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Introduction: Growth-restricted fetuses may have changes in their neuroanatomical structures that can be detected in prenatal imaging. We aim to compare corpus callosal length (CCL) and cerebellar vermian height (CVH) measurements between fetal growth restriction (FGR) and control fetuses and to correlate them with cerebral Doppler velocimetry in growth-restricted fetuses., Methods: This was a prospective cohort of FGR after 20 weeks of gestation with ultrasound measurements of CCL and CVH. Control cohort was assembled from fetuses without FGR who had growth ultrasound after 20 weeks of gestation. We compared differences of CCL or CVH between FGR and controls. We also tested for the correlations of CCL and CVH with middle cerebral artery (MCA) pulsatility index (PI) and vertebral artery (VA) PI in the FGR group. CCL and CVH measurements were adjusted by head circumference (HC)., Results: CCL and CVH were obtained in 68 and 55 fetuses, respectively. CCL/HC was smaller in FGR fetuses when compared to control fetuses (difference = 0.03, 95% CI: [0.02, 0.04], p < 0.001). CVH/HC was larger in FGR fetuses compared to NG fetuses (difference = 0.1, 95% CI: [-0.01, 0.02], p = < 0.001). VA PI multiples of the median were inversely correlated with CVH/HC (rho = -0.53, p = 0.007), while CCL/HC was not correlated with VA PI. Neither CCL/HC nor CVH/HC was correlated with MCA PI., Conclusions: CCL/HC and CVH/HC measurements show differences in growth-restricted fetuses compared to a control cohort. We also found an inverse relationship between VA PI and CVH/HC. The potential use of neurosonography assessment in FGR assessment requires continued explorations., (© 2024 S. Karger AG, Basel.)

Introduction: The aim of the study was to identify predictors of poor outcomes in monochorionic diamniotic twin (MCDA) pregnancies with selective fetal growth restriction (sFGR), irrespective of the umbilical artery (UA) Doppler abnormalities., Methods: Single-center retrospective analysis of MCDA twins diagnosed with sFGR that opted for expectant management between 2010 and 2021. The presence of any of the following variables in the growth-restricted fetus: low amniotic fluid volume (DVP ≤2 cm), lack of a cycling bladder, absent or reversed flow in the ductus venosus (DV) with atrial contraction, and elevated middle cerebral artery peak systolic velocity (MCA-PSV) defined as ≥1.50 multiples of the median was categorized as complicated. sFGR cases were classified as simple in the absence of the above-mentioned variables., Results: Overall, 63.3% of cases qualified as simple, and 36.7% were complicated. Intertwin EFW discordance was higher in the complicated category (26 vs. 33%, p = 0.0002). The median gestational age at delivery was earlier (33 weeks vs. 30.5 weeks, p = 0.002), and the likelihood of survival was lower in the complicated category (p < 0.0001). The likelihood of two survivors to discharge was lower in type I complicated cases (70% in complicated type I vs. 97.1% in simple type I, p = 0.0003). On logistic regression analysis, an increase in the "complicated" score negatively correlated with two survivors to discharge (p < 0.0001). An ROC curve was created, and the AUC was 0.79. Increasing intertwin EFW discordance also decreased the probability of two survivors to discharge., Conclusion: The presence of oligohydramnios, lack of a cycling bladder, abnormal DV Doppler, and elevated MCA-PSV in the growth restricted fetus is associated with poor perinatal outcomes and a lower likelihood of having two survivors to discharge. The addition of intertwin EFW discordance to these variables helped improve the survival predictability., (© 2024 S. Karger AG, Basel.)

Objective: The aim of this work was to identify independent risk factors influencing the achievement of vaginal delivery among women undergoing labor induction for late-onset fetal growth restriction (FGR)., Methods: This was a retrospective cohort study of 201 singleton pregnancies with late-onset FGR (diagnosed >32 + 0 weeks) that required labor induction with cervical ripening from 37 + 0 weeks, either with dinoprostone (from 2014 to 2015) or Foley balloon (from 2016 to 2018). Independent factors for successful vaginal delivery were identified. A prediction model of vaginal delivery with the identified factors was made using logistic regression and bootstrapping with 1,000 re-samples performed for bias correction., Results: Perinatal results were more favorable in the vaginal delivery group, with significantly lower neonatal admission rates (4.0 vs. 13.7%) and lower composite neonatal morbidity (4.0 vs. 15.7%). The labor induction method (Foley balloon), higher cerebro-placental ratio, lower pre-gestational BMI, and absence of pre-eclampsia were identified as independent factors associated to vaginal delivery. The area under the curve of the model was of 0.75 (95% CI 0.70-0.79)., Conclusions: The use of a Foley balloon is the only modifiable risk factor to improve the chances of vaginal delivery when attempting induction of labor in singleton pregnancies with late-onset FGR., (© 2019 S. Karger AG, Basel.)

Objective: To assess the predictive ability of the ultrasound estimated percentile weight (EPW) at 35 weeks of pregnancy to predict adverse perinatal outcomes (APOs) at term delivery according to 5 fetal growth standards, including population, population-customized, and international references., Methods: This was a retrospective cohort study of 9,585 singleton pregnancies. Maternal clinical characteristics, fetal ultrasound data obtained at 35 weeks and pregnancy and perinatal outcomes were used to calculate EPWs to predict APOs according to: the customized and noncustomized (NC) Miguel Servet University Hospital (MSUH), the customized Figueras, the NC INTERGROWTH-21st, and the NC World Health Organization (WHO) international standards. APOs were defined as the occurrence of cesarean or instrumental delivery for nonreassuring fetal status, 5-min Apgar score < 7, arterial cord blood pH <7.10, or stillbirth. The predictive ability of EPW for APOs was analyzed using the area under the curve (AUC), and sensitivities were calculated for different false-positive rates (FPRs)., Results: For a 10% FPR, detection rates for total APOs ranged between 12.7% with the customized MSUH (AUC 0.52; 95% CI 0.50-0.55) and 14.4% with the NC MSUH standard (AUC 0.55; 95% CI 0.53-0.57) for EPW by ultrasound; and from 22.0% with the customized MSUH standard (AUC 0.60; 95% CI 0.58-0.63) to 27.8% with the NC WHO (AUC 0.65; 95% CI 0.63-0.68) for EPW at delivery., Conclusions: The predictive capacity of the EPW for APOS is limited and similar, by both ultrasound and at delivery, for the 5 growth standards, without significant differences between customized and NC standards., (© 2019 S. Karger AG, Basel.)

Background: Multifetal pregnancies are considered high-risk pregnancies compared to singleton pregnancies. Monochorionic diamniotic (MCDA) twin pregnancies tend to have a more complicated intrauterine course than their dichorionic counterparts. The most common complications are twin-to-twin transfusion syndrome (TTTS), selective fetal growth restriction (sFGR), and unexplained intrauterine fetal demise (IUFD). Early recognition of pregnancies at risk of developing complications will be helpful for counselling the parents and preparing them for necessary interventions in case a complication arises., Objectives: The aim of our study was to assess the role of discordant crown-rump length (dCRL), discordant nuchal translucency (dNT), and discordant abdominal circumference (dAC) measurements in isolation and in combination at the 11-13+6 weeks' scan in predicting the development of TTTS, sFGR, and IUFD., Methods: All MCDA twin pregnancies with structurally normal, both live fetuses at the 11-13+6 weeks' scan were followed up by FMF (Fetal Medicine Foundation)-certified operators for development of TTTS, sFGR, and single/double IUFD until delivery. Discordance of CRL, NT, and AC of more than or equal to 10% was considered a "marker," and its presence was correlated with the occurrence of specific antenatal complications, i.e., TTTS, sFGR, and single or double IUFD., Results: Combination of two markers predicted MCDA-related complications in the majority of cases (70.8% positive predictive value). Combination of dNT and dAC was the strongest predictor (80% positive predictive value)., Conclusions: In our population of MC twin pregnancies, dCRL, dNT, and dAC at the 11+0-13+6 weeks' scan, in isolation, had a low predictive value for antenatal complications, i.e., TTTS, sFGR, and single/double IUFD. However, the presence of at least two markers in the first trimester could predict complications in the majority of these pregnancies. The combination of dNT and dAC appears to be the best., (© 2020 S. Karger AG, Basel.)

Objective: To evaluate a dual-imaging modality approach to obtain a combined estimation of venous blood oxygenation (SνO2) using susceptibility-weighted magnetic resonance imaging (SWI-MRI), and blood perfusion using power Dopp-ler ultrasound (PDU) and fractional moving blood volume (FMBV) in the brain of normal growth and growth-restricted fetuses., Methods: Normal growth (n = 33) and growth-restricted fetuses (n = 10) from singleton pregnancies between 20 and 40 weeks of gestation were evaluated. MRI was performed and SνO2 was calculated using SWI-MRI data obtained in the straight section of the superior sagittal sinus. Blood perfusion was estimated using PDU and FMBV from the frontal lobe in a mid-sagittal plane of the fetal brain. The association between fetal brain SνO2 and FMBV, and the distribution of SνO2 and FMBV values across gestation were calculated for both groups., Results: In growth-restricted fetuses, the brain SνO2 values were similar, and the FMBV values were higher across gestation as compared to normal growth fetuses. There was a significantly positive association between SνO2 and FMBV values (slope = 0.38 ± 0.12; r = 0.7; p = 0.02) in growth-restricted fetuses. In normal growth fetuses, SνO2 showed a mild decreasing trend (slope = -0.7 ± 0.4; p = 0.1), whereas FMBV showed a mild increasing trend (slope = 0.2 ± 0.2; p = 0.2) with advancing gestation, and a mild but significant negative association (slope = -0.78 ± 0.3; r = -0.4; p = 0.04) between these two estimates., Conclusion: Combined MRI (SWI) and ultrasound (FMBV) techniques showed a significant association between cerebral blood oxygenation and blood perfusion in normal growth and growth-restricted fetuses. This dual-imaging approach could contribute to the early detection of fetal "brain sparing" and brain oxygen saturation changes in high-risk pregnancies., (© 2019 S. Karger AG, Basel.)

Objective: Mean uterine artery pulsatility index (meanUAPI) is commonly measured at 11-13+6 weeks to predict adverse pregnancy outcomes including hypertensive disorders and small-for-gestational age. The aims of this study were to establish a population-specific reference range for meanUAPI at <11 weeks, to determine if an abnormal meanUAPI at <11 weeks was associated with adverse pregnancy outcome, and to assess changes in meanUAPI between <11 weeks and 11-13+6 weeks., Methods: A prospective cohort was examined at <11 weeks and at 11-13+6 weeks to develop reference ranges for meanUAPI. Based on these regression models, meanUAPI Z-scores were compared between outcome groups using a two-sample t test. Longitudinal changes in the meanUAPI between <11 and 11-13+6 weeks were assessed by two-way mixed ANOVA., Results: Prior to 11 weeks, there was no significant difference in meanUAPI between normal (n = 622) and adverse (n = 80) outcomes (mean [95% CI]: 2.62 [2.57-2.67] and 2.67 [2.50-2.84], respectively; p = 0.807). At 11-13+6 weeks, meanUAPI was significantly higher in the adverse (n = 66) compared with the normal (n = 535) outcome group (mean [95% CI]: 1.87 [1.70-2.03] and 1.67 [1.63-1.72], respectively; p = 0.040). There was a statistically significant decrease (p < 0.0001) in meanUAPI between the two time points., Conclusion: MeanUAPI measured at <11 weeks' gestation does not appear to be a useful marker for the prediction of placental-related adverse pregnancy outcomes, supporting an argument for the prediction of risk at 11-13+6 weeks' gestation., (© 2019 S. Karger AG, Basel.)

Introduction: In intrauterine growth restriction (IUGR), increased uteroplacental vascular impedance contributes to preferential flow to left ventricle (LV), with consequent alteration of its compliance and increased left atrial (LA) pressure. Pulmonary vein pulsatility index (PVPI) reflects the increased impedance to LA filling and could be used as a cardiac monitoring parameter in IUGR., Material and Methods: A total of 27 IUGR fetuses (group 1), 28 fetuses with appropriate growth for gestational age from hypertensive mothers (group 2), and 28 controls (group 3) were studied. Pulsatility indices (PIs) of pulmonary veins and ductus venosus were calculated by Doppler echocardiography. Obstetric ultrasound was used to assess the PIs of uterine, umbilical, and middle cerebral arteries. Statistical analysis used analysis of variance, post-hoc Tukey, and Pearson's tests., Results: Mean PVPI was higher in IUGR group (1.27 ± 0.39) when compared to groups 2 (1.02 ± 0.37; p = 0.01) and 3 (0.75 ± 0.12; p < 0.001). In group 2, moderate correlation between PVPI and ductus venosus pulsatility index (DVPI) was found but not between PVPI and cerebroplacental ratio (CPR)., Discussion: Higher PVPI in IUGR reflects decreased LV compliance and altered LA dynamics. As LV dysfunction precedes right ventricle, our results suggest that PVPI could be an early echocardiographic parameter of fetal diastolic function in IUGR., (© 2018 S. Karger AG, Basel.)

Objective: The aim of this work was to compare the accuracy of the cerebroplacental ratio (CPR), Intergrowth 21st standards (IG21), customized growth (CG), and local population references (LPR) in the prediction of intrapartum fetal compromise (IFC)., Methods: This was a prospective study of 714 fetuses that underwent an ultrasound examination at 34-41 weeks and were delivered within a 2-week interval. The CPR was converted into multiples of the median and the estimated fetal weight (EFW) transformed into CG, IG21, and LPR centiles. IFC was defined as a composite of abnormal cardiotocogram, intrapartum pH requiring cesarean section, 5-min Apgar score, and admission to pediatric care units. The accuracies of the CPR and the EFW centiles for the prediction of IFC were evaluated alone and in combination with other gestational characteristics using univariate and multivariate analysis., Results: Individually, the CPR was the parameter that best predicted the existence of IFC (AUC = 0.66). The multivariate analysis showed that the best prediction was again achieved with the CPR, alone or in combination with any of the EFW centiles (AUC = 0.74). No significant differences were seen between the different centile methods., Conclusion: The best prediction of IFC is obtained with CPR. Evaluation of CPR should be encouraged in term and late-preterm fetuses., (© 2019 S. Karger AG, Basel.)

Introduction: We aimed to clarify the survival rate without brain abnormalities (BA) after fetoscopic laser photoco-agulation (FLP) for monochorionic diamniotic twin gestations (MCDA) with selective intrauterine growth restriction (sIUGR) accompanied by abnormal umbilical artery (UA) Doppler waveforms and isolated oligohydramnios in the sIUGR twin., Materials and Methods: This retrospective study included 52 cases that underwent FLP. The main outcome was survival rate without BA of the twins at age 28 days. BA was defined as severe intraventricular hemorrhage and periventricular leukomalacia on postnatal ultrasonography., Results: Median gestational age at FLP was 20 (16-24) weeks. Ten cases were classified as type III based on Doppler for the UA. For all cases, including 20 cases of anterior placenta, FLP was completed without major intraoperative complications. Amnioinfusion was required in 49 cases for better fetoscopic visualization. Fetal loss occurred in 29 sIUGR twins and two larger twins, whereas one larger twin experienced neonatal death. Survival rates without BA were 44% (n = 23) for sIUGR twins and 94% (n = 49) for the larger twins., Discussion: FLP for MCDA with sIUGR presenting with oligohydramnios in the sIUGR twin might be considered a prenatal treatment option., (© 2018 S. Karger AG, Basel.)

Background: Pregnancies complicated with small for gestational age (SGA) neonates are reported with maternal circulatory maladaptations., Objectives: We aimed to understand the pathophysiology of the maternal circulation in normotensive SGA pregnancies and to point out the trimestral differences from those with appropriate-to-large (non-SGA [NGA]) neonates., Methods: An observational study was conducted in 3 trimestral cohorts of normotensive pregnancies, categorized after birth according to neonatal birth weight percentile (BW%) as SGA (BW% ≤10, n = 158) or NGA (BW% > 10, n = 1,038). Standardized electrocardiogram-Doppler ultrasound, impedance cardiography, and bio-impedance were used to assess the maternal heart, arteries, veins, and fluid., Results: Diastolic blood pressure and mean arterial pressure were not significantly different, unless in the third trimester. In SGA compared to NGA pregnancies, total peripheral resistance (TPR) was higher and total arterial compliance, cardiac output (CO), and total body water (TBW) were lower throughout pregnancy. Venous return-enhancing functions were activated. In NGA but not SGA pregnancies, a positive correlation was found between BW% and CO + TBW and a negative correlation between BW% and TPR., Conclusions: SGA pregnancies are characterized by lower maternal body fluid volume and CO, while normal blood pressures are maintained via increased TPR already from the first trimester onwards. Pregnancy-induced hemodynamic changes are superimposed on these characteristics., (© 2019 S. Karger AG, Basel.)

Introduction: The structural correspondence of neurodevelopmental impairments related to intrauterine growth restriction (IUGR) that persists later in life remains elusive. Moreover, early postnatal stimulation strategies have been proposed to mitigate these effects. Long-term brain connectivity abnormalities in an IUGR rabbit model and the effects of early postnatal environmental enrichment (EE) were explored., Materials and Methods: IUGR was surgically induced in one horn, whereas the contralateral one produced the controls. Postnatally, a subgroup of IUGR animals was housed in an enriched environment. Functional assessment was performed at the neonatal and long-term periods. At the long-term period, structural brain connectivity was evaluated by means of diffusion-weighted brain magnetic resonance imaging and by histological assessment focused on the hippocampus., Results: IUGR animals displayed poorer functional results and presented altered whole-brain networks and decreased median fractional anisotropy in the hippocampus. Reduced density of dendritic spines and perineuronal nets from hippocampal neurons were also observed. Of note, IUGR animals exposed to enriched environment presented an improvement in terms of both function and structure., Conclusions: IUGR is associated with altered brain connectivity at the global and cellular level. A strategy based on early EE has the potential to restore the neurodevelopmental consequences of IUGR., (© 2017 S. Karger AG, Basel.)

Aim: To determine whether Doppler evaluation at 20-24 weeks of gestation can predict reduced fetal size later in pregnancy or at birth., Methods: Fetal biometry and Doppler velocimetry were performed in 2,986 women with a singleton pregnancy at 20-24 weeks of gestation. Predictive performances of the umbilical artery pulsatility index (UA-PI) or the mean uterine artery pulsatility index (UtA-PI) >95th percentile, middle cerebral artery pulsatility index, or cerebroplacental ratio (CPR) <5th percentile for early small for gestational age (SGA; <34 weeks of gestation), late SGA (≥34 weeks of gestation), or SGA at birth (birthweight <10th percentile) were analyzed., Results: The prevalence of early SGA, late SGA, and SGA at birth was 1.1, 9.6, and 14.7%, respectively. A CPR <5th percentile had a positive likelihood ratio (LR+) of 8.2 (95% confidence interval [CI] 5.7-12.0) for early SGA, a LR+ of 1.6 (95% CI 1.1-1.2) for late SGA, and a LR+ of 1.9 (95% CI 1.4-2.6) for SGA at birth. A UtA-PI >95th percentile was associated with late SGA and SGA at birth, while an UA-PI >95th percentile was associated with early SGA. Associations were higher in fetuses with an estimated fetal weight <10th percentile., Conclusion: Fetal biometry and Doppler evaluation at 20-24 weeks of gestation can predict early and late SGA as well as SGA at birth., (© 2017 S. Karger AG, Basel.)

Objective: We assessed whether umbilical cord blood placental growth factor (PlGF) levels at delivery are associated with fetal growth., Methods: From a prospective population-based cohort study we included 3,461 live singleton births. Fetal growth was assessed by birth weight, fetal growth pattern, and fetal growth restriction (FGR; decrease in growth between the second trimester and birth of ≥40 percentiles). In all analyses the highest PlGF multiple of the median (MoM) quintile was used as the reference category., Results: Umbilical cord PlGF was neither correlated with maternal second-trimester PlGF (p = 0.08) nor placental weight (p = 0.18), suggesting that PlGF from umbilical cord blood was of fetal origin. Lower PlGF MoM quintiles were associated with a lower birth weight (lowest quintile -0.60 standard deviation [95% confidence interval -0.71 to -0.48, p for trend <0.001]) and a different fetal growth pattern (p < 0.001). Finally, lower PlGF MoM quintiles were associated with FGR (lowest quintile odds ratio 2.00 [95% confidence interval 1.25 to 3.21, p for trend <0.001])., Conclusion: Lower umbilical cord PlGF levels are associated with lower birth weight, deviating fetal growth patterns, and a higher odds of FGR. Hence, cord blood PlGF might be a promising biomarker to determine deviations in fetal growth and FGR retrospectively, enabling follow-up of these neonates., (© 2017 S. Karger AG, Basel.)

Perinatal maternal smoking exposure (PMSE) is one of the major environmental risk factors encountered by the fetus. PMSE is usually associated with adverse pregnancy outcomes that may manifest at different stages of life. Nevertheless, fetal growth restriction is the most common smoking-induced side effect. PMSE induces changes in the maternal multiple organ systems. These alterations may affect placentation, which subsequently affects fetal growth. It is worthy to note, however, that the extent of maternal smoking-induced changes depends mainly on the maternal level of susceptibility. Hence, the perinatal pregnancy outcomes vary depending on the interaction between the triad: the maternal, fetal, and placental modifications, making it more complex. In this review, we try to unveil the effect of smoking-induced maternal changes on the maternal immune, endocrine, and metabolic pathways and their impact on fetal growth., (© 2017 S. Karger AG, Basel.)

Introduction: This study investigates patterns of intertwin size discordance in dichorionic diamniotic (DCDA) and monochorionic diamniotic (MCDA) twin pregnancies., Material and Methods: Ultrasound measurements of twin pregnancies, from 14 weeks to term, were collected by 9 hospitals over a 10-year period. This analysis considers the modelled and observed levels of discordance in abdominal circumference (AC) and estimated fetal weight (EFW) in relation to gestational age. Fitted models were analysed to produce charts displaying the expected range of intertwin discordance in AC and EFW at any given examination., Results: The dataset for analysis included a total of 9,866 ultrasound examinations in 1,802 DCDA and 323 MCDA twin pregnancies. The 95th percentile of intertwin discordance in EFW increased from 18.3% (95% CI, 17.8-18.7%) at 20 weeks to 21.9% (95% CI, 21.3-22.4%) at 30 weeks for DCDA pregnancies. The 95th percentile for intertwin discordance in AC was stable at 10-11% for this period. Slightly higher levels of discordance were observed for MCDA than for DCDA pregnancies., Discussion: The expected range of intertwin discordance in EFW and AC shows differences with gestational age and between DCDA and MCDA pregnancies., (© 2016 S. Karger AG, Basel.)

Introduction: Chronic reduction of oxygen and nutrient delivery to the fetus has been related to neurodevelopmental problems. Placental underperfusion induces a significant reduction in oxygen and nutrient delivery, whereas maternal undernutrition causes mainly nutrient deficiency. A comparison of the neurodevelopmental effects of both situations in pregnant rabbits was performed., Materials and Methods: The placental underperfusion model was induced after uteroplacental vessel ligation at 25 days of pregnancy. The undernutrition model was induced after a reduction of 70% of the basal maternal intake at 22 days of pregnancy. Neurobehavioral tests were applied in the derived offspring at the neonatal period and over the long term. Structural brain differences were evaluated by brain networks obtained from diffusion magnetic resonance imaging., Results: Birth weight was significantly lower in both cases. However, stillbirth was only increased in the placental underperfusion model. Cases from both models presented poorer neurobehavioral performance and network infrastructure, being more pronounced in the placental underperfusion model., Discussion: Prenatal insults during the last third of gestation resulted in functional and structural disturbances. The degree of neurodevelopmental impairment and its association with structural brain reorganization seemed to be related to the type of the prenatal insult, showing stronger effects in the placental underperfusion model., (© 2017 S. Karger AG, Basel.)

Objective: To study the umbilical artery (UA) half-peak systolic velocity deceleration time (hPSV-DT) in pregnancies complicated by fetal growth restriction (FGR)., Methods: The study included 266 singleton, high-risk pregnancies with an estimated fetal weight <10th percentile, which were examined between 24 and 40 weeks' gestation and delivered within a week from the last ultrasound evaluation. UA hPSV-DT was measured with Doppler ultrasound in the same wave used to measure the pulsatility index. UA hPSV-DT values were correlated with perinatal outcome., Results: UA hPSV-DT <5th percentile was found in 87 and 98% of fetuses with moderate and severe FGR, respectively. 94% of fetuses with a UA hPSV-DT <90 ms had poor perinatal outcome including perinatal death or prolonged admission to the neonatal intensive care unit. None of the fetuses had a UA hPSV-DT <70 ms. Perinatal death occurred in 39 fetuses; UA hPSV-DT was abnormal in all of them, with 95% of these fetuses having values of ≤120 ms. In the group of fetuses with absent/reverse end-diastolic velocity in the UA, the perinatal mortality rate was 51% for those with a UA hPSV-DT ≤90 ms and only 23% for those having a UA hPSV-DT >90 ms (p < 0.01)., Conclusions: UA hPSV-DT seems to be a useful technique in the evaluation of pregnancies at risk for FGR and perinatal death. Additionally, hPSV-DT was shown to be a good predictor of perinatal death, with values of <90 ms corresponding to imminent risk of intrauterine demise and values of <70 ms being likely to be incompatible with intrauterine life., (© 2015 S. Karger AG, Basel.)

Objective: To evaluate the intermediate intracardiac diastolic velocities in fetuses with growth restriction., Methods: Doppler waveforms of the two atrioventricular valves were obtained. Peak velocities of the E (early) and A (atrial) components, and the lowest intermediate velocity (IDV) between them, were measured in 400 normally grown and in 100 growth-restricted fetuses. The prevalence of abnormal IDV, E/IDV, and A/IDV ratios in fetuses presenting with perinatal death or acidemia at birth (pH ≤7.1) was estimated., Results: IDV was significantly lower and E/IDV ratios significantly higher in the two ventricles of growth-restricted fetuses with reduced diastolic velocities in the umbilical artery (p < 0.05). In 13 fetuses presenting with perinatal death or acidemia at birth, 11 (85%) had either an E/IDV or A/IDV ratio >95th percentile, whereas 5 (38%) showed absent or reversed atrial velocities in the ductus venosus (DV-ARAV; p < 0.04). Fetuses without DV-ARAV but with elevated E/IDV ratios in either ventricle were nearly 7-fold more likely to have perinatal demise or acidemia at birth (OR 6.9, 95% CI 1.4-34) than those with E/IDV ratios <95th percentile., Conclusion: The E/IDV and A/IDV ratios in the two cardiac ventricles might provide information about the risk of perinatal demise or acidemia in growth-restricted fetuses., (© 2015 S. Karger AG, Basel.)

Objective: This study aimed to assess the cardiac function of healthy and pathological fetuses by measuring radial velocity using phased tracking (PT). Based on phase differences, PT allows the displacement of a specified point to be detected with improved spatial and temporal resolution., Methods: PT was used to assess cardiac radial velocity in the basal free wall of the left and right ventricles in 134 healthy fetuses, 10 second-trimester intrauterine growth-restricted (IUGR) fetuses, and 10 recipient twins with twin-to-twin transfusion syndrome (TTTS). Maximum velocities were measured in systole and early diastole., Results: Maximum radial velocity was successfully measured in 126 healthy fetuses (94%) at gestational ages of 16-40 weeks. Systolic and early diastolic maximum velocities increased with gestational age in both ventricles. As compared with controls, IUGR fetuses had significantly lower early diastolic maximum velocities in the right ventricle, and recipient twins with TTTS had significantly lower systolic and early diastolic maximum velocities in both ventricles., Conclusions: PT demonstrated right ventricular diastolic dysfunction in second-trimester IUGR fetuses as well as systolic and diastolic dysfunctions in both ventricles in recipient twins with TTTS. PT could be useful for evaluating fetal cardiac radial function.

In the modern world, cardiovascular disorders are the leading cause of mortality in developed countries, which in most cases undergo a long subclinical phase that can last decades before the first clinical symptoms appear. Aside from the well-known risk factors related to lifestyle and genetics, there is growing evidence that in a proportion of cases, the predisposition to cardiovascular disease lies in prenatal life. Moreover, numerous historical cohort studies and animal models have shown a clear association between low birth weight and increased cardiovascular mortality in adulthood, including increased risk of hypertension, diabetes, dyslipidemia and coagulation disorders in children and adults. Besides premature birth, low birth weight in the majority of the cases is caused by intrauterine growth restriction (IUGR), which affects up to 10% of all births. Several clinical and experimental studies showed that IUGR fetuses present signs of cardiac dysfunction in utero that persist postnatally and may condition higher cardiovascular risk later in life. The present review discusses the importance of the long-term cardiovascular follow-up of the patients who suffered early or late IUGR in utero, particularly with regard to the long-term epidemiological studies in adults, prospective studies in children and the possible mechanisms that trigger IUGR and cardiovascular programming. Considering the high prevalence of IUGR and the progressing availability of intervention strategies, it is of the highest clinical relevance to detect cardiovascular risks as early as possible, to introduce timely preventive interventions and to adapt the lifestyle, in order to improve the long-term cardiovascular health outcome of IUGR cases., (Copyright © 2013 S. Karger AG, Basel.)

Objective: The terms early- and late-onset fetal growth restriction (FGR) are commonly used to distinguish two phenotypes characterized by differences in onset, fetoplacental Doppler, association with preeclampsia (PE) and severity. We evaluated the optimal gestational age (GA) cut-off maximizing differences among these two forms., Patients and Methods: A cohort of 656 consecutive singleton pregnancies with FGR was created. We used the decision tree analysis to evaluate the GA cut-off that best discriminated perinatal mortality, association with PE and adverse perinatal outcome (fetal demise, early neonatal death, neonatal acidosis at birth, and 5-min Apgar score <7)., Results: We identified 32 weeks at diagnosis as the optimal cut-off, resulting in two groups with 7.1 and 0%, p < 0.001 perinatal mortality, 35.1 and 12.1%, p < 0.001 association with PE, and 13.4 and 4.6%, p < 0.001 composite adverse perinatal outcome. Abnormal versus normal umbilical artery (UA) Doppler classified two groups with 10.6 and 0.2%, p < 0.001 perinatal mortality, 50.0 and 11.8%, p < 0.001 association with PE, and 18.2 and 4.2%, p < 0.001 composite adverse perinatal outcome., Conclusions: UA Doppler discriminated better the two forms of FGR with average early- and late-onset presentation, higher association with PE and poorer outcome. In the absence of UA information, a GA cut-off of 32 weeks at diagnosis maximizes differences between early- and late-onset FGR.

Fetal growth restriction (FGR) can emerge as a complication of placental dysfunction and increases the risk for neurodevelopmental delay. Marked elevations of umbilical artery (UA) Doppler resistance that set the stage for cardiovascular and biophysical deterioration with subsequent preterm birth characterize early-onset FGR. Minimal, or absent UA Doppler abnormalities and isolated cerebral Doppler changes with subtle deterioration and a high risk for unanticipated term stillbirth are characteristic for late-onset FGR. Nutritional deficiency manifested in lagging head growth is the most powerful predictor of developmental delay in all forms of FGR. Extremes of blood flow resistance and cardiovascular deterioration, prematurity and intracranial hemorrhage increase the risks for psychomotor delay and cerebral palsy. In late-onset FGR, regional cerebral vascular redistribution correlates with abnormal behavioral domains. Irrespective of the phenotype of FGR, prenatal tests that provide precise and independent stratification of risks for adverse neurodevelopment have yet to be determined.

Objective: To examine the possible relationship between maternal and fetal characteristics and pregnancy outcomes on fetal and maternal cell-free (cf) DNA in maternal plasma at 11-13 weeks' gestation., Methods: cfDNA was extracted from maternal plasma of 1,949 singleton pregnancies and chromosome-selective sequencing was used to determine the proportion of cfDNA and total cfDNA counts which was of fetal and maternal origin. Multivariate regression analysis was used to determine whether specific maternal and fetal characteristics and pregnancy complications, such as preeclampsia (PE), early spontaneous preterm birth (SPB) and delivery of small for gestational age (SGA) neonates, were significant predictors of fetal and maternal cfDNA in maternal plasma., Results: The fetal and maternal cfDNA plasma concentration increased with serum pregnancy-associated plasma protein-A and free β-human chorionic gonadotropin level, was higher in women of Afro-Caribbean and East-Asian racial origin than in Caucasians, and lower in smokers, but it was not significantly altered in pregnancies complicated by PE, SPB or SGA. The fetal cfDNA level was inversely related to maternal weight and uterine artery pulsatility index, and maternal cfDNA increased with maternal weight., Conclusions: The fetal and maternal cfDNA level in maternal plasma is affected by maternal and fetal characteristics, but it is not altered in pregnancy complications., (Copyright © 2013 S. Karger AG, Basel.)

Objectives: We tested the hypothesis whether a texture analysis (TA) algorithm applied to MRI brain images identified different patterns in small for gestational age (SGA) fetuses as compared with adequate for gestational age (AGA)., Study Design: MRI was performed on 83 SGA and 70 AGA at 37 weeks' GA. Texture features were quantified in the frontal lobe, basal ganglia, mesencephalon, cerebellum and cingulum. A classification algorithm based on discriminative models was used to correlate texture features with clinical diagnosis., Results: Region of interest delineation in all areas was achieved in 61 SGA (12 vasodilated) and 52 AGA; this was the sample for TA feature extraction which allowed classifying SGA from AGA with accuracies ranging from 90.9 to 98.9% in SGA versus AGA comparison and from 93.6 to 100% in vasodilated SGA versus AGA comparison., Conclusions: This study demonstrates that TA can detect brain differences in SGA fetuses. This supports the existence of brain microstructural changes in SGA fetuses., (Copyright © 2013 S. Karger AG, Basel.)

Objective: Cardiovascular status in fetal growth restriction (FGR) can be classified by the severity of individual Doppler abnormalities (early and late) or by the rate of clinical progression. We tested the hypothesis that aspects of the fetal cardiovascular status in FGR affect neonatal cardiovascular findings., Study Design: FGR cases [abdominal circumference <5th percentile and an elevated umbilical (MCA) artery (UA) pulsatility index] had UA, middle cerebral artery and ductus venosus (DV) Doppler. Positive UA end-diastolic velocity and/or a low MCA pulsatility index denoted early and absent/reversed UA end-diastolic velocity, whereas an increased DV pulsatility index for veins denoted late responses. The rate of progression was classified into mild, progressive and severe. After delivery, shunt dynamics and blood flow across the patent ductus arteriosus (PDA), foramen ovale and atriaventricular valves, myocardial contractility and pharmacologic pressor requirement were noted at neonatal echocardiography. These findings were related to prenatal Doppler parameters., Results: In 94 patients, only individual Doppler parameters related to neonatal echocardiographic findings. Absent/reversed UA DV significantly predicted PDA with right to left shunt (p = 0.016). The pressor need for cardiovascular instability was observed in neonates with abnormal prenatal DV Doppler and with lower birth weights delivered at earlier gestational age (p < 0.0001 for both). Pressor need was significantly related to neonatal death (Nagelkerke R² = 0.35, p = 0.002)., Conclusion: A markedly abnormal UA Doppler predisposes growth-restricted neonates to persistence of fetal circulation associated with right to left shunting. Abnormal venous Doppler is a risk factor for cardiovascular instability which in turn significantly contributes to neonatal mortality. Further clarification of the neonatal cardiovascular transition may be helpful in guiding early neonatal assessment and management., (Copyright © 2012 S. Karger AG, Basel.)

Objective: To assess the value of gestational age and cardiovascular Doppler indices in predicting perinatal mortality in a multicenter cohort of early-onset intrauterine growth-restricted (IUGR) fetuses., Methods: A multicenter prospective cohort study including 157 early-onset (<34 weeks) IUGR cases with abnormal umbilical artery (UA) Doppler was conducted. Cardiovascular assessment included the ductus venosus (DV), the aortic isthmus flow index (IFI), and the myocardial performance index (MPI). Isolated and combined values to predict the risk of perinatal death were evaluated by logistic regression and by decision tree analysis, where the gestational age at delivery, UA, and middle cerebral artery (MCA) were also included as covariates., Results: Perinatal mortality was 17% (27/157). All parameters were significantly associated with perinatal death, with individual odds ratios (OR) of 25.2 for gestational age below 28 weeks, 12.1 for absent/reversed DV atrial flow, 5.3 for MCA pulsatility index <5th centile, 4.6 for UA absent/reversed diastolic end-flow, 1.8 for IFI <5th centile, and 1.6 for MPI >95th centile. Decision tree analysis identified gestational age at birth as the best predictor of death (<26 weeks, 93% mortality; 26-28 weeks, 29% mortality, and >28 weeks, 3% mortality). Between 26 and 28 weeks, DV atrial flow allowed further stratification between high (60%) and low risk (18%) of mortality., Conclusions: Gestational age largely determines the risk of perinatal mortality in early-onset IUGR before 26 weeks and later than 28 weeks of gestation. The DV may improve clinical management by stratifying the probability of death between 26 and 28 weeks of gestation., (Copyright © 2012 S. Karger AG, Basel.)

Monochorionic (MC) twins represent a significant proportion of perinatal morbidity and mortality. Overall, 1 of 3 MC twin pregnancies will develop complications in relation to the MC placenta and the presence of interfetal placental anastomoses. From a clinical standpoint, these complications can be grouped into four main types of clinical problems: chronic transfusion, acute transfusion, growth discordance, and discordant malformation. Differential diagnosis of MC twin complications is still challenging due to frequent overlap of their clinical signs and the complex relationships between them. Clinical experience demonstrates that most instances of wrong management derive from failure to comply with a basic set of rules for diagnosis and management. In this review, we propose a simplified approach to the understanding of MC twin pregnancy, its potential complications, and the key concepts allowing adequate differential diagnosis and targeted management., (Copyright © 2012 S. Karger AG, Basel.)

Objective: To examine aortic systolic blood pressure (SBP(Ao)), pulse wave velocity (PWV) and augmentation index (adjusted to a heart rate of 75 beats per minute, AIx-75) at 11-13 weeks' gestation in pregnancies delivering small for gestational age (SGA) neonates with and without preeclampsia (PE)., Methods: At 11+0 to 13+6 weeks' gestation, maternal history was recorded and PWV, AIx-75, SBP(Ao), uterine artery pulsatility index (PI) and maternal serum pregnancy-associated plasma protein-A (PAPP-A) were measured. We compared women with (n = 337) and without (n = 48) PE that delivered SGA neonates with unaffected controls (n = 6,429)., Results: In the SGA group without PE, compared to unaffected controls, there was no significant difference in AIx-75 (1.03 vs. 1.00 multiple of the median, MoM), PWV (0.98 vs. 1.00 MoM) or SBP(Ao) (1.01 vs. 1.00 MoM), but uterine artery PI was increased (1.10 vs. 1.00 MoM) and PAPP-A decreased (0.85 vs. 1.00 MoM). In SGA with PE, compared to unaffected controls, there was increased AIx-75 (1.13 vs. 1.00 MoM), SBP(Ao) (1.09 vs. 1.00 MoM), uterine artery PI (1.40 vs. 1.00 MoM) and decreased PAPP-A (0.72 vs. 1.00 MoM), but no significant difference in PWV (1.05 vs. 1.00 MoM)., Conclusion: In pregnancies with SGA neonates, impaired placentation is reflected in low PAPP-A and high uterine artery PI at 11-13 weeks' gestation. In the SGA group with PE, but not in those without PE, there is increased SBP(Ao) and AIx-75., (Copyright © 2012 S. Karger AG, Basel.)

Structural evaluation of the fetal heart is well established. Functional evaluation using pulsed-wave Doppler may also be performed. E/A ratios express the relationship between the maximal velocities of the E and A waveforms of ventricular filling. In normal fetuses, E/A ratios are usually <1 but show a constant increment during gestation, mainly related to the increment of the E wave. In intrauterine growth restriction (IUGR) fetuses, E/A ratios are lower compared to values in normally grown fetuses at the same gestational age. Cardiac outflows provide information on the time-velocity integral that, combined with the vessel area, allows calculation of the left and right cardiac outputs. In normal fetuses there is a predominance of the right ventricle (55-60%) in contributing to the combined cardiac output. In IUGR fetuses this predominance shifts to the left ventricle in order to increase the flow to the upper part of the fetal body and brain. The myocardial performance index (MPI) also provides information on systolic and diastolic cardiac function. The MPI is an early and consistent marker of cardiac dysfunction which becomes altered in early stages of chronic hypoxia or in cases with cardiac overload such as in twin-to-twin transfusion syndrome., (Copyright © 2012 S. Karger AG, Basel.)

Objective: To establish a normal range of birthweight with gestational age (GA) at delivery and examine the contribution of maternal characteristics in defining growth restriction in stillbirths., Methods: In 69,895 normal singleton pregnancies, regression analysis was used to determine the association of birthweight with GA and maternal characteristics. The proportion of 290 stillbirths classified as small for GA depending on inclusion or exclusion of maternal characteristics was determined., Results: In normal pregnancies, there was a polynomial association between birthweight and GA. Birthweight increased with maternal weight, height and parity and was lower in Africans and South Asians than in Caucasians. Birthweight for GA was reduced in antepartum stillbirths (n = 243; p < 0.0001) but not in intrapartum stillbirths (n = 47; p = 0.334). There was no significant difference in the proportion of antepartum stillbirths with birthweight below the 10th percentile when birthweight was corrected for GA only compared to correction for GA and maternal characteristics (53.1 vs. 54.3%). The birthweight was below the 10th percentile in 71.8% of antepartum stillbirths at <32 weeks' gestation, in 47.2% at 33-36 weeks and in 31.5% at ≥37 weeks., Conclusion: Correction of birthweight for maternal characteristics does not alter the proportion of stillbirths that are small for GA., (Copyright © 2012 S. Karger AG, Basel.)

Objective: To investigate glomerular development and expression of insulin and insulin-like growth factor receptors in an experimental model of intrauterine growth restriction (IUGR)., Material and Methods: We studied three groups of Sprague-Dawley fetuses: IUGR - restricted by ligation of the right uterine artery; C-IUGR - left horn controls, and EC - external controls (non-manipulated). Body and organs were weighed, and glomerular number and volume were analyzed. Expression of IRβ, IRS-1, IRS-2 and IGF-IRβ was analyzed in liver, intestine and kidneys by immunoblotting., Results: Organ/body weight ratios were similar. In IUGR, glomerular number and volume were increased compared to C-IUGR and EC (p<0.001). In the IUGR liver, increases were found in IGF-IRβ compared to C-IUGR and EC; IRβ compared to EC, and IRS-2 compared to C-IUGR. However, decreases in IRβ were noted in IUGR compared to C-IUGR; IRS-1 compared to C-IUGR and EC, and IRS-2 compared to EC. In IUGR intestine, increases were detected in IRβ, IRS-1 and IGF-IRβ compared to C-IUGR and EC. In IUGR kidneys, increases were observed in IRβ and IGF-IRβ compared to C-IUGR and EC, and IRS-1 compared to EC. Decreased IRS-2 in the intestine and kidney were noticed in IUGR compared to C-IUGR and EC., Conclusion: IUGR fetuses had less glomeruli and alterations in insulin receptors, which may be associated with an increased risk of disease occurrence in adulthood., (Copyright © 2010 S. Karger AG, Basel.)

Unlabelled: Fetuses with digestive anomalies such as gastroschisis may present intrauterine growth restriction (IUGR) and shortened intestines., Objective: The aim of this study was to assess the influence caused by amniotic fluid (AF) in intestinal length and somatic growth in an experimental gastroschisis fetal model at two distinct gestational ages., Material and Method: Fetal rats were operated according to Correia-Pinto on 2 different days of gestation: day 18.5 (group I) and day 19.5 (group II). Each group was divided into three sub-groups: fetuses with gastroschisis (G), control (C) and sham(S). Body measurements and histological analysis were done., Result: Body measurement analysis showed: average body weight (g) in group I was G = 5.32, C = 5.68, S = 5.86; group II was G = 5.32, C = 5.80, S = 5.66. Average intestine weight (g) in group I was G = 0.283, C = 0.238, S = 0.231; group II was G = 0.272, C = 0.231, S = 0.233. Average intestine length (mm) in group I was G = 125, C = 216, S = 209; group II was G = 148, C = 226, S = 226. Histological analysis showed a decrease in the number and size of the intestinal microvillae and a light edema of serosa., Conclusion: Gastroschisis had a direct correlation with IUGR and the time of exposure of the fetuses to AF had no influence on body weight in gastroschisis fetuses but did interfere with intestinal length., (Copyright (c) 2005 S. Karger AG, Basel.)

Both insulin and estrogen are well recognized as growth-promoting substances at physiological concentrations, but they function as teratogens at high doses. Both agents can affect alterations in fetal and maternal serum human alpha-fetoprotein (HAFP) levels during pregnancy. In the present study, we have employed animal models of both insulin and estrogen fetotoxicity and teratogenicity in order to study the growth-regulatory properties of HAFP and its derived peptides (HAFP/PEP). We report here the effects of HAFP/PEP on fetotoxicity, congenital malformations, and growth retardation in developing chick and murine fetuses. In the insulin model, HAFP/PEP were effective in reducing both fetal mortality and anatomic anomalies, with the result that growth-retarded fetuses were produced. With HAFP/PEP treatment, fetal demise was reduced by as much as 73 and 63% in murine and chick fetuses, respectively, while fetal anomalies were diminished by 50% during chick development. Genebank searches of identity/similarity in a HAFP/PEP fragment identified matches with a number of proteins associated with glucose, pH, ionic, osmotic, and oxidative stresses, and with heat shock, in addition to stress proteins related to protein folding/unfolding processes. It was proposed that the peptide segment on HAFP may represent a topographic 'hotspot', sensitive to stress/shock conditions, which exhibits a propensity for conformational alteration in the tertiary structure of the fetal protein., (Copyright 2003 S. Karger AG, Basel)

Objective: To evaluate alterations of arterial and ductus venosus blood flow velocities during deterioration and their interdependence., Methods: 37 high-risk pregnancies complicated by umbilical absent or reverse end-diastolic flow velocities (AREDV) were monitored by measurement of the pulsatility index of the umbilical artery, middle cerebral artery and ductus venosus waveforms., Results: The mean observation period was 16.5 days. There was a significant change in the pulsatility of waveforms in all vessels over the observation period. Compared with the ductus venosus, pulsatility of waveforms in the middle cerebral artery diverged from the normal range 2.2 weeks earlier. Increase in pulsatility in the umbilical artery was concomitant with venous but not with cerebral flow alterations. In addition, there was a correlation between the increase of venous but not arterial pulsatility and perinatal acidemia. Variability of pulsatility index values of the umbilical artery and the ductus venosus but not of the middle cerebral artery increased towards delivery., Conclusions: Ductus venosus Doppler allows detection of further deterioration in centralized fetuses with umbilical AREDV. However, striking short-term variability has to be taken into account when considering this parameter., (Copyright 2003 S. Karger AG, Basel)

Objective: Subject of the study was the significance of umbilical artery Doppler velocimetry findings for the further course of pregnancy and fetal outcome in cases of twin pregnancies., Methods: In 206 cases of twin pregnancy, the umbilical artery was examined using Doppler velocimetry in the median 9 days prior to delivery, and the result was correlated with the further course of pregnancy and fetal outcome. 174 pregnancies showed normal Doppler findings of the umbilical artery (group A), 32 twin pregnancies showed pathological Doppler findings of at least one twin (group B). The median of the maternal age and the parity between the groups were not different., Results: In group B (pathological Doppler findings), intrauterine growth retardation and pre-eclampsia occurred 5 times more often than in group A (normal Doppler findings). The total rate of cesarean sections was not different between the study populations; the rate of deliveries by cesarean section in group B was significantly increased by a factor of 2.4 due to a pathological CTG. The median birth weight and the gestational age at birth were significantly lower in group B (1,660 g; 35 weeks) as compared to group A (2,460 g; 37 weeks; p<0.001). In group B, the rate of premature deliveries up to reaching the 34th week of gestation was 3. 4 times higher; the rate of SGA newborns was 6.3 times higher. Perinatal mortality was increased by a factor of 1.5 in group B compared to group A., Conclusion: The Doppler velocimetry findings have considerable effects on the further course of a multiple pregnancy. In case of pathological Doppler findings, early hospitalization and close monitoring of the pregnancy should be performed. In cases of additional pathological findings (maternal illness, pathological Doppler findings of fetal blood vessels), termination of the pregnancy has to be considered., (Copyright 2000 S. Karger AG, Basel.)

Intrauterine growth retardation is a pathology which is found in 3-10% of all pregnancies and it is associated with around 20-25% of all fetal intrauterine deaths and with long-term neurologic sequelae. It presents an increased risk of distress during labor and delivery and a greater risk of perinatal mortality. The causes of IUGR and the cardiac and venous Doppler in normal fetuses are analyzed, and the hemodynamic cardiac modifications in IUGR fetus are discussed. The fetal cardiac function in intrauterine growth retardation shows a redistribution of the fetal cardiac output, which tends to favor the left ventricle as the mechanism to compensate for the uteroplacental insufficiency. The Doppler velocity indices are modified as the fetal condition progressively deteriorates and they represent an important tool for the management of the complicated pregnancy., (Copyright 2000 S. Karger AG, Basel.)

Objective: Spectral analysis was conducted on fetal heart rate fluctuations for the purpose of investigating the change in gestational age and examining the usefulness as a method of estimating fetal blood gas., Study Design: Five hundred and twenty-nine pregnant women with a single normal fetus and 26 women with intrauterine growth restriction (IUGR) were studied during the 20th to 38th gestational weeks. In cases of IUGR, fetal blood gas levels were evaluated with percutaneous umbilical blood sampling. A time series of fetal heart rate fluctuation was obtained with a 1. 15-MHz ultrasonic transducer, and power spectral analysis of 200 consecutive stable beats was performed with an autoregression method. Integrated areas of 0.025-0.125 cycles/beat were defined as low-frequency areas (LFAs) and were examined in normal fetuses. In addition, the relation between LFA and fetal blood gas values was studied., Results: As pregnancy progressed, LFA increased with a cubic regression equation (Y = 6.484 - 0.764X + 0.029X2 - 0.00034X3). The correlation coefficient was 0.625 (p < 0.05). In the cases of IUGR, DeltaLFA was highly correlated with DeltapO2 and DeltapH (correlation coefficient, 0.650 and 0.618, respectively)., Conclusions: Measurement of LFA provides insight into the development of fetal autonomic function and also may serve as a quantitative index of fetal well-being in mid-pregnancy.

Objective: To determine the value of Doppler ultrasonographic examinations of the uterine artery in high-risk collectives and their importance as compared to examinations of the umbilical artery., Methods: In 142 patients with fetal growth retardation (birth weight <10th percentile) and/or pre-eclampsia/HELLP syndrome (as defined by ACOG criteria), the umbilical artery and the uterine arteries were examined bilaterally using a 3.5/5-MHz color Doppler system (Acuson 128). The patients were assigned to six groups according to the Doppler findings (uterine artery unilaterally/bilaterally normal/pathologic and umbilical artery normal/pathologic). For each group, the median of the birth weight and the gestational age at delivery was determined and the frequency of occurrence of complications was calculated., Results: In cases with pathologic results in all three vessels, the median gestational age at delivery and the median birth weight were significantly lower than in all other subgroups. Of the cases with pathologic findings in the umbilical artery only, 6% had pre-eclampsia/HELLP syndrome. However, this complication developed in 90% of the cases with pathologic findings in both uterine arteries. If only the umbilical artery was examined (and not the uterine arteries) the Doppler results were normal in 40 (28%) of the patients in our high-risk group, thus incorrectly simulating undisturbed placental hemodynamics., Conclusions: Examination of both uterine arteries is an indispensable element of Doppler examination to assess placental performance and risk to the fetus.

Objective: To determine whether severe, early-onset intrauterine growth restriction (IUGR) is associated with abnormal umbilical venous pressure (UVP) secondary to increased placental impedance., Methods: 42 singleton fetuses underwent fetal blood sampling from the umbilical vein during evaluation for severe, early-onset IUGR (diagnosed < 32 weeks or symmetrical IUGR diagnosed at any time in gestation). IUGR was confirmed at delivery. The UVP was measured with a solid-state transducer and corrected for amniotic fluid pressure. The ultimate cause of IUGR assigned was based on the antenatal laboratory and postnatal findings. Seven fetuses had a chromosome abnormality, 4 congenital viral infection, 8 miscellaneous causes and 23, by exclusion, uteroplacental (UP) dysfunction. Procedures complicated by fetal bradycardia were excluded because bradycardia raises the UVP., Results: The mean gestation was 31.4 weeks (range 23-38). The umbilical artery resistance index (UA RI) was significantly higher in fetuses with IUGR secondary to either UP dysfunction or a chromosome abnormality compared to the remaining categories of IUGR. The UVP fell outside the 95% confidence interval in only 3 fetuses - 2 with aneuploidy (a 1:7 translocation with a normal UA RI and a mosaic trisomy 21), and 1 with UP dysfunction. The UVP rose with advancing gestation independent of the underlying cause of IUGR. There was an inverse relationship between UVP and the UA RI independent of gestation (r2 = 0.08, p < 0.05). There was an inverse relationship between the UA RI and both the UV pH and PO2 in the fetuses with UP dysfunction. However, there was no relationship between the UVP and either UVpH, UVPCO2, or UVpO2., Conclusions: These findings indicate that placental impedance has little clinically relevant impact on the UVP.

Objective: This study was designed to evaluate if fetal diastolic cardiac function is compromised in small-for-gestational-age (SGA) fetuses with documented fetal well-being at the biophysical profile., Study Design: We have compared indices of diastolic cardiac flow in singleton SGA fetuses with forward diastolic flow in the umbilical artery at Doppler velocimetry and documented fetal well-being (n = 10) with those of appropriate-for-gestational-age (AGA) controls with documented fetal well-being matched for gestational age at ultrasound (n = 20)., Results: At the mitral valve, velocity time integral (VTI) (0.059+/-0.011 vs. 0.069+/-0.011 m, p = 0.04), peak velocity of the A wave (0.426+/-0.043 vs. 0.498+/-0.087 m/s, p = 0.005), and acceleration time of the E wave (0.046+/-0.004 vs. 0.053+/-0.007 s, p = 0.008) were significantly different between SGA and AGA fetuses. At the right atrioventricular valve, only VTI was significantly different between SGA and AGA fetuses (0.065+/-0.014 vs. 0.078+/-0.011, p = 0.03)., Conclusions: These findings suggest that SGA fetuses have significantly lower left and right ventricular diastolic filling compared with AGA fetuses without significant changes in diastolic function.

Objective: The study of fetal lung circulation by means of pulmonary Doppler investigation., Methods: Pulmonary Doppler ultrasound obtained with color pulsed-Doppler with a 3.5- to 5-MHz probe. Measure of resistance index and pulsatility index., Patients: 47 pregnant women with singleton, between 18 and 39.5 weeks of gestation, were recruited to have pulmonary Doppler ultrasound. Seven fetuses had intrauterine fetal growth retardation (IUGR). Overall, 50 Doppler velocity waveforms were measured., Results: Resistance and pulsatility index were measured in all patients and at each examination. Resistance index (0.86 +/- 0.03) and pulsatility index (2.46 +/- 0.34) were found to be stable during pregnancy. Pulmonary pulsatility index in IUGR fetuses (2.71 +/- 0.33) were found to be higher than those in normotrophic infants (p = 0.006), whereas no difference was found in resistance index between the same subgroups. Moreover, no difference was found in pulsatility index measurements between preterm small-for-gestational age fetuses and normotrophic fetuses measured between 36 and 39.5 weeks of gestation (2.68 +/- 0.31 vs. 2.49 +/- 0.28)., Conclusion: Pulmonary resistance index is not statistically different between normotrophic and IUGR fetuses. In contrast, pulmonary pulsatility index is significantly higher in IUGR fetuses when compared to normotrophic fetuses. Pulmonary Doppler ultrasound should be evaluated in a larger trial and correlation between Doppler measurements and fetal lung maturation should be studied.

Purpose: To study the effect of betamethasone and dexamethasone on fetal heart rate in 55 growth-retarded fetuses., Material and Methods: Fifty-five fetuses with intrauterine growth retardation were exposed in utero to betamethasone (group 1, n = 32) or dexamethasone (group 2; n = 17). Six fetuses received both steroids alternatively at weekly intervals. Computerized cardiotocograms were recorded and analyzed retrospectively. Traces were obtained before, 1 day, 2 days and 4-7 days after treatment was started., Results: One day after treatment was started, both steroids were associated with an initial increase in fetal heart rate variation that was higher with dexamethasone. Short-term variation was significantly decreased during the betamethasone course. All parameters returned to their pretreatment values within a week., Conclusion: Dexamethasone and betamethasone had similar effects compatible with a transient damping effect on fetal heart rate variability that reached significance only with betamethasone.

The loss of middle cerebral artery compensatory vasodilation appears to be ominous in fetuses with absent end-diastolic umbilical waveforms. The authors report a case with a loss of the 'brain-sparing effect' 24 h before fetal death. Current pathophysiological explanations are discussed.

Ultrasound examination at 9 weeks of gestation in a 34-year-old primigravida showed a twin pregnancy, with discrepancy in the sizes of the two gestational sacs, whereas the crown-rump lengths and fetal heart rates were virtually identical-the result being an abnormal sac size/crown-rump length ratio (early oligohydramnios). By 14 weeks discordant heart rates and umbilical artery flow velocities were detected, the discordance between the twins increasing as pregnancy progressed. Biparietal diameters, femoral lengths, and abdominal circumferences were also progressively discordant, and at 28 weeks the smaller twin had no heart beat. At 30 weeks the patient was delivered of a live 1,350-gram infant and a 400-gram dead fetus. This case suggests, in contradistinction to several previous reports, that fetal discordance in twin pregnancies (and perhaps intrauterine growth retardation in general) may be present as early as the first trimester.

One hundred and three intrauterine growth retardation (IUGR) pregnancies were scheduled for pulsed Doppler ultrasound of the common carotid and the umbilical artery, nonstress and contraction stress tests (NST/CST) as well as vibroacoustic stimulation tests (VAST). The last examinations < 3 days before birth were compared by receiver-operator characteristics: Results of the resistance indices of fetal common carotid/umbilical artery and NST were more predictive of later fetal distress during labour, compared to CST and VAST (p < 0.001/< 0.01). Similar results were found for the prediction of low pH and Apgar values, though differences were less pronounced. Our results suggest that stressful examinations should be abolished from mother and fetus in the supervision of IUGR.

Fetal hypoxemia is one of the most frequent causes of intrauterine growth retardation (IUGR). In chronic fetal hypoxia, peripheral blood flow and blood flow to the kidneys is reduced to maintain heart, brain and adrenal perfusion, the 'brain-sparing effect'. In kidneys the cells of the proximal tubules seem to be most sensitive to hypoxia caused by reduced blood flow. Damage to the cells of the proximal tubules can be easily diagnosed by urinary levels of N-acetyl-beta-D-glucosaminidase (NAG), an enzyme present in high concentrations in these cells. The aim of the present study was to define the levels of NAG in the amniotic fluid, to diagnose damage to the cells of the proximal renal tubules in fetuses, and to correlate them with a detectable brain-sparing effect. The study was conducted on a total of 55 pregnancies: 9 pregnancies were complicated by IUGR, and the remaining 46 normal pregnancies formed the control group. Higher levels of NAG were detected in the amniotic fluid from the IUGR-complicated pregnancies (p < 0.025). In particular, fetuses with IUGR had high levels of NAG in the amniotic fluid in 8 of 9 cases (+ 2 SD compared with controls), while 1 had normal concentrations. In the 8 cases with high concentrations of NAG in the amniotic fluid, velocimetric Doppler study documented a brain-sparing effect, which was not present in the 1 fetus with normal NAG levels. In conclusion, high levels of NAG in the amniotic fluid may identify in uterus fetuses with renal damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Cordocentesis has permitted the study of fetal thyroid function. In normal pregnancy, fetal blood thyroid-stimulating hormone (TSH), thyroid hormones and thyroid-binding globulin increase with advancing gestation demonstrating functional maturation of the pituitary, thyroid and liver, respectively. The administration of thyroid-releasing hormone to the mother produces a rapid increase in fetal TSH from at least 25 weeks gestation. In hypoxemic growth-retarded fetuses, the concentrations of TSH are higher, and the concentrations of total and free thyroxine are lower than in appropriately grown fetuses. In anemic fetuses from red cell-isoimmunized pregnancies, serum TSH and thyroid hormone concentrations are increased. In some chromosomally abnormal fetuses, particularly those with trisomy 21, TSH is increased.

Cerebral Doppler measurements seem to be a future method to evaluate the degree of fetal hypoxemia. The aim of this study was (1) to elaborate standard curves for the different cerebral vessels in our own population, and (2) to describe the predictive value of Doppler measurements for intrauterine growth retardation (IUGR) and fetal acidosis. We recorded cerebral flow velocity waveforms from 71 normal pregnancies to establish standard curves for the following vessels: proximal middle cerebral artery, distal middle cerebral artery and posterior cerebral artery. Finally, we calculated the cerebroplacentar index (CPI) for each case. The predictive values from the different vessels were determined in 24 patients with IUGR and 17 cases with fetal acidosis. The poor sensitivity and the low positive predictive value of each cerebral vessel is probably explained by the rather long interval between the last Doppler assessment and delivery (22 +/- 23 days). Reducing the interval to less than 7 days, the distal middle cerebral artery and the CPI were pathological in 4 cases out of 5 fetuses that underwent cesarean section for fetal distress. These latter results have encouraged us to use cerebral Doppler flow velocity to detect fetal hypoxemia. In conclusion, the middle cerebral artery blood flow in its distal part seems to be the finest parameter to predict fetal acidosis, and this vessel should be used to optimize obstetrical management of high-risk pregnancies.