4.8 Article

Assisted Reproductive Technologies Are Associated With Cardiovascular Remodeling In Utero That Persists Postnatally

Journal

CIRCULATION
Volume 128, Issue 13, Pages 1442-1450

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCULATIONAHA.113.002428

Keywords

fertilization in vitro; pediatrics; pregnancy; reproductive techniques; assisted; ventricular remodeling

Funding

  1. Agencia de Gestio d'Ajuts Universitaris i de Recerca-Generalitat de Catalunya, Spain [2009SGR 1099]
  2. Instituto de Salud Carlos III
  3. Fondo Europeo de Desarrollo Regional de la Union Europea, Spain [PI11/00051, PI11/01709]
  4. Centro para el Desarrollo Tecnico Industrial (cvREMOD) of the Ministerio de Economia y Competitividad y Fondo de inversion local para el empleo, Spain
  5. Ministerio de Economia y Competitividad PN de I+D+I, Spain [SAF2009-08815]
  6. Cerebra Foundation for the Brain Injured Child, Carmarthen, Wales, UK
  7. Thrasher Research Fund, Salt Lake City, UT
  8. Mexican National Council for Science and Technology (CONACyT, Mexico City, Mexico)
  9. Programa de Intensificacion Actividad Investigadora en el Sistema Nacional de Salud Instituto de Salud Carlos III
  10. Fundacio la Caixa
  11. ICREA Funding Source: Custom

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Background Assisted reproductive technologies (ARTs) have been shown to be associated with general vascular dysfunction in late childhood. However, it is unknown whether cardiac remodeling is also present and if these changes already manifest in prenatal life. Our aim was to assess fetal and infant (6 months of age) cardiovascular function in ART pregnancies. Methods and Results This prospective cohort study included 100 fetuses conceived by ART and 100 control pregnancies. ART fetuses showed signs of cardiovascular remodeling, including a more globular heart with thicker myocardial walls, decreased longitudinal function (tricuspid ring displacement in controls: median, 6.5 mm [interquartile range, 6.1-7.1 mm]; tricuspid ring displacement in ART: 5.5 mm [interquartile range, 5.1-6.1]; P<0.001), impaired relaxation, and dilated atria (atrial area in controls, 1.46 cm(2) [interquartile range, 1.2-1.5 cm(2)]; atrial area in ART, 1.6 cm(2) [interquartile range, 1.3-1.8 cm(2)]; P<0.001). Additionally, ART infants showed persistence of most cardiac changes and a significant increase in blood pressure and aortic intima-media thickness (systolic blood pressure in controls, 74 mm Hg [interquartile range, 67-83 mm Hg]; systolic blood pressure in ART, 83 mm Hg [interquartile range, 75-94 mm Hg]; P<0.001; aortic intima-media thickness in controls, 0.52 mm [interquartile range, 0.45-0.56 mm]; aortic intima-media thickness in ART, 0.64 mm [interquartile range, 0.62-0.67]; P<0.001). We could not demonstrate that our findings were directly caused by ART because of their association with various confounding factors, including intrauterine growth restriction or factors related to the cause of infertility. Conclusions Children conceived by ART manifest cardiac and vascular remodeling that is present in fetal life and persists in postnatal life, suggesting opportunities for early detection and potential intervention. The underlying mechanisms and the effect of potential confounders such as growth restriction or prematurity remain to be elucidated.

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