ISUOG Consensus Statement on maternal hemodynamic assessment in hypertensive disorders of pregnancy and fetal growth restriction

Clinical Standards Committee

The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, and high‐quality teaching and research, related to diagnostic imaging in women's healthcare. The ISUOG Clinical Standards Committee (CSC) has the remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus‐based approach, from experts, for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines and Consensus Statements are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. The ISUOG CSC documents are not intended to establish a legal standard of care because interpretation of the evidence that underpins them may be influenced by individual circumstances, local protocol and available resources. Approved Guidelines and Consensus Statements can be distributed freely with the permission of ISUOG (info@isuog.org).

INTRODUCTION

Pregnancy presents a unique cardiovascular challenge. Profound maternal hemodynamic adjustments result from a complex interplay between the maternal cardiovascular system and uteroplacental perfusion, which permits fetal development while maintaining healthy maternal homeostasis ¹ , ² , ³ , ⁴ , ⁵ . Failure to meet this challenge can lead to maternal hypertensive complications (hypertensive disorders of pregnancy (HDP)) and/or fetal growth disorders (fetal growth restriction (FGR)) ⁶ , ⁷ , ⁸ , ⁹ .

Monitoring and management of HDP and FGR has been based largely on maternal blood pressure (BP) monitoring and fetal growth assessment ¹⁰ . Promising research offers the prospect of a less reactive and more proactive approach. Maladaptation to the requirements of pregnancy can be detected in a preclinical phase of HDP and FGR by maternal hemodynamic assessment, offering opportunities for targeted hemodynamic interventions ¹¹ , ¹² , ¹³ , ¹⁴ , ¹⁵ . Pregnancy also serves as a stress test for future cardiovascular health, especially if superimposed upon subclinical cardiometabolic or cardiovascular vulnerabilities ¹¹ , ¹⁶ , ¹⁷ , ¹⁸ , ¹⁹ .

This Consensus Statement provides an update on the role of maternal hemodynamic assessment in HDP and FGR.

METHODS

A proposal for this Consensus Statement was submitted to and evaluated by the ISUOG CSC. The authors of this Consensus are members of the International Working Group on Maternal Hemodynamics (https://maternalhemodynamics.com/) and were involved in both the development and the writing stages. Members of the International Working Group on Maternal Hemodynamics who were not involved in the writing of this Consensus were invited to review the document (reviewing group) and those who responded are acknowledged. Stakeholders were not included in the writing process.

This process was not intended to represent a systematic review. The preselected topics were divided among the authors, who worked in pairs and performed a literature search. T.S. collated the document and proposed the key points. The final document and key points were revised by all authors. Several meetings were organized to discuss any points on which there was not initial consensus, until complete agreement was reached. The document was then finalized after comments from the reviewing group, the ISUOG CSC and the ISUOG Board of Trustees.

The authors of this Consensus Statement are experts in the field of maternal hemodynamics and have expressed their opinion based on the available literature and evidence. Any clinician applying this Consensus is expected to use their independent medical judgement in the context of the individual clinical circumstances to determine patient care.

MATERNAL HEMODYNAMIC ASSESSMENT: METHODOLOGY AND REPRODUCIBILITY

Traditionally, peripheral BP is measured by auscultation using an arm cuff connected to a manometer. Increasingly, automated oscillometric devices, validated for pregnancy, are becoming the recommended standard ²⁰ , ²¹ . Further developments have allowed additional analysis of the arterial waveform for estimation of central BP and arterial function. Markers of arterial stiffness and compliance, such as pulsed‐wave velocity and the augmentation index (AIx) ²² , ²³ , help to understand the pathophysiology behind HDP and FGR, predict cardiovascular complications, and evaluate and direct prevention and treatment ²⁴ , ²⁵ , ²⁶ .

Cardiac output

Assessment of central hemodynamic factors that determine BP (cardiac output (CO, in L/min) and systemic vascular resistance (SVR, in dyne.s/cm⁵)) is increasingly accessible using easily operable devices ²⁷ . Considering the pivotal role of central hemodynamic functioning, this Consensus Statement focuses primarily on CO assessment.

CO is the product of stroke volume (SV) and heart rate (HR) (CO = SV × HR). Accuracy of its evaluation is improved by averaging measurements over several heartbeats ³ , ⁴ , ⁵ , to compensate for respiratory variations. After 20 gestational weeks, CO is best evaluated with the woman in a left lateral position, to minimize caval and aortic compression by the gravid uterus ²⁸ , ²⁹ . The heart can rapidly modulate CO in order to meet the demands of pregnancy, with a wide range of normality (4–20 L/min) depending on activity level, age, fitness, body size, gestational age and metabolic rate. While trimester‐specific reference ranges exist, device‐specific normalization, that takes into account maternal age and posture, does not. Indexing for actual or prepregnancy body surface area or height may be of additional value when comparing measurements between individuals ²⁷ , ³⁰ , ³¹ , ³² . Individual or separate CO measurements can be of value for instant hemodynamic assessment, while repeated or continuous measurements are appropriate for trend analysis.

With knowledge of CO and BP, SVR can be calculated ((SVR = 80 × (MAP − RAP)/CO) in dyne.s/cm⁵), where MAP represents mean arterial pressure and RAP is right atrial pressure. RAP (or central venous pressure) is usually low in pregnancy (0–5 mmHg) and therefore is usually omitted from the calculation ³³ , ³⁴ . Arterial function can also be evaluated by Doppler assessment of peripheral vessels, for example the uterine and/or opthalmic arteries.

Reference techniques

CO is determined most accurately by invasive measurements using thermodilution or indicator (lithium) dilution, or by cardiac magnetic resonance imaging (MRI). The former require insertion of intracardiac, central venous and/or arterial catheters (e.g. pulmonary artery catheters), limiting their indication to critically ill pregnant women in an intensive care unit setting ³³ , ³⁴ . Cardiac MRI is non‐invasive, but its limited availability and high cost restrict its use in an obstetric context ²⁸ , ³⁵ .

Ultrasound

Transthoracic echocardiography permits non‐invasive assessment of CO by measuring the left ventricular outflow tract diameter and pulsed‐wave Doppler outflow signal along with HR. It has been validated against invasive measurements in severely ill pregnant women and can be considered an alternative reference technique ³⁶ , ³⁷ . Transthoracic echocardiography enables evaluation of systolic and/or diastolic function (assessing ejection fraction using two‐dimensional and/or M‐mode imaging, strain and strain rate using speckle tracking, tricuspid annular plane systolic excursion (TAPSE), and mitral inflow using pulse‐wave and tissue Doppler imaging) and preload assessment (atrial size and inferior vena cava size and collapsibility) ³⁸ , ³⁹ , ⁴⁰ .

Other techniques

Another means of assessing CO is with a non‐invasive mobile device, using a continuous‐wave Doppler transducer placed in the suprasternal notch ⁴⁰ . This technique is limited by assumptions regarding the left ventricular outflow tract diameter and acoustic guidance for probe orientation. However, by including more heartbeats in the calculation, the accuracy is enhanced.

An inert gas rebreathing technique can be used to calculate CO based on Fick's principle ⁴¹ . A blood‐soluble and an insoluble gas are delivered though a closed breathing assembly and relative levels over a few respiratory cycles are measured by a gas analyzer in the mouthpiece. As with pulmonary artery catheters, pulmonary blood flow or right ventricular output is measured, which is usually identical to left ventricular output. In obstetrics, this technique is more suited for research than clinical practice ⁴² .

With impedance and reactance cardiography, a very‐low‐amplitude high‐frequency current is transmitted between skin electrodes on the thorax. CO can be estimated by calculating differences in impedance (bioimpedance) or phase shifts (bioreactance) induced by changing blood flow during the cardiac cycle ⁴³ , ⁴⁴ . Pulse‐contour analysis estimates CO from a peripheral arterial waveform, which can be obtained invasively or non‐invasively ³³ , ⁴⁵ . Both impedance and reactance cardiography and pulse‐contour methods are operator‐independent and permit continuous monitoring for trend analysis, but their algorithms to calculate CO are based on assumptions that may affect accuracy.

Most non‐invasive techniques lack validation in pregnancy against reference techniques. The few that have been compared with reference techniques often fail the current rigorous standards for absolute values and trend analysis ⁴⁶ . Consequently, CO values obtained with one technique are not comparable with those obtained using another technique, and the techniques cannot be used interchangeably. Still, it would be unwise to disregard the benefits from these devices, as their accessibility permits the gathering of large amounts of valuable hemodynamic information. In addition, using a single device repeatedly in the same patient overcomes the differences between techniques and allows the investigation of changes over time. As such, these techniques may be valuable for monitoring changes as pregnancy progresses.

Key points

• After 20 gestational weeks, the assessment of maternal CO should be performed with the woman in a left lateral position.

• While no non‐invasive technique is a true gold standard for CO assessment in pregnancy, transthoracic echocardiography has undergone extensive validation.

• Different techniques for non‐invasive assessment of maternal CO cannot be used interchangeably.

• Despite the lack of rigorous standardization and systematic differences between techniques, evaluation of the changes in maternal CO over time might be valuable in obstetric practice.

MATERNAL HEMODYNAMIC ADAPTATION TO HEALTHY PREGNANCY

During pregnancy, the mother's body undergoes cardiovascular changes leading to hemodynamic adaptations required to respond to the increasing metabolic and oxygen demands from the uterus, placenta and fetus and to prepare the mother for possible blood loss during delivery (Figure 1). To understand the possible role of maternal hemodynamics in pathological conditions, it is important to understand these changes in healthy pregnancy, as normal maternal hemodynamic adaptation is a prerequisite for development of a normal pregnancy ⁴² , ⁴⁷ .

Figure 1.

Major maternal hemodynamic changes in healthy pregnancy. CO, cardiac output; GFR, glomerular filtration rate; HR, heart rate; IVRT, isovolumetric relaxation time; LA, left atrial; LV, left ventricular; MAP, mean arterial pressure; RAAS, renin–angiotensin– aldosterone system; RBC, red blood cells; SV, stroke volume; SVR, systemic vascular resistance.

Maternal hemodynamic changes in healthy pregnancy

Maternal hemodynamic changes can be observed during the menstrual cycle. Compared to the follicular phase, during the luteal phase, the HR, plasma volume (PV), CO and central and peripheral arterial compliance are increased, while the MAP and SVR are decreased ⁴⁸ . Similar changes are present early in pregnancy, from 6 weeks of gestation, prior to the development of a placental circulation ⁴² , ⁴⁸ , ⁴⁹ .

The hypothesized mechanism underlying maternal hemodynamic changes in early pregnancy (Figure 2) is that a fall in SVR, by up to 20–25% ⁵⁰ , acts as the trigger event, most likely due to reduced vascular tone, leading to a decrease in MAP and a compensatory increase in CO⁵¹. The initial increase in CO is caused by an increase in HR ⁴⁸ . These changes are accompanied by renin–angiotensin–aldosterone‐system (RAAS) activation due to increases in renal plasma flow and glomerular filtration rate and reduction in MAP ⁴⁸ , ⁵¹ . The result of RAAS activation is sodium and water reabsorption, with consequent PV expansion, hemodilution and increased preload ⁵² . The increased preload leads to improved cardiac filling during diastole. Together with decreased cardiac afterload, this results in increased SV and, consequently, in increased CO⁴⁸. As a result of increased preload, the maternal heart undergoes changes: the left atrial diameter, left ventricular diastolic and systolic dimensions and ventricular wall thickness all increase, resulting overall in increased cardiac mass, surface area (so‐called myocardial eccentric hypertrophy) and performance ⁵ , ⁵³ . Maternal cardiac morphological changes start at around 8 weeks of gestation, but become significant at around 12 weeks of gestation ⁵² .

Figure 2.

Early maternal hemodynamic changes in healthy pregnancy. hCG, human chorionic gonadotropin; NO, nitric oxide, Pg, progesterone; RAAS, renin–angiotensin–aldosterone system.

The maintenance of CO is also guaranteed by decreased cardiac afterload, which is accomplished by the decrease in SVR, while the normal perfusion pressure is associated with higher arterial compliance ⁵⁴ . Concomitantly, increased venous compliance accommodates a higher quantity of PV, contributing to preload increase and further maintenance of CO⁴⁸.

A detailed discussion of molecular pathways is beyond the scope of this document, but it has been hypothesized that hormonal influences, including estrogen and human chorionic gonadotropin secreted by the synciotrophoblast, and other factors (e.g. relaxin, vascular endothelial factor, nitric oxide (NO)) play a role in physiological maternal hemodynamic adaptation early in pregnancy ⁴⁸ , which would mean that the earliest maternal hemodynamic changes in pregnancy develop independently from the fetoplacental unit.

After the early first‐trimester changes, healthy pregnancy is characterized by various hemodynamic adaptations, including further increases in CO and PV, decreases in SVR and MAP, and changes in maternal cardiac function.

Cardiac output

Increasing cardiac preload and concomitant decreasing afterload result in progressively higher SV and CO in the first trimester of pregnancy. SV increases by 15–25% early in pregnancy and plateaus by about 20 weeks ⁵⁵ , ⁵⁶ . In the second half of pregnancy, the increase in SV is reversed, so that near term there is no difference between pregnant and non‐pregnant women ⁵⁶ . The increased CO is also caused by the higher maternal HR, which increases by 15–30% early in pregnancy and continues to increase gradually until term. The CO increases overall by 20–50% and peaks by mid to late pregnancy, reaching a maximum mean difference of 1.41 L/min between 29 and 35 weeks of gestation ⁵⁵ , ⁵⁶ . It remains controversial as to whether CO increases until term ⁵⁷ or decreases late in pregnancy ⁵⁸ ; inconsistencies in results between studies can be explained by differences in their design and/or methodology, population and other factors. CO returns to prepregnancy values from 2 weeks postpartum ¹ .

Plasma volume

PV starts to increase early in pregnancy, peaks during the second trimester and changes minimally throughout the third trimester, returning to normal levels after 6 weeks postpartum ⁴ . Around one‐third of the PV is contained in the arterial compartment, while two‐thirds are located in the venous compartment and represent a hemodynamically inactive intravascular volume ⁵⁹ .

Systemic vascular resistance

SVR decreases, with an overall 30% decrease early in pregnancy ⁵⁵ and nadir in the late second trimester ⁵⁶ .

Mean arterial pressure

MAP decreases during pregnancy until 24 weeks of gestation, because the increase in CO is not sufficient to balance the fall in SVR. Both systolic and diastolic BP decrease; however, the reduction in diastolic BP is greater than that in central and brachial systolic BP⁴⁹. There is also a significant fall in AIx (i.e. arterial stiffness), which explains the reduced central systolic BP. Central systolic BP reflects better than brachial systolic BP the uterine artery pressure, which contributes to the uteroplacental perfusion ⁴⁹ . The BP returns to baseline levels during the third trimester ⁵⁵ , ⁵⁶ .

Maternal heart

Increased preload and concomitant decreased afterload have a positive effect on maternal cardiac function in the first trimester of pregnancy. The change in left ventricular diastolic function in the first trimester appears to be determined by an increased contribution of passive left ventricular filling ⁴ . In advanced gestation, left ventricular diastolic function seems to worsen progressively, as reflected by a decreased E‐wave to A‐wave (E/A) ratio ⁴ .

Morphological changes start in the first trimester and continue throughout pregnancy, peaking around 30 weeks. The left ventricular mass increases by approximately 50% ⁵⁵ . Myocardial eccentric hypertrophy observed during healthy pregnancy represents a reversible and uncomplicated phenomenon that has usually resolved by 6 months postpartum ⁶⁰ , ⁶¹ .

Key points

• Important maternal hemodynamic changes occur in the first weeks of pregnancy.

• Placentation is not necessary for maternal hemodynamic changes to occur in early healthy pregnancy.

• Maternal hemodynamic changes are important for adequate uterine and placental perfusion and adequate nutrient and oxygen supply to the placenta and fetus.

• Maternal hemodynamic changes represent a reversible process in healthy pregnancy, which reverts in the postpartum period.

• It is crucial to understand the physiological maternal hemodynamic changes that take place in healthy pregnancy, in order to understand their role in pathological conditions.

MATERNAL HEMODYNAMIC ADAPTATION TO MULTIPLE PREGNANCY

More profound maternal hemodynamic changes have been reported in uncomplicated multiple compared with singleton pregnancies, including higher CO and lower SVR across gestation ⁶² , ⁶³ , ⁶⁴ . The greater increase of circulating blood volume and the higher concentrations of vasodilating hormones, such as prostaglandins and progesterone, are thought to drive these changes ⁶⁵ .

In uncomplicated twin gestation, changes in maternal systolic and diastolic function have been documented from the first to the third trimester ⁶⁶ , ⁶⁷ , ⁶⁸ . In particular, diastolic and mean BP show a U‐shaped trend through gestation, reaching their nadir at midgestation. Based on serial echocardiograms, left ventricular systolic function, expressed either by classical parameters (ejection fraction or fractional shortening) or by tissue Doppler parameters (longitudinal contractility, quantified by S′ (myocardial velocity during isovolumetric longitudinal contraction)) worsens progressively during pregnancy ⁶² , ⁶⁷ . Moreover, relative diastolic dysfunction is observed, as evidenced by a progressive reduction in the mitral E‐wave and an increase in the A‐wave velocities, together with consistent modifications of the tissue Doppler parameters (reduction in E′ and increase in A′) ⁶⁷ . These findings indicate that the maternal heart is subjected to profound adjustments during the course of a twin gestation, regardless of whether there are cardiovascular complications.

The progressive decrease of ventricular performance may depend on the volume overload ⁶⁵ , and, in the late stages of apparently uneventful twin gestation, may lead to increased end‐systolic residual volumes in the ventricle, thus contrasting with the early diastolic phase and promoting active atrial contribution to left ventricular filling across the atrioventricular valves. In other words, the late stages of an uncomplicated twin pregnancy at the level of the maternal heart may mimic diastolic dysfunction as observed in the early stages of chronic cardiac insufficiency. It is noteworthy that similar findings, suggestive of early diastolic dysfunction, have been described at postpartum echocardiography in women who developed preterm or severe pre‐eclampsia (PE) in a singleton gestation ¹⁷ , ⁶⁹ .

At second‐trimester maternal echocardiography, the left ventricular mass is increased in twin pregnancies compared with singletons, but there are only subtle differences in systolic and diastolic left ventricular functional indices ⁷⁰ . The pattern of cardiac changes is similar between monochorionic and dichorionic twin pregnancies. These cardiovascular changes resemble those seen in singletons in late gestation and suggest physiological remodeling in response to the increase in volume loading rather than decompensation of the maternal cardiovascular system.

Changes in maternal cardiac function in uncomplicated twin gestation, from early to late pregnancy, include an increase in CO and a parallel decrease in SVR. It is unclear how these cardiac findings differ with respect to chorionicity. Using serial transthoracic echocardiography, one study reported lower maternal CO in second‐trimester monochorionic vs dichorionic twin pregnancies, possibly because of the smaller increase in the circulating blood volume ⁶⁶ . In contrast, another study recently showed a higher CO in the second trimester in monochorionic compared to dichorionic twin pregnancies ⁶⁸ . Most cardiac parameters revert towards the values of early pregnancy soon after delivery, with the exception of some indices of systolic function, such as fractional shortening, ejection fraction and tissue Doppler S′, which have been reported to remain significantly below those observed in the first trimester ⁶⁷ . This may indicate that the workload caused to the maternal heart by the increased circulating volumes may still affect the ventricular contractility in the early postpartum period and that complete recovery is delayed.

Key points

• Uncomplicated twin pregnancy is associated with more profound maternal hemodynamic changes than those seen in singleton pregnancy, and the maternal heart is exposed to more profound adjustments, most likely due to volume overload.

• Maternal left ventricular systolic function shows progressive worsening during uncomplicated twin pregnancy.

• In the late stages of uncomplicated twin pregnancy, there may be signs of maternal diastolic dysfunction.

MATERNAL HEMODYNAMICS IN HYPERTENSIVE DISORDERS OF PREGNANCY

Maternal hemodynamics in pre‐eclampsia phenotypes

The first classification of PE phenotypes was based on the timing of clinical disease onset, before (‘early‐onset’) or after (‘late‐onset’) 34 weeks of gestation ⁷¹ , ⁷² . Early‐onset PE typically follows a more aggressive course, presenting with severe symptoms of maternal organ dysfunction or with poor fetal growth that precedes the development of maternal hypertension, in association with serum markers of immune and endothelium activation ⁷³ . The maternal hemodynamic characteristics are markedly different between the two phenotypes, both in the clinical ¹⁴ and in the latent ¹⁴ , ⁷⁴ phase of the disease ¹⁵ . A new classification system has been proposed that is based on maternal hemodynamics and fetal growth ¹⁴ , ¹⁵ , ⁷⁵ , ⁷⁶ . PE associated with FGR is characterized by low CO and high SVR, in both preclinical and overt phases of the disease. PE associated with normal fetal growth is not characterized by low CO, while the SVR in the preclinical phase of the disease is low and may increase in the overt phase. This classification allows discrimination between two PE phenotypes, one characterized by vascular‐resistance‐induced hypertension (‘resistance‐dominant HDP’) and the other by intravascular‐volume‐induced hypertension (‘volume‐dominant HDP’) (Figure 3). As such, the fundamental physiological definition of BP as the product of CO and SVR (Ohm's law) is pertinent: hypertension is the result of either increased SVR, increased CO or both ⁶ , ⁷⁷ .

Figure 3.

Diagram representing two phenotypes of hypertensive disorders of pregnancy (HDP): (a) resistance‐dominant HDP and (b) volume‐dominant HDP. FGR, fetal growth restriction; AGA, appropriate‐for‐gestational age.

The theory that the placenta is the main etiological driver of PE is challenged by the observation of subclinical abnormal hemodynamic function already present in the preconception stage in women who subsequently developed PE ⁴⁷ , ⁷⁸ . An increasing number of clinical, epidemiological and experimental observations support that the abnormal placentation process associated with PE is a result of, rather than a cause of, abnormal maternal hemodynamic function ⁷ . Latent suboptimal hemodynamic function before conception predisposes not only to gestational complications, but also to early‐onset cardiovascular disease in later life ⁷⁹ , ⁸⁰ , ⁸¹ . Moreover, abnormal intrauterine hemodynamics may be a direct link between poor fetal growth and early‐onset adult cardiovascular and renal disease ⁸² . While impaired maternal cardiovascular performance plays a role in the poor development of placentation, we should not overlook the contribution of immune‐system dysfunction, which is observed when defective trophoblast invasion occurs in early gestation ⁸³ . The association between confirmed poor maternal hemodynamics and the immune system should be a focus of future research ⁸⁴ .

The classification of PE into resistance‐dominant or volume‐dominant phenotypes challenges the reported longitudinal hemodynamic evolution from early pregnancy until term in women who eventually develop PE ⁶ . In all studies reported since 1990, a hemodynamic imbalance between CO and SVR was present at all stages of pregnancy in women who developed PE ⁸ , ⁷⁸ , ⁸⁵ . Early‐onset PE typically presents with first‐trimester increased SVR and a blunted rise of CO ⁸⁵ . Late‐onset PE, on the other hand, starts with high CO and normal SVR ⁸ . This imbalance can remain unchanged ⁸ , ⁵⁷ , or convert from a high‐CO circulation to a high‐resistance circulation with advancing gestation ⁸ , probably due to endothelial damage and intravascular overload ⁸⁶ , thereby establishing a ‘vicious circle’ that, in association with hypoalbuminemia and impaired cerebral blood flow autoregulation, strongly predisposes to eclampsia ⁸⁷ .

Gestational hypertension

Gestational hypertension (GH) also presents with both volume‐dominant and resistance‐dominant phenotypes ⁸ , ⁸⁵ . Contrary to HDP associated with renal damage, abnormal maternal venous Doppler characteristics are absent in GH⁶, raising the question as to whether PE‐related symptoms of organ dysfunction may relate to venous congestion induced by increased intravenous pressure, reduced venous capacitance or external venous compression due to raised intra‐abdominal pressure ⁸⁸ .

Overall, this evidence supports the abandonment of two traditional concepts of obstetrics. Firstly, the mechanistic time‐dependent classification into early‐onset and late‐onset PE has no clinical relevance, and is meaningful only from an epidemiological perspective. Secondly, the very term ‘pre‐eclampsia’ no longer bears any clinical meaning once we recognize the truly different pathophysiological pathways, which simply share similar downstream symptoms. Thus, PE and GH should be considered under the same umbrella, that is, HDP, with different clinical facets. Accordingly, herein, we use the broader term, ‘HDP’, unless otherwise indicated (e.g. when discussing studies focused only on PE).

Key points

• Maternal hemodynamic assessment differentiates two HDP phenotypes: resistance‐dominant and volume‐dominant (CO‐dominant).

• These phenotypes are linked though not invariably to the gestational age at onset of HDP.

• The most important clinical factor that discriminates between the two HDP phenotypes is the presence of FGR.

• Abnormal maternal hemodynamic function is present in preconception and preclinical stages of HDP.

MATERNAL HEMODYNAMICS IN FETAL GROWTH RESTRICTION

Throughout healthy pregnancy, maternal CO correlates positively with fetal growth velocity and birth weight, and the physiological reduction in SVR is associated with increased birth weight. This is in line with the observation of an interaction between maternal cardiac and placental function ⁸⁹ ; the decrease in SVR coincides with the reduction of resistance in the uteroplacental circulation. Moreover, there is a significant correlation between fetal Doppler indices and maternal hemodynamics. Maternal SVR, CO, heart contractility and dynamicity of circulation all seem to influence the blood flow rate in the umbilical vein ⁹⁰ . The evidence of a correlation between maternal, placental and fetal circulations ⁹¹ highlights the importance of hemodynamic assessment in cases of inadequate fetal growth.

The most common cause of FGR is so‐called uteroplacental insufficiency, resulting from defective placentation, and, traditionally, FGR has been defined as a ‘placental syndrome’ ⁹² , ⁹³ . The poorly functioning placenta restricts nutrient supply to the fetus and prevents normal fetal growth. This condition is characterized by defective trophoblast invasion, abnormal uterine artery adaptation and increased placental vascular resistance.

A new interpretation of the pathophysiology of FGR has stemmed from the premise that placental function is dependent on its perfusion ¹⁵ , ⁹³ . Thus, adequate systemic cardiovascular adaptation in pregnancy is crucial to ensure optimal placental function. Large population studies have identified the occurrence of FGR as an important risk factor for the development of cardiovascular disease later in a woman's life, with the highest risk in cases of the most severe and early FGR ⁹⁴ , ⁹⁵ , regardless of the simultaneous presence of PE.

The definition of FGR is based on fetal biometry and Doppler evaluation, and it is classified as early or late according to whether it presents before or after 32 weeks of pregnancy, respectively ⁹⁶ .

Early fetal growth restriction

Early FGR has low incidence (0.5%) and is characterized by high‐impedance uterine circulation, frequent association with HDP, high risk of perinatal mortality and morbidity, and poor neonatal outcome due to prematurity ⁹⁷ . While it is known that defective trophoblast invasion with subsequent failure of spiral artery adaptation is associated with early FGR ⁹² , maternal hemodynamic assessment provides further insight, linking evidence of uteroplacental dysfunction with signs of maternal cardiovascular impairment in pregnancies with early FGR.

Women with a prepregnancy or early‐pregnancy abnormal maternal hemodynamic profile, with low CO, high SVR and a hypovolemic state, have an increased risk of developing FGR ⁴⁷ , ⁹⁸ , and this hemodynamic profile is maintained during the pregnancy. These hemodynamic alterations can be identified in apparently healthy women at different preclinical stages before manifestation of the disease, and SVR seems to be the most important predictive factor ⁹⁹ , ¹⁰⁰ . The fact that in patients with chronic hypertension there is an increased risk of FGR further supports the hypothesis that the maternal cardiovascular system plays a crucial role in the pathogenesis of abnormal placental function ⁹⁹ , ¹⁰¹ .

Late fetal growth restriction

Compared with early FGR, late FGR is less closely associated with HDP, abnormal placental development and spiral artery remodeling. The main clinical challenge is its correct identification and diagnosis, firstly, due to the subtle clinical manifestations and, secondly, due to the fact that FGR might also exist in fetuses with size (abdominal circumference (AC) or estimated fetal weight (EFW)) > 10^th percentile ⁹⁷ , ¹⁰² , ¹⁰³ . However, late FGR, with a prevalence of around 5–10%, is much more common than early FGR and thus has an important clinical impact ⁹⁷ .

The association between late FGR and placental histopathological lesions is less evident than that in early FGR, and the differences compared with healthy pregnancy are often very subtle ¹⁰⁴ . Late FGR, compared with early FGR, shows less pronounced changes in uterine artery impedance ⁹² . In about one‐third of all pregnancies, there is a worsening of uterine artery Doppler in the late third trimester ¹⁰⁵ , suggesting that this late variation in uterine vascular resistance is not related to trophoblast invasion but is an effect of changes that involve the maternal cardiovascular system ¹⁰⁶ . In these cases, there is a higher risk of low birth‐weight percentile ¹⁰⁵ . This observation explains the low predictive capacity of uterine artery Doppler velocimetry to identify late FGR and suggests the importance of maternal hemodynamic assessment in these cases. The second trimester may be optimal for maternal cardiovascular assessment for identification of patients at risk of developing late FGR ¹³ .

In pregnancies complicated by late FGR, maternal hemodynamic parameters do not show physiological cardiovascular adaptation, but show a flat, static pattern, with low CO and high SVR ¹⁰⁶ .

Small‐for‐gestational age

When fetal size (AC or EFW) is below the 10^th percentile, a priority is to differentiate between small‐for‐gestational age (SGA) and FGR. Some SGA fetuses might be constitutionally small but otherwise healthy and, consequently, at lower risk of adverse outcome. Identification of these pregnancies is important for their correct management and to avoid maternal anxiety and overtreatment. Thus, biophysical parameters other than size are required to differentiate SGA from FGR (e.g. fetal growth velocity, fetoplacental Doppler velocimetry, biomarkers) ⁹⁷ , ¹⁰³ , ¹⁰⁷ . Maternal hemodynamics could play an important role in differentiating FGR from SGA. A normotensive pregnancy complicated by FGR is characterized by lower maternal HR, lower CO and higher SVR, while a pregnancy with a SGA fetus is characterized by a maternal hemodynamic profile similar to that of a healthy pregnancy ¹³ , ¹⁰⁸ . Assessment of umbilical vein blood flow might provide even more detailed insights into the imbalance between fetal demand and maternal cardiovascular and placental availability ⁹⁰ , ⁹¹ , ¹⁰⁹ , ¹¹⁰ .

Key points

• Maternal hemodynamic parameters, such as CO and SVR, are associated with fetal growth and birth weight.

• Women with a hypodynamic circulation before and early in pregnancy are at higher risk of their pregnancy being affected by FGR.

• Early FGR is characterized by profound maternal hemodynamic changes, similar to those present in HDP with FGR.

• Late FGR is characterized by less pronounced maternal hemodynamic alterations, suggesting late maternal hemodynamic maladaptation to fetoplacental requirements.

• Maternal hemodynamics, biomarkers and umbilical vein blood flow evaluation might provide additional information to differentiate SGA from FGR, but further research is needed.

MATERNAL HEMODYNAMICS AND CARDIOVASCULAR DISEASE LATER IN LIFE

There is growing evidence that the abnormal hemodynamic and echocardiographic findings that are common in women with HDP do not resolve following delivery. Many women continue to be hypertensive in the immediate postnatal period, with some exhibiting signs of cardiac dysfunction ¹⁶ , ¹⁷ , ¹¹¹ , and some are at risk of cardiovascular disease later in life ¹¹² . Data from a recent randomized controlled trial (RCT) suggest that long‐term cardiovascular health may be improved by close monitoring and effective control of BP in the immediate postnatal period ¹¹³ . Given these findings, increasingly, the hemodynamic assessment and management of women following HDP is considered important.

Risk of cardiovascular disease after HDP

The development of chronic hypertension after pregnancy complicated by HDP largely explains the increased risk of developing cardiovascular disease ¹¹¹ , ¹¹² . A meta‐analysis showed that postpartum hypertension occurred five times more frequently in the first year following delivery in women affected by HDP¹¹². The risk of HDP and/or chronic hypertension is related to obesity ¹¹⁴ , social deprivation ¹¹⁵ and pre‐existing or gestational diabetes ¹¹⁵ . The association of cardiovascular disease with specific risk factors after an episode of HDP remains subject to diverse interpretation. Dyslipidemia ¹¹⁶ , metabolic syndrome ¹⁸ and accelerated rate of systematic atherosclerosis have been discussed regarding their possible link with an increased incidence of cardiovascular disease ¹¹⁷ . It seems likely that a cardiovascular system with subclinical impairment might be stressed by the demands during pregnancy, and/or that the endothelial stress of HDP accelerates damage of a dysfunctional cardiovascular system ¹¹⁸ .

The use of cardiovascular risk scoring does not improve prediction of postpartum cardiovascular complications, but, recently, a prediction model including maternal demographic characteristics, BP and echocardiographic parameters in the peripartum period identified women at risk of postpartum hypertension ¹¹⁹ , ¹²⁰ .

Understanding factors that influence HDP for tailored proactive prevention later in life

HDP during pregnancy is a critical event affecting future cardiovascular health. Understanding the origin of HDP in pregnancy could help in proactively suggesting tailored preventive measures for the postpartum period and later in life. For instance, HDP associated with high placental oxidative stress, i.e. a high ratio between soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and placental growth factor (PlGF), are more frequently associated with FGR ¹¹⁸ . In the postpartum period, women who had HDP with lower values of PlGF showed worse cardiac structure, increased BP levels and higher lipid levels ¹²¹ . A recent meta‐analysis confirmed that women who had early‐onset PE, which is more frequently associated with FGR, had even higher risk of cardiovascular disease later in life ¹²² .

Whatever the cause and clinical phenotype of the disease, there is a dose‐dependent effect between severity of HDP and likelihood of adverse cardiovascular outcome ¹⁶ . Preventive measures should be guided by a better understanding of the most likely cause of the HDP⁷.

Peripartum and postpartum echocardiographic assessment

Profound echocardiographic changes are seen in most women with HDP, including increased left ventricular mass, cardiac remodeling and diastolic dysfunction ¹¹³ , ¹²³ . Women with a history of PE also have altered cardiac structure and evidence of diastolic and myocardial dysfunction in the early years after delivery ¹²⁴ , ¹²⁵ . Despite this evidence, there are no recommendations regarding cardiac evaluation after HDP. However, women presenting with symptoms of dyspnea or signs of intravascular volume overload require echocardiographic evaluation ¹²³ .

Compared to women with HDP and normal echocardiograpy, those with HDP with severe left ventricular remodeling and diastolic dysfunction at echocardiography are more likely to develop chronic hypertension in the next decade ¹²⁶ .

Optimal method and frequency of blood pressure measurement postpartum

According to a Norwegian population‐based study, BP life‐course trajectories remained higher in a HDP cohort compared to controls ¹²⁷ . This study supports the interpretation of HDP not as causal, but rather as a marker of a pre‐existing subclinical disease, and that diastolic BP does not return to ‘normal’ levels during the postpartum period following HDP. Whatever the interpretation, longitudinal BP measurements should be undertaken in the postpartum period, as either home or scheduled ambulatory BP monitoring. One trial proved that postpartum BP telemonitoring is effective, achieving 8‐fold fewer hypertension‐related readmissions ¹²⁸ . It is well‐tolerated by patients, is a better predictor of end organ damage than clinical measurement ¹²⁹ and may also reduce ethnic health disparities in postpartum care related to compliance.

Severe hypertension can occur postpartum, with the average latency period between delivery and BP levels that necessitate treatment being approximately 6 days ¹³⁰ . These findings suggest that it is sensible to measure BP for at least the first 10 days postpartum ¹³⁰ . Given the significant diurnal variation in BP in women with HDP, with BP climbing in the afternoon and evening in approximately 50% of women, twice‐daily readings would seem appropriate ¹³¹ .

A trial of postpartum BP self‐monitoring and self‐management via remote medication advice and feedback in women who experienced HDP demonstrated high acceptability, adherence and accuracy, and a significant improvement in BP control ¹³² . BP control was better whilst on treatment, but, more importantly, the diastolic BP was on average 4.5 mmHg lower 6 months postpartum, approximately 3 months after stopping medication. A follow‐up study 4 years postpartum demonstrated that the diastolic BP was more than 7 mmHg lower in those originally randomized to postpartum BP self‐management vs those treated with standard care ¹³³ . This is highly suggestive of a window of opportunity to optimize long‐term cardiovascular health by optimal monitoring and management of BP postpartum.

Optimal antihypertensive medication

Optimal management strategies once hypertension and/or cardiovascular dysfunction has been confirmed postpartum remain largely undetermined. It is likely that the findings from a furosemide RCT could be adopted to treat women with hypervolemic hyperdynamic late preterm or term HDP, using a 5‐day course of 20‐mg oral furosemide ¹³⁴ . However, no specific guidelines are available for long‐term prevention or therapeutic intervention, except for the American Heart Association's recommendation regarding HDP as an additional risk factor to guide prescription of statins as a risk‐reduction measure ¹³⁵ .

Angiotensin‐converting enzyme (ACE) inhibitors were tested in a double‐blind randomized placebo‐controlled trial in the postpartum period in patients who had early‐onset PE ¹³⁶ . This trial fell short of proving a reduction in SVR, yet patients in the treated arm showed lower diastolic BP, better diastolic function and improved left ventricular remodeling at 6 months postpartum. Obstetrician‐gynecologists, physicians and primary‐care doctors should exploit the ‘fourth trimester’ to help improve the future cardiovascular health of women who have been exposed to HDP.

Key points

• Maternal hemodynamic alterations present during HDP may persist in the postpartum period and predispose women to increased cardiovascular risk later in life.

• Women with a history of HDP and symptoms of dyspnea or signs of volume overload should undergo an echocardiographic evaluation.

• Longitudinal BP measurements, obtained by either home or ambulatory monitoring, should be carried out in the postpartum period in women with a history of HDP.

• In women with a history of HDP, postpartum monitoring of BP should continue for at least the first 10 days and should be performed at least twice per day.

• Women who experienced HDP should be counseled proactively regarding life‐style changes (e.g. diet, smoking habit, exercise).

IMPLICATIONS FOR PREDICTION, PREVENTION AND MANAGEMENT

The association between HDP and FGR and maternal changes in cardiovascular function, both before and after development of the clinical syndrome, presents an opportunity for using assessment of maternal hemodynamics in the clinical setting.

Potential for prediction

Despite evidence of maternal cardiovascular maladaptation in pregnancies destined to develop HDP and FGR, prediction of these conditions in early pregnancy is not feasible given the wide overlap between physiological and pathological changes. The performance of first‐trimester prediction of PE using biomarkers (PlGF), uterine artery Doppler and maternal characteristics (BP and body mass index (BMI)) presents a promising ‘proof‐of‐principle’ algorithm, and assessment of second‐trimester uterine artery Doppler has been well described ¹³⁷ .

Prevention

Given the relationship between high SVR prior to pregnancy ⁴⁷ and risk factors such as high BMI and low PV ¹³⁸ , ¹³⁹ , it is tempting to consider that optimizing maternal cardiovascular function prior to pregnancy might reduce the risk of HDP and FGR. Exercise in women with previous PE improves cardiovascular function, returning it to that of a sedentary woman ¹⁴⁰ , and results from a meta‐analysis suggest that exercise prior to pregnancy reduces the incidence of placental syndromes ¹⁴¹ . Non‐pharmacological vasoactive dietary nitrates might reduce BP in hypertensive pregnant women ¹³⁶ . No study has examined the potential for nitrates and exercise in reducing the risk of HDP or PE in high‐risk women, though the rationale for this is compelling. Other treatments, such as low‐dose aspirin ¹⁴² , have been proposed for the prevention of PE; however, with the relationship to maternal hemodynamic parameters being unclear, their description is beyond the scope of this document.

Management of established HDP and/or fetal growth restriction

Despite major pharmacological advances in the treatment of hypertension in the non‐pregnant population, treatments for hypertension in HDP and PE have remained largely unchanged over the last 50 years. Adrenoceptor antagonists (such as labetalol) and the competitive alpha‐adrenoceptor blocker, doxazosin, calcium channel antagonists (such as nifedipine), vasodilators (such as hydralazine) and centrally acting dopamine antagonists (such as alpha‐methyldopa) are the mainstay of antihypertensive therapy during pregnancy. The definitive treatment for HDP and PE is delivery; hence, iatrogenic preterm birth is common, usually indicated because of uncontrolled maternal hypertension, organ dysfunction or risk of seizures.

Therapy for HDP principally involves strategies to lower BP. This can be achieved by one or both of two mechanisms: by causing vasodilation and, thus, decreasing SVR, or by decreasing CO. Currently, these treatments are used variably with respect to the timing of onset of HDP and the presence of FGR. Knowledge of the two phenotypes of HDP, resistance‐dominant and volume‐dominant, could provide a potential opportunity for targeted antihypertensive therapy that seeks to compensate for the underlying cardiovascular deficit, although it is important to note that targeting BP in PE may compromise a growth‐restricted fetus ¹⁵ . As FGR frequently coexists with PE, especially at earlier gestational ages, at least theoretically, it is important for CO and BP to be maintained in order not to compromise the uteroplacental circulation.

The pathophysiological concept of a bimodal hemodynamic pattern of HDP has important clinical implications. The BP‐lowering pharmacological mechanisms of different antihypertensive drugs differ, offering opportunities for phenotype‐specific treatment of hypertension in pregnancy ¹⁴³ , ¹⁴⁴ , ¹⁴⁵ . Calcium channel blockers predominantly reduce arteriolar hypertonia, resulting in lower SVR with a subsequent rise in CO ¹⁴⁶ , ¹⁴⁷ . Beta‐blocking agents are less active in vascular resistance‐dominant HDP and, for this reason, clinical management protocols have been reported proposing the replacement of beta blockers by calcium channel blockers after 24 h in non‐responsive cases ¹⁴⁸ . Treatment of women with HDP with beta blockers, including labetalol, has been associated with lower neonatal birth weight ¹⁴⁹ ; therefore, their use should be considered carefully in cases of HDP with poor fetal growth. RCTs are currently running to evaluate the gestational and neonatal outcome of targeted antihypertensive treatment in resistance‐dominant or volume‐dominant HDP ¹⁴³ , ¹⁵⁰ .

Discrimination between resistance‐dominant HDP and volume‐dominant HDP also challenges general guidelines recommending a ‘one‐for‐all’ pharmacological treatment ¹⁵¹ and stimulates further exploration of the role of targeted pharmacological treatment in both latent and clinical stages of disease. New and currently unexplored management options include treatment with diuretics in cases of volume‐dominant HDP ¹⁵² and/or NO donors targeting the activated endothelium of arterial, microcirculatory and venous parts of the circulation ¹⁵³ , ¹⁵⁴ . A previous observational study suggests that vasodilator therapy improves birth weight and growth velocity in FGR ¹⁵⁵ . More studies are required to identify whether targeting therapy in HDP in this way achieves better BP control or improved obstetric outcome.

Additional preventive and therapeutic approaches include the possible immune‐modulation impact of low‐molecular‐weight heparin in HDP associated with FGR ¹⁵⁶ .

Sildenafil prolonged gestation by a non‐significant 4 days ¹⁵⁷ and its use in clinical practice has been curtailed due to findings of increased neonatal death due to pulmonary hypertension in trials in pregnancies affected by severe early‐onset FGR ¹⁵⁸ , ¹⁵⁹ . No benefit in terms of prolongation of gestation has been reported from the use of esomeprazole, pravastatin ¹⁶⁰ , ¹⁶¹ or antithrombin ¹⁶² . There is evidence to support the prolongation of gestation in expectantly managed PE with administration of metformin, although more studies are needed ¹⁶³ . NO donor S‐nitrosoglutathione has demonstrated efficacy in improving proteinuria and arterial and platelet function in women with severe early‐onset PE, suggesting a potential disease‐modifying mechanism of action ¹⁵³ , ¹⁶⁴ , ¹⁶⁵ .

Key points

• Maternal hemodynamic changes precede the development of clinical symptoms in pregnancies with PE and FGR, opening a window of opportunity for prediction and prevention.

• Exercise, dietary nitrates and control of BP prior to and in early pregnancy may improve hemodynamic indices but have not been shown to reduce the incidence of PE and FGR in women at high risk.

• Knowledge of the two cardiovascular phenotypes of HDP could provide a potential opportunity for targeted antihypertensive therapy to replace a ‘one‐size‐fits‐all’ pharmacological approach to HDP.

• Calcium channel blockers are preferred in women with high SVR and low CO (usually PE/HDP associated with FGR, i.e. the resistance‐dominant phenotype).

• Beta‐blocking agents should be used with care in cases of HDP associated with FGR.

AREAS FOR RESEARCH

From the evidence outlined above, it is clear that the assessment of maternal hemodynamics adds information to current knowledge on the pathophysiology of gestational complications. However, it is unclear to what extent these assessments are clinically useful and cost‐efficient. Further research is required to address the following areas.

Applicability in clinical practice

Future research should focus on identifying the most effective techniques and maternal hemodynamic parameters, used either individually or in combination, and on establishing their normal reference ranges²⁷. The potential value of assessing the currently unexplored pathophysiological mechanism of the maternal venous system and body water volumes, independently or in combination with cardiac and arterial function, should be investigated ⁸⁵ . Whether hemodynamic testing is better limited to a selected high‐risk population or offered to all pregnant women should also be explored.

Screening for gestational complications

Prospective longitudinal studies that include preconceptional data are required to improve our understanding of changes in maternal hemodynamics and to clarify whether, in pregnancies affected by HDP, the cardiovascular profile is altered due to maladaptation in the index pregnancy, or pre‐existing pathology in the cardiovascular system is unmasked by pregnancy ⁷⁸ , ¹⁶⁶ . The feasibility and relevance of preconceptional screening remains to be explored.

Little is known regarding changes in maternal hemodynamics in the preclinical phase, among pregnant women at risk of developing PE who are taking low‐dose aspirin, calcium supplements and/or vitamin C. Furthermore, newly emerging screening strategies using biophysical parameters only should be evaluated ¹⁶⁷ . Future prognostic studies are required to evaluate the optimum structure and timing of a screening program that could help to identify women at risk of developing HDP and pregnancy complications. The program should use current available reference ranges for both maternal cardiac function ³² and arterial stiffness ²² . They should report parameters appropriately adjusted for confounding factors and identify optimum timing of, and parameters for, screening.

PE is a risk factor for short‐ and long‐term cardiovascular disease. Research is required to identify the optimum postpartum screening program that could identify women at risk of long‐term cardiovascular dysfunction and guide future management in subsequent pregnancies ¹² , ¹⁶ , ¹⁸ .

Few studies have examined changes in maternal hemodynamics among pregnant women with multiple pregnancy or reduced fetal movements, those undergoing induction of labor and those who require regional anesthetics at the time of delivery. Future studies should provide guidance regarding the benefits of maternal hemodynamic assessment in the clinical setting in these cases.

Diagnosis of medical disorders

Assessment of maternal hemodynamics, including venous function and volume homeostasis, is useful to discriminate between GH, PE and normotensive FGR ⁶ , ⁸⁵ . This approach can also help distinguish volume‐dominant from resistance‐dominant GH⁶. However, the feasibility and applicability of these methodologies require further evaluation.

The use of point‐of‐care/near‐patient testing and continuous monitoring is increasing, revolutionizing maternal healthcare. Future investigators should report maternal hemodynamic parameters appropriately adjusted for confounding factors and identify optimum timing of, and parameters for, screening.

Gestational diabetes is noted to be associated with maladaptation of the cardiovascular system in pregnancy. Future studies are required to evaluate the optimum timing for screening, correlate findings to clinical outcomes and critically evaluate the role of metformin therapy and modulation of arterial stiffness ²² , ¹⁶⁸ , ¹⁶⁹ , ¹⁷⁰ , ¹⁷¹ , ¹⁷² .

Management of HDP

Volume‐dominant and resistance‐dominant HDP are two different pathophysiological phenotypes ⁷⁶ , ¹⁰⁶ , ¹⁷³ . It remains to be determined whether targeted antihypertensive treatment may improve obstetric and neonatal outcome ¹⁵⁰ . Large RCTs are needed to evaluate the potential therapeutic benefit of targeting variable components of the maternal hemodynamic maladaptation syndrome observed in pregnant women with HDP. The algorithmic model that combines the Z‐score of multiple parameters of maternal hemodynamics will need further validation to assess whether it could guide treatment and assess the treatment response ¹⁷⁴ , ¹⁷⁵ . Hemodynamics‐assisted monitoring of gestational complications might be useful to improve obstetric and neonatal outcome, but this approach has yet to be validated ¹⁰⁶ , ¹⁷⁶ . The implementation of maternal hemodynamic assessment is an opportunity to explore the application and effectiveness of currently unexplored antihypertensive treatments, such as diuretics ¹⁷⁶ , ¹⁷⁷ , ¹⁷⁸ and nitrates ¹⁷⁹ , ¹⁸⁰ , ¹⁸¹ .

Prevention

As the subpopulation of younger parturients with morbidities is on the rise, hemodynamic assessment provides opportunities to initiate prevention strategies with the aim of improving maternal cardiovascular function before conception ¹⁸² . The same applies to women with a history of PE, in whom prevention strategies could potentially be initiated during the interpregnancy interval ¹⁴⁰ . The clinical relevance of these interventions remains to be explored.

Obesity is associated with low‐grade chronic inflammation in adipose tissue, diastolic dysfunction and arterial stiffness ¹⁸³ ; studies should examine how this contributes in general to vascular dysfunction and, more specifically, to the pathogenesis of hypertension and vascular stiffening ¹⁸⁴ , ¹⁸⁵ .

CONCLUSION

Maternal hemodynamic assessment provides additional clinical information that is useful for management of pregnancies complicated by HDP and/or FGR. Moreover, it opens a window of opportunity for prediction and prevention of maternal hemodynamic maladaptation, which may benefit both the index pregnancy and future maternal cardiovascular health.

CONSENSUS STATEMENTS

• After 20 weeks of gestation, assessment of maternal hemodynamics should be performed with the woman in a left lateral position.

• Different techniques of maternal hemodynamic evaluation cannot be used interchangeably.

• Maternal hemodynamics differentiates two HDP phenotypes: resistance‐dominant and volume‐dominant.

• Women with resistance‐dominant HDP (usually HDP associated with FGR) should be treated with a vasodilator, such as calcium channel blockers.

• Women with volume‐dominant HDP (usually HDP with appropriate‐for‐gestational‐age fetal growth) should be treated with beta‐blocking agents.

• Maternal hemodynamic evaluation might be useful in preconception and preclinical stages of HDP as an opportunity for prediction and prevention, but further research is required.

• An echocardiographic assessment should be performed in women with a history of HDP and symptoms of dyspnea or volume overload.

• Maternal hemodynamics should be evaluated in the postpartum period in women with a history of HDP, to identify those at increased risk of cardiovascular disease later in life.

• In women with a history of HDP, longitudinal BP measurements are recommended in the postpartum period.

• Women with a history of HDP should be counseled proactively regarding life‐style changes.

Collaborators

We would like to thank the following members of the International Maternal Hemodynamic Group for their critical revision and contribution to this document:

J. J. Duvekot, Department of Obstetrics and Gynecology, Erasmus MC University Medical Center, Rotterdam, the Netherlands

C. Ghossein‐Doha, Department of Obstetrics and Gynecology, Maastricht University Medical Centre, Maastricht, the Netherlands; and Research School GROW, University of Maastricht, Maastricht, the Netherlands

C. McEniery, Division of Experimental Medicine and Immunotherapeutics, University of Cambridge, Cambridge, UK

F. Mecacci, Department of Obstetrics and Gynecology, Department of Experimental, Clinical and Biomedical Sciences, Careggi University Hospital, University of Florence, Florence, Italy

G. P. Novelli, Division of Cardiology, Depatment of Medicine, Tor Vergata Polyclinic, Rome, Italy

B. Vasapollo, Department of Surgical Sciences, Tor Vergata University, Rome, Italy; and Department of Obstetrics and Gynecology, Policlinico Casilino Hospital, Rome, Italy

I. Wilkinson, Division of Experimental Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK

CITATION

This Consensus Statement should be cited as: ‘Stampalija T, Lees C, Ghi T, Cornette J, Gyselaers W, Ferrazzi E, Mousa T, Spaanderman M, Thilaganathan B, Valensise H and Collaborators. ISUOG Consensus Statement on maternal hemodynamic assessment in hypertensive disorders of pregnancy and fetal growth restriction. Ultrasound Obstet Gynecol 2025; 66: 681–696.

DATA AVAILABILITY STATEMENT

Data sharing is not applicable to this article as no new data were created or analyzed in this study.