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Faculty have requested this content not be shared on social media
CME Credit Offered
CME Credit Offered
Abstract Award
Abstract Award
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Poster Session 1

(272) Sex differences in cord blood inflammation at birth in offspring exposed to gestational diabetes mellitus

Thursday, January 30, 2025
10:30 AM – 12:30 PM  
Objective: Exposure to gestational diabetes mellitus (GDM) in utero can lead to adverse offspring cardiometabolic and neurodevelopmental outcomes, with boys and girls at different degrees of risk. Programming of innate immune responses, i.e. "trained immunity," may be a key driver of vulnerability vs resiliency in the face of future immune challenges. Sex-specific mechanisms represent a significant knowledge gap. We have previously shown that in GDM, placental expression of IGFBP1 – an anti-inflammatory biomarker of maternal insulin sensitivity – is reduced in pregnancies with a male fetus but increased with a female fetus. Here, we tested the hypothesis that cord blood markers of innate immune activation are increased in males exposed to GDM in utero but decreased in females.

Study Design:

40 pregnant individuals with live singleton term births enrolled in the MGH pregnancy biorepository (Aug. 2020 - Feb. 2024) were included: 20 with GDM (N=10 females, 10 males) and 20 without GDM (N=10 females, 10 males). Proinflammatory cytokines/chemokines associated with innate immune responses were quantified in umbilical cord plasma collected at delivery using a 20-Plex bead-based immunoassay (ThermoFisher). The impact of fetal sex and GDM on cord plasma analyte concentrations was assessed by two-way ANOVA. Spearman correlations were calculated between placental IGFBP1 expression and cord plasma analytes.

Results:

Placental IGFBP1 is inversely correlated with cord plasma TNF-α (p=0.046), a key proinflammatory cytokine – Fig. 1A. C-C motif chemokine ligand 3 (CCL3) levels are sexually dimorphic: higher in GDM-exposed males and lower in GDM-exposed females (GDM-sex interaction term on 2-way ANOVA p=0.007); CCL4 showed a similar trend (p=0.088) – Fig. 1B. IFN-α, IL-6, and IL-17A levels are elevated in males (p=0.029, p=0.007, p=0.047) independent of GDM – Fig. 2.

Conclusion:

In GDM, cord plasma levels of chemokines associated with innate immunity are sexually dimorphic and may relate to proinflammatory signaling pathways in the placenta. These results point to potential sex-specific mechanisms of immune programming in GDM.