Abnormal fetal heart rate patterns during the active phase of labor: the value of fetal oxygen saturation

Objective: To determine the predictive value of intrapartum fetal oxygen saturation (SO₂) for prediction of an umbilical artery pH less than 7.15 at birth in labors complicated by abnormal fetal heart rate traces. Study design: Eighty-five primigravidas in spontaneous labor complicated by abnormal fetal heart rate traces underwent fetal SO₂ monitoring using the fetal pulse oximetry technique. Cases with an SO₂ of < 30% were delivered by Cesarean section. Umbilical artery pH was measured at birth in all women. Results: With the value set of 30% as the cut-off point of fetal oxygen saturation, the positive predictive value for umbilical artery pH of < 7.15 was 61.5% and the negative predictive value was 95.8%, with a sensitivity of 72% and a specificity of 93%. Conclusions: Fetal pulse oximetry is a promising technique for assessment of fetal well-being during labor and may decrease the number of unnecessary Cesarean sections.     

The effects of overcoming experimental bladder outflow obstruction in fetal sheep

Objective: To develop an ovine model of fetal bladder outflow obstruction and to investigate the effect on the kidney of surgical relief of the obstruction in the prenatal period. Methods: Ultrasound examination and amniocentesis were performed on 68 date-bred pregnant ewes at day 57 of pregnancy (term = 150 days). Fetal gender was determined using a molecular technique to identify single male fetuses. The urethra and urachus were ligated at hysterotomy on 20 of these fetuses at 75 days' gestation. Comparisons were made with six controls that did not undergo operation. Changes that occurred in fetal urinary tract appearance were detected using serial ultrasound examinations. Seven obstructed cases chosen at random had further prenatal surgery on day 94 to decompress the obstructed urinary tract by vesicostomy. The animals were killed at 110 days' gestation and post-mortem studies were performed. Results: Fourteen days after surgical obstruction, there were increases in the summed renal lengths (33 mm vs. 28 mm, p = 0.003) and renal pelvis anteroposterior (A-P) diameters (8 mm vs. 5.5 mm, p = 0.02). In the group allocated to receive surgical decompression, 9 days' relief of obstruction resulted in significant reductions in summed renal lengths (30 mm vs. 41 mm, p = 0.024; controls 31 mm) and renal pelvis A-P diameters (5.8 mm vs. 8.9 mm, p = 0.012; controls < 2 mm). Post-mortem histological examination in the surgical decompression group revealed an estimated number of glomeruli similar to controls and greater than in the obstructed cases. Conclusion: Surgical relief of fetal bladder outflow obstruction in ovine mid-pregnancy results in improved renal appearance on ultrasonic and histopathological examinations.     

Accuracy of the TDx-FLM assay of amniotic fluid: a comparison of vaginal pool samples with amniocentesis

Objective: The purpose of this study was to evaluate the use of the TDx-FLM fluorescence polarization assay on vaginal pool fluid in patients with preterm premature rupture of membranes (PPROM). Methods: A prospective matched-pairs study was performed at a tertiary care center. For each patient enrolled, amniotic fluid samples were obtained by sterile speculum examination and by amniocentesis within 12 h of each other. Inclusion criteria were the presence of PPROM and a gestational age of 30-36 weeks. The samples were analyzed separately using the TDx-FLM assay in the same laboratory. The results were compared using a paired Student t test. Results: A total of 16 patients received both amniocentesis and vaginal collection of amniotic fluid. The mean gestational age at amniocentesis was 33.3 weeks (SD 1.9). In every case, the vaginal pool TDx-FLM result was lower than the amniocentesis result. The mean difference in the assays between the two fluid sources was 35% (range 17-63%, p < 0.001). Amniocentesis suggested a mature result in 12 cases (75%), an indeterminate result in two cases (12.5%), and an immature result in two cases (12.5%). Vaginal pool fluid suggested a mature result in four cases (25%), an indeterminate result in nine cases (56%), and an immature result in three cases (19%). Using the cut-off values validated for amniocentesis specimens as a standard for comparison, vaginal pool TDx-FLM assay had 42% sensitivity, 100% specificity, 100% positive predictive value and 36% negative predictive value for predicting lung maturity. Conclusions: The TDx-FLM assay on vaginal pool samples of amniotic fluid yielded results that were significantly different from those of amniocentesis samples. At this point, the assay is only clinically useful for vaginal pool samples when a mature result is obtained.     

Second-trimester uterine artery Doppler screening in unselected populations: a review

Objective: Doppler ultrasound provides a non-invasive method for the study of the uteroplacental circulation. In normal pregnancy, impedance to flow in the uterine arteries decreases with gestation, which may be the consequence of trophoblastic invasion of the spiral arteries and their conversion into low-resistance vessels. Pre-eclampsia and fetal growth restriction are associated with failure of trophoblastic invasion of spiral arteries, and Doppler studies, in these conditions, have shown that impedance to flow in the uterine arteries is increased. A series of screening studies involving assessment of impedance to flow in the uterine arteries have examined the potential value of Doppler in identifying pregnancies at risk of the complications of impaired placentation. This review examines the findings of Doppler studies in unselected populations. Methods: Searches of a computerized medical database were performed to identify relevant studies. Only those studies that provided sufficient data to allow calculation of the performance of the test were included in the analysis. Likelihood ratios were calculated for each study and are reported for pre-eclampsia, fetal growth restriction and perinatal death as well as for more severe forms of pre-eclampsia and fetal growth restriction. Results: The literature search identified 19 relevant studies, four of which were excluded from the further analysis. The main characteristics and results of the 15 remaining studies provided discrepant results, which may be the consequence of differences in Doppler technique for sampling, the definition of abnormal flow velocity waveform, differences in the populations examined, the gestational age at which women were studied and different criteria for the diagnosis of pre-eclampsia and fetal growth restriction. Nevertheless, the studies provided evidence that increased impedance to flow in the uterine arteries is associated with increased risk for subsequent development of pre-eclampsia, fetal growth restriction and perinatal death. In addition, women with normal impedance to flow in the uterine arteries constituted a group that have a low risk of developing obstetric complications related to uteroplacental insufficiency. Conclusions: The review suggests that increased impedance to flow in the uterine arteries in pregnancies attending for routine antenatal care identifies about 40% of those who subsequently develop pre-eclampsia and about 20% of those who develop fetal growth restriction. Following a positive test, the likelihood of these complications is increased by about 6 and 3.5 times, respectively.     

Prospective delivery of reliably dated term infants of diabetic mothers without determination of fetal lung maturity: comparison to historical control

Objective: To determine whether omitting fetal lung maturity (FLM) testing prior to delivery in term pregnancies complicated by gestational (GDM) and pregestational diabetes mellitus would increase the risk of neonatal respiratory distress syndrome (RDS). Methods: In a 2-year study (1990-91), 1457 pregnant women with accurately dated pregnancies were enrolled after 37 completed weeks and prospectively followed through delivery without FLM testing (study group). The prevalence of RDS and other neonatal outcomes was compared with a historical control group (n = 713, 1988-89) who had undergone determination of lecithin/sphingomyelin ratio prior to delivery at term. Logistic regression analysis was performed to determine independent predictors of RDS. Results: The study group compared to the control group had less severe diabetes: diet-controlled GDM, 35% vs. 18%, respectively; insulin-requiring GDM, 42% vs. 42%, respectively; undiagnosed type-2 diabetes, 14% vs. 31%, respectively; and pre-existing diabetes, 9.6% vs. 8.8%, respectively, p < 0.001. RDS rates in the study group (0.8%) and control group (1.0%) were not significantly different, nor were rates of resuscitation at delivery, neonatal intensive care admission or hospitalization days. Logistic regression analysis found only Cesarean delivery to be independently predictive (adjusted OR 2.21, 95% CI 2.04-2.27) of RDS. Non-predictive variables included FLM testing, diabetic classification, insulin use, poor third-trimester glycemic control, chronic hypertension, pre-eclampsia, labor, neonatal gender, gestational age or large-for-gestational-age fetuses. Conclusions: Routine FLM testing did not change the RDS prevalence in reliably dated, term infants of diabetic mothers and should be abandoned. Delivery by Cesarean section was associated with increased RDS.     

Detection of fetal growth restriction in patients with chronic hypertension: is it feasible?

Objective: To determine the utility of sonographic estimated fetal weight (EFW) in diagnosing intrauterine growth restriction (IUGR, birth weight < 10% for gestational age) in patients with chronic hypertension. Methods: All pregnant patients with hypertension delivered during a 5-year period at three centers were identified retrospectively. Patients with gestational hypertension, pre-eclampsia, diabetes mellitus, fetal anomalies and absence of a sonographic examination within 3 weeks of delivery were excluded. Likelihood ratio (LR) and guidelines established by the Evidence-Based Medicine Working Group were used to determine whether sonographic EFW is a reliable diagnostic test to detect IUGR. Results: At the three centers, there were 264 patients with chronic hypertension (122, 77 and 65 at centers I, II and III, respectively). The incidence of IUGR ranged from 13% to 27% but was similar at the three locations (p = 0.064). The LR (with 95% confidence interval (CI)) of detecting IUGR was 4.4 (95% CI 2.5, 7.7), 2.3 (95% CI 1.4, 3.7) and 6.1 (95% CI 2.7, 13.7) at centers I, II and III, respectively. Based on the proportions of abnormal growth, we required 253 and 71 newborns with fetal growth restriction at centers I and II, respectively, to have narrow confidence intervals around the clinically important LR of 10. The extremely low incidence of IUGR at center III (13%) precluded the estimation of required sample size. Conclusion: Use of Evidence-Based Medicine Working Group guidelines indicates that sonographic EFW is slightly to moderately useful in detecting fetal growth restriction in patients with chronic hypertension.     

Elevation of MCP-1 and MCP-1/VEGF ratio in cerebrospinal fluid of amyotrophic lateral sclerosis patients

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with progressive cell death of upper and lower motor neurons. In this study, we measured monocyte chemotactic protein-1 (MCP-1) and vascular endothelial growth factor (VEGF) levels in cerebrospinal fluid (CSF) and serum by enzyme-linked immunosorbent assay (ELISA) in 42 ALS patients, and compared these levels with those of control subjects with other neurodegenerative disorders or with those of normal controls. MCP-1 levels in CSF were significantly higher in ALS patients than in the control group. VEGF levels in CSF tended to be lower in ALS patients than in the control group, but not significantly. A positive correlation was found between MCP-1 levels in CSF of ALS patients and the total Norris scale. The elevation of MCP-1/VEGF ratio in CSF was more specific to ALS patients compared to other neurological diseases such as Parkinson's disease (PD) and spinocerebellar ataxia (SCA) and to controls. Our data suggested that both MCP-1 levels and MCP-1/VEGF ratio in CSF may be useful markers for the clinical diagnosis of ALS.     

GPR30 deficiency causes increased bone mass,mineralization, and growth plate proliferative activity in male mice

Estrogen regulation of the male skeleton was first clearly demonstrated in patients with aromatase deficiency or a mutation in the ERα gene. Estrogen action on the skeleton is thought to occur mainly through the action of the nuclear receptors ERα and ERβ. Recently, in vitro studies have shown that the G protein–coupled receptor GPR30 is a functional estrogen receptor (ER). GPR30‐deficient mouse models have been generated to study the in vivo function of this protein; however, its in vivo role in the male skeleton remains underexplored. We have characterized size, body composition, and bone mass in adult male Gpr30 knockout (KO) mice and their wild‐type (WT) littermates. Gpr30 KO mice weighed more and had greater nasal‐anal length (p < .001). Both lean mass and percent body fat were increased in the KO mice. Femur length was greater in Gpr30 KO mice, as was whole‐body, spine, and femoral areal bone mineral density (p < .01). Gpr30 KO mice showed increased trabecular bone volume (p < .01) and cortical thickness (p < .001). Mineralized surface was increased in Gpr30 KO mice (p < .05). Bromodeoxyuridine (BrdU) labeling showed greater proliferation in the growth plate of Gpr30 KO mice (p < .05). Under osteogenic culture conditions, Gpr30 KO femoral bone marrow cells produced fewer alkaline phosphatase–positive colonies in early differentiating osteoblast cultures but showed increased mineralized nodule deposition in mature osteoblast cultures. Serum insulin‐like growth factor 1 (IGF‐1) levels were not different. These data suggest that in male mice, GPR30 action contributes to regulation of bone mass, size, and microarchitecture by a mechanism that does not require changes in circulating IGF‐1. © 2011 American Society for Bone and Mineral Research.     

Targeting VEGF and Its Receptors for the Treatment of Osteoarthritis and Associated Pain

Increased vascular endothelial growth factor (VEGF) levels are associated with osteoarthritis (OA) progression. Indeed, VEGF appears to be involved in OA‐specific pathologies including cartilage degeneration, osteophyte formation, subchondral bone cysts and sclerosis, synovitis, and pain. Moreover, a wide range of studies suggest that inhibition of VEGF signaling reduces OA progression. This review highlights both the potential significance of VEGF in OA pathology and pain, as well as potential benefits of inhibition of VEGF and its receptors as an OA treatment. With the emergence of the clinical use of anti‐VEGF therapy outside of OA, both as high‐dose systemic treatments and low‐dose local treatments, these particular therapies are now more widely understood. Currently, there is no established disease‐modifying drug available for patients with OA, which warrants continued study of the inhibition of VEGF signaling in OA, as stand‐alone or adjuvant therapy. © 2016 American Society for Bone and Mineral Research.