The immunological profile of maternal obesity at 28 weeks gestation underpins common negative pregnancy outcomes

Abstract

Maternal obesity has been implicated in adverse pregnancy outcomes such as miscarriage, preeclampsia and gestational diabetes mellitus (GDM) and poses a risk to the neonate. There is a knowledge gap surrounding obesity and changes to the maternal immune system. Hypothesis: Obesity exacerbates systemic inflammation in pregnant women at 28 weeks of gestation. Samples: Peripheral blood was collected from fasted women at 26–28 weeks of gestation; all were GDM-negative Results: Insulin (p=<0.0001) and PAI-1 (p=0.0487) levels were increased in obese versus non-obese pregnant women. Obese women had a relative neutrophilia (p=0.0429) accompanied by diminished eosinophil (p=0.0178) and NKT cell (p=0.0124) numbers. The inflammatory cytokine profile of MNCs was mostly unchanged with obesity but the Th profile of pregnant women with obesity appears skewed towards Th17: on stimulation with CytoStim™, IL-6 (p=0.0183), TNFα (p=0.0478), IL-17F (p=0.0183) and IL-22 (p=0.0183) levels were increased; Th2 cells (p=0.0250) were also reduced with maternal obesity. Monocyte phenotypes showed some changes with obesity; on intermediate monocytes, CD86 (p=0.0068) was decreased yet CD163 (p=0.0421) was increased, and CCR2 expression was elevated on classical (p=0.0040) and intermediate (p=0.0340) monocytes. There is a shift to Th1 and Th17 in obesity in the general populations, whereas pregnancy is associated with a shift to Th2 and Treg. Here, we show that this profile is compromised in maternal obesity, which might underpin detrimental effects on pregnancy. Further research should investigate homogenous populations of cells such as eosinophils, monocytes and T cells, to further understand the immunological consequences of maternal obesity.