Key result
Higher mid-pregnancy MMP-12 linked to ~89% lower odds of combined preeclampsia and SGA birth.
Why the study?
Preeclampsia and small for gestational age births share pathophysiologic pathways, but their pathophysiological differences and similarities required evaluation.
Do mid-pregnancy circulating cardiovascular and inflammatory protein levels differ in women who subsequently develop preeclampsia and/or small for gestational age births compared to healthy controls?
Case-Control (n=890)
No
Do mid-pregnancy circulating cardiovascular and inflammatory protein levels differ in women who subsequently develop preeclampsia and/or small for gestational age births compared to healthy controls?
Mid-pregnancy alterations in cardiovascular and inflammatory proteins, particularly MMP-12 and PlGF, are associated with the subsequent development of preeclampsia and small for gestational age births, highlighting shared and distinct pathophysiological pathways before clinical onset.
Lower mid-pregnancy MMP-12 and PlGF should not yet change practice; hypothesis-generating for shared placentation pathways in preeclampsia and SGA.
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.
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Callbo et al. (2026) conducted a case-control in Preeclampsia and small for gestational age (SGA) births (n=890). Mid-pregnancy circulating cardiovascular and inflammatory proteins (e.g., MMP-12, PlGF) vs. Uncomplicated pregnancies (controls) was evaluated on Association of mid-pregnancy matrix metalloproteinase-12 (MMP-12) levels with combined preeclampsia and SGA birth (aOR 0.11, 95% CI 0.05-0.23, p=<0.001). Mid-pregnancy circulating levels of matrix metalloproteinase-12 and placental growth factor were consistently lower in women who subsequently developed preeclampsia or SGA births, with the strongest association in the combined disorder.
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