Sex-specific associations of sedentary behaviour and physical activity with placental and fetal IL-6 in pregnant women with obesity. Impact on neonatal adiposity in the DALI randomised controlled trial

Aims: To investigate: i) the association of sedentary time (ST) and moderate-to-vigorous physical activity (MVPA) during pregnancy with placental interleukin-6 (IL-6) expression and cord venous IL-6 content in women with obesity; and ii) cord venous markers mediating the relationship of ST/MVPA and placental IL-6 with neonatal adiposity. Methods: Among 134 participants, ST and MVPA were assessed using accelerometry at three gestational periods. Placental IL-6 mRNA was quantified using Nanostring technology. Cord blood concentrations of glucose, leptin, insulin, C-peptide and IL-6 were determined. Neonatal fat percentage was calculated from skinfold measurements. Results: Increasing MVPA from inclusion (<20 weeks) to 24–28 or 35–37 weeks, and reducing ST to 24–28 weeks, were associated with higher IL-6 expression in female placentas (p < 0.05). Increasing MVPA from inclusion to 24–28 weeks was associated with lower cord venous IL-6 levels in male fetuses (p = 0.006). Lower cord glucose and insulin concentrations and insulin resistance mediated the association between increased placental IL-6 and reduced neonatal adiposity (p < 0.05). Conclusions: In women with obesity, increasing MVPA and reducing ST during pregnancy is associated with higher IL-6 expression in female placentas and lower cord IL-6 in male fetuses. Higher placental IL-6 expression is linked to reduced fetal insulinemia and insulin resistance, contributing to lower neonatal adiposity. Twitter summary/social media: In pregnant women with obesity, higher moderate-vigorous physical activity and lower sedentary time upregulate placental IL-6 expression, which in turn is related to lower neonatal adiposity through reduced fetal insulinemia and insulin resistance. Clinical trial registration number: ISRCTN70595832.