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      Biochemical Markers for Prediction of Hypertensive Disorders of Pregnancy Translated title: BIOHEMIJSKI MARKERI ZA PREDIKCIJU HIPERTENZIVNIH POREMEĆAJA U TRUDNOĆI

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          Summary

          Background

          Gestational hypertension (GH) and pre eclampsia (PE) are the most common gestational complications. Several placental biochemical markers are used to predict GH/PE, but with conflicting results.

          Methods

          The study aim was to estimate the biochemical markers’ ability to predict hypertensive disorders in pregnancy. On the first ultrasonographic examination, 104 healthy pregnant women were recruited. At the regular pregnancy check-ups, BMI, blood pressure, occurrence of gestational hypertension (early or late onset), preeclampsia, eclampsia and other complications were recorded. Serum concentrations (in multiples of median – MoM) of human chorionic gonadotropin (HCG) and pregnancyassociated plasma protein A (PAPPA) were measured from the 11th to 14th gestational week, while HCG, alpha feto protein (AFP), estriol and inhibin were determined between the 16th and 19th gestational week.

          Results

          Hypertensive disorders throughout pregnancy were diagnosed in 20.2% women. Early-onset GH was registered in 7 and PE in 6 patients, while 14 had late-onset GH and 10 additional women PE. There were no significant differences (p≥0.05) in biochemical markers concentrations between women with and without GH/PE. PAPPA levels in the first and HCG in the second trimester correlated with early and late GH/PE. Moreover, higher AFP concentrations were registered in women with preeclampsia signs/symptoms. According to ROC analysis, AFP>1.05 MoM properly identified 80% of GH/PE cases. Obtained models imply that HCG, PAPPA and AFP should be used for GH/PE prediction.

          Conclusions

          Biochemical markers HCG, PAPPA and AFP could be useful in predicting gestational hypertension and preeclampsia. However, different markers should be used for early and late onset GH/PE.

          Kratak sadržaj

          Uvod

          Gestacijska hipertenzija (GH) i preeklampsija (PE) najčešće su gestacijske komplikacije. Nekoliko placentnih biohemijskih markera koristi se za predikciju GH/PE, ali sa oprečnim rezultatima.

          Metode

          Cilj studije bila je procena mogućnosti korišćenja biohemijskih markera za predikciju hipertenzivnih poremećaja u trudnoći. Na prvom ultrasonografskom pregledu, u studiju su uvrštene 104 zdrave trudnice. Na redovnim pregledima tokom trudnoće registrovani su ITM, krvni pritisak, pojava gestacijske hipertenzije (rani ili kasni početak), preeklampsija, eklampsija i druge komplikacije. Serumske kon centracije (izražene u umnošcima medijane – MOM) humanog horionskog gonadotropina (HCG) i plazma proteina vezanog za trudnoću (PAPPA) merene su u periodu od 11. do 14. gestacijske nedelje, dok su HCG, alfa feto protein (AFP), estriol i inhibin određivani između 16. i 19. nedelje.

          Rezultati

          Hipertenzivni poremećaji tokom trudnoće dijagnostikovani su kod 20,2% žena. Rana gestacijska hiper tenzija registrovana je kod 7, a preeklampsija kod 6 pacijentkinja, dok je kasnu gestacijsku hipertenziju imalo 14, a preeklampsiju 10 žena. Nije bilo statistički značajne razlike (p>0,05) u vrednostima biohemijskih markera kod pacijentkinja sa ili bez GH/PE. Vrednosti PAPPA u prvom i HCG-a u drugom trimestru korelirale su sa pojavom rane i kasne GH/PE. S druge strane, kod pacijentkinja sa znacima i simptomima preeklampsije registrovane su povišene koncentracije AFP-a. Prema ROC analizi, AFP > 1,05 MoM precizno identifikuje 80% slučajeva GH/PE. Dobijeni modeli podrazumevaju da HCG, PAPPA i AFP treba koristiti za predviđanje GH/PE.

          Zaključak

          Biohemijski markeri HCG, PAPPA i AFP mogu biti korisni u predikciji gestacijske hipertenzije i preeklampsije. Ipak, za GH/PE sa ranim i kasnim početkom trebalo bi koristiti različite markere.

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          Most cited references27

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          Placental origins of adverse pregnancy outcomes: potential molecular targets: an Executive Workshop Summary of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

          Although much progress is being made in understanding the molecular pathways in the placenta that are involved in the pathophysiology of pregnancy-related disorders, a significant gap exists in the utilization of this information for the development of new drug therapies to improve pregnancy outcome. On March 5-6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a 2-day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap. Particular emphasis was given to the identification of important molecular pathways that could serve as drug targets and the advantages and disadvantages of targeting these particular pathways. This article is a summary of the proceedings of that workshop. A broad number of topics were covered that ranged from basic placental biology to clinical trials. This included research in the basic biology of placentation, such as trophoblast migration and spiral artery remodeling, and trophoblast sensing and response to infectious and noninfectious agents. Research findings in these areas will be critical for the formulation of the development of future treatments and the development of therapies for the prevention of a number of pregnancy disorders of placental origin that include preeclampsia, fetal growth restriction, and uterine inflammation. Research was also presented that summarized ongoing clinical efforts in the United States and in Europe that has tested novel interventions for preeclampsia and fetal growth restriction, including agents such as oral arginine supplementation, sildenafil, pravastatin, gene therapy with virally delivered vascular endothelial growth factor, and oxygen supplementation therapy. Strategies were also proposed to improve fetal growth by the enhancement of nutrient transport to the fetus by modulation of their placental transporters and the targeting of placental mitochondrial dysfunction and oxidative stress to improve placental health. The roles of microRNAs and placental-derived exosomes, as well as messenger RNAs, were also discussed in the context of their use for diagnostics and as drug targets. The workshop discussed the aspect of safety and pharmacokinetic profiles of potential existing and new therapeutics that will need to be determined, especially in the context of the unique pharmacokinetic properties of pregnancy and the hurdles and pitfalls of the translation of research findings into practice. The workshop also discussed novel methods of drug delivery and targeting during pregnancy with the use of macromolecular carriers, such as nanoparticles and biopolymers, to minimize placental drug transfer and hence fetal drug exposure. In closing, a major theme that developed from the workshop was that the scientific community must change their thinking of the pregnant woman and her fetus as a vulnerable patient population for which drug development should be avoided, but rather be thought of as a deprived population in need of more effective therapeutic interventions.
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            Review: Biochemical markers to predict preeclampsia.

            Worldwide the prevalence of preeclampsia (PE) ranges from 3 to 8% of pregnancies. 8.5 million cases are reported yearly, but this is probably an underestimate due to the lack of proper diagnosis. PE is the most common cause of fetal and maternal death and yet no specific treatment is available. Reliable biochemical markers for prediction and diagnosis of PE would have a great impact on maternal health and several have been suggested. This review describes PE biochemical markers in general and first trimester PE biochemical markers specifically. The main categories described are angiogenic/anti-angiogenic factors, placental proteins, free fetal hemoglobin (HbF), kidney markers, ultrasound and maternal risk factors. The specific biochemical markers discussed are: PAPP-A, s-Flt-1/PlGF, s-Endoglin, PP13, cystatin-C, HbF, and α₁-microglobulin (A1M). PAPP-A and HbF both show potential as predictive biochemical markers in the first trimester with 70% sensitivity at 95% specificity. However, PAPP-A is not PE-specific and needs to be combined with Doppler ultrasound to obtain the same sensitivity as HbF/A1M. Soluble Flt -1 and PlGF are promising biochemical markers that together show high sensitivity from the mid-second trimester. PlGF is somewhat useful from the end of the first trimester. Screening pregnant women with biochemical markers for PE can reduce unnecessary suffering and health care costs by early detection of mothers at increased risk for PE, thus avoiding unnecessary hospitalization of pregnant women with suspect or mild PE and enabling monitoring of the progression of the disease thereby optimizing time for delivery and hopefully reducing the number of premature births. Copyright © 2012 Elsevier Ltd. All rights reserved.
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              First-trimester maternal factors and biomarker screening for preeclampsia.

              Preeclampsia (PE), which affects about 2% of pregnancies, is a major cause of maternal and perinatal morbidity and mortality. PE can be subdivided into early onset PE with delivery <34 weeks' gestation and late onset PE with delivery ≥34 weeks. Early onset PE is associated with a higher incidence of adverse outcome. This review illustrates that effective screening for the development of early onset PE can be provided in the first-trimester of pregnancy. Screening by a combination of maternal risk factors, mean arterial pressure, uterine artery Doppler, maternal serum pregnancy-associated plasma protein-A and placental growth factor can identify about 95% of cases of early onset PE for a false-positive rate of 10%.
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                Author and article information

                Journal
                J Med Biochem
                J Med Biochem
                jomb
                jomb
                Journal of Medical Biochemistry
                Sciendo
                1452-8258
                1452-8266
                March 2019
                01 March 2019
                : 38
                : 1
                : 71-82
                Affiliations
                [1 ]Clinic of Obstetrics and Gynecology , deptClinical Center of Serbia , Belgrade, Serbia
                [2 ]deptMedical Faculty , universityUniversity of Belgrade , Belgrade, Serbia
                [3 ]deptInstitute of Medical Biochemistry, Medical Faculty , universityUniversity of Belgrade , Belgrade Serbia
                [4 ]Clinic of Cardiology , deptClinical Center of Serbia Belgrade Serbia
                Author notes
                [* ] Dusica Kocijancic, MD, Ob/Gyn Clinic of Obstetrics and Gynecology, Clinical Center of Serbia Koste Todorovica 26, 11000 Belgrade, Serbia Telephone: +381113615592 dusicakocijancic@ 123456yahoo.com
                Article
                jomb-2018-0001
                10.2478/jomb-2018-0001
                6298456
                30820186
                b883a912-2855-476a-b9b3-5114104db4b7
                © 2019 Dušica Kocijančić Belovic, Snežana Plešinac, Jelena Dotlić, Ana Savić Radojević, Slavica Akšam, Mirjana Marjanović Cvjetićanin, Aleksandar Kocijančić, published by Sciendo

                This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

                History
                : 19 December 2017
                : 27 January 2018
                Page count
                Pages: 12
                Categories
                Original Paper

                gestational hypertension,preeclampsia,hcg,afp,estriol,inhibin,gestacijska hipertenzija,preeklampsija, hcg

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