Parental infertility and offspring cardiometabolic trajectories up to 25 years: a pooled analysis of three European cohorts

ObjectiveTo assess whether parental infertility is associated with differences in cardiometabolic trajectories in offspring from childhood to 25 years of age. DesignPooled analysis of three European pregnancy cohort studies. SubjectsUp to 14,609 singletons from three pregnancy cohorts (the UK Avon Longitudinal Study of Parents and Children, the Portuguese Geracao 21, and the Amsterdam Born Children and their Development study). ExposureParental infertility defined as time-to-pregnancy [≥]12 months. Main Outcome MeasuresTrajectories of body mass index (BMI), waist circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, and glucose from childhood to 25 years of age were compared in offspring of couples with and without infertility. Trajectories were modelled using mixed-effects models with natural cubic splines adjusting for cohort, sex of the offspring, and maternal factors (age, body mass index, smoking, educational level, parity, and ethnicity). Predicted levels of cardiometabolic traits up to 25 years of age were compared by parental infertility. ResultsOffspring of couples with infertility had increasingly higher BMI (difference in mean predicted levels by age 25: +1.09 kg/m2, 95% confidence interval [0.68 to 1.50]) and suggestively higher DBP at age 25 (+1.21 mmHg [0.00 to 2.43]). Their LDL-C tended to be higher, and their HDL-C values tended to be lower over time (age 25, LDL-C: +4.07% [-0.79 to 8.93]; HDL-C: -2.78% [-6.99 to 1.43]). At middle-late adolescence, offspring of couples with infertility had higher waist circumference (age 17: +1.05 cm [0.11 to 1.99]) and SBP (age 17: +0.93 mmHg [0.044 to 1.81]), but these differences attenuated at later ages. No clear inter-group differences in triglyceride and glucose trajectories were observed. Further adjustment for paternal age, body mass index, smoking, and educational level, and both parents history of diabetes and hypertension in the cohort with this information available (Avon Longitudinal Study of Parents and Children) did not attenuate inter-group differences. ConclusionOffspring of couples with infertility have increasingly higher BMI over the years, suggestively higher blood pressure levels, and tend to have greater values of LDL-C and lower values of HDL-C with age.