Circulating pregnancy hormone relaxin as a first trimester biomarker for preeclampsia

Objective: 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. Methods: Relaxin was initially measured in first-trimester samples of women who developed late-onset preeclamptic (LO-PE; delivery >= 34 weeks; 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 < 34 weeks; n = 57), and uncomplicated pregnancies (n = 469) in Utrecht, the Netherlands. Results: 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. Conclusion: 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.