Serum cytokine levels in congenital diaphragmatic hernia: predictive impact for the need for extracorporeal membrane oxygenation?

Background: Congenital diaphragmatic hernia (CDH) is a common cause of neonatal respiratory failure and a malformation associated with high mortality and morbidity. Extracorporeal membrane oxygenation (ECMO) is one of treatment options for CDH. Despite the ultrasound based lung-to-head ratio and the fetal lung volume determination, there is no reliable prenatal parameter for the clinical course and outcome of fetuses with CDH, in particular for the need of ECMO. Aim: The objective of the study was to investigate serum cytokine profiles and immune response from newborns with CDH requiring ECMO compared to CDH infants without ECMO and healthy newborns. Methods: We used multiplexed immunoassays based on Luminex beat technology to measure cytokines (Eotaxin, GCSF, GMCSF, IFNa2, IFNg, IL10, IL12p40, IL12p70, IL13, IL15, IL17, IL1a, IL1b, IL2, IL3, IL4, IL5, IL6, IL7, IL8, IP10, MCP1, MIP1a, MIP1b, TNFa, TNFb) in serum of newborns with CDH receiving ECMO (n=16) and conventional ventilation (n=27). Serum was collected before (baseline) and 24, 48 and 72 hours during ECMO and ventilation. Cord blood cytokines from healthy term newborns served as controls (n=13). Results: From the examined cytokines IFNg, IL12p70, IL13, IL15, IL17, IL1b, IL2, IL4, IL5, and TNFb were found to be under the detection limit of 3.2 pg/ml in CDH and healthy newborns. The concentrations of remaining cytokines at baseline were significantly elavated in newborns with CDH compared to controls. ECMO group showed higher median levels of IL10 and IL8at baseline compared to ventilated CDH infants (97.4 vs. 46.2 pg/ml and 48.3 vs. 30.6 pg/ml, both p<0.05). With cardiopulmory bypass, IL10 concentration showed a significant decreasing pattern. Baseline serum level and change in IL10 were not associated with fetal lung volume, pre-ECMO oxygenation-index and outcome of CDH. Conclusion: These findings suggest that inflammatory reaction and activation is associated with CDH. Thus, the high circulating levels and decreasing pattern of anti-inflammatory IL10 in CDH patients under ECMO treatment indicate that IL10 may be useful as a marker of the severity of CDH and as parameter for the need of ECMO intervention.