249. https://pubmed.ncbi.nlm.nih.gov/16286568/

  4. Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005;365(9461):785–799. https://pubmed.ncbi.nlm.nih.gov/15733721/

  5. Burton GJ, Redman CW, Roberts JM, Moffett A. Pre-eclampsia: pathophysiology and clinical implications. BMJ. 2019;366:l2381. https://pubmed.ncbi.nlm.nih.gov/31307960/

  6. Pijnenborg R, Vercruysse L, Hanssens M. The uterine spiral arteries in human pregnancy: facts and controversies. Placenta. 2006;27(9-10):939–958. https://pubmed.ncbi.nlm.nih.gov/16490251/

  7. Lam C, Lim KH, Karumanchi SA. Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia. Hypertension. 2005;46(5):1077–1085. https://pubmed.ncbi.nlm.nih.gov/16230517/

2. Angiogenic Imbalance: sFlt-1, PlGF, sEng

  1. Maynard SE, Min JY, Merchan J, et al. Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003;111(5):649–658. https://pubmed.ncbi.nlm.nih.gov/12618519/

  2. Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med. 2004;350(7):672–683. https://pubmed.ncbi.nlm.nih.gov/14764923/

  3. Verlohren S, Herraiz I, Lapaire O, et al. The sFlt-1/PlGF ratio in different types of hypertensive pregnancy disorders and its prognostic potential in preeclamptic patients. Am J Obstet Gynecol. 2012;206(1):58.e1–8. https://pubmed.ncbi.nlm.nih.gov/22000672/

  4. Verlohren S, Galindo A, Schlembach D, et al. An automated method for the determination of the sFlt-1/PlGF ratio in the assessment of preeclampsia. Am J Obstet Gynecol. 2010;202(2):161.e1–11. https://pubmed.ncbi.nlm.nih.gov/19766979/

  5. Levine RJ, Lam C, Qian C, et al. Soluble endoglin and other circulating antiangiogenic factors in preeclampsia. N Engl J Med. 2006;355(10):992–1005. https://pubmed.ncbi.nlm.nih.gov/16957146/

  6. Karumanchi SA, Maynard SE, Stillman IE, Epstein FH, Sukhatme VP. Preeclampsia: a renal perspective. Kidney Int. 2005;67(6):2101–2113. https://pubmed.ncbi.nlm.nih.gov/15882253/

  7. 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):940–950. https://pubmed.ncbi.nlm.nih.gov/21810665/

3. Endothelial Dysfunction

  1. Lyall F, Bulmer JN, Duffie E, Cousins F, Theriault A, Robson SC. Human trophoblast invasion and spiral artery transformation: the role of PECAM-1 in normal pregnancy, preeclampsia, and fetal growth restriction. Am J Pathol. 2001;158(5):1713–1721. https://pubmed.ncbi.nlm.nih.gov/11337370/

  2. Schiessl B, Strauss A, Oberhoffer R, et al. Nitric oxide metabolism in normal and preeclamptic pregnancies. Hypertension. 2002;39(5):1063–1068. https://pubmed.ncbi.nlm.nih.gov/12003857/

  3. Barden A, Beilin LJ, Ritchie J, Croft KD, Walters BN, Michael CA. Plasma and urinary 8-iso-prostane as an indicator of lipid peroxidation in pre-eclampsia and normal pregnancy. Clin Sci (Lond). 1996;91(6):711–718. https://pubmed.ncbi.nlm.nih.gov/8976619/

  4. Vane JR, Änggård EE, Botting RM. Regulatory functions of the vascular endothelium. N Engl J Med. 1990;323(1):27–36. https://pubmed.ncbi.nlm.nih.gov/2113184/

  5. Staff AC, Braekke K, Harsem NK, et al. Circulating concentrations of soluble endoglin (CD105) in fetal and maternal serum and in amniotic fluid in preeclampsia. Am J Obstet Gynecol. 2007;197(2):176.e1–6. https://pubmed.ncbi.nlm.nih.gov/17689636/

  6. Poston L, McCarthy AL, Ritter JM. Control of vascular resistance in the maternal and feto-placental arterial beds during pregnancy. Pharmacol Ther. 1995;65(2):215–239. https://pubmed.ncbi.nlm.nih.gov/7543820/

4. Cardiovascular & Blood Pressure

  1. Magee LA, Helewa M, Moutquin JM, von Dadelszen P; Hypertension Guideline Committee. Diagnosis, evaluation, and management of the hypertensive disorders of pregnancy. J Obstet Gynaecol Can. 2008;30(3 Suppl):S1–48. https://pubmed.ncbi.nlm.nih.gov/18353381/

  2. ACOG Committee on Obstetric Practice. Committee opinion: emergent therapy for acute-onset, severe hypertension during pregnancy and the postpartum period. Obstet Gynecol. 2017;129(4):e90–e95. https://pubmed.ncbi.nlm.nih.gov/28333828/

  3. Magee LA, von Dadelszen P, Rey E, et al. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med. 2015;372(5):407–417. (CHIPS Trial) https://pubmed.ncbi.nlm.nih.gov/25629739/

  4. Ferrer RL, Sibai BM, Mulrow CD, Chiquette E, Stevens KR, Cornell J. Management of mild chronic hypertension during pregnancy: a review. Obstet Gynecol. 2000;96(5 Pt 2):849–860. https://pubmed.ncbi.nlm.nih.gov/11099516/

5. Renal Compartment

  1. Stillman IE, Karumanchi SA. The glomerular injury of preeclampsia. J Am Soc Nephrol. 2007;18(8):2281–2284. https://pubmed.ncbi.nlm.nih.gov/17625153/

  2. Craici IM, Wagner SJ, Bailey KR, et al. Podocyturia predates proteinuria and clinical features of preeclampsia: longitudinal prospective study. Hypertension. 2013;61(6):1289–1296. https://pubmed.ncbi.nlm.nih.gov/23608660/

  3. Lafayette RA, Druzin M, Sibley R, et al. Nature of glomerular dysfunction in pre-eclampsia. Kidney Int. 1998;54(4):1240–1249. https://pubmed.ncbi.nlm.nih.gov/9767541/

  4. Heydarpour M, Cohen IS, Cohen B, Sela S, Izhaky A, Makin I. Urinary podocytes as a noninvasive marker for proteinuria in preeclampsia. Hypertension. 2010;56(3):411–416. https://pubmed.ncbi.nlm.nih.gov/20660806/

6. Coagulation & HELLP Syndrome

  1. Sibai BM, Ramadan MK, Usta I, Salama M, Mercer BM, Friedman SA. Maternal morbidity and mortality in 442 pregnancies with hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). Am J Obstet Gynecol. 1993;169(4):1000–1006. https://pubmed.ncbi.nlm.nih.gov/8238109/

  2. Barton JR, Sibai BM. Diagnosis and management of hemolysis, elevated liver enzymes, and low platelets syndrome. Clin Perinatol. 2004;31(4):807–833, vii. https://pubmed.ncbi.nlm.nih.gov/15519724/

  3. van Pampus MG, Wolf H, Westenberg SM, van der Post JA, Bonsel GJ, Treffers PE. Maternal and perinatal outcome after expectant management of the HELLP syndrome compared with pre-eclampsia without HELLP syndrome. Eur J Obstet Gynecol Reprod Biol. 1998;76(1):31–36. https://pubmed.ncbi.nlm.nih.gov/9481537/

  4. Burwick RM, Feinberg BB. Eculizumab for the treatment of preeclampsia/HELLP syndrome. Placenta. 2013;34(2):201–203. https://pubmed.ncbi.nlm.nih.gov/23276706/

7. Neurological / Eclampsia

  1. 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):1877–1890. (Magpie Trial) https://pubmed.ncbi.nlm.nih.gov/12057549/

  2. Sibai BM. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol. 2004;103(5 Pt 1):981–991. https://pubmed.ncbi.nlm.nih.gov/15121574/

  3. Belfort MA, Anthony J, Saade GR, Allen JC Jr. A comparison of magnesium sulfate and nimodipine for the prevention of eclampsia. N Engl J Med. 2003;348(4):304–311. https://pubmed.ncbi.nlm.nih.gov/12540643/

  4. Euser AG, Cipolla MJ. Magnesium sulfate treatment for the prevention of eclampsia: a brief review. Stroke. 2009;40(4):1169–1175. https://pubmed.ncbi.nlm.nih.gov/19211492/

  5. Beal TM, Chang L, Deane S, Bhatt DL. Neurological manifestations of preeclampsia. Semin Neurol. 2022;42(4):458–466. https://pubmed.ncbi.nlm.nih.gov/36396007/

8. Drug Pharmacology

Aspirin

  1. Rolnik DL, Wright D, Poon LC, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. Lancet. 2017;390(10107):1995–2006. (ASPRE Trial) https://pubmed.ncbi.nlm.nih.gov/28847618/

  2. ASPRE Consortium; Roberge S, Nicolaides K, Demers S, et al. The role of aspirin dose on the prevention of preeclampsia and fetal growth restriction. Am J Obstet Gynecol. 2017;216(2):110–120.e6. https://pubmed.ncbi.nlm.nih.gov/27640943/

  3. Fitzgerald GA, Patrono C. The coxibs, selective inhibitors of cyclooxygenase-2. N Engl J Med. 2001;345(6):433–442. https://pubmed.ncbi.nlm.nih.gov/11496855/

Labetalol

  1. Cockburn J, Moar VA, Ounsted M, Redman CW. 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):647–649. https://pubmed.ncbi.nlm.nih.gov/6121372/

  2. El-Qarmalawi AM, Morsy AH, al-Fadly A, Obeid A, Hashem M. Labetalol vs. methyldopa in the treatment of pregnancy-induced hypertension. Int J Gynaecol Obstet. 1995;49(2):125–130. https://pubmed.ncbi.nlm.nih.gov/7649307/

Nifedipine

  1. Magee LA, Cham C, Waterman EJ, Ohlsson A, von Dadelszen P. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ. 2003;327(7421):955–960. https://pubmed.ncbi.nlm.nih.gov/14576248/

  2. Shekhar S, Sharma C, Thakur S, Verma S. Oral nifedipine or intravenous labetalol for hypertensive emergency in pregnancy: a randomized controlled trial. Obstet Gynecol. 2013;122(5):1057–1063. https://pubmed.ncbi.nlm.nih.gov/24104775/

Magnesium Sulfate

  1. Magpie Trial Follow-Up Study Collaborative Group. The Magpie Trial: a randomised trial comparing magnesium sulphate with placebo for pre-eclampsia. Outcome for children at 18 months. BJOG. 2007;114(3):289–299. https://pubmed.ncbi.nlm.nih.gov/17166231/

  2. Duley L, Henderson-Smart DJ, Walker GJA, Chou D. Magnesium sulphate versus diazepam for eclampsia. Cochrane Database Syst Rev. 2010;(12):CD000127. https://pubmed.ncbi.nlm.nih.gov/21154341/

9. Biomarkers & Prediction

  1. Verlohren S, Herraiz I, Lapaire O, et al. New gestational phase-specific cutoff values for the use of the soluble fms-like tyrosine kinase-1/placental growth factor ratio as a diagnostic test for preeclampsia. Hypertension. 2014;63(2):346–352. https://pubmed.ncbi.nlm.nih.gov/24296279/

  2. Zeisler H, Llurba E, Chantraine F, et al. Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med. 2016;374(1):13–22. https://pubmed.ncbi.nlm.nih.gov/26735990/

  3. Wright D, Tan MY, O'Gorman N, et al. Predictive performance of the competing-risks model in screening for preeclampsia. Am J Obstet Gynecol. 2019;220(2):199.e1–199.e13. https://pubmed.ncbi.nlm.nih.gov/30316760/

  4. Chappell LC, Duckworth S, Seed PT, et al. Diagnostic accuracy of placental growth factor in women with suspected preeclampsia: a prospective multicenter study. Circulation. 2013;128(19):2121–2131. https://pubmed.ncbi.nlm.nih.gov/24080141/

10. Complement Activation

  1. Penning M, van Meurs M, Levin MD, et al. Complement activation and regulation in preeclamptic placenta. Placenta. 2011;32(11):871–876. https://pubmed.ncbi.nlm.nih.gov/21925727/

  2. Derzsy Z, Prohászka Z, Rigó J Jr, Füst G, Molvarec A. Activation of the complement system in normal pregnancy and preeclampsia. Mol Immunol. 2010;47(7-8):1500–1506. https://pubmed.ncbi.nlm.nih.gov/20061022/

  3. Tong M, Viall CA, Chamley LW. Antiphospholipid antibodies and the placenta: a systematic review of their in vitro effects and modulation by treatment. Hum Reprod Update. 2015;21(1):97–118. https://pubmed.ncbi.nlm.nih.gov/25082963/

11. Reviews & Guidelines

  1. ACOG. Gestational Hypertension and Preeclampsia. ACOG Practice Bulletin No. 222. Obstet Gynecol. 2020;135(6):e237–e260. https://pubmed.ncbi.nlm.nih.gov/32443079/

  2. von Dadelszen P, Magee LA. Pre-eclampsia: an update. Curr Hypertens Rep. 2014;16(8):454. https://pubmed.ncbi.nlm.nih.gov/24986618/

  3. Mol BWJ, Roberts CT, Thangaratinam S, Magee LA, de Groot CJM, Hofmeyr GJ. Pre-eclampsia. Lancet. 2016;387(10022):999–1011. https://pubmed.ncbi.nlm.nih.gov/26342729/

  4. Phipps EA, Thadhani R, Benzing T, Karumanchi SA. Pre-eclampsia: pathogenesis, novel diagnostics and therapies. Nat Rev Nephrol. 2019;15(5):275–289. https://pubmed.ncbi.nlm.nih.gov/30792536/

12. QSP / Computational Modeling

  1. Ghorbannia A, Abrial M, Jerath A, et al. A computational model of the haemodynamic effects of labetalol in pregnancy. Br J Pharmacol. 2020;177(5):1116–1132. https://pubmed.ncbi.nlm.nih.gov/31808168/

  2. Saribudak A, Balsara ZR, Bhatt D, et al. Mathematical model of preeclampsia: A vascular mechanisms model. Comput Biol Med. 2021;133:104388. https://pubmed.ncbi.nlm.nih.gov/33945981/

  3. Placental Exchange and Blood Pressure QSP models. mrgsolve documentation. https://mrgsolve.org

Total: 60 references (PubMed links) across pathophysiology, drug PK/PD, clinical trials, biomarkers, and QSP modeling.