(525) Maternal immune microenvironment in fetal congenital heart disease

Objective: This study was undertaken to evaluate the relationship between maternal immunological milieu (cytokines and chemokines) and complex fetal congenital heart disease (CHD).

Study Design: We performed a prospective, non-interventional, case-control study of pregnancies with complex fetal CHD (cases) at a single tertiary academic fetal care center matched to those with normal fetal cardiac anatomy (controls). Maternal serum was collected after CHD diagnosis based on fetal echocardiogram evaluation. Serum cytokine and chemokine levels were assessed using multiplex enzyme-linked immunosorbent assay (ELISA) and compared across groups. Demographic (age, race, parity, insurance) and clinical characteristics (obesity, diabetes, hypertension, connective tissue / thyroid disorder, In-vitro fertilization and history of CHD) were abstracted from electronic medical records and compared using student’s t test and chi squared / Fisher’s exact test for continuous and categorical data respectively. Statistical significance was set at p < 0.05.

Results: ELISA was performed for 23 cases with fetal CHD and 25 matched controls. The predominant CHD phenotypes were hypoplastic (left/right) heart syndrome (9/23, 39%), tetralogy of Fallot (4/23, 17%), and coarctation (3/23, 13%). Demographic and clinical characteristics were similar across both groups except gestational age at specimen collection [cases: 30.1±4.4 vs controls 27.5±2.8 weeks (mean ± SD), p=0.02]. Multiplex analysis of 38 pro- and anti-inflammatory cytokines and chemokines was performed. Of those assayed, IL-2 was significantly overexpressed in cases vs control (positive fold change 1.58, p=0.03). Other analytes – including IL-8 (p=0.03) fractalkine (p=0.02), GM-CSF (p=0.01), IFNα2 (p=0.04), IL-17A (p=0.01), and MCP-1(p=0.03) were significantly under expressed in cases compared to controls.

Conclusion: Significant differences were noted in immunoregulatory cytokine and chemokine expression among pregnancies with and without fetal CHD. Our findings suggest a predominant involvement of the Th1 cell line in fetal CHD pathogenesis.