Late-gestation maternal undernutrition induces circulatory redistribution while preserving uteroplacental function independent of fetal glycaemic state.

Programming effects of maternal undernutrition on fetal metabolic and cardiovascular systems are well elucidated, yet a detailed characterization of maternal haemodynamics is not available. This study used comprehensive cardiovascular magnetic resonance (CMR) imaging to quantify maternal haemodynamics after 29 days (111-140 days) of late-gestation undernutrition (LGUN) in pregnant sheep. Control ewes received 100% of metabolizable energy requirements (MERs, n = 15), whereas LGUN ewes were globally nutrient restricted to 50% MER (n = 18), with a subset of fetuses undergoing continuous glucose infusion (LGUN + G, n = 6/18).

Acute-on-chronic: using magnetic resonance imaging to disentangle the haemodynamic responses to acute and chronic fetal hypoxaemia.

Introduction: The fetal haemodynamic response to acute episodes of hypoxaemia are well characterised. However, how these responses change when the hypoxaemia becomes more chronic in nature such as that associated with fetal growth restriction (FGR), is less well understood. Herein, we utilised a combination of clinically relevant MRI techniques to comprehensively characterize and differentiate the haemodynamic responses occurring during acute and chronic periods of fetal hypoxaemia.

Echocardiographic assessment of cardiovascular physiology of preterm miniature piglets supported with a pumped artificial placenta system.

Objectives: We evaluated fetal cardiovascular physiology and mode of cardiac failure in premature miniature piglets on a pumped artificial placenta (AP) circuit.

Methods: Fetal pigs were cannulated via the umbilical vessels and transitioned to an AP circuit composed of a centrifugal pump and neonatal oxygenator and maintained in a fluid-filled biobag. Echocardiographic studies were conducted to measure ventricular function, umbilical blood flow, and fluid status.

Fetal Hemodynamics, Early Survival, and Neurodevelopment in Patients With Cyanotic Congenital Heart Disease.

Background: Fetuses with cyanotic congenital heart disease (CHD) exhibit profound fetal circulatory disturbances that may affect early outcomes.

Objectives: This study sought to investigate the relationship between fetal hemodynamics and early survival and neurodevelopmental (ND) outcomes in patients with cyanotic CHD.

Methods: In this longitudinal observational study, fetuses with cyanotic CHD underwent late gestational fetal cardiovascular magnetic resonance (CMR) to measure vessel blood flow and oxygen content.

Pulmonary Vascular Regulation in the Fetal and Transitional Lung.

Fetal lungs have fewer and smaller arteries with higher pulmonary vascular resistance (PVR) than a newborn. As gestation advances, the pulmonary circulation becomes more sensitive to changes in pulmonary arterial oxygen tension, which prepares them for the dramatic drop in PVR and increase in pulmonary blood flow (PBF) that occur when the baby takes its first few breaths of air, thus driving the transition from fetal to postnatal circulation. Dynamic and intricate regulatory mechanisms control PBF throughout development and are essential in supporting gas exchange after birth.

Feasibility of MRI assessment of maternal-fetal oxygen transport and consumption relative to maternal position in healthy late gestational pregnancies.

Late gestational supine positioning reduces maternal cardiac output due to inferior vena caval (IVC) compression, despite increased collateral venous return. However, little is known about the impact of maternal position on oxygen (O ) delivery and consumption of the gravid uterus, fetus, placenta and lower limbs. We studied the effects of maternal positioning on these parameters in 20 healthy pregnant subjects at 36 ± 2 weeks using magnetic resonance imaging (MRI); a follow-up MRI was performed 6-months postpartum (n = 16/20).

Impact of the Addition of a Centrifugal Pump in a Preterm Miniature Pig Model of the Artificial Placenta.

The recent demonstration of normal development of preterm sheep in an artificial extrauterine environment has renewed interest in artificial placenta (AP) systems as a potential treatment strategy for extremely preterm human infants. However, the feasibility of translating this technology to the human preterm infant remains unknown. Here we report the support of 13 preterm fetal pigs delivered at 102 ± 4 days (d) gestation, weighing 616 ± 139 g with a circuit consisting of an oxygenator and a centrifugal pump, comparing these results with our previously reported pumpless circuit ( = 12; 98 ± 4 days; 743 ± 350 g).

Intrauterine growth restriction alters the activity of drug metabolising enzymes in the maternal-placental-fetal unit.

Purpose: Ten percent of pregnancies are affected by intrauterine growth restriction (IUGR), and evidence suggests that affected neonates have reduced activity of hepatic cytochrome P450 (CYP) drug metabolising enzymes. Given that almost all pregnant individuals take medications and additional medications are often required during an IUGR pregnancy, we aimed to determine the impact of IUGR on hepatic CYP activity in sheep fetuses and pregnant ewes.

Methods: Specific probes were used to determine the impact of IUGR on the activity of several CYP isoenzymes (CYP1A2, CYP2C19, CYP2D6 and CYP3A) in sheep fetuses and pregnant ewes.

Redox ratio in the left ventricle of the growth restricted fetus is positively correlated with cardiac output.

Intrauterine growth restriction (IUGR) is a result of limited substrate supply to the developing fetus in utero, and can be caused by either placental, genetic or environmental factors. Babies born IUGR can have poor long-term health outcomes, including being at higher risk of developing cardiovascular disease. Limited substrate supply in the IUGR fetus not only changes the structure of the heart but may also affect metabolism and function of the developing heart.

Impact of maternal late gestation undernutrition on surfactant maturation, pulmonary blood flow and oxygen delivery measured by magnetic resonance imaging in the sheep fetus.

Restriction of fetal substrate supply has an adverse effect on surfactant maturation in the lung and thus affects the transition from in utero placental oxygenation to pulmonary ventilation ex utero. The effects on surfactant maturation are mediated by alteration in mechanisms regulating surfactant protein and phospholipid synthesis. This study aimed to determine the effects of late gestation maternal undernutrition (LGUN) and LGUN plus fetal glucose infusion (LGUN+G) compared to Control on surfactant maturation and lung development, and the relationship with pulmonary blood flow and oxygen delivery ( ) measured by magnetic resonance imaging (MRI) with molecules that regulate lung development.

Open or closed: Changes in ductus arteriosus flow patterns at birth using 4D flow MRI in newborn piglets.

The ductus arteriosus (DA) functionally closes during the transition from fetal to postnatal life because of lung aeration and corresponding cardiovascular changes. The thorough and explicit measurement and visualization of the right and left heart output during this transition has not been previously accomplished. We combined 4D flow MRI (dynamic volumetric blood flow measurements) and T2 relaxometry (oxygen delivery quantification) in surgically instrumented newborn piglets to assess the DA.

Maternal and Fetal Hemodynamic Adaptations to Pregnancy and Clinical Outcomes in Maternal Cardiac Disease.

Background: Although insufficient maternal cardiac output (CO) has been implicated in poor outcomes in mothers with heart disease (HD), maternal-fetal interactions remain incompletely understood. We sought to quantify maternal-fetal hemodynamics with the use of magnetic resonance imaging (MRI) and explore their relationship with adverse events.

Methods: Pregnant women with moderate or severe HD (n = 22; mean age 32 ± 5 years) were compared with healthy control women (n = 21; 34 ± 3 years).

An MRI approach to assess placental function in healthy humans and sheep.

Key Points: Human placental function is evaluated using non-invasive Doppler ultrasound of umbilical and uterine artery pulsatility indices as measures of resistance in placental vascular beds, while measurement of placental oxygen consumption ( ) is only possible during Caesarean delivery. This study shows the feasibility of using magnetic resonance imaging (MRI) in utero to measure blood flow and oxygen content in uterine and umbilical vessels to calculate oxygen delivery to and by the gravid uterus, uteroplacenta and fetus. Normal late gestational human uteroplacental by MRI was ∼4 ml min  kg fetal weight, which was similar to our MRI measurements in sheep and to those previously measured using invasive techniques.

Achieving sustained extrauterine life: Challenges of an artificial placenta in fetal pigs as a model of the preterm human fetus.

Artificial placenta (AP) technology aims to maintain fetal circulation, while promoting the physiologic development of organs. Recent reports of experiments performed in sheep indicate the intrauterine environment can be recreated through the cannulation of umbilical vessels, replacement of the placenta with a low-resistance membrane oxygenator, and incubation of the fetus in fluid. However, it remains to be seen whether animal fetuses similar in size to the extremely preterm human infant that have been proposed as a potential target for this technology can be supported in this way.

Impact of resveratrol-mediated increase in uterine artery blood flow on fetal haemodynamics, blood pressure and oxygenation in sheep.

New Findings: What is the central question of this study? Uterine artery blood flow helps to maintain fetal oxygen and nutrient delivery. We investigated the effects of increased uterine artery blood flow mediated by resveratrol on fetal growth, haemodynamics, blood pressure regulation and oxygenation in pregnant sheep. What is the main finding and its importance? Fetuses from resveratrol-treated ewes were significantly larger and exhibited a haemodynamic profile that might promote peripheral growth.

Umbilical vein infusion of prostaglandin I increases ductus venosus shunting of oxygen-rich blood but does not increase cerebral oxygen delivery in the fetal sheep.

Key Points: The ductus venosus (DV) is a dynamic fetal shunt that allows substrate-rich blood from the umbilical vein to bypass the hepatic circulation. In vitro studies suggest a direct role of prostaglandin I (PGI ) in the regulation of DV tone; however, the extent of this regulation has not been determined in utero. 4D flow and T oximetry magnetic resonance imaging can be combined to determine blood flow and oxygen delivery within the fetal circulation.

Technique for comprehensive fetal hepatic blood flow assessment in sheep using 4D flow MRI.

Key Points: The comprehensive visualization and quantification of in vivo fetal hepatic haemodynamics, particularly the shunting of ductus venosus blood, has been elusive and is not yet fully understood. We introduce the combination of chronically instrumented fetal sheep and 4D flow MRI of the whole fetal liver, which allows retrospective blood flow measurement in all visible vessels as well as qualitative assessment. The applicability and usefulness of this technique is exhibited in normally grown fetal Merino sheep in mid- and late-gestation with detailed dynamic distribution of hepatic blood flow presented.

Feasibility of ventricular volumetry by cardiovascular MRI to assess cardiac function in the fetal sheep.

Key Points: The application of fetal cardiovascular magnetic resonance imaging (CMR) to assess fetal cardiovascular physiology and cardiac function through the quantification of ventricular volumes has previously been investigated, but the approach has not yet been fully validated. Ventricular output measurements calculated from heart rate and stroke volumes (SV) of the right and left ventricles measured by ventricular volumetry (VV) exhibited a high level of agreement with phase-contrast (PC) blood flow measurements in the main pulmonary artery and ascending aorta, respectively. Ejection fraction of the right ventricle, which is lower than that of the left ventricle in postnatal subjects, was similar to the left ventricular ejection fraction in the fetus; probably due to the different loading conditions present in the fetal circulation.

Normal human and sheep fetal vessel oxygen saturations by T2 magnetic resonance imaging.

Key Points: Human fetal Doppler ultrasound and invasive blood gas measurements obtained by cordocentesis or at the time of delivery reveal similarities with sheep (an extensively used model for human fetal cardiovascular physiology). Oxygen saturation (SO ) measurements in human fetuses have been limited to the umbilical and scalp vessels, providing little information about normal regional SO differences in the fetus. Blood T2 MRI relaxometry presents a non-invasive measure of SO in the major fetal vessels.

Understanding Fetal Hemodynamics Using Cardiovascular Magnetic Resonance Imaging.

Human fetal circulatory physiology has been investigated extensively using grey-scale ultrasound, which provides excellent visualization of cardiac anatomy and function, while velocity profiles in the heart and vessels can be interrogated using Doppler. Measures of cerebral and placental vascular resistance, as well as indirect measures of intracardiac pressure obtained from the velocity waveform in the ductus venosus are routinely used to guide the management of fetal cardiovascular and placental disease. However, the characterization of some key elements of cardiovascular physiology such as vessel blood flow and the oxygen content of blood in the arteries and veins, as well as fetal oxygen delivery and consumption are not readily measured using ultrasound.

Subcutaneous maternal resveratrol treatment increases uterine artery blood flow in the pregnant ewe and increases fetal but not cardiac growth.

Key Points: Substrate restriction during critical developmental windows of gestation programmes offspring for a predisposition towards cardiovascular disease in adult life. This study aimed to determine the effect of maternal resveratrol (RSV) treatment in an animal model in which chronic fetal catheterisation is possible and the timing of organ maturation reflects that of the human. Maternal RSV treatment increased uterine artery blood flow, fetal oxygenation and fetal weight.

Uterine artery and umbilical vein blood flow are unaffected by moderate habitual physical activity during pregnancy.

Objective: This study aims to noninvasively quantify blood flow in the uterine arteries (UTAs) and umbilical vein (UV) using phase-contrast magnetic resonance imaging (PC-MRI) and test whether these correlate with maternal fitness parameters.

Method: Resting UTA and UV flows were measured in 23 healthy 30 ± 3-year-old women who engaged in moderate-intensity physical activity during pregnancy. Participant fitness was characterized in the second and third trimesters using the submaximal oxygen uptake (VO ) test measuring heart rate (HR), VO , ventilation (ventilatory equivalent [VE]/VO ), and the Borg rating of perceived exertion (respiratory quotient [RQ]).

MR imaging of the fetal heart.

In the last decade, technological advances have enabled the acquisition of high spatial and temporal resolution cardiac magnetic resonance imaging (MRI) in the fetus. Fetal cardiac MRI has emerged as an alternative to ultrasound, which may be helpful to confirm a diagnosis of congenital heart disease when ultrasound assessment is hampered, for example in late gestation or in the setting of oligohydramnios. MRI also provides unique physiologic information, including vessel blood flow, oxygen saturation and hematocrit, which may be helpful to investigate cardiac and placental diseases.