Generic placeholder image

Current Women`s Health Reviews


ISSN (Print): 1573-4048
ISSN (Online): 1875-6581

Review Article

Predictive Biochemical Factors for Pre-eclampsia in Early Pregnancy

Author(s): Lorna Muscat Baron and Byron Baron*

Volume 19, Issue 1, 2023

Published on: 01 April, 2022

Article ID: e270122200581 Pages: 16

DOI: 10.2174/1573404818666220127112925

Price: $65


Pre-eclampsia (PE) is one of the major pregnancy complications, affecting up to 10 % of all pregnancies in some regions of the world. The clinical diagnosis, characterised by hypertension and proteinuria often late during pregnancy, with the added inability to treat (other than delivery), can lead to significant morbidity and mortality in both mother and unborn foetus. Moreover, as yet, only low dose aspirin administration is accepted as a preventive measure for PE. This puts more pressure to identify diagnostic and prognostic biomarkers of PE from blood or urine for the non-invasive screening of pregnant women before pregnancy becomes complicated. Over the years, a number of DNA and protein molecules, such as cell-free DNA, VEGF, sFLT1, PlGF, PP-13, ADMA, and several other biomarkers, have been linked to specific pathophysiological observations and proposed as predictive markers for PE. However, their reliability and reproducibility have been put to the test by numerous studies. The aim of this review is to cover the key clinical and biochemical features of pregnancies complicated by PE and evaluate the robustness of data gathered from various studies in order to better understand the link between the proposed biomarkers and the development of PE so as to better quantify their relevance in diagnostic or prognostic applications. The overall goal is to use such biomarkers for earlier detection, better molecular monitoring, and, where possible, lessening of symptoms, hopefully leading to a reduction in the yearly PE-related deaths worldwide.

Keywords: Pre-eclampsia, pregnancy complications, endothelial dysfunction, biomarkers, diagnosis, prognosis.

Graphical Abstract
Boeldt DS, Bird IM. Vascular adaptation in pregnancy and endothelial dysfunction in preeclampsia. J Endocrinol 2017; 232(1): R27-44.
[] [PMID: 27729465]
Grill S, Rusterholz C, Zanetti-Dällenbach R, et al. Potential markers of preeclampsia-a review. Reprod Biol Endocrinol 2009; 7(1): 70.
[] [PMID: 19602262]
Portelli M, Baron B. Clinical presentation of preeclampsia and the diagnostic value of proteins and their methylation products as biomarkers in pregnant women with preeclampsia and their newborns. J Pregnancy 2018; 2018: 2632637.
[] [PMID: 30050697]
Program, National High Blood Pressure Education.; Report of the national high blood pressure education program working group on high blood pressure in pregnancy. Am J Obstet Gynecol 2000; 183(1): S1-S22.
[] [PMID: 10920346]
ACOG Committee on Practice Bulletins--Obstetrics. ACOG practice bulletin. Diagnosis and management of preeclampsia and eclampsia. Number 33, January 2002. Obstet Gynecol 2002; 99(1): 159-67.
[PMID: 16175681]
Nelson DB, Ziadie MS, McIntire DD, Rogers BB, Leveno KJ. Placental pathology suggesting that preeclampsia is more than one disease. Obstet Gynecol 2014; 210(1): 66.
Wagner LK. Diagnosis and management of preeclampsia. Am Fam Physician 2004; 70(12): 2317-24.
[PMID: 15617295]
Burton GJ, Fowden AL. The placenta: A multifaceted, transient organ. Philos Trans R Soc Lond B Biol Sci 2015; 370(1663): 20140066.
[] [PMID: 25602070]
Warrington JP, George EM, Palei AC, Spradley FT, Granger JP. Recent advances in the understanding of the pathophysiology of preeclampsia. Hypertension 2013; 62(4): 666-73.
[] [PMID: 23897068]
Portelli M, Baron B. Biochemical dysregulation of pre-eclampsia and gestational diabetes mellitus. In: Sharma N, Ed. Prediction of Maternal and Fetal Syndrome of Preeclampsia. London, UK: IntechOpen 2019.
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): 649-58.
[] [PMID: 12618519]
Venkatesha S, Toporsian M, Lam C, et al. Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat Med 2006; 12(6): 642-9.
[] [PMID: 16751767]
Haram K, Svendsen E, Abildgaard U. The HELLP syndrome: clinical issues and management. A review. BMC Pregnancy Childbirth 2009; 9(1): 8.
[] [PMID: 19245695]
Thadhani R, Mutter WP, Wolf M, et al. First trimester placental growth factor and soluble fms-like tyrosine kinase 1 and risk for preeclampsia. J Clin Endocrinol Metab 2004; 89(2): 770-5.
[] [PMID: 14764795]
Gai W, Sun K. Epigenetic biomarkers in cell-free DNA and applications in liquid biopsy. Genes (Basel) 2019; 10(1): 32.
[] [PMID: 30634483]
Kim SY, Kim HJ, Park SY, Han YJ, Choi JS, Ryu HM. Early Prediction of Hypertensive Disorders of Pregnancy Using Cell-Free Fetal DNA, Cell-Free Total DNA, and Biochemical Markers. Fetal Diagn Ther 2016; 40(4): 255-62.
[] [PMID: 26998901]
Kolarova TR, Gammill HS, Nelson JL, Lockwood CM, Shree R. At Preeclampsia Diagnosis, Total Cell-Free DNA Concentration is Elevated and Correlates With Disease Severity. J Am Heart Assoc 2021; 10(15): e021477.
[] [PMID: 34310191]
Silver RM, Myatt L, Hauth JC, et al. Cell-free total and fetal DNA in first trimester maternal serum and subsequent development of preeclampsia. Am J Perinatol 2017; 34(2): 191-8.
[PMID: 27398706]
Chua S, Wilkins T, Sargent I, Redman C. Trophoblast deportation in pre-eclamptic pregnancy. Br J Obstet Gynaecol 1991; 98(10): 973-9.
[] [PMID: 1751443]
DiFederico E, Genbacev O, Fisher SJ. Preeclampsia is associated with widespread apoptosis of placental cytotrophoblasts within the uterine wall. Am J Pathol 1999; 155(1): 293-301.
[] [PMID: 10393861]
Lun FM, Chiu RW, Chan KC, Leung TY, Lau TK, Lo YM. Microfluidics digital PCR reveals a higher than expected fraction of fetal DNA in maternal plasma. Clin Chem 2008; 54(10): 1664-72.
[] [PMID: 18703764]
Lo YM, Chan KC, Sun H, et al. Maternal plasma DNA sequencing reveals the genome-wide genetic and mutational profile of the fetus. Sci Transl Med 2010; 2(61): 61ra91.
[] [PMID: 21148127]
Leung TN, Zhang J, Lau TK, Chan LY, Lo YM. Increased maternal plasma fetal DNA concentrations in women who eventually develop preeclampsia. Clin Chem 2001; 47(1): 137-9.
[] [PMID: 11148193]
Holzgreve W, Ghezzi F, Di Naro E, Gänshirt D, Maymon E, Hahn S. Disturbed feto-maternal cell traffic in preeclampsia. Obstet Gynecol 1998; 91(5 Pt 1): 669-72.
[PMID: 9572208]
Al-Mufti R, Hambley H, Albaiges G, Lees C, Nicolaides KH. Increased fetal erythroblasts in women who subsequently develop pre-eclampsia. Hum Reprod 2000; 15(7): 1624-8.
[] [PMID: 10875878]
Kilian O, Alt V, Heiss C, et al. New blood vessel formation and expression of VEGF receptors after implantation of platelet growth factor-enriched biodegradable nanocrystalline hydroxyapatite. Growth Factors 2005; 23(2): 125-33.
[] [PMID: 16019434]
Demir R, Kayisli UA, Seval Y, et al. Sequential expression of VEGF and its receptors in human placental villi during very early pregnancy: Differences between placental vasculogenesis and angiogenesis. Placenta 2004; 25(6): 560-72.
[] [PMID: 15135240]
Kurtoglu E, Avci B, Kokcu A, et al. Serum VEGF and PGF may be significant markers in prediction of severity of preeclampsia. J Matern Fetal Neonatal Med 2016; 29(12): 1987-92.
[] [PMID: 26333278]
Gaber K, Hamdy E, Hanafy A. Soluble endoglin as a new marker for prediction of pre-eclampsia in early pregnancy. Middle East Fertil Soc J 2010; 15(1): 42-6.
Bersinger NA, Ødegård RA. Second- and third-trimester serum levels of placental proteins in preeclampsia and small-for-gestational age pregnancies. Acta Obstet Gynecol Scand 2004; 83(1): 37-45.
[] [PMID: 14678084]
Noorbakhsh M, Kianpour M, Nematbakhsh M. Serum levels of asymmetric dimethylarginine, vascular endothelial growth factor, and nitric oxide metabolite levels in preeclampsia patients. ISRN Obstet Gynecol 2013; 2013: 104213.
Wu FT, Stefanini MO, Mac Gabhann F, Kontos CD, Annex BH, Popel AS. VEGF and soluble VEGF receptor-1 (sFlt-1) distributions in peripheral arterial disease: An in silico model. Am J Physiol Heart Circ Physiol 2010; 298(6): H2174-91.
[] [PMID: 20382861]
Eleuterio NM, Palei AC, Rangel Machado JS, Tanus-Santos JE, Cavalli RC, Sandrim VC. Correlations between circulating levels of adipokines and anti-angiogenic factors in women with BMI <30 and a late-onset preeclampsia. Hypertens Pregnancy 2014; 33(1): 72-80.
[] [PMID: 24380505]
Kim YN, Lee DS, Jeong DH, Sung MS, Kim KT. The relationship of the level of circulating antiangiogenic factors to the clinical manifestations of preeclampsia. Prenat Diagn 2009; 29(5): 464-70.
[] [PMID: 19242927]
Bian Z, Shixia C, Duan T. First-trimester maternal serum levels of sFLT1, PGF and ADMA predict preeclampsia. PLoS One 2015; 10(4): e0124684.
[] [PMID: 25906026]
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.
[] [PMID: 16957146]
Lai J, Garcia-Tizon Larroca S, Peeva G, Poon LC, Wright D, Nicolaides KH. Competing risks model in screening for preeclampsia by serum placental growth factor and soluble FMS-like tyrosine kinase-1 at 30-33 weeks’ gestation. Fetal Diagn Ther 2014; 35(4): 240-8.
[] [PMID: 24853452]
Tsiakkas A, Saiid Y, Wright A, Wright D, Nicolaides KH. Competing risks model in screening for preeclampsia by maternal factors and biomarkers at 30–34 weeks’ gestation. Obstet Gynecol 2016; 215(1): 87.
Shokry M, Bedaiwy MA, Fathalla MM, Alsemary A, Elwakil S, Murphy A. Maternal serum placental growth factor and soluble fms-like tyrosine kinase 1 as early predictors of preeclampsia. Acta Obstet Gynecol Scand 2010; 89(1): 143-6.
[] [PMID: 20021269]
Widmer M, Cuesta C, Khan KS, et al. Accuracy of angiogenic biomarkers at 20weeks’ gestation in predicting the risk of pre-eclampsia: A WHO multicentre study. Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 2015; 5(4): 330-8.
[] [PMID: 26597750]
Tarallo V, Tudisco L, De Falco S. A placenta growth factor 2 variant acts as dominant negative of vascular endothelial growth factor A by heterodimerization mechanism. Am J Cancer Res 2011; 1(2): 265-74.
[PMID: 21969185]
Levine RJ, Maynard SE, Qian C, et al. Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004; 350(7): 672-83.
[] [PMID: 14764923]
Ghosh SK, Raheja S, Tuli A, Raghunandan C, Agarwal S. Serum PLGF as a potential biomarker for predicting the onset of preeclampsia. Arch Gynecol Obstet 2012; 285(2): 417-22.
[] [PMID: 21735190]
Wortelboer EJ, Koster MP, Cuckle HS, Stoutenbeek PH, Schielen PC, Visser GH. First-trimester placental protein 13 and placental growth factor: Markers for identification of women destined to develop early-onset pre-eclampsia. BJOG 2010; 117(11): 1384-9.
[] [PMID: 20840693]
Romero R, Nien JK, Espinoza J, et al. A longitudinal study of angiogenic (placental growth factor) and anti-angiogenic (soluble endoglin and soluble vascular endothelial growth factor receptor-1) factors in normal pregnancy and patients destined to develop preeclampsia and deliver a small for gestational age neonate. J Matern Fetal Neonatal Med 2008; 21(1): 9-23.
[] [PMID: 18175241]
Karumanchi SA. Angiogenic factors in preeclampsia: From diagnosis to therapy. Hypertension 2016; 67(6): 1072-9.
[] [PMID: 27067718]
Powers RW, Jeyabalan A, Clifton RG, et al. Soluble fms-Like tyrosine kinase 1 (sFlt1), endoglin and placental growth factor (Pl-GF) in preeclampsia among high risk pregnancies. PLoS One 2010; 5(10): e13263.
[] [PMID: 20948996]
Rana S, Powe CE, Salahuddin S, et al. Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation 2012; 125(7): 911-9.
[] [PMID: 22261192]
Baltajian K, Bajracharya S, Salahuddin S, et al. Sequential plasma angiogenic factors levels in women with suspected preeclampsia. Obstet Gynecol 2016; 215(1): 89.
Duff SE, Li C, Garland JM, Kumar S. CD105 is important for angiogenesis: Evidence and potential applications. FASEB J 2003; 17(9): 984-92.
[] [PMID: 12773481]
Nikuei P, Rajaei M, Malekzadeh K, Nejatizadeh A, Mohseni F, AtashAbParvar A. accuracy of soluble endoglin for diagnosis of preeclampsia and its severity. Iran Biomed J 2017; 21(5): 312-30.
[] [PMID: 28558439]
Wu CC, Bohr DF. Role of endothelium in the response to endothelin in hypertension. Hypertension 1990; 16(6): 677-81.
[] [PMID: 2246034]
Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 1988; 332(6163): 411-5.
[] [PMID: 2451132]
Haynes WG, Webb DJ. The endothelin family of peptides: Local hormones with diverse roles in health and disease? Clin Sci (Lond) 1993; 84(5): 485-500.
Hosoda K, Nakao K, Hiroshi-Arai , et al. Cloning and expression of human endothelin-1 receptor cDNA. FEBS Lett 1991; 287(1-2): 23-6.
[] [PMID: 1652463]
George EM, Palei AC, Granger JP. Endothelin as a final common pathway in the pathophysiology of preeclampsia: Therapeutic implications. Curr Opin Nephrol Hypertens 2012; 21(2): 157-62.
[] [PMID: 22257796]
Alexander BT, Rinewalt AN, Cockrell KL, Massey MB, Bennett WA, Granger JP. Endothelin type a receptor blockade attenuates the hypertension in response to chronic reductions in uterine perfusion pressure. Hypertension 2001; 37(2 Pt 2): 485-9.
[] [PMID: 11230323]
Nishikawa S, Miyamoto A, Yamamoto H, Ohshika H, Kudo R. The relationship between serum nitrate and endothelin-1 concentrations in preeclampsia. Life Sci 2000; 67(12): 1447-54.
[] [PMID: 10983841]
Maltaris T, Scalera F, Schlembach D, et al. Increased uterine arterial pressure and contractility of perfused swine uterus after treatment with serum from pre-eclamptic women and endothelin-1. Clin Sci (Lond) 2005; 109(2): 209-15.
Baksu B, Davas I, Baksu A, Akyol A, Gulbaba G. Plasma nitric oxide, endothelin-1 and urinary nitric oxide and cyclic guanosine monophosphate levels in hypertensive pregnant women. Int J Gynaecol Obstet 2005; 90(2): 112-7.
[] [PMID: 16005006]
Di Iorio R, Marinoni E, Letizia C, Alò P, Villaccio B, Cosmi EV. Adrenomedullin, a new vasoactive peptide, is increased in preeclampsia. Hypertension 1998; 32(4): 758-63.
[] [PMID: 9774376]
Senna AA, Zedan M, El-Salam GE, El-Mashad AI. Study of plasma adrenomedullin level in normal pregnancy and preclampsia. Medscape J Med 2008; 10(2): 29.
[PMID: 18382699]
Kraus D, Feng L, Heine RP, Brown H, Murtha A, Grotegut C. 43: Smoking and preeclamspia protection: Cigarette smoke increases placental adrenomedullin expression and improves trophoblast invasion via the adrenomedullin pathway. Am J Obstet Gynecol 2013; 208(1): S26.
Lawrence JB, Oxvig C, Overgaard MT, et al. The Insulin-like Growth Factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc Natl Acad Sci USA 1999; 96(6): 3149-53.
[] [PMID: 10077652]
Kalousova M, Muravska A, Zima T. Pregnancy-associated plasma protein A (PAPP-A) and preeclampsia. Advances in clinical chemistry. Elsevier 2014; pp. 169-209.
Akolekar R, Etchegaray A, Zhou Y, Maiz N, Nicolaides KH. Maternal serum activin a at 11-13 weeks of gestation in hypertensive disorders of pregnancy. Fetal Diagn Ther 2009; 25(3): 320-7.
[] [PMID: 19776595]
Luewan S, Teja-Intr M, Sirichotiyakul S, Tongsong T. Low maternal serum pregnancy-associated plasma protein-A as a risk factor of preeclampsia. Singapore Med J 2018; 59(1): 55-9.
[] [PMID: 28451695]
Saxena AR, Seely EW, Rich-Edwards JW, Wilkins-Haug LE, Karumanchi SA, McElrath TF. First trimester PAPP-A levels correlate with sFlt-1 levels longitudinally in pregnant women with and without preeclampsia. BMC Pregnancy Childbirth 2013; 13(1): 85.
[] [PMID: 23557166]
Moslemi Zadeh N, Naghshvar F, Peyvandi S, Gheshlaghi P. PP13 and PAPP-A in the first and second trimesters: Predictive factors for preeclampsia? ISRN Obstetrics and Gynecology 2012; 263871.
Nanda S, Yu CK, Giurcaneanu L, Akolekar R, Nicolaides KH. Maternal serum adiponectin at 11-13 weeks of gestation in preeclampsia. Fetal Diagn Ther 2011; 29(3): 208-15.
[] [PMID: 21266793]
Odibo AO, Zhong Y, Goetzinger KR, et al. First-trimester placental protein 13, PAPP-A, uterine artery Doppler and maternal characteristics in the prediction of pre-eclampsia. Placenta 2011; 32(8): 598-602.
[] [PMID: 21652068]
Atis A, Aydin Y, Basol E, Kaleli S, Turgay F, Goker N. PAPP-A levels of late pregnancy in preeclampsia and HELLP syndrome. Arch Gynecol Obstet 2012; 285(1): 45-9.
[] [PMID: 21533533]
Than NG, Pick E, Bellyei S, et al. Functional analyses of placental protein 13/galectin-13. Eur J Biochem 2004; 271(6): 1065-78.
[] [PMID: 15009185]
Hutter S, Knabl J, Andergassen U, et al. Placental expression patterns of galectin-1, galectin-2, galectin-3 and galectin-13 in cases of intrauterine growth restriction (IUGR). Int J Mol Sci 2016; 17(4): 523.
[] [PMID: 27070577]
Sahraravand M, Järvelä IY, Laitinen P, Tekay AH, Ryynänen M. The secretion of PAPP-A, ADAM12, and PP13 correlates with the size of the placenta for the first month of pregnancy. Placenta 2011; 32(12): 999-1003.
[] [PMID: 22015022]
Chafetz I, Kuhnreich I, Sammar M, et al. First-trimester placental protein 13 screening for preeclampsia and intrauterine growth restriction. Obstet Gynecol 2007; 197(1): 35.
De Villiers CP, Hedley PL, Placing S, et al. Placental Protein-13 (PP13) in combination with PAPP-A and free leptin index (fLI) in first trimester maternal serum screening for severe and early preeclampsia. Clin Chem Lab Med 2017; 56(1): 65-74.
[] [PMID: 28704180]
De Muro P, Capobianco G, Lepedda AJ, et al. Plasma PP13 and urinary GAGs/PGs as early markers of pre-eclampsia. Arch Gynecol Obstet 2016; 294(5): 959-65.
[] [PMID: 27161490]
Burger O, Pick E, Zwickel J, et al. Placental protein 13 (PP-13): Effects on cultured trophoblasts, and its detection in human body fluids in normal and pathological pregnancies. Placenta 2004; 25(7): 608-22.
[] [PMID: 15193867]
Ali FT, Ibrahim AM, Hassan NS, Soliman RM. Placental protein 13, galectin 14 and pentraxin 3 for prediction of pre-eclampsia in Egyptian patients. Int J Med Sci Public Health 2018; 7(6): 427-34.
Gadde R, Dayanand C, Sheela SR. Placental protein 13 and asymmetric dimethyl arginine for early assessment of preeclampsia. Biomed Res 2019; 30(2): 319-24.
Spencer K, Cowans NJ, Chefetz I, Tal J, Meiri H. First-trimester maternal serum PP-13, PAPP-A and second-trimester uterine artery Doppler pulsatility index as markers of pre-eclampsia. Ultrasound Obstet Gynecol 2007; 29(2): 128-34.
[] [PMID: 17149788]
Akolekar R, Syngelaki A, Beta J, Kocylowski R, Nicolaides KH. Maternal serum placental protein 13 at 11-13 weeks of gestation in preeclampsia. Prenat Diagn 2009; 29(12): 1103-8.
[] [PMID: 19777530]
Namwanje M, Brown CW. Activins and Inhibins: Roles in Development, Physiology, and Disease. Cold Spring Harb Perspect Biol 2016; 8(7): a021881.
[] [PMID: 27328872]
Birdsall M, Ledger W, Groome N, Abdalla H, Muttukrishna S. Inhibin A and activin A in the first trimester of human pregnancy. J Clin Endocrinol Metab 1997; 82(5): 1557-60.
[] [PMID: 9141549]
Yu J, Shixia CZ, Wu Y, Duan T. Inhibin A, activin A, placental growth factor and uterine artery Doppler pulsatility index in the prediction of pre-eclampsia. Ultrasound Obstet Gynecol 2011; 37(5): 528-33.
[] [PMID: 20737451]
Yu L, Li D, Liao QP, et al. High levels of activin A detected in preeclamptic placenta induce trophoblast cell apoptosis by promoting nodal signaling. J Clin Endocrinol Metab 2012; 97(8): E1370-9.
[] [PMID: 22685232]
Lai J, Pinas A, Syngelaki A, Poon LC, Nicolaides KH. Maternal serum activin-A at 30-33 weeks in the prediction of preeclampsia. J Matern Fetal Neonatal Med 2013; 26(8): 733-7.
[] [PMID: 23205865]
Ree PH, Hahn WB, Chang SW, et al. Early detection of preeclampsia using inhibin a and other second-trimester serum markers. Fetal Diagn Ther 2011; 29(4): 280-6.
[] [PMID: 21252475]
Akolekar R, Minekawa R, Veduta A, Romero XC, Nicolaides KH. Maternal plasma inhibin A at 11-13 weeks of gestation in hypertensive disorders of pregnancy. Prenat Diagn 2009; 29(8): 753-60.
[] [PMID: 19412915]
Phupong V, Paiwattananupant K, Honsawek S. Inhibin A levels and severity of preeclampsia. Arch Gynecol Obstet 2009; 280(2): 183-6.
[] [PMID: 19107499]
Shen Z, Cai LY, Suprapto IS, Shenoy P, Zhou X. Placental and maternal serum inhibin A in patients with preeclampsia and small- for-gestational-age. J Obstet Gynaecol Res 2011; 37(10): 1290-6.
[] [PMID: 21535305]
Miehle K, Stepan H, Fasshauer M. Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia. Clin Endocrinol (Oxf) 2012; 76(1): 2-11.
Eleuterio NM, Palei AC, Rangel Machado JS, Tanus-Santos JE, Cavalli RC, Sandrim VC. Positive correlations between circulating adiponectin and MMP2 in preeclampsia pregnant. Pregnancy Hypertens 2015; 5(2): 205-8.
[] [PMID: 25943646]
Eleuterio NM, Palei AC, Rangel Machado JS, Tanus-Santos JE, Cavalli RC, Sandrim VC. Relationship between adiponectin and nitrite in healthy and preeclampsia pregnancies. Clin Chim Acta 2013; 423: 112-5.
[] [PMID: 23643962]
Abd-Alaleem DI, Attiaa KI, Khalefa AA, Ahmad RA. Adiponectin levels in serum of women with preeclampsia. East Mediterr Health J 2011; 17(7): 575-81.
[] [PMID: 21972480]
Song Y, Gao J, Qu Y, Wang S, Wang X, Liu J. Serum levels of leptin, adiponectin and resistin in relation to clinical characteristics in normal pregnancy and preeclampsia. Clin Chim Acta 2016; 458: 133-7.
[] [PMID: 27154800]
Thagaard IN, Hedley PL, Holm JC, et al. Leptin and Adiponectin as markers for preeclampsia in obese pregnant women, a cohort study. Pregnancy Hypertens 2019; 15: 78-83.
[] [PMID: 30825932]
Salimi S, Farajian-Mashhadi F, Naghavi A, et al. Different profile of serum leptin between early onset and late onset preeclampsia. Dis Markers 2014; 2014: 628476.
[] [PMID: 24591763]
Khosrowbeygi A, Ahmadvand H. Positive correlation between serum levels of adiponectin and homocysteine in pre-eclampsia. J Obstet Gynaecol Res 2013; 39(3): 641-6.
[] [PMID: 23106812]
Taylor BD, Ness RB, Olsen J, et al. Serum leptin measured in early pregnancy is higher in women with preeclampsia compared with normotensive pregnant women. Hypertension 2015; 65(3): 594-9.
[] [PMID: 25510827]
El Shahat AM, Ahmed AB, Ahmed MR, Mohamed HS. Maternal serum leptin as a marker of preeclampsia. Arch Gynecol Obstet 2013; 288(6): 1317-22.
[] [PMID: 23771185]
Doster Y, Cetinkaya Demir B, Atalay MA, Durusoy EE, Kucukkomurcu S. The possible role of serum leptin in preeclampsia. Clin Exp Obstet Gynecol 2016; 43(1): 98-102.
[PMID: 27048026]
Asnafi N, Sharbatdaran M, Hajian K. Comparison of maternal and neonatal serum leptin levels in preeclampsia and normal pregnancy. Iran J Reprod Med 2011; 9(2): 131-4.
[PMID: 25587260]
Beneventi F, Locatelli E, De Amici M, et al. Maternal and fetal Leptin and interleukin 33 concentrations in pregnancy complicated by obesity and preeclampsia. J Matern Fetal Neonatal Med 2019; 1-7.
[PMID: 30856361]
Dorniak-Wall T, Grivell RM, Dekker GA, Hague W, Dodd JM. The role of L-arginine in the prevention and treatment of pre-eclampsia: A systematic review of randomised trials. J Hum Hypertens 2014; 28(4): 230-5.
[] [PMID: 24172291]
Rizos D, Eleftheriades M, Batakis E, et al. Levels of asymmetric dimethylarginine throughout normal pregnancy and in pregnancies complicated with preeclampsia or had a small for gestational age baby. J Matern Fetal Neonatal Med 2012; 25(8): 1311-5.
[] [PMID: 22010788]
Pettersson A, Hedner T, Milsom I. Increased circulating concentrations of Asymmetric Dimethyl Arginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, in preeclampsia. Acta Obstet Gynecol Scand 1998; 77(8): 808-13.
[PMID: 9776593]
Ley K. The role of selectins in inflammation and disease. Trends Mol Med 2003; 9(6): 263-8.
[] [PMID: 12829015]
Bosio PM, Cannon S, McKenna PJ, O’Herlihy C, Conroy R, Brady H. Plasma P-selectin is elevated in the first trimester in women who subsequently develop pre-eclampsia. BJOG 2001; 108(7): 709-15.
[] [PMID: 11467696]
Laskowska M, Laskowska K, Oleszczuk J. Elevated maternal serum sP-selectin levels in preeclamptic pregnancies with and without intrauterine fetal growth restriction, but not in normotensive pregnancies complicated by isolated IUGR. Med Sci Monit 2013; 19: 118-24.
[] [PMID: 23416763]
Dehghani-Firouzabadi R, Tayebi N, Ghasemi N, Tahmasbi Z. The association between second-trimester maternal serum alpha-fetoprotein in 14-22 weeks and adverse pregnancy outcome. Acta Med Iran 2010; 48(4): 234-8.
[PMID: 21279936]
Taché V, Baer RJ, Currier RJ, et al. Population-based biomarker screening and the development of severe preeclampsia in California. Obstet Gynecol 2014; 211(4): 377.
Khosrowbeygi A, Ahmadvand H. Leptin to adiponectin ratio in preeclampsia. Bangladesh Med Res Counc Bull 2013; 39(1): 18-21.
[] [PMID: 23923407]
Rana S, Karumanchi SA, Levine RJ, et al. Sequential changes in antiangiogenic factors in early pregnancy and risk of developing preeclampsia. Hypertension 2007; 50(1): 137-42.
[] [PMID: 17515455]
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): 940-50.
[] [PMID: 21810665]
Drobnjak T, Gizurarson S, Gokina NI, et al. Placental protein 13 (PP13)-induced vasodilation of resistance arteries from pregnant and nonpregnant rats occurs via endothelial-signaling pathways. Hypertens Pregnancy 2017; 36(2): 186-95.
[] [PMID: 28524718]
Gizurarson S, Sigurdardottir ER, Meiri H, et al. Placental protein 13 administration to pregnant rats lowers blood pressure and augments fetal growth and venous remodeling. Fetal Diagn Ther 2016; 39(1): 56-63.
[] [PMID: 26314825]
Gizurarson S, Huppertz B, Osol G, Skarphedinsson JO, Mandala M, Meiri H. Effects of placental protein 13 on the cardiovascular system in gravid and non-gravid rodents. Fetal Diagn Ther 2013; 33(4): 257-64.
[] [PMID: 23406577]

Rights & Permissions Print Export Cite as
© 2024 Bentham Science Publishers | Privacy Policy