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.
Highlights
Intrauterine growth restriction (IUGR), predominately due to placental insufficiency, is one of the main causes of perinatal mortality and morbidity [1,2], and defined as a birth weight below the 10th percentile for gestational age
We developed a computational model of the fetal circulation, including the key elements related to fetal blood redistribution
IUGR was defined as an estimated fetal weight [23] and confirmed birth weight below the 10th percentile according to local reference curves [24] together with a pulsatility index (PI) in the umbilical artery (UA) above 2 standard deviations [25]
Summary
Intrauterine growth restriction (IUGR), predominately due to placental insufficiency, is one of the main causes of perinatal mortality and morbidity [1,2], and defined as a birth weight below the 10th percentile for gestational age. IUGR fetuses, suffering from hypoxia and undernutrition, show Doppler changes in several arteries of the feto-placental circulation such as umbilical artery (UA), middle cerebral artery (MCA), and in the aortic isthmus (AoI). These changes are assessed in clinical practice to stage the severity of IUGR and are thought to reflect blood flow redistribution due to increased peripheral resistance, with decreased brain resistance in order to maximize brain blood supply under an adverse environment. Other clinical studies suggested that AoI flow pattern is influenced by simultaneous changes in both cerebral and peripheral-placental resistances [6,9,10,11]. Some experimental studies in an ovine animal model [12,13,14] have quantified the influence of placental resistance increase in the AoI flow, showing a strong correlation between
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