Exploring the impact of temperature and oxygen partial pressure on the spent nuclear fuel oxidation during its dry management.

The management of Spent Nuclear Fuel (SNF) comprises different stages in which security is demonstrated. Nevertheless, fundamental research can lead to other design options that must be considered. Currently, one of the focuses is the dry interim storage option, as the shortest-term solution until final repositories are available. During this stage, one concern is the oxidation of the fuel. If UO2 (SNF matrix) is exposed to air at high-enough temperature, formation of U3O8 takes place. The larger volume of this phase could entail stresses on the SNF clad, which is the first barrier to prevent radioactive material release. It is known that this oxidation is a temperature-dependent reaction and ensuring an inert atmosphere discards any effect during SNF dry management. However, at what extent temperature and oxygen concentration would have an impact on the U3O8 formation is not established, being the available experimental data very scarce. We follow this oxidation in representative ranges of temperature and oxygen concentration of dry storage facilities by using in-situ Raman spectroscopy. The results show that temperature is a more-affecting factor than the oxygen concentration at the studied conditions. Therefore, efforts to limit temperatures would yield more benefits in preserving fuel matrix integrity.

Interventions to prevent preterm delivery in women with short cervix before fetoscopic laser surgery for twin-twin transfusion syndrome.

OBJECTIVE: Preoperative short cervical length (CL) remains a major risk factor for preterm birth after laser surgery for twin-twin transfusion syndrome (TTTS), but the optimal intervention to prolong pregnancy remains elusive. The objective of this study was to compare secondary methods for the prevention of preterm birth in twin pregnancies with TTTS undergoing fetoscopic laser photocoagulation (FLP), in the setting of a short cervix at the time of FLP, in five North American Fetal Treatment Network (NAFTNet) centers. METHODS: This was a secondary analysis of data collected prospectively at five NAFTNet centers, conducted from January 2013 to March 2020. Inclusion criteria were a monochorionic diamniotic twin pregnancy complicated by TTTS, undergoing FLP, with preoperative CL < 30 mm. Management options for a short cervix included expectant management, vaginal progesterone, pessary (Arabin, incontinence or Bioteque cup), cervical cerclage or a combination of two or more treatments. Patients were not included if the intervention was initiated solely on the basis of having a twin gestation rather than at the diagnosis of a short cervix. Demographics, ultrasound characteristics, operative data and outcomes were compared. The primary outcome was FLP-to-delivery interval. Propensity-score matching was performed, with each treatment group matched (1:1) to the expectant-management group for CL, in order to estimate the effect of each treatment on the FLP-to-delivery interval. RESULTS: A total of 255 women with a twin pregnancy complicated by TTTS and a short cervix undergoing FLP were included in the study. Of these, 151 (59%) were managed expectantly, 32 (13%) had vaginal progesterone only, 21 (8%) had pessary only, 21 (8%) had cervical cerclage only and 30 (12%) had a combination of treatments. A greater proportion of patients in the combined-treatment group had had a prior preterm birth compared with those in the expectant-management group (33% vs 9%; P = 0.01). Mean preoperative CL was shorter in the pessary, cervical-cerclage and combined-treatment groups (14-16 mm) than in the expectant-management and vaginal-progesterone groups (22 mm for both) (P < 0.001). There was no significant difference in FLP-to-delivery interval between the groups, nor in gestational age at delivery or the rate of live birth or neonatal survival. Vaginal progesterone was associated with a decrease in the risk of delivery before 28 weeks' gestation compared with cervical cerclage and combined treatment (P = 0.03). Using propensity-score matching for CL, cervical cerclage was associated with a reduction in FLP-to-delivery interval of 13 days, as compared with expectant management. CONCLUSIONS: A large proportion of pregnancies with TTTS and a short maternal cervix undergoing FLP were managed expectantly for a short cervix, establishing a high (62%) risk of delivery before 32 weeks in this condition. No treatment that significantly improved outcome was identified; however, there were significant differences in potential confounders and there were also likely to be unmeasured confounders. Cervical cerclage should not be offered as a secondary prevention for preterm birth in twin pregnancies with TTTS and a short cervix undergoing FLP. A large randomized controlled trial is urgently needed to determine the effects of treatments for the prevention of preterm birth in these pregnancies. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Blood pressure during pregnancy, neonatal size and altered body composition: the Healthy Start study.

OBJECTIVE: The objective of this study is to estimate associations between changes in maternal arterial pressure during normotensive pregnancies and offspring birth weight and body composition at birth. STUDY DESIGN: Prospective study of 762 pregnant normotensive Colorado women, recruited from outpatient obstetrics clinics. Repeated arterial pressure measurements during pregnancy were averaged within the second and third trimesters, respectively. Multivariable regression models estimated associations between second to third trimester changes in arterial pressure and small-for-gestational-age birth weight, fat mass, fat-free mass and percent body fat. RESULTS: A greater second to third trimester increase in maternal arterial pressure was associated with greater odds of small-for-gestational-age birth weight. Greater increases in maternal diastolic blood pressure were associated with reductions in offspring percent body fat (-1.1% in highest vs lowest quartile of increase, 95% confidence interval: -1.9%, -0.3%). CONCLUSION: Mid-to-late pregnancy increases in maternal arterial pressure, which do not meet clinical thresholds for hypertension are associated with neonatal body size and composition.

[Acromioclavicular instability: arthroscopic and mini-open combined treatment]. / Inestabilidad acromioclavicular. Tratamiento combinado artroscópico y miniinvasivo.

INTRODUCTION: The surgical treatment of acromioclavicular dislocation remains controversial. We describe herein a combined two-stage technique that includes an arthroscopic approach followed by a mini-invasive approach. MATERIAL AND METHODS: 41 patients with acromioclavicular dislocation grades III, IV and V. Acute and chronic lesions and revision surgeries were included during the follow-up. Patients with other shoulder conditions were excluded. Mean age was 28.6 years. Patients were assessed preoperatively with the UCLA and Constant scores, and the pain visual analog scale. The 6- and 12-month postoperative evaluation included X-rays to assess coronal and axial stability, coracoclavicular ossifications, signs of acromioclavicular arthrosis and/or distal clavicular osteolysis. RESULTS: The Constant scores were as follows: 41.3 preoperatively; 89.4 at 6 months; 92.3 at 12 months. The UCLA scores were as follows: 21.7 preoperatively; 29.1 at 6 months; 31.4 at 12 months. The VAS scores were 8.4, 2.3 and 1.2, for the same periods respectively. Two cases had repeated injury due to trauma and one case was dissatisfied with the cosmetic appearance of the scar. The X-ray assessment showed two cases of loss of stability and one case of distal clavicular osteolysis. CONCLUSION: The combination of two reduction methods, a synthetic one and a biological one allows for a solid anatomical reconstruction that is stable in the coronal and axial planes and good medium-term results.

INTRODUCCIÓN: el tratamiento quirúrgico de la luxación acromioclavicular es aún motivo de controversia. En esta publicación se describirá una técnica combinada en la que se realizó un primer tiempo artroscópico y un segundo tiempo con abordaje miniinvasivo. MATERIAL Y MÉTODOS: 41 pacientes con luxación acromioclavicular grados III, IV y V. Para el seguimiento se incluyeron luxaciones agudas, crónicas y cirugías de revisión; se excluyeron pacientes con otras patologías de hombro, la edad promedio fue de 28.6 años. Los pacientes fueron evaluados con el. RESULTADOS: score de UCLA Constant, la escala visual analógica para dolor preoperatorio y control radiológico para evaluar la estabilidad tanto en plano coronal como axial, osificaciones coracoclaviculares, signos de artrosis acromioclavicular y/o osteólisis distal de clavícula a los 6 y 12 meses postoperatorio. se obtuvo un score de Constant preoperatorio de 41.3; 6 meses: 89.4; 12 meses: 92.3. El. CONCLUSIÓN: score de UCLA preoperatorio: 21.7; 6 meses: 29.1 y 12 meses: 31.4. VAS: 8.4; 2.3; 1.2. Hubo dos casos de relesión por trauma y un caso de insatisfacción estética de la cicatriz. En cuanto al examen radiológico se presentaron dos casos de pérdida de estabilidad y un caso de osteólisis distal de clavícula. la combinación de dos métodos de reducción, uno sintético y otro biológico, permitió una reconstrucción anatómica sólida, estable en plano coronal y axial con muy buenos resultados a mediano plazo.

Does meniscus removal affect ACL-deficient knee laxity? An in vivo study.

PURPOSE: The purpose of the present study was to determine, in vivo, the effect of different types of meniscectomy on an ACL-deficient knee. METHODS: Using a computer-assisted navigation system, 56 consecutive patients (45 men and 11 women) were subjected to a biomechanical testing with Lachman test (AP30), drawer test (AP90), internal/external rotation test, varus/valgus rotation test and pivot-shift test. The patients were divided into three groups according to the status of the medial meniscus. Group BH, 8 patients with bucket-handle tear of medial meniscus underwent a subtotal meniscectomy; Group PHB, 19 patients with posterior horn body of medial meniscus tear underwent a partial meniscectomy; and Group CG with isolated ACL rupture, as a control group, with 29 patients. RESULTS: A significant difference in anterior tibial translation was seen at 30 grades and in 90 grades between BH and PHB groups compared to the CG. In response to pivot-shift test, no significant differences in terms of AREA and POSTERIOR ACC were found among the three groups (n.s). Concerning the anterior displacement of the pivot shift a statistically significant differences among the three tested groups was found. CONCLUSION: The present study shows that meniscal defects significantly affect the kinematics of an ACL-deficient knee in terms of anterior tibial translation under static and dynamic testing.

Inestabilidad acromioclavicular. Tratamiento combinado artroscópico y miniinvasivo / Acromioclavicular instability: arthroscopic and mini-open combined treatment

Resumen: Introducción: el tratamiento quirúrgico de la luxación acromioclavicular es aún motivo de controversia. En esta publicación se describirá una técnica combinada en la que se realizó un primer tiempo artroscópico y un segundo tiempo con abordaje miniinvasivo. Material y métodos: 41 pacientes con luxación acromioclavicular grados III, IV y V. Para el seguimiento se incluyeron luxaciones agudas, crónicas y cirugías de revisión; se excluyeron pacientes con otras patologías de hombro, la edad promedio fue de 28.6 años. Los pacientes fueron evaluados con el score de UCLA Constant, la escala visual analógica para dolor preoperatorio y control radiológico para evaluar la estabilidad tanto en plano coronal como axial, osificaciones coracoclaviculares, signos de artrosis acromioclavicular y/o osteólisis distal de clavícula a los 6 y 12 meses postoperatorio. Resultados: se obtuvo un score de Constant preoperatorio de 41.3; 6 meses: 89.4; 12 meses: 92.3. El score de UCLA preoperatorio: 21.7; 6 meses: 29.1 y 12 meses: 31.4. VAS: 8.4; 2.3; 1.2. Hubo dos casos de relesión por trauma y un caso de insatisfacción estética de la cicatriz. En cuanto al examen radiológico se presentaron dos casos de pérdida de estabilidad y un caso de osteólisis distal de clavícula. Conclusión: la combinación de dos métodos de reducción, uno sintético y otro biológico, permitió una reconstrucción anatómica sólida, estable en plano coronal y axial con muy buenos resultados a mediano plazo.

Abstract: Introduction: The surgical treatment of acromioclavicular dislocation remains controversial. We describe herein a combined two-stage technique that includes an arthroscopic approach followed by a mini-invasive approach. Material and methods: 41 patients with acromioclavicular dislocation grades III, IV and V. Acute and chronic lesions and revision surgeries were included during the follow-up. Patients with other shoulder conditions were excluded. Mean age was 28.6 years. Patients were assessed preoperatively with the UCLA and Constant scores, and the pain visual analog scale. The 6- and 12-month postoperative evaluation included X-rays to assess coronal and axial stability, coracoclavicular ossifications, signs of acromioclavicular arthrosis and/or distal clavicular osteolysis. Results: The Constant scores were as follows: 41.3 preoperatively; 89.4 at 6 months; 92.3 at 12 months. The UCLA scores were as follows: 21.7 preoperatively; 29.1 at 6 months; 31.4 at 12 months. The VAS scores were 8.4, 2.3 and 1.2, for the same periods respectively. Two cases had repeated injury due to trauma and one case was dissatisfied with the cosmetic appearance of the scar. The X-ray assessment showed two cases of loss of stability and one case of distal clavicular osteolysis. Conclusion: The combination of two reduction methods, a synthetic one and a biological one allows for a solid anatomical reconstruction that is stable in the coronal and axial planes and good medium-term results.

Early initiation of low-dose aspirin for reduction in preeclampsia risk in high-risk women: a secondary analysis of the MFMU High-Risk Aspirin Study.

OBJECTIVE: Early initiation of low-dose aspirin (LDA) may reduce preeclampsia risk. We sought to determine whether LDA was beneficial when initiated <17w0d, within a trial of high-risk women enrolled <26w0d. STUDY DESIGN: Secondary analysis of the Maternal-Fetal Medicine Units High-Risk Aspirin study, including women enrolled <17w0d, randomized to LDA (60 mg day(-1)) or placebo with chronic hypertension (CHTN, n=186), diabetes (n=191) or prior preeclampsia (n=146). The primary outcome was preeclampsia at any time in pregnancy, secondary outcomes were early preeclampsia (<34w0d), late preeclampsia (⩾34w), small for gestational age (SGA; neonatal birthweight <10th %) and composite (early preeclampsia or SGA). Outcomes were compared by exact Χ(2)-tests. RESULTS: Baseline characteristics were similar between treatment groups. Aspirin was associated with a lower rate of late-onset preeclampsia ⩾34w (17.36% vs 24.42%, P=0.047), with a 41% reduction in women with CHTN (18.28% vs 31.18%, P=0.041). There were no other significant differences in the outcome. CONCLUSION: Aspirin initiated <17w0d reduced the risk for late-onset preeclampsia by 29% supporting the practice of early initiation of aspirin in high-risk women.

Increased trophoblast expression of NFAT5/TonEBP in pre-eclamptic placentas and hyperosmolar-treated BeWo cells.

OBJECTIVES: To assess the concentrations of inositol and sorbitol, and determine the expression of related osmolyte factors [nuclear factor of activated T cells 5, also known as tonicity responsive binding protein (NFAT5/TonEBP); sodium myo-inositol transporter (SLC5A3); and aldose reductase] in placentas of pre-eclamptic (PE) patients and trophoblast BeWo cells subjected to hypertonic stress in vitro. STUDY DESIGN: Control and PE placentas were collected. BeWo cells were cultured and subjected to a hyperosmolar solution for 4h. Western blot analysis was performed on NFAT5, SLC5A3, aldose reductase and ERK proteins. High-performance liquid chromatography was used to determine the levels of inositol and sorbitol in cell lysates. RESULTS: Compared with control placentas, PE placentas showed higher levels of inositol and NFAT5, and lower levels of SLC5A3. Treated BeWo cells showed higher levels of inositol, sorbitol, NFAT5 total protein, SLC5A3 and aldose reductase, and increased ERK activation compared with control BeWo cells. CONCLUSIONS: Hyperosmolar conditions increase the expression of NFAT5 in PE placentas and BeWo cells, and may account for the increased osmolyte levels. NFAT5 may accomplish this through aldose reductase and SLC5A3 in trophoblast cells.

Decreased expression of phosphorylated placental heat shock protein 27 in human and ovine intrauterine growth restriction (IUGR).

INTRODUCTION: Intrauterine growth restriction (IUGR) has been documented to increase placental apoptosis at term. HSP27 has been shown to be involved in the control of apoptosis. Our objective is to determine the expression of phosphorylated HSP27 (p-HSP27) in human IUGR, and to determine the role of HSP27 during gestation in an ovine hyperthermia induced model of IUGR. METHODS: Human placenta tissue samples were collected at term to quantify p-HSP27. Pregnant sheep were placed in hyperthermic (HT) conditions to induce IUGR. Placental tissues were collected at 55 (early), 95 (mid-gestation) and 130 (near-term) days gestational age (dGA) to determined phosphorylated and total HSP27 across the development of IUGR. RESULTS: Phosphorylated HSP27 was significantly reduced in human placenta IUGR compared to controls at term. HSP27 was increased throughout gestation during the development of IUGR in the sheep. P-HSP27 was increased in early gestation (55 dGA), and decreased near term (130 dGA). The near term decrease was localized to the trophoblast cells of the placenta. DISCUSSION AND CONCLUSION: We conclude that decreased p-HSP27 at term is present when placental apoptosis is increased during IUGR. This could be a factor leading to the decreased placental weight observed during IUGR.

Uterine artery blood flow volume in pregnant women with an abnormal pulsatility index of the uterine arteries delivering normal or intrauterine growth restricted newborns.

The aim of this study was to assess and compare uterine artery (UtA) blood flow volume in pregnant patients with an abnormal uterine Doppler pulsatility index (PI) who delivered fetuses with an appropriate weight for gestational age (AGA) or with intrauterine growth restricted (IUGR). We prospectively recruited singleton pregnancies with abnormal uterine arteries P.I. between 18 and 38 weeks of gestation regardless of estimated fetal weight (EFW). Vessel diameter and blood flow velocity were measured along the UtA upstream to the vessel bifurcation in both the right and left UtAs. Uterine blood flow volumes measured in these pregnancies were compared to historical Control-pregnancies. Forty-three patients delivered at term a normal weight newborn (AGA-pregnancies). Thirty patients delivered growth restricted newborns at 32 weeks (i.r. 29-36w) with a median weight of 1160 gr (i.r. 1000-2065 gr) (IUGR-pregnancies). At mid-gestation (18 + 0 - 25 + 6 weeks + days of gestation) a significantly lower uterine blood flow volume per unit weight was observed between the two study groups and compared to controls: 142 ml/min/kg in IUGR-pregnancies, 217 ml/min/kg in AGA-pregnancies and 538 ml/min/kg in Control-pregnancies. These striking differences in blood flow volume were already present at mid-gestation, at a time when EFW was still normal. In late gestation (27 + 0 - 37 + 6 weeks + days of gestation), pregnancies with an abnormal uterine P.I. showed persistently low UtA flow (<50% of controls) even when corrected for fetal weight: 81 ml/min/kg in IUGR-pregnancies, 105 ml/min/kg in AGA-pregnancies, and 193 ml/min/kg in Control-pregnancies; p < 0.0001. Our findings are consistent with other recent studies regarding the association between reduced uterine blood flow volume and fetal growth restriction. However, the study brings new insight into the finding of abnormal uterine P.I. in normally grown fetuses typically dismissed as "falsely abnormal" or "false positive" findings. Our study suggests that blood flow volume measurement may serve as a new tool to assess this group of patients and possibly those with ischemic placental diseases that may provide some basis for therapeutic interventions.

Blood flow volume of uterine arteries in human pregnancies determined using 3D and bi-dimensional imaging, angio-Doppler, and fluid-dynamic modeling.

The primary aim of this pilot study was to study uterine artery (UtA) blood flow volume in uneventful human pregnancies delivered at term, at mid and late gestation by means of 3D and bi-dimensional ultrasound imaging with angio-Doppler combined with fluid-dynamic modeling. Secondary aims were to correlate flow volume to placental site and to UtA Pulsatility Index (PI). Women with singleton, low-risk pregnancies were examined at mid and late gestation. The structure and course of the uterine artery (UtA) was studied in each patient by means of 3D-angio-Doppler and included vessel diameter D, blood flow velocity and PI (measured along the UtA). Fetal weight estimation and placental insertion site were assessed by ultrasound. A robust fluid-dynamic modeling was applied to calculate absolute flow and flow per unit fetal weight. Mean UtA diameter and blood flow velocity increased significantly (p < 0.0001) from mid-gestation to late gestation from 2.6 mm and 67.5 cm/s, to 3.0 mm and 85.3 cm/s, respectively, yielding an increasing absolute flow troughout gestation. h coefficient, derived by fluid-dynamic modeling to calculate mean velocity, increased significantly from 0.52 at mid-gestation to 0.57 at late gestation. UtA blood flow volume ml/min/kg-fetal weight was significantly higher at mid-gestation than at late gestation (535 ml/min/kg vs 193 ml/min/kg; p < 0.0001). In cases with strictly lateral placentas the ipsilateral UtA accommodates at mid and late gestation 63% and 67% of the total UtA flow. In central placentas UtA flow was evenly distributed between the two vessels. An inverse correlation was observed between PI and blood flow volume ml/min/kg (Pearson's coefficient r = -0.54). Our work confirms the technological and methodological limitations in the measurement of uterine artery blood flow. However, Doppler measurements supported by three-dimensional angio imaging of the uterine vessel, high resolution imaging and diameter measurement, and a robust mathematical model of local circulation adds a genuine new area of investigation into human uterine circulation during pregnancy.

Development and mechanisms of fetal hypoxia in severe fetal growth restriction.

Severe fetal growth restriction (FGR) is often associated with hypoxia. We studied FGR hypoxia in an experimental model which is produced by exposing pregnant ewes to a hyperthermic environment. The study utilized simultaneous measurements of several relevant factors, e.g., uterine and umbilical blood flows and O(2) uptakes. Sixteen ewes were divided equally into control (C) and hyperthermic (HT) groups. Hyperthermia (40 degrees C for 12h/35 degrees C for 12h; approximately 35% relative humidity, RH) was maintained for 80 days commencing at approximately 38 days gestational age (dGA term 147+/-3 days). All ewes were then placed in a control environment ( approximately 21 degrees C, 24h; approximately 30% RH) and studied at approximately 134 dGA. Mean HT placental and fetal weights were 39% and 45% of C, respectively (p<0.0001), umbilical O(2) uptake/kg fetus was 76% of C (p<0.01) and umbilical venous PO(2) was reduced (20.2 vs. 29.7 Torr, p<0.001). Contrary to the hypothesis that FGR hypoxia is due to maternal placental hypoperfusion, uterine flow was not reduced in relation to O(2) uptake. The uterine-umbilical venous PO(2) difference was enlarged (38 vs. 23 Torr, p<0.0001). This difference is the expression of a balance between developmental changes in placental structure and oxidative metabolism, which have opposite effects in terms of fetal oxygenation. We postulate that FGR hypoxia results from disproportionate underdevelopment of those changes which allow for a progressive increase in umbilical O(2) uptake.

Doppler and biophysical assessment in growth restricted fetuses: distribution of test results.

OBJECTIVE: Multi-vessel Doppler ultrasonography and biophysical profile scoring (BPS) are used in the surveillance of growth restricted fetuses (IUGR). The interpretation of both tests performed concurrently may be complex. This study examines the relationship between Doppler ultrasonography and biophysical test results in IUGR fetuses. METHODS: Three hundred and twenty-eight IUGR fetuses (abdominal circumference < 5th percentile, elevated umbilical artery (UA) pulsatility index (PI)) had concurrent surveillance with UA, middle cerebral artery (MCA) and ductus venosus (DV) Doppler ultrasonography and BPS (fetal tone, movement, breathing, maximal amniotic fluid pocket and fetal heart rate). Patients were stratified into three groups according to their Doppler examination: (1) abnormal UA alone; (2) brain sparing (MCA-PI > 2 SD below mean for gestational age); and (3) abnormal DV (PI > 2 SD above the mean for gestational age) and BPS groups: (1) normal (> 6/10); (2) equivocal (6/10); and (3) abnormal (< 6/10). Predictions of short-term perinatal outcomes by both modalities were compared for stratification. The distribution and concordance of Doppler and BPS test results were examined for the whole patient group and based on delivery prior to 32 weeks' gestation. RESULTS: Abnormal UA Doppler results alone were observed in 109 fetuses (33.2%), brain sparing in 87 (26.5%) and an abnormal DV in 132 (40.2%). The BPS was normal in 158 (48.2%), equivocal in 68 (20.7%) and abnormal in 102 (31.1%). Both testing modalities stratified patients into groups with comparable acid-base disturbance and perinatal outcome. Of the nine possible test combinations the largest subgroups were: abnormal UA alone/normal BPS (n = 69; 21%) and abnormal DV Doppler/abnormal BPS (n = 62; 18.9%). Assessment of compromise by both testing modalities was concordant in 146 (44.5%) cases. In 182 fetuses with discordant results the BPS grade was better in 115 (63.2%, P < 0.0001). Marked disagreement of test abnormality was present in 57 (17.4%) fetuses. Of these, abnormal venous Doppler in the presence of a normal BPS constituted the largest group (Chi-square P < 0.002). Stratification was not significantly different in patients delivered prior to 32 weeks' gestation. CONCLUSION: Doppler ultrasonography and BPS effectively stratify IUGR fetuses into risk categories, but Doppler and BPS results do not show a consistent relationship with each other. Since fetal deterioration appears to be independently reflected in these two testing modalities further research is warranted to investigate how they are best combined.

Placental development in normal and compromised pregnancies-- a review.

Intrauterine growth restriction (IUGR) is a significant cause of infant mortality and morbidity. It is now clear that IUGR infants exhibit higher rates of coronary heart disease, type 2-diabetes, hypertension and stroke as adults. Therefore, fetal growth not only impacts the outcome of the perinatal period, but also impacts adult well-being. The etiologies of IUGR are numerous, but are often associated with abnormalities in placental structure and function. The process of implantation and placentation requires the production of a plethora of growth factors, cell-adhesion molecules, extracellular matrix proteins, hormones and transcription factors. Many of these exhibit altered expression within the placenta of IUGR pregnancies. However, it has been difficult to fully assess their role during the development of placental insufficiency (PI) in the human, underscoring the need for animal models. Using an ovine model of PI-IUGR we have observed changes in the expression of vascular endothelial growth factor, placental growth factor, their common receptors, as well as angiopoietin 2 and its receptor, Tie 2. We found that changes in these growth factors can be associated with both acute and chronic changes in placental vascular structure and function. These studies and others are providing needed insight into the developmental chronology of placental insufficiency.

Placental expression of VEGF, PlGF and their receptors in a model of placental insufficiency-intrauterine growth restriction (PI-IUGR).

Placental development requires adequate and organized interaction of vascular growth factors and their receptors, including vascular endothelial growth factor (VEGF) and placental growth factor (PlGF). Both VEGF and PlGF, acting through the tyrosine kinase receptors VEGFR-1 and VEGFR-2, have been implicated in playing a role in ovine placental vascular development. The present studies describe the placental expression of components of the VEGF family at two maturational time points (55 and 90 days post coitus, dpc) in a hyperthermic-induced ovine model of placental insufficiency-intrauterine growth restriction (PI-IUGR). Both caruncular and cotyledonary VEGF and PlGF mRNA concentration increased with gestational age (P< 0.05), whereas only cotyledonary VEGF and PlGF protein concentration increased over gestation (P< 0.002). At 55 dpc, VEGF mRNA concentration was elevated in hyperthermic (HT) ewes, compared to control thermoneutral (TN) animals (TN; 0.52+/-0.08 vs HT; 1.27+/-0.17 VEGF/GAPDH, P< 0.001). At 90 dpc, expression of PlGF and VEGF mRNA was not altered by the HT treatment. Both TN cotyledonary VEGFR-1 and VEGFR-2 mRNA expression levels rose significantly over the period studied (P< 0.05 and P< 0.01 respectively). Receptor mRNA concentration in HT cotyledonary tissue was significantly reduced at 90 dpc (VEGFR-1; TN 0.21+/-0.02 vs HT 0.11+/-0.01 VEGFR-1/actin, P< 0.05, VEGFR-2; TN 0.18+/-0.05 vs HT 0.07+/-0.01 VEGFR-2/actin, P< 0.01). Soluble VEGFR-1 (sVEGFR-1) mRNA was not detected in these tissues. These alterations in growth factor and growth factor receptor mRNA expression, as a result of environmental heat stress early in placental development, could impair normal placental vascular development. Furthermore, alterations in VEGF, VEGFR-1 and VEGFR-2 mRNA expression, during the period of maximal placental growth, may contribute to the development of placental insufficiency, and ultimately intrauterine growth restriction.

Temporal sequence of abnormal Doppler changes in the peripheral and central circulatory systems of the severely growth-restricted fetus.

OBJECTIVE: To identify the temporal sequence of abnormal Doppler changes in the fetal circulation in a subset of early and severely growth-restricted fetuses. METHODS: This was a prospective observational study in a tertiary care/teaching hospital. Twenty-six women who were diagnosed with growth-restricted fetuses by local standards before 32 weeks' gestation and who had abnormal uterine and umbilical artery Doppler velocimetry were enrolled onto the study. To compare Doppler changes as a function of time, pulsed-wave Doppler ultrasound was performed on five vessels in the fetal peripheral and central circulations. Doppler examinations were performed twice-weekly and on the day of delivery if the fetal heart rate tracing became abnormal. Doppler indices were scored as abnormal when their values were outside the local reference limits on two or more consecutive measurements. Biometry for assessment of fetal growth was performed every 2 weeks. Computerized fetal heart rates were obtained daily. Delivery was based on a non-reactive fetal heart rate tracing and not on Doppler information. Patients with a severely growth-restricted fetus who were delivered for maternal indications such as pre-eclampsia were excluded. Perinatal outcome endpoints included: intrauterine death, gestational age at delivery, newborn weight, central nervous system damage of grade 2 or greater, intraventricular hemorrhage and neonatal mortality. RESULTS: Mean gestational age and newborn weight at delivery were 29 (standard deviation (SD), 2) weeks and 818 (SD, 150) g, respectively. The sequence of Doppler velocimetric changes was described by onset time cumulative curves that showed two time-related events. First, for each vessel there was a progressive increase in the percent of fetuses developing a Doppler abnormality. Second, severely growth-restricted fetuses followed a progressive sequence of acquiring Doppler abnormalities which were categorized into 'early' and 'late' Doppler changes. Early changes occurred in peripheral vessels (umbilical and middle cerebral arteries; 50% of patients affected 15-16 days prior to delivery). Late changes included umbilical artery reverse flow, and abnormal changes in the ductus venosus, aortic and pulmonary outflow tracts (50% of patients affected 4-5 days prior to delivery). The time interval between the occurrence of early and late changes was significantly different (P < 0.0001) and late changes were significantly associated with perinatal death (P < 0.01). CONCLUSIONS: Doppler velocimetry abnormalities develop in different vessels of the severely growth-restricted fetus in a sequential fashion. Late changes in vascular adaptation by the severely growth-restricted fetus are the best predictor of perinatal death.

DeLee suction. Does it have clinical significance?

OBJECTIVE: To evaluate the null hypothesis that there would be no difference in neonatal outcome in infants who underwent DeLee suction vs. those who underwent bulb suction when thick meconium was present. This difference was defined as a one-day difference in length of stay, two-point difference in the five-minute Apgar score or significant difference in blood gases. STUDY DESIGN: A power calculation based on a one-day length of stay found that 115 patients would be needed in each arm. A cohort of 115 consecutive deliveries with the presence of thick meconium was reviewed during each time period when DeLee suction was utilized and then matched with deliveries that used bulb suction. RESULTS: Two hundred thirty charts were reviewed. Length of stay, one-minute Apgar score, five-minute Apgar score, blood gases, gestational age and incidence of amnioinfusion were compared. There was no significant difference in any variable. Meconium aspiration syndrome in the period studied remained stable at < 1%. CONCLUSION: There was no significant clinical change in neonatal outcome with the abandonment of nasopharyngeal DeLee suction on the perineum when meconium was present. We recommend the use of bulb suction as routine obstetric practice even in the presence of thick meconium.

Early and persistent reduction in umbilical vein blood flow in the growth-restricted fetus: a longitudinal study.

OBJECTIVE: We have previously shown, in a cross-sectional study, that the reduction in umbilical vein blood flow in intrauterine growth-restricted fetuses is due to reduced umbilical vein velocity. The purpose of this longitudinal study in intrauterine growth-restricted fetuses was to determine whether the umbilical vein velocity reduction, which, in turn, reduces blood flow, persists throughout gestation or represents a late event that precedes indicated delivery. STUDY DESIGN: Twenty-one intrauterine growth-restricted fetuses with an abnormal umbilical artery velocimetry underwent serial sonographic and Doppler examinations from 23 to 36 weeks of gestation. Umbilical vein diameter and velocity were measured, and umbilical vein absolute (milliliters per minute) and weight-specific blood flow (milliliters per minute per kilogram) were calculated. Umbilical vein diameter, velocity, and blood flow were expressed per abdominal circumference. Intrauterine growth-restricted findings were compared to local reference data. RESULTS: Intrauterine growth-restricted fetuses showed persistent reductions in umbilical vein blood flow per abdominal circumference and weight-specific blood flow (milliliters per minute per kilogram) from the time of diagnosis of intrauterine growth-restriction. Umbilical vein velocity was reduced in the intrauterine growth-restricted fetuses, although umbilical vein diameter did not change. CONCLUSION: Reduction of umbilical vein blood flow is an early finding in intrauterine growth-restricted fetuses, and it can persist for several weeks until delivery. This reduction in blood flow is due to reduced umbilical vein velocity.

Reduction of subcutaneous mass, but not lean mass, in normal fetuses in Denver, Colorado.

OBJECTIVE: To test the hypothesis that reduced birth weight in normal fetuses born at moderately high altitude (Denver), compared with the birth weight in normal fetuses born at sea level (Milan), is caused by a reduction in both lean mass and subcutaneous fat mass. STUDY DESIGN: Ninety-four normal singleton pregnancies (46 in Denver, 48 in Milan) had serial ultrasonographic axial images obtained to assess subcutaneous tissues of fetuses as a measure of body fat. The abdominal wall thickness and mid upper arm and mid thigh were examined. The equation was: Subcutaneous tissue equals total cross-sectional area minus bone and muscle area. Lean mass included the area of muscle and bone, head circumference, and femur length. RESULTS: Gestational age at delivery was similar between groups. Birth weight was less at Denver's altitude (2991 +/- 79 g versus 3247 +/- 96 g; P =.04). Abdominal wall thickness, mid upper arm, and mid thigh subcutaneous tissues measurements were significantly reduced at Denver's altitude and increased further in significance with advancing gestational age. Lean mass measurements were similar between groups. CONCLUSIONS: The reduced birth weight of the newborns in Denver was the result of a reduction in fetal subcutaneous fat tissue and not lean mass. Ultrasonography can be used to follow subcutaneous measurements longitudinally and to detect differences, and potentially disease processes, in study populations.