Assessment of feto-placental oxygenation and perfusion in a rat model of placental insufficiency using T2* mapping and 3D dynamic contrast-enhanced MRI.

INTRODUCTION: Placental insufficiency may lead to preeclampsia and fetal growth restriction. There is no cure for placental insufficiency, emphasizing the need for monitoring fetal and placenta health. Current monitoring methods are limited, underscoring the necessity for imaging techniques to evaluate fetal-placental perfusion and oxygenation. This study aims to use MRI to evaluate placental oxygenation and perfusion in the reduced uterine perfusion pressure (RUPP) model of placental insufficiency. METHODS: Pregnant rats were randomized to RUPP (n = 11) or sham surgery (n = 8) on gestational day 14. On gestational day 19, rats imaged using a 7T MRI scanner to assess oxygenation and perfusion using T2* mapping and 3D-DCE MRI sequences, respectively. The effect of the RUPP on the feto-placental units were analyzed from the MRI images. RESULTS: RUPP surgery led to reduced oxygenation in the labyrinth (24.7 ± 1.8 ms vs. 28.0 ± 2.1 ms, P = 0.002) and junctional zone (7.0 ± 0.9 ms vs. 8.1 ± 1.1 ms, P = 0.04) of the placenta, as indicated by decreased T2* values. However, here were no significant differences in fetal organ oxygenation or placental perfusion between RUPP and sham animals. DISCUSSION: The reduced placental oxygenation without a corresponding decrease in perfusion suggests an adaptive response to placental ischemia. While acute reduction in placental perfusion may cause placental hypoxia, persistence of this condition could indicate chronic placental insufficiency after ischemic reperfusion injury. Thus, placental oxygenation may be a more reliable biomarker for assessing fetal condition than perfusion in hypertensive disorders of pregnancies including preeclampsia and FGR.

Fetal-placental blood flow and neurodevelopment in childhood: population-based neuroimaging study.

OBJECTIVE: Antenatal Doppler measurements of the fetal umbilical and cerebral circulations can predict perinatal complications; however, it is unclear if subtle variations in antenatal Doppler measurements are associated with long-term neurodevelopmental outcome. In this study, we examined whether antenatal Doppler measurements of the fetal-placental circulation are associated with cognitive and motor abilities and brain morphology in childhood. METHODS: To evaluate differences in long-term sequelae across the continuum of the umbilical and cerebral artery circulations in the general population, we utilized a population-based longitudinal cohort study approach. In women from the Generation R study, we measured second- and third-trimester umbilical artery pulsatility index (UA-PI). Children underwent non-verbal intelligence testing at 4-8 years of age, and at 8-12 years they underwent finger-tapping tests to measure fine motor skills, balance beam tests to measure gross motor skills and brain magnetic resonance imaging. We assessed the relationships between prenatal UA-PI and neurodevelopmental outcome using linear regression. We adjusted for child age and sex, maternal age, education, parity and smoking status. RESULTS: The study sample included 2803 pregnancies. Higher third-trimester UA-PI was associated with poorer fine motor performance (0.41 (95% CI, 0.11-0.70) fewer taps on the finger-tapping test per 1 SD higher UA-PI) and gross motor performance (0.64 (95% CI, 0.20-1.08) fewer steps on the balance beam test per 1 SD higher UA-PI). One SD higher third-trimester UA-PI was also associated with 0.65 (95% CI, 0.04-1.25) points lower intelligence quotient; however, unlike the associations with motor abilities, this finding did not persist after correction for multiple testing. Higher second-trimester UA-PI was associated with smaller brain volume (6.1 (95% CI, 1.0-11.3) cm3 reduction per 1 SD higher UA-PI), but the association did not persist after correction for multiple testing. CONCLUSION: Higher placental vascular resistance may have mild adverse effects on neurodevelopmental outcome at school age. While these effects are subtle at population level, we encourage future research into the role of early circulation in brain development. This information could be used to develop targeted interventions. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Placental MRI and its application to fetal intervention.

OBJECTIVE: Magnetic resonance imaging (MRI) of placental invasion has been part of clinical practice for many years. The possibility of being better able to assess placental vascularization and function using MRI has multiple potential applications. This review summarises up-to-date research on placental function using different MRI modalities. METHOD: We discuss how combinations of these MRI techniques have much to contribute to fetal conditions amenable for therapy such as singletons at high risk for fetal growth restriction (FGR) and monochorionic twin pregnancies for planning surgery and counselling for selective growth restriction and transfusion conditions. RESULTS: The whole placenta can easily be visualized on MRI, with a clear boundary against the amniotic fluid, and a less clear placental-uterine boundary. Contrasts such as diffusion weighted imaging, relaxometry, blood oxygenation level dependent MRI and flow and metabolite measurement by dynamic contrast enhanced MRI, arterial spin labeling, or spectroscopic techniques are contributing to our wider understanding of placental function. CONCLUSION: The future of placental MRI is exciting, with the increasing availability of multiple contrasts and new models that will boost the capability of MRI to measure oxygen saturation and placental exchange, enabling examination of placental function in complicated pregnancies.

Effects of maternal smoking on human placental vascularization: A systematic review.

The abnormal development of placental vascularization leads to placental insufficiency, which further reduces the nutrient and trace exchange between maternal circulation and fetal circulation. These changes cause maternal and fetal complications. The objective of our systematic review was to explore the effects of maternal smoking on placental vascularization. The eligibility criteria were: articles with experimental, quasi-experimental or observational design, performed on human subjects, that study the association, correlation or causation between maternal smoking and changes in placental vascular network. A total of 33 full-text papers were assessed for eligibility, resulting in 12 original articles that were included in the systematic review. Doppler studies confirm reductions in blood flow velocity waveforms and increase in RI in the uterine, umbilical and fetal middle cerebral arteries. These findings are confirmed by morphometric measurements of fetal capillaries in villi that were shown to be smaller in smoke exposure groups.

Maternal Serum Endocan Concentration in Pregnancies Complicated by Intrauterine Growth Restriction.

OBJECTIVES: Endocan plays a role in the development of vascular tissue in health and disease and is an indicator of endothelial cells activation and angiogenesis. Therefore, this study aimed to investigate the relationship between maternal endocan serum level and intrauterine growth restriction (IUGR) as well as ultrasound Doppler flow measurements indicating placental insufficiency. METHODS: This study included a group of women with IUGR (n = 37) and a group of healthy pregnant women (controls, n = 37). The endocan serum concentrations were assessed using commercially available enzyme-linked immunosorbent assay kit. Every woman underwent an ultrasound examination with Doppler flow measurements of the uterine arteries, umbilical vessels, and fetal middle cerebral artery. We used the cerebroplacental ratio (CPR) to determine placental insufficiency. RESULTS: We found significant differences in median (interquartile) endocan serum level (pg/mL) between study and control groups (464 [374-532] vs 339 [189-496], respectively; P < .001). The endocan serum level correlated neither with umbilical cord blood gases nor with Apgar score. Ultrasound Doppler findings revealed significant differences in middle cerebral artery pulsatility index (PI), umbilical artery PI, CPR, as well as mean uterine arteries PI between IUGR group and controls. In the study group, we found significant correlations between the serum endocan and CPR ( R = 0.56, P < .001) as well as between serum endocan and mean uterine arteries PI ( R = 0.46, P = .006). CONCLUSION: Endocan is likely involved in the pathogenesis of IUGR in pregnant women and possibly is a useful marker of endothelial dysfunction in these cases.

Incidence and Management of Umbilical Artery Flow Abnormalities during Open Fetal Surgery.

INTRODUCTION: Umbilical artery (UA) Doppler ultrasound is used to assess uteroplacental insufficiency. Absent or reversed end diastolic flow (AREDF) in the UA is associated with increased perinatal mortality in fetuses with intrauterine growth restriction. We describe the incidence of UA Doppler abnormalities during open fetal surgery. METHODS: We conducted a retrospective review of patients undergoing open in utero myelomeningocele (MMC) repair between 2008 and 2015. Intermittent UA Dopplers were performed during key portions of all cases. Our primary outcome was the rate of any AREDF. Secondary outcomes included analysis of absent versus reversed end diastolic flow (EDF), vasopressor use, and volatile anesthetic and clinical outcomes. RESULTS: Thirty-four of 47 fetuses developed UA Doppler abnormalities intraoperatively. Nineteen had absent EDF and 15 had reversed EDF. No AREDF was present before induction, and all AREDF resolved by postoperative day 1. Ten of 19 (52.6%) patients who received sevoflurane had reversed EDF, versus 5/28 (17.9%) for desflurane, odds ratio (95% CI) 5.11 (1.36-19.16), p = 0.02. One intraoperative fetal death occurred in the AREDF group. DISCUSSION: AREDF is a common phenomenon during open MMC repair. Anesthetic agent choice may influence this risk. Future studies of UA flow during fetal surgery are needed to further evaluate the impact of intraoperative AREDF on fetal well-being.

Placental soluble fms-like tyrosine kinase expression in small for gestational age infants and risk for adverse outcomes.

INTRODUCTION: Soluble fms-like tyrosine kinase 1 (sFLT-1) is an anti-angiogenic factor implicated in the pathogenesis of preterm preeclampsia. We evaluated sFLT-1 expression and placental pathology in pregnancies complicated by small for gestational age (SGA) infants (<10th percentile), without evidence of preeclampsia. METHODS: Clinical and histologic data were compared between groups with high or low sFLT-1 expression determined by immunohistochemistry on archived placentas. RESULTS: Nineteen of 69 placentas showed high sFLT-1 expression. The high sFLT-1 group had higher predelivery median systolic blood pressure (BP); 140 (interquartile range (IQR) 133-152) vs. 126 (118-139) mm Hg (p = 0.003), and median diastolic BP; 87 (78-94) vs. 77.5 (71-86) mm Hg (p = 0.02). Abnormal umbilical Doppler abnormalities were more prevalent; 89.5% vs. 46% (p = 0.001). These pregnancies delivered earlier; 31.9 weeks (28.3-34.7 weeks) vs. 37.1 weeks (33.7-38.7 weeks) (p < 0.001), and infants had lower birthweight; 980 grams (520-1545 grams) vs. 2087.5 grams (1455-2340 grams) (p < 0.001). Placental-weight to fetal-weight ratios, a marker of vascular insufficiency, was increased in the high sFlt-1 group: 0.18 (0.14-0.28) vs 0.15 (0.13-0.18), p = 0.03. Placentas with high sFLT-1 showed more decidual vasculopathy; 42.1% vs. 10.0% (p = 0.005), infarction; 36.8% vs. 14.0% (p = 0.048), distal villous hypoplasia; 78.9% vs. 36.0% (p = 0.001), and fetal thrombotic vasculopathy; 47.4% vs. 16.0% (p = 0.01). DISCUSSION: Placental sFLT-1 expression is upregulated in approximately 28% of non-preeclamptic pregnancies complicated by SGA infants. These pregnancies showed increased placental vascular pathology, more umbilical Doppler abnormalities, and earlier delivery with lower birthweight. A subgroup of non-preeclamptic fetal growth restriction with upregulated sFlt-1 expression may share a common pathogenic pathway with preterm preeclampsia. This subgroup is worthy of additional study.

Using Doppler ultrasound of the uterine and umbilical arteries and disordered angiogenesis markers (sFlt-1/PlGF) in unified monitoring of ischemic placental syndrome patients.

OBJECTIVE: The shared pathogenesis of placental ischemia entitles us to create a single treatment model. We attempted to develop a unified method for monitoring ischemic placental syndrome patients using Doppler ultrasound of the uterine and umbilical arteries and disordered angiogenesis markers sFlt-1 and PlGF. MATERIAL AND METHODS: 182 pregnant women suffering from the ischemic placental syndrome were divided into four groups depending on the severity of their lesions revealed in the Doppler ultrasound examination and weeks of pregnancy. We analyzed the behavior of clinical and biochemical parameters in these groups and the correlations between the ultrasound examination and the disordered angiogenesis markers. RESULTS: In the group of patients demonstrating more severe Doppler ultrasound lesions, the clinical and biochemical parameters were significantly more expressed, whereas unfavorable obstetric events occurred either earlier or more frequently. Lesions revealed in Doppler occur more commonly in groups before 34th week of pregnancy. Disordered angiogenesis markers are significantly correlated with ultrasound examination results. CONCLUSIONS: A unified method for monitoring the ischemic placental syndrome based on pathogenetic, biophysical (Doppler ultrasound), and biochemical (sFlt-1/PlGF) parameters is feasible and constitutes a valuable supplement to the existing standards, while the high correlations between Doppler ultrasound examinations and both sFlt-1 and PlGF point to a shared pathogenesis of the lesions. Intensity of Doppler changes is connected with time of testing and pregnancy duration.

Association of first-trimester angiogenic factors with placental histological findings in late-onset preeclampsia.

OBJECTIVE: To explore in women with late-onset preeclampsia (PE) the association between maternal levels of angiogenic/antiangiogenic factors in the first trimester of pregnancy and histological findings attributable to placental underperfusion (PUP). METHODS: A nested case-control cohort study was conducted in 73 women with pregnancies complicated by late-onset PE (>34 weeks at delivery) matched with controls. First trimester uterine artery Doppler (UtA); maternal levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were retrieved. Placentas were histologically evaluated using a hierarchical and standardized classification system. One-way ANOVA with linear polynomial contrast or linear-by-linear association test was performed to test the hypothesis of a linear association across study groups (controls, PE without PUP and PE with PUP). RESULTS: In 54 (74%) placentas, 89 placental histological findings qualifying for PUP were found. Across study groups, significant values were observed in maternal levels of decreased PlGF (MoM values: 1.53, 1.41 and 1.37; p < 0.001), increased sFlt-1 (MoM values: 3.11, 3.11 and 3.22; p = 0.002), increased sFlt-1/PlGF ratio (MoM values: 2.3, 2.3 and 2.44; p < 0.001), abnormal UtA Doppler (MoM values: 1, 1.26 and 1.32; p < 0.001), and worse perinatal outcomes in terms of gestational age at delivery, cesarean section for not reassuring fetal status, birth weight and neonatal acidosis. DISCUSSION: In late-onset PE an imbalance of circulating angiogenic and anti-angiogenic factors already present at 8-10 weeks of pregnancy was associated with histological findings reflecting placental insufficiency. An early first trimester screening by angiogenic factors might help to identify patients with placental involvement among late-onset PE cases. CONCLUSION: In late-onset preeclampsia, first-trimester uterine Doppler and circulating levels of angiogenic/antiangiogenic factors are associated with placental underperfusion.

Placental volume, vasculature and calcification in pregnancies complicated by pre-eclampsia and intra-uterine growth restriction.

OBJECTIVE: Pre-eclampsia (PET) and intrauterine growth restriction (IUGR), often associated with impaired placental function, are among the most common conditions contributing to increased perinatal mortality and morbidity. This study investigates if three dimensional power Doppler (3DPD) of the placenta and computerised analysis of placental calcification is different between PET/IUGR and normal pregnancies. STUDY DESIGN: This was a prospective cohort study involving 50 women with pre-eclampsia and/or IUGR, or with IUGR only from 24 to 40 weeks' gestation. 3DPD ultrasound was used to calculate placental volume, vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI). Following each scan the percentage of placental calcification was also calculated, by computer analysis. Results were compared with normal (control) values, and findings correlated with maternal and fetal Doppler parameters and placental histology. RESULTS: Volume, VI, and VFI are not influenced by gestational age in PET/IUGR pregnancies. FI was found to increase with gestational age (p=0.009) and was lower than normal in the total study group from 24 to 30 weeks (p=0.006). In the pregnancies affected by PET, whether or not IUGR was present, all three indices were lower than normal values between 24 and 30 weeks (VI: p=0.038, FI: p=0.004, VFI: p=0.015). Vascularisation and flow indices were less than the normal 50th centile in the majority of cases of utero-placental insufficiency (p=0.047), and vascularisation and vascularisation flow indices were lower in cases of accelerated placental maturation (p=0.016 and 0.041 respectively). Placental volume greater than the 50th centile between 24 and 30 weeks was associated with the presence of infarction on histology (p=0.021). Flow index (p=0.002) and vascularisation flow index (p=0.036) were lower in the presence of bilateral uterine artery notches. Calcification, similar to the control group, was related to an increasing UAPI (p=0.041) and MCA PI <5th centile (p=0.010). CONCLUSIONS: The study findings suggest that there may be a role for 3DPD placental assessment of volume, vascularisation and blood flow and computer analysis of placental calcification in the identification and management of PET/IUGR pregnancy.

[Prognostic factors of perinatal short-term outcome in severe placental insufficiency using Doppler sonography to assess end-diastolic absent and reverse blood flow in umbilical arteries]. / Prognosefaktoren des perinatalen Kurzzeitergebnisses bei schwerer Plazentainsuffizienz mit dopplersonografisch enddiastolischem Null- und Rückfluss in der Art. umbilicalis.

Significant placental insufficiency, indicated by Doppler ultrasound findings of absent or reverse end-diastolic flow velocities (AREDV), is associated with increased morbidity and mortality. Analysis of blood flow in the ductus venosus should assist in early intrauterine recognition of threatened foetuses. 58 high-risk pregnancies with umbilical AREDV were repeatedly examined (n=364). Doppler findings were correlated with neonatal signs of deterioration (ratio of normoblasts to leukocytes, pH, base excess, Apgar score), as well as short-term morbidity [need for intubation, duration of assisted respiration, evidence of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC), intraventricular haemorrhage (IVH grade III+IV)] against the analysis of the blood flow findings (normal or increased pulsitility, absence or reverse end-diastolic flow) in the umbilical arteries (AU), the middle cerebral arteries (ACM) and ductus venosus (DV) relating these to birth weight and the duration of the pregnancy. The median period of observation was 12.8 days, 48% of the foetuses showed an abnormal ductus venosus flow and 26% an absent venous or reverse end-diastolic flow. The median date of delivery was 30 weeks, with a mean birth weight of 816 g. 93% were live births with 12% dying postnatally. Although the criteria for postnatal morbidity (BPD, NEC, IVH III+IV) and mortality did not correlate with changes in arterial and venous Doppler parameters in our group, there was a significant relationship between the normoblast count, known to be a marker of chronic hypoxia. The Apgar 10 minte score, umbilical arterial pH and base excess were correlated with changes in the DV flow curves. Healthy survival started, irrespective of arterial or venous blood flow criteria, from 27+0 weeks of pregnancy. If born between 27.0 and 30+6 weeks, the infants were more likely to be healthy the less the blood flow had been compromised. A birth weight of 590 g (sensitivity 62.5%; specificity 93.5%) and gestational age of 28+5 weeks (sensitivity 87.5%; specificity 90.3%) were shown to be cut-off points between healthy survival and survival with serious neonatal complications.

Magnetic resonance imaging-estimated placental perfusion in fetal growth assessment.

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.

Is there a role for cervical assessment and uterine artery Doppler in the first trimester of pregnancy as a screening test for spontaneous preterm delivery?

OBJECTIVE: To evaluate the role of cervical length (CL) and uterine artery pulsatility index (UtA-PI) at 11+0 to 13+6 weeks as predictors of spontaneous preterm delivery (sPTD) in a Chilean population. METHODS: This was a prospective study of asymptomatic women with singleton pregnancies attending for a nuchal translucency scan at 11+0 to 13+6 weeks' gestation and who underwent a transvaginal scan for evaluation of CL and UtA-PI. Exclusion criteria were fetal and pregnancy complications (other than sPTD) and iatrogenic delivery at<34 weeks. Measurements of CL and UtA-PI were adjusted for fetal crown-rump length and maternal characteristics and expressed as multiples of the median (MoM) of the unaffected group. Prediction of sPTD using maternal and pregnancy characteristics was studied using logistic regression analysis. RESULTS: A total of 3480 women were recruited into the study and, after application of exclusion criteria, 3310 were included in the analysis. The rate of sPTD at<34 weeks was 0.9% (n=31). A previous PTD had occurred in 7.4% of parous women. Patients with sPTD in the index pregnancy were characterized by a significantly higher prevalence of previous PTD (12.9% vs 3.7%, P<0.05). No significant difference was found in either CL or UtA-PI between pregnancies with and without subsequent sPTD. Logistic regression analysis showed that smoking and previous PTD were significantly associated with sPTD at<34 weeks. The combination of these characteristics provided a detection rate of 26% with a false-positive rate of 8%. CONCLUSIONS: Neither UtA-PI nor CL during the first trimester was shown to be a useful predictor of early sPTD. However, a combined model that includes smoking and previous PTD predicts approximately one-quarter of those women destined to deliver at<34 weeks, with a false-positive rate of 8%.

[Congenital heart diseases in pregnant women--a risk factor for fetal distress].

The condition of fetoplacental system in pregnant women with congenital heart diseases was studied by means of ultrasound, dopplerometry, cardiotocography, by determination of estradiol, progesterone and placental lactogen in the blood of pregnant women and in the umbilical cord and by means of pathomorphologic study of the placenta. It is shown that congenital heart diseases complicated by heart failure in pregnant women--a important risk factor for fetal distress bouth in the preclinical stage of placental insufficiency (violation of the utero-placental blood flow, changes of fetoplacental hormones levels) and in conjunction with clinical signs of fetal suffering (distress and growth retardation).

[Massive subchorial thrombosis].

Massive subchorial thrombosis (MSCT) is a placental abnormality, the etiology and pathogenesis of which remain inadequately studied. MSCT is characterized by a clinical symptom complex comprising marked intrauterine growth retardation, oligohydramnios, and fetal distress due to placental circulatory problems. Perinatal outcomes are appreciably determined by the term of pregnancy, the degree of placental insufficiency, and neonatal status. Prolonged MSCT makes it possible to diagnose this pathology by echographic and magnetic resonance imaging studies and to attempt to treat placental dysfunction through tocolytic therapy and correction of oligohydramnios, to prolong pregnancy, and to have a viable newborn infant. The clinical and morphological diagnosis of MSCT calls for its differential diagnosis with other focal placental lesions, such as subamniotic, intraplacental, and retroplacental hematomas, cytotrophoblastic cyst, umbilical cord cysts, and chorangioma.

Oxidized low-density lipoproteins in cord blood from neonates with intra-uterine growth restriction.

OBJECTIVE: We verified whether oxidative stress indices (oxidized low-density lipoproteins and malondialdehyde) and inflammatory biomarkers (circulating C-reactive protein, interleukin-6, tumour necrosis factor-α, serum amyloid A and soluble intercellular vascular cell adhesion molecule) are increased in the umbilical vein of placental insufficiency induced intra-uterine growth restricted neonates. STUDY DESIGN: The prospective cohort study, involving 3 tertiary care centers, consists of 200 consecutively recruited pregnant women carrying twins. We chose the twin pregnancy model because both fetuses share the same maternal environment, thereby avoiding potential confounding factors when comparing oxidative stress and inflammation biomarkers. We analysed only twin pairs with one with intra-uterine growth restriction (N=38) defined as fetal growth<10th percentile with abnormal Doppler of the umbilical artery. Blood samples were taken at birth from the umbilical vein. Intra-pair comparisons on the biomarkers were performed using the Student paired t-test. RESULTS: We observed increased cord blood levels of oxidized low-density lipoproteins, (2.394 ± .412 vs 1.296 ± .204, p=.003) but not of malondialdehyde in growth restricted neonates when compared to their normal counterparts. Although indices of inflammation tended to be increased in cord blood from growth restricted newborns, the difference did not reach statistical significance. CONCLUSION: In the twin model, intra-uterine growth restriction is associated with low-density lipoprotein oxidation without apparent dysregulation of inflammation biomarkers. CONDENSATION: Increased oxidized low-density lipoproteins are observed in growth restricted twins compared to their co-twins with normal growth at birth.

Techniques for assessing cardiac output and fetal cardiac function.

Fetal echocardiography was initially used to diagnose structural heart disease, but recent interest has focused on functional assessment. Effects of extracardiac conditions on the cardiac function such as volume overload (in the recipient in twin-twin transfusion syndrome), a hyperdynamic circulation (arterio-venous malformation), cardiac compression (diaphragmatic hernia, lung tumours) and increased placental resistance (intrauterine growth restriction and placental insufficiency) can be studied by ultrasound and may guide decisions for intervention or delivery. A variety of functional tests can be used, but there is no single clinical standard. For some specific conditions, however, certain tests have shown diagnostic value.

[Expression of contractile proteins alpha-actin and myosin of smooth muscle cells and collagen of IV type in human placenta at placental insufficiency in III trimester of pregnancy].

Changes of expression of contractile proteins (alpha-actin and myosin of smooth muscle cell) and of collagen of IV type in stroma of human placental villi were studied at the diagnosed placental insufficiency (PI) in III trimester of pregnancy. The study revealed pronounced disturbances of expression of contractile proteins and collagen of IV type at PI. It is shown that in perivascular envelopes of vessels of stem and intermediate villi there is present a much greater amount of cells expressing smooth muscle actin and myosin. These cells are arranged by the denser concentric layers and more compactly than in norm and fill the intervascular space inside the villi. The width of perivascular envelopes of vessels is higher, while vascular lumens are lower than in norm. In terminal villi the capillary walls are thickened and the number of pericytes immunopositive against the smooth muscle cell alpha-actin and myosin as well as collagen of IV type is increased. The change of synthesis of the cytoskeletal contractile proteins and collagen of IV type is shown to lead to structural disturbances of villi of different types and of perivascular areas and vessels, which doubtlessly indicates their participation in pathogenesis of placental dysfunction and of disturbance of placental hemodynamics.

The effects of absent or reversed end-diastolic umbilical artery Doppler flow velocity.

Abnormal umbilical artery flow with absent or reversed end-diastolic velocity (AREDV) during pregnancy is a strong indication of placental insufficiency. When AREDV occurs prenatally, a close follow-up or expeditious delivery should be contemplated. AREDV in the umbilical artery is associated with intraventricular hemorrhage, bronchopulmonary dysplasia, and perinatal mortality. It may be associated with respiratory distress syndrome, necrotizing enterocolitis, and long-term neurodevelopmental impairment. Available data suggest that women with high-risk pregnancies, such as preeclampsia, gestational hypertension and intrauterine growth restriction, should be evaluated with umbilical artery Doppler velocimetry to reduce the possibility of perinatal mortality and morbidity.