Echocardiographic assessment of fetal cardiac function in the uterine artery ligation rat model of IUGR.

BACKGROUND: Intrauterine growth restriction (IUGR) leads to cardiac dysfunction and adverse remodeling of the fetal heart, as well as a higher risk of postnatal cardiovascular diseases. The rat model of IUGR, via uterine artery ligation, is a popular model but its cardiac sequelae is not well investigated. Here, we performed an echocardiographic evaluation of its cardiac function to determine how well it can represent the disease in humans. METHODS: Unilateral uterine artery ligation was performed at embryonic day 17 (E17) and echocardiography was performed at E19 and E20. RESULTS: Growth-restricted fetuses were significantly smaller and lighter, and had an higher placenta-to-fetus weight ratio. Growth-restricted fetal hearts had reduced wall thickness-to-diameter ratio, indicating left ventricular (LV) dilatation, and they had elevated trans-mitral and trans-tricuspid E/A ratios and reduced left and right ventricular fractional shortening (FS), suggesting systolic and diastolic dysfunction. These were similar to human IUGR fetuses. However, growth-restricted rat fetuses did not demonstrate head-sparing effect, displayed a lower LV myocardial performance index, and ventricular outflow velocities were not significantly reduced, which were dissimilar to human IUGR fetuses. CONCLUSIONS: Despite the differences, our results suggest that this IUGR model has significant cardiac dysfunction, and could be a suitable model for studying IUGR cardiovascular physiology. IMPACT: Animal models of IUGR are useful, but their fetal cardiac function is not well studied, and it is unclear if they can represent human IUGR fetuses. We performed an echocardiographic assessment of the heart function of a fetal rat model of IUGR, created via maternal uterine artery ligation. Similar to humans, the model displayed LV dilatation, elevated E/A ratios, and reduced FS. Different from humans, the model displayed reduced MPI, and no significant outflow velocity reduction. Despite differences with humans, this rat model still displayed cardiac dysfunction and is suitable for studying IUGR cardiovascular physiology.

Uterine Artery Pulsatility Index Assessment at <11 Weeks' Gestation: A Prospective Study.

OBJECTIVE: Mean uterine artery pulsatility index (meanUAPI) is commonly measured at 11-13+6 weeks to predict adverse pregnancy outcomes including hypertensive disorders and small-for-gestational age. The aims of this study were to establish a population-specific reference range for meanUAPI at <11 weeks, to determine if an abnormal meanUAPI at <11 weeks was associated with adverse pregnancy outcome, and to assess changes in meanUAPI between <11 weeks and 11-13+6 weeks. METHODS: A prospective cohort was examined at <11 weeks and at 11-13+6 weeks to develop reference ranges for meanUAPI. Based on these regression models, meanUAPI Z-scores were compared between outcome groups using a two-sample t test. Longitudinal changes in the meanUAPI between <11 and 11-13+6 weeks were assessed by two-way mixed ANOVA. RESULTS: Prior to 11 weeks, there was no significant difference in meanUAPI between normal (n = 622) and adverse (n = 80) outcomes (mean [95% CI]: 2.62 [2.57-2.67] and 2.67 [2.50-2.84], respectively; p = 0.807). At 11-13+6 weeks, meanUAPI was significantly higher in the adverse (n = 66) compared with the normal (n = 535) outcome group (mean [95% CI]: 1.87 [1.70-2.03] and 1.67 [1.63-1.72], respectively; p = 0.040). There was a statistically significant decrease (p < 0.0001) in meanUAPI between the two time points. CONCLUSION: MeanUAPI measured at <11 weeks' gestation does not appear to be a useful marker for the prediction of placental-related adverse pregnancy outcomes, supporting an argument for the prediction of risk at 11-13+6 weeks' gestation.

Assessment of neonatal EEG background and neurodevelopment in full-term small for their gestational age infants.

BACKGROUND: Delayed brain function development in small-gestational-age (SGA) infants has been reported. We aimed to quantify rates of immature neonatal EEG patterns and their association with neurodevelopment in SGA full-term neonates. METHODS: Using a cohort design, 50 SGA (birthweight <10th percentile) and 44 appropriate-gestational-age (AGA) term neonates underwent continuous video-EEG recordings lasting >3 h. Seventy-three of them were assessed at 2-years-old using Bayley-III-Scales. For EEG analysis, several segments of discontinuous/alternating EEG tracings were selected. MAIN OUTCOMES MEASURED: (1) Visual analysis (patterns of EEG maturity); (2) Power spectrum in δ, θ, α and ß frequency bands; and (3) scores in motor, cognitive and language development. RESULTS: (1) SGA infants, compared to AGA, showed: (a) higher percentages of discontinuous EEG, both asynchrony and interhemispheric asymmetry, and bursts with delta-brushes, longer interburst-interval duration and more transients/hour; (b) lower relative power spectrum in δ and higher in α; and (c) lower scores on motor, language and cognitive neurodevelopment. (2) Asymmetry >5%, interburst-interval >5 s, discontinuity >11%, and bursts with delta-brushes >11% were associated with lower scores on Bayley-III. CONCLUSIONS: In this prospective study, SGA full-term neonates showed high rates of immature EEG patterns. Low-birthweight and immaturity EEG were both correlated with low development scores.

Predictors of perinatal outcome in early-onset fetal growth restriction: A study from an emerging economy country.

OBJECTIVE: To identify antenatal predictors of adverse perinatal outcomes in a population of preterm fetuses with early placental insufficiency diagnosed by Doppler abnormalities. METHOD: In this cross-sectional study of a cohort of singleton pregnant women diagnosed with early placental insufficiency, relationships between perinatal variables (arterial and venous Doppler, gestational age, birth weight, oligohydramnios, estimated fetal weight, and fetal weight z-scores) and major neonatal complications were analyzed by logistic regression. RESULTS: Two hundred sixty-five women were delivered, between 24 and 33 weeks gestation. The overall frequency of intact survival was 57.9% (n = 154). Gestational age thresholds for best prediction of survival was 27 + 6 weeks and for intact survival was 29 + 0 weeks gestation. Fetal weight and absent/reversed ductus venosus a-wave were the main predictors of survival in the regression model. When fetal weight was substituted for fetal weight z-score, ductus venosus abnormal Doppler predicted mortality and absent or reversed umbilical artery diastolic velocities predicted intact survival. CONCLUSIONS: This study illustrates the impact of gestational age and fetal weight on perinatal outcomes in early placental insufficiency, with well-defined thresholds. Gestational age and fetal weight, or a combination of fetal weight z-scores and fetal Doppler parameters, were the best predictors of intact survival in our sample.

A systematic review on the utility of non-invasive electrophysiological assessment in evaluating for intra uterine growth restriction.

BACKGROUND: Non-invasive electrophysiological assessment (NIEA) is an evolving area in fetal surveillance and is attracting increasing research interest. There is however, limited data outlining its utility in evaluating intra uterine growth restriction (IUGR). The objective of this study was to carry out a systematic review to outline the utility of NIEA parameters in evaluating IUGR. METHODS: A systematic review of peer reviewed literature was performed, searching PUBMED, Ovid MEDLINE and EMBASE. The outcomes of interest included NIEA parameters [P wave duration, PR interval, QRS duration, QT interval, T/QRS ratio, short term variability (STV) and long term variability (LTV)] and a descriptive summary of relevant studies as well. RESULTS: Sixteen studies were identified as suitable for inclusion. The utility of NIEA parameters were investigated in tabular form. In particular, QRS and QT duration, T/QRS ratio, STV and PRSA analysis displayed utility and merit further consideration in evaluating for IUGR. Issues identified in the review were in relation to variances in definition of IUGR, small sample sizes and the lack of technological consistency across studies. CONCLUSION: NIEA shows promise as an adjunct surveillance tool in fetal diagnostics for IUGR. Larger prospective studies should be directed towards establishing reliable parameters with a focus on uniformity of IUGR definition, technological consistency and the individualisation of NIEA parameters.

Assessment of ventricular contractility in fetuses with an estimated fetal weight less than the tenth centile.

OBJECTIVE: To determine whether abnormal global, transverse, and longitudinal ventricular contractility of the heart in fetuses with an estimated fetal weight <10th centile is present, irrespective of Doppler studies of the umbilical artery and cerebroplacental ratio. STUDY DESIGN: This was a retrospective study of 50 fetuses with an estimated fetal weight <10th centile that were classified based on Doppler results from the pulsatility indices of the umbilical artery and middle cerebral artery, and the calculated cerebroplacental ratio (pulsatility indices of the umbilical artery/middle cerebral artery). Right and left ventricular measurements were categorized into 3 groups: (1) global ventricular contractility (fractional area change), (2) transverse ventricular contractility (24-segment transverse fractional shortening), and (3) basal-apical longitudinal contractility (longitudinal strain, longitudinal displacement fractional shortening, and basal lateral and septal wall annular plane systolic excursion). Z scores for the above measurements were computed for fetuses with an estimated fetal weight <10th centile using the mean and standard deviation derived from normal controls. Ventricular contractility measurements were considered abnormal if their Z score values were <5th centile (z score <-1.65) or >95th centile (Z score >1.65), depending on the specific ventricular measurement. RESULTS: The average gestational age at the time of the examination was 32 weeks 4 days (standard deviation 3 weeks 4 days). None of the 50 study fetuses demonstrated absent or reverse flow of the umbilical artery Doppler waveform. Eighty-eight percent (44/50) of fetuses had one or more abnormal measurements of cardiac contractility of 1 or both ventricles. Analysis of right ventricular contractility demonstrated 78% (39/50) to have 1 or more abnormal measurements, which were grouped as follows: global contractility 38% (19/50), transverse contractility 66% (33/50); and longitudinal contractility 48% (24/50). Analysis of left ventricular contractility demonstrated 1 or more abnormal measurements in 58% (29/50) that were grouped as follows: global contractility 38% (19/50); transverse contractility 40% (20/50); and longitudinal contractility 40% (20/50). Of the 50 study fetuses, 25 had normal pulsatility index of the umbilical artery and cerebroplacental ratios, 80% of whom had 1 or more abnormalities of right ventricular contractility and 56% of whom had 1 or more abnormalities of left ventricular contractility. Abnormal ventricular contractility for these fetuses was present in all 3 groups of measurements; global, transverse, and longitudinal. Those with an isolated abnormal pulsatility index of the umbilical artery (n=11) had abnormalities of transverse contractility of the right ventricular and global contractility in the left ventricle. When an isolated cerebroplacental ratio abnormality was present, the right ventricle demonstrated abnormal global, transverse, and longitudinal contractility, with the left ventricle only demonstrating abnormalities in transverse contractility. When both the pulsatility index of the umbilical artery and cerebroplacental ratio were abnormal (3/50), transverse and longitudinal contractility measurements were abnormal for both ventricles, as well as abnormal global contractility of the left ventricle. CONCLUSIONS: High rates of abnormal ventricular contractility were present in fetuses with an estimated fetal weight <10th centile, irrespective of the Doppler findings of the pulsatility index of the umbilical artery, and/or cerebroplacental ratio. Abnormalities of ventricular contractility were more prevalent in transverse measurements than global or longitudinal measurements. Abnormal transverse contractility was more common in the right than the left ventricle. Fetuses with estimated fetal weight less than the 10th centile may be considered to undergo assessment of ventricular contractility, even when Doppler measurements of the pulsatility index of the umbilical artery, and cerebroplacental ratio are normal.

Assessment of fetal modified myocardial performance index in early-onset and late-onset fetal growth restriction.

AIM: To investigate the changes of modified myocardial performance index (Mod-MPI) in early-onset and late-onset fetal growth restriction (FGR) cases, and its association with adverse perinatal outcome. METHODS: This was a prospective study on 77 early-onset and 100 late-onset FGR cases. Hundred normal fetuses were matched as control groups for early-onset and late-onset FGR groups, respectively. Mod-MPI and vessel Doppler parameters including umbilical artery (UA), ductus venosus (DV), and middle cerebral artery (MCA) were measured. Perinatal outcomes were followed up. Mod-MPI of FGR cases were compared in normal Doppler, abnormal Doppler, and control groups. The association of Mod-MPI and perinatal outcome was investigated, and further efficacy of Mod-MPI predicting adverse outcome was studied. RESULTS: Compared with control groups, both abnormal and normal Doppler groups showed increased Mod-MPI in early-onset and late-onset FGR, respectively. Mod-MPI had no significant difference between abnormal and normal Doppler groups. Mod-MPI was associated with adverse outcome in early-onset FGR (OR = 3.307) and late-onset FGR (OR = 3.412). The sensitivity and specificity of Mod-MPI predicting adverse outcome were 60% and 80% when cutoff value was 0.47 in early-onset FGR. And they were 65% and 70% when cutoff value was 0.50 in late-onset FGR. CONCLUSION: Fetal growth restriction fetuses had increased Mod-MPI. Mod-MPI could be used to predict adverse perinatal outcome of FGR fetuses. Mod-MPI was an effective parameter to supplement vessels' Doppler parameters in monitoring FGR.

Cardiac left heart morphology and function in newborns with intrauterine growth restriction: relevance for long-term assessment.

AIM: To asses the cardiac morphology and functional changes specific for newborns from intrauterine growth restriction (IUGR) pregnancies. MATERIAL AND METHOD: A cohort of IUGR infants were evaluated by serial echocardiographies at delivery and at the first and six months follow-ups. IUGR newborn delivery status was compared to that of newborns in the control group according to gestational age (AGA). RESULTS: Left heart measurements were significantly lower in IUGR newborns compared to AGA babies. Left ventricular size increased at follow-up inthe IUGR group (p<0.05). Systolic dysfunction (the myocardial performance index (MPI)> 0.47) was identified in 40% of the neonates in the IUGR group (16/40), respectively 4.76% in the control group. IUGR neonates had a significantly increased proportion of systolic malfunction (p=0.004). CONCLUSION:  IUGR patients had reduced left ventricle dimensions compared to AGA babies. The MPI stands out as a marker of leftheart function in newborns. Systolic dysfunction was a hallmark of the cardiac adaptation in IUGR neonates.

Prognostic value of the aortic isthmus Doppler assessment on late onset fetal growth restriction.

Background As conflicting results have been reported about the association of reversed flow on the aortic isthmus (AoI) and adverse perinatal results in fetal growth restriction (FGR), we aim to compare perinatal outcomes (including tolerance to labor induction) of late-onset FGR between those with anterograde and reversed AoI flow. Methods This was an observational retrospective cohort study on 148 singleton gestations diagnosed with late-onset FGR (diagnosis ≥32+0 weeks), with an estimated fetal weight (EFW) <10th centile and mild fetal Doppler alteration: umbilical artery (UA) pulsatility index (PI) >95th centile, middle cerebral artery (MCA)-PI <5th centile or cerebral-placental ratio <5th centile. Anterograde AoI flow was present in n=79 and reversed AoI flow in n=69. Delivery was recommended from 37 weeks in both groups. Perinatal results were compared between the groups. Results The global percentage of vaginal delivery of fetuses with anterograde and reversed blood flow was 55.7% vs. 66.7% (P=0.18) and the percentage of cesarean section (C-section) for non-reassuring fetal status was 12.7% vs. 15.9% (P=0.29), respectively. When evaluating those that underwent labor induction, the vaginal delivery rate was 67.9% vs. 77.2% (P=0.17), respectively. There were no significant differences regarding any other perinatal variables and there were no cases of severe morbidity or mortality. Conclusion We observed that the presence of reversed AoI flow does not worsen perinatal outcomes on fetuses with late-onset growth restriction with mild Doppler alterations. Attempt of labor induction is feasible in these fetuses regardless of the direction of AoI flow.

Assessment of the blood flow in kidneys of growth-restricted fetuses using quantitative three-dimensional power Doppler ultrasound.

OBJECTIVE: Fetuses with fetal growth restrictions have higher perinatal mortality rates than fetuses without fetal growth restrictions. Vascularization of the fetal kidney is crucial to fetal growth. Hence, we assessed blood flow and vascularization of fetal kidneys in non-growth-restricted as well as growth-restricted fetuses using quantitative three-dimensional power Doppler ultrasound. MATERIALS AND METHODS: We undertook a prospective study to evaluate the vascular indices of fetal kidneys; i.e., the vascularization index, flow index and vascularization-flow index, in growth-restricted and non-growth-restricted fetuses using three-dimensional power Doppler ultrasound and quantitative three-dimensional histogram analysis. All fetuses from 20 to 40 weeks of gestation were singletons with a normal pregnancy and were followed up to delivery. RESULTS: In total, 209 fetuses without fetal growth restriction and 50 fetuses with fetal growth restriction were included. Our results showed the fetal renal vascularization index, flow index, and vascularization-flow index evaluated by three-dimensional power Doppler ultrasound can differentiate fetuses with fetal growth restriction from fetuses without fetal growth restriction. CONCLUSION: The fetal renal vascularization index, flow index, and vascularization-flow index measured by three-dimensional power Doppler ultrasound can be applied to prenatally detect fetal growth restriction. Our data support assessment of the fetal renal vascularization index, flow index, and vascularization-flow index using three-dimensional power Doppler ultrasound as a useful test for detecting fetuses with fetal growth restriction.

Papel do Doppler do ducto venoso na restrição de crescimento intrauterino / Ductus venosus Doppler assessment in intrauterine growth restriction

Objetivo: O crescimento intrauterino restrito (CIUR) por insuficiência placentária persiste como grande desafio obstétrico. A interrupção da gestação representa a única estratégia de condução e baseia-se na predição de desfechos adversos. O Doppler tem valor reconhecido na avaliação seriada das alterações circulatórias nesses fetos, em geral sequenciais e proporcionais à gravidade do insulto hipóxico. Este estudo objetiva revisar as evidências do papel do Doppler de ducto venoso (DV) na predição de morbimortalidade perinatal em gestações complicadas por CIUR placentário grave e precoce. Métodos: Realizou-se revisão narrativa, com busca de artigos publicados nos últimos 10 anos nas bases Medline/PubMed, Lilacs e Scielo, sendo encontradas 132 referências. Pesquisas com animais e gestações múltiplas foram excluídas. Dos 115 artigos selecionados, 34 foram excluídos por inadequação ao tema. A revisão baseou-se nas demais 81 referências, além de trabalhos de reconhecida relevância no tema. Resultados: Estudos demonstram evidência consistente do papel do Doppler de DV na avaliação de fetos com CIUR, com bom valor preditivo para acidemia fetal e desfecho perinatal adverso. As principais estratégias de monitorização se baseiam na combinação do Doppler de vasos arteriais/venosos e parâmetros biofísicos, mas o Doppler de DV seria o melhor parâmetro isolado para predição de comprometimento fetal grave. Conclusão: A incorporação do Doppler de DV na monitorização de fetos com CIUR grave e precoce é capaz de predizer desfechos perinatais críticos. A avaliação de múltiplos vasos fetais parece aumentar a acurácia, porém não há evidência para embasar a definição de protocolos para o manejo clínico.(AU)

Objective: Intrauterine growth restriction (IUGR) due to early onset placental insufficiency remains to be a great challenge in obstetrical practice. Delivery is still the only available strategy of management, and timing such intervention depends on prediction of adverse outcomes. Dopplervelocimetry studies have recognized value in the evaluation of the sequential hemodynamic changes that are stablished in the arterial and venous circulation of these fetuses, which correlate with the severity of hypoxemic insult. This study aims to review evidence on ductus venosus (DV) Doppler`s role as a predictor of perinatal outcome in pregnancies complicated by severe early onset IUGR. Methods: A Medline/PubMed, Lilacs and Scielo search was performed to identify original articles and systematic reviews published in the last 10 years. Eighty-one references were included in this review, in addition to other papers of recognized relevance in the subject. Results: Studies demonstrate consistent evidence on DV Doppler`s role in the longitudinal evaluation of IUGR fetuses, with adequate predictive value for fetal acidemia and adverse outcome. Monitoring strategies are usually based on a combination of arterial and venous Doppler assessment, in addition to biophysical parameters, but DV Doppler seems to be the best single parameter for prediction of severe fetal compromise. Conclusion: Monitoring of fetuses with severe early-onset IUGR through DV Doppler is able to predict critical perinatal outcomes. Evaluation of multiple fetal vessels seems to increase accuracy of prediction, but to this moment there is not enough evidence to recommend protocols of management.(AU)

IUGR decreases cardiomyocyte endowment and alters cardiac metabolism in a sex- and cause-of-IUGR-specific manner.

Intrauterine growth restriction (IUGR) increases the risk of ischemic heart disease in adulthood. Studies in rats suggest cardiac vulnerability is more pronounced in males and in offspring that were exposed to hypoxia in utero. Therefore, we aimed to test the hypotheses that 1) IUGR adolescent males, but not females, have fewer cardiomyocytes and altered expression of cardiometabolic genes compared with controls; and 2) IUGR due to hypoxia has a greater effect on these parameters compared with IUGR due to nutrient restriction. IUGR was induced in guinea pigs by maternal hypoxia (MH; 10% O2, n = 9) or maternal nutrient restriction (MNR; ~30% reduction in food intake, n = 9) in the second half of pregnancy and compared with control ( n = 11). At 120 days of age, postmortem was performed and the left ventricle perfusion fixed for stereological determination of cardiomyocyte number or snap frozen to determine the abundance of cardiometabolic genes and proteins by quantitative RT-PCR and Western blotting, respectively. MH reduced the number of cardiomyocytes in female ( P < 0.05), but not male or MNR, adolescent offspring. Furthermore, IUGR males had decreased expression of genes responsible for fatty acid activation in the sarcoplasm ( FACS) and transport into the mitochondria ( AMPK-a2 and ACC; P < 0.05) and females exposed to MH had increased activation/phosphorylation of AMP-activated protein kinase-α ( P < 0.05). We postulate that the changes in cardiomyocyte endowment and cardiac gene expression observed in the present study are a direct result of in utero programming, as offspring at this age did not suffer from obesity, hypertension, or left ventricular hypertrophy.

Perinatal loss at term: role of uteroplacental and fetal Doppler assessment.

OBJECTIVE: To examine the associations of uterine artery (UtA) Doppler indices and cerebroplacental ratio (CPR) with perinatal outcome at term. METHODS: This was a retrospective cohort study conducted at a tertiary referral center that included all singleton pregnancies undergoing ultrasound assessment in the third trimester that subsequently delivered at term. Fetal biometry and Doppler assessment, including that of the umbilical artery (UA), fetal middle cerebral artery (MCA) and UtA, were recorded. Data were corrected for gestational age, and CPR was calculated as the ratio of MCA pulsatility index (PI) to UA-PI. Logistic regression analysis was conducted to examine for independent predictors of adverse perinatal outcome. RESULTS: The study included 7013 pregnancies, 12 of which were complicated by perinatal death. When compared with pregnancies resulting in perinatal survival, pregnancies complicated by perinatal death had a significantly higher proportion of small-for-gestational-age infants (25.0% vs 5%; P = 0.001) and a higher incidence of low (< 5th centile) CPR (16.7% vs 4.5%; P = 0.041). A subgroup analysis comparing 1527 low-risk pregnancies that resulted in fetal survival with pregnancies complicated by perinatal death demonstrated that UtA-PI multiples of the median (MoM), CPR < 5th centile and estimated fetal weight (EFW) centile were all associated significantly with the risk of perinatal death at term (all P < 0.05). After adjusting for confounding variables, only EFW centile (odds ratio (OR) 0.96 (95% CI, 0.93-0.99); P = 0.003) and UtA-PI MoM (OR 13.10 (95%CI, 1.95-87.89); P = 0.008) remained independent predictors of perinatal death in the low-risk cohort. CONCLUSION: High UtA-PI at term is associated independently with an increased risk of adverse perinatal outcome, regardless of fetal size. These results suggest that perinatal mortality at term is related not only to EFW and fetal redistribution (CPR), but also to indices of uterine perfusion. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Fetal myocardial performance index in assessment and management of small-for-gestational-age fetus: a cohort and nested case-control study.

OBJECTIVE: To assess the clinical utility of the fetal myocardial performance index (MPI) in assessment and management of the small-for-gestational-age (SGA) fetus/growth-restricted fetus (FGR). METHODS: This was a prospective cohort study in metropolitan Australia of patients referred in the period June 2012 to March 2015 to fetal medicine services at 24-38 weeks' gestation for suspected singleton SGA/FGR (estimated fetal weight (EFW) < 10th centile with or without abnormal umbilical artery (UA) Doppler) pregnancy. Patients had MPI assessed in addition to routine measures, and were followed through to birth. We compared MPI values against those of a local reference population and gestational age-matched controls, and assessed the correlation with perinatal outcome and other Doppler measures. RESULTS: Fifty-two cases were included, 38 diagnosed < 32 weeks and 14 diagnosed ≥ 32 weeks. None demonstrated significantly elevated left, right or delta MPI compared with the reference population or with gestational age-matched controls at the time of first MPI evaluation. There were no consistent longitudinal patterns in MPI that would suggest its clinical utility. The mean ± SD gestational age at delivery was 34.6 ± 3.8 weeks and birth weight was 1.7 ± 0.6 kg, and the median neonatal hospital admission time was 27 days, confirming a pathological cohort. There were no significant correlations between left, right or delta-MPI and perinatal outcome, although there were significant correlations between UA, middle cerebral artery (MCA) and ductus venosus (DV) Doppler and perinatal outcome (birth weight, gestational age at birth and length of neonatal hospital stay). Exploratory subgroup comparisons (EFW < 3rd vs 3rd -10th centile; early- vs late-onset; abnormal vs normal UA Doppler) found only minor differences in MPI, reaching statistical, but not clinical, significance, only in the EFW < 3rd vs 3rd -10th centile comparison. CONCLUSIONS: MPI did not demonstrate clinical utility in either triage or longitudinal follow-up of an SGA/FGR cohort presenting to fetal medicine services. Given that prior research suggesting its utility originates from single-center cohorts, while multicenter, large cohorts have suggested little utility or no additional utility if routine UA/MCA/DV Doppler is performed, publication bias may have affected previous reports. It seems unlikely that MPI has clinical utility in assessment and management of SGA/FGR fetuses. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Three-Dimensional Power Doppler Evaluation of Cerebral Vascular Blood Flow: A Novel Tool in the Assessment of Fetal Growth Restriction.

OBJECTIVES: To determine whether fetuses with fetal growth restriction (FGR) are more likely to have abnormal cerebral vascular flow patterns compared to fetuses who are appropriate for gestational age (AGA) when quantified by using 3-dimensional (3D) power Doppler ultrasound. METHODS: We conducted a prospective cohort study of singleton gestations presenting for growth ultrasound examination between 24 and 36 weeks' gestation. Patients with FGR (estimated fetal weight < 10th percentile) were enrolled and matched 1:1 for gestational age (±7 days) with AGA fetuses. A standardized 3D power Doppler image of the middle cerebral artery territory was obtained from each patient. The vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) were calculated by the Virtual Organ computer-aided analysis technique (GE Healthcare, Milwaukee, WI). These indices were compared between FGR and AGA fetuses and correlated with 2-dimensional Doppler parameters. Neonatal outcomes were also compared with respect to the 3D parameters. RESULTS: Of 306 patients, there were 151 cases of FGR. There was no difference in the VI (6.0 versus 5.7; P = .65) or VFI (2.0 versus 1.8; P = .31) between the groups; however, the FI was significantly higher in FGR fetuses compared to AGA controls (33.9 versus 32.3; P = .009). There was a weak, but significant, negative correlation between the FI and both the middle cerebral artery pulsatility index (r = -0.34; P < .001) and cerebroplacental ratio (r = -0.29; P < .001). Within the FGR group, there was no difference in any of the 3D vascular indices with regard to neonatal outcomes. CONCLUSIONS: Three-dimensional power Doppler measurement of cerebral blood flow, but not the vascularization pattern, is significantly altered in FGR. This measurement may play a future role in distinguishing pathologic FGR from constitutionally small growth.

In vivo assessment of placental elasticity in intrauterine growth restriction by shear-wave elastography.

PURPOSE: In this study, we evaluated the placental elasticity in vivo by shear-wave elastography in pregnant women under follow-up for intrauterine growth restriction (IUGR) and compared the elasticity values to normal pregnancies. MATERIAL AND METHODS: This prospective study included 42 pregnant women with a possible diagnosis of intrauterine growth restriction based on obstetrical grayscale and Doppler ultrasonography and 42 women with a normal pregnancy during the 2nd and 3rd trimester. During follow-up examinations, seven fetuses showed an increased growth and were delivered with a birth-weight above the 10 percentile. However, for statistical purposes we included these seven patients in the IUGR group due to prospective nature of the study. All patients initially underwent obstetrical grayscale and Doppler ultrasonography with measurement of resistivity and pulsatility indices from uterine arteries. Subsequently, elasticity values of the peripheral and central part of the placentas from fetal and maternal surfaces were measured by shear-wave elastography. Following delivery, Apgar scores at 1st and 5th minute, birth weight were collected. For statistical analysis, Mann-Whitney U test was used. ROC curves were plotted and cut-off values for elasticity values were analyzed. RESULTS: Median elasticity values of the central part of the placentas from maternal (28kPa vs 6kPa) and fetal sides (21.5kPa vs 5kPa) were significantly higher in IUGR pregnancies compared to the control group (p<0.001). Similarly, median elasticity values of peripheral part of placentas from maternal (22kPa vs 5.35kPa) and fetal sides (22.5kPa vs 5.3kPa) were significantly higher in IUGR pregnancies compared to the control group (p<0.001). CONCLUSION: Placental stiffness values are significantly higher in patients with IUGR. Shear-wave elastography can be used as a non-invasive, complementary method to gray-scale and Doppler ultrasound for diagnosing IUGR.

Assessment of arterial function in pregnancy: recommendations of the International Working Group on Maternal Hemodynamics.

There is strong evidence supporting the role of maternal arterial dysfunction in pregnancy-specific disorders such as pre-eclampsia and intrauterine growth restriction. As more work is focused towards this field, it is important that methods and interpretation of arterial function assessment are applied appropriately. Here, we summarize techniques and devices commonly used in maternal health studies, with consideration of their technical application in pregnant cohorts. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Assessment of fetal myocardial performance in severe early onset pre-eclampsia (EO-PET) with and without intrauterine growth restriction across deteriorating stages of placental vascular resistance and links to adverse outcomes.

OBJECTIVE: To determine whether fetuses in severe early onset pre-eclampsia (EO-PET) with or without intrauterine growth restriction has cardiac dysfunction across deteriorating stages of placental vascular resistance and whether this dysfunction influences perinatal outcome. STUDY DESIGN: This was a prospective cross-sectional study performed in a tertiary care university medical centre. Sixty pregnant patients with severe early-onset pre-eclampsia between 27 and 32 weeks were recruited and matched with 60 patients having normal pregnancies. An analysis of cardiac function using the myocardial performance index (MPI) and early ventricular filling (E) and late active atrial contraction (A) ratios (E/A ratios) in the study group was performed compared to controls and further analysis was performed based on worsening placental vascular resistance and presence of growth restriction. RESULTS: MPI values were increased in the pre-eclamptic group, irrespective if growth restriction co-exists, compared to controls (0.61 vs 0.38, p<0.001). Its median value progressively increased with worsening placental vascular resistance. For adverse perinatal outcome cut-off MPI values have been suggested. The E/A ratios were significantly decreased in the pre-eclamptic group compared to controls (0.66 vs 0.79, p<0.0001). No adverse outcomes were noted in the control group. CONCLUSION: Fetal cardiac function is significantly impaired in pregnancies complicated by severe early onset pre-eclampsia, irrespective if growth restriction co-exists and worsens with deteriorating grades of placental vascular resistance. The MPI can potentially be integrated into routine fetal surveillance techniques.

Assessment of modified myocardial performance index in foetuses with growth restriction.

AIM: To evaluate the modified myocardial performance index (Mod-MPI) in foetuses with growth restriction and compare this index with appropriate for gestational age foetuses. MATERIAL AND METHODS: A prospective cross-sectional case-control study was conducted involving 76 singleton foetuses between 24 and 34 weeks of gestation divided into three groups (24 appropriate growth foetuses, 30 foetuses with estimated weight between the 3rd and 10th percentiles and 22 foetuses with estimated weight < 3rd percentile, according to the Hadlock table). The Mod-MPI was obtained in the plane of the four chamber view, and the spectral Doppler sample volume was placed in the lateral wall of the aorta, close to the mitral valve. Doppler of umbilical artery was normal in all cases. Analysis of variance (ANOVA) was used to compare the groups and the intra-class correlation coefficient (ICC) was used to assess intra- and inter-observer reproducibility. RESULTS: The mean Mod-MPI in the groups of appropriate for gestational age, estimated weight between the 3rd and 10th percentiles, and estimated weight < 3rd percentile was 0.32 +/- 0.05, 0.35 +/- 0.05 and 0.36 +/- 0.06, respectively; there was no statistical difference between the groups (p = 0.072). There was good intra- and inter-observer reproducibility (ICC = 0.726 and 0.760, respectively). CONCLUSION: Mod-MPI was not significantly different between foetuses appropriate for gestational age and those with growth restriction. Mod-MPI proved to be a feasible and reproducible technique.