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Objective: To compare maternal vascular indices and hemodynamic parameters at 35-37 weeks' gestation in pregnancies complicated by delivery of a small-for-gestational-age (SGA) or growth-restricted (FGR) neonate., Methods: This was a prospective observational study of women with a singleton pregnancy attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. The visit included recording of maternal demographic characteristics, medical history, vascular indices and hemodynamic parameters, which were obtained using a non-invasive operator-independent device and included pulse-wave velocity, augmentation index, cardiac output, stroke volume, central systolic and diastolic blood pressure, total peripheral resistance and heart rate. Women with hypertensive disorders of pregnancy were excluded. SGA was diagnosed if birth weight was < 10 th percentile. FGR was diagnosed if, in addition to birth weight < 10 th percentile, at the 35-37-week scan, uterine artery or umbilical artery pulsatility index (PI) was > 95 th percentile or fetal middle cerebral artery PI was < 5 th percentile., Results: Among the 6413 women included in the study, there were 605 (9.4%) cases of SGA, 133 (2.1%) cases of FGR and 5675 (88.5%) cases that were unaffected by SGA or FGR. Women with SGA or FGR, compared to unaffected pregnancies, had increased peripheral vascular resistance and reduced cardiac output. Central systolic and diastolic blood pressure were increased in the FGR group compared with the unaffected group. Aortic stiffness, as assessed by pulse-wave velocity, and augmentation index did not differ between affected and unaffected pregnancies. In the FGR group, compared with the SGA group, central systolic and diastolic blood pressure were higher, whereas heart rate was lower., Conclusions: SGA and FGR pregnancies exhibit deranged maternal hemodynamic responses compared with unaffected pregnancies. Pregnancies with FGR have higher central blood pressure compared to those with SGA, but it remains unclear whether these differences are driven by the size of the fetus or pathological fetal growth. © 2024 International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: Fetuses with late-onset growth restriction (FGR) have a higher risk of suboptimal neurocognitive performance after birth. Previous studies have reported that impaired brain and cortical development can start in utero. The primary aim of this study was to report midline structure growth and cortical development in fetuses with late-onset FGR according to its severity; the secondary aim was to elucidate whether the severity of FGR, as defined by the presence of abnormal Doppler findings, plays a role in affecting brain growth and maturation., Methods: This was a prospective observational study that included fetuses with late-onset FGR (defined according to the Delphi FGR criteria) undergoing neurosonography between 32 and 34 weeks' gestation. Midline structure (corpus callosum (CC) and cerebellar vermis (CV)) length and cortical development, including the depth of the Sylvian (SF), parieto-occipital (POF) and calcarine (CF) fissures, were compared between late-onset FGR, small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) fetuses. Subgroup analysis according to the severity of FGR (normal vs abnormal fetal Doppler) was also performed. Univariate analysis was used to analyze the data., Results: A total of 52 late-onset FGR fetuses with normal Doppler findings, 60 late-onset FGR fetuses with abnormal Doppler findings, 64 SGA fetuses and 100 AGA fetuses were included in the analysis. When comparing AGA controls with SGA fetuses, late-onset FGR fetuses with normal Doppler findings and late-onset FGR fetuses with abnormal Doppler findings, there was a progressive and significant reduction in the absolute values of the following parameters: CC length (median (interquartile range (IQR)), 43.5 (28.9-56.1) mm vs 41.9 (27.8-51.8) mm vs 38.5 (29.1-50.5) mm vs 31.7 (23.8-40.2) mm; K = 26.68; P < 0.0001), SF depth (median (IQR), 14.5 (10.7-16.8) mm vs 12.7 (9.8-15.1) mm vs 11.9 (9.1-13.4) mm vs 8.3 (6.7-10.3) mm; K = 75.82; P < 0.0001), POF depth (median (IQR), 8.6 (6.3-11.1) mm vs 8.1 (5.6-10.4) mm vs 7.8 (6.1-9.3) mm vs 6.6 (4.2-8.0) mm; K = 45.06; P < 0.0001) and CF depth (median (IQR), 9.3 (6.7-11.5) mm vs 8.2 (5.7-10.7) mm vs 7.7 (5.2-9.4) mm vs 6.3 (4.5-7.2) mm; K = 46.14; P < 0.0001). Absolute CV length was significantly higher in AGA fetuses compared with all other groups, although the same progressive pattern was not noted (median (IQR), 24.9 (17.6-29.2) mm vs 21.6 (15.2-26.1) mm vs 19.1 (13.8-25.9) mm vs 21.0 (13.5-25.8) mm; K = 16.72; P = 0.0008). When the neurosonographic variables were corrected for fetal head circumference, a significant difference in the CC length and SF, POF and CF depths, but not CV length, was observed only in late-onset FGR fetuses with abnormal Doppler findings when compared with AGA and SGA fetuses., Conclusions: Fetuses with late-onset FGR had shorter CC length and delayed cortical development when compared with AGA fetuses. After controlling for fetal head circumference, these differences remained significant only in late-onset FGR fetuses with abnormal Doppler. These findings support the existence of a link between brain development and impaired placental function. © 2024 International Society of Ultrasound in Obstetrics and Gynecology., (© 2024 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To investigate the relationship of umbilical vein flow (UVF) measured close to term with abnormal fetal growth and adverse perinatal outcome in a cohort of pregnancies at low risk of placental insufficiency., Methods: This was a prospective multicenter observational study conducted across two tertiary maternity units. Patients with a singleton appropriate-for-gestational-age fetus between 35 and 38 weeks' gestation were included. Pregnancies at higher risk of placental insufficiency or with fetal anomalies were excluded. At ultrasound examination, the abdominal circumference (AC), umbilical vein diameter and peak velocity of the umbilical vein were measured, and, using these variables, a new variable, UVF/AC, was calculated. The primary outcome was the occurrence of severely stunted fetal growth, defined as a greater than 40-percentile drop between estimated fetal weight at the third-trimester ultrasound and birth weight. The occurrence of adverse perinatal outcome (defined as one of the following: neonatal acidosis (umbilical artery pH < 7.15 and/or base excess > 12 mmol/L) at birth, 5-min Apgar score < 7, neonatal resuscitation or neonatal intensive care unit admission) was analyzed as a secondary outcome., Results: Between April 2021 and March 2023, 365 women were included in the study. The mean UVF/AC at enrolment was 6.4 ± 2.6 mL/min/cm, and 35 (9.6%) cases were affected by severely stunted fetal growth. Severely stunted fetal growth was associated with a lower mean UVF/AC (5.4 ± 2.6 vs 6.5 ± 2.6 mL/min/cm; P = 0.02) and a higher frequency of UVF/AC < 10 th percentile (8/35 (22.9%) vs 28/330 (8.5%); P = 0.01). Moreover, UVF/AC showed an area under the receiver-operating-characteristics curve (AUC) of 0.65 (95% CI, 0.55-0.75; P = 0.004) in predicting the occurrence of severely stunted fetal growth, and the optimal cut-off value of UVF/AC for discriminating between normal and severely stunted fetal growth was 7.2 mL/min/cm. This value was associated with a sensitivity and specificity of 0.77 (95% CI, 0.60-0.90) and 0.33 (95% CI, 0.28-0.39), and positive and negative predictive values of 0.11 (95% CI, 0.07-0.15) and 0.93 (95% CI, 0.87-0.97), respectively. Regarding the occurrence of adverse perinatal outcome, this was associated independently with maternal age (adjusted odds ratio (aOR), 0.93 (95% CI, 0.87-0.99); P = 0.04), UVF/AC Z-score (aOR, 0.53 (95% CI, 0.30-0.87); P = 0.01) and augmentation of labor (aOR, 2.69 (95% CI, 1.28-5.69); P = 0.009). UVF/AC showed an AUC of 0.65 (95% CI, 0.56-0.73; P = 0.005) in predicting the occurrence of adverse perinatal outcome, and the optimal cut-off value of UVF/AC for discriminating between normal and adverse perinatal outcome was 6.7 mL/min/cm. This value was associated with a sensitivity and specificity of 0.70 (95% CI, 0.54-0.83) and 0.40 (95% CI, 0.34-0.45), and positive and negative predictive values of 0.14 (95% CI, 0.09-0.19) and 0.91 (95% CI, 0.85-0.95), respectively., Conclusions: Our data demonstrate an association between reduced UVF close to term, severely stunted fetal growth and adverse perinatal outcome in a cohort of low-risk pregnant women, with a moderate ability to rule out and a poor ability to rule in either outcome. Further studies are needed to establish whether the assessment of UVF can improve the identification of fetuses at risk of subclinical placental insufficiency and adverse perinatal outcome. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: The primary aim of this study was to evaluate the feasibility of automated measurement of fetal atrioventricular (AV) plane displacement (AVPD) over several cardiac cycles using myocardial velocity traces obtained by color tissue Doppler imaging (cTDI). The secondary objectives were to establish reference ranges for AVPD during the second half of normal pregnancy, to assess fetal AVPD in prolonged pregnancy in relation to adverse perinatal outcome and to evaluate AVPD in fetuses with a suspicion of intrauterine growth restriction (IUGR)., Methods: The population used to develop the reference ranges consisted of women with an uncomplicated singleton pregnancy at 18-42 weeks of gestation (n = 201). The prolonged-pregnancy group comprised women with an uncomplicated singleton pregnancy at ≥ 41 + 0 weeks of gestation (n = 107). The third study cohort comprised women with a singleton pregnancy and suspicion of IUGR, defined as an estimated fetal weight < 2.5 th centile or an estimated fetal weight < 10 th centile and umbilical artery pulsatility index > 97.5 th centile (n = 35). Cineloops of the four-chamber view of the fetal heart were recorded using cTDI. Regions of interest were placed at the AV plane in the left and right ventricular walls and the interventricular septum, and myocardial velocity traces were integrated and analyzed using an automated algorithm developed in-house to obtain mitral (MAPSE), tricuspid (TAPSE) and septal (SAPSE) annular plane systolic excursion. Gestational-age specific reference ranges were constructed and normalized for cardiac size. The correlation between AVPD measurements obtained using cTDI and those obtained by anatomic M-mode were evaluated, and agreement between these two methods was assessed using Bland-Altman analysis. The mean Z-scores of fetal AVPD in the cohort of prolonged pregnancies were compared between cases with normal and those with adverse outcome using Mann-Whitney U-test. The mean Z-scores of fetal AVPD in IUGR fetuses were compared with those in the normal reference population using Mann-Whitney U-test. Inter- and intraobserver variability for acquisition of cTDI recordings and offline analysis was assessed by calculating coefficients of variation (CV) using the root mean square method., Results: Fetal MAPSE, SAPSE and TAPSE increased with gestational age but did not change significantly when normalized for cardiac size. The fitted mean was highest for TAPSE throughout the second half of gestation, followed by SAPSE and MAPSE. There was a significant correlation between MAPSE (r = 0.64; P < 0.001), SAPSE (r = 0.72; P < 0.001) and TAPSE (r = 0.84; P < 0.001) measurements obtained by M-mode and those obtained by cTDI. The geometric means of ratios between AVPD measured by cTDI and by M-mode were 1.38 (95% limits of agreement (LoA), 0.84-2.25) for MAPSE, 1.00 (95% LoA, 0.72-1.40) for SAPSE and 1.20 (95% LoA, 0.92-1.57) for TAPSE. In the prolonged-pregnancy group, the mean ± SD Z-scores for MAPSE (0.14 ± 0.97), SAPSE (0.09 ± 1.02) and TAPSE (0.15 ± 0.90) did not show any significant difference compared to the reference ranges. Twenty-one of the 107 (19.6%) prolonged pregnancies had adverse perinatal outcome. The AVPD Z-scores were not significantly different between pregnancies with normal and those with adverse outcome in the prolonged-pregnancy cohort. The mean ± SD Z-scores for SAPSE (-0.62 ± 1.07; P = 0.006) and TAPSE (-0.60 ± 0.89; P = 0.002) were significantly lower in the IUGR group compared to those in the normal reference population, but the differences were not significant when the values were corrected for cardiac size. The interobserver CVs for the automated measurement of MAPSE, SAPSE and TAPSE were 28.1%, 17.7% and 15.3%, respectively, and the respective intraobserver CVs were 33.5%, 15.0% and 17.9%., Conclusions: This study showed that fetal AVPD can be measured automatically by integrating cTDI velocities over several cardiac cycles. Automated analysis of AVPD could potentially help gather larger datasets to facilitate use of machine-learning models to study fetal cardiac function. The gestational-age associated increase in AVPD is most likely a result of increasing cardiac size, as the AVPD normalized for cardiac size did not change significantly between 18 and 42 weeks. A decrease was seen in TAPSE and SAPSE in IUGR fetuses, but not after correction for cardiac size. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: We have shown previously that third-trimester growth in small fetuses (estimated fetal weight (EFW) < 10 th percentile) with birth weight (BW) < 10 th percentile is heterogeneous using individualized growth assessment (IGA). We aimed to test our hypothesis that individual growth patterns in small fetuses with BW > 10 th percentile are also variable but in different ways., Methods: This was a study of 191 cases with EFW < 10 th percentile and BW > 10 th 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 (GPRI WT ) and percentile). The findings from the AGA cohort were compared with those from small fetuses (EFW < 10 th percentile) with BW < 10 th percentile (small-for-gestational-age (SGA) cohort)., Results: 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 GPRI WT 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., Conclusions: 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., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To investigate if the extent of absent end-diastolic flow (AEDF) on umbilical artery (UA) Doppler velocimetry predicts pregnancy outcome., Methods: This was a retrospective observational study based on data from 25 000 Doppler examinations of UA flow performed between 1998 and 2017 at the Blood Flow Laboratory, Level III Perinatal Center, Lund, Sweden. All pregnancies with AEDF in the UA were identified, and the duration of AEDF as a proportion of the total duration of the cardiac cycle (T a /T tot ratio) was measured in digital images of the Doppler spectrum recorded at the last examination showing AEDF before delivery. Clinical data on pregnancies and neonatal outcomes were extracted from the regional perinatal database and the hospital patient records. The predictive performance of the T a /T tot ratio for intrauterine death and any (intrauterine or postnatal) death was assessed., Results: A total of 170 fetuses (122 (72%) singletons and 48 (28%) twins) were included in the study. Median gestational age at birth was 189.5 days (range, 163-279 days) (i.e. 27 + 0 weeks (range, 23 + 2 to 39 + 6 weeks)), birth weight was 650 g (range, 320-3326 g) and deviation from expected birth weight (standard deviation score) was -2.975 (range, -6.38 to 0.69). There were 15 (9%) intrauterine and 26 (15%) postnatal deaths. The principal outcome variables and their relationship with Doppler velocimetry results did not differ significantly between singletons and twins, giving a rationale for using the T a /T tot ratio in the total study group. Mean T a /T tot ratio was 0.42 ± 0.08 and 0.34 ± 0.08 in stillborn and liveborn fetuses, respectively (P = 0.002). For fetuses examined before 30 weeks' gestation, a T a /T tot ratio cut-off of 0.30 predicted intrauterine death with 92% sensitivity and a negative predictive value (NPV) of 98% (area under receiver-operating-characteristics curve (AUC), 0.74) and predicted any death with 83% sensitivity and a NPV of 85% (AUC, 0.66)., Conclusions: In fetuses with AEDF in the UA, duration of absent flow for at least 30% of the total cardiac cycle length might predict the risk of fetal demise, even when assessed before 30 weeks' gestation. This finding is particularly relevant to growth-restricted fetuses. After evaluation in further studies, the extent of AEDF might facilitate obstetric decision-making in very preterm growth-restricted fetuses. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To describe the short- and long-term outcomes of infants with early-onset fetal growth restriction (FGR) and umbilical artery absent or reversed end-diastolic flow (AREDF), delivered before 30 weeks' gestation and managed proactively., Methods: This was a retrospective cohort study of fetuses delivered for fetal indication before 30 completed weeks' gestation that had early-onset FGR (defined as estimated fetal weight more than 2 SD below the mean) with AREDF in the umbilical artery (FGR group), at the level-3 perinatal unit in Lund, Sweden, between 1998 and 2015. Perinatal outcome and neurodevelopment at ≥ 2 years of age in surviving infants were compared with those of a group of infants without small-for-gestational-age birth weight or any known fetal Doppler changes delivered before 30 weeks in Lund during the corresponding time period (non-FGR group). In the FGR group, the main indication for delivery was the Doppler finding of AREDF in the umbilical artery., Results: There were 139 fetuses (of which 26% were a twin/triplet) in the FGR group and 946 fetuses (of which 28% were a twin/triplet) in the non-FGR group. The FGR infants had a median birth weight of 630 g (range, 340-1165 g) and gestational age at birth of 187 days (range, 164-209 days), as compared with 950 g (range, 470-2194 g) and 185 days (range, 154-209 days), respectively, in the non-FGR group. The rate of fetal mortality did not differ between the two groups (5.0% and 5.4% in the FGR and non-FGR groups, respectively). All seven intrauterine deaths in the FGR group occurred before 26 weeks' gestation. In the FGR group compared with the non-FGR group, severe intraventricular hemorrhage was less frequent and bronchopulmonary dysplasia and septicemia were more frequent (P = 0.008, P < 0.001 and P = 0.017, respectively). In the FGR group, the survival rate at 2 years (83% of liveborn infants) and the rate of cerebral palsy (7%) did not differ significantly from those in the non-FGR group (82% and 8%, respectively). The rate of survival without neurodevelopmental impairment was higher in the non-FGR group (83%) than in the FGR group (62%) (P < 0.001), as well as in infants in the FGR group delivered at or after 26 weeks (72%) compared with those delivered before 26 weeks (40%) (P = 0.003). Within the FGR group, outcomes were similar between twins and singletons and, in those who survived beyond 2 years, outcomes were similar between fetuses with absent and those with reversed end-diastolic flow in the umbilical artery., Conclusions: Infants delivered very preterm after severe FGR with AREDF in the umbilical artery had a similar rate of survival as did non-FGR infants of corresponding gestational age; however, they were at higher risk of neurodevelopmental impairment, the risk being most pronounced following birth before 26 weeks. Gestational age remains an important factor associated with the prognosis of early-onset FGR; nevertheless, the present results support the hypothesis, which should be tested prospectively, that fetuses with early-onset FGR and umbilical artery AREDF may benefit from early intervention rather than expectant management, and that umbilical artery Doppler findings could be incorporated into clinical protocols for cases very early in gestation. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: Echocardiographic studies have reported that fetuses with low birth weight, compared to those with normal birth weight, have globular hearts and reduced cardiac function. Dichotomizing continuous variables, such as birth weight, may be helpful in describing pathology in small studies but can prevent us from identifying physiological responses in relation to change in size. The aim of this study was to explore associations between fetal cardiac morphology and function and birth weight, as a continuous variable, as well as uterine artery (UtA) pulsatility index (PI), as an indirect measure of placental perfusion, and the cerebroplacental ratio (CPR), as an indirect measure of fetal oxygenation., Methods: This was a prospective study of 1498 women with singleton pregnancy undergoing routine ultrasound examination at 35 + 0 to 36 + 6 weeks' gestation. Pregnancies complicated by pregestational or gestational diabetes mellitus, chronic hypertension, pregnancy-induced hypertension or pre-eclampsia were excluded from the analysis. Conventional and more advanced echocardiographic modalities, such as speckle tracking, were used to assess fetal cardiac function in the right and left ventricles. The morphology of the fetal heart was assessed by calculating the right and left sphericity indices. In addition, the PI of the UtA, umbilical artery (UA) and fetal middle cerebral artery (MCA) was determined and the CPR was calculated by dividing MCA-PI by UA-PI. Multiple linear regression models were used to assess determinants of fetal echocardiographic parameters., Results: The study population included 146 (9.7%) small-for-gestational-age (SGA) fetuses with birth weight < 10 th percentile and 68 (4.5%) with fetal growth restriction (FGR). In the SGA and FGR groups, compared to the non-SGA and non-FGR fetuses, respectively, there was a more globular right ventricle and reduced left and right ventricular systolic function, and, from the left ventricular diastolic functional indices, the E/A ratio was increased. There was a linear association of right ventricular sphericity index, indices of left and right ventricular systolic function and E/A ratio with birth-weight Z-score. There were no significant associations between cardiac morphological and functional indices and UtA-PI Z-score or CPR Z-score., Conclusions: This screening study at 35-37 weeks' gestation has demonstrated that birth weight is a determinant of fetal cardiac morphology and function but UtA-PI and CPR, as indirect measures of placental perfusion and fetal oxygenation, are not. This suggests that the differences in fetal cardiac indices between small and appropriately grown fetuses may be part of a normal physiological response to change in fetal size rather than part of a pathological adaptation to abnormal placental perfusion and fetal oxygenation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: Both excessive and restricted fetal growth are associated with changes in cardiac geometry and function at birth. There are significant issues when indexing cardiac parameters for body size in the neonatal period. The aims of this study were to determine to what extent cardiac geometry is dependent on body size in term and preterm neonates with restricted or excessive fetal growth and how this is affected by adiposity., Methods: This was a cross-sectional study of neonates born between 31 and 42 weeks of gestation, divided into three groups: (1) small-for-gestational age (SGA, birth weight > 2 SD below the mean); (2) large-for-gestational age (LGA, birth weight > 2 SD above the mean); and (3) appropriate-for-gestational-age controls (AGA, birth weight ≤ 2 SD from the mean). Cardiac geometry and function were compared between the study groups, adjusting for body size. The potential impact of infant adiposity and maternal disease was assessed., Results: In total, 174 neonates were included, of which 39 were SGA, 45 were LGA and 90 were AGA. Body size was reflected in cardiac dimensions, with differences in cardiac dimensions disappearing between the SGA and AGA groups when indexed for body surface area (BSA) or thoracic circumference. The same was true for the differences in atrial and ventricular areas between the LGA and AGA groups. However, left ventricular inflow and outflow tract dimensions did not follow this trend as, when indexed for BSA, they were associated negatively with adiposity, resulting in diminished dimensions in LGA compared with AGA and SGA neonates. Adiposity was associated positively with left ventricular mass, right ventricular length and area and right atrial area. The SGA group showed increased right ventricular fractional area change, possibly reflecting differences in the systolic function of the right ventricle. We found evidence of altered diastolic function between the groups, with the mitral valve inflow E- to lateral E'-wave peak velocity ratio being increased in the LGA group and decreased in the SGA group., Conclusions: Cardiac geometry is explained by body size in both term and preterm AGA and SGA infants. However, the nature of the relationship between body size and cardiac dimensions may be influenced by adiposity in LGA infants, leading to underestimation of left ventricular inflow and outflow tract dimensions when adjusted for BSA. Adjustments for thoracic circumference provide similar results to those for BSA. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: Our primary aim was to confirm whether intertwin discordance in ventricular strain and ductus venosus (DV) time intervals predicts twin-twin transfusion syndrome (TTTS). Secondary aims were to create gestational-age ranges for ventricular strain in uncomplicated monochorionic diamniotic (MCDA) twin pregnancies without selective intrauterine growth restriction (sIUGR) and to characterize the relationship of ventricular strain with gestational age in MCDA twin pregnancies with sIUGR that did not develop TTTS., Methods: In the period 2015-2018, we enrolled 150 MCDA twin pregnancies consecutively into this prospective, blinded study of global longitudinal left and right ventricular strain. With the observer blinded to twin pairing and pregnancy outcome, videoclips of the four-chamber view, which had been recorded during ultrasound surveillance in the usual window for development of TTTS (16-26 completed gestational weeks), underwent offline measurement of strain. Uncomplicated MCDA twin pregnancies, without sIUGR, were used to test the association between strain, gestational age and estimated fetal weight using mixed-effects multilevel regression. Inter-rater reliability was tested in 208 strain measurements in 31 fetuses from pregnancies which did not develop TTTS and within-fetus variation was assessed in 16 such fetuses, in which multiple four-chamber views were taken on the same day. The effect of sIUGR on strain in otherwise uncomplicated MCDA twin pregnancy was analyzed. MCDA twin pregnancies were defined as 'pre-TTTS' when, having been referred for TTTS evaluation, they did not satisfy Quintero staging criteria, but subsequently developed TTTS requiring laser treatment. MCDA pregnancies which did not develop TTTS comprised the 'non-TTTS' group. Cardiovascular parameters measured in these cases included tissue Doppler parameters and DV early filling time as a percentage of the cardiac cycle (DVeT%). Intertwin strain and DVeT% discordance was compared between non-TTTS and pre-TTTS cases, matched for gestational age., Results: Paired strain data were available for intertwin comparison in 127/150 MCDA twin pregnancies, comprising 14 pre-TTTS and 113 non-TTTS pregnancies, after exclusions. Scans were collected at a median frame rate of 97 (range, 28-220) Hz. Laser therapy was performed at a median gestational age of 20.6 (range, 17.2-26.6) weeks. There were no group differences in right (RV) or left (LV) ventricular strain discordance between 68/113 non-TTTS and 13/14 pre-TTTS MCDA twin pregnancies < 20 completed gestational weeks (RV, P = 0.338; LV, P = 0.932). DVeT% discordance > 3.6% was found in eight of 13 pre-TTTS pregnancies. In non-TTTS pregnancies, the estimated variability in ventricular strain within each twin during the day was high (RV, 19.7; LV, 12.9). However, within each pair (intertwin variation), variability was low (RV, 5.5; LV, 2.9). Interclass correlation reflecting the proportion of total variability represented by the variability between twin pairs was low (RV, 0.22; LV, 0.18). Both RV (P < 0.001) and LV (P = 0.025) strain showed a negative association with gestational age. Among non-TTTS MCDA twin pregnancies, LV strain was, on average, higher by 1.83 in sIUGR compared with normally grown fetuses (P = 0.023), with no statistically significant difference in RV strain (P = 0.271)., Conclusions: Although ventricular strain has been reported previously as a possible predictor of developing TTTS, in this blinded, prospective study, we found no significant intergroup differences in ventricular strain in pre-TTTS compared with age-matched non-TTTS MCDA twin pregnancies. We recommend using DVeT% discordance as a more practical screening tool in MCDA twin pregnancies. This study also provides new information on the changes with gestational age, and the biological and technical variation, of global longitudinal ventricular strain in uncomplicated MCDA twin pregnancies and those with isolated sIUGR. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To analyze the value of the soluble fms-like tyrosine kinase-1/placental growth factor (sFlt-1/PlGF) ratio in predicting the time to delivery in early-onset fetal growth restriction (FGR) with preserved antegrade umbilical artery (UA) flow at diagnosis., Methods: This was a prospective observational single-center cohort study of pregnancies with early-onset (< 32 + 0 weeks) FGR and antegrade UA flow, in which maternal serum sFlt-1/PlGF ratio was determined at diagnosis. FGR was defined as estimated fetal weight < 3 rd centile or < 10 th centile with UA pulsatility index > 95 th centile, fetal middle cerebral artery pulsatility index < 5 th centile or cerebroplacental ratio < 5 th centile. The previously described sFlt-1/PlGF ratio cut-off value of 85 for facilitating the diagnosis of pre-eclampsia was assessed in the prediction of the need to deliver in < 1 week and ≥ 4 weeks., Results: In total, 120 cases were included. There were 116 (96.7%) liveborn neonates and 108 (90.0%) perinatal survivors. Median (interquartile range (IQR)) gestational age at diagnosis of early-onset FGR was 27.1 (25.7-29.4) weeks. Median (IQR) sFlt-1/PlGF ratio at diagnosis was 196 (84-474). Ninety (75.0%) cases had a sFlt-1/PlGF ratio ≥ 85. Among pregnancies with a liveborn neonate, median (IQR) interval to delivery in the groups with sFlt-1/PlGF ratio < 85 and ≥ 85 was 41 (22-54) days and 11 (4-20) days, respectively (P < 0.01). The probability of having to deliver within 1 week after diagnosis was 0% and 35.6% in those with sFlt-1/PlGF ratio < 85 and ≥ 85, respectively (P = 0.03), and the probability of delaying delivery for ≥ 4 weeks was 72.4% and 19.5%, respectively (P < 0.01)., Conclusion: sFlt-1/PlGF ratio < 85 at diagnosis of early-onset FGR with antegrade UA flow identifies a group of pregnancies in which the need to deliver within 1 week is very low and the interval to delivery is expected to be prolonged for ≥ 4 weeks in > 70% of cases. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To investigate the association between absent or reversed end-diastolic flow (ARED) on umbilical artery Doppler ultrasound and poor neurological outcome at 2 years of age after very preterm birth associated with suspected fetal growth restriction (FGR) or maternal hypertensive disorders., Methods: The study population comprised all very preterm (22-31 completed weeks) singleton pregnancies delivered because of suspected FGR and/or maternal hypertensive disorders that had umbilical artery Doppler and 2-year follow-up available included in EPIPAGE-2, a prospective, nationwide, population-based cohort of preterm births in France in 2011. Univariate and two-level multivariable logistic regression analyses were used to assess the association of ARED in the umbilical artery, as compared with normal or reduced end-diastolic flow, with severe or moderate neuromotor and/or sensory disability and with an Ages and Stages Questionnaire (ASQ) score below a threshold. This was defined as a score more than 2 SD below the mean in any of the five domains, at age 2, adjusting for gestational age at delivery. ASQ is used to identify children at risk of developmental delay requiring reinforced follow-up and further evaluation. Descriptive statistics and bivariate tests were weighted according to the duration of the inclusion periods., Results: The analysis included 484 children followed up at 2 years of age, for whom prenatal umbilical artery Doppler ultrasound was available. Among them, 8/484 (1.6%) had severe or moderate neuromotor and/or sensory disability, and 156/342 (45.4%) had an ASQ score below the threshold. Compared with normal or reduced end-diastolic flow in the umbilical artery (n = 305), ARED (n = 179) was associated with severe or moderate neuromotor and/or sensory disability (adjusted odds ratio (OR), 11.3; 95% CI, 1.4-93.2) but not with an ASQ score below the threshold (adjusted OR, 1.2; 95% CI, 0.8-1.9)., Conclusion: Among children delivered before 32 weeks of gestation due to suspected FGR and/or maternal hypertensive disorder who survived until 2 years of age, prenatal ARED in the umbilical artery was associated with a higher incidence of severe or moderate neuromotor and/or sensory disability. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction., Methods: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10 th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20-week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored., Results: The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n = 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5 th percentile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33 weeks and 1.0 at 34-36 weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a stronger association., Conclusion: In this prospective multicenter study, signs of cerebral blood flow redistribution were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology., (© 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To assess the value of computerized cardiotocography (cCTG) with calculation of fetal heart rate (FHR) short-term variability (STV) in early preterm fetal growth restriction (FGR) for prevention of fetal death and neonatal asphyxia, neonatal morbidity, and 2-year neurodevelopmental impairment., Methods: This was a retrospective cohort study of all women who were admitted to the Amsterdam University Medical Center-AMC between 2003 and 2015 due to FGR and/or pre-eclampsia, and who were delivered by prelabor Cesarean section, or had a fetal death, before 32 weeks' gestation. STV of all available cCTG registrations during the 5 days preceding fetal death or delivery was calculated retrospectively, and FHR decelerations were classified visually as absent, 1-2/h or recurrent (> 2/h). Adverse outcome endpoints were defined as fetal death, neonatal asphyxia at birth (including fetal death), neonatal death, major neonatal morbidity and 2-year neurodevelopmental outcome. A simulation analysis was performed to assess the incidence of adverse outcome using two thresholds for cCTG: (1) highly abnormal (STV < 2.6 ms before 29 weeks and < 3.0 ms thereafter, and/or recurrent FHR decelerations); and (2) moderately abnormal (STV < 3.5 ms before 29 weeks and < 4.0 ms thereafter, and/or recurrent FHR decelerations). Three management strategies were assessed using a strict schedule for the frequency of cCTG recordings: (1) cCTG without use of fetal arterial Doppler; (2) cCTG with additional fetal arterial Doppler after 29 weeks; and (3) cCTG with additional fetal arterial Doppler after 27 weeks., Results: Included were 367 pregnancies (3295 cCTG recordings), of which 20 resulted in fetal death and 347 were delivered by Cesarean section before the onset of labor. Cesarean delivery was indicated by fetal condition in 94% of cases and by maternal condition in 6%. Median gestational age at delivery was 30 (interquartile range (IQR), 28-31) weeks and median birth weight was 900 (IQR, 740-1090) g. Six cases of fetal death were not anticipated by standard practice using visual assessment of CTG. A last highly abnormal cCTG was associated with fetal death and with neonatal asphyxia (including fetal death; n = 99), but not with major neonatal morbidity and 2-year neurodevelopmental outcome. Moderately abnormal cCTG had no significant association with any endpoint. Simulation analysis showed that a strategy that combined cCTG results with umbilicocerebral ratio or umbilical absent or reversed end-diastolic flow could detect all fetal deaths., Conclusions: Computerized CTG in combination with fetal arterial Doppler, with a strict protocol for the frequency of recordings, is likely to be more effective than visual CTG assessment for preventing fetal death in early preterm FGR. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To explore the effect on perinatal outcome of different fetal monitoring strategies for early-onset fetal growth restriction (FGR)., Methods: This was a cohort analysis of individual participant data from two European multicenter trials of fetal monitoring methods for FGR: the Growth Restriction Intervention Study (GRIT) and the Trial of Umbilical and Fetal Flow in Europe (TRUFFLE). All women from GRIT (n = 238) and TRUFFLE (n = 503) who were randomized between 26 and 32 weeks' gestation were included. The women were grouped according to intervention and monitoring method: immediate delivery (GRIT) or delayed delivery with monitoring by conventional cardiotocography (CTG) (GRIT), computerized CTG (cCTG) only (GRIT and TRUFFLE) or cCTG and ductus venosus (DV) Doppler (TRUFFLE). The primary outcome was survival without neurodevelopmental impairment at 2 years of age., Results: Gestational age at delivery and birth weight were similar in both studies. Fetal death rate was similar between the GRIT and TRUFFLE groups, but neonatal and late death were more frequent in GRIT (18% vs 6%; P < 0.01). The rate of survival without impairment at 2 years was lowest in pregnancies that underwent immediate delivery (70% (95% CI, 61-78%)) or delayed delivery with monitoring by CTG (69% (95% CI, 57-82%)), increased in those monitored using cCTG only in both GRIT (80% (95% CI, 68-91%)) and TRUFFLE (77% (95% CI, 70-84%)), and was highest in pregnancies monitored using cCTG and DV Doppler (84% (95% CI, 80-89%)) (P < 0.01 for trend)., Conclusions: This analysis supports the hypothesis that the optimal method for fetal monitoring in pregnancies complicated by early-onset FGR is a combination of cCTG and DV Doppler assessment., Trial Registration: GRIT ISRCTN41358726 and TRUFFLE ISRCTN56204499. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology., (© 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To evaluate the association between fetal growth restriction (FGR) and maternal hemodynamic parameters using multivariable analysis, adjusting for major confounding factors, such as hypertensive disorders of pregnancy (pre-eclampsia and gestational hypertension)., Methods: A prospective cohort study was conducted between January 2013 and April 2016. Two cohorts of patients were recruited, between 24 and 39 weeks of gestation, in a high-risk outpatient setting. These cohorts comprised 49 appropriate-for-gestational-age singleton fetuses and 93 that were FGR (abdominal circumference (AC) at recruitment in the second half of pregnancy ≤ 10 th percentile with a previous normal AC at 20-22 weeks). Maternal echocardiography was performed at the time of enrolment and included hemodynamic parameters of systolic and diastolic function and cardiac remodeling indices. Data were analyzed using a multivariable generalized linear model to estimate the association of FGR with maternal hemodynamic parameters after adjusting for significant confounding factors., Results: In the multivariable analysis, after adjustment for hypertensive disorders of pregnancy and smoking, FGR was associated with a 14% increase in maternal total vascular resistance, 16% reduction in cardiac output, 13% reduction in left ventricular mass and 11% reduction in heart rate; similar results were observed for the corresponding indexed parameters. Hypertensive disorders of pregnancy in the absence of FGR were associated with a 25% increase in total vascular resistance, 16% increase in left ventricular mass and 14% reduction in diastolic function; similar results were observed for the corresponding indexed parameters., Conclusion: FGR is significantly and independently associated with several maternal hemodynamic parameters, even after adjustment for major confounding factors, such as hypertensive disorders of pregnancy. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Fetal growth restriction (FGR) is a major risk factor for stillbirth and most commonly arises from uteroplacental insufficiency. Despite clinical examination and third-trimester fetal biometry, cases of FGR often remain undetected antenatally. Placental insufficiency is known to be associated with altered blood flow resistance in maternal, placental and fetal vessels. The aim of this study was to evaluate the performance of individual and combined Doppler blood flow resistance measurements in the prediction of term small-for-gestational age and FGR., Methods: This was a prospective study of 347 nulliparous women with a singleton pregnancy at 36 weeks' gestation in which fetal growth and Doppler measurements were obtained. Pulsatility indices (PI) of the uterine arteries (UtA), umbilical artery (UA) and fetal vessels were analyzed, individually and in combination, for prediction of birth weight < 10 th , < 5 th and < 3 rd centiles. Doppler values were converted into centiles or multiples of the median (MoM) for gestational age. The sensitivities, positive and negative predictive values and odds ratios (OR) of the Doppler parameters for these birth weights at ∼ 90% specificity were assessed. Additionally, the correlations between Doppler measurements and other measures of placental insufficiency, namely fetal growth velocity and neonatal body fat measures, were analyzed., Results: The Doppler combination most strongly associated with placental insufficiency was a newly generated parameter, which we have named the cerebral-placental-uterine ratio (CPUR). CPUR is the cerebroplacental ratio (CPR) (middle cerebral artery PI/UA-PI) divided by mean UtA-PI. CPUR MoM detected FGR better than did mean UtA-PI MoM or CPR MoM alone. At ∼ 90% specificity, low CPUR MoM had sensitivities of 50% for birth weight < 10 th centile, 68% for < 5 th centile and 89% for < 3 rd centile. The respective sensitivities of low CPR MoM were 26%, 37% and 44% and those of high UtA-PI MoM were 34%, 47% and 67%. Low CPUR MoM was associated with birth weight < 10 th centile with an OR of 9.1, < 5 th centile with an OR of 17.3 and < 3 rd centile with an OR of 57.0 (P < 0.0001 for all). CPUR MoM was also correlated most strongly with fetal growth velocity and neonatal body fat measures, as compared with CPR MoM or UtA-PI MoM alone., Conclusions: In this cohort, a novel Doppler variable combination, the CPUR (CPR/UtA-PI), had the strongest association with indicators of placental insufficiency. CPUR detected more cases of FGR than did any other Doppler parameter measured. If these results are replicated independently, this new parameter may lead to better identification of fetuses at increased risk of stillbirth that may benefit from obstetric intervention. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Maternal hemodynamics in pregnancy is associated with fetal growth and birth weight, which in turn are associated with offspring cardiovascular disease later in life. The aim of this study was to quantify the extent to which birth weight is associated with cardiac structure and function in adolescence., Methods: A subset of offspring (n = 1964; 55% female) of the Avon Longitudinal Study of Parents and Children were examined with echocardiography at a mean age of 17.7 (SD, 0.3) years. The associations of birth-weight Z-score for sex and gestational age with cardiac structure (assessed by relative wall thickness, left ventricular mass index (LVMI) and left atrial diameter index), systolic function (assessed by ejection fraction and left ventricular wall velocity) and diastolic function (assessed by early/late mitral inflow velocity (E/A) and early mitral inflow velocity/mitral annular early diastolic velocity (E/e')) were evaluated. Linear regression models were adjusted for several potential confounders, including maternal prepregnancy body mass index, age, level of education and smoking during pregnancy., Results: Higher birth-weight Z-score was associated with lower E/A (mean difference, -0.024; 95% CI, -0.043 to -0.005) and E/e' (mean difference, -0.05; 95% CI, -0.10 to -0.001) and higher LVMI (mean difference, 0.38 g/m 2.7 ; 95% CI, 0.09 to 0.67). There was no or inconsistent evidence of associations of birth-weight Z-score with relative wall thickness, left atrial diameter and measurements of systolic function. Further analyses suggested that the association between birth-weight Z-score and LVMI was driven mainly by an association observed in participants born small-for-gestational age and it did not persist when risk factors in adolescence were accounted for., Conclusions: Higher birth weight adjusted for sex and gestational age was associated with differences in measures of diastolic function in adolescence, but the observed associations were small. It remains to be determined the extent to which these associations translate into increased susceptibility to cardiovascular disease later in life. © 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology., (© 2018 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To compare maternal hemodynamics and perinatal outcome, in pregnancies that do not develop pre-eclampsia (PE) or deliver a small-for-gestational-age (SGA) neonate, between those identified at 11-13 weeks' gestation as being screen positive or negative for preterm PE, by a combination of maternal factors, mean arterial pressure, uterine artery pulsatility index, serum placental growth factor and pregnancy associated plasma protein-A., Methods: This was a prospective longitudinal cohort study of maternal cardiovascular function, assessed using a bioreactance method, in women undergoing first-trimester screening for PE. Maternal hemodynamics and perinatal outcome were compared between screen-positive and screen-negative women who did not have a medical comorbidity, did not develop PE or pregnancy-induced hypertension and delivered at term a live neonate with birth weight between the 5 th and 95 th percentiles. A multilevel linear mixed-effects model was used to compare the repeated measures of cardiac variables, controlling for maternal characteristics., Results: The screen-negative group (n = 926) had normal cardiac function changes across gestation, whereas the screen-positive group (n = 170) demonstrated static or reduced cardiac output and stroke volume and higher mean arterial pressure and peripheral vascular resistance with advancing gestation. In the screen-positive group, compared with screen-negative women, birth-weight Z-score was shifted toward lower values, with prevalence of delivery of a neonate below the 35 th , 30 th or 25 th percentile being about 70% higher, and the rate of operative delivery for fetal distress in labor also being higher., Conclusion: Women who were screen positive for impaired placentation, even though they did not develop PE or deliver a SGA neonate, had pathological cardiac adaptation in pregnancy and increased risk of adverse perinatal outcome. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the effect of fetal growth restriction (FGR) at term on fetal and neonatal cardiac geometry and function., Methods: This was a prospective study of 87 pregnant women delivering at term, comprising 54 normally grown and 33 FGR pregnancies. Fetal and neonatal conventional and spectral tissue Doppler and two-dimensional speckle tracking echocardiography were performed a few days before and within hours after birth. Fetal cardiac geometry, global myocardial deformation and performance and systolic and diastolic function were compared between normal and FGR pregnancies before and after birth., Results: Compared with normally grown fetuses, FGR fetuses exhibited more globular ventricular geometry and poorer myocardial deformation and cardiac function (left ventricular (LV) sphericity index (SI), 0.54 vs 0.49; right ventricular (RV) SI, 0.60 vs 0.54; LV torsion, 1.2 °/cm vs 3.0 °/cm; LV isovolumetric contraction time normalized by cardiac cycle length, 121 ms vs 104 ms; interventricular septum early diastolic myocardial peak velocity/atrial contraction myocardial diastolic peak velocity ratio, 0.60 vs 0.71; P < 0.01 for all). The poorest perinatal outcomes occurred in FGR fetuses with the most impaired cardiac functional indices. When compared with normally grown neonates, FGR neonates showed persistent alteration in cardiac parameters (LV-SI, 0.53 vs 0.50; RV-SI, 0.54 vs 0.44; LV torsion, 1.1 °/cm vs 1.4 °/cm; LV myocardial performance index (MPI'), 0.52 vs 0.42; P < 0.01 for all). Paired comparison of fetal vs neonatal cardiac indices in FGR demonstrated that birth was associated with a significant improvement in some, but not all, cardiac indices (RV-SI, 0.60 vs 0.54; RV-MPI', 0.49 vs 0.39; P < 0.001 for all)., Conclusions: Compared with normal pregnancies, FGR fetuses and neonates at term exhibit altered cardiac indices indicative of myocardial impairment that reflect adaptation to placental hypoxemia and alterations in hemodynamic load around the time of birth. Elucidating potential mechanisms that contribute to the alterations in perinatal cardiac adaptation in FGR could improve management and aid the development of better therapeutic strategies to reduce the risk of adverse pregnancy outcome. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To investigate whether abdominal circumference growth velocity (ACGV) improves the prediction of perinatal outcome in small-for-gestational-age (SGA) fetuses beyond that afforded by estimated fetal weight (EFW) and cerebroplacental ratio (CPR)., Methods: A cohort of 235 singleton SGA fetuses at 36-38 weeks' gestation was examined. ACGV, EFW and CPR centiles were calculated. ACGV centile was determined using data from a large database of 19-21- and 36-38-week scans in an unselected population. Binary variables of ACGV < 10 th , EFW < 3 rd and CPR < 5 th centiles were defined as abnormal. Two composite adverse outcomes (CAO) were explored: CAO-1 defined as at least one of umbilical artery pH < 7.10, 5-min Apgar score < 7 or neonatal unit admission, and CAO-2 that included in addition hypoglycemia, intrapartum fetal distress and perinatal death. Univariate and multivariate logistic regression analyses were performed to analyze the relationship between the three risk factors and their predictive value for CAO. The change in screening performance afforded by adding ACGV to EFW and CPR was assessed and receiver-operating characteristics (ROC) curves were calculated., Results: ACGV < 10 th centile was an independent risk factor for CAO. The sensitivity, specificity, positive and negative likelihood ratios of a predictive model based on EFW < 3 rd centile and CPR < 5 th centile were, respectively, 51%, 70%, 1.71 and 0.69 for CAO-1 and 41%, 70%, 1.39 and 0.83 for CAO-2. After addition of ACGV < 10 th centile to the model, the respective values were 82%, 46%, 1.54 and 0.38 for CAO-1 and 71%, 47%, 1.34 and 0.62 for CAO-2. Using continuous variables, the areas under the ROC curves improved marginally from 0.669 (95% CI, 0.604-0.729) to 0.741 (95% CI, 0.677-0.798) for CAO-1 and from 0.646 (95% CI, 0.580-0.707) to 0.700 (95% CI, 0.633-0.759) for CAO-2 after addition of ACGV to the model., Conclusions: ACGV is a risk factor for adverse neonatal outcome that is independent of EFW and of CPR, although any improvement in the prediction of adverse outcome is not statistically significant. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: As birth weight is a critical predictor of outcome in neonates with congenital heart defect (CHD), the common problem of poor fetal growth in this population is clinically important. However, it is not well understood and the impact of fetal hemodynamics on fetal growth and birth weight in those with CHD has not been assessed. In this study, we sought to evaluate the association between combined cardiac output (CCO) and fetal middle cerebral artery (MCA) and umbilical artery (UA) pulsatility indices (PIs) and fetal growth in different subgroups of CHD, and to study the effects of fetal hemodynamics on late gestational weight gain. We hypothesized that fetuses with CHD will have lower CCO and be smaller at birth., Methods: This was a retrospective review of fetal echocardiograms from 67 fetuses diagnosed with hypoplastic left heart syndrome (HLHS, n = 30), non-HLHS single ventricle (SV) (n = 20) or dextrotransposition of the great arteries (d-TGA, n = 17), compared with normal controls (n = 42). CCO was calculated using valvar area, velocity-time integral and heart rate and indexed to estimated fetal weight. MCA- and UA-PI were calculated using systolic, diastolic and mean velocities. Fetal biometry was recorded. Regression models were used to study trends in CCO, MCA- and UA-PI and fetal biometry over gestational age. To evaluate fetal weight gain in late gestation, Z-scores of estimated fetal weight at 30 weeks and birth weight were compared. Regression analysis was used to determine the associations of CCO, indexed CCO and MCA- and UA-PI at 30 weeks with birth weight, length and head circumference Z-scores, in addition to weight gain late in gestation. The gestational age of 30 weeks was chosen based on previous studies that found evidence of poor weight gain in fetuses with CHD in late gestation, starting at around that time., Results: CCO increased with gestation in all four groups but the rate was slower in fetuses with HLHS and in those with SV. MCA-PI was lower in fetuses with HLHS compared with in those with non-HLHS-SV throughout gestation, suggesting different cerebral blood distribution. At the end of gestation, rate of fetal weight gain slowed in those with HLHS and in those with SV (similar to CCO curves), and head circumference growth rate slowed in all groups but controls. CCO, indexed CCO and MCA- and UA-PI did not correlate with any of the birth measurements or with weight gain late in gestation in fetuses with CHD., Conclusions: We found no associations of CCO or MCA- and UA-PI with late gestational weight gain or biometry at birth in fetuses with CHD. This does not support fetal hemodynamics as the primary driver of suboptimal fetal growth in fetuses with SV. Future research could further explain genetic and placental abnormalities that may affect fetal growth in those with CHD. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: The cerebroplacental ratio (CPR) has been proposed for the routine surveillance of pregnancies with suspected fetal growth restriction (FGR), but the predictive performance of this test is unclear. The aim of this study was to determine the accuracy of CPR for predicting adverse perinatal and neurodevelopmental outcomes in suspected FGR., Methods: PubMed, EMBASE, CINAHL and Lilacs were searched from inception to 31 July 2017 for cohort or cross-sectional studies reporting on the accuracy of CPR for predicting adverse perinatal and/or neurodevelopmental outcomes in singleton pregnancies with FGR suspected antenatally based on sonographic parameters. Summary receiver-operating characteristics (ROC) curves, pooled sensitivities and specificities, and summary likelihood ratios (LRs) were generated., Results: Twenty-two studies (including 4301 women) met the inclusion criteria. Summary ROC curves showed that the best predictive accuracy of CPR was for perinatal death and the worst was for neonatal acidosis, with areas under the summary ROC curves of 0.83 and 0.57, respectively. The predictive accuracy of CPR was moderate to high for perinatal death (pooled sensitivity and specificity of 93% and 76%, respectively, and summary positive and negative LRs of 3.9 and 0.09, respectively) and low for composite of adverse perinatal outcomes, Cesarean section for non-reassuring fetal status, 5-min Apgar score < 7, admission to the neonatal intensive care unit, neonatal acidosis and neonatal morbidity, with summary positive and negative LRs ranging from 1.1 to 2.5 and 0.3 to 0.9, respectively. An abnormal CPR result had moderate accuracy for predicting small-for-gestational age at birth (summary positive LR of 7.4). CPR had a higher predictive accuracy in pregnancies with suspected early-onset FGR. No study provided data for assessing the predictive accuracy of CPR for adverse neurodevelopmental outcome., Conclusion: CPR appears to be useful in predicting perinatal death in pregnancies with suspected FGR. Nevertheless, before incorporating CPR into the routine clinical management of suspected FGR, randomized controlled trials should assess whether the use of CPR reduces perinatal death or other adverse perinatal outcomes. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To assess whether, in a cohort of patients with a small-for-gestational-age (SGA) fetus with estimated fetal weight ≤ 10 th percentile, maternal hemodynamics, fetal biometry and Doppler indices at presentation can predict the subsequent development of an abnormal fetal Doppler index or delivery of a baby with birth weight < 3 rd percentile., Methods: This was a prospective observational cohort study conducted at a specialist clinic for the management of pregnancies with a SGA fetus at King's College Hospital, London, UK. The study population comprised 86 singleton pregnancies with a SGA fetus, presenting at a median gestational age of 32 (range, 26-35) weeks. We measured maternal cardiac function using a non-invasive transthoracic bioreactance monitor, as well as mean arterial pressure, fetal biometry, and umbilical artery (UA), fetal middle cerebral artery (MCA) and uterine artery (UtA) pulsatility indices (PI), and the deepest vertical pool of amniotic fluid. Z-scores of these variables were calculated based on reported reference ranges and the values were compared between pregnancies with evidence of an abnormal fetal Doppler index at presentation (Group 1), those that had developed an abnormal Doppler index at a subsequent visit (Group 2) and those that did not develop an abnormal Doppler index throughout pregnancy (Group 3). Abnormal fetal Doppler was defined as UA-PI > 95 th percentile and/or MCA-PI < 5 th percentile. Differences in measured variables at presentation were also compared between pregnancies delivering a baby with birth weight < 3 rd percentile and those delivering a baby with birth weight ≥ 3 rd percentile. Multivariate logistic regression analysis was used to determine significant predictors of birth weight < 3 rd percentile and evolution from normal to abnormal fetal Doppler., Results: In the study population, 14 (16%) cases were in Group 1, 19 (22%) in Group 2 and 53 (62%) in Group 3. Birth weight was < 3 rd percentile in 39 (45%) cases and ≥ 3 rd percentile in 47 (55%). There was decreased cardiac output and stroke volume and increased peripheral vascular resistance compared with a normal population, and the deviations from normal were most marked in Group 1. Pregnancies with birth weight < 3 rd percentile, compared with those with birth weight ≥ 3 rd percentile, had greater deviations from normal in fetal biometry, maternal cardiac output, stroke volume, heart rate, peripheral vascular resistance and UtA-PI. Multivariate logistic regression analysis demonstrated that, in the prediction of birth weight < 3 rd percentile, maternal hemodynamic profile provided significant improvement to the prediction provided by maternal demographics, fetal biometry, UtA-PI, UA-PI and MCA-PI (difference between areas under receiver-operating characteristics curves, 0.18 (95% CI, 0.06-0.29); P = 0.002). In contrast, there was no significant independent contribution from maternal hemodynamics in the prediction of the subsequent development of abnormal fetal Doppler., Conclusions: In pregnancies with a SGA fetus, there is decreased maternal cardiac output and stroke volume and increased peripheral vascular resistance, and the deviations from normal are most marked in cases of redistribution in the fetal circulation and reduced amniotic fluid volume. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To determine if, in a high-risk group of women in the first half of pregnancy, those who develop pre-eclampsia (PE) with fetal growth restriction (FGR) demonstrate distinct hemodynamics compared with those with PE in the absence of FGR (PE only)., Methods: Cardiac output (CO), peripheral vascular resistance (PVR) and mean arterial pressure (MAP) were measured at the first hospital visit at 9-24 weeks' gestation in 69 women who had chronic hypertension and 67 who had had a hypertensive disorder in a previous pregnancy. These women were divided into five groups according to pregnancy outcome. In total, 19 subsequently developed PE only, 22 developed PE with FGR, 17 developed pregnancy-induced hypertension, 39 had chronic hypertension without PE or FGR and 39 had had a hypertensive disorder in a previous pregnancy without PE, pregnancy-induced hypertension or FGR in the index pregnancy. The hemodynamic values in each of these groups were compared with those in a cohort of 300 low-risk women with normal pregnancy., Results: In all the high-risk groups, PVR and MAP were higher than in women with a normal pregnancy, but CO was lower in the group of women with PE and FGR, whereas in the other high-risk groups, it was not significantly different from normal., Conclusions: In women who develop PE, there is evidence of high PVR and MAP from the first half of pregnancy, whilst PE and FGR are associated with failure in physiological expansion of CO. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Fetuses with growth restriction have been reported to have an abnormal sphericity index (SI), which is indicative of the shape of the ventricular chambers of the heart. Our aim was to evaluate the SI for 24 transverse segments distributed from base to apex of the right (RV) and left (LV) ventricles to determine whether, in small-for-gestational-age (SGA) fetuses, the SI is abnormal at locations other than the basal segment., Methods: We evaluated 30 SGA fetuses between 25 and 37 weeks of gestation. SI was computed for both ventricles by dividing the end-diastolic mid-basal-apical length by each of 24 end-diastolic transverse segmental widths, from base (Segment 1) to apex (Segment 24). For each ventricle, the Z-score and centile for the SI from each of the 24 segments were computed using the mean and SD from published equations. The 24-segment method, defining abnormal SI as values < 10 th centile or > 90 th centile, was compared with that of using only the basal segment by chi-square analysis to determine the number of fetuses identified with an abnormal SI., Results: In 23 of the 30 (77%) SGA fetuses, at least one of the 24 transverse segments in one or both ventricles had an abnormal SI; in 17% of cases, both ventricles were affected, in 23% of cases only the RV was involved and in 37% of cases only the LV was involved. Compared with the 24-segment model, significantly fewer fetuses with an abnormal SI were identified using only basal Segment 1, from the RV base (58%, 7/12; P < 0.01) or only Segment 12, in the mid portion of the RV (50%, 6/12; P < 0.005). Combining measurements of Segment 1 and Segment 12 from the RV identified 83% of fetuses with at least one abnormal SI and was not significantly different from using the 24-segment model. Similarly, significantly fewer fetuses with an abnormal SI were identified using only LV basal Segment 1 (63%, 10/16; P < 0.006) or only Segment 12, in the mid portion of the LV (75%, 12/16; P < 0.03), when compared with the 24-segment model. Combining measurements of both LV Segment 1 and Segment 12 identified 81% (13/16) of fetuses with an abnormal SI and was not significantly different from using the 24-segment model., Conclusion: The 24-segment SI of RV and LV provides a comprehensive method with which to examine the shape of the ventricular chambers and identifies more SGA fetuses with an abnormal SI than are identified using only the basal segment SI. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

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 (< 5 th 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 < 5 th 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., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To compare the association between risk of emergency Cesarean delivery (CD) and non-customized vs customized ultrasound estimated fetal weight (EFW) at 36 weeks' gestation, determine whether addition of ultrasound EFW to a model based on maternal characteristics alone improved prediction of emergency CD, assess the screening performance of a multivariable model using both EFW and maternal characteristics to predict emergency CD, and determine whether women at high predicted risk of emergency CD based on this model had higher risk of maternal and perinatal morbidity compared with screen-negative women., Methods: We studied 3047 low-risk (no pre-existing medical conditions or acquired complications of pregnancy) nulliparous women from the prospective Pregnancy Outcome Prediction study (Cambridge, UK) cohort, who underwent ultrasound EFW at ∼36 weeks' gestation. Both the women and their clinicians were blinded to fetal biometry results. Emergency CD was defined as delivery by Cesarean section in pregnancies in which the date of delivery had not been prearranged. Additional candidate predictors of emergency CD evaluated were maternal age, height, body mass index (BMI), weight gain, fetal abdominal circumference growth velocity and fetal sex. External validation of the predictive model was performed using routinely collected data from 55 337 births in Scotland between 2003 and 2008. Women with an estimated risk of emergency CD ≥ 40% were defined as screen positive., Results: Blinded EFW was associated strongly with the risk of emergency CD (coefficient for increase of 1 SD in EFW, 0.39 (95% CI, 0.30-0.48); odds ratio (OR), 1.48 (95% CI, 1.35-1.62)). The coefficient for customized EFW was similar (0.42 (95% CI, 0.33-0.51); OR, 1.53 (95% CI, 1.39-1.67)); hence, for simplicity, non-customized EFW was employed subsequently. A multivariable logistic regression model combining maternal characteristics (age, height, BMI and weight gain between 12 and 36 weeks) was moderately predictive of emergency CD (area under the receiver-operating characteristics curve (AUC) = 0.68). Addition of blinded EFW to the model increased the AUC to 0.71 and improved prediction (likelihood-ratio test P < 0.0001). Based on this model, 189 (6.2%) women were screen positive and 48% of these delivered by CD. Screen-positive women had elevated risks of severe postpartum hemorrhage (relative risk (RR), 2.49; 95% CI, 1.83-3.38), any adverse neonatal outcome (RR, 1.86; 95% CI, 1.22-2.82) and severe adverse neonatal outcome (RR, 4.03; 95% CI, 1.35-12.03) compared with screen-negative women. The risks of these events were also higher compared with women who had a term CD for breech presentation. The model was similarly predictive of the risk of emergency CD and perinatal morbidity when evaluated using the dataset from Scotland., Conclusions: Ultrasound EFW at 36 weeks, combined with maternal characteristics, can identify women who are at increased risk of subsequent emergency CD. These women are at increased risk of maternal and perinatal morbidity compared with women at low risk of emergency CD and those having CD for breech presentation at term. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Although no clear evidence exists, many international guidelines advocate early-term delivery of small-for-gestational-age (SGA) fetuses. The aim of this study was to determine whether a risk-stratification protocol in which low-risk SGA fetuses are managed expectantly beyond 37 weeks affects perinatal and maternal outcomes., Methods: This was an impact study examining data collected over a 39-month period (1 January 2013 to 30 April 2016) at a tertiary referral unit. The study included women who were referred to the fetal medicine unit with a singleton non-anomalous fetus diagnosed antenatally as SGA (estimated fetal weight < 10 th centile) from 36 + 0 weeks' gestation. In 2014, a protocol for management of SGA was introduced, which included risk stratification with surveillance and expectant management after 37 weeks for lower-risk babies (protocol group). This was compared with the previous strategy, which recommended delivery at around 37 weeks (pre-protocol group). Primary outcome was neonatal composite adverse outcome., Results: In the pre-protocol group, there were 138 SGA babies; in the protocol group there were 143. Mean gestational ages at delivery were 37.4 weeks in the pre-protocol group and 38.2 weeks in the protocol group (P = 0.04). The incidence of neonatal composite adverse outcome was lower in the protocol group (9% vs 22%; P < 0.01), as was neonatal unit admission (13% vs 39%; P < 0.01). Induction of labor and Cesarean section rates were lower, and vaginal delivery rate (83% vs 60%; P < 0.01) was higher, in the protocol group. Most of the differences were as a result of delayed delivery of SGA babies that were stratified as low risk., Conclusions: The findings of this study suggest that protocol-based management of SGA babies may improve outcome, and that identification of moderate SGA should not in isolation prompt delivery. Larger numbers are required to assess any impact on perinatal mortality. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the test performance of 47 biomarkers and ultrasound parameters for the prediction of delivery of a small-for-gestational-age (SGA) infant and adverse perinatal outcome in women presenting with suspected pre-eclampsia., Methods: This was a prospective, multicenter observational study in which 47 biomarkers and ultrasound parameters were measured in 397 women with a singleton pregnancy presenting with suspected preterm pre-eclampsia between 20 + 0 and 36 + 6 weeks' gestation, with the objective of evaluating them as predictors of subsequent delivery of a SGA infant and adverse perinatal outcome. Women with confirmed pre-eclampsia at enrollment were excluded. Factor analysis and stepwise logistic regression were performed in two prespecified groups stratified according to gestational age at enrollment. The primary outcome was delivery of a SGA infant with a birth weight < 3 rd customized centile (SGA-3), and secondary outcomes were a SGA infant with a birth weight < 10 th customized centile and adverse perinatal outcome., Results: In 274 women presenting at 20 + 0 to 34 + 6 weeks' gestation, 96 (35%) delivered a SGA-3 infant. For prediction of SGA-3, low maternal placental growth factor (PlGF) concentration had a sensitivity of 93% (95% CI, 84-98%) and negative predictive value (NPV) of 90% (95% CI, 76-97%) compared with a sensitivity of 71% (95% CI, 58-82%) and a NPV of 79% (95% CI, 68-87%) for ultrasound parameters (estimated fetal weight or abdominal circumference < 10 th centile). No individual biomarker evaluated had a better performance than did PlGF, and marker combinations made only small improvements to the test performance. Similar results were found in 123 women presenting between 35 + 0 and 36 + 6 weeks' gestation., Conclusion: In women presenting with suspected preterm pre-eclampsia, measurement of PlGF offers a useful adjunct for identifying those at high risk of delivering a SGA infant, allowing appropriate surveillance and timely intervention. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology., (© 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.)

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) < 10 th 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 < 3 rd vs 3 rd -10 th 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 < 3 rd vs 3 rd -10 th 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., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To evaluate whether the magnitude of change in the cerebroplacental ratio (CPR) after 30 weeks' gestation is a better predictor of adverse pregnancy outcome compared with a single CPR measurement at 35-37 weeks. A secondary aim was to evaluate whether the utility of CPR at 35-37 weeks was enhanced after adjusting for change in gestational age., Methods: This was a retrospective cohort study of women who had at least two ultrasound scans between 30 and 37 weeks' gestation, with the final scan at 35-37 weeks. Exclusion criteria were major congenital abnormality, aneuploidy, multiple pregnancy and unknown middle cerebral artery pulsatility index or umbilical artery pulsatility index. A normal reference range for CPR was derived from a separate cohort of women with normal outcome and a Generalised Additive Model for Location, Scale and Shape was fitted to derive standardized centiles. These reference centiles were then used to calculate Z-scores for the study cohort. Logistic regression models and receiver-operating characteristics (ROC) curves were used to evaluate the predictive utility of CPR Z-score at last CPR measurement and the change in CPR on mode of delivery, neonatal outcome and composite neonatal outcome. The area under the ROC curve (AUC) for each model was compared before and after adjustment for parity, hypertension, diabetes, body mass index and smoking status., Results: A total of 1860 women met the inclusion criteria. There was no association between the magnitude of change in CPR and composite adverse pregnancy outcome (P = 0.92). Of the outcomes that made up the composite, an increase in CPR Z-score over time was associated with a lower risk for emergency Cesarean delivery (P < 0.001) and emergency Cesarean delivery for non-reassuring fetal status (P = 0.02). It was also associated with a lower risk of birth weight < 10 th centile (P = 0.01) and hypoglycemia (P = 0.001). There was no significant difference between the AUCs of last CPR Z-score and last CPR Z-score adjusted for the change in gestational age in predicting pregnancies at risk for adverse outcome., Conclusions: Our results suggest that both the individual CPR Z-score and the magnitude and direction of change in CPR Z-score can identify pregnancies at risk of various adverse perinatal outcomes. However, the CPR Z-score at 35-37 weeks' gestation appears to be a better predictor. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: In the TRUFFLE (Trial of Randomized Umbilical and Fetal Flow in Europe) study on the outcome of early fetal growth restriction, women were allocated to one of three groups of indication for delivery according to the following monitoring strategies: (1) reduced fetal heart rate (FHR) short-term variation (STV) on cardiotocography (CTG); (2) early changes in fetal ductus venosus (DV) waveform (DV-p95); and (3) late changes in fetal DV waveform (DV-no-A). However, many infants per monitoring protocol were delivered because of safety-net criteria, for maternal or other fetal indications, or after 32 weeks of gestation when the protocol was no longer applied. The objective of the present posthoc subanalysis was to investigate the indications for delivery in relation to 2-year outcome in infants delivered before 32 weeks to further refine management proposals., Methods: We included all 310 cases of the TRUFFLE study with known outcome at 2 years' corrected age and seven fetal deaths, excluding seven cases with inevitable perinatal death. Data were analyzed according to the allocated fetal monitoring strategy in combination with the indication for delivery., Results: Overall, only 32% of liveborn infants were delivered according to the specified monitoring parameter for indication for delivery; 38% were delivered because of safety-net criteria, 15% for other fetal reasons and 15% for maternal reasons. In the CTG-STV group, 51% of infants were delivered because of reduced STV. In the DV-p95 group, 34% of infants were delivered because of abnormal DV and, in the DV-no-A group, only 10% of infants were delivered accordingly. The majority of infants in the DV groups were delivered for the safety-net criterion of spontaneous decelerations in FHR. Two-year intact survival was highest in the DV groups combined compared with the CTG-STV group (P = 0.05 for live births only, P = 0.21 including fetal death), with no difference between DV groups. A poorer outcome in the CTG-STV group was restricted to infants delivered because of FHR decelerations in the safety-net subgroup. Infants delivered because of maternal reasons had the highest birth weight and a non-significantly higher intact survival., Conclusions: In this subanalysis of infants delivered before 32 weeks, the majority were delivered for reasons other than the allocated monitoring strategy indication. Since, in the DV group, CTG-STV criteria were used as a safety net but in the CTG-STV group, no DV safety-net criteria were applied, we speculate that the slightly poorer outcome in the CTG-STV group might be explained by the absence of DV data. The optimal timing of delivery of fetuses with early intrauterine growth restriction may therefore be best determined by monitoring them longitudinally, with both DV and CTG monitoring. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To explore whether, in early fetal growth restriction (FGR), the longitudinal pattern of fetal heart rate (FHR) short-term variation (STV) can be used to identify imminent fetal distress and whether abnormalities of FHR recordings are associated with 2-year infant outcome., Methods: The original TRUFFLE study assessed whether, in early FGR, delivery based on ductus venosus (DV) Doppler pulsatility index (PI), in combination with safety-net criteria of very low STV on cardiotocography (CTG) and/or recurrent FHR decelerations, could improve 2-year infant survival without neurological impairment in comparison with delivery based on CTG monitoring only. This was a secondary analysis of women who delivered before 32 weeks and had consecutive STV data recorded > 3 days before delivery and known infant outcome at 2 years of age. Women who received corticosteroids within 3 days of delivery were excluded. Individual regression line algorithms of all STV values, except the last one before delivery, were calculated. Life tables and Cox regression analysis were used to calculate the daily risk for low STV or very low STV and/or FHR decelerations (below DV group safety-net criteria) and to assess which parameters were associated with this risk. Furthermore, it was assessed whether STV pattern, last STV value or recurrent FHR decelerations were associated with 2-year infant outcome., Results: One hundred and forty-nine women from the original TRUFFLE study met the inclusion criteria. Using the individual STV regression lines, prediction of a last STV below the cut-off used by the CTG monitoring group had sensitivity of 42% and specificity of 91%. For each day after study inclusion, the median risk for low STV (CTG group cut-off) was 4% (interquartile range (IQR), 2-7%) and for very low STV and/or recurrent FHR decelerations (below DV group safety-net criteria) was 5% (IQR, 4-7%). Measures of STV pattern, fetal Doppler (arterial or venous), birth-weight multiples of the median and gestational age did not usefully improve daily risk prediction. There was no association of STV regression coefficients, a low last STV and/or recurrent FHR decelerations with short- or long-term infant outcomes., Conclusion: The TRUFFLE study showed that a strategy of DV monitoring with safety-net criteria of very low STV and/or recurrent FHR decelerations for delivery indication could increase 2-year infant survival without neurological impairment. This post-hoc analysis demonstrates that, in early FGR, the daily risk of abnormal CTG, as defined by the DV group safety-net criteria, is 5%, and that prediction is not possible. This supports the rationale for CTG monitoring more often than daily in these high-risk fetuses. Low STV and/or recurrent FHR decelerations were not associated with adverse infant outcome and it appears safe to delay intervention until such abnormalities occur, as long as DV-PI is within normal range. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Fetal growth restriction (FGR) is a powerful determinant of poor perinatal outcome. From our previous work in pregnancies at high risk of development of hypertension we found impaired cardiovascular adaptation early in gestation in those destined to deliver growth-restricted infants. In this study, we monitored serially maternal hemodynamics from the first to third trimester in a similar high-risk cohort, in order to determine whether this distinct hemodynamic profile found at presentation persisted throughout pregnancy in those complicated by FGR., Methods: This was a prospective observational study based at a specialist antenatal hypertension clinic at a tertiary hospital in London. Maternal hemodynamics were evaluated serially using a non-invasive bioreactance method in pregnant women referred to the clinic with a history of chronic hypertension or a history of hypertensive disorder in a previous pregnancy. Differences in maternal hemodynamic parameters were compared between women who delivered a baby with a birth weight ≥ 10 th vs < 10 th percentile and ≥ 5 th vs < 5 th percentile., Results: Eighty-four pregnant women were included in the study. Mean gestational age at presentation was 14.3 weeks. Sixteen women delivered babies with a birth weight < 10 th percentile and 11 with a birth weight < 5 th percentile. In pregnancies with a birth weight ≥ 10 th percentile, longitudinal maternal hemodynamics showed a pattern consistent with well-established physiological changes in pregnancy, i.e. a reduction in vascular resistance and an increase in cardiac output with advancing gestation until mid-pregnancy. However, women who delivered babies with a birth weight < 10 th percentile showed a static pattern with no change during gestation and lower cardiac output and higher peripheral vascular resistance. Similar differences were seen when the 5 th percentile was used to discriminate between appropriately-grown and growth-restricted babies., Conclusion: Serial assessment of maternal hemodynamics in high-risk women identifies distinctive trends associated with pregnancies destined to deliver babies with birth weights < 10 th and < 5 th percentiles. These pregnancies have a suppressed and static maternal cardiac output and stroke volume, and have consistently raised peripheral vascular resistance. This suggests that, in women with chronic hypertension or a history of hypertensive disorder in a previous pregnancy, FGR is associated with a primary and persistent failure of maternal cardiovascular adaptation in pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To describe the physiological pattern of gestational plasma volume adjustments in normal singleton pregnancy and compare this with the pattern in pregnancies complicated by pregnancy-induced hypertension, pre-eclampsia or fetal growth restriction., Methods: We performed a meta-analysis of the current literature on plasma volume adjustments during physiological and complicated pregnancies. Literature was retrieved from PubMed (NCBI) and EMBASE (Ovid) databases. Included studies reported both reference plasma volume measurements (non-pregnant, prepregnancy or postpartum) and measurements obtained during predetermined gestational ages. Mean differences bet ween the reference and pregnancy plasma volume measurements were calculated for predefined intervals of gestational age using a random-effects model described by DerSimonian and Laird., Results: Thirty studies were included in the meta-analysis with publication dates ranging from 1934 to 2007. Plasma volume increased in the first weeks of pregnancy, with the steepest increase occurring during the second trimester. Plasma volume continued to increase in the third trimester with a pooled maximum increase of 1.13 L (95% CI, 1.07-1.19 L), an increase of 45.6% (95% CI, 43.0-48.1%) in physiological pregnancies compared with the reference value. The plasma volume expansion in gestational hypertensive and growth-restricted pregnancies was 0.80 L (95% CI, 0.59-1.02 L), an increase of 32.3% (95% CI, 23.6-41.1%) in the third trimester, a smaller increase than in physiological pregnancies (P < 0.0001)., Conclusions: During physiological pregnancy, plasma volume increases by, on average, more than 1 L as compared with non-pregnant conditions. In pregnancies complicated by pregnancy-induced hypertension, pre-eclampsia or fetal growth restriction, plasma volume increase in the third trimester is 13.3% lower than in normal pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Adaptación fisiológica del volumen del plasma materno durante el embarazo: una revisi\xF3n sistemática y metaanálisis RESUMEN OBJETIVO: Describir el patrón fisiológico de los cambios en el volumen del plasma gestacional en embarazos normales con feto único y compararlo con el patrón en los embarazos complicados por hipertensión gestacional, preeclampsia o restricción del crecimiento fetal. MÉTODOS: Se realizó un metaanálisis de la literatura actual sobre los cambios en el volumen de plasma durante embarazos complicados y fisiológicos. La literatura se obtuvo de las bases de datos PubMed (NCBI) y EMBASE (Ovid). Los estudios incluidos mencionaban tanto mediciones de referencia del volumen plasmático (no embarazada, antes del embarazo o después del parto) como mediciones tomadas a edades gestacionales predeterminadas. Se calcularon las medias de las diferencias entre las mediciones de referencia y las del embarazo para el volumen plasmático a intervalos predefinidos de la edad gestacional, utilizando un modelo de efectos aleatorios descrito por DerSimonian y Laird., Resultados: En el metaanálisis se incluyeron treinta estudios con fechas de publicación entre 1934 y 2007. El volumen plasmático aumentó en las primeras semanas de embarazo y el mayor incremento se produjo durante el segundo trimestre. El volumen de plasma continuó aumentando en el tercer trimestre con un aumento combinado máximo de 1,13L (IC 95%, 1,7-1,19 L), lo que supone un aumento del 45,6% (IC 95%, 43,0-48,1%) en embarazos fisiológicas en comparación con el valor de referencia. El aumento del volumen plasmático en los embarazos con hipertensión y con crecimiento intrauterino restringido fue de 0,80L (IC 95%, 0,59-1,02 L), lo que supone un aumento del 32,3% (IC 95%, 23,6-41,1%) en el tercer trimestre, y un incremento menor que en los embarazos fisiológicos (P <0,0001)., Conclusiones: Durante el embarazo fisiológico el volumen de plasma aumenta, en promedio, más de 1L, en comparación con el de las no embarazadas. En los embarazos complicados por hipertensión gestacional, preeclampsia o restricción del crecimiento fetal, el aumento del volumen plasmático en el tercer trimestre es un 13,3% menor que en el embarazo normal. :meta : ,、。 : meta。PubMed(NCBI)EMBASE(Ovid)。(、)。DerSimonianLaird,。 : Meta30,19342007。,。,1.13 L(95% CI,1.07~1.19 L),,45.6%(95% CI,43.0%~48.1%)。0.80 L(95%CI,0.59~1.02 L),32.3%(95% CI,23.6%~41.1%),(P<0.0001)。 : ,,1 L。、,13.3%。., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To investigate whether Doppler pulsatility indices (PIs) of the fetal circulation in cases of fetal growth restriction (FGR) are associated with the general movements (GMs) of the neonate after birth., Methods: This was a prospective observational cohort study including pregnancies with FGR diagnosed between June 2012 and September 2014. A diagnosis of FGR was based on an abdominal circumference or estimated fetal weight < 10 th percentile (in conjuction with abnormal Doppler) or declining fetal growth of at least 30 percentiles with respect to previous size measurements. Doppler parameters of the umbilical artery (UA), fetal middle cerebral artery (MCA) and ductus venosus (DV) were measured maximally 1 week prior to delivery. Cerebroplacental ratio (CPR) was calculated as MCA-PI divided by UA-PI. We assessed the quality of neonatal GMs 7 days after birth, around the due date if cases were born preterm, and at 3 months post-term. We performed a detailed analysis of the motor repertoire by calculating a motor optimality score (MOS)., Results: Forty-eight FGR cases were included with a median gestational age at delivery of 35 (range, 26-40) weeks. UA-PI, MCA-PI and CPR correlated strongly (ρ, -0.374 to 0.472; P < 0.01) with the MOS on day 7 after birth, but DV-PI did not. Doppler PI measurements did not correlate with MOS at 3 months post-term., Conclusion: Fetal arterial Doppler measurements are associated with the quality of neonatal GMs 1 week after birth, but this association is no longer evident at 3 months post-term. Brain sparing in particular is associated strongly with GMs of an abnormal quality. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: Intrauterine growth restriction is associated with increased cardiovascular risk later in life but the link between fetal disease and postnatal risk is not well-documented. We evaluated longitudinally the association between cardiovascular remodeling in small-for-gestational-age (SGA) fetuses and at 6 months of age., Methods: A cohort of 80 SGA fetuses (defined by estimated fetal and birth weights < 10(th) centile) delivered > 34 weeks' gestation was compared with 80 normally grown age-matched control fetuses, with follow-up at 6 months of corrected age (i.e. 6 months from estimated date of delivery according to first-trimester crown-rump length). Cardiovascular evaluation included a comprehensive echocardiographic assessment in both fetuses and infants and blood pressure and aortic intima-media thickness (aIMT) measurement in infants. Parameters were adjusted by linear regression analysis for gender, gestational age at delivery, pre-eclampsia, prenatal glucocorticoid exposure, Cesarean delivery, admission to neonatal intensive care unit and body surface area., Results: Both pre- and postnatally, when compared with controls, the SGA group showed a more globular cardiac shape (left sphericity index: controls 2.06 vs SGA 1.87 (P = 0.022) prenatally and 1.92 vs 1.67 (P = 0.007) postnatally), as well as signs of systolic longitudinal dysfunction (systolic annular peak velocity (S'): 7.2 vs 6.3 cm/s (P = 0.003) prenatally and 7.9 vs 6.4 cm/s (P < 0.001) postnatally; tricuspid annular plane systolic excursion: 7.2 vs 6.8 mm (P = 0.015) prenatally and 16.0 vs 14.2 mm (P < 0.001) postnatally) and diastolic dysfunction (left isovolumetric relaxation time: 46 vs 52 ms (P < 0.001) prenatally and 50 vs 57 ms (P = 0.034) postnatally). In addition, infants in the SGA group had increased mean blood pressure (mean: 61 vs 70 mmHg, P < 0.001) and maximum aIMT (0.57 vs 0.66 mm; P < 0.001)., Conclusions: Primary cardiovascular changes are already present in the SGA fetus and persist at 6 months of age. These data support prenatal cardiovascular remodeling as a mechanistic pathway of increased risk later in life in cases of SGA, regardless of Doppler abnormalities. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To investigate whether prenatal Doppler parameters in growth-restricted fetuses are correlated with neonatal circulatory changes., Methods: In 43 cases of suspected fetal growth restriction (FGR), serial Doppler measurements of umbilical artery (UA) and middle cerebral artery (MCA) pulsatility index (PI) were performed. The last measurement, closest to delivery (< 1 week before birth), was used for analysis. Neonatal circulation was assessed for 2 h/day on Days 1-5, 8 and 15 by near-infrared spectroscopy (NIRS) of the cerebral, renal and splanchnic regions. We calculated fractional tissue oxygen extraction (FTOE) as: (arterial oxygen saturation - NIRS value)/arterial oxygen saturation. The following ratios were calculated: cerebroplacental ratio (CPR; MCA-PI/UA-PI), cerebrorenal ratio (CRR; cerebral/renal FTOE) and cerebrosplanchnic ratio (CSR; cerebral/splanchnic FTOE). Spearman's rank correlation coefficient (ρ) was calculated between prenatal Doppler parameters and neonatal NIRS variables. These analyses were carried out for the entire group, and separately for cases of early FGR (delivered < 34 weeks) and late FGR (≥ 34 weeks)., Results: Fetal Doppler parameters correlated with neonatal NIRS variables on Days 1-3: UA-PI correlated with renal FTOE (Day 1: ρ = 0.454, P < 0.01) and CRR (Day 1: ρ = -0.517, P < 0.001). MCA-PI correlated with cerebral FTOE on Day 2 (ρ = 0.469, P < 0.01), approached statistical significance on Day 3 but was not correlated on Day 1. CPR correlated with CRR (Day 1: ρ = 0.474, P < 0.01). Most associations lost their statistical significance when early and late FGR subgroups were considered separately., Conclusion: Low MCA-PI and low CPR, indicating brain sparing before birth, are associated with low CRR after birth, indicating relatively greater blood flow to the cerebrum than to the renal region. Based on the results of this study, it could be speculated that if brain sparing is present in the fetal circulation, it persists during the first 3 days after birth. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To determine the acute effects of corticosteroids on the cardiovascular system in growth-restricted fetuses., Methods: This was a prospective cohort study conducted at a tertiary hospital between January 2011 and October 2013. Fetal cardiovascular function in fetuses with intrauterine growth restriction (IUGR) was assessed immediately before and 24 h after the first dose of betamethasone, administered in routine management of IUGR. Fetal arterial and venous Dopplers were assessed. Fetal cardiac function was evaluated by tissue Doppler echocardiography, with the assessment of both left and right ventricular function by calculating myocardial performance index (MPI') and E':A' ratios. Values were compared before and after exposure., Results: Seventeen patients were included at a mean gestational age of 34 + 1 (range, 29 + 1 to 37 + 4) weeks. Fifteen fetuses were below the 5(th) percentile and two were below the 10(th) percentile for estimated fetal weight and abdominal circumference and all had no interval growth during a 2-week period. There was a decrease in right MPI' (from 0.56 to 0.47; P = 0.007) after corticosteroid exposure but no change in left MPI' (from 0.49 to 0.48). Right MPI' was higher than left MPI' before exposure (0.56 vs 0.49, respectively; P = 0.001), but not after exposure (P = 0.55). There was no change in left or right ventricular E':A' ratios and no difference was detected in umbilical artery, middle cerebral artery or ductus venosus pulsatility index following administration of corticosteroids., Conclusions: Corticosteroids altered right-sided, but not left-sided, tissue Doppler MPI' in IUGR fetuses, with no detectable change in arterial or venous Doppler pulsatility indices. Before exposure, the mean right MPI' was higher than the left. However, after exposure, there was no difference, suggesting that corticosteroids may reverse the negative effect of IUGR on fetal heart function. Large prospective studies with a larger sample size are needed to confirm this finding. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To assess the role of intertwin discrepancy in middle cerebral artery peak systolic velocity (MCA-PSV) for the prediction of late selective intrauterine growth restriction (sIUGR) at birth and birth weight discrepancy of > 25% (BW-25) in otherwise uncomplicated monochorionic-diamniotic (MCDA) twin pregnancies., Methods: This was a cohort study including all MCDA pregnancies followed in a tertiary fetal medicine unit between 2008 and 2013. Exclusion criteria were referral after first trimester, abnormal karyotype, structural anomalies, twin-to-twin transfusion syndrome, twin anemia-polycythemia sequence and sIUGR detected before 28 weeks. MCA-PSV values of both twins measured in the second trimester (18-24 weeks) and early third trimester (26-32 weeks) were converted in multiples of the median (MoM). sIUGR was defined as birth weight < 5(th) centile. The relationship between MCA-PSV discrepancy, sIUGR and BW-25 was assessed by logistic regression analysis. Receiver-operating characteristics (ROC) curves were used to ascertain the predictive value of MCA-PSV discrepancy for such complications., Results: In total, 136 MCDA twin pregnancies were included in the analysis. Thirty (22.1%) were complicated with sIUGR at birth and 12 (8.8%) were complicated with BW-25. Logistic regression analysis identified MCA-PSV discrepancy as an independent predictor for sIUGR. ROC curves identified third-trimester MCA-PSV discrepancy as the best predictor for both sIUGR (area under ROC curve (AUC), 0.73 (95% CI, 0.62-0.85)) and BW-25 (AUC, 0.79 (95% CI, 0.65-0.93)). The optimal cut-off point for MCA-PSV discrepancy was 0.30 MoM (sensitivity, 70% and specificity, 69% for sIUGR; sensitivity, 83% and specificity, 72% for BW-25)., Conclusion: In MCDA twin pregnancies, MCA-PSV discrepancy is associated with both sIUGR at birth and BW discordance. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To evaluate the effects of transdermal nitroglycerin (GTN) and sildenafil citrate on Doppler velocity waveforms of the uterine (UtA), umbilical (UA) and fetal middle cerebral (MCA) arteries in pregnancies with intrauterine growth restriction (IUGR)., Methods: This was a prospective study of 35 singleton pregnancies (gestational age, 24-31 weeks) with IUGR and abnormal UtA and UA Doppler waveforms. We compared maternal arterial blood pressure and Z-scores of the pulsatility index (PI) of UtA, UA and fetal MCA before and after application of a transdermal GTN patch (average dose, 0.4 mg/h), oral sildenafil citrate (50 mg) or placebo. Statistical analysis was performed by ANOVA for paired samples., Results: There was a significant decrease in UtA-PI after application of GTN (21.0%) and sildenafil citrate (20.4%). A significant reduction in UA-PI was also observed for both GTN (19.1%) and sildenafil citrate (18.2%). There was no difference in UtA- and UA-PI when the GTN and sildenafil groups were compared. No changes in Doppler velocimetry were observed in the placebo group and no significant change in MCA-PI was observed in any group. Maternal arterial blood pressure decreased with administration of both GTN and sildenafil citrate in those with pre-eclampsia., Conclusion: The use of transdermal GTN or sildenafil citrate in pregnancies with IUGR is associated with a significant reduction in both UtA and UA Doppler PI, as well as maternal arterial blood pressure. Neither drug affected the MCA-PI. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To evaluate in-vivo placental perfusion fraction, estimated by magnetic resonance imaging (MRI), as a marker of placental function., Methods: A study population of 35 pregnant women, of whom 13 had pre-eclampsia (PE), were examined at 22-40 weeks' gestation. Within a 24-h period, each woman underwent an MRI diffusion-weighted sequence (from which we calculated the placental perfusion fraction), venous blood sampling and an ultrasound examination including estimation of fetal weight, amniotic fluid index and Doppler velocity measurements. The perfusion fractions in pregnancies with and without fetal growth restriction were compared and correlations between the perfusion fraction and ultrasound estimates and plasma markers were estimated using linear regression. The associations between the placental perfusion fraction and ultrasound estimates were modified by the presence of PE (P  <  0.05) and therefore we included an interaction term between PE and covariates in the models., Results: The median placental perfusion fractions in pregnancies with and without fetal growth restriction were 21% and 32%, respectively (P = 0.005). The correlations between placental perfusion fraction and ultrasound estimates and plasma markers were highly significant (P = 0.002 and P = 0.0001, respectively). The highest coefficient of determination (R(2)  = 0.56) for placental perfusion fraction was found for a model that included pulsatility index in the ductus venosus, plasma level of soluble fms-like tyrosine kinase-1, estimated fetal weight and presence of PE., Conclusion: The placental perfusion fraction has the potential to contribute to the clinical assessment of cases with placental insufficiency., (© 2015 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To assess maternal vascular structure and function in pregnancies complicated by fetal growth restriction (FGR), in women with and without pre-eclampsia (PE) at the time of FGR diagnosis., Methods: We evaluated 124 women with a pregnancy complicated by FGR, of whom 60 had PE and 64 did not, and compared these findings to those of 110 normal women (controls). The group of FGR pregnancies without PE was further subdivided according to gestational age at FGR diagnosis into early onset (< 32 weeks) or late onset (≥ 32 weeks). Maternal carotid intima-media thickness (IMT), blood pressure (BP), carotid artery distensibility (CD), circumferential wall stress (CWS) and inferior vena cava (IVC) collapsibility were assessed by ultrasound at the time of FGR diagnosis., Results: Compared to controls, cases of FGR with PE showed increased maternal carotid IMT (0.425 (interquartile range (IQR), 0.381-0.486) vs 0.409 (IQR, 0.386-0.439) mm; P = 0.021), BP (mean, 109 (IQR, 101-117) vs 82  (IQR, 77-89) mmHg; P  < 0.001) and CWS (19.7 (IQR, 17.0-22.7) vs 12.2 (IQR, 11.1-13.7) kPa; P < 0.001), and reduced CD (25.3 (IQR, 15.7-35.6) vs 31.9 (IQR, 25.4-41.1) kPa(-1)  × 10(-3) ; P = 0.037) and IVC collapsibility indices (0.07 (IQR, 0.06-1.11) vs 0.10 (IQR, 0.06-0.13); P  =  0.136). Similarly, compared to controls, in cases of FGR without PE maternal carotid IMT (0.436  (IQR, 0.392-0.476) mm; P  = 0.001) and BP (88 (IQR, 81-95) mmHg; P < 0.001) were increased but CD and IVC collapsibility were similar. When analysis was subclassified according to gestational age at diagnosis, IMT and CWS were significantly increased only in early-onset FGR while BP was increased in both groups., Conclusion: Normotensive women with pregnancy complicated by FGR share some subclinical vascular features with those of women with PE, which further reinforces the notion that, at least in a proportion of cases, there is a common placental disease that influences maternal cardiovascular features., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To review systematically the evidence on impact of cerebral redistribution, as assessed by fetal middle cerebral artery (MCA) Doppler, on neurological outcomes in small-for-gestational-age (SGA) or growth-restricted fetuses., Methods: For this systematic review, MEDLINE was searched for all controlled studies reporting neurological outcomes in SGA or growth-restricted babies with cerebral redistribution based on MCA Doppler indices, from inception to September 2013. We used relative risk or odds ratios, with 95% CI, to identify the association of cerebral redistribution with neurological outcomes., Results: The search yielded 1180 possible citations, of which nine studies were included in the review, with a total of 1198 fetuses. Definitions of SGA and cerebral redistribution were variable, as was study quality. Data could not be synthesized in meta-analyses because of heterogeneity in outcome reporting. Cerebral redistribution was not associated with increased risk of intraventricular hemorrhage in neonates (five studies; n = 806). When present in preterm fetuses, cerebral redistribution was associated with normal Neonatal Behavioral Assessment Scale (NBAS) scores at 40 weeks (one study; n = 62) but abnormal psychomotor development at 1 year of age on the Bayley scale (one study; n = 172). When present in term SGA fetuses, cerebral redistribution was associated with increased risk of motor and state organizational problems on NBAS (two studies; n = 158), and lower mean percentile scores in communication and problem solving at 2 years of age on the Ages and Stages Questionnaire (one study; n = 125)., Conclusions: SGA fetuses with cerebral redistribution may be at higher risk of neurodevelopmental problems. More data are needed from adequately controlled studies with long-term follow-up before conclusions can be drawn. If these findings are true, there is a need to re-evaluate timing of delivery in the management of SGA fetuses, particularly when cerebral redistribution is found at term gestation., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Among late-onset small fetuses, a combination of estimated fetal weight (EFW), cerebroplacental ratio (CPR) and mean uterine artery (UtA) pulsatility index (PI) can predict a subgroup of fetuses with poor perinatal outcome; however, the association of these criteria with fetal cardiac structure and function is unknown. Our aim was to determine the presence and severity of signs indicating cardiac dysfunction in small fetuses, classified as intrauterine growth-restricted (IUGR) or small-for-gestational age (SGA), according to EFW, CPR and UtA-PI., Methods: A cohort of 209 late-onset small fetuses that were delivered > 34 weeks of gestation was divided in two categories: SGA (n = 59) if EFW was between the 3(rd) and 9(th) centiles with normal CPR and UtA-PI; and IUGR (n = 150) if EFW was < 3(rd) centile, or < 10(th) centile with a CPR < 5(th) centile and/or UtA-PI > 95(th) centile. The small population was compared with 150 appropriately grown fetuses (controls). Fetal cardiac morphometry and function were assessed by echocardiography using two-dimensional M-mode, conventional and tissue Doppler., Results: Compared with controls, both IUGR and SGA fetuses showed larger and more globular hearts (mean left sphericity index ± SD: controls, 1.8 ± 0.3; SGA, 1.5 ± 0.2; and IUGR, 1.6 ± 0.3; P < 0.01) and showed signs of systolic and diastolic dysfunction, including decreased tricuspid annular plane systolic excursion (mean ± SD: controls, 8.2 ± 1.1; SGA, 7.4 ± 1.2; and IUGR, 6.9 ± 1.1; P < 0.001) and increased left myocardial performance index (mean ± SD: controls, 0.45 ± 0.14; SGA, 0.51 ± 0.08; and IUGR, 0.57 ± 0.1; P < 0.001)., Conclusions: Despite a perinatal outcome comparable to that of normal fetuses, the population of so-defined SGA fetuses showed signs of prenatal cardiac dysfunction. This supports the concept that at least a proportion of them are not 'constitutionally small' and that further research is needed., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To investigate the potential value of uterine artery (UtA) pulsatility index (PI) and mean arterial pressure (MAP) at 19-24 weeks' gestation, in combination with maternal characteristics and medical history and fetal biometry in the prediction of delivery of small-for-gestational-age (SGA) neonates in the absence of pre-eclampsia (PE) and to examine the potential value of such assessment in deciding whether the third-trimester scan should be performed at 32 and/or 36 weeks' gestation., Methods: This was a screening study in 63 975 singleton pregnancies, including 3702 (5.8%) that delivered SGA neonates with birth weight < 5(th) percentile (SGA < 5(th) ) in the absence of PE. Multivariable logistic regression analysis was used to determine if screening by a combination of maternal factors, fetal head circumference (HC), abdominal circumference (AC), femur length (FL), UtA-PI and MAP had significant contribution in predicting SGA neonates. A model was developed to select gestational age for the third-trimester assessment, at 32 and/or 36 weeks, based on the results of screening at 19-24 weeks., Results: The detection rates (DRs) of combined screening by maternal factors, fetal biometry and UtA-PI at 19-24 weeks were 90%, 68% and 44% for SGA < 5(th) delivering < 32, 32-36 and ≥ 37 weeks' gestation, respectively, at a false-positive rate (FPR) of 10%. The performance of screening was not improved by the addition of MAP. The DR of SGA < 5(th) delivering at 32-36 weeks improved from 68% to 90% with screening at 32 rather than at 19-24 weeks. Similarly, the DR of SGA < 5(th) delivering ≥ 37 weeks improved from 44% with screening at 19-24 weeks to 59% and 76% when screening at 32 and 36 weeks, respectively. In a hypothetical model, it was estimated that if the desired objective of prenatal screening is to predict about 80% of the cases of SGA < 5(th) , it would be necessary to select 17% of the population at the 19-24-week assessment to be reassessed at 32 weeks and 38% to be reassessed at 36 weeks; 62% would not require a third-trimester scan., Conclusion: Prenatal prediction of a high proportion of SGA neonates necessitates the undertaking of screening in the third trimester of pregnancy in addition to assessment in the second trimester, and the timing of such screening, at 32 and/or 36 weeks, should be contingent on the results of the assessment at 19-24 weeks., (Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To investigate time intervals of the ductus venosus (DV) flow velocity waveform (FVW) and those of the cardiac cycle that correspond with each DV-FVW component in fetuses with intrauterine growth restriction (IUGR) due to placental insufficiency., Methods: Women with a pregnancy complicated by IUGR were recruited into the study, as was a normal control group. Time intervals for systolic (S) and diastolic (D) components were measured in DV-FVW as follows: S(DV), from the nadir of the a-wave during atrial contraction to the nadir between the S-wave and D-wave; D(DV), from the nadir between S-wave and D-wave to the nadir of the a-wave. Regarding cardiac cycles, the following variables were measured from ventricular inflow through the tricuspid valve (TV) and mitral valve (MV): S(TV) and S(MV), from the second peak of ventricular inflow caused by atrial contraction (A-wave) to the opening of the atrioventricular valve; D(TV) and D(MV), from the opening of the atrioventricular valve to the peak of the A-wave. In the IUGR group, only the last examination performed within 1 week of delivery was used for analysis. All variables were analyzed statistically using Z-scores., Results: Data were obtained from 249 normal fetuses and 26 fetuses with IUGR. Compared to normal fetuses, S(DV) showed a significant decrease (P < 0.001), while D(DV) showed a significant increase (P < 0.001) in the IUGR group. Regarding cardiac cycles, S(TV) and S(MV) showed significant decreases (P = 0.014 and P < 0.001, respectively) and D(TV) and D(MV) showed significant increases (P = 0.008 and P = 0.002, respectively) in fetuses with IUGR., Conclusion: Time-interval alterations of DV-FVW in growth-restricted fetuses reflect the hemodynamic events caused by placental insufficiency., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)