Maternal Low Volume Circulation Relates to Normotensive and Preeclamptic Fetal Growth Restriction

Abstract

This narrative review summarizes current evidence on the association between maternal low volume circulation and poor fetal growth. Though much work has been devoted to the study of cardiac output and peripheral vascular resistance, a low intravascular volume may explain why high vascular resistance causes hypertension in women with preeclampsia (PE) that is associated with fetal growth restriction (FGR) and, at the same time, presents with normotension in FGR itself. Normotensive women with small for gestational age babies show normal gestational blood volume expansion superimposed upon a constitutionally low intravascular volume. Early onset preeclampsia (EPE; occurring before 32 weeks) is commonly associated with FGR, and poor plasma volume expandability may already be present before conception, thus preceding gestational volume expansion. Experimentally induced low plasma volume in rodents predisposes to poor fetal growth and interventions that enhance plasma volume expansion in FGR have shown beneficial effects on intrauterine fetal condition, prolongation of gestation and birth weight. This review makes the case for elevating the maternal intravascular volume with physical exercise with or without Nitric Oxide Donors in FGR and EPE, and evaluating its role as a potential target for prevention and/or management of these conditions.

Keywords: body water volume; cardiac output; fetal growth; intravascular volume; maternal hemodynamic changes in pregnancy; vascular resistance; venous hemodynamics.

FIGURE 1

Comparative gestational evolution of maternal cardiac output (A), total vascular resistance (B), and total body water volume (C), as measured by the bioimpedance technology between uncomplicated pregnancies (UP), normotensive fetal growth restriction (FGR), and preeclampsia with FGR (PEFGR). Values are expressed as multiples of mean first trimester values in UP. Figures adapted from 10, 11, and 28.

FIGURE 2

Illustration of the constant fluid exchange between intravascular and interstitial volumes at the level of the microcirculation. This interconnectivity indicates that plasma volume changes cannot be interpreted without knowledge of interstitial water volume, or indirectly via measurement of total body water volume. Normotensive fetal growth restriction relates to a constitutionally low intravascular volume, remaining lower in uncomplicated pregnancies despite normal gestational volume expansion. Early onset preeclampsia, on the other hand, is a state of increased adrenergic activation (155), shifting blood from the venous capacitance bed into the circulation and despite this, cardiac output fails to rise. This can only be explained by a shift from the intravascular compartment to the interstitium, which is in line with clinical signs, such as malleolar or pulmonary edema, in early onset preeclampsia. The arrows indicate the principle of volume estimation by bioimpedance spectrum analysis of intracellular (green) and extracellular (blue) compartments, the latter being the sum of intravascular and interstitial volumes.

FIGURE 3

Different types of venous Doppler waveforms in maternal and fetal circulations, varying between triphasic (A), biphasic (B), and monophasic (C) to flat (D). In the fetus and non-pregnant adults, triphasic patterns are found close to the heart [hepatic veins (HV)], whereas flat patterns are present at distant locations [limbs, umbilical veins (UV)]. During uncomplicated pregnancy, HV patterns shift from (A–D). In the clinical stage of preeclampsia with FGR, biphasic HV patterns become triphasic (orange arrow), whereas in term preeclampsia, monophasic patterns evolve to biphasic (brown arrow). In ductus venosus (DV) of FGR fetuses, a shift from biphasic to triphasic patterns occurs simultaneously with deteriorating fetal condition (green arrow). (SV: fetal splenic vein).