Growth patterns and cardiovascular abnormalities in SGA fetuses: 2. Normal growth and progressive growth restriction

Objective To characterize abnormal growth processes and their associated cardiovascular abnormalities in SGA fetuses using Individualized Growth Assessment (IGA). Methods This longitudinal investigation utilized a SGA cohort [EFW and BW <10th percentile] derived from the PORTO study. Fetuses categorized by their Fetal Growth Pathology Score [FGPS1] patterns [Pattern 2 {n = 12}, Pattern 3 {n = 11}, Pattern 5 {n = 13}] were evaluated. Growth pathology was measured using the -FGPS1 and the individual composite Prenatal Growth Assessment Score {-icPGAS]. Paired cardiovascular assessments utilized measurements of the Pulsatility Index [umbilical artery {UA}, middle cerebral artery {MCA}, ductus venosus {DV}] and the myocardial performance index [MPI; heart]. Outcome variables were birth age [preterm or, term] and birth weight [small or normal (IGA criteria)]. Results Pattern 2 was usually characterized by a single, growth abnormality (67% of cases) of variable magnitude that occurred within two weeks of delivery {median onset age: 37.6 weeks}. The incidence of UA abnormalities was low (25%) while those of MCA and DV/MPI were high {60%, 42%}. Most neonates were of normal size (67%) and delivered at term (67%). Pattern 3 had an initial progressive growth restriction phase, followed by constant but abnormally low growth. Growth pathology had an early onset (median age: 31.6 weeks), was moderate but persistently abnormal. The incidences of cardiovascular abnormalities were moderate [30–50%]. Most neonates were abnormally small (80%) but delivered at term (90%). Pattern 5 had an initial progressive phase with an early onset [onset age {median}: 31.6 weeks]. However, this process was arrested and returned toward normal. Growth pathology magnitudes were minor as were the incidences of cardiovascular abnormalities. Neonatal size was usually normal and all fetuses delivered at term. Conclusions Characteristics of SGA Growth Restricted, Patterns 2, 3 and 5 are clearly different from those found in SGA Normal or SGA Growth Restricted Pattern 1 groups. They also differed from one another, indicating that growth restriction can manifest itself in several different ways. Pattern 2 is similar to “late” growth restriction reported previously. Patterns 3 and 5 are novel and have been designated as “adaptive” and “recovering” types of growth restriction.

Background Fetal growth restriction is being defined as either “early” or “late” depending on age of onset. A recent investigation using individualized assessment has identified five different growth restriction patterns. No previous study has related these patterns to cardiovascular abnormalities. Objectives To determine growth patterns in small fetuses (BW < 10th percentile) using Individualized Growth Assessment (IGA) and to relate cardiovascular abnormalities found with Doppler ultrasound to these patterns. Study design A secondary analysis was carried out in 126 fetuses from the PORTO data set having both estimated weights and birth weights below the 10th percentile. Only fetuses with 2nd and 3rd trimester biometry scans appropriate for IGA and cardiovascular assessments were studied. There was one-to-one matching of biometry and Doppler evaluations in the 3rd trimester. Composite growth parameters were used to quantify growth pathology at individual time points (individual composite Prenatal Growth Assessment Score (icPGAS)) and during the 3rd trimester (Fetal Growth Pathology Score {FGPS1}). Normal and growth restriction patterns were identified using plots of FGPS1 values. Doppler measurements were classified as normal or abnormal based on published cross-sectional standards. Outcome variables were birth weight and birth age. Results In these SGA cases, 38.2% showed normal fetal growth and 61.8% had growth restriction. In the latter, seven different patterns were observed. Pattern 1 was most common (43.5%), followed by Patterns 5 (16.7%), 2 (15.4%) and 3 (14.1%). The characteristics of Pattern 1 indicated progressive growth restriction while Pattern 5 demonstrated recovery from an initial growth abnormality. Cardiovascular abnormalities were quite variable, with those in the umbilical artery being most frequent in Patterns 1 and 3. Pattern 2 had the highest incidence of middle cerebral artery abnormalities. Umbilical artery abnormalities were similar in the Normal and Pattern 5 groups as were those for the middle cerebral artery. Other cardiovascular abnormalities had low frequencies except in Pattern 2 where the ductus venosus incidence was high. Abnormally small neonates, as identified with IGA, were seen primarily in Patterns 1, 3 and 6 (80–88%). Premature deliveries occurred most frequently in Pattern 1 (56%), followed by Pattern 2 (33%). Conclusions Growth in this SGA Group was very heterogeneous with a significant proportion of these small fetuses growing normally. Growth restriction did not appear to be a single process but was manifest as seven different FGPS1 patterns. Both growth pathology and cardiovascular abnormalities differed among patterns. Further investigation will be required to determine how specific growth abnormalities are related to fetal cardiovascular changes over time.

We have shown previously that third-trimester growth in small fetuses (estimated fetal weight (EFW) < 10th percentile) with birth weight (BW) < 10th percentile is heterogeneous using individualized growth assessment (IGA). We aimed to test our hypothesis that individual growth patterns in small fetuses with BW > 10th percentile are also variable but in different ways. This was a study of 191 cases with EFW < 10th percentile and BW > 10th percentile (appropriate-for-gestational-age (AGA) cohort), derived from the PORTO study. Composite size parameters were used to quantify growth pathology at individual third-trimester timepoints (individual composite prenatal growth assessment score (-icPGAS)). The fetal growth pathology score 1 (-FGPS1), calculated cumulatively from serial -icPGAS values, was used to characterize third-trimester growth patterns. Vascular-system evaluation included umbilical artery (UA) and middle cerebral artery (MCA) Doppler velocimetry. Outcome variables were birth age (preterm/term delivery) and BW (expressed as growth potential realization index for weight (GPRIWT ) and percentile). The findings from the AGA cohort were compared with those from small fetuses (EFW < 10th percentile) with BW < 10th percentile (small-for-gestational-age (SGA) cohort). The AGA cohort was found to have 134 fetuses (70%) with normal growth pattern and 57 (30%) with growth restriction based on IGA criteria. Seven growth-restriction -FGPS1 patterns were observed, including the previously defined progressive, late, adaptive and recovering types. The recovering type was the most common growth pattern in the AGA cohort (50.9%). About one-third of fetuses without any evidence of growth restriction had significant unexplained abnormalities in the UA (34%) and MCA (31%) and elevated mean GPRIWT values (113 ± 12.5%). Comparison of the AGA and SGA cohorts indicated a significant difference in the distribution of -FGPS1 growth patterns (P = 0.0001). Compared with the SGA cohort, the AGA cohort had more fetuses with a normal growth pattern (70% vs 38%) and fewer cases with growth restriction (30% vs 62%). While the recovering type was the most common growth-restriction pattern in the AGA cohort (51%), the progressive type was the primary growth-restriction pattern in the SGA cohort (44%). No difference in the incidence of MCA or UA abnormality was found between the SGA and AGA cohorts when comparing subgroups of more than 10 fetuses. Both normal-growth and growth-restriction patterns were observed in the AGA cohort using IGA, as seen previously in the SGA cohort. The seven types of growth restriction defined in the SGA cohort were also identified in AGA cases, but their distribution was significantly different. In one-third of cases without evidence of growth pathology in the AGA cohort, Doppler abnormalities in the UA and MCA were seen. This heterogeneity underscores the difficulty of accurate classification of fetal and neonatal growth status using conventional population-based methods. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

To determine whether a single elevated myocardial performance index (MPI) value in the third trimester of pregnancy is a marker for later adverse obstetric outcomes in stable placental-mediated disease, defined as well-controlled pre-eclampsia (PE) on a single agent and/or uncompensated intra-uterine growth restriction (IUGR). Fifty-five foetuses whose mothers had stable placental-mediated disease, either mild pre-eclampsia controlled on a single agent, and/or uncompensated IUGR in the third trimester, attending the Foetal Unit at Inkosi Albert Luthuli Hospital, Durban, South Africa were prospectively recruited with 55 matched controls. Recorded data for the subjects included demographic data of maternal age and parity, sonographic data of estimated foetal weight (EFW) and amniotic fluid index (AFI), myocardial performance index (MPI), and foetal Doppler data of the umbilical artery (UA), middle cerebral artery (MCA) and ductus venosus (DV). The mean gestational age in the controls, the IUGR and any PE cases was 31.4, 31.8 and 31.0 weeks, respectively. The distribution of MPI values was significantly lower in the controls compared to all other groups. The highest standardised MPI values were observed in the PE-IUGR group, where a median of 5.62 was observed. The only significant differences observed between the PE and IUGR groups was the UA resistance index (p = 0.01), where the IUGR cases tended to have higher UA values compared to the combined PE group. Borderline statistical significance was observed for the MCA resistance index values ( p = 0.05) between these groups. The overall adverse event rate in the cases was 49%. The highest rate was observed in the PE + IUGR group, where eight out of 12 (67%) experienced adverse events. MPI z-scores served as a good marker of adverse events, as evidenced by the total area under the curve (AUC) of 0.90 on the ROC curve. A cut-off value of 4.5 on the MPI z-score conferred a sensitivity of 89% and specificity of 68% for an adverse event later in pregnancy. In univariate logistic regression, MPI z-score, AFI, EFW, UA Doppler, CPR category, DV Doppler and MCA Doppler were assessed separately as potential predictors of adverse outcome. The only significant predictor of adverse outcome was MPI z-score. A single elevated value of the MPI ( z-score > 4.5) in the third trimester in stable placental-mediated disease was a strong indicator of adverse obstetric outcomes later in pregnancy. This has the potential to be incorporated in conjunction with standard monitoring models in stable placental-mediated disease to predict an adverse event later in pregnancy and thus to reduce perinatal morbidity and mortality.

Objectives: “Heart sparing” refers to prominent antegrade fetal coronary artery (CA) blood flow readily visualized by color Doppler and is a harbinger of poor outcome in growth restricted fetus, but little is known of the features and presentation of heart sparing in normally grown fetuses. Our objective was to describe heart sparing effects in normally grown fetuses, and compare the presentation and outcome of heart sparing between fetuses with growth restriction and those who were normally grown.Methods: In a series of fetuses with prominent antegrade CA flow, we assessed Doppler flow profiles in the aortic isthmus, ductus venosus (DV), umbilical vein (UV), umbilical artery (UA) and middle cerebral artery (MCA). We calculated MCA and UA systolic/diastolic ratios and the cerebral placental ratio, and measured fetal biometry. We evaluated cardiac function using the myocardial performance index (MPI) and the cardiovascular profile score (CVPS).Results: Ten fetuses with heart sparing had normal DV flow at 24–36.6 (mean 30.9) weeks of gestation. Five had growth restriction (Group 1); 4/5 had normal MPI and CVPS, and one died. Five were normally grown (Group 2); 5/5 had elevated MPI and decreased CVPS, of these 2 died in utero and one died immediately after birth despite urgent delivery. Coronary arteries were normal after birth or autopsy.Conclusions: Heart sparing confers a poor prognosis in fetal growth restriction and in normally grown fetuses with cardiac dysfunction. We suggest CA flow be assessed in all high-risk fetuses.

Guideline No. 442: Fetal Growth Restriction: Screening, Diagnosis, and Management in Singleton Pregnancies

After completing this article, readers should be able to: Uteroplacental circulatory insufficiency (UPI) accounts for more than 70% of intrauterine growth restriction (IUGR) (1) and is associated with an increased risk of hypoxemic stress and nutritional deficiency. Both of these threats are concomitant and, to some extent, interrelated, but more importantly, both could lead to the feared complication of UPI—cerebral damage and secondary neurodevelopmental disabilities. To better appreciate the challenge involved in establishing the best time to deliver fetuses that have placental insufficiency, this article is divided in two parts. In the first section, present knowledge of the pathophysiology of fetal hypoxemia and nutritional deficiency in the context of UPI is reviewed briefly. The second section is devoted to a critical appraisal of the criteria currently applied to reach the decision that a fetus that has IUGR should be delivered.Fetal arterial oxygen (O2) concentrations are the result of relative proportions of blood that has different O2 saturations from various venous channels (the two venae cavae, the pulmonary veins, the coronary sinus, and the umbilical vein) draining into the cardiac cavities. Final arterial O2 saturation, therefore, predominantly is dictated by the volume of better-oxygenated blood arriving from the umbilical circulation. Normally, because of its low vascular resistance, the placenta accommodates 50% of the fetal combined cardiac output. Any change in this determinant part of venous return necessarily has a significant impact on intrauterine O2 delivery, even if Po2 in the umbilical vein is within normal range. Experimental (2)(3) and clinical (4)(5) investigations have established that UPI, which is associated with increased placental vascular resistance, causes fetal hypoxemia primarily by reducing umbilical blood flow. The fetus, however, still can maintain adequate cerebral oxygenation because of the many adaptive defense mechanisms summarized in the Table T1. (6) This condition corresponds to the “compensated phase” of hypoxemia. Nitric oxide appears to be an important factor, both in control of resting tone of the fetal cerebral vasculature (7) and as a mediator of the cerebral vasodilatory response to hypoxia. (8)The clinical and ultrasonographic features of the compensated phase of fetal hypoxemia are well-defined. Fetal weight gain is deficient but present. Results of conventional monitoring tools, such as nonstress testing (NST), computerized cardiotocogram (cCTG), and biophysical profile, (9) are all within the normal range. With Doppler monitoring, diastolic flow in the umbilical artery is either decreased or absent (Fig. 1A). The presence of an increased diastolic component in the middle cerebral artery is the rule, reflecting cerebral vasodilatation (Fig. 1B) and the so-called “brain-sparing effect.” At the level of the ductus venosus, the degree of red cell deceleration during atrial contraction (“a” wave) is usually within the normal range, confirming normal ventricular compliance (Fig. 1C). The physician can conclude with confidence that placental circulatory insufficiency is present with moderate hypoxemia but without cerebral hypoxia. The duration of moderate hypoxemic stress is, however, an additional element whose impact on postnatal life remains difficult to evaluate.In severe hypoxemia, the defense system is overwhelmed, resulting in metabolic acidemia and cerebral hypoxia. (10) The clinical and ultrasonographic features of this “decompensated phase” are well-documented. Fetal weight gain is nil or insignificant. Oligohydramnios usually is associated. The NST and cCTG show a reduction of fetal heart rate variability, and the biophysical profile is abnormal. In the umbilical artery, Doppler velocimetry shows either an absent or, more frequently, holodiastolic retrograde flow (Fig. 2A). Signs of cerebral vasodilatation are apparent (Fig. 2B). Ventricular diastolic dysfunction is expressed by an abnormally deep “a” wave on the ductus venosus, reaching the zero velocity line or sometimes being retrograde (Fig. 2C). In fetuses that have severe acidosis and are close to circulatory collapse, cerebral vasodilatation can disappear, heralding imminent fetal demise. (11)Fetal development depends on the availability of essential substrates that interact with the fetal genetic drive to growth. Oxygen, amino acids, and principally glucose have been shown to be major substrates for fetal growth and energy production. (12) Compelling evidence suggests that insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) play a major role in mediating the chain of metabolic events associated with fetal development. (13)(14)(15)(16) Expression of these growth factors can be modified by extrinsic influences such as nutrient supply and oxygen. Reduced nutrient availability is accompanied by a rapid and sustained decline of IGF bioactivity, at least in the rat. More disturbing is the observation in transgenic mice that the abnormal expression of IGFBP-1, an inhibitor of IGF action not normally expressed in the brain, results in suppression of brain growth. (17) Although species differences are possible, these data, transposed to the clinical setting, could mean that growth-restricted fetuses, even if delivered before the appearance of signs of hypoxic injury to the central nervous system, might still be at risk of neurodevelopmental disabilities and adverse health events in postnatal life. It is generally assumed, however, that the recirculation process that characterizes the “brain-sparing effect” of the compensated phase of hypoxemia by maintaining oxygen delivery to the brain (18) also should provide sufficient essential substrates for adequate brain development. (19) This would explain the asymmetric growth classically observed in such fetuses, characterized by diminished somatic growth and normal head size.Although oxygen and substrates might be satisfactorily supplied to the brain during the compensated phase of UPI, epidemiologic investigations into the long-term consequences of fetal nutrient deprivation indicate a higher incidence of diabetes, hypertension, and coronary artery disease among adults who were smaller than normal at birth. (20)(21)(22) Such findings strongly suggest interactions between genotype and the intrauterine environment, with resulting changes in gene expression. Finally, the widely accepted concept that reduced weight gain is part of the fetal defense system by decreasing oxygen consumption is flawed by the fact that hyperplastic development occurs in some vital organs strictly during the fetal period, especially the brain and the heart.IUGR, therefore, must be considered as the response to an inadequate environmental condition to ensure successful fetal survival, but this adaptive process can produce adverse fetal, neonatal, and adult consequences.Based on the pathophysiology of fetal nutritional deficits, evidence of growth restriction alone could be a valid indication for delivery to prevent the impact of fetal undernutrition on cardiovascular and metabolic diseases in adult life. However, systematic delivery of all fetuses that exhibit growth deficiency would increase significantly the incidence of preterm births and the well-known risks associated with prematurity. The Growth Restriction Intervention Trial evaluated the effect of early versus delayed delivery in the presence of abnormal umbilical artery Doppler velocimetry. (23)(24) The results of this multicenter study showed no significant difference in overall perinatal mortality rate between early and delayed delivery, resulting from increased fetal mortality associated with expectant management and increased neonatal mortality associated with early intervention. The median Griffith developmental quotient in survivors at 2 years of age was similar in both groups. Whether early delivery makes a difference in general health later in life remains to be elucidated.At present, it generally is agreed that as long as the “compensated phase” is efficient in maintaining adequate cerebral oxygenation, pregnancy prolongation is justified. Most attending perinatologists only intervene in the absence of a minimal weight gain or the appearance of signs of “decompensation.” The problem with this approach is that alterations in fetal heart rate (documented by NST, cCTG) and biophysical profile (fetal body movement and tone) are manifestations of central nervous system impairment and correlate well with the development of metabolic acidemia and intrauterine death, (25) which must be avoided. Furthermore, due to impressive improvements in the management of preterm neonates in recent decades, the survival rate is becoming less of an issue and no longer can be considered as the only outcome measure in the assessment of IUGR pregnancy management. In reality, among the offspring delivered to mothers according to conventional approaches, neurodevelopmental disabilities, including learning and attention deficits, behavioral disorders, and in severe cases, cerebral palsy and mental retardation, have been diagnosed in 30% to 50% of survivors. (26)Obviously, the optimal timing of delivery of fetuses that have IUGR should be based on reliable criteria that allow perinatologists to identify those that shortly will experience decompensation. These criteria should avoid too early delivery and extreme prematurity as well as too late fetal extraction, thus preventing the risk of prolonged exposure to nutrient deficits and hypoxic acidemia. Unfortunately, reliable criteria of impending decompensation in such fetuses currently are not available. (27)(28)The ratio between pulsatility indices of the umbilical and cerebral arteries, which reflects the “brain-sparing effect,” has been shown to be of little help in preventing neurologic abnormalities in fetuses that have IUGR. (29) Much now is being expected from venous Doppler velocimetry in the search for markers of impending breakdown of the fetal defense mechanism against hypoxemia. (30)(31)(32)(33) The flow velocity waveforms of the veins close to the heart are influenced by cyclic atrial pressures changes. Two forward waves are observed: one during atrial filling concomitant to ventricular systole (s wave), the other during the early part of diastole corresponding to ventricular relaxation (D wave). During the second part of diastole, atrial contraction causes a deceleration of the venous flow (“a” wave), which normally remains anterograde. The deepness of the “a” wave varies according to ventricular compliance, with lower compliance associated with a deeper “a” wave. When the loss of compliance is severe, the deceleration can reach the zero velocity line or even become retrograde. The major drawback with venous Doppler velocimetry is that it reflects the diastolic function of the myocardium, which is much more resistant to low oxygen supply than brain cells. Waiting for arbitrarily determined venous Doppler abnormalities to occur, therefore, might be too late in terms of brain integrity. The “brain-sparing effect” is another confounding element to interpretation of venous velocimetry because blood flow redistribution maintains normal or close to normal cerebral perfusion on the one hand and, consequently, normal venous return through the superior vena cava on the other hand. Meanwhile, increased placental vascular resistance and the secondary decline in placental blood flow, added to vasoconstriction of the mesenteric vascular network, decrease volume flow through the inferior vena cava. The resulting blood redistribution causes a deeper atrial deceleration wave in the inferior compared with the superior vena cava (34) without necessarily associated myocardial diastolic dysfunction. Although linkage of fetal arterial and venous Doppler velocimetry with fetal heart rate monitoring recently has been demonstrated to decrease the perinatal morbidity and mortality of fetuses that have IUGR, postnatal neurodevelopmental outcome of the survivors was not taken into consideration in these studies. (30)(35) The degree of changes in ductus venosus Doppler waveforms that would correspond to impending cerebral hypoxia is presently unknown. The answer could come from the TRUFFLE randomized trial comparing the results of deliveries based on cCGT with ductus venosus Doppler. (36)Experimental and clinical data support the incorporation of Doppler flow velocity waveforms through the aortic isthmus among the noninvasive markers of fetal well-being. (2)(37) The aortic isthmus is localized between the left subclavian artery perfused by the left ventricle and the ductus arteriosus perfused by the right ventricle. It represents the only link between the two parallel ventriculoarterial systems. Because of this unique anatomic position, isthmic flow velocity waveforms are influenced not only by downstream impedance of the subdiaphragmatic circulation but also by changes in arterial tone in the upper part of the body, especially the brain. In normal circumstances, due to the low resistance of the placental vascular bed, there is an antegrade flow in the isthmus during diastole. (38) In the presence of increased placental vascular resistance, changes in diastolic flow in the isthmus precede those in the umbilical artery, decreasing early in the process and rapidly becoming retrograde. (39)(40) When flow reverses in the aortic isthmus because of UPI, blood coming from the pulmonary artery and descending aorta is diverted from its normal destination (primarily the placenta), and the brain is partly perfused by blood deprived of placental or maternal substrates essential for its development and by red cells poorly saturated with oxygen. The greater the reverse isthmic flow, the higher the risk of prenatal cerebral damage. However, the dichotomized categorization of diastolic flow through the aortic isthmus (forward versus reverse) does not allow establishment of a cut-off point beyond which the risk of cerebral hypoxia is significantly increased. An isthmic flow index (IFI), therefore, was designed that takes into account the amount and direction of diastolic isthmus flow on a continuous scale. The IFI is obtained by dividing the sum of systolic and diastolic Doppler flow velocity integrals by systolic flow integrals (IFI=S+D/S). Normal values for this index were published recently. (41) Under normal conditions, systolic and diastolic flows are antegrade, and the IFI is always above 1. The IFI becomes equal to 1 when no flow is recorded during diastole in the isthmus with increased placental resistance. In more severe cases, reverse flow appears in diastole; the IFI is lower than 1 but is still positive because of the dominant forward flow in systole. In very severe cases, reverse diastolic flow is dominant, and the IFI is negative.Correlation between the IFI and the postnatal developmental outcome of 48 fetuses that had placental circulatory insufficiency was assessed in a pilot study. (37) All fetuses were delivered according to conventional criteria. An inverse correlation was found between the IFI and postnatal neurodevelopmental outcome. An IFI of 0.7 was suggested by this study as a cut-off value on which the decision to deliver could be based. However, a larger study is needed before reaching a final conclusion on this cut-off point. It is noteworthy that 16 of 35 fetuses considered to be in a safe zone (IFI &gt;0.7) and theoretically protected from cerebral hypoxia manifested evidence of neurodevelopmental impairment. This observation could reinforce the concept that in growth-restricted fetuses, the integrity of the central nervous system depends not only on oxygen delivery but also on the sufficient availability of essential substrates.Timing delivery in pregnancies complicated by IUGR is a major issue that remains unresolved. To date, no single test can discriminate between fetuses that will benefit from immediate delivery and those that will profit from a more conservative approach. A combination of parameters, including gestational age, severity of IUGR, and results of prenatal testing, still is advocated by most investigators. Combined efforts of multidisciplinary groups of investigators should focus on finding noninvasive markers of impending cerebral hypoxia that would encompass both venous and arterial Doppler velocimetries. Emphasis should be placed on postnatal neurodevelopment and the general health status of the survivors, rather than on immediate fetal or neonatal survival.

Doppler velocimetry for predicting fetal death in a twin pregnancy

To investigate hemodynamic effects after antenatal corticosteroids (ACS) administration in appropriate for gestational age (AGA) and early growth restricted (GR) fetuses by measurement of Doppler cardiovascular function parameters. Prospective cohort study. AGA and GR singleton pregnancies receiving ACS for fetal lung maturation between 24 + 0-33 + 6 weeks were enrolled. Feto-placental vascular hemodynamics were studied by: umbilical artery (UA) pulsatility index (PI), middle cerebral artery (MCA) PI, renal artery (RenA) PI. Cardiac function was evaluated by ductus venosus (DV) PI and by echocardiographic parameters: E to A wave ratios (E/A) and mitral and tricuspid annular plane systolic excursion (MAPSE and TAPSE) for diastolic function, left and right myocardial performance index (MPI) for overall (diastolic and systolic) function. A single operator performed all the measurements at 3 different time points (E): E0 before or within 4 hours of ACS administration (baseline examination), E1 24-48 hours after the first dose and E2 7 days after the second dose of ACS. The values were expressed as z-scores. Pairwise comparisons with paired t-test were performed to compare measurements before and after exposure to ACS. 25 AGA and 20 GR fetuses (mean gestational age: 31 + 1 and 30 + 6, respectively) were included in the analysis. In the AGA group ACS administration was associated with a significant reduction in UA PI. In the GR fetuses ACS temporarily (E0-E1) restored UA-end diastolic flow (EDF) in 6 of 9 fetuses with A/R-EDF ("Return of EDF phenomenon") and produced a significant increase (worsening) in right MPI (both in E1-E2 and in E0-E2). ACS administration is associated with UA vasodilation in both AGA and GR fetuses and with an increase in right MPI in the latter group. This suggests a worsening in cardiac function in GR fetuses.

BackgroundIntrauterine growth restriction (IUGR) is a common diagnosis in obstetrics and carries an increased risk of perinatal mortality and morbidity. Identification of IUGR is crucial because proper evaluation and management can result in a favourable outcome. Cardiovascular dysfunction and remodelling is a central feature of IUGR. The aim of the study was to use the left modified myocardial performance index (MPI), assess cardiac function in foetuses with intrauterine growth restriction (IUGR) compared to healthy foetuses, and to connect the relationship between changes in MPI and perinatal outcome. A prospective study was conducted with 60 singleton foetuses between 24 and 40 weeks of gestation without foetal chromosomal abnormalities or major malformations, divided into two groups: 30 women with intrauterine growth restriction (30 women) and another 30 women with normal pregnancies (foetal growth pattern appropriate for gestational age and normal heart findings with normal sinus rhythm) who were matched for gestational age and served as the controls. Trans-abdominal ultrasound examination was done with 3.5–7-MHz curvilinear Probe (GE Medical US equipment). The umbilical arteries, middle cerebral artery, and ductus venosus all had blood flow velocity waveforms recorded. The pulsatility index (PI), cerebroplacental ratio (CPR), and Doppler velocimetry (DV) of the umbilical artery were all measured. All foetuses had their myocardial performance index assessed. Normal and abnormal umbilical artery(UA) Doppler, as well as normal and abnormal MCA Doppler, were used to examine the intrauterine growth restriction group. Foetal growth restrictions (FGR) foetuses' Mod-MPI values were compared to gestation-matched controls. The outcomes of the perinatal period were documented.ResultsIntrauterine growth restriction foetuses with defective umbilical arteries Doppler had a substantially higher mean left myocardial performance index (mean 0.58 SD 0.093) than healthy foetuses (mean 0.45SD 0.070) (P 0.001). When compared to the control group, IUGR foetuses with abnormal left myocardial performance index had a significantly worse perinatal outcome and higher morbidity. When compared to intrauterine growth restriction foetuses with normal MPI, intrauterine growth restriction foetuses with defective left MPI had a significantly worse perinatal outcome (whether the UA Doppler was normal or abnormal). Based on the perinatal result, the foetal myocardial performance index was linked to the severity of foetal impairment in intrauterine growth restriction foetuses.ConclusionMPI has the potential to be a useful technique for evaluating IUGR pregnancies and predicting neonatal outcome. Within the IUGR foetuses, MPI foetal echocardiographic characteristics can define a high-risk group.

To estimate the value of gestational age at birth and fetal Doppler parameters in predicting the risk of neonatal cranial abnormalities in intrauterine growth-restricted (IUGR) fetuses born between 28 and 34 weeks' gestation. Fetal Doppler parameters including umbilical artery (UA), middle cerebral artery (MCA), aortic isthmus, ductus venosus and myocardial performance index were evaluated in a cohort of 90 IUGR fetuses with abnormal UA Doppler delivered between 28 and 34 weeks' gestation and in 90 control fetuses matched for gestational age. The value of gestational age at birth and fetal Doppler parameters in predicting the risk of ultrasound-detected cranial abnormalities (CUA), including intraventricular hemorrhage, periventricular leukomalacia and basal ganglia lesions, was analyzed. Overall, IUGR fetuses showed a significantly higher incidence of CUA than did control fetuses (40.0% vs 12.2%, respectively; P < 0.001). Within the IUGR group, all predictive variables were associated individually with the risk of CUA, but fetal Doppler parameters rather than gestational age at birth were identified as the best predictor. MCA Doppler distinguished two groups with different degrees of risk of CUA (48.5% vs 13.6%, respectively; P < 0.01). In the subgroup with MCA vasodilation, presence of aortic isthmus retrograde net blood flow, compared to antegrade flow, allowed identification of a subgroup of cases with the highest risk of CUA (66.7% vs 38.6%, respectively; P < 0.05). Evaluation of fetal Doppler parameters, rather than gestational age at birth, allows identification of IUGR preterm fetuses at risk of neonatal brain abnormalities.

Objective Prenatal ultrasound (US) has been shown to overestimate the incidence of suspected fetal growth restriction (FGR) in gastroschisis cases. This is largely because of altered sonographic abdominal circumference (AC) measurements when comparing gastroschisis cases with population nomograms. Individualized Growth Assessment (IGA) evaluates fetal growth using serial US measurements that allow consideration of the growth potential for a given case. Our goal was to assess the utility of IGA for distinguishing normal and pathological fetal growth in gastroschisis cases. Study design Pregnancies with prenatally diagnosed fetal gastroschisis were managed and delivered at a single academic medical center. US fetal biometry including head circumference (HC), abdominal circumference (AC), and femur diaphysis length (FDL), and neonatal measurements including birthweight and HC were collected and analyzed for 32 consecutive fetal gastroschisis cases with at least two 2nd and two 3rd trimester measurements. Second trimester growth velocities were compared to a group of 118 non-anomalous fetuses with normal neonatal growth outcomes. Gastroschisis cases were classified into groups based on fetal growth pathology score (FGPS9) patterns. Agreement between IGA (FGPS9) and serial conventional estimated fetal weight (EFW) measurements for determining growth pathology was evaluated. Neonatal size outcomes were compared between conventional birthweight classifications for determining small for gestational age (SGA) and IGA Growth Potential Realization Index (GPRI) for weight and head circumference measurements. Results Fetal growth pathology score (FGPS9) measurements identified three in-utero growth patterns: no growth pathology, growth restriction and recovery, and progressive growth restriction. In the no growth pathology group (n = 19), there was 84% agreement between IGA and conventional methods in determining pathological growth in both the 3rd trimester and at birth. In the growth restriction and recovery group (n = 7), there was 71% agreement both in the 3rd trimester and at birth between IGA and conventional methods. In the progressive growth restriction group (n = 5), there was 100% agreement in the 3rd trimester and 60% agreement at birth between IGA and conventional methods. Conclusion We present the first study using IGA to evaluate normal and pathological fetal growth in prenatally diagnosed gastroschisis cases. IGA was able to delineate two 3rd trimester growth pathology patterns – one with persistent growth restriction and another with in-utero growth recovery. Further validation of these initial findings with larger cohorts is warranted.

After completing this article, readers should be able to: 1. Describe the calculations used to measure fetal systemic and placental vascular impedance in the umbilical artery via Doppler ultrasonography. 2. Delineate the two primary uses of measurement of middle cerebral artery flow velocity. 3. List the fetal conditions in which Doppler flow velocity has been studied. The Doppler principle, discovered by Johann Christian Andreas Doppler in 1842, (1) was used initially in astronomy and later in the military, in various branches of industry, and more recently in medicine. Doppler shift is based on the perceived change in frequency of an energy waveform as the source and the receiver move toward or away from each other. The Doppler shift principle applies to light waves as well as sound waves. In biology, Doppler ultrasonography is used noninvasively, primarily to measure flow velocity in blood vessels. Flow velocity depends on the volume and speed of effluent relative to the diameter of the vessel. Estimating fetal vascular resistance through study of Doppler flow velocity provides a means to assess, albeit indirectly, fetal physiology and pathology. Johnson and colleagues (2) in 1965, made the earliest mention of the use of Doppler effect in obstetrics. The use of Doppler ultrasonography to investigate the pattern of waveforms in the umbilical artery during pregnancy initially was reported in 1977 by Fitzgerald and Drumm. (3) Subsequently, Wladimiroff and associates (4) reported on Doppler assessment of cerebral blood flow in the human fetus. The addition of color mapping has enhanced the utility of the Doppler effect in sonographic assessment of the fetus. The fetal umbilical artery (UA) and middle cerebral artery (MCA) have evolved as the primary targets of fetal Doppler studies (Figs. 1 and 2). Figure 1. Color Doppler view of circle of Willis. Arrows show anterior (ACA), middle (MCA), and posterior cerebral …

Absent/reverse flow in the umbilical artery: A very poor prognosis

ISUOG Practice Guidelines: role of ultrasound in twin pregnancy.