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  • It is noteworthy that in

    2024-04-03

    It is noteworthy that in both cases there is a higher risk for prematurity [44], [61], [97], [98] and for deliveries of newborn small for GA [89], [95], [97], [98]. sFlt-1:PlGF has been showed to be inversely correlated with GA at birth, since 86% of pregnant women who gave birth at <34 weeks had rates higher than 85 [81]. Other biomarkers and experimental treatments have a promising future according to the literature. The serum level of placental glycoprotein pregnancy-associated plasma protein-A (PAPP-A) and of placental protein 13 (PP13), associated with Doppler ultrasound of the uterine artery, have a predictive value of approximately 70% [87], [99] and 86% [22], [87], with 5% and 10% false positive results, respectively; the concentration of PAPP-A and PP13 is higher in PE. Similarly, serum levels of fetal hemoglobin, of α1-microglobulin, of activin A, of inhibin A, and of cellular metabolism products become altered in PE, and appear to significantly contribute to the progression of the disease [87], [100], [101]. Laboratory tests indicate elevated levels of urinary prolactin in PE accompanied by HELLP syndrome or eclampsia [95]; as well as high plasma levels of malondialdehyde (10.72±2.20mmol/ml) than in normotensive women (9.53±2.45mmol/ml), and positively associated with maternal plasma sFlt-1 levels [47]. It is also observed an increase in plasma levels of sTNF-R1 [29.34 (16.76–55.29) vs. 4.45 (3.94–5.10) pg/ml] and sTNF-R2 (8698±1602 vs. 6508±1241pg/ml) when compared with non-pregnant women [58]. A recent study developed with 4380 offsprings from preeclamptic pregnancies, highlighted the first genome-wide significant susceptibility locus (rs4769613), located nearby Flt-1 gene encoding Fms-like tyrosine kinase-1. Higher sodium salt of rs4769613 showed strong relation with offspring from pregnancies with late PE or which birth weights exceeded the tenth centile. Thus, this finding reinforces the hereditary risk associated with PE, since a placental isoform of sFlt-1 is implicated in its etiopathogenesis [102]. Experimental treatments are another promising research area. According to a multicentric study, 10mg of pravastatin (a hydrophilic statin) helps diminishing PE and premature delivery in pregnant women at high risk for PE. In this study, placebo group (10 subjects) had four women who developed PE and five had preterm deliveries before 37 weeks compared with none PE cases and one preterm delivery in pravastatin group (10 subjects). In addition, a higher concentration of PlGF and a reduction of sFlt-1 and sEng concentration was observed in the group receiving pravastatin. It is also noted that five newborns from women in placebo group were admitted to an intermediate nursery or to neonatal intensive care unit, while in the other group, only two newborns required such attention [103]. Another research that evaluated the removal of sFlt-1 by whole-blood apheresis using charged dextran sulfate column, pointed out that pregnant women who received apheresis treatment presented a reduction in serum levels of sFlt-1. Comparing the mean pre-apheresis and post-apheresis sFlt-1 concentration, there was a reduction from 17,394 (range 7916–35,301) pg/ml to 14,265 (6446–26,259) pg/ml, respectively; an average reduction in sFlt-1 concentration of 18% (7%–28%) per treatment. It is still outstanding a decrease in protein/creatinine (P/C) ratios following apheresis in almost all pregnant women. When compared the mean starting P/C ratio and post-treatment values there was a reduction from 6.5g/g (0.4–16.9g/g) to 3.2 (0.2–8.6) g/g, respectively; an average reduction in P/C ratio of 44% [104]. Although in the future it will be possible to establish an efficient and effective diagnostic tool, the management of PE needs to follow three key principles: prevention, early screening, and treatment. Therefore, the identification of and risk calculation for PE is important, since dietary changes, smoking cessation, comorbidity monitoring, blood pressure (BP), and weight gain, for example, can contribute to the prevention of this condition [105].