Introduction: Polycystic ovary syndrome (PCOS) is a common condition affecting up to 18% of reproductive-aged women. It is associated with reproductive, metabolic and psychological dysfunction. While the genetics of PCOS are as yet not fully understood, it is recognised as a familial condition. Limited research suggests that offspring of women with PCOS have altered insulin resistance, glucose intolerance, lipids and leptin, however other markers of cardio-metabolic function have not been characterised.
Methods: A cross-sectional comparison of cord blood parameters in the offspring of women with (n=55) and without (n=55) PCOS. Women were further categorised into those with (n=82) and without (n=28) gestational diabetes, and subgrouped by treatment status (metformin n=33, insulin n=43 or unknown n=6). Outcomes included core blood insulin, glucose, leptin, lipids and inflammatory cytokines.
Results: Offspring of women with and without PCOS had similar cord blood markers on unadjusted analysis. On models adjusting for GDM, maternal race, maternal age, birth weight, gestational age, infant gender, method of delivery and smoking status, offspring of women with PCOS had elevated leptin (p=0.040) and granulocyte-macrophage-colony-stimulating factor (GMCSF; p=0.043). GDM, irrespective of PCOS status, was associated with increased glucose (p<0.001) and high density lipoproteins (p<0.001), and decreased CRP (p<0.001). Treatment of GDM with metformin decreased glucose levels compared to insulin (p=0.024), while the other measures were unaffected by treatment.
Conclusion: The elevation in cord blood GMCSF and leptin with PCOS indicates potential programming of cardiometabolic systems in-utero, independent of GDM or treatment status. These programming effects may become exacerbated in combination with the increased glucose and high density lipoprotein concentrations that occurs with gestational diabetes. This research contributes to a mechanistic understanding of the intergenerational impact of PCOS. These markers can be evaluated in future PCOS intervention studies to evaluate the efficacy of the intervention and provide understanding of biological mechanisms involved.