Fetal growth restriction (FGR) is a common obstetric complication and remains one of the leading causes of stillbirth, neonatal mortality, and short- and long-term neonatal morbidity worldwide [1–7]. It reflects a failure of the fetus to achieve its genetically determined growth potential, most commonly due to placental insufficiency. Accurate antenatal identification of fetuses affected by true growth restriction is essential, as inappropriate diagnosis may lead either to unnecessary iatrogenic preterm delivery or to delayed intervention with adverse perinatal outcomes [8].

In routine clinical practice, estimated fetal weight (EFW) below the 10th percentile is frequently used as a screening threshold for FGR. However, this approach has important limitations. A substantial proportion of fetuses classified as small for gestational age (SGA) are constitutionally small but otherwise healthy, while some growth-restricted fetuses may remain above conventional percentile cut-offs [9, 10]. This diagnostic uncertainty is particularly evident in fetuses with EFW between the 3rd and 10th percentiles, representing a clinically heterogeneous “borderline” group in which the distinction between pathological FGR and physiological smallness remains challenging.

To address these limitations, the Delphi consensus proposed a standardized definition for placental-mediated FGR, combining biometric criteria with Doppler abnormalities in the umbilical and cerebral circulation [11]. While this approach has improved diagnostic accuracy, Doppler alterations often represent relatively late manifestations of placental dysfunction. Therefore, there is a growing need for more sensitive parameters capable of detecting early fetal compromise before conventional Doppler indices become abnormal [12, 13].

The fetal heart plays a central role in the adaptive response to chronic hypoxia and undernutrition associated with placental insufficiency. Cardiac remodeling and subclinical myocardial dysfunction are considered key pathophysiological features of both early- and late-onset FGR [14, 15]. However, fetal cardiac dysfunction is often subclinical and may not be detected using standard Doppler parameters until advanced stages of disease [16].

The myocardial performance index (MPI), also known as the Tei index, is a Doppler-derived parameter that simultaneously reflects systolic and diastolic cardiac function and is relatively independent of heart rate and ventricular geometry [17]. The modified myocardial performance index (M-MPI), incorporating valve click landmarks, has improved reproducibility and feasibility in fetal cardiac assessment [18–21]. Previous studies have demonstrated that abnormalities in MPI may precede changes in umbilical artery or middle cerebral artery Doppler waveforms, suggesting early cardiac involvement in growth-restricted fetuses [17–21].

Despite growing evidence supporting the role of M-MPI in FGR, data specifically addressing its utility in distinguishing fetuses within the borderline growth percentile range remain limited. In particular, the clinical significance of M-MPI assessment in fetuses with EFW between the 3rd and 10th percentiles has not been clearly established.

The aim of this prospective study was to evaluate fetal cardiac function using the modified myocardial performance index in fetuses classified according to the Delphi consensus criteria, and to compare M-MPI values among fetuses with EFW below the 3rd percentile, between the 3rd and 10th percentiles, and above the 10th percentile. We hypothesized that M-MPI may detect early cardiac dysfunction in growth-restricted fetuses, particularly within the borderline 3rd–10th percentile group, before conventional Doppler parameters become abnormal.

Fetal growth status was classified according to the Delphi consensus criteria for placental-mediated fetal growth restriction, which combine biometric parameters with Doppler findings to improve diagnostic accuracy and reduce false-positive and false-negative classification of FGR [11]. Estimated fetal weight (EFW) was calculated using standard biometric measurements and appropriate fetal growth charts.

Based on EFW percentiles, fetuses were categorized into three groups:

This stratification was specifically chosen to evaluate fetal cardiac function in the borderline growth group (3rd–10th percentile), in which differentiation between constitutionally small fetuses and true fetal growth restriction remains clinically challenging.

All ultrasound examinations were performed using standardized obstetric ultrasound equipment by experienced operators. Fetal biometry, including biparietal diameter, head circumference, abdominal circumference, and femur length, was obtained according to established measurement techniques. Amniotic fluid volume was assessed using the amniotic fluid index.

Doppler studies included assessment of the umbilical artery and middle cerebral artery. Pulsatility indices were recorded, and the cerebroplacental ratio was calculated where appropriate. Doppler measurements were obtained during fetal quiescence, in the absence of fetal breathing movements, and averaged over at least three consecutive uniform waveforms, in line with standard obstetric Doppler practice [12].

Fetal cardiac function was evaluated using the modified myocardial performance index (M-MPI), a Doppler-derived parameter that reflects global systolic and diastolic myocardial performance [17]. M-MPI was measured from the left ventricular outflow tract using pulsed-wave Doppler, with clear identification of mitral and aortic valve opening and closure clicks to improve measurement reproducibility, as previously described [18–21].

Isovolumetric contraction time (IVCT), isovolumetric relaxation time (IVRT), and ejection time (ET) were recorded, and M-MPI was calculated using the formula: M-MPI = (IVCT + IVRT) / ET

All measurements were obtained during fetal apnea and in the absence of gross fetal movements. Each parameter was measured at least three times, and the mean value was used for statistical analysis.

Maternal demographic characteristics, including age, height, weight, body mass index, gravidity, parity, and obstetric history, were recorded at enrollment. Delivery outcomes, including mode of delivery and neonatal birth weight, were obtained from hospital medical records after birth.

In this prospective study, we evaluated fetal cardiac function using the modified myocardial performance index in fetuses classified according to the Delphi consensus criteria. The principal finding of our study is that fetuses with estimated fetal weight below the 10th percentile—including those within the borderline 3rd–10th percentile range—exhibited significantly impaired myocardial performance despite having largely normal conventional Doppler parameters. This finding suggests that subclinical cardiac dysfunction may be present before overt Doppler signs of placental insufficiency become evident [17–21].

Accurate differentiation between constitutionally small fetuses and those affected by true fetal growth restriction remains a major clinical challenge, particularly in the 3rd–10th percentile group [9, 10]. Conventional Doppler indices such as umbilical artery and middle cerebral artery pulsatility indices are widely used in clinical practice; however, these parameters often reflect relatively late stages of fetal hemodynamic adaptation [12, 13]. In our cohort, Doppler indices and cerebroplacental ratio did not differ significantly between groups, whereas M-MPI parameters demonstrated clear alterations in growth-restricted fetuses. These findings support previous observations that myocardial functional changes may precede detectable arterial Doppler abnormalities [17–21].

The fetal heart plays a central role in the adaptive response to chronic hypoxia and reduced nutrient supply associated with placental dysfunction. Cardiac remodeling and myocardial dysfunction are considered key pathophysiological features of both early- and late-onset fetal growth restriction [14, 15]. Prolongation of isovolumetric contraction and relaxation times and shortening of ejection time, as observed in our study, reflect impaired global myocardial performance and reduced cardiac efficiency. Consequently, the observed increase in M-MPI values in fetuses below the 10th percentile likely represents early myocardial involvement as part of the fetal adaptive response to placental insufficiency [16].

Our findings are consistent with previous studies reporting elevated MPI values in fetuses with fetal growth restriction, even in the absence of abnormal umbilical artery Doppler findings [17–21]. Previous research has demonstrated that MPI abnormalities may occur before deterioration of arterial or venous Doppler waveforms and before a reduction in amniotic fluid volume is detected [12, 13]. The present study extends these observations by specifically demonstrating that fetuses within the borderline growth percentile range exhibit myocardial functional impairment comparable to that observed in fetuses with more severe growth restriction.

From a clinical perspective, these results suggest that incorporation of M-MPI assessment into the evaluation of fetuses with suspected growth restriction may provide additional information beyond standard Doppler surveillance. In particular, M-MPI may help identify fetuses at risk of subclinical compromise within the 3rd–10th percentile range, potentially aiding decisions regarding closer surveillance and optimal timing of delivery. This may be especially relevant in cases where reliance on biometric criteria alone could lead either to unnecessary early delivery or to delayed intervention with adverse perinatal outcomes [11, 12].

The strengths of this study include its prospective design, the use of standardized Delphi consensus criteria for fetal growth classification [11], and the systematic assessment of fetal cardiac function using the modified MPI technique [18–21]. However, several limitations should be acknowledged. First, this was a single-center study, which may limit the generalizability of the findings. Second, although the sample size was sufficient to demonstrate significant differences in M-MPI parameters, the study was not powered to evaluate perinatal morbidity or long-term neonatal outcomes. Third, interobserver variability for M-MPI measurements was not formally assessed, although measurements were performed by experienced operators using standardized techniques.

Future studies with larger, multicenter cohorts are warranted to validate these findings and to determine whether incorporation of M-MPI into clinical algorithms improves perinatal outcomes. Longitudinal studies assessing the relationship between antenatal M-MPI alterations and postnatal cardiovascular or neurodevelopmental outcomes would further clarify the prognostic value of this parameter [14, 15].

In conclusion, our findings demonstrate that fetal myocardial performance is significantly impaired in fetuses with estimated fetal weight below the 10th percentile, including those within the borderline 3rd–10th percentile range, even in the absence of abnormal conventional Doppler findings. These results suggest that subclinical cardiac dysfunction may precede overt hemodynamic deterioration in fetuses affected by placental insufficiency.

Assessment of the modified myocardial performance index may provide valuable additional information in the evaluation of suspected fetal growth restriction, particularly in clinically ambiguous cases. Incorporation of M-MPI into antenatal surveillance may help improve risk stratification and guide follow-up strategies in fetuses with borderline growth parameters.

Further large-scale and longitudinal studies are warranted to confirm these findings and to determine the impact of M-MPI–guided management on perinatal and long-term outcomes.