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.