Parental infertility and offspring cardiometabolic trajectories: a pooled analysis of three European cohorts

Objective
To assess whether parental infertility is associated with differences in cardiometabolic trajectories in offspring.

Design
Pooled analysis of three European pregnancy cohort studies.

Subjects
14,609 singletons from three pregnancy cohorts: the UK Avon Longitudinal Study of Parents and Children, the Portuguese Geraçao 21, and the Amsterdam Born Children and their Development study. Each cohort contributed data up to age 26, 12, and 13, respectively.

Exposure
Parental infertility defined as time-to-pregnancy ≥12 months (n = 1,392, 9.5%).

Main Outcome Measures
Trajectories 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 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.

Results
Offspring 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 [-0.003 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 age 17, offspring of couples with infertility had higher waist circumference (+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 inter-group differences in triglyceride and glucose trajectories were observed. Further adjustment for paternal age, body mass index, smoking, and educational level, and both parent’s 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.

Conclusion
Offspring of couples with infertility relative to those of fertile couples 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.