Associations Between Paternal Obesity and Cardiometabolic Alterations in Offspring via Assisted Reproductive Technology

Context Both assisted reproductive technology (ART) and obesity are associated with adverse cardiometabolic alterations in offspring. However, the combined effects of paternal obesity and ART on offspring cardiometabolic health are still unclear.Objective To clarify cardiometabolic changes in offspring of obese fathers conceived using ART. This was a retrospective cohort study conducted between June 2014 and October 2019 at a center for reproductive medicine. A total of 2890 singleton visits aged 4-10 years were followed. Age-and sex-specific z-score of body mass index (BMI), blood pressure, insulin resistance, and lipid profile were examined.Results We observed a strong association between paternal BMI categories and offspring BMI, blood pressure, and insulin resistance. Compared with offspring of fathers with normal weight, multivariable-adjusted mean differences for BMI z-score were 0.53 (95% CI 0.37-0.68) for obese fathers, 0.17 (95% CI 0.05-0.30) for overweight fathers, and -0.55 (95% CI -0.95-0.15) for underweight fathers; corresponding values for systolic blood pressure z-score were 0.21(95% CI 0.07-0.35), 0.10 (95% CI -0.01-0.21), and -0.24 (95% CI -0.59-0.11), and corresponding values for homeostatic model assessment for insulin resistance z-score were 0.31 (95% CI 0.16-0.46), 0.09 (95% CI -0.02-0.21), and -0.11 (95% CI -0.48-0.28), respectively. The mediation analyses suggested that 57.48% to 94.75% of the associations among paternal obesity and offspring cardiometabolic alterations might be mediated by offspring BMI.Conclusion Paternal obesity was associated with an unfavorable cardiometabolic profile in ART-conceived offspring. Mediation analyses indicated that offspring BMI was a possible mediator of the association between paternal obesity and the offspring impaired metabolic changes.