Abstract
Preeclampsia, a multi-system hypertensive disorder, is associated with perturbations in the maternal cardiovascular system during early pregnancy. The corpus luteal hormone relaxin, a potent vasodilator, may contribute to physiological circulatory changes especially in early gestation when circulating levels are highest. This study investigated whether first trimester circulating relaxin may be a suitable biomarker for the early prediction of preeclampsia. Relaxin was initially measured in first-trimester samples of women who developed late-onset preeclamptic (LO-PE; delivery≥34weeks; n=33) and uncomplicated pregnancies (n=25) in Pittsburgh, USA. Subsequently, to expand the group numbers, relaxin was measured in women who developed LO-PE (n=95), early-onset preeclamptic (EO-PE; delivery<34weeks; n=57), and uncomplicated pregnancies (n=469) in Utrecht, the Netherlands. In the Pittsburgh subjects, low relaxin levels (lowest centile: <p10) showed an adjusted odds ratio (OR) of 5.29 (95%CI 1.10-25.5) for LO-PE. In the Utrecht population, low relaxin levels (<p10) demonstrated adjusted ORs of 1.45 (95%CI 0.54-3.90) and 2.03 (95%CI 1.06-3.88) for EO-PE and LO-PE respectively, the latter increasing to an adjusted OR of 3.18 (95%CI 1.41-7.20) when newborn weight was<10%. Serum relaxin concentrations slightly improved the detection rate of a previously derived prediction model for LO-PE from 42.5% to 45.1% at a fixed 10% false-positive rate. Relaxin shows little improvement in the performance of first trimester prediction models, which does not support its clinical implementation as a biomarker. Although this study was only correlational, the results point to a possible pathophysiologic role for low relaxin levels in pregnancies that later develop LO-PE.
Highlights
Preeclampsia, a gestation-specific hypertensive syndrome affecting 3–5% of all pregnant women, is a leading cause of maternal and perinatal morbidity and mortality [1]
We evaluated pregnancy-associated plasma protein A (PAPP-A), free beta human chorionic gonadotrophin, A Disintegrin And Metalloprotease 12 (ADAM-12) and placental growth factor (PlGF), previously established as biomarkers of preeclampsia, in the context of relaxin
We observed a clear association of low first trimester relaxin concentrations with LO-PE but not with Early-onset preeclampsia (EO-PE)
Summary
Preeclampsia, a gestation-specific hypertensive syndrome affecting 3–5% of all pregnant women, is a leading cause of maternal and perinatal morbidity and mortality [1]. Due to impaired placental function, women with preeclampsia often give birth to a small for gestational age (SGA) infant [6,7]. Early-onset preeclampsia (EO-PE) is associated with more severe placental pathology [9,10], and a higher rate of fetal growth restriction [11,12]. Both LO- and EO-PE confer an increased risk
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