亲代不孕是否与子代心血管代谢的差异有关？

Objective

目的

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

评估亲代不孕是否与子代心血管代谢变化趋势的差异有关。

Design

研究设计

Pooled observational analysis in three prospective cohorts.

对三个前瞻性队列研究进行综合观察分析。

Setting

研究背景

Three nationwide pregnancy cohorts.

三个全国性妊娠队列。

Patients

研究对象

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.

根据英国雅芳父母与儿童纵向研究（Avon Longitudinal Study of Parents and Children）、葡萄牙Geracao 21研究（the Portuguese Geracao 21）以及阿姆斯特丹出生儿童及其发展研究（the Amsterdam Born Children and Their Development study），共纳入14609名单身人士。每项队列研究分别提供研究对象年龄在26岁，12岁以及13岁前的相应数据。

Intervention

干预

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

将父母未避孕未孕时间≥12 个月定义为亲代不孕不育（n = 1,392，9.5%）。

Main Outcome Measures

主要观察指标

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.

比较不孕不育夫妇和非不孕不育夫妇子代的身体质量指数(BMI), 腰围，收缩压，舒张压，低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、甘油三酯及血糖水平。采用混合效应模型及对变化轨迹进行建模，并以自然立方样条函数调整队列、子代性别及母亲因素（包含年龄、BMI、吸烟、教育水平、生育次数和种族）。将子代25岁之前心血管代谢特征的预测水平与父母不孕不育情况进行比较。

Results

结果

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.

不孕不育夫妇后代的BMI越来越高(25岁预测水平的均差为：1.09 kg/ m2, 95%可信区间[0.68-1.50])，25岁时舒张压也明显升高（1.21 mmHg，[0.003 - 2.43])。且随年龄增长，LDL-C水平呈升高趋势，而HDL-C呈下降趋势(年龄：25岁，LDL-C: 4.07% [0.79-8.93]；HDL-C: 2.78%[6.99-1.43])。17 岁时，不孕不育夫妇子女的腰围较大（1.05cm，[0.11-1.99]），且收缩压较高（年龄：17 岁；0.93 mmHg[0.044-1.81]），但随着年龄增长，这些差异逐渐减小。甘油三酯和血糖水平变化趋势未观察到组间差异。在包含这些信息的队列研究(Avon Longitudinal Study of parents and Children)中，针对父亲年龄、BMI、吸烟、教育水平，以及父母双方的糖尿病和高血压病史进行进一步校正，并未减弱组间差异。

Conclusion

结论

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.

与生育正常的夫妇相比，不孕夫妇的子代多年后BMI逐渐增高，血压水平似乎也更高，并且随着年龄增长，LDL-C值更高，而HDL-C值更低。

参考文献：Parental infertility and offspring cardiometabolic trajectories: a pooled analysis of three European cohortsHernáez, Álvaro et al. Fertility and Sterility, Volume 121, Issue 5, 853 - 863