Amniotic fluid biomarkers of fetal stress response to cardiac dysfunction in twin-twin transfusion syndrome

Abstract

Recipient twin (RT) cardiovascular changes in twin-twin transfusion syndrome (TTTS) are associated with increased mortality. This relationship is likely related to a cascade of pathophysiologic changes in the RT progressing to multisystem organ failure. We sought to evaluate biomarkers of inflammation, stress, and tissue injury within amniotic fluid (AF) of RTs undergoing selective fetoscopic laser photocoagulation (SFLP) for TTTS and examine their relationship with fetal echocardiographic findings. AF samples from RTs were obtained from 39 monochorionic-diamniotic pregnancies complicated by TTTS. Those without preoperative fetal echocardiograms or evidence of selective intrauterine growth restriction were excluded from analysis with 24 remaining samples. 15 commonly utilized clinical biomarkers for inflammation, stress, and tissue injury were assessed using a flow-cytometry based multiplex immunoassay. Fetal echocardiograms were performed prior to SFLP with myocardial performance index (MPI) utilized as a measure of cardiac dysfunction. Pearson’s correlation was used for data analysis. RT Left ventricular MPI (LV-MPI) ranged from 0.28-0.74, with 11/24 RTs demonstrating abnormal MPI for GA (Z-score > 2). RT AF cortisol (r = 0.4527, p = 0.020), IL-6 (r = 0.44, p = 0.025), CRP (r = 0.431, p = 0.028), and myoglobin (r = 0.401, p = 0.042) levels correlated with recipient left ventricular MPI (LV-MPI). AF cortisol strongly correlated with AF myoglobin (r = 0.576, p < 0.001). RT with abnormal LV-MPI exhibited significantly higher AF cortisol levels compared to those with normal LV-MPI (p = 0.029). RT amniotic fluid demonstrates markers of inflammation, stress and cardiac injury in recipient twins with cardiac dysfunction. These markers may be indicators of disease progression in TTTS secondary to cardiac dysfunction. The presence of these markers implicate stress and the immune response in the pathophysiologic response to cardiac dysfunction in TTTS.