Abstract
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
[http://dx.doi.org/10.1530/JOE-16-0340] [PMID: 27729465]
[http://dx.doi.org/10.1186/1477-7827-7-70] [PMID: 19602262]
[http://dx.doi.org/10.1155/2018/2632637] [PMID: 30050697]
[http://dx.doi.org/10.1067/mob.2000.107928] [PMID: 10920346]
[PMID: 16175681]
[PMID: 15617295]
[http://dx.doi.org/10.1098/rstb.2014.0066] [PMID: 25602070]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.113.00588] [PMID: 23897068]
[http://dx.doi.org/10.5772/intechopen.85843]
[http://dx.doi.org/10.1172/JCI17189] [PMID: 12618519]
[http://dx.doi.org/10.1038/nm1429] [PMID: 16751767]
[http://dx.doi.org/10.1186/1471-2393-9-8] [PMID: 19245695]
[http://dx.doi.org/10.1210/jc.2003-031244] [PMID: 14764795]
[http://dx.doi.org/10.3390/genes10010032] [PMID: 30634483]
[http://dx.doi.org/10.1159/000444524] [PMID: 26998901]
[http://dx.doi.org/10.1161/JAHA.121.021477] [PMID: 34310191]
[PMID: 27398706]
[http://dx.doi.org/10.1111/j.1471-0528.1991.tb15334.x] [PMID: 1751443]
[http://dx.doi.org/10.1016/S0002-9440(10)65123-1] [PMID: 10393861]
[http://dx.doi.org/10.1373/clinchem.2008.111385] [PMID: 18703764]
[http://dx.doi.org/10.1126/scitranslmed.3001720] [PMID: 21148127]
[http://dx.doi.org/10.1093/clinchem/47.1.137] [PMID: 11148193]
[PMID: 9572208]
[http://dx.doi.org/10.1093/humrep/15.7.1624] [PMID: 10875878]
[http://dx.doi.org/10.1080/08977190500126306] [PMID: 16019434]
[http://dx.doi.org/10.1016/j.placenta.2003.11.011] [PMID: 15135240]
[http://dx.doi.org/10.3109/14767058.2015.1072157] [PMID: 26333278]
[http://dx.doi.org/10.1016/j.mefs.2010.03.009]
[http://dx.doi.org/10.1111/j.1600-0412.2004.00277.x] [PMID: 14678084]
[http://dx.doi.org/10.1152/ajpheart.00365.2009] [PMID: 20382861]
[http://dx.doi.org/10.3109/10641955.2013.837174] [PMID: 24380505]
[http://dx.doi.org/10.1002/pd.2203] [PMID: 19242927]
[http://dx.doi.org/10.1371/journal.pone.0124684] [PMID: 25906026]
[http://dx.doi.org/10.1056/NEJMoa055352] [PMID: 16957146]
[http://dx.doi.org/10.1159/000359968] [PMID: 24853452]
[http://dx.doi.org/10.3109/00016340903289892] [PMID: 20021269]
[http://dx.doi.org/10.1016/j.preghy.2015.09.004] [PMID: 26597750]
[PMID: 21969185]
[http://dx.doi.org/10.1056/NEJMoa031884] [PMID: 14764923]
[http://dx.doi.org/10.1007/s00404-011-1960-4] [PMID: 21735190]
[http://dx.doi.org/10.1111/j.1471-0528.2010.02690.x] [PMID: 20840693]
[http://dx.doi.org/10.1080/14767050701830480] [PMID: 18175241]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.06421] [PMID: 27067718]
[http://dx.doi.org/10.1371/journal.pone.0013263] [PMID: 20948996]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.054361] [PMID: 22261192]
[http://dx.doi.org/10.1016/j.ajog.2016.01.168]
[http://dx.doi.org/10.1096/fj.02-0634rev] [PMID: 12773481]
[http://dx.doi.org/10.18869/acadpub.ibj.21.5.312] [PMID: 28558439]
[http://dx.doi.org/10.1161/01.HYP.16.6.677] [PMID: 2246034]
[http://dx.doi.org/10.1038/332411a0] [PMID: 2451132]
[http://dx.doi.org/10.1016/0014-5793(91)80007-P] [PMID: 1652463]
[http://dx.doi.org/10.1097/MNH.0b013e328350094b] [PMID: 22257796]
[http://dx.doi.org/10.1161/01.HYP.37.2.485] [PMID: 11230323]
[http://dx.doi.org/10.1016/S0024-3205(00)00736-0] [PMID: 10983841]
[http://dx.doi.org/10.1016/j.ijgo.2005.04.018] [PMID: 16005006]
[http://dx.doi.org/10.1161/01.HYP.32.4.758] [PMID: 9774376]
[PMID: 18382699]
[http://dx.doi.org/10.1016/j.ajog.2012.10.217]
[http://dx.doi.org/10.1073/pnas.96.6.3149] [PMID: 10077652]
[http://dx.doi.org/10.1159/000235878] [PMID: 19776595]
[http://dx.doi.org/10.11622/smedj.2017034] [PMID: 28451695]
[http://dx.doi.org/10.1186/1471-2393-13-85] [PMID: 23557166]
[http://dx.doi.org/10.1159/000322402] [PMID: 21266793]
[http://dx.doi.org/10.1016/j.placenta.2011.05.006] [PMID: 21652068]
[http://dx.doi.org/10.1007/s00404-011-1912-z] [PMID: 21533533]
[http://dx.doi.org/10.1111/j.1432-1033.2004.04004.x] [PMID: 15009185]
[http://dx.doi.org/10.3390/ijms17040523] [PMID: 27070577]
[http://dx.doi.org/10.1016/j.placenta.2011.10.005] [PMID: 22015022]
[http://dx.doi.org/10.1515/cclm-2017-0356] [PMID: 28704180]
[http://dx.doi.org/10.1007/s00404-016-4111-0] [PMID: 27161490]
[http://dx.doi.org/10.1016/j.placenta.2003.12.009] [PMID: 15193867]
[http://dx.doi.org/10.1002/uog.3876] [PMID: 17149788]
[http://dx.doi.org/10.1002/pd.2375] [PMID: 19777530]
[http://dx.doi.org/10.1101/cshperspect.a021881] [PMID: 27328872]
[http://dx.doi.org/10.1210/jcem.82.5.3934] [PMID: 9141549]
[http://dx.doi.org/10.1002/uog.8800] [PMID: 20737451]
[http://dx.doi.org/10.1210/jc.2011-2729] [PMID: 22685232]
[http://dx.doi.org/10.3109/14767058.2012.755167] [PMID: 23205865]
[http://dx.doi.org/10.1159/000322742] [PMID: 21252475]
[http://dx.doi.org/10.1002/pd.2279] [PMID: 19412915]
[http://dx.doi.org/10.1007/s00404-008-0886-y] [PMID: 19107499]
[http://dx.doi.org/10.1111/j.1447-0756.2010.01513.x] [PMID: 21535305]
[http://dx.doi.org/10.1016/j.preghy.2015.03.001] [PMID: 25943646]
[http://dx.doi.org/10.1016/j.cca.2013.04.027] [PMID: 23643962]
[http://dx.doi.org/10.26719/2011.17.7.575] [PMID: 21972480]
[http://dx.doi.org/10.1016/j.cca.2016.04.036] [PMID: 27154800]
[http://dx.doi.org/10.1016/j.preghy.2018.12.002] [PMID: 30825932]
[http://dx.doi.org/10.1155/2014/628476] [PMID: 24591763]
[http://dx.doi.org/10.1111/j.1447-0756.2012.02015.x] [PMID: 23106812]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.114.03979] [PMID: 25510827]
[http://dx.doi.org/10.1007/s00404-013-2915-8] [PMID: 23771185]
[PMID: 27048026]
[PMID: 25587260]
[PMID: 30856361]
[http://dx.doi.org/10.1038/jhh.2013.100] [PMID: 24172291]
[http://dx.doi.org/10.3109/14767058.2011.632037] [PMID: 22010788]
[PMID: 9776593]
[http://dx.doi.org/10.1016/S1471-4914(03)00071-6] [PMID: 12829015]
[http://dx.doi.org/10.1111/j.1471-0528.2001.00170.x] [PMID: 11467696]
[http://dx.doi.org/10.12659/MSM.883780] [PMID: 23416763]
[PMID: 21279936]
[http://dx.doi.org/10.1016/j.ajog.2014.03.026]
[http://dx.doi.org/10.3329/bmrcb.v39i1.15805] [PMID: 23923407]
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.087700] [PMID: 17515455]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.034793] [PMID: 21810665]
[http://dx.doi.org/10.1080/10641955.2017.1295052] [PMID: 28524718]
[http://dx.doi.org/10.1159/000381914] [PMID: 26314825]
[http://dx.doi.org/10.1159/000345964] [PMID: 23406577]