Assessment of Cardiovascular Health of Children Ages 6 to 10 Years Conceived by Assisted Reproductive Technology

Abstract

IMPORTANCEAssisted 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. OBJECTIVE 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. EXPOSURES Conception by ART. MAIN OUTCOMES AND MEASURES 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. RESULTS 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/m 2.7 vs 28.28 [3.54] g/m 2.7 ; 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).

Subjects Conceived through Assisted Reproductive Technologies Display Normal Arterial Stiffness

“…There is contradictory evidence on cardiovascular health of ART subjects. Several studies consider early vascular alterations in subjects conceived after using ART, potentially leading to increased cardiovascular morbidity and mortality later in life, as possible long-term health consequences [ 15 , 16 , 17 ]. A meta-analysis conducted by Guo et al revealed a significantly increased blood pressure, suboptimal cardiac diastolic function and elevated vessel thickness as a conspicuous cardiovascular risk profile of the ART offspring [ 18 ].…”

Temporary Increased LDL-C in Offspring with Extreme Elevation of Maternal Preconception Estradiol: A Retrospective Cohort Study

“…Previous studies, including ours, indicated that offspring conceived through in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) showed less favorable metabolic health manifesting as differential peripheral body fat deposit, 1 , 2 elevated blood pressure, 3 deteriorate gluco-metabolism, 4–6 raised triglycerides (TG), 7 and decreased low-density lipoprotein cholesterol (LDL-C) levels. 5 According to the DOHaD theory, metabolic changes in later life can be traced back to abnormal exposure during early life.…”

Murine blastocysts generated by in vitro fertilization show increased Warburg metabolism and altered lactate production

“…While the great majority of children born with these technologies are healthy, it has also been suggested that ARTs could be associated with an increased risk of adverse perinatal outcome and possibly an increased predisposition to adult-onset chronic diseases ( Berntsen et al, 2019 ; Kleijkers et al, 2014 ; Qin et al, 2017 ). In particular, several reports have shown that ART offspring display altered growth pattern ( Ceelen et al, 2009 ; Kleijkers et al, 2016 ), increased risk of cardiometabolic dysfunction ( Ceelen et al, 2008 ; Guo et al, 2017 ), higher systolic and diastolic blood pressures ( Cui et al, 2021 ; Guo et al, 2017 ; Meister et al, 2018 ), premature vascular aging ( Meister et al, 2018 ), altered lipid metabolism ( Guo et al, 2017 ), and increased the prevalence of cerebral palsy ( Goldsmith et al, 2018 ). Therefore, assessing the health of ART offspring and understanding the safety of ART is of critical importance.…”