Intrapartum Fetal Compromise in Late-Onset Fetal Growth Restriction Using the Modified Myocardial Performance Index: A Prospective Cohort Study.

To evaluate amniotic fluid volume with Doppler parameters and its association with composite adverse perinatal outcomes (CAPOs) in fetal growth restriction (FGR). This study was conducted prospectively in a tertiary referral center between 2023 and 2024 on pregnant women diagnosed with early- and late-onset FGR. Fetal ultrasonographic measurements, including deepest vertical pocket (DVP) for amniotic fluid, and Doppler parameters including uterine artery (UtA) systolic/diastolic (S/D) and pulsatility index (PI), middle cerebral artery (MCA) S/D and PI, and umbilical artery (UA) S/D and PI, were conducted following fetal biometry. The cerebroplacental ratio (CPR), cerebral ratio, cerebro-placental-uterine ratio (CPUR), and amniotic-umbilical-to-cerebral ratio (AUCR) were all calculated. Pregnant women diagnosed with FGR were planned to give birth after 37 weeks' gestation, unless a pregnancy complication requiring earlier delivery occurred. We assessed perinatal outcomes subsequent to delivery, with CAPOs defined as the presence of at least one adverse outcome: 5th minute APGAR score <7, respiratory distress syndrome (RDS), umbilical cord blood pH <7.2, and neonatal intensive care unit (NICU) admission. The study included 132 participants, divided into early- (n = 32) and late-onset FGR (n = 100) groups. AUCR was significantly lower in fetuses with late-onset FGR who experienced CAPOs. Multivariate analysis showed gestational age at birth and birth weight were significant predictors of CAPOs in early-onset FGR, while gestational age, birth weight, and AUCR were significant predictors in late-onset FGR. CPR, UCR, and CPUR did not show significance in predicting CAPOs in both early- and late-onset FGR on multivariate analysis. AUCR is a potential reliable marker for predicting adverse perinatal outcomes in late-onset FGR.

Diagnosis and management of fetal growth restriction: the ISUOG guideline and comparison with the SMFM guideline.

Background:Doppler ultrasound of fetal vessels plays an important role in diagnosing fetal growth restriction (FGR). It also aids in early detection of fetal compromise and clinical decision making. Aim: To determine the efficacy of the pulsatility index (PI) of the fetal umbilical artery (UA) and middle cerebral artery (MCA) in the third trimester of pregnancy for predicting adverse perinatal outcomes in the growth restricted fetuses. To study the differences in Doppler profiles in early- and late FGR (EFGR and LFGR, respectively) and their association with adverse outcomes. Materials and methods:The study was approved by the Institute's Ethical Committee. Informed consent was taken from study participants. Eighty singleton pregnancies in the third trimester, which had been diagnosed with FGR, were studied. The UA and MCA Doppler PI and cerebroplacental ratio (CPR) (ratios of PI of MCA/UA) as well as perinatal outcomes were recorded. Adverse perinatal outcomes included perinatal death, hypoxia, seizures, respiratory distress, prolonged Neonatal Intensive Care Unit (NICU) stay, and low Apgar scores at one minute and five minutes. Statistical association of PI with adverse outcomes and differences in Doppler profiles of EFGR and LFGR were studied. Results:Abnormal pulsatility in fetal vessels was associated with adverse perinatal outcomes. The UA PI was the most sensitive (66%) and CPR the most specific parameter (80%) for predicting adverse perinatal outcomes. Absent or reversal of diastolic flow in UA was associated with adverse perinatal outcomes in 75% and 40% of cases, respectively. The UA PI was the most sensitive parameter in both EFGR (70%) and LFGR (66%) and specific Doppler parameter in EFGR (75%). However, CPR and MCA PI were the most specific (89%) and diagnostically accurate in LFGR (79%). Conclusion:The UA PI is the most sensitive Doppler parameter for predicting adverse perinatal outcomes. Cerebroplacental ratio has a high specificity and accuracy and is an important parameter in LFGR cases.

We thank Prof. Lees et al. for their comments regarding our study1 in which we endeavored to apply the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG)2 and Society for Maternal–Fetal Medicine (SMFM)3 definitions of fetal growth restriction (FGR) to a pre-existing cohort of patients with the aim to compare their performance in predicting neonatal small-for-gestational age (SGA) and composite adverse neonatal outcome. As outlined in the Discussion, our study has limitations. In table S1 of the study, we report that six of the 53 fetuses with late-onset FGR according to the ISUOG definition had estimated fetal weight (EFW) or fetal abdominal circumference (AC) crossing centiles of more than 2 quartiles on growth centiles. Our group has previously compared the ability of the Delphi criteria for FGR (including AC or EFW crossing > 2 quartiles) with that of EFW < 10th percentile for gestational age to predict neonatal SGA, and did not find the Delphi criteria to be a better predictor4. Furthermore, other studies have shown that the addition of fetal growth velocity between 20 and 36 weeks' gestation does not improve the ability of EFW at 35–37 weeks to predict delivery of a SGA neonate5. Lees et al. also questioned the utilization of neonatal SGA as a proxy for FGR. We agree with the authors that most fetuses with EFW or AC < 10th percentile but > 3rd percentile for gestational age and normal fetal surveillance (umbilical artery Doppler, non-stress test or biophysical profile) are less likely to have poor perinatal outcome. However, the optimal way to incorporate Doppler evaluation of the middle cerebral artery, uterine artery and ductus venosus, or the cerebroplacental ratio, in the management of early- and late-onset FGR is not yet clear6-8. We also agree that labeling more fetuses as being growth restricted may not reflect an increase in the detection of those fetuses that truly have placental pathology and would benefit from early intervention. Nevertheless, in our study, we aimed to compare the performance of the different diagnostic criteria for FGR of the two leading governing bodies in fetal medicine. Lastly, we agree that the prediction of adverse outcome in FGR pregnancies, especially those with late-onset FGR, is poor by both definitions of FGR. Unfortunately, the optimal definition and management protocol for FGR remains elusive and we acknowledge that some of the guidelines developed by both the SMFM and ISUOG for the diagnosis and management of FGR are not supported by high-level evidence. However, the simplicity of the SMFM diagnostic criteria, which are based on only AC and/or EFW, makes easier their implementation across the globe.

Background This study aimed to investigate fetal cardiac functions by spectral tissue Doppler imaging (s-TDI) in pregnancies complicated with late-onset fetal growth restriction (LO-FGR) and small-for-gestational age (SGA). Methods Forty pregnancies complicated with late-onset FGR and 40 pregnancies complicated with SGA between the 34th and 37th weeks of gestation were enrolled in this study. Forty gestational age-matched pregnant women with no obstetrics complication were randomly selected as a control group. Small fetuses were classified as fetal growth restriction or SGA according to estimated fetal weight (EFW), umbilical artery pulsatility index (PI), cerebroplacental ratio (CPR) and uterine artery PI. s-TDI measurements were obtained at the right atrioventricular valve annulus. Results SGA and LO-FGR fetuses had significantly lower A' and S' values, and higher E'/A' ratio than the control group (P < 0.001). In comparison to controls, significantly prolonged isovolumetric contraction time (ICT') and isovolumetric relaxation time (IRT') and, significantly shortened ejection time (ET') were observed in fetuses with SGA and LO-FGR. Increased myocardial performance index (MPI') values were also found in fetuses with SGA and LO-FGR compared to controls. Conclusion The signs of cardiac dysfunction were observed both in fetuses with SGA and LO-FGR. The fetal cardiac function assessment with s-TDI could be a valuable method in the diagnosis of true growth restricted fetuses and in the management of these fetuses.

This study aimed to evaluate the performance of sonographic biometric and Doppler parameters assessed at a routine third trimester scan, in combination with maternal characteristics, in predicting small-for-gestational-age (SGA) neonates and adverse perinatal outcomes. This was a cohort study of low-risk singleton pregnancies undergoing routine ultrasound between 35+0 and 37+6 weeks. Demographic characteristics, estimated fetal weight (EFW) and abdominal circumference (AC) centiles, and Doppler indices, including the Pulsatility Index (PI) of the Umbilical Artery (UA), Middle Cerebral Artery (MCA), and Uterine Artery (UtA) were evaluated. The Cerebroplacental ratio (CPR) was calculated, all indices were converted into Multiples of the Median (MoM). Multivariable logistic regression analysis was performed. Receiver-operating curves (ROC) were created to determine factors predictive of an SGA neonate with birthweights <3rd, 5th, and 10th centile and composite adverse perinatal outcomes (CAPO), which was comprised of intrauterine death, neonatal death, and neonatal intensive care unit admission. A total of 14,161 pregnancies were included. EFW centile (adjusted odds ratio (aOR) 0.91 (95% CI, 0.9-0.92), p < 0.001) (aOR 0.9 (95% CI, 0.89-0.91), p < 0.001), UA PI (aOR 4.6 (95% CI, 2.2-9.6), p < 0.001) (aOR 2.5 (95% CI, 1.1-6.1), p < 0.04), MCA PI (aOR 0.37 (95% CI, 0.2-0.7), p = 0.002) (aOR 0.26 (95% CI, 0.12-0.59), p = 0.001), CPR (aOR 0.23 (95% CI, 0.13-0.42), p < 0.001) (aOR 0.25 (95% CI, 0.12-0.53), p < 0.001), and UtA PI (aOR 2.5 (95% CI, 1.68-3.83), p < 0.001) (aOR 2.2 (95% CI, 1.31-3.6), p = 0.003) were independent predictors of SGA <5th and SGA <3rd or SGA with CAPO, respectively. The combination of EFW, CPR, and UtA PI was associated with an Area under the curve (AUC) of 0.93 (95% CI 0.92-0.94), p < 0.001 for both outcomes. In an unselected population, the UA PI, MCA PI, CPR, and UtA PI are independent predictors of SGA and adverse perinatal outcomes. The combination of these parameters can reliably predict SGA and adverse perinatal outcomes with a high degree of accuracy.

Background: Fetal growth restriction (FGR) is a major contributor to perinatal morbidity and mortality, frequently resulting from placental insufficiency. Doppler ultrasonography of the umbilical artery (UA) and middle cerebral artery (MCA) provides valuable insights into placental resistance and fetal adaptation. Aim: To evaluate and compare the role of umbilical and cerebral artery Doppler in pregnancies with FGR and in normal fetuses. Methods: This prospective cross-sectional study was conducted over 18 months (June 2023 – Dec 2024) in the Department of Obstetrics and Gynaecology, Adichunchanagiri Institute of Medical Sciences and Research Centre, Karnataka. Singleton pregnancies between 32–36 weeks were included. Women underwent ultrasound and color Doppler evaluation . UA and MCA pulsatility indices (PI), systolic/diastolic ratios (S/D), and cerebroplacental ratio (CPR) were measured. Estimated fetal weight was classified as appropriate for gestational age (AGA) or small for gestational age (SGA). Doppler findings were correlated with gestational age, fetal growth, and perinatal outcomes. Results: Abnormal Doppler indices were significantly more common in FGR pregnancies compared to normal pregnancies. Elevated UA PI and S/D ratio indicated increased placental resistance, while reduced MCA PI demonstrated the “brain-sparing effect.” Low CPR was strongly associated with adverse perinatal outcomes, including low birth weight, low APGAR scores, and NICU admission. In contrast, normal pregnancies exhibited progressively declining UA resistance and stable MCA PI with advancing gestation. Conclusion: Combined assessment of UA and MCA Doppler, particularly CPR, is a reliable, non-invasive tool for differentiating constitutionally small from growth-restricted fetuses. Incorporating these Doppler parameters into routine antenatal surveillance enables early detection of fetal compromise and aids in optimizing delivery timing, thereby improving perinatal outcomes.

The aim of this study is to determine the fetal modified myocardial performance index (Mod-MPI) and E-wave/A-wave peak velocities (E/A ratio) in deteriorating grades of intrauterine growth restriction (IUGR) and its link to adverse outcomes defined as perinatal death, hypoxic ischemic encephalopathy, neonatal resuscitation, neonatal cord pH <7.15, intraventricular hemorrhage and bronchopulmonary dysplasia. Forty three pregnant women with IUGR defined as the abdominal circumference <10th percentile for gestational age and umbilical resistance index >2 standard deviations in the third trimester of pregnancy were matched for gestational age and maternal age with 43 women with appropriate-for-gestational-age fetuses. The IUGR group was subdivided on the basis of multivessel Doppler anomalies into different grades of growth restriction. Mod-MPI and E/A ratio were determined and linked to perinatal outcome. The median Mod-MPI was significantly higher in growth-restricted fetuses compared with controls (0.59 vs 0.37, p < 0.001) and increased with severity of IUGR, the classification of which was based on degree of abnormality of the umbilical resistance index, presence of arterial redistribution and degree of abnormality of the ductus venosus (DV) Doppler indices. A cut-off Mod-MPI value of 0.54 conferred a sensitivity of 87% [confidence interval (CI): 66-97%], specificity of 75% (CI: 55-91%) and a likelihood ratio (LR) of 3.47 for an adverse outcome. A cut-off Mod-MPI value of 0.67 conferred a sensitivity of 100% (CI: 54-100%), specificity of 81% (CI: 65-92%) and LR of 5.28 for perinatal death. No abnormal outcomes occurred in controls. In logistic regression analysis, the MPI remained a significant predictor of adverse outcome after adjusting for gestational age of delivery, fetal weight, E/A ratio, maternal age, DV Doppler indices, amniotic fluid index and umbilical artery resistance index [adjusted odds ratio, 95% CI: 2.60 (1.15-5.83), p-value 0.02]. MPI fared significantly better than the E/A ratio as a predictor of adverse outcome (area under the receiver operating characteristic curve of 0.94 and 0.76, p < 0.001). Fetal myocardial performance deteriorates with severity of growth restriction. There is an association between severity of the MPI elevation and rates of adverse perinatal outcome. The Mod-MPI and E/A ratio have the potential to be integrated into routine surveillance techniques of the growth-restricted fetus. © 2014 John Wiley & Sons, Ltd.

This study aimed to assess fetal cardiac left ventricular function in healthy pregnant women by calculating the modified myocardial performance index (Mod-MPI) and to construct reference ranges for the Turkish population. One-hundred-two randomly selected healthy singleton pregnant women ranging between 25 and 39 gestational weeks were included in the study. Left fetal Mod-MPI was measured for each pregnant woman. Women with chronic systemic diseases or fetuses with chromosomal or structural abnormalities were excluded from the study. Mitral valve (MV) and aortic valve (AoV) clicks were used as landmarks to define the following time periods that were used to calculate the Mod-MPI: isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and ejection time (ET). The mean Mod-MPI was 0.42±0.10. The mean IRT, ICT, and ET were 43.5±10.2, 27.27±8.1, and 170.5±16.9, respectively. A significant correlation was found between Mod-MPI and gestational age, umbilical artery systolic/diastolic (UA S/D) ratio and the middle cerebral artery pulsatility index (MCA PI) values (r=0.199, p=0.047, r=-0.328, p=0.001, and r=-0.0349, p=0.001, respectively) Conclusions. The current study`s results will be a reference for future studies, especially studies investigating pathological conditions that impact fetal cardiac function.

Planning management and delivery of the growth-restricted fetus

The aim of this study was to investigate the role of cerebroplacental ratio (CPR) in the final prenatal care for neonatal respiratory diseases and to analyze the risk of relevant factors associated with neonatal respiratory disorders. A prospective cohort study of 795 singleton pregnancies was conducted. The pulsatility indices (PI) of the umbilical artery (UA) and the middle cerebral artery (MCA) were measured, and the MCA to UA ratio (CPR) was determined. The severity of the case is determined by whether or not the newborn has respiratory problems. Compare the CPR correlation between the two groups and examine the illness prediction factors through a binary logistic regression method. Of the 795 participants, 124 had neonatal respiratory disorders. The mean values of CPR between neonatal respiratory diseases group and control group were 1.78±0.6, 1.97±0.9, respectively (P < 0.001). Maternal age, abortion history, cesarean section history, placental thickness, placental maturity, and amniotic fluid index (AFI) were determined to have no significant link between the two groups after comparison analysis (P > 0.05). It could be found that compared with the control group, CPR MoM indicators of neonatal respiratory distress syndrome, neonatal pneumonia and wet lung disease all show significant decreases. In binary logistic regression analysis, among the variables included in the model, CPR (OR:2.90, P = 0.015), fetal heart monitoring (OR:5.26, P < 0.001), delivery mode (OR:2.86, P < 0.001) and gestational age of delivery (OR:0.92, P < 0.001) were statistically significant in both groups. The findings of this study showed that infant respiratory problems were substantially related to CPR value. The correlation indicates that CPR was a powerful reference marker for respiratory disorders.

Background: Fetal growth restriction (FGR) is a major contributor to adverse perinatal outcomes and is primarily driven by placental insufficiency and chronic fetal hypoxia. While arterial Doppler abnormalities are widely used in clinical surveillance, less is known about venous hemodynamics and intracardiac structural adaptations in FGR. In particular, the clinical relevance of foramen ovale (FO) morphometry and inferior vena cava (IVC) Doppler parameters in different FGR phenotypes remains incompletely understood. This study aimed to evaluate FO measurements and IVC Doppler indices in early- and late-onset FGR and to investigate their associations with adverse perinatal outcomes. Methods: This prospective observational study included 240 singleton pregnancies: 120 fetuses with FGR and 120 gestational age-matched appropriate-for-gestational-age controls. FGR was defined according to Delphi consensus criteria and classified as early onset (<32 weeks) or late onset (≥32 weeks). Ultrasonographic assessment included FO and right atrium dimensions, FO-to-right atrium (FO/RA) ratio, IVC diameter, and IVC Doppler indices (pulsatility index [PI], preload index [PLI], and peak velocity index for veins [PVIV]). A composite adverse perinatal outcome (CAPO) was recorded. Receiver operating characteristic (ROC) curve analysis and multivariable logistic regression were performed. Results: Compared with controls, fetuses with FGR exhibited significantly smaller FO dimensions, lower FO/RA ratios, reduced IVC diameters, and higher IVC Doppler indices (all p < 0.05). The FO/RA ratio demonstrated the highest discriminative performance for CAPO (AUC 0.722). In multivariable analysis, a 0.1-unit increase in the FO/RA ratio was independently associated with a reduced risk of CAPO (OR 0.57), whereas higher IVC PI values were associated with an increased risk (OR 2.64). IVC Doppler alterations were less pronounced in early-onset FGR. Conclusions: FO morphometry and IVC Doppler parameters reflect complementary stages of fetal cardiovascular adaptation in fetal growth restriction, with FO changes representing early adaptive responses and IVC Doppler alterations indicating more advanced hemodynamic compromise, and this may provide additional value for perinatal risk stratification.

Background Reduced lung function at birth has evident antenatal origins and is associated with an increased risk of wheezing and asthma later in life. Little is known about whether blood flow in the fetal pulmonary artery, may impact postnatal lung function. Objective Our primary aim was to investigate the potential associations between fetal Doppler blood flow velocity measures in the fetal branch pulmonary artery, and infant lung function by tidal flow-volume (TFV) loops at three months of age in a low-risk population. Our secondary aim was to explore the association between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries, and the same lung function measures. Methods In 256 non-selected pregnancies from the birth cohort study Preventing Atopic Dermatitis and ALLergies in Children (PreventADALL) we performed fetal ultrasound examination with Doppler blood flow velocity measurements at 30 gestational weeks (GW). We recorded the pulsatility index, peak systolic velocity, time-averaged maximum velocity, acceleration time/ejection time ratio, and time velocity integral primarily in the proximal pulmonary artery close to the pulmonary bifurcation. The pulsatility index was measured in the umbilical and middle cerebral arteries and the peak systolic velocity in the middle cerebral artery. The cerebro-placental ratio (ratio between pulsatility index in the middle cerebral and umbilical arteries) was calculated. Infant lung function was assessed using TFV loops in awake, calmly breathing three months old infants. The outcome was the time to peak tidal expiratory flow to expiratory time ratio (t PTEF/t E), t PTEF/t E <25th percentile, and tidal volume per kg body weight (V T/kg). Potential associations between fetal Doppler blood flow velocity measures and infant lung function were assessed using linear and logistic regressions. Results The infants were born at median (min - max) 40.3 (35.6 − 42.4) GW, with a mean (SD) birth weight of 3.52 (0.46) kg, and 49.4% were females. The mean (SD) t PTEF/t E was 0.39 (0.1) and the 25th percentile was 0.33. Neither univariable nor multivariable regression models revealed any associations between fetal pulmonary blood flow velocity measures and t PTEF/t E, t PTEF/t E <25th percentile, or V T/kg at three months of age. Similarly, we did not observe associations between Doppler blood flow velocity measures in the umbilical and middle cerebral arteries and infant lung function measures. Conclusion In a cohort of 256 infants from the general population, fetal third-trimester Doppler blood flow velocity measures in the branch pulmonary, umbilical, and middle cerebral arteries were not associated with infant lung function measures at three months of age.

Objective To determine whether there are any changes in fetal cardiac function in pregnant women with velamentous cord insertion by using the myocardial performance index and whether there are any influence on perinatal outcome. Methods Seventy singleton pregnant women diagnosed with velamentous cord insertion at 28-40 weeks of gestation were recruited to the study from January 2016 to December 2018. They were matched with 89 healthy women with normal pregnancies. Using Doppler echocardiography, the modified myocardial performance index (Mod-MPI) and ratios of E wave/A wave peak velocities (E/A) were determined. The Doppler indices of ductus venosus and umbilical and middle cerebral arteries were also determined in both groups. Adverse perinatal outcome was defined as fetal distress, admission to neonatal intensive care unit, neonatal asphyxia, and respiratory acidosis. Results The Mod-MPI (t=4.593, P 0.05 for all). Receiver operating characteristic analysis revealed>0.45 as the optimal cut-off level for MPI in perinatal adverse outcome prediction (sensitivity: 83.3%; specificity: 38.1%; area under the curve: 0.690; 95% confidence interval: 0.580-0.799). Conclusions Fetuses of pregnant women with velamentous cord insertion have significantly impaired cardiac function. There is an association between the MPI elevation and adverse perinatal outcome. The Mod-MPI has the potential to provide a theoretical basis for monitoring intrauterine environment. Key words: Velamentous cord insertion; Fetal cardiac function; Myocardial performance index

To determine the magnitude of fetal growth restriction (FGR) using fetal Doppler integrated with antenatal ultrasound in third-trimester screened pregnant women at Agra in northern India. Screened participants underwent routine third-trimester ultrasound assessments integrating fetal Doppler studies. Any one or more of mean uterine artery (UtA) or umbilical artery (UA) pulsatility index > 95th centile, middle cerebral artery (MCA) or cerebroplacental ratio (CPR) PI < 5th centile, absent or reversed end-diastolic velocity, or ductus venosus PI > 95th centile was considered abnormal Doppler studies. Fetuses with estimated fetal weight (EFW) < 3rd percentile or EFW 3rd to 10th percentile with abnormal Doppler were categorised as FGR. Fetuses with EFW 3rd to 10th percentile and normal Doppler were classified as small for gestational age (SGA) and EFW 10th to 50th percentile and abnormal Doppler were classified as appropriate for gestational age (AGA) fetuses with adapted growth restriction. Among 1065 screened participants, 142 fetuses (13.33%) had an EFW < 10th centile and 139 (13.05%) fetuses had both EFW and fetal AC < 10th centile. Stage 1 FGR was identified in 58 (5.45%) fetuses, 75 fetuses (7.04%) were classified as SGA and 77 (7.23%) were adapted growth-restricted AGA fetuses. Reclassifying FGR after integrating Doppler assessments reduced magnitude by 52.13, 51.11, and 76.82% from the estimates of FGR derived based on EFW < 10th centile alone, both EFW and fetal AC < 10th centile and either EFW or fetal AC < 10th centile respectively. Integrating fetal Doppler studies with routine third-trimester ultrasound assessment significantly reclassifies FGR with a huge reduction in the proportion of fetuses that need more intense surveillance in the third trimester.