Association of Assisted Reproductive Technologies With Arterial Hypertension During Adolescence

Meister, Théo A.; Rimoldi, Stefano F.; Soria, Rodrigo; Arx, Robert von; Messerli, Franz H.; Sartori, Cláudio; Scherrer, Urs; Rexhaj, Emrush

doi:10.1016/j.jacc.2018.06.060

Cited by 136 publications

(90 citation statements)

References 42 publications

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“…Many human assisted reproductive techniques occur either in seminal plasma-free environments and/or where embryos are transferred into a uterine environment that has not been primed by seminal plasma. Indeed, studies are now identifying significant changes in cardiometabolic health of children derived from assisted reproductive techniques (Meister et al 2018).…”

Section: Discussionmentioning

confidence: 99%

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

Morgan

Paganopoulou

Akhtar

et al. 2019

The Journal of Physiology

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Key points A low protein diet had minimal effects on paternal cardiovascular function or renin–angiotensin system activity. Paternal low protein diet modified F1 neonatal and adult offspring renin–angiotensin system activity and cardiovascular function in a sperm and/or seminal plasma specific manner. Paternal low protein diet modified F1 male offspring testicular expression of central epigenetic regulators. Significant changes in F2 neonatal offspring growth and tissue angiotensin‐converting enzyme activity were programmed by paternal low protein diet in a sperm and/or seminal plasma specific manner. Abstract Although the impact of maternal diet on adult offspring health is well characterized, the role that a father's diet has on his offspring's health remains poorly defined. We establish the significance of a sup‐optimal paternal low protein diet for offspring vascular homeostasis and define the sperm and seminal plasma specific programming effects on cardiovascular health. Male C57BL6 mice were fed either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 7 weeks. Using artificial insemination, in combination with vasectomized male mating, we generated offspring derived from either NPD or LPD sperm (devoid of seminal plasma) but in the presence of NPD or LPD seminal plasma (devoid of sperm). We observed that either LPD sperm or seminal fluid at conception impaired adult offspring vascular function in response to both vasoconstrictors and dilators. Underlying these changes in vascular function were significant changes in serum, lung and kidney angiotensin‐converting enzyme (ACE) activity, established in F1 offspring from 3 weeks of age, maintained into adulthood and present also within juvenile F2 offspring. Furthermore, we observed differential expression of multiple central renin–angiotensin system regulators in adult offspring kidneys. Finally, paternal diet modified the expression profiles of central epigenetic regulators of DNA methylation, histone modifications and RNA methylation in adult F1 male testes. These novel data reveal the impact of sub‐optimal paternal nutrition on offspring cardiovascular well‐being, programming offspring cardiovascular function through both sperm and seminal plasma specific mechanisms over successive generations.

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Section: Discussionmentioning

confidence: 99%

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

Morgan

Paganopoulou

Akhtar

et al. 2019

The Journal of Physiology

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“…Hansen et al studied more than 210,000 children born in Western Australia between 1994 and 2002 and found an increased risk of intellectual disability for children conceived by ART (10). Researchers also reported an increase in arterial hypertension in children conceived by ART, probably due to ART-induced premature vascular aging (13,14). Fetus conceived by ART also showed signs of cardiovascular remodeling, including a more globular heart, thick myocardial walls, decreased longitudinal functions, impaired relaxation, and dilated atria (15).…”

Section: Introductionmentioning

confidence: 99%

Children Conceived by Assisted Reproductive Technology Prone to Low Birth Weight, Preterm Birth, and Birth Defects: A Cohort Review of More Than 50,000 Live Births During 2011–2017 in Taiwan

et al. 2020

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Objectives: The use of assisted reproductive technology (ART) has increased rapidly in Taiwan. The purpose of this study is to discuss the risks of low birth weight, preterm birth, and birth defect for children conceived by assisted reproductive technology in Taiwan.Methods: Both National ART report database and National birth reports were obtained from the Health Promotion Administration in the Ministry of Health and Welfare in Taiwan. The cohort included live births (n = 1,405,625) and children conceived by ART (n = 50,988/172,818 cycles) from 2011 to 2017. The prevalence of low birth weight, preterm birth, and birth defect were compared between the ART and natural pregnancy groups.Results: Children conceived by ART displayed a higher rate of low birth weight as compared to those in the natural pregnancy group (p < 0.001), even when analyses were restricted to singleton births (p < 0.001). A higher rate of preterm birth (p < 0.001) was also observed in children conceived by ART even when analyses were restricted to singleton births (p < 0.05). A significant increased rate of birth defects was noted from children conceived by ART (p < 0.05). Conclusions:With the increasing need for and use of ART-conceptions, the likelihood of risks induced or related to Assistant Reproductive Technology (ART) has drawn considerable attention in recent years. Taiwan, as one of the leading countries with outstanding ART performances and modern medical care, the result of the current study suggests that further consideration and tighter regulations and policy are needed with regard to the use of ART.

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“…Although the overwhelming number of children born with the aid of ART and NIFT are healthy and developing normally, reports of potential increases in the incidence of premature birth, low birth weight, congenital abnormalities, and imprinting disorders in the ART group are concerning . Increasingly, data suggest that children born with ART are at greater risk of developing adult onset cardiovascular dysfunction, including premature atherosclerosis, systemic hypertension, the persistence of fetal cardiovascular remodeling, vascular endothelial dysfunction, and exaggerated hypoxic pulmonary vasoconstriction . For example, a few studies that included small numbers have shown that children conceived via ART have systemic vascular endothelial dysfunction, as demonstrated by selective impairment of endothelium‐dependent vasodilation utilizing flow‐mediated dilation, increased carotid artery stiffness with intima‐medial hypertrophy, and increased systemic blood pressure .…”

Section: Introductionmentioning

confidence: 99%

“…[5][6][7][8] Increasingly, data suggest that children born with ART are at greater risk of developing adult onset cardiovascular dysfunction, including premature atherosclerosis, systemic hypertension, the persistence of fetal cardiovascular remodeling, vascular endothelial dysfunction, and exaggerated hypoxic pulmonary vasoconstriction. 5,[9][10][11][12] For example, a few studies that included small numbers have shown that children conceived via ART have systemic vascular endothelial dysfunction, as demonstrated by selective impairment of endothelium-dependent vasodilation utilizing flowmediated dilation, increased carotid artery stiffness with intimamedial hypertrophy, and increased systemic blood pressure. 9,12 Importantly, compared to age-matched controls, healthy children conceived via ART display an exaggerated hypoxic pulmonary vasoconstricting response at altitude, that is associated with right ventricular dysfunction.…”

Section: Introductionmentioning

confidence: 99%

“…5,[9][10][11][12] For example, a few studies that included small numbers have shown that children conceived via ART have systemic vascular endothelial dysfunction, as demonstrated by selective impairment of endothelium-dependent vasodilation utilizing flowmediated dilation, increased carotid artery stiffness with intimamedial hypertrophy, and increased systemic blood pressure. 9,12 Importantly, compared to age-matched controls, healthy children conceived via ART display an exaggerated hypoxic pulmonary vasoconstricting response at altitude, that is associated with right ventricular dysfunction. 9,11 Although baseline pulmonary hemodynamic parameters were normal in these children, the exaggerated pulmonary vascular response to hypoxia is likely indicative of endothelial dysfunction.…”

Section: Introductionmentioning

confidence: 99%

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Outcomes of pulmonary vascular disease in infants conceived with non‐IVF fertility treatment and assisted reproductive technologies at 1 year of age

Fineman

Baer

Chambers

et al. 2019

Pediatric Pulmonology

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Background Assisted reproductive technologies (ARTs) have been associated with the development of endothelial dysfunction. Objective To determine potential differences in outcomes associated with pulmonary vascular disease in infants born to mothers receiving any infertility treatment including ART and non‐IVF fertility treatments (NIFTs). Design/Methods The sample was derived from an administrative database containing detailed information on infant and maternal characteristics for live‐born infants in California (2007‐2012) with gestational age (GA) 22 to 44 weeks. Cases were defined as infants with ICD‐9 code for pulmonary vascular disease (PVD) and records for ART/NIFT. Controls were randomly selected at a 1:4 ratio. The primary outcome was 1‐year mortality. Crude and adjusted odds ratio (OR) with 95% confidence interval (CI) were calculated. Results We identified 159 cases and 636 controls. Mothers that utilized ART/NIFT were older, to be of the Caucasian race, to have pre‐eclampsia, private insurance, and education >12 years (P < .001). Cases compared to controls were more premature, had lower birth weights, and were more often the product of a multiple gestation pregnancy (P < .001). Cases had a higher 1‐year mortality (18.2% vs 9.1%; OR: 2.2; 95% CI: 1.4, 3.6), more severe PVD (86.2% vs 72.3%; OR: 2.4; 95% CI: 1.5, 3.9), and a longer hospital stay (66.7 ± 73.0 vs 32.5 ± 47.2 days; P < .001) than controls. However, when adjusting for GA these differences become statistically insignificant. Conclusion Children born following ART/NIFT with PVD had increased mortality compared to infants with PVD but without ART/NIFT. The primary driver of this relationship is prematurity.

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Association of Assisted Reproductive Technologies With Arterial Hypertension During Adolescence

Cited by 136 publications

References 42 publications

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

Children Conceived by Assisted Reproductive Technology Prone to Low Birth Weight, Preterm Birth, and Birth Defects: A Cohort Review of More Than 50,000 Live Births During 2011–2017 in Taiwan

Outcomes of pulmonary vascular disease in infants conceived with non‐IVF fertility treatment and assisted reproductive technologies at 1 year of age

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