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ProblemHealthy pregnancy is associated with a physiologic increase in inflammatory responses. The objective of this study was to assess changes in plasma cytokines associated with uncomplicated pregnancy.Method of studyTo examine these changes, plasma levels of immune response mediators from healthy gravidas (N = 115, gestation weeks 23‐30) were compared with those from healthy non‐pregnant women (N = 42). Comparisons were performed using multiplex analysis for Th1 activity‐related cytokines (IFN‐γ, IL‐2, sIL‐2Rα, IL‐12[P70], and IL‐27), Th2 activity‐related cytokines (IL‐4, IL‐5, and IL‐13), other immune response mediators (GM‐CSF, IL‐1β, sIL‐1RI, IL‐6, IL‐8, IL‐15, IL‐17A, IL‐17F, IL‐21, IL‐22, IL‐23, TGFβ1, TGFβ2, TGFβ3, and TNFα), regulatory T cell–related cytokines (IL‐10 and sTNFRII), adipokines (adiponectin, leptin, PAI‐1, and resistin), chemokines (IP‐10, MCP‐1, and MIP‐1β), and hematopoietic growth factor IL‐7.ResultsMultivariate linear regression models showed increased levels of IL‐7, Th1‐, and Treg activity‐related cytokines and decreased levels of adipokines and chemokines in healthy gravidas compared with healthy non‐pregnant women. Additionally, season of the year, age, pre‐pregnancy body mass index, and HLA‐DR/DQ genotypes for type 1 diabetes risk showed different and sometimes reciprocal influence on cytokine levels.ConclusionOur study stresses the importance of profiling immune response mediators during pregnancy to better understand the effect of healthy pregnancy on cytokine levels.

Aims/Introduction Gestational diabetes (GDM) is characterized by low‐grade systemic inflammation, which manifests as changes in the levels of cytokines in the blood. We aimed to investigate plasma immune mediators during gestational weeks 23–28 in 213 women at risk for GDM, and to find associations between GDM and its complications. Materials and Methods We quantified the levels of adipokines: adiponectin, leptin, plasminogen activator inhibitor‐1 and resistin; chemokines: C‐C motif chemokine ligand 2 (CCL2), CCL4, C‐X‐C motif chemokine ligand 8 (CXCL8) and CXCL10; and cytokines: granulocyte‐macrophage colony‐stimulating factor, interferon‐γ, interleukin (IL)‐1β, soluble (s)IL‐1RI, IL‐2, sIL‐2Ra, IL‐4, IL‐5, IL‐6, IL‐7, IL‐10, IL‐12(p70), IL‐13, IL‐15, IL‐17A, IL‐17F, IL‐21, IL‐22, IL‐23, IL‐27, transforming growth factor (TGF)‐β1, TGF‐β2, TGF‐β3, tumor necrosis factor‐α and soluble tumor necrosis factor receptor 2 using the Milliplex®MAP Magnetic Bead assay on Luminex®200™, and compared the results with clinical data from pregnancy and post‐partum follow up. Results Lower levels of adiponectin and higher levels of CCL2 (Wilcoxon test, P = 3.4E‐03 and P = 0.03, respectively) were found in women with GDM. IL‐27 levels were associated with lower odds of GDM (adjusted logistic regression 0.90, P = 2.4E‐03), and showed a risk association with glutamic acid decarboxylase autoantibody positivity (adjusted odds ratio 1.13, P = 2.8E‐03). Similarly, higher IL‐22 levels increased the odds of glutamic acid decarboxylase autoantibody positivity (adjusted odds ratio 4.23, P = 0.04). TGF‐β1 was associated with post‐partum fasting glucose levels, and CCL4 with post‐partum C‐peptide levels (linear regression, P = 0.04 and P = 0.01, respectively). Women who developed pregnancy complications had higher levels of CXCL10 and CCL4 (linear regression, P = 7.0E‐04 and P = 0.01, respectively). Conclusions Plasma adiponectin and CCL2 concentrations distinguish women with GDM. IL‐27 and IL‐22 levels might select women with an autoimmune reaction, whereas increased TGF‐β1 and CCL4 are associated with post‐partum glucose and insulin metabolism.

Background: Gestational diabetes mellitus (GDM) can cause maternal and neonatal health problems, and its prevalence is increasing worldwide. We assessed the screening of GDM during a 7-year period and compared the outcome of pregnancies at high risk for GDM. Methods: We analyzed non-selected pregnant women (n = 5021) receiving antenatal care in Tartu University Hospital, Estonia in 2012–2018. Pregnant women were classified based on the absence or presence of GDM risk factors as low risk (n = 2302) or high risk for GDM (n= 2719), respectively. The latter were divided into subgroups after the oral glycose tolerance test (OGTT): GDM (n = 423), normal result (n = 1357) and not tested (n = 939). Results: The proportion of women with GDM risk factors increased from 43.5% in 2012 to 57.8% in 2018, and the diagnosis of GDM more than doubled (5.2% vs. 13.7%). Pregnancies predisposed to GDM but with normal OGTT results were accompanied by an excessive gestational weight gain and increased odds to deliver a LGA baby (AOR 2.3 (CI 1.8–3.0)). Conclusions: An increasing number of pregnancies presenting GDM risk factors are diagnosed with GDM. Pregnant women with GDM risk factors are, despite normal OGTT, at risk of increased weight gain and LGA newborns.