Circulating follistatin-like 3 and its association with postpartum cardiovascular dysfunction and severe maternal morbidity

Abstract

Objectives: Despite postpartum cardiovascular dysfunction being the leading cause of pregnancy-related mortality in the United States, it is difficult to identify at-risk patients. The objective of this study was to determine if antepartum follistatin-like 3 levels correlate with postpartum cardiovascular dysfunction and maternal morbidity.

Study design: This observational cohort study included pregnant patients ≥ 18 years old and singleton gestation < 41 weeks who delivered at the University of Chicago between May 2017 and November 2020.

Main outcome measures: The primary outcome was postpartum cardiovascular dysfunction, defined as postpartum hypertension, cardiomyopathy, and pulmonary edema. The secondary outcome was severe maternal morbidity.

Results: The final cohort included 408 women. Elevated FSTL3 levels were associated with postpartum cardiovascular dysfunction (OR per unit increase in FSTL3, 1.02 [95 % CI: 1.01, 1.04]; p < 0.001). After adjustment for gestational age at delivery, maternal age, BMI, nulliparous status, hypertensive disorders of pregnancy, smoking, and diabetes, the association between FSTL3 levels and cardiovascular dysfunction persisted (p = 0.03), with good model discrimination between events (c-statistic 0.88). FSTL3 levels were also associated with severe maternal morbidity (OR per unit increase 1.02 [95 % CI: 1.01, 1.03]; p < 0.0001). Additionally, Activin A levels were associated with cardiovascular dysfunction and severe maternal morbidity (c = 0.84, p = 0.01; c = 0.87, p = 0.02 respectively).

Conclusions: Higher follistatin-like 3 levels were associated with postpartum cardiovascular dysfunction and severe maternal morbidity. Follistatin-like 3 may be causal in cardiovascular dysfunction, and further work should define its potential as a biomarker.