Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.
Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China.
JAMA Netw Open. 2021 Nov 1;4(11):e2132602. doi: 10.1001/jamanetworkopen.2021.32602.
Assisted reproductive technology (ART) has been widely used for treatment of infertility and has brought millions of births worldwide. The health of offspring conceived by ART has been of much concern, and adverse cardiovascular health outcomes have been reported by previous studies.
To assess the cardiovascular health of children conceived by ART.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted among participants recruited from November 2017 to February 2019. Participants were 382 children conceived by ART who were selected from a single reproductive center and 382 children who were naturally conceived, randomly selected from a primary school, and matched by sex, age, and maternal age at the child's birth (2 years older or younger). Data were analyzed from March 2019 through December 2019.
Conception by ART.
Blood pressure was measured, and echocardiography was performed to determine left ventricular structural and functional parameters. Adjusted relative wall thickness (aRWT) was found for age, with high RWT defined as an aRWT of 0.375 or more.
Among 764 children aged 6 to 10 years, 382 children were conceived by ART (mean [SD] age, 7.20 [1.21] years; 201 [52.6%] boys) and 382 children were naturally conceived (mean [SD] age, 7.20 [1.21] years; 201 [52.6%] boys). Children conceived by ART had statistically significantly increased mean (SD) height (130.2 [9.5] cm vs 128.5 [8.1] cm; P = .007) and body mass index (17.6 [3.6] vs 17.1 [2.7]; P = .03). Those conceived by ART, compared with children in the matched control group, had statistically significantly increased blood pressure (mean [SD] systolic blood pressure, 105.5 [6.9] mm Hg vs 103.5 [8.4] mm Hg; adjusted P < .001; mean [SD] diastolic blood pressure, 67.2 [5.6] mm Hg vs 62.2 [6.3] mm Hg ; adjusted P < .001), left ventricular systolic dysfunction (mean [SD] left ventricular ejection fraction, 64.61% [3.20%] vs 66.70% [3.89%]; adjusted P < .001), and diastolic dysfunction (mean [SD] early/late mitral/tricuspid diastolic velocities ratio, 1.66 [0.28] vs 2.21 [0.36]; adjusted P < .001). They also had statistically significantly increased parameters of left ventricular structure, including mean (SD) left ventricular mass index (31.97 [5.04] g/m2.7 vs 28.28 [3.54] g/m2.7; adjusted P < .001) and RWT (3.30 [0.41] mm vs 2.98 [0.14] mm; adjusted P < .001). Additionally, children conceived by ART had statistically significantly increased prevalence of left ventricular hypertrophy (9 children [2.4%] vs 2 children [0.5%]; P = .03), high RWT (61 children [16.0%] vs 0 children; P < .001), and left ventricle remodeling patterns, including concentric remodeling (60 children [15.7%] vs 0 children), eccentric hypertrophy (8 children [2.1%] vs 2 children [0.5%]), and concentric hypertrophy (1 child [0.3%] vs 0 children) (P for left ventricle remodeling < .001).
This study found that children conceived by ART had increased blood pressure and unfavorable changes in left ventricular structure and function compared with children who were naturally conceived. These findings suggest that further studies are needed to investigate the potential mechanisms and long-term outcomes associated with these differences.
辅助生殖技术(ART)已被广泛用于治疗不孕,并在全球范围内带来了数以百万计的生育。ART 所孕育的后代的健康一直备受关注,先前的研究报告了不良的心血管健康结局。
评估通过 ART 受孕的儿童的心血管健康。
设计、地点和参与者:本队列研究于 2017 年 11 月至 2019 年 2 月期间在一个单一的生殖中心选择的 382 名通过 ART 受孕的儿童和从一所小学随机选择的、按性别、年龄和儿童出生时母亲年龄(大 2 岁或 2 岁以下)匹配的 382 名自然受孕的儿童中进行。数据于 2019 年 3 月至 2019 年 12 月进行分析。
ART 受孕。
测量血压,并进行超声心动图检查以确定左心室结构和功能参数。发现了调整后的相对壁厚度(aRWT),其随年龄而变化,高 RWT 定义为 aRWT 为 0.375 或更高。
在 6 至 10 岁的 764 名儿童中,382 名儿童通过 ART 受孕(平均[SD]年龄,7.20[1.21]岁;201[52.6%]男孩),382 名儿童自然受孕(平均[SD]年龄,7.20[1.21]岁;201[52.6%]男孩)。与自然受孕的儿童相比,通过 ART 受孕的儿童的平均身高(130.2[9.5]cm 比 128.5[8.1]cm;P=0.007)和体重指数(17.6[3.6]比 17.1[2.7];P=0.03)有统计学意义的增加。与匹配对照组的儿童相比,通过 ART 受孕的儿童的血压(平均[SD]收缩压,105.5[6.9]mmHg 比 103.5[8.4]mmHg;调整后 P<0.001;平均[SD]舒张压,67.2[5.6]mmHg 比 62.2[6.3]mmHg;调整后 P<0.001)、左心室收缩功能障碍(平均[SD]左心室射血分数,64.61%[3.20%]比 66.70%[3.89%];调整后 P<0.001)和舒张功能障碍(平均[SD]早期/晚期二尖瓣/三尖瓣舒张速度比,1.66[0.28]比 2.21[0.36];调整后 P<0.001)有统计学意义的增加。他们的左心室结构参数也有统计学意义的增加,包括平均(SD)左心室质量指数(31.97[5.04]g/m2.7 比 28.28[3.54]g/m2.7;调整后 P<0.001)和 RWT(3.30[0.41]mm 比 2.98[0.14]mm;调整后 P<0.001)。此外,通过 ART 受孕的儿童左心室肥厚(9 名儿童[2.4%]与 2 名儿童[0.5%];P=0.03)、高 RWT(61 名儿童[16.0%]与 0 名儿童;P<0.001)和左心室重构模式(包括向心性重构[60 名儿童[15.7%]与 0 名儿童]、偏心性肥厚[8 名儿童[2.1%]与 2 名儿童[0.5%])和向心性肥厚[1 名儿童[0.3%]与 0 名儿童]的发生率有统计学意义的增加(左心室重构 P<0.001)。
本研究发现,与自然受孕的儿童相比,通过 ART 受孕的儿童的血压和左心室结构和功能有不利的变化。这些发现表明,需要进一步研究以探讨这些差异相关的潜在机制和长期结局。