Postnatal persistence of fetal cardiovascular remodelling associated with assisted reproductive technologies: a cohort study

Valenzuela-Alcaráz, Brenda; Serafini, A.; Bijnens, Bart; Casals, Gemma; Rodríguez‐López, Mérida; García‐Otero, Laura; Cruz‐Lemini, M.; Sitges, Marta; Balasch, Juan; Gratacós, E.; Crispi, F.

doi:10.1111/1471-0528.15246

Cited by 43 publications

(32 citation statements)

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“…Fetuses conceived by assisted reproductive technologies also display a cardiac phenotype of concentric ventricular remodeling together with atrial dilatation, decreased longitudinal motion, and impaired relaxation [16,24]. It is postulated to be a response to a predominantly right pressure overload, and it is consistent with studies reporting increased pulmonary pressures in children conceived by assisted reproductive technologies.…”

Section: Globular Shapesupporting

confidence: 59%

“…The first reports of fetal myocardial hypertrophy with cardiomegaly were associated with maternal diabetes and proposed to be mediated by fetal hyperinsulinemia [24]. It is characterized by enlarged hearts, thickening of the myocardium, and increased shortening fraction and lon- gitudinal motion [25].…”

Section: Myocardial Hypertrophy With Cardiomegalymentioning

confidence: 99%

“…It is characterized by enlarged hearts, thickening of the myocardium, and increased shortening fraction and lon- gitudinal motion [25]. Myocardial hypertrophy particularly affects the septum and may lead to left ventricular outflow obstruction [24]. The use of antiretroviral drugs -particularly zidovudine, which induces cardiac mitochondrial toxicity and thus decreased intrinsic contractility -during pregnancy has been reported to be associated with a characteristic pattern of concentric hypertrophy with larger hearts, increased myocardial wall thickness, and more spherical ventricles (Fig.…”

Section: Myocardial Hypertrophy With Cardiomegalymentioning

confidence: 99%

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Main Patterns of Fetal Cardiac Remodeling

et al. 2020

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The heart is a central organ in the fetal adaptation to an adverse environment. Fetal cardiac changes may persist postnatally and increase the risk of cardiovascular disease in adulthood. Knowledge about fetal cardiac structural as well as functional remodeling has radically improved over the last few years. As it occurs in postnatal life, the fetal heart remodels -changing its structure and shape -to adapt to an insult. Several conditions have been reported to be associated with fetal cardiac remodeling including intrauterine growth restriction, diabetes, exposure to antiretroviral drugs, conception by assisted reproductive technologies, pulmonary stenosis, and other congenital heart diseases. Here we summarized the main observable patterns of cardiac remodeling, i.e., globular shape, hypertrophy without dilation, and hypertrophy with cardiomegaly. We discuss the potential pathophysiology behind different types of remodeling. Defining precisely the distinct patterns of fetal cardiac remodeling is critical for advancing in the understanding of fetal cardiovascular programming and its consequences on adult health, and potentially for the design of preventive strategies that might have an impact on long-term cardiovascular health.

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Section: Globular Shapesupporting

confidence: 59%

Section: Myocardial Hypertrophy With Cardiomegalymentioning

confidence: 99%

Section: Myocardial Hypertrophy With Cardiomegalymentioning

confidence: 99%

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Main Patterns of Fetal Cardiac Remodeling

et al. 2020

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“…For example, IT use was associated with advanced maternal age, and more likely to have private insurance and >12 years of education. Previous studies have also demonstrated advanced maternal age . Interestingly, US states that have mandated health insurance coverage for ART procedures, have rates of ART approximately 1.5 times the national rate .…”

Section: Discussionmentioning

confidence: 96%

“…Previous studies have also demonstrated advanced maternal age. 6,9,11,36,37 Interestingly, US states that have mandated health insurance coverage for ART procedures, have rates of ART approximately 1.5 times the national rate. 36 Finally, although to our knowledge education level has not been previously compared, both insurance and education can be considered surrogate markers for increased income, which has been associated with increased IT use.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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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).

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Postnatal persistence of fetal cardiovascular remodelling associated with assisted reproductive technologies: a cohort study

Abstract: Cardiovascular changes described in fetuses conceived by ART, persist in children at 3 years of age.

Cited by 43 publications

References 30 publications

Main Patterns of Fetal Cardiac Remodeling

Main Patterns of Fetal Cardiac Remodeling

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

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

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