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.

Carbohydrate and fatty acid perturbations in the amniotic fluid of the recipient twin of pregnancies complicated by twin-twin transfusion syndrome in relation to treatment and fetal cardiovascular risk

“…In MCDA pregnancies affected by TTTS, a small number of studies, targeting specific areas of metabolism have been reported (22,23). Molecular patho-mechanistic changes have been observed in angiogenic growth factors (24), cytokine levels (25) and gene transcripts in amniotic fluid and maternal plasma which appear to predict fetal outcome (26,27).…”

Maternal vascular endothelial growth factor receptor and interleukin levels in pregnant women with twin-twin transfusion syndrome

“…IL-6, IL-1β, TNF-α, IL-10, IL-4, IL-8 and TIMP-1 levels are higher in the amniotic fluid than in plasma suggesting that the abnormality of cytokine expression in pregnant women with TTTS by laser as local cytokine release. In addition, no significant difference in the plasma and amniotic laser-mediated intoxicating cytokine concentrations of the patients except for the decrease in epidermal growth factor in the amniotic fluid after treatment compared to those before treatment [32]. Although IL-8 levels are not detected in our study subjects, IL-6 levels are increased in twin pregnant women with TTTS after surgical treatment suggesting a role of IL-6 in response to the treatment, and thus that IL-6 may serve as a marker for the prognosis of surgical treatment in twin pregnant women with TTTS.…”

Comparison of Pregnancy Outcomes of Previable and Periviable Rupture of Membranes After Laser Photocoagulation for Twin–Twin Transfusion Syndrome

“…For this reason, the latency data were examined, and, interestingly, earlier surgery is associated with longer latency yet still lower survival. Previously, it has been shown that in twin–twin transfusion syndrome there are higher levels of inflammatory markers in the amniotic fluid 26 than in maternal serum, and likely in a physiologic protective mechanism, an increase in tissue inhibitor of metalloproteinases. 27 Perhaps an imbalance in the in-utero environment results in PROM, and further evaluation of the levels of inflammatory markers, matrix metalloproteinases, and their inhibitors at the time of surgery is warranted as these markers may provide insight into a patient's risk of postoperative PROM and may better elucidate the mechanism by which postoperative PROM occurs.…”