Longitudinal changes in serum immune markers during normal pregnancy in a North-Indian population

Problem The objective of this study was to examine levels of cytokines across normal term pregnancy in an Indian population. Additionally we have also explored for possible associations between inflammatory markers and fetal growth parameters. Method of Study A multiplex panel of 24 analytes was used to examine levels of inflammatory markers in maternal serum at three time points during pregnancy and in cord blood from women with no reported comorbidities who delivered a singleton live baby at term (N = 23), enrolled in the GARBH-Ini pregnancy cohort. Linear mixed models were applied to construct longitudinal cytokine trajectories with gestational age. Pearson correlation was used to calculate intra-visit correlation between cytokines. Principal component analysis (PCA) was performed to examine cytokine combinations prevalent across pregnancy, and their association with fetal growth parameters was determined by multivariable regression. Results Significant increase in sFLT-1, Flt3L, PLGF, IL-4, and IL-18 and a decrease in VCAM-1 concentrations was seen across pregnancy. The cytokine concentrations in cord blood differed substantially as compared to maternal levels across gestation. Some cytokines were closely correlated with each other in distinct patterns across pregnancy. Gestational age specific combination of cytokines were seen to be associated with different fetal growth parameters. Conclusions This study for the first time provides reference concentrations for the longitudinal expression of immune markers across pregnancy in an Indian population providing a much needed baseline to compare with pregnancies leading to adverse outcomes. Growth factors showed maximum longitudinal variation with gestational age and strong correlations were identified between various cytokines at all time points across pregnancy.