Abstract

To assess the ability of non-invasive cardiac output monitoring (NICOM®), a novel method of non-invasive maternal hemodynamic assessment using bioreactance, in combination with first trimester biomarkers to predict the evolution of gestational hypertension (GH), pre-eclampsia (PE) and normotensive fetal growth restriction (FGR). Low risk nulliparous women were enrolled in a single center prospective observational study. NICOM® assessments were performed at 14 weeks’ gestation and data obtained on cardiac output (CO), indexed CO (adjusted for maternal body surface area; COI), total peripheral resistance (TPR), indexed TPR (adjusted for maternal body surface area; TPRi), stroke volume (SV), indexed SV (adjusted for maternal body surface area; SVi) and heart rate (HR). Maternal serum samples were obtained in the first trimester and the following markers were analysed: placental growth factor (PLGF; Cobas Roche); soluble fms-like tyrosine-1 (s-flt-1; Elecsys®) Apelin 13 (Nori® ELISA) and mean platelet volume (MPV). Corrleation between cardiac variables and biomarkers was assessed using Spearman coefficient. Discriminant analysis was employed to model GH, PE and FGR with NICOM® and biomarker measurements as predictors. Logistic regression was performed on variables of interest via SAS version 9.0. The haemodynamic profile of pregnancies complicated by uteroplacental disease- GH (n=13), PE (n=5) and FGR (n=18) were compared to 61 healthy unaffected pregnant controls.Apelin 13 demonstrated a negative correlation with TPRi (r=-0.29, p=0.004), and a positive correlation with COi (r=0.29, p=0.005). In the prediction of PE s-flt-1 and MPV had a combined prediction model AUC 0.88 (p=0.01). Whereas in the prediction of FGR s-flt-1, SV and TPRI had a combined prediction model AUC 0.76 (p=0.007). Apelin 13 is an inodilator produced by the normal placenta in pregnancy. This study shows the hemodynamic effects of Apelin 13 are present as early as 14 weeks' gestation. Down regulation of placental Apelin 13 has been linked with PE and lower serum Apelin with FGR, from 20 weeks' gestation onwards. However, this association was not present at 14 weeks' gestation. In addition to its known use in PE, first trimester s-flt-1 may have an role in the prediction of FGR which is strengthened by the addition of hemodynamic variables.

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