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

Abstract

Intrauterine growth restriction (IUGR) due to placental insufficiency is associated with blood flow redistribution in order to/nmaintain delivery of oxygenated blood to the brain. Given that, in the fetus the aortic isthmus (AoI) is a key arterial/nconnection between the cerebral and placental circulations, quantifying AoI blood flow has been proposed to assess this/nbrain sparing effect in clinical practice. While numerous clinical studies have studied this parameter, fundamental/nunderstanding of its determinant factors and its quantitative relation with other aspects of haemodynamic remodeling has/nbeen limited. Computational models of the cardiovascular circulation have been proposed for exactly this purpose since/nthey allow both for studying the contributions from isolated parameters as well as estimating properties that cannot be/ndirectly assessed from clinical measurements. Therefore, a computational model of the fetal circulation was developed,/nincluding the key elements related to fetal blood redistribution and using measured cardiac outflow profiles to allow/npersonalization. The model was first calibrated using patient-specific Doppler data from a healthy fetus. Next, in order to/nunderstand the contributions of the main parameters determining blood redistribution, AoI and middle cerebral artery/n(MCA) flow changes were studied by variation of cerebral and peripheral-placental resistances. Finally, to study how this/naffects an individual fetus, the model was fitted to three IUGR cases with different degrees of severity. In conclusion, the/nproposed computational model provides a good approximation to assess blood flow changes in the fetal circulation. The/nresults support that while MCA flow is mainly determined by a fall in brain resistance, the AoI is influenced by a balance/nbetween increased peripheral-placental and decreased cerebral resistances. Personalizing the model allows for quantifying/nthe balance between cerebral and peripheral-placental remodeling, thus providing potentially novel information to aid/nclinical follow up.This study was partially supported by grants from Instituto de Salud Carlos III and Ministerio de Economia y Competitividad (ref. PI11/00051, PI11//n01709, PI12/00801 and SAF2012-37196); Fondo Europeo de Desarrollo Regional de la Unio/ń/nn Europea ‘‘Una manera de hacer Europa’’, Spain; Obra Social ‘La Caixa’,/nSpain; Cerebra Foundation for the Brain Injured Child (Carmarthen, Wales, UK); and the Seventh Framework Programme (FP7/2007-2013) under grant agr/neement/nNo. 611823. PGC was supported by the Programa de Ayudas Predoctorales de Formacio/ń/nn en investigacio/ń/nn en Salud (FI12/00362) from the Instituto Carlos III,/nSpain. MCL wishes to express her gratitude to the Mexican National Council for Science and Technology (CONACyT, Mexico City, Mexico) for supporting h/ner/npredoctoral stay at Hospital Clinic, Barcelona, Spain. The funders had no role in study design, data collection and analysis, decision to publish, or/npreparation of/nthe manuscrip