Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; Blanquerna School of Health Sciences, Universitat Ramon Llull, Barcelona, Spain; Consorcio CIBER, M.P. Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain.
MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom; Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Fertil Steril. 2024 May;121(5):853-863. doi: 10.1016/j.fertnstert.2024.01.017. Epub 2024 Jan 17.
To assess whether parental infertility is associated with differences in cardiometabolic trajectories in offspring.
Pooled observational analysis in three prospective cohorts.
Three nationwide pregnancy cohorts.
A total of 14,609 singletons from 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 ages 26, 12, and 13 years, respectively.
Parental infertility is defined as time-to-pregnancy of ≥12 months (n = 1,392, 9.5%).
Trajectories of body mass index (BMI), waist circumference, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol (LDL-C) level, high-density lipoprotein cholesterol (HDL-C) level, triglycerides level, and glucose level were compared in the offspring of couples with and without infertility. Trajectories were modeled using mixed-effects models with natural cubic splines adjusting for cohort, sex of the offspring, and maternal factors (age, BMI, smoking, educational level, parity, and ethnicity). Predicted levels of cardiometabolic traits up to 25 years of age were compared with parental infertility.
Offspring of couples with infertility had increasingly higher BMI (difference in mean predicted levels by age 25 years: 1.09 kg/m2, 95% confidence interval [0.68-1.50]) and suggestively higher diastolic blood pressure at age 25 years (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 years, LDL-C: 4.07% [-0.79 to 8.93]; HDL-C: -2.78% [-6.99 to 1.43]). At age 17 years, offspring of couples with infertility had higher waist circumference (1.05 cm [0.11-1.99]) and systolic blood pressure (age: 17 years; 0.93 mmHg [0.044-1.81]), but these differences attenuated at later ages. No intergroup differences in triglyceride and glucose level trajectories were observed. Further adjustment for paternal age, BMI, smoking, and educational level, and both parents' histories of diabetes and hypertension in the cohort with this information available (Avon Longitudinal Study of Parents and Children) did not attenuate intergroup differences.
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.
评估父母不孕是否与后代的心脏代谢轨迹差异相关。
三个前瞻性队列的汇总观察性分析。
三个全国性的妊娠队列。
来自英国雅芳纵向父母与子女研究、葡萄牙 21 世代和阿姆斯特丹出生的儿童及其发育研究的 14609 名单胎。每个队列分别贡献了 26、12 和 13 岁时的数据。
父母不孕定义为受孕时间≥12 个月（n=1392，9.5%）。
比较不孕夫妇和正常夫妇的后代的体重指数（BMI）、腰围、收缩压、舒张压、低密度脂蛋白胆固醇（LDL-C）水平、高密度脂蛋白胆固醇（HDL-C）水平、甘油三酯水平和血糖水平的轨迹。使用混合效应模型，通过自然三次样条调整队列、后代的性别以及母亲因素（年龄、BMI、吸烟、教育水平、产次和种族）来拟合轨迹。将 25 岁前的心脏代谢特征的预测水平与父母不孕进行比较。
与正常夫妇相比，不孕夫妇的后代 BMI 逐渐升高（25 岁时的平均预测水平差异：1.09kg/m2，95%置信区间[0.68-1.50]），并且在 25 岁时舒张压也有升高趋势（1.21mmHg[-0.003 至 2.43]）。随着时间的推移，他们的 LDL-C 趋于升高，HDL-C 值趋于降低（年龄：25 岁，LDL-C：4.07%[-0.79 至 8.93]；HDL-C：-2.78%[-6.99 至 1.43]）。在 17 岁时，不孕夫妇的后代腰围（1.05cm[0.11-1.99]）和收缩压（年龄：17 岁；0.93mmHg[0.044-1.81]）更高，但这些差异在以后的年龄阶段会减弱。在随后的年龄阶段，未观察到甘油三酯和血糖水平轨迹的组间差异。在有可用信息的队列（雅芳纵向父母与子女研究）中，进一步调整父亲年龄、BMI、吸烟和教育水平以及父母双方的糖尿病和高血压史，也未能减弱组间差异。
与正常夫妇相比，不孕夫妇的后代 BMI 逐年升高，血压水平升高，LDL-C 升高，HDL-C 降低。
