Assessment of fetal cardiac function using the modified myocardial performance index in fetuses with growth restriction: a prospective observational study

Abstract

Background

Accurate differentiation between constitutionally small fetuses and those affected by true fetal growth restriction (FGR) remains a major clinical challenge, particularly in fetuses with estimated fetal weight between the 3rd and 10th percentiles. Conventional Doppler parameters may remain normal until late stages of placental insufficiency. The modified myocardial performance index (M-MPI) has been proposed as a sensitive marker of early fetal cardiac dysfunction.

Methods

This prospective observational study included 157 singleton pregnancies at ≥ 32 weeks of gestation. Fetuses were classified into three groups according to abdominal circumference (AC) percentiles (< 3rd percentile, 3rd–10th percentile, and > 10th percentile), using a classification framework informed by the Delphi consensus definition of fetal growth restriction. Fetal biometry, amniotic fluid index, umbilical artery and middle cerebral artery Doppler measurements were obtained. Fetal cardiac function was assessed using the modified myocardial performance index. Delivery outcomes were recorded. Comparisons among groups were performed using appropriate statistical tests.

Results

Maternal demographic and obstetric characteristics were similar among groups. Umbilical artery Doppler, middle cerebral artery Doppler, cerebroplacental ratio, and amniotic fluid index did not differ significantly between groups (all p > 0.05). In contrast, both fetuses below the 3rd percentile and those between the 3rd and 10th percentiles exhibited significantly prolonged isovolumetric contraction and relaxation times, shortened ejection time, and increased M-MPI values compared with fetuses above the 10th percentile (p < 0.05). No significant differences in M-MPI parameters were observed between the <3rd percentile and 3rd–10th percentile groups.

Conclusions

Fetuses with abdominal circumference below the 10th percentile, including those within the borderline 3rd–10th percentile range, demonstrate subclinical cardiac dysfunction despite normal conventional Doppler findings. Assessment of the modified myocardial performance index may provide valuable additional information in the evaluation of suspected fetal growth restriction.

Introduction

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 an inaccurate 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, which represent 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 AC 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 stratified according to abdominal circumference (AC) percentiles, within the conceptual framework of the Delphi consensus definition of fetal growth restriction [11]. We compared M-MPI values among fetuses with AC 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 fetuses with impaired fetal growth, particularly within the borderline 3rd–10th percentile group, before conventional Doppler parameters become abnormal.

Materials and methods

Study design and population

This prospective observational study was conducted at the Department of Obstetrics and Gynecology, Van Yuzuncu Yil University Faculty of Medicine, between May 2021 and October 2021. Pregnant women with singleton pregnancies at or beyond 32 weeks of gestation who attended the outpatient clinic for routine antenatal follow-up were consecutively screened for eligibility. As all participants were enrolled at or beyond 32 weeks of gestation, the study cohort represents late-onset, rather than early-onset, fetal growth restriction.

Gestational age was determined based on first-trimester crown–rump length measurement or, when unavailable, on the last menstrual period consistent with second-trimester ultrasonographic findings. Pregnancies complicated by major fetal structural anomalies, chromosomal abnormalities, congenital fetal cardiac disease, multiple gestations, or intrauterine infections were excluded. Fetuses with abnormal umbilical or middle cerebral artery Doppler findings were also excluded, so that M-MPI was assessed before the development of Doppler abnormalities. In addition, cases in which modified myocardial performance index (M-MPI) measurement could not be reliably obtained due to technical limitations, including severe maternal obesity or suboptimal acoustic windows, were excluded from the analysis.

The study protocol was approved by the local institutional ethics committee, and written informed consent was obtained from all participants prior to enrollment.

Fetal growth classification

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 AC percentiles, fetuses were categorized into three groups:

1. AC < 3rd percentile.

2. AC between the 3rd and 10th percentiles.

3. AC > 10th percentile.

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. Group assignment was based on AC percentiles. Because an AC below the 3rd percentile constitutes a solitary criterion for placental-mediated fetal growth restriction in the Delphi consensus, the <3rd percentile group is consistent with true growth restriction, whereas the 3rd–10th percentile group, in the absence of abnormal umbilical artery or cerebral Doppler, corresponds to small-for-gestational-age fetuses. Umbilical and middle cerebral artery Doppler were obtained for all fetuses and were within normal limits in all cases, as abnormal Doppler findings constituted an exclusion criterion; these measurements were therefore not used as additional classification criteria.

Ultrasound and Doppler assessment

All ultrasound examinations were performed by experienced operators using standardized obstetric ultrasound equipment. Fetal biometry, including biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur length (FL), 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].

Modified myocardial performance index measurement

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] (Figs. 1 and 2).

Fig. 1.

Measurement of the modified myocardial performance index (M-MPI). M-MPI = (IVCT + IVRT)/ET, where IVCT is the isovolumetric contraction time, IVRT the isovolumetric relaxation time, and ET the ejection time (normal value approximately 0.36). The pulsed-wave Doppler sample volume is positioned at the level of the left ventricular (LV) outflow tract, including the medial wall of the ascending aorta, so that left ventricular inflow and outflow signals are recorded simultaneously. The schematic (lower left) and the representative Doppler tracing (lower right) illustrate the time intervals used to derive the index. D, diastole; S, systole; RV, right ventricle

Fig. 2.

Pulsed-wave Doppler recording of mitral valve inflow obtained in an apical four-chamber view, showing the early (E) and late atrial (A) diastolic filling waves used to calculate the E/A ratio. R, right

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

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.

Clinical and perinatal data

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.

Statistical analysis

Statistical analyses were performed using IBM SPSS Statistics version 27.0 (IBM Corp., Armonk, NY, USA). The distribution of the variables was assessed using the Kolmogorov–Smirnov test. Descriptive statistics were presented as mean, standard deviation, median, minimum and maximum for quantitative variables, and as frequencies and percentages for qualitative variables.

Independent quantitative variables were compared using the Kruskal–Wallis test, and pairwise post hoc comparisons were performed using the Mann–Whitney U test with Bonferroni correction. Independent qualitative variables were compared using the chi-square test, or Fisher’s exact test when the assumptions of the chi-square test were not met. A p-value < 0.05 was considered statistically significant.

Results

Study population

A total of 157 pregnant women meeting the inclusion criteria were enrolled in the study. According to abdominal circumference percentiles, 51 fetuses were classified as having AC below the 3rd percentile, 56 fetuses between the 3rd and 10th percentiles, and 50 fetuses above the 10th percentile.

There were no significant differences among the three groups with respect to maternal age, height, weight, body mass index, gravidity, parity, number of previous abortions, or obstetric history (all p > 0.05) (Table 1).

Table 1.

Maternal and obstetric characteristics of the study groups

Characteristic	< 3rd percentile (n = 51)	3rd–10th percentile (n = 56)	> 10th percentile (n = 50)	p value
Gestational age (weeks) (Mean ± SD)	36.1 ± 2.1	36.0 ± 2.1	36.0 ± 2.0	0.967K
Maternal age (years) (Mean ± SD)	27.5 ± 5.6	27.4 ± 4.8	27.7 ± 5.2	0.944K
Body mass index (kg/m²) (Mean ± SD)	27.4 ± 3.9	27.3 ± 4.1	27.5 ± 4.2	0.978K
Gravidity (Median)	3.0	2.0	2.0	0.833K
Parity (Median)	2.0	1.0	1.0	0.632K
Mode of Delivery : VB (n = 108) CS (n = 49)	36 (%33.3) 15 (%30.6)	39 (%36.1) 17 (%34.7)	33 (%30.6) 17 (%34.7)	0.779 × 2 0.92 × 2
Birth weight (gram) (Mean ± SD)	2568 ± 451	2648 ± 431	2958 ± 393y, z	< 0.001K

BMI Body mass index, VB Vaginal birth, CS Cesarean section, SD Standard deviation

x² Chi-square (Fisher’s exact test)

K Kruskal–Wallis test; post hoc pairwise comparisons were performed using the Mann–Whitney U test with Bonferroni correction

y significantly different compared with the <3rd percentile group (p < 0.05)

z significantly different compared with the 3rd–10th percentile group (p < 0.05)

Fetal biometric and Doppler findings

As groups were defined by abdominal circumference percentiles, AC differed significantly among groups by definition. Consistent with this, estimated fetal weight, which is closely correlated with AC, was also significantly lower in the <3rd percentile and 3rd–10th percentile groups compared with the > 10th percentile group (p < 0.05). No significant difference in estimated fetal weight was observed between the <3rd percentile and 3rd–10th percentile groups (p > 0.05).

Total amniotic fluid index values did not differ significantly among the three groups (p > 0.05). Similarly, umbilical artery pulsatility index, middle cerebral artery pulsatility index, cerebroplacental ratio, and E/A ratio showed no statistically significant differences between groups (all p > 0.05) (Table 2).

Table 2.

Fetal Doppler parameters and myocardial performance index measurements

Characteristic	< 3rd percentile (n = 51)	3rd–10th percentile (n = 56)	> 10th percentile (n = 50)	p value
EFW (Gram) (Mean ± SD)	2205 ± 460.3	2268 ± 457.6	2499 ± 473.9y, z	0.004K
Total AFI (cm) (Mean ± SD)	11 ± 2.9	11.5 ± 3.2	12.0 ± 2.2	0.195K
Ua PI (Mean ± SD)	1.1 ± 0.5	1.0 ± 0.2	1.0 ± 0.3	0.927K
Ua S/D (Mean ± SD)	2.8 ± 1.0	2.8 ± 1.0	2.5 ± 0.6	0.247K
MCA PI (Mean ± SD)	1.3 ± 0.3	1.6 ± 1.1	1.4 ± 0.4	0.536K
E/A (Mean ± SD)	0.8 ± 0.2	0.7 ± 0.1	0.7 ± 0.2	0.315K
CPR (Mean ± SD)	1.4 ± 0.7	1.7 ± 0.6	1.5 ± 0.5	0.631K
IVCT (Mean ± SD)	56.4 ± 13.7	60.5 ± 16.8	35.8 ± 6.7y, z	< 0.001K
IVRT (Mean ± SD)	63.3 ± 18.3	68.6 ± 26.4	38.9 ± 6.8y, z	< 0.001K
ET (Mean ± SD)	207.8 ± 36.0	201 ± 38.8	190.9 ± 15.3y, z	0.011K
MPI (Mean ± SD)	0.59 ± 0.15	0.67 ± 0.26	0.39 ± 0.04y, z	< 0.001K

EFW Estimated fetal weight, AFI Amniotic fluid index, UA Umbilical artery, PI Pulsatility index, S/D Systolic/diastolic ratio, MCA Middle cerebral artery, CPR Cerebroplacental ratio, IVCT Isovolumetric contraction time, IVRT Isovolumetric relaxation time, ET Ejection time, MPI Myocardial performance index, SD Standard deviation

x² Chi-square (Fisher’s exact test)

K Kruskal–Wallis test; post hoc pairwise comparisons were performed using the Mann–Whitney U test with Bonferroni correction

y significantly different compared with the <3rd percentile group (p < 0.05)

z significantly different compared with the 3rd–10th percentile group (p < 0.05)

Modified myocardial performance index parameters

Significant differences were observed in modified myocardial performance index parameters among the study groups. Both the <3rd percentile and the 3rd–10th percentile groups demonstrated significantly prolonged isovolumetric contraction time (IVCT) and isovolumetric relaxation time (IVRT) compared with the > 10th percentile group (p < 0.05 for both). No significant differences in IVCT or IVRT were detected between the <3rd percentile and 3rd–10th percentile groups (p > 0.05).

Ejection time (ET) was significantly shorter in fetuses with AC below the 3rd percentile and between the 3rd and 10th percentiles compared with fetuses above the 10th percentile (p < 0.05), whereas no significant difference was observed between the <3rd percentile and the 3rd–10th percentile groups.

Consequently, modified myocardial performance index (M-MPI) values were significantly higher in both the <3rd percentile and 3rd–10th percentile groups compared with the > 10th percentile group (p < 0.05). M-MPI values did not differ significantly between the <3rd percentile and 3rd–10th percentile groups (p > 0.05) (Table 2).

Perinatal outcomes

The distribution of mode of delivery did not differ significantly among the three groups (p > 0.05). Neonatal birth weight was significantly lower in the <3rd percentile and 3rd–10th percentile groups compared with the > 10th percentile group (p < 0.05), while no significant difference was observed between the <3rd percentile and the 3rd–10th percentile groups.

Discussion

In this prospective study, we evaluated fetal cardiac function using the modified myocardial performance index in fetuses stratified according to abdominal circumference percentiles. The principal finding of our study is that fetuses with abdominal circumference 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]. As our cohort comprised exclusively pregnancies at or beyond 32 weeks of gestation, the present findings pertain to late-onset growth restriction, in which placental compromise is typically milder and umbilical artery Doppler frequently remains normal; this is consistent with the preserved arterial Doppler indices observed in our cohort and limits direct extrapolation of the results to early-onset disease. 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 a standardized, AC percentile–based classification consistent with the Delphi consensus solitary criterion [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, no formal a priori power or sample-size calculation was performed; 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 and intraobserver variability for M-MPI measurements was not formally assessed, although measurements were performed by experienced operators using standardized techniques. Fourth, growth groups were defined using AC percentiles; although an AC below the 3rd percentile meets the solitary Delphi criterion for fetal growth restriction, the contributory Doppler criteria of the consensus definition were not applied, and the 3rd–10th percentile group is therefore best regarded as small-for-gestational-age and may include constitutionally small but otherwise healthy fetuses. Fifth, comparisons were based on univariate analyses, and M-MPI values were not adjusted for potential confounders such as gestational age, maternal characteristics, or underlying hemodynamic factors. Sixth, perinatal outcomes such as neonatal intensive care unit admission and neonatal morbidity were not evaluated; consequently, the proposed clinical utility of M-MPI for risk stratification should be regarded as preliminary and requires confirmation in outcome-based studies.

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].

Conclusion

In conclusion, our findings demonstrate that fetal myocardial performance is significantly impaired in fetuses with abdominal circumference 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. As perinatal and neonatal outcomes were not analysed in the present study, whether incorporation of M-MPI into antenatal surveillance improves risk stratification or follow-up strategies in fetuses with borderline growth parameters remains to be established in future outcome-based studies.

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.

Authors’ contributions

A. Wote the manuscript, B. Complete the statistics , All authors reviewed the manuscript

Funding

No funding was used in this study.

Data availability

The datasets generated and/or analysed during the current study are not publicly available due to patient confidentiality and the small number of cases, which may compromise anonymity. However, the data are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The research protocol was approved by the Van Yuzuncu Yil University ethics committee (approval date: 29.04.2021, decision no: 08). All participants were informed and their written consent was obtained. Our study was conducted in accordance with the Declaration of Helsinki.

Consent for publication

Not applicable. No identifying images or personal clinical information of participants are included in this manuscript.

Competing interests

The authors declare no competing interests.