A case-control study of mid-pregnancy circulating cardiovascular proteins in women with subsequent preeclampsia and small for gestational age births.

Preeclampsia and small for gestational age (SGA) births share pathophysiologic pathways involving the cardiovascular system, inflammation, and placentation. To evaluate their pathophysiological differences and similarities, we compared alterations in mid-pregnancy circulating protein levels in women with subsequent preeclampsia and/or SGA birth. We used the Olink cardiovascular panel II to measure 92 mid-pregnancy plasma proteins in healthy pregnant women with subsequent uncomplicated pregnancies (controls; n = 480), term (≥ 37 weeks) preeclampsia (n = 233), preterm (< 37 weeks) preeclampsia (n = 40), SGA birth (n = 106), or combined preeclampsia and SGA birth (n = 31). False discovery rate-adjusted Kruskal-Wallis and Dunn's post-hoc tests identified protein level differences between controls and each adverse outcome group. Compared with controls, mid-pregnancy protein alterations were most common in women with subsequent term preeclampsia, particularly involving the cardiovascular proteins angiotensin-converting enzyme 2 and B-type natriuretic peptide. Across all outcomes, matrix metalloproteinase-12 and placental growth factor were lower compared to controls, particularly in those with combined disorder. In summary, cardiovascular and inflammatory protein alternations were most common in women with subsequent preeclampsia. Shared dysregulation of matrix metalloproteinase-12 and placental growth factor, both known regulators of placentation and the vascular system, suggests their involvement in both preeclampsia and SGA births, albeit the pathways may differ.