The Role of Serum Markers and Uterine Artery Doppler in Identifying At-Risk Pregnancies

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Normal Placental Development

The human embryo undergoes interstitial implantation by invading the maternal decidua at the blastocyst stage.3 Differentiation of the trophectoderm yields multiple cell lineages, including extravillous trophoblasts, which invade maternal spiral vessels to form a hemochorial placenta in which fetal trophoblasts are bathed directly by maternal blood.4 However, maternal blood flow in the spiral vessels is initially limited by endovascular plugs5 and early placental development occurs in a state

Overview

Maternal serum analytes provide minimally invasive tests of fetal and placental endocrine function as well as endothelial dysfunction. The failure of trophoblastic invasion may be related to dysregulated secretory activity of the trophoblasts; whereas, alteration in the surface layer of the syncytiotrophoblast may contribute to leakage of human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP) into maternal circulation.16, 17 Reduced placental size or defective syncytiotrophoblast

Uterine Artery Doppler

Failure of spiral artery remodeling as reflected by enhanced uterine artery resistance has been linked to adverse pregnancy outcomes.72, 73 Increased resistance to uterine artery blood flow can be measured noninvasively by Doppler studies of the myometrial segments of the uterine arteries (Fig. 1A). The indices used to quantify uterine artery resistance include systolic (S) to diastolic (D) velocity ratio (S/D), pulsatility index (PI), resistive index (RI), and early diastolic notching.

Multiparameter tests

Since none of the current single parameter tests are sufficiently predictive of adverse pregnancy outcomes, many investigators have attempted to improve the predictive value of tests by combining them.42, 45, 67, 71, 91, 92 The use of multiple parameters seeks to increase specificity and sensitivity by exploring the different disease pathways. Generally, abnormal uterine artery Doppler, a reflection of inadequate trophoblastic invasion, is combined with abnormal biomarkers presumably resulting

Summary and future perspectives

Measures of placental dysfunction have the potential to identify pregnancies at increased risk of adverse outcomes. At the present time, the ability of any single one to accurately predict these outcomes is poor. The use of first-trimester and second-trimester biochemical markers in combination with uterine artery Doppler shows the greatest potential for screening tools. Adequately powered prospective studies using standardized methodology are necessary to further evaluate the choice of

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    • Serum markers in quadruple screening associated with adverse pregnancy outcomes: A case–control study in China

      2020, Clinica Chimica Acta
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      Adverse maternal and fetal complications usually occur in the third trimester of pregnancy, but the underlying pathology is largely determined in the early stages of pregnancy, and this response is initially adaptive. However, it leads to extensive systemic endothelial dysfunction and an imbalance in circulating vasoactive factors [15]. Before clinical manifestations, changes in these serum markers can be used as predictors of adverse pregnancy outcomes.

    • Combined use of serum MCP-1/IL-10 ratio and uterine artery Doppler index significantly improves the prediction of preeclampsia

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      Changes in these factors' plasma concentrations during pregnancy have been used as biomarkers for the prediction as well as early diagnosis of preeclampsia. It was reported that a combined use of biochemical markers with uterine artery Doppler in the second trimester could be an efficient screening tool for assessing the risk of preeclampsia [9]. The goal of this study is to characterize the changes of candidate circulating factors, monocyte chemotactic protein-1 (MCP-1, or CCL2) and IL-10, under preeclamptic conditions, and apply them alone or in combination with Doppler ultrasonography for the prediction of preeclampsia.

    • Diagnosis of pre-eclampsia and assessment of severity through examination of the placenta with acoustic radiation force impulse elastography

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      For these reasons, it is very important to include the diagnosis and follow-up of pre-eclampsia in pregnancy tracking. Multiple serum markers (e.g. serum β-human chorionic gonadotropin and pregnancy-associated plasma protein A) combined with Doppler ultrasonography to evaluate the blood flow velocity in the maternal uterine artery have shown promise in the identification of patients at increased risk of pre-eclampsia [8,9]. However, these tests might not be sufficiently accurate in identifying patients at risk or those who already have this complication [10].

    • Pregnancy-associated plasma protein a (papp-a) and preeclampsia

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      Recent papers have shown that Doppler ultrasonography is more accurate in the second trimester, but there are encouraging results for first trimester screening with a combination of biomarkers. Doppler ultrasonography is also the most predictive marker for preeclampsia, but current data do not support its use for routine screening [16,36–38]. These different results for the early versus late and low- versus high-risk populations suggest that preeclampsia may be a heterogeneous disease [37].

    • Toxicity assessment on trophoblast cells for some environment polluting chemicals and 17β-estradiol

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      In most of the studies low β-hCG levels in early gestation have been associated to early fetal loss (Braunstein et al., 1978; Goetzl et al., 2004 and Goetzl, 2010; van Ravenswaaij et al., 2011). In contrast to the low levels of hCG in the first trimester, high levels in the second trimester have been linked to pregnancy complications such as preeclampsia, intrauterine growth restriction and preterm birth (Tuuli and Odibo, 2011; Towner et al., 2006). Even though it is difficult to translate the data obtained in vitro with the pathophysiological conditions, any effect on the concentration of β-hCG by external substances might result in problems during pregnancy.

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    Funding support: none.

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