Increased maternal cytokine production and congenital heart defects

Abstract

Congenital heart defects (CHDs) are a major cause of infant mortality. Most CHDs are thought to result from genetic, lifestyle, and environmental factors that include maternal obesity, diabetes, toxicant exposure, and alterations in anti-oxidant capacity. Since these well-documented risk factors are also associated with immune dysregulation, we sought to compare the maternal immune response in mothers carrying a fetus with a CHD with those mothers whose pregnancies were not affected by any birth defect. We conducted a case-control study to examine the maternal cytokine profile using multiplex technology in pregnant mothers (subject mean=26 weeks’ gestation). This investigation revealed that whole blood cultures derived from case mothers produced higher levels of certain cytokines and chemokines compared with cultures from control subjects when activated with mitogen. Cultures from case subjects produced higher levels of IL-10, IL-13, IL-4, IL-5, IL-17, and IL-6, when stimulated with mitogen compared with control subjects. Plasma levels of chemokine MIP-1α were higher in cases compared with controls. In contrast, C-reactive protein levels were not statistically different. These results demonstrate the need to further examine the maternal cytokine signature in CHD-affected pregnancies. This information could pave the way toward maternal immunotherapeutic intervention to prevent CHDs, and novel biomarker discovery to improve pre-natal diagnosis.