Background

From structural fetal cardiology to functional fetal cardiology

The classical task of prenatal cardiac diagnosis is to determine whether the fetal heart is structurally normal and, if congenital heart disease is present, to define its anatomy, risk, expected postnatal physiology, and perinatal management. This task remains fundamental. A correct structural diagnosis can determine the place and timing of delivery, the need for prostaglandin therapy, neonatal intensive care, catheter intervention, or cardiac surgery. Current fetal echocardiography guidelines therefore emphasise segmental analysis, standard views, colour and spectral Doppler, rhythm evaluation, and perinatal planning [1-3].

At the same time, daily fetal cardiology practice increasingly reveals another group of patients: fetuses with a structurally normal heart but abnormal cardiac size, geometry, flows, rhythm, or myocardial performance. Similar functional abnormalities may also occur in fetuses with congenital heart disease and can change the clinical meaning of the structural diagnosis. Respondek-Liberska described these abnormalities in the Polish monograph on functional disorders of the fetal cardiovascular system, emphasising that they are frequently encountered but may be underestimated, misinterpreted as malformations, or detached from the physiological context of fetal circulation [4].

In this review, the concept of functional medicine is used as a clinical analogy rather than as an alternative to evidence-based cardiology. Functional medicine, in its most useful academic meaning, regards disease as an endpoint of changing function and seeks mechanisms that precede overt disease [5]. Applied to the fetus, this means that a mild tricuspid regurgitation jet, right-heart predominance, increased pulmonary artery diameter, elevated myocardial performance index, or pericardial effusion should not be described only as isolated signs. Each finding should raise the question of mechanism: preload, afterload, myocardial injury, ductal constriction, altered pulmonary resistance, infection, placental pathology, cord compression, abnormal streaming, arrhythmia, or emerging heart failure.

Definition of functional fetal cardiac changes

Functional fetal cardiac changes can be defined as abnormalities of fetal cardiovascular size, geometry, flow, rhythm or performance that do not necessarily arise from primary cardiac malformation but reflect adaptation, maladaptation, or decompensation of fetal circulation. They include a broad spectrum: disproportion of the four-chamber view – the right ventricle (RV) and left ventricle (LV) are usually near equal, with mild right dominance possible later in gestation. Significant disproportion may be suspected when RV/LV > 1.2 in the second trimester or > 1.3 in the third trimester; marked third-trimester RV predominance, e.g. > 1.5, is concerning [4], and great vessels; valvular regurgitation; abnormal flow through the ductus arteriosus, foramen ovale, ductus venosus, pulmonary veins, umbilical vein or umbilical artery; cardiomegaly; abnormal pulmonary vascular flow; arrhythmias; myocardial hypertrophy or contractility impairment; pericardial effusion; hydrops and fetal heart failure [4, 6-9].

This distinction is clinically important. A structurally normal fetal heart may show functional abnormalities, whereas a fetus with congenital heart disease may have either preserved function or significant additional functional compromise. Thus, normal heart anatomy should not be equated with normal fetal cardiovascular physiology.

Material and methods

This article is a narrative review and conceptual synthesis. The source material included Respondek-Liberska’s monograph on functional abnormalities of the fetal cardiovascular system [4], current fetal echocardiography guidelines and scientific statements [1-3], selected literature on fetal valvular regurgitation, fetal heart failure, ductal constriction and false-positive coarctation [6-12], and the author’s publication cycle on fetal echocardiographic changes in relation to placental thickness, abnormal fetal/neonatal lung development, and nuchal cord entanglement [13-17].

The review was organised around three pathophysiologic axes of the fetal haemodynamic environment: the placenta, the fetal lungs, and the umbilical cord. Attention was paid to abnormalities that may be detected by routine or targeted fetal echocardiography in the third trimester and that can occur both in fetuses with normal heart anatomy and in fetuses with congenital heart disease. Because this was a narrative review, no formal systematic review protocol, meta-analysis, or risk-of-bias assessment was performed.

Results

Spectrum of functional abnormalities of the fetal heart

The functional phenotype of the fetal cardiovascular system can be grouped into five major domains. The first is geometry: chamber disproportion, right atrial and right ventricular enlargement, widening of the main pulmonary artery, abnormal pulmonary artery-to-aorta ratio, increased cardiothoracic area ratio, or cardiomegaly assessed by cardiothoracic area ratio (CTAR) or transverse cardiac diameter. The second is flow and valve function: tricuspid, mitral, pulmonary, or aortic regurgitation; turbulent flow; abnormal ductal, foramen ovale, venous or pulmonary flows. The third is myocardial performance: abnormal Tei index/myocardial performance index (Tei index should be interpreted using gestational-age- and method-specific norms). Published fetal LV and RV myocardial performance index means are approximately 0.46 ±0.08 and 0.47 ±0.09; values above the 95^th centile, or roughly > 0.60-0.65 depending on method, suggest impaired global myocardial performance [1, 2, 4, 15-17], decreased shortening fraction, abnormal annular motion, and ventricular hypertrophy. The fourth is rhythm and conduction: premature beats, tachyarrhythmia, bradycardia, and atrioventricular block. The fifth is decompensation: pericardial effusion, combined atrioventricular valve regurgitation, abnormal ductus venosus flow, hydrops, and fetal heart failure [4, 6-9]. Echocardiographic tools used for functional cardiovascular assessment are presented in Table 1.

Disproportion is a useful example. In fetal life, right-sided dominance may be physiological, but progressive or marked disproportion at the atrial, ventricular, or great-vessel level is not a diagnosis by itself; it is a prompt to search for the mechanism of volume or pressure overload, altered streaming, or extracardiac disease. Respondek-Liberska defined fetal disproportion as right-left asymmetry that can involve the atria, ventricles, and/or great vessels and emphasised that it often emerges in the third trimester as fetal blood flow is redistributed [4].

Preferential streaming and the right-heart physiology of fetal life

Fetal circulation is not a miniature version of postnatal circulation. The right ventricle contributes substantially to combined cardiac output and ejects through the pulmonary artery and ductus arteriosus into the descending aorta. In the right atrium, venous streams from the inferior vena cava, ductus venosus, and superior vena cava interact. Oxygen-rich blood from the ductus venosus is preferentially directed through the foramen ovale toward the left atrium, whereas blood from the systemic veins is directed toward the tricuspid valve and right ventricle. Therefore, modest changes in venous return, ductal patency, pulmonary resistance, fetal position, or cord compression may alter the visible balance between right and left heart structures [4].

This physiology explains why functional echocardiography must interpret the heart together with the placenta, umbilical cord, ductus venosus, ductus arteriosus, foramen ovale, and fetal lungs. A widened pulmonary artery, increased pulmonary artery to aorta (PA/Ao) ratio, or right ventricular enlargement may represent a structural lesion, but it may also represent redistribution of fetal flow, pulmonary vascular maladaptation, transient ductal constriction, or the haemodynamic effect of nuchal cord entanglement [4, 10, 12, 18].

Functional valve regurgitation: a common sign with multiple mechanisms

Functional tricuspid regurgitation is one of the best-known examples of a functional fetal cardiac abnormality. It was reported in approximately 6% to 7% of fetuses with normal heart anatomy in early fetal cardiology studies [6, 7]. Its mechanism may include increased preload, increased afterload, myocardial dysfunction, arrhythmia, infection, or transient ductal constriction. Mild, protosystolic tricuspid regurgitation with preserved fetal cardiovascular status may be benign, but holosystolic or high-velocity regurgitation, regurgitation associated with cardiomegaly, abnormal ductus venosus flow, pericardial effusion, or impaired ventricular performance requires a broader diagnostic search [4, 6-8].

The same interpretive principle applies to mitral, pulmonary, and aortic regurgitation. Isolated mild pulmonary regurgitation may reflect transient pulmonary vascular immaturity or increased pulmonary vascular resistance, whereas persistent or high-velocity regurgitation may require exclusion of semilunar valve dysplasia, ductal constriction, or rare structural lesions. Combined tricuspid and mitral regurgitation is especially important because it may indicate more advanced volume overload, myocardial injury, or fetal heart failure [4, 8, 9].

Cardiomegaly and fetal heart failure

Cardiac size should be assessed in both structurally normal hearts and congenital heart disease. Respondek-Liberska emphasised that many fetal heart defects are not accompanied by cardiomegaly; therefore, cardiomegaly can be an independent marker of fetal risk rather than a direct consequence of the malformation itself [4]. CTAR is a practical screening and monitoring measure; a normal value is approximately 0.30, whereas CTAR greater than 0.45 indicates cardiomegaly [4].

When cardiomegaly is accompanied by pericardial effusion, ventricular dysfunction, abnormal venous Doppler, atrioventricular valve regurgitation, or hydrops, the fetus should be evaluated for heart failure. The cardiovascular profile score (CVPS) provides a semiquantitative approach to fetal cardiovascular compromise, and it has been used in the surveillance of fetal hydrops and heart failure; CVPS has 10-point score: five domains, each 0-2 points. Lower scores indicate worse fetal cardiovascular compromise [1, 2, 4, 8, 9]. Functional echocardiography should therefore not only describe cardiomegaly but also determine whether it is compensated, progressive, or part of a decompensated cardiovascular profile.

Placental model: thick placenta and severity-weighted fetal dysfunction

The placenta is a central component of the fetal cardiovascular circuit. In a recent retrospective study, placental thickness was analysed in 1452 third-trimester fetal echocardiograms and categorised as 40 mm or less, 41-69 mm, and 70 mm or greater [13]. The study introduced a severity-weighted diagnostic system in which diagnoses were grouped as congenital heart defects, cardiac dysfunctions, extracardiac malformations, and extracardiac dysfunctions. Each diagnosis was assigned a weight according to clinical severity rather than counted simply as present or absent [13].

This approach parallels the idea of classifying fetal cardiac diagnoses not only by anatomy but also by clinical weight, as proposed in the Polish fetal cardiology classification of Respondek-Liberska and Slodki [19]. The placental-thickness study showed that thick placentas correlated more clearly with weighted extracardiac dysfunction and, to a lesser degree, with weighted cardiac dysfunction, whereas structural malformations showed weak or absent correlation with placental thickness [13]. These findings support the concept that placental enlargement may be a marker of fetal systemic stress or dysregulation and that functional fetal echocardiographic signs may reflect dynamic physiology more closely than static malformation categories.

Pulmonary model: prenatal signs suggesting abnormal pulmonary vascular adaptation

The fetal lungs are a low-flow, high-resistance vascular bed during fetal life, but they are also preparing for the dramatic postnatal fall in pulmonary vascular resistance. Functional echocardiography can indirectly identify abnormal pulmonary vascular adaptation by detecting a pattern of right-heart pressure overload. In the author’s recent study of abnormal fetal/neonatal lung development, fetuses that later developed neonatal pulmonary hypertension showed a characteristic prenatal pattern that included cardiomegaly, dilation of the main pulmonary artery, tricuspid regurgitation, ventricular or atrial disproportion, and, in some cases, interventricular septal hypertrophy [14].

This observation is particularly relevant in the differential diagnosis of suspected coarctation of the aorta. Third-trimester right-left disproportion and a relatively narrow aortic isthmus are classically associated with possible coarctation, but false-positive diagnoses are common. A pulmonary vascular phenotype can mimic coarctation by producing right-sided predominance, pulmonary artery dilation, and altered ductal-aortic relationships. Therefore, when a fetus is referred for suspected coarctation, functional assessment should include not only the aortic arch but also the PA/Ao ratio (normal mean PA/Ao is about 1.16-1.17, and values should preferably be interpreted against gestational-age-specific centiles or Z-scores [14]), right-heart loading, tricuspid regurgitation, pulmonary venous return, ductal flow, and signs of pulmonary vascular maladaptation [10, 11, 14].

Umbilical cord model: nuchal cord as a modifier of fetal cardiac function

Nuchal cord entanglement is common, but its functional significance in a given fetus depends on tightness, number of loops, fetal position, Wharton’s jelly, venous return, and possible neurovascular compression. The author’s publication cycle examined echocardiographic parameters in fetuses with one or two loops of the umbilical cord around the neck in the third trimester and compared them with fetuses without nuchal cord entanglement [15-17].

In the initial echo-sonographic analysis, fetuses wrapped with the umbilical cord were evaluated by colour Doppler and echocardiographic parameters, demonstrating the practical relevance of cord position during the third-trimester examination [15]. In a subsequent study on cardiac adaptation and preferential streaming, fetuses with one or two nuchal cord loops had a larger main pulmonary artery diameter and higher PA/Ao ratio; fetuses with two loops also had a higher CTAR [16]. In The Nuchal Cord Conundrum, Tei index values for both ventricles were higher in fetuses with one or two nuchal cord loops, whereas the umbilical artery pulsatility index was not significantly different among groups [17].

These findings suggest that nuchal cord may influence myocardial performance and preferential streaming without necessarily changing standard umbilical artery Doppler. Proposed mechanisms include stimulation or compression of the vagus nerve, compression of the carotid arteries, altered venous return, and transient redistribution of fetal flow [17]. From a practical viewpoint, the presence of a nuchal cord, particularly a double nuchal cord, should be documented during fetal echocardiography because it may widen the pulmonary artery, increase the PA/Ao ratio, enlarge the heart, and simulate or exaggerate signs usually associated with coarctation or pulmonary hypertension [16-18].

Three pathophysiologic models of functional fetal cardiac changes are presented in Table 2.

False-positive coarctation as a functional diagnostic problem

False-positive coarctation is one of the most clinically important examples of a structural-looking diagnosis that may be driven by functional physiology. Disproportion of ventricles and great vessels, a narrow aortic isthmus, and right-heart dominance may raise suspicion of coarctation, but these signs are not specific. Measurement of the great vessels in the mediastinum, including the PA/Ao relationship, may help distinguish true from false-positive coarctation in the third trimester [10]. However, even this approach must be interpreted together with the full fetal cardiovascular context.

The differential diagnosis of a coarctation-like pattern includes true coarctation, pulmonary hypertension or abnormal pulmonary vascular adaptation, fetal infection, extracardiac anomalies, persistent left superior vena cava, ductal constriction, arrhythmia, and nuchal cord entanglement [4, 10, 11, 14, 18]. Therefore, functional fetal echocardiography is not only a tool for detecting new abnormalities, but it is also a safeguard against overdiagnosis and unnecessary anxiety or intervention.

Severity-weighted interpretation of fetal cardiac dysfunction

A purely descriptive list of abnormalities may not capture the fetus’s clinical risk. A fetus with mild isolated protosystolic tricuspid regurgitation and a fetus with cardiomegaly, pericardial effusion, abnormal venous Doppler, and atrioventricular valve regurgitation both have functional findings, but their clinical meaning differs substantially. The severity-weighted system used in the placental-thickness study is therefore conceptually important: it measures the burden of dysfunction, not merely the presence of signs (Table 3) [13].

A practical severity-weighted framework for fetal cardiac dysfunction can be modelled on fetal cardiac defect classifications and on CVPS principles [8, 9, 13, 19]. Such a framework should remain clinically flexible and requires prospective validation, but it may help to standardise reports, follow-up intervals, and communication with obstetricians and neonatologists.

Discussion

The fetal heart as an informational organ

The central message of functional fetal cardiology is that the fetal heart can function as an informational organ (Figure 1). It receives and integrates signals from the placenta, umbilical cord, lungs, fetal metabolism, infection status, and maternal environment. A fetal echocardiographic sign may therefore represent the earliest visible cardiac expression of an extracardiac process. In this sense, functional echocardiography translates the concept of functional medicine into fetal cardiology: it searches for the mechanism of dysfunction before irreversible disease or decompensation is established [4, 5] (Table 2 – functional cardiac phenotypes).

This approach does not diminish the value of structural diagnosis. On the contrary, it makes structural diagnosis more precise because it asks whether the observed morphology reflects anatomy, physiology, or both. A fetus with right-heart dominance may have coarctation, but it may also have pulmonary vascular maladaptation, nuchal cord-related preferential streaming, ductal constriction, infection, or a transient physiologic variant. A fetus with normal heart anatomy may have relevant cardiovascular dysfunction, while a fetus with congenital heart disease may have preserved fetal circulation until birth. The clinical task is to separate these patterns.

Functional abnormalities in a structurally normal heart

Normal heart anatomy with functional cardiovascular abnormality should be recognised as a distinct prenatal diagnostic category. Examples include isolated or contextual tricuspid regurgitation, chamber disproportion, cardiomegaly, main pulmonary artery dilation, pulmonary regurgitation, transient ductal constriction, abnormal pulmonary flows, arrhythmias, pericardial effusion, and early heart failure. This category is important because statements such as “no heart defect was confirmed after birth” can be misleading if the prenatal diagnosis was never a malformation but a functional abnormality requiring explanation, monitoring, and sometimes postnatal follow-up [4].

The clinical relevance of such findings depends on timing, severity, persistence, and context. Mild tricuspid regurgitation in the first trimester carries a different diagnosis than new holosystolic tricuspid regurgitation in the late third trimester. A mildly enlarged right ventricle may be a physiological variant, whereas progressive right ventricular hypertrophy with ductal constriction or pulmonary vascular signs is a pathophysiological marker. Therefore, functional abnormalities should be reported with their context, not as isolated labels.

Functional abnormalities in congenital heart disease

Functional abnormalities also matter when congenital heart disease is present. Two fetuses with the same structural diagnosis may have different fetal and neonatal risk depending on ventricular function, valve regurgitation, cardiomegaly, venous Doppler, rhythm, and pulmonary vascular adaptation. For example, fetal Ebstein anomaly, critical aortic stenosis, pulmonary outflow obstruction, or single-ventricle physiology may be tolerated or may progress to hydrops depending on loading conditions and myocardial reserve. Similarly, a fetus with suspected coarctation may require differentiation between true arch obstruction and a functional coarctation-like pattern caused by abnormal streaming or pulmonary hypertension [10, 11, 14, 18].

For this reason, classification of congenital heart disease in fetal cardiology should be complemented by classification of functional cardiovascular status. Structural diagnosis answers the question “what is the anatomy?” Functional diagnosis answers “how is the fetus coping with this circulation today, and what is changing over time?”.

Suggested functional fetal echocardiography algorithm

A practical fetal functional assessment can be organised into five steps. First, perform standard structural evaluation: situs, four-chamber view, atrioventricular and ventriculoarterial connections, outflow tracts, three-vessel view, aortic and ductal arches, and pulmonary and systemic venous return. Second, perform functional evaluation: heart size, CTAR, chamber disproportion, PA/Ao ratio, valve regurgitation, Tei index or other myocardial performance parameters, shortening fraction, annular motion if available, ductal flow, ductus venosus, umbilical artery and vein, middle cerebral artery, rhythm, and pericardial space. Third, evaluate the haemodynamic environment: placental thickness and echogenicity, amniotic fluid, cord course and nuchal loops, fetal growth pattern, fetal lung development, pulmonary venous and arterial flows, maternal infection, metabolic disease, and medications or polyphenol-rich products that may affect the ductus arteriosus [4, 12].

Fourth, assign clinical severity. The abnormality may be innocent, adaptive, significant, or decompensated. Fifth, determine management: observation, repeat echocardiography, additional maternal or fetal testing, referral to a fetal cardiology centre, hospitalisation, transplacental therapy when indicated, delivery planning, and neonatal preparation. This stepwise approach can reduce both underdiagnosis of functional fetal compromise and overdiagnosis of structural disease.

The functional cardiac phenotype on fetal echocardiography is shown in Figure 2.

Limitations and future directions

Several limitations must be acknowledged. Functional fetal echocardiography is operator dependent, and some parameters have gestational-age, equipment, and measurement variability. Thresholds for abnormality may differ between centres. The causal links between placental thickness, nuchal cord, pulmonary vascular adaptation, and fetal cardiac function require prospective validation. The proposed severity-weighted scale is a conceptual framework derived from existing clinical experience and published studies; it should be tested against perinatal outcomes, neonatal cardiovascular status, and longer-term child development.

Future studies should combine structured fetal echocardiographic reporting with placental assessment, standardised documentation of umbilical cord course, fetal lung evaluation, and postnatal outcomes. Such studies could determine whether functional echocardiographic markers improve prediction of neonatal respiratory failure, pulmonary hypertension, cardiovascular compromise, or the need for specialised delivery planning.

Conclusions

Prenatal cardiology should develop as both a structural and functional discipline. The fetal heart reflects not only cardiac anatomy but also the haemodynamic environment created by the placenta, umbilical cord, fetal lungs, and maternal-fetal circulation.

Functional fetal cardiac abnormalities may occur in structurally normal hearts and in congenital heart disease. In both settings, they require pathophysiologic interpretation rather than purely morphologic description.

Functional echocardiography detects fetal adaptation or decompensation through assessment of cardiac size, chamber and vessel geometry, PA/Ao ratio, CTAR, valvular regurgitation, ductal and venous flows, pulmonary vascular signs, myocardial performance, and rhythm.

Thick placenta, abnormal fetal/neonatal lung development, and nuchal cord entanglement provide three clinically useful models in which the fetal heart can show early signs of systemic stress, pulmonary vascular maladaptation, or preferential streaming (Figure 3).

A severity-weighted system for fetal cardiac dysfunction may improve risk stratification because it accounts for the clinical weight of abnormalities rather than just their number. Prospective validation is needed before such a system can be used as a formal prognostic tool.

Acknowledgements

The author acknowledges Professor Maria Respondek-Liberska for establishing the conceptual and clinical framework of functional abnormalities of the fetal cardiovascular system and for her contribution to the development of Polish prenatal cardiology.

Disclosures

Ethical considerations: none.

This research received no external funding.

The authors declare no conflict of interest.