Maternal Plasma and Amniotic Fluid Cytokines in Monochorionic, Diamniotic Twin Pregnancies Complicated by Twin-to-Twin Transfusion Syndrome

Abstract

Introduction: Cytokine imbalance has been implicated in placental-related pathologies, i.e. recurrent miscarriage and pre-eclampsia. Such conditions are more prevalent in multiple pregnancies. Twin-to-twin transfusion syndrome (TTTS) is associated with asymmetric placental blood flow and intra-cardiac pressures. We hypothesised that cytokine expression may be aberrant in this condition and that fetoscopic laser ablation (FLA) may cause local cytokine release. Material and Methods: A prospective cohort of monochorionic, diamniotic twins with TTTS (n = 23) was studied. Circulating T helper cell type 1 (TH1)/TH2 maternal cytokines and cytokine-related and angiogenic factors were measured in plasma and amniotic fluid before and after FLA by human FASTQuant or ELISA. Basal comparisons were made with uncomplicated monochorionic and dichorionic (DC) twins. Results: Median maternal plasma platelet-derived growth factor-BB was highest in uncomplicated DC twins (p = 0.049), whereas tissue inhibitor of metalloproteinases (TIMP)-1 was highest in TTTS twins (p = 0.003). In TTTS amniotic fluid, interleukin (IL)-6, IL-1β, tumour necrosis factor-α, IL-10, IL-4, IL-8, interferon-γ, TIMP-1 and intercellular adhesion molecule-1 were significantly higher than maternal plasma concentrations. There were no significant differences in plasma or amniotic fluid cytokines after FLA, with the exception of amniotic fluid keratinocyte growth factor, which was significantly reduced. Discussion: TTTS is associated with minimal changes in cytokine levels when compared to uncomplicated twins, although the majority of cytokine levels were higher in amniotic fluid than maternal blood. It does not appear that FLA evokes a significant change in cytokines.