A computational model of the fetal circulation to quantify blood redistribution in intrauterine growth restriction

PLoS Comput Biol. 2014 Jun 12;10(6):e1003667. doi: 10.1371/journal.pcbi.1003667. eCollection 2014 Jun.

Abstract

Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to maintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial connection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this brain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental understanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has been limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since they allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be directly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed, including the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow personalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to understand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery (MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this affects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the proposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The results support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance between increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying the balance between cerebral and peripheral-placental remodeling, thus providing potentially novel information to aid clinical follow up.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aorta / physiology
  • Computer Simulation*
  • Female
  • Fetal Growth Retardation / physiopathology*
  • Fetus / blood supply*
  • Hemodynamics / physiology*
  • Humans
  • Middle Cerebral Artery / physiology
  • Models, Cardiovascular*
  • Placenta / blood supply*
  • Pregnancy
  • Pregnancy Trimester, Third / physiology

Grants and funding

This study was partially supported by grants from Instituto de Salud Carlos III and Ministerio de Economia y Competitividad (ref. PI11/00051, PI11/01709, PI12/00801 and SAF2012-37196); Fondo Europeo de Desarrollo Regional de la Unión Europea “Una manera de hacer Europa”, Spain; Obra Social ‘La Caixa’, Spain; Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); and the Seventh Framework Programme (FP7/2007-2013) under grant agreement No. 611823. PGC was supported by the Programa de Ayudas Predoctorales de Formación en investigación en Salud (FI12/00362) from the Instituto Carlos III, Spain. MCL wishes to express her gratitude to the Mexican National Council for Science and Technology (CONACyT, Mexico City, Mexico) for supporting her predoctoral stay at Hospital Clinic, Barcelona, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.